New Synthetic Approaches to Alk-1-enyl Sulfones and Sulfoxides

Università di Pisa
Facoltà di Scienze Matematiche Fisiche e Naturali
Dottorato di ricerca in Scienze Chimiche-XIX ciclo
Scuola di Dottorato “G. Galilei”
Ph.D. Thesis
New Synthetic Approaches to
Alk-1-enyl Sulfones and
Sulfoxides
Supervisor
Prof. Rita Menicagli
Candidate
Giovanni Signore
External referee
Dr. Vittorio Farina

A tutte le persone che, nel corso della
vita, mi hanno aiutato a crescere;
perché se sono arrivato fino qui non è
soltanto merito mio.

Desidero rigraziare il Prof. Sbrana per avermi concesso di usufruire del
suo spettrometro di massa e Marco Martinelli per avermi insegnato ad
usarlo; il Dr. Malanga per l’ aiuto fornitomi nella conclusione di questo
dottorato, la Prof. Menicagli per aver posto le fondamenta della mia
formazione scientifica, il Dr. Farina, che mi ha dato la possibilità di
vivere un’ esperienza entusiasmante, il Prof. Lazzaroni per essersi sempre
preoccupato di aiutarmi nella scelta del mio futuro, la Prof. Iuliano per il
supporto discreto in certi momenti.
Non posso dimenticare Luca, Elisa, Alberto e Chiara, compagni di pranzi
in Dipartimento, piacevoli cene e vacanze avventurose; il “Dream Team”
di Chimica Industriale, ormai disperso ma sempre unito, e tutti gli amici
che nel corso del tempo si sono aggiunti a questo splendido gruppo.
Infine, un ringraziamento speciale va alla mia famiglia: mia nonna per la
fiducia in me; i miei genitori per il supporto costante nel corso del lungo
cammino che mi ha portato fino qui, mia sorella per l’ affetto che mi ha
sempre dimostrato, ed Attila, che risolve ogni problema con un gioco ed
un letto su cui dormire. E naturalmente Silvia, compagna fedele e sincera
in ogni momento, per avermi pazientemente sopportato in tutti questi anni.

Questa tesi è stata svolta presso il Dipartimento di Chimica e
Chimica Industriale dell’ Università di Pisa

Abstract
This thesis is mainly devoted to the study of new synthetic approaches to alk-1enyl
sulfoxides and sulfones, important intermediates in organic synthesis. New
reactions were found that allowed the synthesis of these substances in excellent
yields under simple and practical conditions. Dialkyl alk-1-enyl aluminum
reagents, both uncomplexed or complexed with pyridine, were effective in the
formation of a) alk-1-enyl sulfoxides; b) alk-1-enyl sulfones; c) N-acyl-2-alkenyl-
2H-dihydropyridine derivatives, depending on the reaction conditions.
More specifically, this work describes the following results:
a) Uncomplexed organoaluminum reagents reacted smoothly with aluminum
sulfinates, produced in situ from sulfonyl chlorides and Et3Al, to afford alk-
1-enyl sulfoxides in good yields (72-75%). Reaction of sulfonyl chlorides
with pyridine-complexed alanes, in the presence of triphenylphosphine as
reducing agent, afforded the sulfoxides in up to 94% yield; a reasonable
mechanism is proposed. It was also found that sulfinyl chlorides react with
alkynyl aluminum reagents only with a partial conversion to give alkynyl
sulfoxides in modest yields (43-57%).
b) Reaction of pyridine-complexed alanes with sulfonyl chlorides, in the
presence of Ph3PO, afforded the corresponding sulfones in good yields
(75%). The more reactive uncomplexed alanes effectively alkenylated
sulfonyl chloride-pyridine complexes albeit in very variable (40-90%)
yields; CuCl was found to improve the yields of these reactions.
c) Finally, a new approach was developed to the synthesis of N-acyl-2-alkenyl-
2H-dihydropyridine and dihydroisoquinoline derivatives via reaction of
alkenyl aluminum reagents complexed with pyridine or isoquinoline and
acid halides.
i

Publications
The following results obtained in the context of this thesis work have been so
far published in the form of poster presentations at international conferences or
scientific articles:
Articles
ii
1. Signore, G.; Samaritani, S.; Malanga, C.; Menicagli, R. "Reinheckel
Protocol Revisited: Synthesis of (E)-α,β-unsaturated Sulfoxides" Synthesis
762-764 (2006)
2. Signore, G.; Calderisi, M.; Malanga, C.; Menicagli, R. "Alkenylalanepyridine
complexes in a new synthesis of aryl alk-1-enyl sulfoxides"
Tetrahedron 63(1), 177-182 (2007)
Poster presentations
1. Signore, G.; Samaritani, S.; Malanga, C.; Menicagli, R. "The Reinheckel
protocol revisited: a useful approach to α,β-unsaturated sulfoxides" pre-
OMCOS13 "Recent advances in organometallic chemistry and applied
catalysis", Paris, 15-16 July 2005, Abstract Book, P35
2. Signore, G.; Menicagli, R.; Samaritani, S.; Calderisi, M. "Alk-1-enyl
alanes in the synthesis of unsaturated aryl sulfoxides". OMCOS13 "13th
IUPAC international symposium on organometallic chemistry directed
towards organic synthesis", Geneva, 17-21 July 2005, Abstract Book P169
3. Signore, G.; Malanga, C.; Menicagli, R. "Unsaturated organoalanes in the
synthesis of (2H) dihydropyridines and (2H) dihydroquinolines" ICOMC-
XXII, "International conference in organometallic chemistry" Zaragoza,
23-28 July 2006, Abstract book P 442

Table of acronyms and abbreviations
AcO Acetate
AIBN 4,4’-azoisobutyrronitrile
Ar Aryl
Alk Alkyl
Bn Benzyl
Bu Butyl
BuLi Butyllithium
CAN Cerium ammonium
nitrate
Cp Cyclopentadienyl
Dba dibenzylidene acetone
DIBAL-H di-i-butyl aluminum
hydride
DMAD dimethylamino
dicarboxilate
DMAP 4-(N,N-dimethylamino)-pyridine
DMF dimethylformamide
Et Ethyl
F20TPPFe iron tetrakis
(pentafluorophenyl)
porphyrine
Fur Furyl
Hex Hexyl
LDA Lithium di i-propyl
amide
LiHDMS lithium hexamethyl
disilazide
MCPBA m-Chloroperbenzoic
acid
Me Methyl
Ment Mentyl
MMPP Magnesium mono
peroxy phtalate
Ms Methanesulfonyl
NBS N-Bromo succinimide
NIS N-iodo succinimide
PCC pyridine chloro
chromate
Ph Phenyl
Pr Propyl
Py Pyridine
r.t. room temperature
TBA Tetrabutylammonium
TBSO t-Butyldimethylsilyloxy
TfO Trifluoro
methansulfonate
THF tetrahydrofuran
TMSO Trimethylsilyloxy
Tol Tolyl
Ts p-Toluenesulfonyl
iii

Table of Contents
Abstract........................................................................................................................i
Publications.................................................................................................................ii
Table of acronyms and abbreviations .....................................................................iii
Table of Contents ....................................................................................................... v
Introduction................................................................................................................ 1
Part I Literature overview......................................................................3
Synthesis of alk-1-enyl sulfones and sulfoxides: state of the art ............................ 5
1.1 Introduction.................................................................................................... 5
1.2 Synthesis of alk-1-enyl sulfones .................................................................... 6
1.2.1 Synthesis from other sulfur derivatives.................................................... 6
1.2.2 Sulfones via formation of new C-S bonds ............................................. 13
1.2.3 Sulfones via addition-elimination of good leaving groups .................... 18
1.2.4 Sulfones via condensation reactions ...................................................... 22
1.3 Synthesis of alk-1-enyl sulfoxides............................................................... 25
1.3.1 Alk-1-enyl sulfoxides from other sulfur derivatives.............................. 25
1.3.2 Alk-1-enyl sulfoxides by nucleophilic substitution at the sulfur
atom........................................................................................................ 30
1.3.3 Alk-1-enyl sulfoxides via condensation reactions ................................. 32
Part II Results ........................................................................................35
New synthetic approaches to alk-1-enyl sulfoxides............................................... 37
2.1 Introduction.................................................................................................. 37
2.2 Syntesis of alk-1-enyl sulfoxides using aluminum sulfinates...................... 38
2.2.1 General remarks ..................................................................................... 38
2.2.2 Preliminary experiments ........................................................................ 39
2.2.3 Study of the reaction .............................................................................. 41
2.3 Alk-1-enyl sulfoxides starting from sulfonyl chlorides and pyridinecoordinated
alanes........................................................................................ 43
2.3.1 Preliminary attempts of cross-coupling reactions in the presence of
palladium complexes.............................................................................. 43
2.3.2 Alk-1-enyl sulfoxides from pyridine-complexed alanes and
sulfonyl chlorides in the presence of triphenylphosphine...................... 47
2.3.3 Mechanistic details................................................................................. 50
2.4 Alk-1-enyl sulfoxides starting from sulfinyl chlorides................................ 56
2.4.1 General remarks ..................................................................................... 56
New synthetic approaches to unsaturated sulfones .............................................. 61
v

3.1 Introduction ..................................................................................................61
3.2 Alkenyl sulfones starting from sulfonyl chloride-pyridine complexes ........62
3.2.1 Use of dialkyl alk-1-enyl alanes as alkenylating agents.........................62
3.2.2 The "copper effect".................................................................................64
3.2.3 Reaction of Grignard reagents with sulfonyl chloride-pyridine
adducts ....................................................................................................67
3.3 Alk-1-enyl sulfones starting from pyridine-complexed alanes and
sulfonyl chlorides in the presence of Ph3PO ................................................69
Reissert-like reactions of dialkyl alk-1-enyl aluminum-pyridine complexes
with acid chlorides....................................................................................................75
4.1 Introduction ..................................................................................................75
4.2 Preliminary experiments...............................................................................76
4.3 Study of the reaction.....................................................................................77
4.4 Mechanistic considerations ..........................................................................81
Conclusions ...............................................................................................................83
Part III Experimental section.............................................................. 87
Experimental section ................................................................................................89
6.1 Chemicals and instruments...........................................................................89
6.1.1 Purification of solvents and reagents......................................................89
6.1.2 Instruments .............................................................................................89
6.2 Synthesis of the starting reagents .................................................................90
6.2.1 Synthesis of di-i-butyl aluminum hydride (DIBAL-H)..........................90
6.2.2 Synthesis of benzenesulfinyl chloride ....................................................90
6.2.3 Synthesis of 1-N-benzoyl imidazole.......................................................90
6.2.4 Synthesis of 8-trimethylsilyloxyquinoline..............................................91
6.3 General procedures.......................................................................................91
6.3.1 Hydroalumination of alkynes .................................................................91
6.3.2 Synthesis of unsolvated dialkyl alk-1-ynyl alanes..................................92
6.3.3 Synthesis of alk-1-enyl sulfoxides via aluminum sulfinates ..................92
6.3.4 Synthesis of aryl alk-1-enyl sulfoxides using pyridinated organo
alanes ......................................................................................................92
6.3.5 Synthesis of unsaturated sulfoxides from unsolvated alanes and
benzenesulfinyl chloride in the presence of Ph3PO................................93
6.3.6 Synthesis of alk-1-enyl sulfones from sulfonyl chlorides and
pyridine-coordinated alanes in the presence of Ph3PO...........................93
6.3.7 Synthesis of alk-1-enyl sulfones using sulfonyl chloride-pyridine
complexes and uncomplexed alanes.......................................................93
6.3.8 Synthesis of alk-1-enyl sulfones using sulfonyl chloride-pyridine
complexes and uncomplexed alanes in the presence of CuCl ................94
6.3.9 Synthesis of unsaturated sulfones using sulfonyl chloride-pyridine
complexes and Grignard reagents...........................................................94
vi

6.3.10 Synthesis of alkenylated 2H-dihydropyridine and 2Hdihydroisoquinoline
derivatives ............................................................. 94
6.3.11 Cyclization of 1-(2-bromoacetyl)-2-(hex-1-enyl)-8trimethylsilyloxy-2H-dihydroquinoline
................................................. 95
6.4 Characterization of the products synthesized .............................................. 96
6.4.1 Alk-1-enyl and alk-1-ynyl sulfoxides .................................................... 96
6.4.2 Unsaturated sulfones ............................................................................ 101
6.4.3 Dihydropyridine and dihydroquinoline derivatives ............................. 105
6.4.4 NMR studies of di-i-butyl hex-1-enyl alane derivatives...................... 110
Bibliography ........................................................................................................... 113
vii

Introduction
Sulfone and sulfoxide functional groups are useful auxiliaries in organic
synthesis, even though they are seldom present in the target products; their use in
synthesis could at a first sight seem to be plagued by low atom economy, since
these groups are usually removed at some intermediate stage. However, their
utility in synthesis is enough to overcome this limitation in many cases.
α,β-Unsaturated sulfones are widely employed as key intermediates in organic
chemistry, due to the excellent stereoelectronic control on proximal and remote
reaction centers. Although the sulfone functional group is seldom found in the
target molecule, synthetic pathways can often be simplified by its use; for a few
selected examples one may cite the synthesis of L(-)-Prostaglandin E2 1 and of
some other natural products. 2 In addition to their directing effects, sulfones can be
easily converted to other functional groups. This important feature of the
chemistry of sulfones has been extensively reviewed, 3 and only a few among the
most useful transformations are mentioned here. It is worth citing the substitution
reaction with aryl Grignard reagents, 4 lithium acetylides or nucleophiles in the
presence of palladium catalysts, 5,6 conversion into α-ketols, 7 reduction to
hydrocarbons, addition of their α-carbanions to carbonyl compounds and
subsequent elimination (Julia reaction), 8,9 reduction with lithium-naphthalenide
and trapping with carbonyl compounds, 10 olefination, 11 reduction to sulfides 12
(Scheme 1).
R
R'
R''
R'''
R
R
R'
H
1) BuLi
O
2)
R'' R'''
3) H3O +
R'
Ar
Na/Hg
ArMgBr, Ni cat
R
R'
SO 2Ar
1)BuLi
2)(TMSO) 2
R''
AlMe 2
Scheme 1: Some reactions performed with the sulfone functional group
R'
R
Nu -
R'
Pd cat
R
O
R
R''
R'
Nu
1

The reactivity of sulfoxides resembles under many aspects that of sulfones, and
it is possible to easily remove this functional group also, when necessary. Among
the transformations that the sulfoxide functional group can undergo, some of the
most important ones are the modified Julia 13 and Julia-Lythgoe 11 olefinations, the
Pummerer reaction, 14,15 reduction with Al/Hg, 16 and thermal fragmentation. 17
The most interesting feature of sulfoxides, however, is constituted by the
stereogenicity of the sulfur center, which makes them an important tool in
asymmetric synthesis. 18,19,20 The stereogenic sulfur center can exercise a great
level of stereoelectronic control. 21,22 The above mentioned features of stereogenic
sulfur prompted the development of new synthetic routes to these derivatives, in
order to further expand their role as auxiliaries in diastereo- and enantioselective
reactions.
Many methodologies to prepare unsaturated sulfur derivatives have been
reported in the literature; a general overview of the most important approaches is
reported in Chapter 1. However, there is always room for new approaches
possessing the requisites of being simple to execute, high-yielding, and of general
applicability.
The aim of this work was to develop new approaches which could afford
unsaturated sulfones and sulfoxides through a practical procedure. In this context,
the peculiar reactivity of dialkyl alkenyl alanes was of great interest; it has been in
fact shown that these reagents efficiently and often selectively transfer the
unsaturated moiety, preferentially over the two alkyl residues. This fact rendered
interesting to study their applicability to the synthesis of sulfoxides and sulfones;
the results obtained in this study are reported in Chapters 2 and 3.
2

Part I
Literature overview

Chapter 1
Synthesis of alk-1-enyl sulfones and
sulfoxides: state of the art
1.1 Introduction
In the past few decades unsaturated sulfones and sulfoxides have been widely
employed as useful intermediates in organic synthesis. Sulfones display their
synthetic potential in a wide range of transformations, 3,4,5,23,24,25,26,27,28,29,30,31
which are particularly useful due to the large stereoelectronic control this
functional group can exert. 32,33,34,35,36,37,38,39 These characteristics have led to the
description of sulfones as chemical chameleons, 40 are due to their ability to
stabilize adjacent carbanions and to be displaced by nucleophiles.
The chemistry of unsaturated sulfoxides is characterized by diverse and
interesting reactivity, 41,42,43 and these compounds have proven to be extremely
valuable intermediates in organic synthesis. Polarization of the unsaturated bond
by the sulfone and the sulfoxide functional group allows a large number of
chemical transformations. Moreover, sulfoxides show their full potential in the
field of asymmetric synthesis. It is well known that chiral sulfoxides can exert a
great level of stereochemical control on adjacent transformations. 44,45 This feature
has contributed to their use as chiral building blocks in the synthesis of natural
and bioactive compounds. 21 A great deal of attention has been paid to the
development of efficient synthetic approaches to sulfones and sulfoxides: the most
widespread methodologies will be discussed later in this chapter. Given the scope
5

of this thesis work, the analysis of the literature focus on the synthesis of achiral
compounds.
1.2 Synthesis of alk-1-enyl sulfones
As stated in the introduction to this chapter, synthesis of unsaturated sulfones
has been widely investigated and reviewed 2,46 during the past few decades. Due to
the chemical versatility of the sulfone moiety, different synthetic approaches have
been developed, depending on the particular feature to be considered. The
possible pathways will be here divided in four main cathegories, depending on the
reaction site considered:
1. Synthesis from other sulfur derivatives (including oxidative routes)
2. Formation of new C-S bonds
3. Elimination of good leaving groups in position β to the sulfur atom
(including addition/elimination sequences)
4. Condensation reactions
It will be clear from the following sections that the first approach does not
provide a general approach to sulfones, because different sulfur derivatives, (e.g.
sulfides or acetylenic sulfoxides) which are necessary for those synthesis, are
difficult to prepare with broad generality and regioselectivity. On the other hand,
many of the reported approaches often presents remarkable stereoselectivity
problems and are useful in the synthesis of sulfones from conformationally fixed
alkenes. As it will be shown, one of the most promising and versatile fields in the
synthesis of sulfones is the direct formation of the C-S bond, which will be the
topic of this thesis work.
1.2.1 Synthesis from other sulfur derivatives
In this section attention will be focused on the synthesis of sulfones which do
not involve formation of new C-S bonds, and can be roughly divided into two
classes: oxidative routes starting from sulfides and non-oxidative routes, most of
which employ alkynyl sulfones as starting materials. Due to their importance, a
significant part of this section will deal with oxidative routes, whereas approaches
starting from different sulfones will be discussed in the last part; particular
attention will be devoted to the partial reduction of acetylenic sulfones.
6 Chapter 1

Oxidative routes to sulfones
Oxidation of sulfides and sulfoxides represents the most general and widely
employed synthetic pathway for the synthesis of sulfones, 47 and much work 48,49
has been done to provide efficient and selective protocols amenable to the
synthesis of unsaturated sulfones. The main problem with this strategy, as long as
alk-1-enyl sulfones are concerned, is the possibility of oxidation of the double
bond. Sulfoxides are intermediates in the oxidation process of sulfides to sulfones;
for this reason, oxidations to sulfoxides and sulfones are usually studied
toghether. It is often sufficient to add just one molar equivalent of oxidizing agent
to a sulfide in order to obtain the sulfoxide in high yields; as reported in Section
1.3.1, many oxidizing systems used are the same both for sulfones and
sulfoxides. 50
It has been known for a long time 51 that acetylenic sulfides can be efficiently
and simply oxidized to the corresponding sulfones in good yields by treatment
with hydrogen peroxide in acetic acid. Many common oxidizing agents, such mchloroperbenzoic
acid (MCPBA), have been successfully employed in the
oxidation of acetylenic sulfides to sulfones. 52,53 Perbenzoic acid 54 , Oxone 55 and
other oxidizing agents 50 are widely employed in the preparation of acetylenic
sulfones; the same protocol is applicable to vinyl sulfides. As reported in Scheme
1.1, fluorinated vinyl sulfides react smoothly with MCPBA 56 affording
difluoro alk-1-enyl sulfones, in good yields (77-88%) under mild reaction
conditions.
F
O O F
S
F
MCPBA, CH2Cl2, r.t.
S
F
R
R
77-88%
R= Me, Et, n-Pr, c-Hex, Ph
Scheme 1.1: Oxidation of alk-1-enyl sulfides to sulfones with MCPBA
Recent oxidative approaches to sulfones have sought to find more
chemoselective or more environmentally friendly systems. The periodic acid/CrO3
couple was shown to be superior to other systems in the preparation of sulfones,
for what concerns selectivity and handling. 57 Oxidations processes performed
whith these reagents tolerate a wide range of functionalities (e.g. alcohols,
aldehydes, nitriles), and are very valuable for the synthesis of functionalyzed
unsaturated sulfones. Oxidation with Oxone, described for the first time in
1981, 58 has been later modified by using tetrabutylammonium-Oxone system
Synthesis of alk-1-enyl sulfones and sulfoxides: state of the art 7

(TBA-Oxone) 59 . Contrarily to the original procedure, the improved procedure
does not require the use of water or ethanol and affords alk-1-enyl sulfones in
good yields under anhydrous conditions. This protocol appears to be very
chemoselective, and although slower than the corresponding oxidation with
Oxone, 55 it constitutes a valuable oxidizing system.
S
O O
F20TPPFe (0.1-0.25%)
R S
H2O2 (2 equiv.), EtOH
r.t., 15min
93-94%
R=H, Ph
F20TPPFe=iron tetrakis-(pentafluorophenyl)porphyrin
Scheme 1.2: Oxidation of alk-1-enyl sulfides to the corresponding sulfones using H2O2 and
F20TPPFe as catalyst
The long-time known oxidation with hydrogen peroxide has been extensively
studied, and a new catalyst based on a Fe-porphyrine complex has been recently 60
introduced (Scheme 1.2). The reaction is fast, high-yielding, and affords sulfones
or sulfoxides nearly selectively depending on the stoichiometric ratio between
H2O2 and the sulfide. Conjugated or isolated double bonds are unaffected.
BnO
p-Tol
S
O
OH
OMe
MMPP
BnO
MeOH, r.t., 2-3h S O OMe
p-Tol
O
O
8 Chapter 1
OH
R
MsCl, Py
BnO
O
0 o O
C, 12-24h O S
Tol-p
OMe
Scheme 1.3: Oxidation of sulfides to the corresponding sulfones in the synthesis of vinyl
sulfone-modified pent-2-enofuranosides
Magnesium monoperoxyphtalate (MMPP) has been recently 61 reported to
oxidize sulfides to sulfones in the synthesis of anomerically pure vinyl sulfonemodified
pent-2-enofuranosides and hex-2-enopyranosides, without degradation
of the other functional groups present in the molecule. The β-hydroxy sulfone
affords the vinyl derivative after mesylation and base-induced elimination. This
reaction pathway is reported in Scheme 1.3.
Non-oxidative routes to sulfones
Many interesting approaches to structurally complex alkenyl sulfones hinge on
the chemistry of unsaturated sulfones themselves. In this context, vinyl and
acetylenic sulfones are versatile building blocks; furthermore vinyl sulfones,

whose preparation is rather trivial, are often commercially available, whereas
acetylenic sulfones are readily prepared, as discussed later in this chapter.
Cross-metathesis has recently been used in the synthesis of sulfones, starting
from vinyl sulfone and the appropriate alkenes. 62 The reaction shows a good
functional group tolerance and complete E stereoselectivity. The major drawback
is the incompatibility of many metathesis catalysts with the sulfone functional
group. Moreover it seems that there is no general catalyst suitable for all
substrates, and choice of the appropriate catalyst is then rather empirical. An
example that illustrates the synthetic potential of the reaction is shown in Scheme
1.4.
Ph S
O O
+
Ph "Ru"
R
CH2Cl2, rfx., 3-24h Ph S
O O
R= OH, OTBS 53-71%
Scheme 1.4: Synthesis of alk-1-enyl sulfones by cross-methathesis reaction between vinyl
sulfone and alkenes
This protocol is not amenable to the synthesis of alk-1-enyl sulfoxides; it has
been reported that the sulfoxide functional group poisons the catalyst.
Arylboronic acids easily react with vinyl sulfones in a Mizoroki–Heck type
reaction with Pd(OAc)2 as catalyst. The reaction proceeds in good yields only in
the presence of oxygen. 63 Vinyl and alkyl boronic acids are completely
unreactive. This method is interesting because it makes it possible to transfer βaryl
substituted alkenyl chains, regardless of the nature of substituents on the
aromatic ring; on the other hand, the reaction fails when an alkyl-substituted
alkenyl chain is transferred. The reaction is shown in Scheme 1.5.
Ar B(OH) 2
+
O O
S
Ph
Pd(OAc) 2 (10 mol%)
Na 2CO 3 (2 equiv.)
Synthesis of alk-1-enyl sulfones and sulfoxides: state of the art 9
Ph
O O
S
DMF, O2, 60 oC Ar Ph
Ar= p-Tol, m-NO 2Ph, p-BrPh, p-MeOPh
70-84%
Scheme 1.5: Synthesis of alk-1-enyl sulfones by reaction of a vinyl sulfone with arylboronic
acids
The triple bond of aryl sulfonyl acetylenes is susceptible to the attack of carbon
nucleophiles. Depending on the nature of the organometallic reagent and on the
stoichiometric ratio between reagents, it is possible to obtain alkenyl or alkyl
R

sulfones. With appropriate choice of the organometallic system, it is possible to
transfer a wide range of residues.
Many organometallic reagents have been used in the preparation of alkenyl
sulfones by this approach: cuprates give the most interesting results. Addition of
organocopper derivatives can be stereoselective depending on the nature of the
reagent. 64 Grignard reagents in the presence of CuBr (Scheme 1.6, reaction a) 65
easily react with alkynyl sulfoxides, affording the addition products in low
stereoselectivity; cuprates (Scheme 1.6, reactions b and c) 64,66,67 and dialkyl zinc,
in the presence of copper salts (Scheme 1.6, reaction d), 67 give the desired
products in variable yields and stereochemical purities. Grignard reagents and
organolithium compounds, in the absence of catalysts, often react by a different
pathway displacing the sulfonyl group. 68
a)
b)
c)
d)
Me 3SiO
EtMgBr
R
Ph
ZnEt 2
+
+
+
Me
O O
S
Ph
R'
Me
O O
S
Ph
O O
S
Ph
CuBr, THF
-78 o C
1) (Me3SiCH2) 2CuMgCl
2) Allyl bromide
O O
S
Ph
Cu(BF 4) 2
Me 3Si
1) Et2O, -70 o Cu(BF4) 2
C, 30min
2) MeOH
O O
S
Ph
80%
10 Chapter 1
Ph
Me
Me
90%
CH 2Cl 2, 25 o C, 2-3h
H 2O (1.5 equiv.), DMAD (1 equiv.)
R= i-Pr, t-Bu, α-Fur
R''= CH3, CH(OH)CH(CH3) O O
S
Ph
Me O O
Et
S
Ph
82%
R O
Scheme 1.6: Addition of organometallic derivatives to acetylenic sulfones
R'
41-70%
O O
S
Ph
Cp2Zr(H)Cl (Schwartz’s reagent) reacts with the triple bond of acetylenic
sulfones, affording the (Z)-alkenyl zirconium derivatives in excellent yields and
nearly complete regio- and stereoselectivity; the resulting intermediates have
proven to be valuable in the synthesis of new sulfur-containing compounds.
Hydrolysis of the alkenyl zirconium derivative leads to the (E)-alk-1-enyl sulfone.

When electrophiles other than water are added, substituted alkenyl sulfones can be
obtained 69 (Scheme 1.7). The stereoselectivity of the hydrozirconation process is
complete for aryl-substituted alkynyl sulfones affording the (E)-isomer, whereas
alkyl substituted sulfones often give poorer results, leading to mixtures of E and Z
isomer.
Ph
O O
S
Ar
2) E +
1) Cp2Zr(H)Cl, r.t., 5min
O O
S
Ar
Synthesis of alk-1-enyl sulfones and sulfoxides: state of the art 11
Ph
E
51-70%
Scheme 1.7: Addition of Schwartz’s reagent to acetylenic sulfones and products arising after
quenching with electrophiles
The β-zirconyl sulfone intermediate can also react with different reaction
partners, usually in the presence of copper halides or other transition metal
catalysts; this feature can be used in the synthesis of more synthetically interesting
compounds, 70 as reported in Scheme 1.8. The reactivity of alkenyl zirconium
intermediates opens a practical route to sulfonyl enynes, which are obtained by
coupling with alkynyl halides in the presence of copper chloride.
Ph
O O
S
Ph
Cp 2Zr(H)Cl
r.t., 5min
Cp 2ClZr
Ph
O O
S
Ph
Allyl bromide
Pd(PPh3) 4
R
O
R Cl
CuBr
CuCl
Scheme 1.8: Reactions of β-zirconyl sulfone derivatives
Br
Ph
O O
S
Ph
51%
R O
O O
Ph
S
65-70%
Ph
Ph
R
O O
S
Ph
62-70%
Addition of Mg phenylselenate to acetylenic sulfones provides very versatile
intermediates which can further react with carbonyl compounds (Scheme 1.9).
The reported reactions are typical of organomagnesium derivatives. 71,72
Unfortunately, formation of the bimetallic alkenyl sulfur derivative is not
stereoselective, leading to a mixture of E and Z products. Furthermore, the two

isomers tend to equilibrate quickly to a 1/1 ratio. This leads, upon addition of an
aldehyde, to the formation of a mixture of stereoisomers.
Ph
O O
S
Ph
PhSeMgBr
-20 o C, 5min
PhSe
Ph
O O
S
Ph
MgBr
12 Chapter 1
Cl
H 2O
O
H
PhSe
Ph
PhSe O O
Ph
S
Ph
H
76%
HO
O O
S
Ph
75%
Scheme 1.9: Addition of PhSeMgBr to acetylenic sulfones and subsequent reactions
The protocol has been improved by mixing the aldehyde and the acetylenic
sulfone in the presence of Mg phenylselenate. Under these conditions, the
aldehyde efficiently traps the organomagnesium intermediate and gives the (Z)isomer
of the secondary alcohol as the sole product (Scheme 1.10).
Ph
O O
O
S
Ph + H +
Cl
PhSeMgBr
THF/CH 2Cl 2
-20 o C, 5min
PhSe
Ph
HO
O O
S
Ph
Scheme 1.10: Addition of PhSeMgBr to acetylenic sulfones in the presence of aldehydes
Hydrogenation of acetylenic sulfones with the Lindlar catalyst gives (Z)-alk-1enyl
sulfones or unreacted starting material, depending on reaction conditions. 73,74
Dry hydrogen bromide and chloride add chemo- and regioselectively to sulfonyl
acetylenes, in the presence of copper halides, affording β-halo alkenyl sulfones in
good yields (Scheme 1.11). 50
H
O O
S
Ph
HX, CuX
X= Cl, Br
X
O O
S
Ph
75%
Scheme 1.11: Addition of dry hydrogen halides to benzenesulfonyl acetylene
β-Iodo triflones, obtained by reaction of lithium iodide in glacial acetic acid
with benzenesulfonyl acetylene, have been further modified to dienyl triflones 75
Cl
Cl

y Stille coupling. The ability of alkynyl sulfones to easily undergo radical
additions opens a synthetically useful route to alk-1-enyl sulfones. In addition, it
was reported that in the presence of the Lewis acid Cl2AlEt, alkenes and alkynyl
sulfones undergo an ene reaction to yield alkenyl sulfones 76 (Scheme 1.12). The
reaction is reported to be quite general for cylic and acyclic alkenes, although
highly variable yields (20-89%) are obtained.
+
H
O O
S
Ph
Et 2AlCl
O O
S
Ph
Scheme 1.12: Ene reaction of alkenes with acetylenic sulfone in the presence of Lewis acids
1.2.2 Sulfones via formation of new C-S bonds
Formation of sulfones via direct formation of C-S bonds is a powerful tool in
the synthesis of alk-1-enyl sulfones, although somewhat less employed than the
methods described in the previous section. The interesting feature of this approach
is the possibility to obtain target products with a limited number of synthetic
steps, starting from commercially available reagents. Moreover, in many
approaches the double bond stereochemistry of the starting reagents is already
defined, and high degrees of stereospecificity can be achieved. It is possible to
classify the methodologies resulting in the formation of C-S bonds into two main
groups:
Synthesis of alk-1-enyl sulfones and sulfoxides: state of the art 13
66%
1. Nucleophilic substitution at sulfonyl sulfur by alkenyl derivatives
2. Addition of sulfur derivatives onto alkynes
The first approach involves the use of organometallic reagents, which react
either in the presence of transition metal catalysts or by radical mechanism,
whereas the second one mostly involves radical reactions of sulfur derivatives.
The analysis of synthetic methods will be divided into two parts according to the
above classification.
Nucleophilic substitution at sulfonyl sulfur with alkenyl derivatives
The formation of new C-S bonds to obtain unsaturated sulfones has been
widely studied. It was claimed that aryl sulfonyl chlorides undergo a crosscoupling
reaction with alkenyl stannanes in the presence of palladium complexes
as catalysts. 77 The reaction (Scheme 1.13) seems to be general for many aryl

sulfonyl chlorides and alkenyl stannanes. Evidence for the presence of a radical
mechanism 78 is provided by the otherwise inexplicable lack of reactivity of
tributyl vinyl stannane, which is rationalized with the poor stability of the vinyl
radical.
O O
R S Cl
+
n-Bu 3Sn
R'
Pd(PPh3) 4
70 oC, 15min R S
O O
60-90%
R=Ar, Me
14 Chapter 1
R'
+ n-Bu 3SnCl
Scheme 1.13: Reaction between alkenyl stannanes and sulfonyl chlorides in the presence of
palladium catalyst
Moreover, it was recently reported 79,80 that sulfonyl chlorides oxidatively add
to palladium or nickel catalysts and the resulting species undergo desulfonylation
by SO2 elimination. 81
Whatever mechanism is involved, the reaction is interesting in consideration of
the wide availability of sulfonyl chlorides, as well as the simple synthetic
procedure and good yields. The need for preparing alkenyl stannanes constitutes a
limitation for this procedure.
Alkenyl zirconium derivatives have been claimed 82 to react with aryl or alkyl
sulfonyl chlorides in the absence of catalyst, affording alkenyl sulfones under
mild reaction conditions and short reaction times. As shown in Scheme 1.14,
hydrozirconation and the subsequent coupling reaction are both stereoselective,
and the pure (E)-isomer is recovered in satisfactory to good yields.
Alkenylzirconium derivatives are compatible with a large number of functional
groups, and this feature makes the reported method suitable for the preparation of
functionalized sulfones.
R
Cp2Zr(H)Cl, THF
30min-1h, r.t. ClCp2Zr R
R=Ar, Alk R'=Ar, Alk
R'SO2Cl 1h30min-3h, 40 oC R' S
O O
50-78%
Scheme 1.14: Alk-1-enyl sulfones starting from organozirconium derivatives and sulfonyl
chlorides
The drawback of this synthetic approach is the fact that zirconium derivatives
are highly expensive, and their use is thus confined to the preparation of sulfones
on a small scale.
R

A recent approach reported by Fuchs et al. 75 allows the synthesis of triflones by
nucleophilic attack of acetylides on triflic anhydride. Addition of lithium
acetylides to triflic anhydride provides the triflone in very good yields (75-87%).
The addition of triflic anhydride to the acetylide causes the formation of
substantial amounts of diacetylenic byproducts, arising from the substitution of
the triflone moiety by the organometallic reagents. This method, shown in
Scheme 1.15, gives easy access to a diverse group of alkynyl triflones. Further
reaction with lithium iodide and acetic acid in THF, under mild conditions,
affords β-iodo alkenyl triflones in very good yields.
R
Li
+ (CF3SO2) 2O
Et 2O
-78 o C, 30min
R
O O
S
75-87%
LiI, AcOH
CF3 THF, 0 oC, 15min
O O
S
Synthesis of alk-1-enyl sulfones and sulfoxides: state of the art 15
R
I
93-95%
Scheme 1.15: Synthesis of alkynyl triflones starting from triflic anhydride and lithium
acetylides
Palladium-catalyzed reactions can be used in the synthesis of alkenyl sulfones
from alkenyl triflates and sodium sulfinates. According to the proposed
mechanism, the triflate adds oxidatively to the palladium catalyst. Sodium aryl
sulfinate substitutes the triflate ligand on the palladium center. Reductive
elimination affords the alkenyl sulfone. This method has been succesfully applied
to the synthesis of many cyclic aryl alkenyl sulfones in moderate to good yields; 83
an example is reported in Scheme 1.16.
OTf
+
NaO 2S
Me
Pd 2(dba) 3
Xantphos
Cs 2CO 3
toluene
60 o C
S
O O
Scheme 1.16: Synthesis of alkenyl sulfones from alkenyl triflates and sodium sulfinates using
a Pd catalyst
Copper(II) sulfinates can be prepared from sulfinic acids and copper carbonate,
or used in situ, reacting smoothly under sonochemical conditions with alkynyl
halides, and affording alkynyl sulfones in moderate to good yields. Acetylenic
iodides give very good yields of the sulfone, whereas the use of bromides leads to
substantial amounts of byproducts; as a consequence, the yields of the sulfone
drastically drop. Yields are also dependent on the nature of the acetylenic system
used. In particular, phenylacetylene gives the best results, whereas alkyl-
Me
CF 3

substituted acetylenes react in poor yields. 84 The reaction is shown in Scheme
1.17.
Ar
I
+ (Ar'SO2) 2Cu
THF
Sonication
O O
S
Ar'
16 Chapter 1
Ar
49-94%
Scheme 1.17: Synthesis of alkynyl sulfones from alkynyl iodides and copper sulfinates under
sonochemical conditions
Although not widely used, alkenyl mercury halides react with sulfinates under
photochemical conditions 85 affording the corresponding alkenyl sulfones in
moderate to good yields, with complete stereospecificity. The reaction works well
with both aryl and alkyl sulfinates, and substitution on the alkene is tolerated.
Vinyl mercurials which are sterically hindered at the α position to the metal atom
(R’’’, Scheme 1.18) fail to afford the coupling products. Aryl and alkyl mercury
halides do not give any product with this process.
R SO2Na + R'
R''
HgX
R'''
hv
15-40h
R S
O O
R'''
R'
31-85%
Scheme 1.18: Synthesis of alkenyl sulfones by photoinduced reaction between alkenyl
mercury halides and sodium sulfinates
Addition of sulfur derivatives onto alkynes
This approach is based on the tendency of sulfur derivatives to react under
radical conditions. Sulfonyl radicals, generated by photoinduced reaction starting
from aryl sulfonyl iodides, stereoselectively add to alkynes, 86 affording (E)-β-iodo
alkenyl sulfones in good yields (Scheme 1.19).
Me
O
O
S I
+
R
R'
hv
Et2O O O
S
69-87%
Scheme 1.19: Synthesis of β-iodo alkenyl sulfones by photoinduced reaction of sulfonyl
iodides and alkynes
I
R
R'
R''
Me

Addition of sulfonyl chlorides and bromides to acetylenes in the presence of
copper (II) chloride affords α-chloro alkenyl sulfones. This reaction gives
mixtures of cis and trans products via a radical pathway; 87,88 studies have been
performed to improve the stereoselectivity. 89,90 In the absence of light, sulfonyl
bromides selectively afford the trans product. 91
Sulfonyl chlorides add to terminal and internal alkynes, in the presence of
cuprous chloride, affording β-chloro vinyl sulfones. 92 Yields are, however, modest
and variable (10-58%), and the reaction is not completely stereoselective,
affording E/Z mixtures where the major isomer depends on the polarity of the
solvent.
Free-radical selenosulfonylation of acetylenes is a useful synthetic route to βselenosubstituted
vinyl sulfones, 93,94,95 which are in turn readily susceptible to
further transformations. 96 An example of the applicability of selenosulfonylation
followed by substitution and applied to the synthesis of alkenyl sulfones is
reported in Scheme 1.20.
O
O
Ar S SePh
+
R
R'
AIBN
PhSe
52-94%
O O
S
Ar
Synthesis of alk-1-enyl sulfones and sulfoxides: state of the art 17
R
R'
R''CuSePhLi
R''
R
O O
S
Ar
R'
52-94%
Scheme 1.20: Selenosulfonation of acetylenes under radical conditions and substitution of
selenide with copper reagents
Subsequent extensions have been performed on enynes. 97 The competition
between 1,2 and 1,4 addition causes a remarkable variability of yields, which
strongly depend on the nature of the enyne employed; moreover stereoselectivity
is, in most cases, incomplete.

Ph
SeR 2
a)
b)
PhSO2Na R'OH
3h
PhSO2H i-PrOH
3h
R 2Se
O O
S
Ph
RO O O
S
Ph
Ph
60-92%
R2Se O O
S
Ph
Ph
R
O O
S
Ph
Ph
2 3
76-79%
73-86%
Scheme 1.21: Addition of sulfinyl derivatives to alkynyl selenonium salts and further
modification of the selenonium intermediate.
Use of organoselenium species in the synthesis of alk-1-enylsulfones is not
limited to the above reported reactions. Organoselenium species have been used 98
in the synthesis of β-functionalyzed vinyl sulfones. In this process, it has been
shown that alkynyl selenonium salt can react with sodium benzenesulfinate.
Intermediate 1 (Scheme 1.21, path a) is formed in protic solvents, and subsequent
addition of alkoxide stereoselectively affords the β-alkoxy substituted alkenyl
sulfones. When sulfinic acid is used in the first step, intermediate 2 is formed,
which can be reacted with different nucleophiles (Scheme 1.21, path b). In the
latter case, the use of alkynyllithium derivatives leads to enyne sulfones 3 in good
yield (73-86%).
1.2.3 Sulfones via addition-elimination of good leaving groups
This approach represents one of the best known methods for the synthesis of
alk-1-enyl sulfones, and has been reviewed in the case of cycloalkenyl sulfones. 2
The most common strategies are chlorosulfenylation/oxidation/elimination 99,100 or
chlorosulfonylation/elimination sequences, whose general pathways are depicted
in Scheme 1.22.
18 Chapter 1
H
Ph
1
RO -
Li
R

R
R'
ArSX
R
R'
X
ArSO 2X
SAr
RCO 3 H
Synthesis of alk-1-enyl sulfones and sulfoxides: state of the art 19
R
R'
X
SO 2Ar
elim
X= Hal,OR
R
R' SO 2Ar
Scheme 1.22: Common strategies for the synthesis of alkenyl sulfones from stereodefined
olefins
These approaches have remarkable synthetic applicability when the starting
alkene is conformationally fixed and hence the stereochemistry of the resulting
sulfone is defined. This feature makes the reported approach the method of choice
for the synthesis of cycloalkenyl sulfones, whereas its applicability decreases
when applied to acyclic alkenes: in this case E/Z mixtures are often produced.
Additions of sulfonyl chlorides to conformationally defined alkenes, 101102
dienes 103 and trienes in the presence of copper chloride as catalyst opens up a new
route to alkenyl, dienyl and trienyl sulfones, which can be obtained from the
addition products by simple treatment with triethylamine at room temperature
(Scheme 1.23); yields are modest. 90 As reported, this strategy has been applied to
the synthesis of acyclic dienyl sulfones, but stereochemical problems arise and
complex E/Z mixtures are formed. 102
+
p-Tol S O O CuCl
Cl
O
Tol-p
O S
Cl
44%
Et 3N
C 6H 6, r.t., 2h
S Tol-p
O
O
94%
Scheme 1.23: Copper-catalyzed addition of sulfonyl chlorides to dienes followed by
elimination
Addition of sulfonyl chlorides to the double bond in the presence of copper (I)
or (II) salts as catalysts occurs when silyl ethylene is used. 88 In this case
elimination of hydrochloric acid with triethylamine affords the pure (E)-isomer in
acceptable yields (70-74%). β-Acetoxy alkyl sulfones are interesting starting
materials for the synthesis of alkenyl sulfones by means of elimination reactions. 25

Radical addition/elimination sequences are valuable, considering ability of the
sulfur atom to stabilize adjacent radicals. As reported in Section 1.2.2 addition to
acetylenes can be exploited in a direct synthesis of alkenyl sulfones. Differently
from what observed in the reaction with acetylenes, sulfonyl iodides are
completely unreactive towards alkenes. Addition of a catalytic amount of copper
(II) chloride causes the rapid formation of the β-iodo alkyl sulfone, as shown in
Scheme 1.24. Upon basic treatment these intermediates can evolve to alkenyl
sulfones which are isolated in good yields (50-75%). 104 Given the fact that
sulfonyl iodides are rather unstable, these intermediates are prepeared
immediately prior to their use or stored for short times at low temperature.
O O
S
Ar I
+
R
R'
CuCl 2, Et 3NI
CH 3CN
0-40 o C, 2-4h
I O O
S
R Ar
R'
66-95%
Et3N C6H6, r.t.
O O
S
R Ar
R'
76-90%
Scheme 1.24: Synthesis of alk-1-enyl sulfones by addition of sulfonyl iodide to alkenes
followed by base-induced elimination
A closely related radical addition-elimination sequence, which affords
unsaturated sulfones in good yields, has been recently reported. 105 In this
sequence (Scheme 1.25) styrenes react with sodium sulfinate, cerium ammonium
nitrate (CAN) and sodium iodide, giving the products in good yields. Linear
alkenes afford vinyl sulfones in similar yields, while cyclic alkenes give poor
results. The proposed mechanism involves the addition of the sulfinyl radical to
the alkene, followed by reaction with iodine and subsequent in situ HI elimination
to give the unsaturated sulfone; CAN may have the role of radical initiator.
p-Tol
SO 2Na
+
R
CAN, NaI
CH3CN 0 oC, 45min
63-87%
20 Chapter 1
R
O O
S
Tol-p
Scheme 1.25: Synthesis of alk-1-enyl sulfones by CAN-mediated reaction of sodium sulfinate
with alkenes
β-Sulfonyl acetals undergo stereospecific elimination in the presence of nbutyllithium,
to afford intermediate 4 (Scheme 1.26). In the presence of two molar
equivalents of n-butyllithium, compound 4 is regioselectively lithiated at the αposition
vs. the sulfonyl group. Further reaction with suitable electrophiles can
give a variety of vinyl sulfones in acceptable to good yields (Scheme 1.26). 106

O O OMe n-BuLi
Ph
S
OMe
O O
1) n-BuLi
Ph
S
OMe
2) E +
O O
S
Ph
56-87%
Synthesis of alk-1-enyl sulfones and sulfoxides: state of the art 21
4
E
OMe
Scheme 1.26: Synthesis of trisubstituted alkenyl sulfones by reaction of β-sulfonyl acetal with
n-butyllithium and electrophiles
β-Hydroxy sulfones are useful precursors to alkenyl sulfones. Treatment with
MsCl and pyridine affords the alkenyl sulfones under mild conditions. This
approach has been employed in the synthesis of enantiomerically pure γ-hydroxy
vinyl sulfones. 107 The necessary β keto sulfones can be easily obtained by reaction
of α-lithiated alkyl sulfones with N-acyl-benzotriazoles. 108
Selenosulfonation of alkenes has been studied in order to achieve regio- and
stereospecific approaches to alk-1-enyl sulfones. It was found 109,110,111 that
selenosulfonates add to olefins at room temperature in the presence of boron
trifluoride or, at higher temperatures, in absence of catalyst. The resulting βseleno
sulfones can be converted to alk-1-enyl sulfones by simple treatment with
MCPBA followed by spontaneous selenoxide fragmentation, which affords
products in very good yields and excellent stereochemical purities. The whole
transformation is illustrated in Scheme 1.27.
O O
S
R SePh
+
.
R
R''
BF3 OEt2
CH2Cl2 R R'' O O
S
PhSe Ar
MCPBA
CH2Cl2, r.t. R
R'' O O
S
Ar
R' r.t., 18-27h
R'
R'
62-89%
77-100%
Scheme 1.27: Addition/elimination sequence of selenosulfonates and alkenes
Analogously to the selenosulfonation of alkenes, formation of sulfonyl mercury
compounds, followed by elimination, represents a good method for obtaining
alkenyl sulfones. It was reported 112 that sodium sulfinate adds stereoselectively
trans to alkenes in the presence of mercury (II) chloride. The reaction proceeds in
water at room temperature, and the resulting sulfonyl mercury derivatives 5 give
alkenyl sulfones via reaction with bromine and then with excess of triethylamine.

ArSO2Na + HgCl2 +
R
R'
R O O
H2O, r.t.
1) Br
S
2, C6H6, r.t.
24-46h ClHg Ar 2) Et3N (3 equiv.)
R'
73-96%
5
Scheme 1.28: Synthesis of alkenyl sulfones through sulfonyl mercury intermediates
O O
S
Ar
R'
59-84%
The process is shown in Scheme 1.28; overall yields in sulfones are acceptable.
Stereoselectivity is good only when the reaction is carried out on cyclic alkenes.
The extreme toxicity of organomercury compounds is a strong limitation to this
method.
1.2.4 Sulfones via condensation reactions
Condensation reactions are a widely employed and high-yielding pathway to
alk-1-enyl sulfones. In the past few decades attention was directed towards the use
of the Horner-Wittig reaction and the Knoevenagel condensation of aldehydes
with alkyl sulfones. The Horner-Wittig approach, starting from sulfonomethyl
phosphonates, was proposed as a practical route to alkenyl sulfones. The starting
material is lithiated at low temperatures and the resulting anion is then added to
the appropriate carbonyl derivative (Scheme 1.29). Unsaturated sulfones are thus
obtained, usually with excellent (E) stereochemical purities when aldehydes are
employed, 113 while the use of ketones often leads to isomeric mixtures.
O O O 1) BuLi
(EtO) 2P S
Ph 2)
O
22 Chapter 1
R 1
R 2
R 2
R 1
O O
S
Ph
72-97%
Scheme 1.29: Horner-Wittig approach to unsaturated sulfones starting from sulfonomethyl
phosphonates
The need to separately prepare alkyl sulfonyl phosphonates, which requires an
additional synthetic step, represents the main drawback of this approach. Efforts
have been devoted to the development of a one-pot Horner-Wittig reaction. Two
examples among the many procedures available will be briefly described here.
Sulfonyl fluorides had been used for the synthesis of sulfonyl-stabilized
methylenetriphenylphosphoranes. 114 Recently it has been reported that it is
possible to achieve, with an analogous process, the one-pot synthesis of alkenyl
sulfones. 115 Addition of the appropriate aldehyde to the anionic intermediate 6
(Scheme 1.30) leads to the desired product in reasonable yield; the
stereochemistry of products is usually E.
R

O
(EtO) 2P
R
1) LiHMDS (2 equiv.)
-78 o C
2)PhSO 2F
-78 o C to r.t.
O O O
(EtO) 2P S
Ph
R
6
O
R' H
-78 o 1)
C to r.t.
2) H2O Synthesis of alk-1-enyl sulfones and sulfoxides: state of the art 23
R'
R
O
S
52-75%
Scheme 1.30: Wittig-Horner approach to unsaturated sulfones by in situ formation of
sulfonomethyl phosphonate
α-Functionalized unsaturated sulfones can be obtained in good yields starting
from chloro- or methoxy-methyl phenyl sulfone (Scheme 1.31). 116 In this case,
when aromatic aldehydes are employed (R”=H), acetylenic sulfones can be
obtained in good yields by treatment of the intermediate alkenyl sulfone with t-
BuOK. Aliphatic aldehydes give complex mixtures of products under these
conditions. 117
O
Ph
O
S
X
1) BuLi (2 equiv.)
2) (EtO) 2P(O)Cl
-78 oC, 30min
O O O
Ph
S P(OEt) 2
X Li
X=Cl,OMe
O
R' R''
-78 o 1)
C to r.t.
2) H2O O
R' R''
-78 o 1)
C to r.t.
2) t-BuOK
R''=H
O
Ph
R'' O O
R'
S
Ph
X
69-85%
R'
O O
S
Ph
Scheme 1.31: Horner-Wittig approach to unsaturated sulfones by in situ formation of
substituted sulfonomethyl phosphonates
It was reported 118 that allyl sulfones can be lithiated and the resulting anion
condensed with aldehydes. Treatment of intermediate 7 with alkyl halides gives βalkoxy
sulfones 8, which afford dienyl sulfones upon base-catalyzed elimination
(Scheme 1.32). The choice of the conditions used for the base-promoted
elimination of the ethoxy group greatly influences both yields and stereochemical
purity of the dienyl sulfone. The elimination step proceeds in fairly good yields
(60-70%), and the process represents a valid synthetic route to dienyl sulfones,
which are usually obtained in remarkable stereoselectivity.

R
1)BuLi
2) R'CHO,
THF, -35 o O
O S
Ph
C
R
LiO R'
RO
O
R''X
S
Ph
O R
7 8
O
S O
Ph
Scheme 1.32: Reaction of lithiated allyl sulfones with aldehydes, subsequent addition of alkyl
halides and base-promoted formation of dienyl sulfones
Treatment of alkyl sulfones with EtMgBr, followed by reaction with prop-2ynal,
affords β keto sulfone 9 which, upon treatment with Tf2O-Hünig’s base,
gives the labile product 10 (Scheme 1.33). 119
O O
Me
S
Ar
1) EtMgBr, 0 oC O
R
H
2) PCC, CH 2Cl 2
R
24 Chapter 1
R'
Base
R
R'
O
S O
Ph
O
SO2Ar EtN(i-Pr) 2
(CF3SO2) 2O
-78
R SO2Ar 25-44%
oC 9 10
62-98%
Scheme 1.33: Synthesis of sulfonyl diynes by condensation of sulfonyl carbanions with
aldehydes and dehydration
1-Sulfonyl ethyl phosphonate has been recently reported to be a useful
precursor for the synthesis of trifluoromethylated enynyl sulfones in good yields.
The proposed synthesis involves deprotonation of the starting material with nbutyllithium,
reaction with trifluoroacetic anhydride and addition of acetylides to
the resulting carbonyl compound.
O
(EtO) 2P
O O
S
Ph
Me
1) BuLi
2) (CF3CO) 2O
O O O
(EtO) 2P S
Ph
O Me
CF 3
R
R
Li
MgBr
R
R
CF 3
57-76%
O O
S Ph
F3C Me
45-54%
O O
S
Me
Ph
Scheme 1.34: Synthesis of (E) and (Z) trifluoromethylated sulfonyl enynes by reaction of
organometallic derivatives with trifluoroacetylated sulfonyl phosphonates

The nature of the alkynylating agent (organolithium or Grignard reagents)
influences the stereochemistry of the product (Scheme 1.34), making it possible to
obtain stereoselectively (E) or (Z)-enynyl sulfones. 120
Knoevenagel condensation of aryl aldehydes with sulfones has proven to be an
effective method for the synthesis of alk-1-enyl sulfones. The reaction is shown in
a general form in Scheme 1.35 and many different substrates were studied in order
to explore its scope.
O O
S
R
Y
+
R 1
O
R 2
Y R 2
Synthesis of alk-1-enyl sulfones and sulfoxides: state of the art 25
R
O
S O
Scheme 1.35: Synthesis of alkenyl sulfones by Knoevenagel condensation
The most widespread methods involve the presence of carbonyl compounds, 121
carboxylic groups, 122,123 or esters 124 in the starting sulfone (Y in Scheme 1.35).
The major problem in this approach is constituted by the variable stereochemistry
of the products, which is dependent on the steric hindrance of the alkenes;
furthermore, the yields are not excellent. Much effort has been expended in order
to optimize this reaction, and recently a very effective catalyst, Na2CaP2O7, has
been reported; 125 it allows the Knoevenagel reaction between 2-
(phenylsulfonyl)acetonitrile and aromatic aldehydes, affording alkenyl sulfones in
50-94% yield.
1.3 Synthesis of alk-1-enyl sulfoxides
The synthesis of unsaturated sulfoxides, both in their racemic and optically
active form, has been extensively reviewed. 21,45,126 Synthetic pathways to
sulfoxides are often similar to those examined for sulfones; due to this similarity
the same classification will be employed.
1.3.1 Alk-1-enyl sulfoxides from other sulfur derivatives
Oxidative routes
Oxidation of sulfides as route to sulfoxides has been investigated starting from
1865, and still remains one of the most important approaches to sulfoxides. This
methodology has been extensively studied, both for the synthesis of
racemic 49,127,128,129,130 and optically active 131 sulfoxides, and many oxidizing
R 1

systems have been proposed, including hydrogen peroxide, 132 organic peracids,
chromic acid, nitric acid, 133 halogens, iodosobenzene, 134 sodium
hypochlorite. 135,136 The main problem involved in this method is the overoxidation
to the corresponding sulfone, which depends on the oxidizing system used. In
most cases, however, reaction conditions are mild enough to obtain sulfoxides in
good yields, even when sensitive groups are present. It has been shown that
sulfoxides are intermediates in the oxidation of sulfides to sulfones; for this
reason, many oxidative approaches to unsaturated sulfones can be also used to
prepare unsaturated sulfoxides. 52,60 These methods have already been described in
Section 1.2.1 and will not be discussed further.
The preparation of 1-vinyl alk-1’-ynyl sulfoxides starting from the
corresponding sulfides has been reported (Scheme 1.36); 137 both H2O2 or peracids
can be used as oxidants.
R
S
H2O2 or MCPBA
CH3COOH or CH2Cl2 r.t., 40h
26 Chapter 1
R
O
S
67-84%
Scheme 1.36: Oxidation of alk-1-ynyl vinyl sulfides to sulfoxides with hydrogen peroxide
Organic peracids are known to be powerful oxidizing agents under mild
conditions, and their ability to oxidize sulfides to sulfoxides can be efficiently
employed in the synthesis of sulfoxides that are sensitive to bases. 138 An example
is reported in Scheme 1.37, where thiiranedialene is quantitatively oxidized at 0
o C using MCPBA. 139
S
MCPBA
Scheme 1.37: Oxidation of thiiranedialene with MCPBA
Sodium metaperiodate is a good oxidant for sulfides, and has been used for the
synthesis of 1-butadienyl phenyl sulfoxide 140 (Scheme 1.38).
O
S

Ph
S
NaIO 4
MeOH, 0 o C
Ph O
S
Scheme 1.38: Oxidation of 1-butadienyl phenyl sulfide with sodium metaperiodate
Its use is not completely general, and in some cases no reaction is observed. 141
Non-oxidative routes
Although non-oxidative routes to alk-1-enyl sulfoxides are less employed than
oxidative ones, this field seems very promising, and has recently received
considerable attention. As with oxidative routes, many approaches resemble very
closely those already discussed for alk-1-enyl sulfones. Hydrozirconation of
alkynyl sulfur derivatives, 70,142 already discussed in Section 1.2.1, has recently
attracted much attention, due to its stereoselectivity and the versatility of
organozirconium intermediates, which are precursors to a host of more complex
systems. The anti-stereoselectivity obtained in this procedure, which is likely to
be due to the coordinating effect of the sulfoxide group, is not always complete
and depends on the bulk of the substituent in the position β to the sulfoxide group
(Scheme 1.39). Poor yields (23%) are obtained when aryl-substituted alkynyl
sulfoxides are used as starting materials, and are in the range 39-47% when alkylsubstituted
alkynyl sulfoxides are used.
R
O
S
Ar
R=Pr, n-Alk
E + =H + , NBS
Synthesis of alk-1-enyl sulfones and sulfoxides: state of the art 27
76%
O
Cp2Zr(H)Cl, r.t., 5min Cp2ClZr E
S
R Ar
+
R
E
O
S
Ar
39-47% (R=n-Alk)
23% (R=Ar)
Scheme 1.39: Hydrozirconation and trapping of alkynyl sulfoxides with electrophiles
In a recently reported synthesis of alkenyl disulfoxides, alkynyl sulfoxides
have been used both as sulfinyl source and as acceptors; palladium-catalyzed
sulfinyl zincation 143 can afford alkenyl disulfoxides in good yields, (Scheme 1.40,
path a). The mechanism involved is still uncertain, but presumably proceeds
through the following steps: a) oxidative addition with insertion of the palladium
catalyst in the (sp)C-S bond; b) substitution of the sulfinyl group by the ethyl
group of diethylzinc; this leads to the formation of an ethylzinc sulfinate with
regeneration of the catalyst; c) addition of ethylzinc sulfinate to the alkynyl

sulfoxide. This protocol presents an interesting feature, because it allows one to
perform sulfinyl zincation on alkynes different from the alkynyl sulfoxide itself.
This is due to the strong tendency of alkynyl sulfoxides to oxidatively add to
palladium, which makes the oxidative addition step very selective. It is therefore
possible to obtain highly functionalyzed alkenyl sulfoxides, as reported in Scheme
1.40, path b. A drawback of this process is the loss of the alkynyl chain present on
the sulfoxide, which causes the whole reaction to suffer from low atom economy.
a)
b)
R
t-Bu
O
S
O
S
Ar
Tol-p
Pd(dba) 3 CHCl3
Et2Zn (2 equiv.)
THF
-78 o 1)
C
+
2) H 3O +
R
.
O
OR'
28 Chapter 1
O
S
Ar
1)
R
82-97%
O
S
.
Ar
Pd(dba) 3 CHCl3
Et 2Zn (2 equiv.)
THF
-78 o C
2) H 3O +
O
S
p-Tol
R
O
C
48-98%
Scheme 1.40: Sulfinyl zincation of alkynyl sulfoxides in the presence of palladium catalysts
Organozinc derivatives 144 add in good yields to alkynyl sulfoxides in the
presence of catalytic amounts of copper salts. This route affords many structurally
different products; the great functional group tolerance of organozinc derivatives
makes this approach very valuable in the synthesis of alk-1-enyl sulfoxides
(Scheme 1.41, path a).
Moreover, if a suitable electrophile is added to the reaction mixture before the
hydrolysis, more complex derivatives can be obtained in good yields (Scheme
1.41, path b).
OR'

a)
b)
R
R
O
S
O
S
Ar
Ar
Cu(OTf) 2
THF
-78 o 1)
C
2) H3O +
R'ZnX
1)
Cu salt
THF
-78 o Et2Zn C
2) Allyl bromide
Synthesis of alk-1-enyl sulfones and sulfoxides: state of the art 29
R'
Et
R
O
S
70-94%
R
O
S
40-88%
Scheme 1.41: Addition of organozinc derivatives to alkynyl sulfoxides in the presence of
copper catalysts
Alkynyl sulfoxides afford cis or trans alkenyl sulfoxides by simple reduction
with DIBAL-H (or LiAlH4) or H2/RhCl(PPh3)3 respectively; products are obtained
in excellent yields with complete stereoselectivity (Scheme 1.42). 145
Stereochemistry of the hydroalumination is anti, due to the coordinating effect of
sulfoxide group; this is in good agreement with what reported for analogous
reactions performed on propargilic alcohols.
R
O
S
Ar
DIBAL-H, 15min
THF or Toluene
-90 oC or
LiAlH4, 30min
THF
-90 oC H2 (1 atm)
ClRh(PPh3) 3
benzene
r.t.
R
R
O
S
Ar
Al(Bu-i) 2
O
S
59-97%
Ar
H 3O +
Ar
Ar
R
H
O
S
84-95%
Scheme 1.42: Reduction of alkynyl sulfoxides to cis- or trans- alkenyl sulfoxides
Hydrostannylation of alkynyl sulfoxides can be performed with trialkyltin
hydrides, and in this case a stable α-stannyl alkenyl sulfoxide is obtained.
Ar

Bu
O
S
Ar
Bu 3SnH, 18h
hexane
r.t.
Pd(PPh3) 4
benzene
-78 o Bu3SnH C
Bu
Bu
87%
30 Chapter 1
85%
O
S
SnBu 3
O
S
SnBu 3
Ar
Ar
2)
E/Z=7.5/1
1) NIS
THF, r.t. Bu
O
S
Ar
R'
SnBu 3
Pd 2(dba) 3 5%
AsPh 3 20%
BHT (1 equiv.)
THF, r.t., 2h
R'
70-81%
Scheme 1.43: Reduction of alkynyl sulfoxides with tributyltin hydride and further
modification to dienyl sulfoxides
This intermediate is useful for further modifications and, in particular,
iodolysis has been successfully employed to afford β-iodo sulfoxides, which can
be cross-coupled with alkenyl stannanes to give 2-dienyl sulfoxides in good yield
(Scheme 1.43). 146
The Michael addition of malonate ion to acetylenic sulfoxides, which affords
the trans-addition products exclusively, is one of the oldest methods for the
functionalization of alkynyl sulfoxides. 147 It is also reported that addition of
malonate ion to β-bromo alkenyl sulfoxides affords, after elimination of HBr, the
corresponding alkenyl sulfoxides in good yields. Reaction of organocopper
derivatives with alkynyl sulfoxides affords instead the cis addition product
only; 148,149 it is noteworthy that monoalkyl copper derivatives give good yields,
while the more reactive dialkyl cuprates lead mainly to substitution products of
the sulfinyl moiety.
1.3.2 Alk-1-enyl sulfoxides by nucleophilic substitution at the
sulfur atom
Nucleophilic substitution at sulfur by carbon nucleophiles is one of the most
important approaches to racemic and optically active unsaturated sulfoxides.
Sulfinic acid derivatives are known since 1926 150 to be excellent substrates for
reactions involving Grignard reagents, and organocopper derivatives have been
shown to effectively alkylate sulfinyl esters. 126 The Andersen protocol, developed
in the 1960s, 151 is one of the most important routes to the synthesis of

enantiomerically pure sulfoxides. This method allows alkylation of chiral
sulfinates with organometallic reagents and affords the corresponding sulfoxides
in good yields and optical purities with inversion of configuration at S. 152 This
approach has been widely applied to the synthesis of chiral alkenyl
sulfoxides 153,154 (Scheme 1.44).
R
MgBr
E/Z=70/30
+
O
Ph S O-(l)-Ment
THF/benzene
r.t.
Ph
74%
S
R
E/Z=70/30
Scheme 1.44: The Andersen protocol applied to the synthesis of optically active alkenyl
sulfoxides
The same protocol has been successfully applied to the synthesis of
enantiomerically pure alkynyl sulfoxides, precursors of cis or trans alkenyl
sulfoxides, by one of the reduction methods described above (Section 1.3.1). 154
Due to the great interest in the synthesis of enantiomerically pure sulfoxides,
preparation of chiral sulfinates in satisfactory yields and optical purities is a task
of great interest; as a consequence, much effort has been devoted to finding novel
chiral sulfinates, which are able to overcome the limitations of the Andersen
protocol regarding yield and easy access to both enantiomers. 155,156,157
Sulfinyl chlorides are reported to react readily with alkenyl zirconium
derivatives, affording the unsaturated sulfoxides in good yields. 158 The reaction is
shown in Scheme 1.45 and is performed with α-stannyl vinyl zirconium
complexes 11. α-Stannyl-substituted alkenyl sulfoxides can be obtained
stereospecifically in good yields with this method. The presence of a stannyl
substituent at the α-position of the sulfinyl group creates a handle for further
reaction, e.g. by means of palladium-catalyzed cross coupling reactions.
R
SnR3' Cp2Zr(H)Cl
THF
r.t., 5min
R
ZrCp 2Cl
SnR 3'
11
R''SOCl R
Synthesis of alk-1-enyl sulfones and sulfoxides: state of the art 31
O
S
SnR 3'
63-80%
R''
O
Ph 2I + Cl -
Pd(PPh 3) 4
CuI
2h
R
O
S
R''
Ph
75%
Scheme 1.45: Synthesis of alkenyl sulfoxides by reaction of α-stannyl zirconium complexes
with sulfinyl chlorides
Alkynylation of sulfinyl chlorides with lithium acetylides has been reported to
proceed in satisfactory yields. 159 It has also been claimed that vinyl Grignard
reagents and alkenyl alanes give the sulfoxides under mild reaction conditions

(toluene, 0 o C) although in modest yields. The results, however, appear erratic
depending on the substrate used, and it is reported that the starting sulfinyl
chlorides present some stability problem.
1.3.3 Alk-1-enyl sulfoxides via condensation reactions
As already seen for sulfones, sulfoxides can also be obtained by condensation
reactions; the remarkable acidity of protons bonded in α-position to sulfinyl
functional group, makes this approach attractive. 160 The classical Wittig-Horner
approach (Scheme 1.46), relies on the deprotonation of arenesulfinyl
methanephosphonates 12 and its subsequent reaction with aldehydes; this
approach has been developed in the following years, by using phase-transfer
catalysis. 161 The main disadvantage of this approach is represented by the
formation of E/Z isomers mixtures, whose composition strongly depends on the
nature of the aldehyde employed, 162 even though many attempts have been
reported to overcome these limitations. 163,164
O
(EtO) 2P
12
O
S
Me
+
O
R H
n-BuLi, THF
-78 o C to 0 o C
32 Chapter 1
R
70%
O
S
Me
Scheme 1.46: Synthesis of alkenyl sulfoxides by Wittig-Horner reaction of arenesulfinyl
methanephosphonates anion with aldehydes
The necessary arenesulfinyl methanephosphonates can be obtained from the
arenesulfenyl methanephosphonates by controlled oxidation at sulfur atom or by
reaction of anions of dialkyl methanephosphonates with sulfinate esters. A
significative improvement in the stereoselectivity of the Wittig-Horner reaction,
applied to the synthesis of racemic and chiral sulfoxides, has been recently
achieved with the use of α-sulfinyl phosphonium ylides, generated in situ from
methyltriphenylphosphonium iodide, n-BuLi and methyl p-toluenesulfinate. 165 It
has also been reported that formation of sulfonyl phosphite and condensation with
aldehydes can be performed in situ. 166
2 Ph3P + - n-BuLi
CH3I 2
Ph 3P
H
H
O
R' S OMe
Ph 3P
O
S R'
RCHO
O
R' S
50-88%
R
E/Z=68/32-100/0
Scheme 1.47: Synthesis of alkenyl sulfoxides by Wittig reaction of α sulfinyl phosphonium
ylides

The reaction, illustrated in Scheme 1.47, often proceeds with nearly complete
(E) stereoselectivity and, if p-methylphenyl menthyl sulfinate is employed,
affords the alkenyl sulfoxides with excellent enantiomeric excesses.
In a similar approach, [(α-chloro)sulfinylmethyl]diphenylphosphine oxides are
used in a Wittig synthesis of α-chloro alkenyl sulfoxides. The reaction is shown in
Scheme 1.48 and the resulting products are obtained stereoselectively and in good
yields. 167,168 The starting phosphonates 13 are obtained in two steps starting from
tosyloxymethyl triphenylphosphine oxide.
O
(C 6H 5) 2P
Cl
13
O
S
R
LDA, THF
-50 o -50
C to r.t.
o 1)
C
2)
R'CHO
Synthesis of alk-1-enyl sulfones and sulfoxides: state of the art 33
R'
Cl
O
56-87%
Scheme 1.48: Synthesis of α-chloro alkenyl sulfoxides by Wittig reaction of [(α-chloro)sulfinylmethyl]-diphenylphosphine
oxides
The Knoevenagel condensation represents a useful route to unsaturated
sulfoxides; this approach has been recently studied, and applications have resulted
in one-pot sequencies to γ-keto and γ-hydroxy alk-1-enyl sulfoxides. 169 Chiral
derivatives can be obtained when a chiral bis sulfoxide is employed in the
condensation step.
Anions derived from deprotonation at the α position of the sulfinyl group add
to aldehydes, forming β-hydroxy sulfoxides. Subsequent elimination 170 or
mesylation-elimination 171 sequences afford the desired products in good yields
and complete stereoselectivity. This can be followed by an intramolecular Heck
reaction, which affords cyclic dienyl sulfoxides (Scheme 1.49). 171 Quenching of
the alkoxide intermediate with acetyl chloride, followed by base-catalyzed
elimination, also afford alk-1-enyl sulfoxides in good yields. 172
S R

O
p-Tol S Me 2)
LDA
THF, -78 oC p-Tol S
1)
I
O
H
O OH
34 Chapter 1
I
MsCl, Et 3N
CH 2Cl 2, r.t.
p-Tol S
O
72% 60%
Scheme 1.49: Synthesis of cyclic dienyl sulfoxides
I
O
S Tol-p
Addition of carbanion of p-tolyl methyl sulfoxide to esters leads to the
formation of β-keto sulfoxides. This reaction can be performed on unsaturated
esters; enolization with LDA and quenching at low temperature with t-butyl
dimethylsilyl triflate leads to the synthesis of stereochemically pure dienyl
sulfoxides in high yields. 173 Conservation of chiral information on the sulfur atom
during deprotonation and alkylation processes constitutes an interesting and
synthetically useful feature of this process.
Me 3Si
Li
O
S
Ph
+
R
O
R'
THF
-70 oC R'
R O
S
Ph
66-87%
Scheme 1.50: Synthesis of alkenyl sulfoxides starting from silyl sulfinyl derivatives
Sulfinyl silyl derivatives have been used in the synthesis of alk-1-enyl
sulfoxides. 174 The first step is the deprotonation of the sulfinyl silyl precursor,
which after addition to an aldehyde, affords the alkenyl sulfoxide upon warming
to room temperature (Scheme 1.50). Although the yields are usually quite good,
the stereochemistry of the product is uncertain, even when aldehydes are
employed.

Part II
Results

Chapter 2
New synthetic approaches to alk-1-enyl
sulfoxides
2.1 Introduction
The literature analysis reported in the previous part demonstrated that alk-1enyl
sulfoxides can be conveniently synthesized starting from sulfur derivatives
and reagents bearing an alkenyl functional group. 82,175,176,177 This approach
simplifies the synthesis of these compounds, affording the products in high yields
under practical conditions. Sulfonyl and sulfinyl chlorides are among the most
readily accessible sulfur derivatives, and their utilization in the synthesis of
unsaturated sulfoxides represents an obvious choice. Sulfinyl chlorides are in the
correct oxidation state for the synthesis of sulfoxides, and thus seem reasonable
starting reagents; sulfonyl chlorides, on the other hand, require a reduction step to
afford sulfoxides. However, the high reactivity and the moisture sensitivity of
sulfinyl chlorides limits their utilization in synthesis. Both sulfinyl and sulfonyl
chlorides have been employed successfully in the synthesis of unsaturated
sulfoxides during the course of this thesis work. The results obtained, as well as
differences in the reactivity of the two substrates, are discussed in the present
chapter. Sulfonyl chlorides were studied first in consideration of their widespread
availability and their low cost, whereas sulfinyl chlorides were employed only
later, and were particularly useful since their reactivity explained some
mechanistic details which had the subject of the study on the reactivity of sulfonyl
37

chlorides. The discussion on the reactivity of sulfinyl chlorides will be dealt with
in Section 2.4.
Organoaluminum derivatives, although somewhat underemployed in organic
chemistry, represent an interesting class of organometallic reagents, and show
their full synthetic potential in the transfer of unsaturated chains. Dialkyl alk-1enyl
alanes are easily accessible in nearly quantitative yields from the
corresponding alkynes by the well known hydroalumination reaction, which
occurs with complete (E) stereoselectivity; with respect to reactivity, the
unsaturated moiety at Al often shows a remarkable reactivity and is transferred
preferentially over the alkyl groups. Surprisingly, as shown in the literature
analysis, use of these derivatives in the synthesis of unsaturated sulfoxides has
been neglected, the sole exception being represented by scattered reports; 159 this
thesis work was thus mainly devoted to the study of the reactivity of alanes in the
preparation of unsaturated sulfoxides. The present chapter deals with the use of
these compounds as alkenylating agents vs. sulfonyl and sulfinyl chlorides.
2.2 Syntesis of alk-1-enyl sulfoxides using aluminum
sulfinates
2.2.1 General remarks
It is well known since the 1960s that aluminum arylsulfinates react with
trialkyl- and triaryl alanes giving many structurally different aryl alkyl or diaryl
sulfoxides in high yields. This reaction, illustrated in Scheme 2.1, has been
extensively studied by Reinheckel et al., 178,179,180 and represents an economical
and high-yielding approach to sulfoxides. The reaction proceeds through the in
situ formation of the intermediate aluminum aryl sulfinate 15. This compound is
obtained from the corresponding aryl sulfonyl chloride by treatment with
equimolar amounts of triethyl aluminum or diethyl aluminum chloride at room
temperature, working at high concentration. Addition of a symmetrical alane gives
the desired aryl sulfoxides 16.
38 Chapter 2

S Cl
O
O
Ar
Et 3Al
r.t. 5min.
S OAlEt O
2
Ar
S
Ar
R O
AlR3 + EtCl + R2Al O AlR2 15 16
Scheme 2.1: Reinheckel protocol for the synthesis of sulfoxides using aluminum sulfinates and
alanes
The method can be performed in rather short times (30 minutes) at room
temperature. This protocol has, however, a major limitation: alkyl sulfonyl
chlorides do not react cleanly; it was in fact reported that the alkylaluminum
sulfinates obtained are completely unreactive towards the alanes in the second
step of the process, and after hydrolysis the alkyl sulfinic acid is obtained. This
feature of the reaction limits the scope of this protocol to the preparation of
sulfoxides bearing at least one aryl substituent. The importance of alkenyl
sulfoxides prompted to test whether this approach could be extended to the use of
alkenyl alanes; the possibility of developing a one-pot procedure made this
method even more attractive. The main problem involved in the extension to
dialkyl alkenyl alanes may be, in comparison to trialkyl or triaryl alanes, 178,179,180
any incomplete selectivity in the transfer of the unsaturated residue.
2.2.2 Preliminary experiments
Preliminary experiments were performed using experimental conditions similar
to those employed by Reinheckel, 180 following the procedure reported in Scheme
2.2. In particular, the synthesis of the aluminum sulfinate was performed in
dichloromethane solution, at high concentration (1-1.5 M). The (E)-di-i-butyl hex-
1-enyl aluminum, prepared by hydroalumination of 1-hexyne, was added in
stoichiometric ratio to the homogeneous solution of the aluminum sulfinate.
S Cl
O
O
Et 3Al
r.t. 5min.
S OAlEt O
2
(i-Bu) 2Al
O Bu-n
S
New synthetic approaches to alk-1-enyl sulfoxides 39
Bu-n
+ EtCl + (i-Bu)2Al O Al(Bu-i) 2
Scheme 2.2: Synthesis of alkenyl sulfoxides using aluminum sulfinates
The product was isolated in a disappointing yield (26%, Table 2.1 entry 1), i.e.
lower than the yields reported by Reinheckel. This is due to the scarce reactivity
of the dialkyl alk-1-enyl aluminum, which is considerably lower than that of
trialkyl and triaryl alanes. Neither refluxing the reaction nor the addition of 1 extra
equivalent of di-i-butyl hex-1-enyl aluminum improved the yield.

The experiment was repeated at higher concentrations (4M in
dichloromethane) and using 3,3-dimethyl but-1-enyl aluminum (entry 2). The
yield was also rather disappointing, and did not improve even after 10 hours of
reflux, or after addition of 0.5 extra equivalents of organometallic reagent.
Table 2.1: Reaction of aluminum sulfinates with dialkyl alk-1-enyl alanes
S Cl
O
O
Et3Al CH2Cl2 r.t. 5 min.
S OAlEt O
2
O R
(i-Bu) 2Al
S
R
+ EtCl + (i-Bu)2Al
5h
O Al(Bu-i) 2
Entry a (i-Bu)2AlR Product Solvent T( o C) Yield(%) b
1
2
3
Bu-n
Bu-t
Bu-t
4 c Bu-t
5 c Bu-t
6 c Bu-t
O Bu-n
S
O Bu-t
S
O Bu-t
S
O Bu-t
S
O Bu-t
S
O Bu-t
S
CH2Cl2/C6H14
1/1
CH2Cl2/C6H14
1/1
CH2Cl2/C6H14
1/1
CH2Cl2/C6H14
5/95
25 26
25 27
45 35
68 72
i-octane 99 0
THF 68 0
a All the reactions were performed using an (i-Bu)2AlR/PhSO2Cl=1/1 ratio if not
otherwise stated; b Evaluated on the isolated, chemically pure product and referred to
the sulfonyl chloride; c Reaction performed using an (i-Bu)2AlR/PhSO2Cl=1.5/1 ratio.
An experiment was carried out by refluxing the reaction mixture immediately
after the addition of the alane (entry 3). Under these conditions the product was
isolated in considerably higher yield than in the previous experiments. This
suggested that an increase of the reaction temperature could enhance the yield. To
increase the temperature, a reaction was performed using a solvent mixture
enriched in hexane (95%), together with a 1.5/1 alane/aluminum sulfinate ratio;
the product was obtained in 72% yield (entry 4). When, however, an even higher
temperature (99 o C) was used, performing the reaction in i-octane, no trace of the
desired product was detected in the reaction mixture (entry 5). This may be due to
the thermal decomposition of the alane. 181
40 Chapter 2

In further experiments, use of THF as solvent was studied considering that:
1. Ether-complexed alanes can be prepared more readily than the
corresponding unsolvated analogues; in particular, their synthesis starting
from Grignard reagents is very practical;
2. Synthetic interest in the reaction would be greater if ether-complexed
alanes could be employed; the choice of solvent, as well as functional
group tolerance, would be greater.
The reaction was performed at the boiling point of the solvent, at a temperature
similar to that employed in entry 4, in which hexane was employed as solvent. In
this case (entry 6) no trace of the desired sulfoxide was obtained, even after
prolonged reaction times.
It is tempting to conclude from the above experimental results that the effect of
the solvent in this reaction is correlated with its Lewis basicity. The other critical
factor is the reaction temperature, i.e. an optimum temperature must be selected so
that the alane does not decompose but is activated enough to react with the Al
sulfinate. Entries 4 and 6 in Table 2.1, where the reaction temperature is quite
similar but yields are remarkably different, clearly show the influence of the
Lewis basicity of the solvent. In the light of these results, it is probable that the
higher reactivity of trialkyl and triaryl alanes which, according to Reinheckel,
smoothly react even at room temperature, is due to their greater Lewis acidity. An
interesting feature emerging from this preliminary study is the complete transfer
selectivity: the unsaturated sulfoxide was always the sole sulfur-containing
product detected in the reaction mixtures; the lower than quantitative yields are
probably due to incomplete alane reaction. The unreacted alane and aluminum
sulfinate are likely lost in the aqueous work-up, after quenching, thus preventing
an accurate mass balance.
2.2.3 Study of the reaction
Once reasonable conditions were found for the reaction under study, attention
was directed toward the generalization of the procedure on different substrates.
With this aim, the reactivity of different dialkyl alk-1-enyl alanes and sulfonyl
chlorides was examined, using the same reaction conditions reported in Table 2.1,
entry 4.
The results obtained in this study are summarized in Table 2.2. The reaction
proceeds in similar yields and reaction times regardless of the organometallic
New synthetic approaches to alk-1-enyl sulfoxides 41

eagent, as long as the latter is unsubstituted at the carbon α to aluminum (Table
2.2, entries 1-5). Interestingly, yields obtained employing methanesulfonyl
chloride as starting material are quite similar to those observed when aryl sulfonyl
chlorides are used (Table 2.2, entry 1 vs. 5).
Table 2.2: Alk-1-enyl sulfoxides using aluminum sulfinates
S Cl
O
O
R'
Et 3Al
CH 2Cl 2
r.t. 5 min.
S
R'
OAlEt (i-Bu) 2Al
R
O
2
(1.5 equiv.)
O R
+ EtCl S +
Hexane, rfx.
(i-Bu)2Al
5h
R'
O Al(Bu-i) 2
Entry a (i-Bu)2AlR R’SO2Cl Product Yield(%) b
O
Hex-n O
1 S
Cl
O
Hex-c O
2 S
Cl
O
Bu-n O
3 S
Cl
Bu-t 4 Me
S
O
Bu-n O
5 Me S
Cl
Et
6 Et
O
O
O
O
S
Cl
Cl
O Hex-n
S
O Hex-c
S
O Bu-n
S
O Bu-t
S
42 Chapter 2
Me
O Bu-n
S
Me
Et
O Et
S
a All the rections were performed using an (i-Bu)2AlR/R’SO2Cl=1.5/1 molar
ratio at the temperature of 68 o C; b Calculated on the isolated, chemically pure
product and referred to the sulfonyl chloride.
These results show that reaction conditions found during this work are efficient
for the synthesis of alk-1-enyl sulfoxides starting from alkyl sulfonyl chlorides, in
contrast to what reported by Reinheckel. The main limitation of this reaction is the
failure to obtain alkynyl sulfoxides starting from dialkyl alk-1-ynyl alanes. In
these cases no trace of product could be recovered even after prolonged reaction
times.
In conclusion, this reaction represents a major extension over the Reinheckel
protocol, allowing the synthesis of aryl as well as alkyl alk-1-enyl sulfoxides. The
reaction is easy to perform and leads to satisfactory yields. Two main features
make this protocol particularly attractive: first, selectivity in the transfer of the
75
75
75
72
75
0

unsaturated chain was always complete: GLC-MS and NMR analyses did not
show any trace of alkyl transfer byproducts in any of the reaction mixtures. The
excellent selectivity of the transfer process allows an extremely simple hydrolysis
procedure: it is in fact sufficient to adsorb the reaction mixture on silica gel and
elute with dichloromethane to obtain the pure product; the second feature consists
in the extremely high level of stereoselectivity both in the hydroalumination step
and in the subsequent transfer of the unsaturated chain; this allows formation of
the stereochemically pure (E)-isomers from each reaction.
2.3 Alk-1-enyl sulfoxides starting from sulfonyl
chlorides and pyridine-coordinated alanes
2.3.1 Preliminary attempts of cross-coupling reactions in the
presence of palladium complexes
The literature analysis in the preceding part discussed an interesting synthetic
pathway to alk-1-enyl sulfones. 77 This approach, shown in Scheme 2.3, is a crosscoupling
reaction between alkenyl stannanes and sulfonyl chlorides, catalyzed by
palladium complexes. As discussed in the previous section, there are some doubts
about the mechanism of this reaction, and the possibility of a radical mechanism
cannot be ruled out. Despite these considerations, the method seemed attractive in
view of the simplicity of the procedure and the good yields obtained. With a slight
modification of this approach, alk-1-enyl sulfones could perhaps be obtained
starting from sulfonyl chlorides and dialkyl alk-1-enyl alanes, which in turn are
obtained by hydroalumination of alkynes. The advantage of alanes vs.
organostannanes is the lower toxicity and simpler synthesis of the former.
O O
R S Cl
+
n-Bu 3Sn
R'
Pd(PPh3) 4
70 oC, 15min R S
O O
60-90%
R=Ar, Me
New synthetic approaches to alk-1-enyl sulfoxides 43
R'
+ n-Bu 3SnCl
Scheme 2.3: Reaction of sulfonyl chlorides with organostannanes in the presence of palladium
catalysts
Preliminary attempts were carried out in the presence of PdCl2(PPh3)2 or
Pd(PPh3)4, using CH2Cl2 as solvent. Under these reaction conditions both
triethylaluminum and, after longer reaction times, (E)-di-i-butyl hex-1-enyl
aluminum, afforded aluminum sulfinate as the sole product (Scheme 2.4).

Formation of this product was established by isolating the sulfinic acid after acidic
aqueous work-up. This reaction is in good agreement with what reported by
Reinheckel on the formation of aluminum sulfinates.
S Cl
O
O
AlR 3
CH2Cl2 "Pd", r.t., 15 min
S OAlR O
2
+ EtCl
44 Chapter 2
H 2O
S H
O
O
Scheme 2.4: Attempted cross-coupling between organoalanes and sulfonyl chlorides
These results clearly suggest that the uncatalyzed reaction between trialkyl
alanes and sulfonyl chlorides is too fast to allow for Pd catalysis. Under these
conditions, the Pd catalyst was not active enough to oxidatively add to the
sulfonyl chloride, thereby starting the catalytic cycle; the preferred reaction
pathway was the formation of the aluminum sulfinate, even when dialkyl alk-1enyl
alanes were employed, although in this case small amounts (20%) of (E) ptolyl
hex-1-enyl sulfoxide and the corresponding sulfone were detected, in a
nearly 1/1 ratio. Other experiments were carried out employing THF as solvent,
with the aim of forming an alane-THF complex and thereby reduce the reactivity
of the alane. Complexes of alanes have lower Lewis acidity, and are expected to
be less reactive in the formation of the aluminum sulfinate.
O
O Cl
S
+ AlEt 3
THF
"Pd"
O
S
O S
17
+ Et2Al O AlEt 2
Scheme 2.5: Cross-coupling reaction between triethyl aluminum and benzenesulfonyl chloride
conducted in THF
The exploration of a variety of experimental conditions did not significantly
improve the yield; the major change in the outcome of the reaction was
represented by the formation of appreciable amounts (75%) of S-phenylbenzenethiosulfonate
17, as reported in Scheme 2.5. This is in good agreement
with previous reports 182 on the formation of S-aryl-arylthiosulfonates by action of
LiAlH4 in mild conditions, which is reported to occur via formation of intermedite
aluminum sulfinates. 183 On the basis of such results, the effect of pyridine as
solvating agent for alanes was examined; this may modulate their reaction course.
Depending on the order of addition of the reagents, one could obtain two effects:

1. Complexation of alanes with pyridine could moderate their reactivity. It is
well documented in the literature that alane-pyridine complexes show a
lower reactivity, 184 due to lower Lewis acidity. 185,186
2. Sulfonyl chlorides could react with pyridine, and this could result in the
activation of such intermediate towards substitution at sulfur. This reaction
pathway is precedented in the chemical literature. 187
As described in more detail later, both effects can operate in this reaction,
depending on the reaction conditions. Activation of sulfonyl chloride with
pyridine and subsequent alkylation by uncomplexed organoalanes and Grignard
reagents in the synthesis of sulfones will be discussed in Section 3.2.
As far as reaction of complexed alanes is concerned, the preformed pyridinetriethyl
aluminum complex, was completely unreactive towards benzenesulfonyl
chloride both using THF and CH2Cl2. However, the (E) di-i-butyl hex-1-enyl
aluminum/pyridine complex 18, whose formation was evidenced by NMR
analysis (Table 2.6), reacted with tosyl chloride in the presence of a catalytic
amount (3 mol %) of Pd(PPh3)4, affording the unsaturated sulfone 19 in 48% yield
(Scheme 2.6). Two remarkable facts were observed during this reaction: the
triphenylphosphine present as ligand on the palladium catalyst was completely
oxidized to triphenylphosphine oxide, and an appreciable amount of p-tolyl hex-1enyl
sulfoxide 20 was also isolated. The sulfoxide was isolated in nearly
equimolar amounts vs. the triphenylphosphine originarily present (Scheme 2.6).
O
O Cl
S
Me
O
S
O
Bu-n
+ N
Pd(PPh3) 4
Hexane/THF 1:1
+
(i-Bu) 2Al
Bu-n
3h r.t.
Me
Me
18 19 20
New synthetic approaches to alk-1-enyl sulfoxides 45
48%
O Bu-n
S
9%
+ PPh 3O
Scheme 2.6: Reaction of di-i-butyl hex-1-enyl alane-pyridine complex and tosyl chloride in the
presence of Pd(PPh 3) 4
Further experimentation showed that addition of further triphenylphosphine to
the reaction mixture led to the immediate formation of more sulfone 19, and
concomitant appearance of alkenyl sulfoxide 20 was also observed. Formation of
20 could be ascribed to a direct reaction between sulfonyl chloride, the pyridinealane
complex 18 and triphenyl phosphine, or to the reduction of sulfone 19 by
12%

the triphenylphosphine. A control experiment was carried out using stoichiometric
amounts of triphenylphosphine and no palladium. As shown in Scheme 2.7, many
products were isolated, the major ones being (E)-hex-1-enyl p-tolyl sulfone 19,
(E)-hex-1-enyl p-tolyl sulfoxide 20 and i-butyl p-tolyl sulfoxide. The formation of
the unsaturated sulfone clearly demonstrated that the palladium catalyst acted only
as triphenylphosphine source, and that sulfone was produced by non-Pd pathway.
O
O Cl
S
Me
+
N
(i-Bu) 2Al
Bu-n
PPh3 Hexane/THF
r.t., 15min
O
S
O
46 Chapter 2
Me
Bu-n O
S
+
Me
18 19 20
Bu-n
+
S Bu-i
Scheme 2.7: Reaction of tosyl chloride and di-i-butyl hex-1-enyl alane in the presence of
stoichiometric amounts of triphenylphosphine
O
Me
+ PPh 3O
The reaction temperature was then lowered to 0 o C to increase the selectivity of
the process; under these conditions the unsaturated sulfoxide 20 was the sole
product detected; it was recovered in a 48% yield. This fact suggested that sulfone
20 is not intermediate in the formation of sulfoxide. It reasonable to assume that,
were the reduction of sulfone 19 to sulfoxide 20 to take place as the second step in
the reaction, a lower temperature should disfavor or in any case slow the process
down, and thus a higher yields of sulfone should be observed. To definitively
prove that sulfone was not an intermediate, a reaction was performed adding a
known amout (35% mol/mol) of an authentic sample of sulfone 19 to the
preformed alkenylalane-pyridine complex 18. After the addition of the other
reagents (0.9 equivalents of tosyl chloride and 1.2 equivalents of
triphenylphosphine) and of the appropriate internal standard, the reaction progress
was monitored by GLC. The sulfone was effectively reduced by triphenyl
phosphine under these reaction conditions, but the reduction was quite slow,
requiring several hours, in contrast with the few seconds that are sufficient to
perform the main reaction; this suggested that formation of sulfoxide proceeded
through another pathway. In addition, simply mixing sulfone and
triphenylphosphine did not lead to the formation of sulfoxide nor to the oxidation
of triphenylphoshpine (68 o C, 24h). From the above data, it was reasonable to
assume that sulfone and sulfoxide were formed by two different pathways. Both
processes were investigated in detail; the results obtained in the synthesis of

sulfoxide are discussed below, whereas the synthesis of sulfone will be considered
in Section 3.3.
2.3.2 Alk-1-enyl sulfoxides from pyridine-complexed alanes and
sulfonyl chlorides in the presence of triphenylphosphine
On the basis of the preliminary experiments described in the previous section,
the effect of temperature, reagent ratio and solvent was examined. The results are
reported in Table 2.3. A major factor is the nature of the solvent employed (entries
8-10), while stoichiometry and temperature play a marginal, although not
negligible, effect (entries 1-7).
N
(i-Bu) 2Al
Table 2.3: Effect of reaction parameters on the yield
Bu-n
+
S Cl
O
O
Me
PPh3 0 oC 10min
Me
New synthetic approaches to alk-1-enyl sulfoxides 47
O
S
Bu-n + Ph3PO + N
(i-Bu) 2Al
Cl
Entry Pyridine a TsCl a PPh3 a Solvent Yield(%) b,c
1 1 0.9 0.9 THF/Hexane 1/1 50
2 1 2 2 THF/Hexane 1/1 23
3 1 0.9 0.9 THF/ Hexane 1/1 43 d
4 1 1.35 0.9 THF/ Hexane 1/1 61
5 1 0.45 0.45 THF/ Hexane 1/1 42
6 2 0.9 0.9 THF/ Hexane 1/1 59
7 2 1.8 0.9 THF/ Hexane 1/1 64
8 1 0.9 0.9 Hexane 23
9 1 0.9 0.9 THF 83 e
10 1 0.9 0.9 CH2Cl2 87
a Molar ratio with respect to the organometallic reagent; b Calculated on the
isolated, chemically pure product, based on the limiting reagent between the
alane and the sulfonyl chloride; c Maximum yield was usually achieved
within 10 min from the addition of triphenylphosphine; d Reaction
temperature was -30 o C; e The reaction took 3h to go to completion
From the collected data, we conclude that solvents endowed with Lewis base
properties, e.g. THF, reduce the reaction rate but maximize the yield (entries 9-10
vs. 8); it is also evident that CH2Cl2 is the best solvent among the ones tested, and
it was used in all the subsequent reactions. In order to improve the yields further,
the reaction was then optimized performing a chemiometric analysis on the
system. The chemiometric analysis is increasingly employed in chemistry,
because it allows one to achieve a complete or nearly complete description of the
system studied by performing only a limited number of experiments. 188 Basically,

a chemiometric approach considers the system studied as a multivariate system, in
which one or more parameters have to be maximized by varying a number of
different independent variables. The interesting feature of this approach is that it
allows, even in the case of complex systems, to locate the absolute maximum of
the variable examined, and not a local maximum, which is often found employing
a univariate method (i.e. varying the reaction parameters one at time). Moreover, a
complete description of the system is achieved, which allows one to gain a better
control of the reaction.
Table 2.4: Chemiometric analysis of the sulfoxide formation reaction
N
(i-Bu) 2Al
Bu-n
+
S Cl
O
O
Me
PPh3 CH2Cl2 0 oC Entry a (i-Bu)2AlR TsCl b PPh3 b Yield(%) c
1 1 1 1.6 62
2 1 1.18 1.52 69
3 1 1.2 1.2 72
4 1 1 1.1 71
5 1 0.8 1.2 83
6 1 0.78 1.52 71
7 1 1.2 1.4 60
8 1 0.8 1.4 93
9 1 1.02 1.4 91.5
10 1 0.98 1.42 88
11 1 1.02 1.42 91
a All the reactions were performed at 0 o C in CH2Cl2; b
Molar ratio referred to the alkenyl alane; c Measured
using internal standard (n-nonadecane)
A multivariate fitting analysis afforded the following values for the coefficients
of the previous equation:
1
2
48 Chapter 2
2
1
Me
O
S
2
2
Bu-n
Y = 89. 94 − 5.
5X
− 9.
05X
− 22.
84X
−15.
15X
+ 5.
77X
X
The R-squared value was found to be 0.986, thus indicating an excellent fitting
of the experimental values. Graphical representation of the equation obtained is
given in Figure 2.1, and clearly shows the dome-like shape of the function: Yield
= f(PPh3,TsCl); the axes in the figure represent the values of the parameters
studied, normalized between -1 and 1.
1
2

Figure2.1: Contour representation of the function obtained with the
chemiometric analysis. PPh 3/alane ratio (1.10-1.60) is reported on the X axis;
TsCl/alane ratio (0.83-1.17) is reported on the Y axis; both ratios were
normalized in the range (-1;1)
The analysis of the fitting function allows one to identify the experimental
conditions for maximum yield. On the basis of the theoretical results a dialkyl alk-
1-enyl alane/tosyl chloride/triphenylphosphine = 1/0.92/1.35 ratio would give the
best yield, which was estimated to be 91%±4 at the 95% confidence level. A
reaction using this optimized ratio afforded the pure product in an excellent 94%
yield, in good agreement with predictions.
It was interesting to examine whether, and to what extent, the optimized
conditions for the synthesis of (E)-p-tolyl hex-1-enyl alane were general for the
synthesis of different substrates. It seemed unlikely that such finely tuned reaction
conditions could be optimal for the synthesis of structurally different substrates.
Reactions were conducted employing the same optimized reaction conditions
found before, and as shown in Table 2.5, yields of all products are similar,
provided that the stereoelectronic requirements of the system are not too different
from those of the chosen model.
Noteworthy is the result reported in entry 6; triphenylphosphine was
completely oxidized, but only a modest yield (35%) of the desired sulfoxide was
observed. The low yield observed in this case is presumably due to a reaction
between the acidic protons α to the sulfonyl moiety and pyridine present in the
reaction mixture. This hypothesis seems to be confirmed by what reported in the
literature on reactions between amines and sulfonyl chlorides. 189 The relatively
unreactive dialkyl alk-1-ynyl alanes are completely unreactive towards sulfonyl
chlorides also in this reaction, analogously to what observed in Section 2.2.3.
New synthetic approaches to alk-1-enyl sulfoxides 49

Table 2.5: Alk-1-enyl sulfoxides starting from pyridine-complexed alanes and
sulfonyl chlorides in the presence of triphenylphosphine
N
(i-Bu) 2Al
S
R'
Cl
O
1.35 PPh3 + O
R'
R
S
O
CH2Cl2, 0
R
o 0.92 + Ph
C
3PO +
N
10min
(i-Bu) 2Al
Cl
Entry a (i-Bu)2AlR R’SO2Cl Product Yield(%) b
Hex-n 1 Me
S
50 Chapter 2
O
O
Hex-c 2 Me
S
Cl
O
O
Bu-t 3 Me
S
Cl
O
O
O
Bu-n O
4 S
Cl
Ph 5 Me
S
O
Bu-n O
6 Me S
Cl
Cl
O
O
Cl
O Hex-n
S
Me
O Hex-c
S
Me
O Bu-t
S
Me
O Bu-n
S
Ph
O
S
Me
Ph
O Bu-n
S
a All reactions were conducted in CH2Cl2 at 0 o C employing a ratio
(i-Bu)2AlR/R’SO2Cl/PPh3 of 1/0.92/1.35; b Calculated on the isolated,
chemically pure product; c Yield did not increase even after 24 h.
2.3.3 Mechanistic details
The attention was then directed at the analysis of the mechanistic details of the
reaction under study. The very fast kinetics of the reaction made the direct
observation of reaction intermediates problematic, but some important
observations could be made:
1. The intermediacy of alk-1-enyl sulfones en route to the corresponding
sulfoxide can be confidently ruled out. As stated before, a reaction carried
out adding a known amount of sulfone to the reaction mixture proved that
sulfone is reduced only at a remarkably slower rate. It is clear that
phosphine reduces preferentially and almost selectively the sulfonyl
Me
94
92
89
70
75
35 c

chloride, which in fact disappears from the reaction mixture almost
instantaneously. The presence of a Lewis acid is necessary to reduce the
sulfone, since in the absence of alanes the sulfone could not be reduced (68
o C, 48 h).
2. The formation of sulfinyl chloride by reduction of sulfonyl chloride with
triphenylphosphine and pyridine, represented in Scheme 2.8, can be
excluded too.
S Cl
O
O
PPh 3
O
S Cl
O R
(i-Bu) 2Al
S
R
+ Ph3PO + (i-Bu) 2AlCl + Ph3PO Scheme 2.8: Possible reaction pathway involving a sulfinyl chloride
As will be more extensively explained in Section 2.4, benzenesulfinyl
chloride reacts with both uncomplexed and pyridine-complexed dialkyl
alk-1-eyl alanes affording a very complex reaction mixture, as represented
in Scheme 2.9. The alkenyl sulfoxide is detectable only in traces. On the
other hand, when triphenylphosphine oxide is employed as catalyst,
alkenyl sulfoxides are obtained in fairly good yields (35-57%). However,
under these conditions pyridine-complexed alk-1-enyl alanes fail to give
the sulfoxide, affording instead appreciable amounts of S-S coupling
products, mostly 21 and 22.
R
(i-Bu) 2Al
+
Ph S O
O
S S
Cl
Ph
O
CH2Cl2 S S
+
0 Ph
o N C
Ph
Ph
21 22
Scheme 2.9: Reaction between alanes and sulfinyl chlorides
3. As stated above, sulfinyl chlorides afford aryl alk-1-enyl sulfoxides in the
presence of catalytic or stoichiometric amounts of triphenylphosphine
oxide, and it is thus probable that some common intermediate exists in
these two reactions.
The presence of free sulfinyl chloride in the examined reaction is however
unlikely, due to the high reactivity of this compound towards pyridinecomplexed
and uncomplexed alanes; the key intermediate in the synthesis
of sulfoxides is likely to be somewhat less reactive that a sulfinyl chloride.
New synthetic approaches to alk-1-enyl sulfoxides 51

On the basis of the above observation, a resonable mechanism is depicted in
Scheme 2.10. In this proposal, after the complexation of unsaturated alane 23 with
pyridine, which affords intermediate 24, addition of sulfonyl chloride would lead
to complex 25. Addition of triphenylphosphine to this intermediate would lead to
the formation of 26 by substitution of pyridine on the sulfur center, and to its
isomer 27, in which the phosphorus atom is bound to the oxygen of sulfonyl
chloride. Final substitution of triphenylphosphine oxide by the alkenyl chain
present on the alane would bring about formation of the sulfoxide.
(i-Bu) 2Al
23
(i-Bu) 2AlCl + Ph3PO +
Ar
O
S
R
R
Py (i-Bu) 2Al
RSO2Cl 24
52 Chapter 2
N
R
(i-Bu) 2Al
O
Ar S O
PPh 3
27
Cl
R
(i-Bu) 2Al
O O Cl
Ar S N
25
(i-Bu) 2Al
R
PPh 3
O O
R
Ar S PPh 3
Scheme 2.10: Proposed reaction pathway for the synthesis of alk-1-enyl sulfoxides starting from
pyridine-alane complexes, triphenylphosphine and sulfonyl chlorides
NMR studies were performed to find the intermediates in the reaction and
confirm the mechanistic hypothesis advanced. As shown in Figure 2.2, when a
stoichiometric amount of pyridine is added to a benzene solution of the di-i-butyl
hex-1-enyl alane (Scheme 2.10, compounds 23 and 24), a dramatic change in the
chemical shifts of the alane and pyridine protons is observed (Figure 2.2, black
and red spectra). This confirms the formation of some kind of alane-pyridine
complex. The pyridine bound to the alane can be freed upon addition of a stronger
ligand; it was in fact verified that addition of the more basic 4-(N,N-dimethyl)aminopyridine
(DMAP) causes decomplexation of pyridine and formation of a
new DMAP-di-i-butyl hex-1-enyl aluminum complex. This complex is unreactive
in the above reaction.
26
Cl

Figure 2.2: NMR spectra of intermediates in the reaction

Upon addition of tosyl chloride, noticeable changes occur in chemical shifts of
tosyl chloride, pyridine and di-i-butyl hex-1-enyl aluminum, suggesting formation
of a pyridine-tosyl chloride complex still bound to the alane (Figure 2.2, green
spectrum); the presence of a simple pyridine-tosyl chloride complex can be ruled
out by the absence of signals characteristics of uncomplexed alane. Moreover, the
tosyl chloride-pyridine complex shows remarkably different chemical shifts from
those of the species present in the solution (Figure 2.2, green vs. blue spectra).
The most plausible structure is depicted in Scheme 2.10, compound 25, which is
in good agreement with the spectroscopic evidence. A synoptical view of the 1 H
chemical shifts for the different species is shown in Table 2.6.
After addition of triphenylphosphine, the reaction proceeds too quickly to be
monitored by NMR, and all the structures proposed in Scheme 2.10 should be
regarded as speculative. However, intermediate 27, if present, is likely to afford
the sulfoxide; it is in fact reasonable to assume that reactivity of compound 27 is
similar to that of the intermediate 28 formed when sulfinyl chloride is reacted
with triphenylphosphine oxide; as stated before and shown in Scheme 2.11,
compound 28 affords sulfoxides in fairly good yields.
Ph
O
S
+ Ph3PO Cl
Ar S Cl
O
O
PPh3 28
(i-Bu) 2Al
R
O
S
Ar
45-57%
+ Ph3PO R
+ (i-Bu) 2AlCl
Scheme 2.11: Reaction between sulfinyl chlorides, uncomplexed alanes and triphenyl phosphine
oxide
The proposed mechanism succeeds in the explanation of some experimental
features of the reaction. In particular, complete oxidation of triphenylphosphine
and disappearance of sulfonyl chloride is always observed even when alkenyl
sulfoxide does not form. It is evident from the mechanism depicted in Scheme
2.10 that intermediate 27 affords, after hydrolysis, sulfinic acid and
triphenylphosphine oxide; these are in fact the sole products recovered in the case
in which the alane is not able to transfer the unsaturated chain to the sulfur center.
The proposed mechanism requires decomplexation of the alane from the
nitrogen ligand in the very first step of the reaction.
This is in good agreement with the observation that using DMAP as ligand
shuts down the reaction. It was verified by NMR that DMAP is able to
quantitatively substitute pyridine in the complex with the alane; it is likely that
54 Chapter 2

this complex is too stable to react with sulfonyl chloride, and this inhibits the first
step of the reaction (formation of compound 25, Scheme 2.10). On the other hand,
heteroaromatic derivatives with basicity similar to that of pyridine (e.g.
isoquinoline, 4-ethyl pyridine) afford the sulfoxides in identical yields to those
observed when pyridine is employed. When triethylamine is used as ligand, the
reaction affords a nearly equimolar amount of sulfone and sulfoxide, in low
overall yield (25%). It should be noted that this result is similar to that obtained
when unsolvated alanes were used; triethylamine is known as a weak ligand for
alanes, due to the steric hindrance of the ethyl chains. Likely, the formed complex
is too labile to effectively moderate the reactivity of the alane, which reacts as its
uncomplexed form.
Table 2.6: Chemical shifts (expressed in Hertz) of the species evidenced in
Scheme 2.10
Proton
Free
a
compounds a
a
b
c
Al
d
a
b
a
c
e
f
g
i-Bu2AlR + Py a
h
m
n
m p
o
i
l
N
l
q p
O O
S
Cl
i-Bu2AlR + Py +
New synthetic approaches to alk-1-eyl sulfoxides 55
o
TsCl a
TsCl + Py a
a 330.3 364 353 -
b 601 646 636 -
c 111.5 126 117 -
d 1770 1895 1884 -
e 2242 1935 1929 -
f 629 708 699 -
g 345-390 405-480 390-465 -
h 345-390 405-480 390-465 -
i 227 269 265 -
l 2543 2513 2514 2538
m 2002 1942 1950 2000
n 2101 2038 2061 2099
o 2258 - 2260 2263
p 1936 - 1960 1959
q 503 - 522 521.5
a All spectra were recorded on a Varian Infinity spectrometer, at the frequency of 300
MHz. The signals were referred to the residual signal of C6H6, set exactly at 2134.36 Hz.
Hz were used instead of the more common ppm to better evidence even small changes in
chemical shifts.
In conclusion, this new synthetic approach to aryl alk-1-enyl sulfoxides starting
from sulfonyl chlorides, pyridine-alane complexes and triphenylphosphine affords

the products in excellent yields, often greater than 90%. This reaction can be
performed one-pot, under very mild conditions using inexpensive reagents; the
reagents are in simple stoichiometric ratios, and this provides an efficient
utilization of the organometallic reagent; this should be compared with the
synthesis of alk-1-enyl sulfoxides with aluminum sulfinates, described in Section
2.2, which required an alane/sulfinyl chloride molar ratio of 1.5/1, and thus yields
based on the organometallic reagents were about 50%. As for the previous
reaction, the process is completely stereoselective, affording pure (E)-isomers.
2.4 Alk-1-enyl sulfoxides starting from sulfinyl
chlorides
2.4.1 General remarks
As already discussed, sulfinyl chlorides can be considered as the most direct
precursors to alk-1-enyl sulfoxides, because the sulfur atom is already in the
appropriate oxidation state. This feature allows the synthesis of unsaturated
sulfoxides without the need for a reducing agent. Sulfinyl chlorides are
unfortunately very reactive, and due to their sensitivity toward water it is
necessary to store and handle them under inert atmosphere.
Ph S O
+ (i-Bu) 2Al
Cl
CH2Cl2, r.t.
Bu-n
30min
Ph S
56 Chapter 2
O
Bu-n
O O
Ph S + S +
15%
21 22
Scheme 2.12: Reaction between benzenesulfinyl chloride and di-i-butyl hex-1-enyl aluminum
Ph
S S
Ph Ph
+ (i-Bu) 2AlCl
The use of such compounds was taken into consideration despite the
limitations involved with their use; it was in fact of interest to try to gain access to
alk-1-enyl sulfoxides by a pathway different from the reductive ones examined
above. A study of the reactivity of sulfinyl chlorides vs. alanes may be useful in
explaining some mechanistic details of the previous reaction. As discussed in
Section 2.3.3, one may want to consider the possibility that sulfinyl chlorides
were formed during the course of the reaction.

Ph S O
PPh3O Cl (1 equiv.)
O
Ph S O
Cl
28
PPh 3
(i-Bu) 2Al
Bu-n
CH2Cl2, r.t., 30min
O Bu-n
S
52%
Scheme 2.13: Reaction between benzenesulfinyl chloride and di-i-butyl hex-1-enyl alane in the
presence of Ph3PO
New synthetic approaches to alk-1-eyl sulfoxides 57
Ph
29
+ (i-Bu) 2AlCl +Ph3PO A reaction was first performed by reacting benzenesulfinyl chloride with
unsolvated (E)-di-i-butyl hex-1-enyl aluminum. The corresponding sulfoxide was
recovered in a very modest yield (15%) and S-phenylbenzenethiosulfonate 21 and
of diphenyl disulfide 22 were detected (Scheme 2.12).
It is clear from this preliminary experiment that sulfinyl chlorides are too
reactive to afford the sulfoxide in good yields. It is in fact possible that sulfinyl
chloride reacted in the presence of Lewis acids by a radical pathway to give the
homocoupled product; this would be not unprecedented in the chemistry of these
sulfur derivatives. Pyridine-coordinated alanes also gave disappointing results,
leading to a mixture of S-S coupling products and affording the sulfoxides only in
traces. This could be explained by postulating a ligand exchange in solution,
resulting in the activation of the sulfinyl chloride towards the undesired reaction.
Taking into account the mechanistic proposal discussed in Section 2.3.3, it is
likely that the sulfinyl chloride may react with triphenylphosphine oxide,
affording intermediate 28 (Scheme 2.13). This reaction would support the
presence of intermediate 27 en route to sulfoxides.
To verify this assumption, the benzenesulfinyl chloride-triphenylphosphine
oxide complex was formed, and its formation was confirmed by 31 P NMR
spectroscopy through the observation of a 3.6 ppm upfield shift of the P signal
with respect to triphenylphosphine oxide; when di-i-butyl hex-1-enyl aluminum
was added, sulfoxide 29 was obtained in 52% yield (Scheme 2.13) as the only
identifiable product. The unreacted sulfinyl chloride is likely lost during the
workup as sulfinic acid, and therefore an accurate mass balance was not carried
out.
In addition to supporting the mechanistic hypothesis advanced in Section 2.3.3,
this reaction represented an interesting approach to the synthesis of aryl alk-1-enyl
sulfoxides, and it was therefore useful to study the effect of the amount of
triphenylphosphine oxide on the reaction yield. The results showed that the use of
0.5-1 equivalent of triphenylphosphine oxide gave uniform yields, i.e. the reaction
is, to some extent, catalytic (the oxide is not consumed stoichiometrically) but a

further reduction to 0.25 equivalents causes the yield to drop (32%). Finally,
different substrates were tested, to study the scope of this reaction; the results are
collected in Table 2.7.
Table 2.7: Sulfoxides starting from benzenesulfinyl chloride and alanes in the
presence of triphenylphosphine oxide
S Cl O
Ph3PO CH2Cl2 S OPPh Cl
O
3
Alk2Al R
CH2Cl2 R' S O
+Alk2AlCl R
+ Ph3PO Entry a (i-Bu)2AlR Product Yield(%) b
1
Bu-n
2 Bu-t
3 Bu-t
4
O Bu-n
S
58 Chapter 2
O
S
O
S
O
S
Bu-n
a All the reactions were performed at room temperature using
an Alk2AlR/PhSOCl/PPh3O=1/1/0.5 ratio; b Calculated on the
isolated, chemically pure product
As shown in Table 2.7, yields are usually around 50%. However, sulfinyl
chlorides react with moisture, and this feature makes it rather difficult to quantify
the conversion, which presumably is not quantitative. This hypothesis is supported
by the fact that no byproduct was found in any of the reaction mixtures. This
approach is the only method among those reported in this study which can be
successfully employed to synthesize aryl alk-1-ynyl sulfoxides in acceptable
yield. As already stated, dialkyl alk-1-ynyl alanes were in fact completely
unreactive in all the other approaches examined. Despite the low conversions, the
above reaction is particularly interesting due to the lack of byproducts, which
simplifies isolation and purification of products. Moreover, the possibility to
obtain acetylenic sulfoxides gives an easy access to (Z)-alkenyl sulfoxides, which
Bu-t
52
57
43
48

can be obtained by one of the reduction methods reported in the literature 145 and
previously discussed (Section 1.3.1).
New synthetic approaches to alk-1-eyl sulfoxides 59

Chapter 3
New synthetic approaches to unsaturated
sulfones
3.1 Introduction
During the preliminary studies on the synthesis of alk-1-enyl sulfoxides with
pyridine-coordinated alanes and triphenylphosphine (Section 2.3.1), appreciable
amounts of sulfones were obtained as byproducts. Other experiments proved that
the sulfone was not produced by the palladium-catalyzed cross-coupling reaction,
but it was formed by a different mechanism (Scheme 2.7). Direct reaction
between sulfonyl chloride and dialkyl alk-1-enyl alanes could also be excluded
because, as already described in Section 2.2, this reaction leads mainly to the
formation of aluminum sulfinates.
It was reasonable to hypothesize the presence of two possible pathways:
1. Formation of a sulfonyl chloride-pyridine adduct (compound 30, Scheme
3.1) and subsequent substitution by the organo alane;
2. Formation of a sulfonyl chloride-triphenylphosphine oxide adduct
(compound 31, Scheme 3.1) and substitution by pyridine-coordinated
alane;
61

Me
O O
Cl
O O
Cl
S
N
S PPh3 O
30
Scheme 3.1: Plausible intermediates in the formation of sulfones starting from sulfonyl chlorides
Both these intermediates were thoroughly investigated, and this chapter deals
with the results obtained. The first part will be dedicated to the discussion of
reactivity of intermediate 30, and the use of triphenylphosphine oxide as catalyst
(through intermediate 31) will be discussed later.
3.2 Alkenyl sulfones starting from sulfonyl chloridepyridine
complexes
3.2.1 Use of dialkyl alk-1-enyl alanes as alkenylating agents
The first few experiments were performed with the simplest system among
those considered in the previous chapter, the sulfonyl chloride-pyridine adduct. It
is well known that reaction with heteroaromatic nitrogen ligands, such as
pyridine, activate sulfonyl chlorides to nucleophilic substitution at sulfur. During
the NMR studies on the reactivity of pyridine-coordinated alanes with sulfonyl
clorides (Section 2.3.3), it was demonstrated that a sulfonyl chloride-pyridinealane
complex 25 is formed under mild conditions; unfortunately, this compound
turned out to be unreactive, and did not evolve to sulfone even after prolonged
reaction times.
A reaction was performed by slowly adding di-i-butyl-hex-1-enyl aluminum 23
to a stirred CH2Cl2 solution of sulfonyl chloride-pyridine adduct 30. Sulfone 19
was isolated in 47% yield; a 50% conversion, based on the recovered sulfonyl
chloride, was observed (Scheme 3.2).
62 Chapter 3
Me
31

O
O N
S
Cl
+
(i-Bu) 2Al
Bu-n
CH 2Cl 2, r.t.
O
O S
Me
Me
30 23
19
Bu-n
New synthetic approaches to unsaturated sulfones 63
47%
+
N
(i-Bu) 2Al
Cl
Scheme 3.2: Reaction of di-i-butyl hex-1-enyl aluminum with tosyl chloride-pyridine adduct
An analogous experiment, performed by adding pyridine – alane complexes to
tosyl chloride-pyridine adducts, demonstrated the complete inertness of
complexed alanes towards sulfonyl chloride-pyridine adducts. Attention was then
turned to the more reactive uncomplexed alanes. When the above reaction was
carried out adding the alane over a 15 min, increases in yield (68%) and
conversion (80%) were observed.
The effect of the addition rate of the organometallic reagent on the yield was
studied in several experiments, and it was noted that conversion and yield
increased with the addition rate. When fast additions were performed (less than 30
seconds) the product was isolated with a yield of 90% and a conversion of 96%.
Similar results were obtained when this procedure was adopted for other alanes
with slightly different substituents (Table 3.1).
The conversion seems to depend on the steric bulk of the moiety that is being
transferred. Assuming that the less sterically hindered the alkenyl moiety, the
more reactive the organometallic compound, one could speculate that alanes are
deactivated or consumed by some slow process. Remarkably, the sulfone is
always the only isolated product obtained under these conditions. Even in the case
of methanesulfonyl chloride, where a discrepancy between conversion and yield is
evident, this is presumably due to the work-up, since no product other than the
sulfone was observed. Finally, this procedure allows for the preparation of alkyl
alk-1-enyl sulfones in synthetically useful yields (Table 3.1, entry 5); these
derivatives are not obtainable with the other methods discussed later in this
chapter.

Table 3.1: Alk-1-enyl sulfones from sulfonyl chloride-pyridine adducts and
dialkyl alk-1-enyl alanes
O O
R' S Cl
N
O O Cl
R' S N
(i-Bu) 2Al
R
CH2Cl2, r.t., 30min
R' S
O O
Entry a (i-Bu)2AlR Product Conversion (%) b Yield(%) c
1
2
3
4
Bu-n
Hex-c
Bu-t
5 d Bu-n
Ph
O
O S
Me
O
O S
Me
O
O S
Me
O
O S
Me
O
O S
Me
Bu-n
Hex-c
Bu-t
Ph
Bu-n
64 Chapter 3
R
96 90
72 68
57 54
45 40
n.d. e 75
a All reactions were performed by fast addition of the alane to a CH2Cl2
solution of sulfonyl chloride-pyridine adduct at r.t.; b Based on recovered
sulfonyl chloride; c Calculated on the isolated, chemically pure product; d
Methanesulfonyl chloride was used; e The work-up did not allow the recovery
of the reagent.
3.2.2 The "copper effect"
In our preliminary experiments, it was observed that the Lewis acidity of the
alane was an important variable. This was particularly evident from the fact that
the use of pyridine completely inhibited the reaction. On this basis, the incomplete
conversion of tosyl chloride, observed when slow addition or when sterically
hindered alanes were used, could be understood.

(i-Bu) 2Al
Bu-n
+
S N
O
O
Me
Cl
O
O S
New synthetic approaches to unsaturated sulfones 65
Me
Cl
(i-Bu) 2Al
O
O
Bu-n
S
Me
+
Slow
N
(i-Bu) 2Al
Bu-n
Scheme 3.3: Ligand equilibrium hypothesized to explain partial conversion in the synthesis of
sulfones
Given that when fast additions are performed good conversions are achieved, it
is likely that a slow ligand exchange takes place, thus diminishing the
concentration of active alane. The postulated equilibrium is represented in
Scheme 3.3. It is evident that the concentration of pyridine increases with
conversion; when the addition is slow or the reaction of the alane is not fast
enough, there is a sufficiently high concentration of pyridine arising from the
ligand exchange step to efficiently bind the alane; the complexed organometallic
compound is unreactive toward the sulfonyl chloride-pyridine complex, thus
hindering conversion.
To overcome this problem, which limited the synthetic utility of the reaction, it
was necessary to free the alane from the pyridine originating from the ligand
displacement; the simple solution was to find a co-reagent which strongly
complexed pyridine, without interfering in other ways with the reaction. Cuprous
chloride (CuCl) was chosen for the following reasons:
1. The electronegativity of copper and aluminum is such that transmetallation
processes should not be involved.
2. Copper, both in oxidation state I and II, is known to form very stable
complexes with pyridine; formation of such compounds would free the
alane, thus allowing the reaction to proceed.
+
Cl
N

The reactions taken in consideration were the lowest yielding using the general
procedure. Any “copper effect” should more evident in these situations, and
increase the synthetic utility of the process.
Table 3.2: Copper effect on the reaction between sulfonyl chloride/pyridine
complexes and dialkyl alk-1-enyl alanes
p-Tol S O O
Cl
N
p-Tol
(i-Bu) 2Al
R
S O O Cl
N
1)
2) CuCl
CH2Cl2, r.t.
p-Tol S
Cl
(i-Bu) 2Al
O O
66 Chapter 3
R
+ CuCl(Py) n
Entry a (i-Bu)2AlR Product Yield(%) b Yield(%) b,c
1
2
3
4
Bu-n
Hex-c
Bu-t
Ph
O
O S
Me
O
O S
Me
O
O S
Me
O
O S
Me
Bu-n
Hex-c
Bu-t
Ph
49 75
72 80
54 69
40 62
a All the reactions were performed by adding the organometallic reagent to the
CH2Cl2 solution of the sulfonyl chloride/pyridine complex, allowing the reaction
to reach maximum conversion (2 hours); b By gas chromatography (internal
standard n-nonadecane); c After adding 0.5 molar equivalents of CuCl.
In all cases, the organometallic reagent was added to the stirred solutions of
sulfonyl chloride-pyridine adduct, and reactions were stirred until no further
conversion was achieved, as monitored by GLC analysis. When this happened,
variable amounts (between 0.25 and 0.75 equivalents) of CuCl were then added to
the reaction mixture. The appearance of an intense light-blue color was
immediately observed in all cases, and after a few minutes (usually 15 minutes)
GLC analysis evidenced a remarkable increase in the conversion (Table 3.2). The
effect of copper chloride on the reaction could be rationalized with the following
facts:

1. A catalytic role of copper can be ruled out. In fact, addition of copper
chloride to the reaction mixture immediately prior or after that of the alane
led only to the formation of degradation products, mostly arising from the
reductive disproportionation of sulfonyl chloride. It is possible that copper
chloride may react with sulfonyl chloride, leading to radical species which
can be responsible for the observed degradation products. The ability of
copper chloride to react with sulfonyl chlorides giving radical
intermediates is well documented. 90,92
2. Evidence for the complexation of pyridine with copper was obtained from
NMR studies of the reaction mixtures. When uncomplexed alanes were
mixed with sulfonyl chloride-pyridine complexes, spectra recorded in
benzene-d6 solutions showed signals characteristic of the following
species: a) sulfonyl chloride-pyridine complex; b) alkenyl sulfone; c)
pyridine-alane complex; d) two different di-i-butyl aluminum chloride
species, presumably bound to pyridine or to the sulfone. These signals are
in excellent agreement with the hypothesis reported in Scheme 3.3. As
increasing amounts of copper chloride were added, an increase in
conversion was evident; moreover, some broad peaks characteristics of
copper-pyridine complexes appeared in the NMR spectra.
From the results presented above, it is tempting to conclude that copper salts
interact with pyridine in the reaction mixture. The alane is thus freed to react with
the sulfonyl chloride-pyridine complex. In conclusion, the method described
herein represents a significant route to alk-1-enyl sulfones. The reaction of
uncomplexed dialkyl alkenyl alanes with sulfonyl chloride-pyridine adducts
affords the alkenyl sulfones in good yields and transfer selectivity; the conversion
can be increased by addition of copper chloride as scavenger for pyridine; as in
the case of sulfoxides, the stereoselectivity in the hydroalumination step and in the
transfer of the alkenyl chain allows for the preparation of the stereochemically
pure (E)-isomer.
3.2.3 Reaction of Grignard reagents with sulfonyl chloridepyridine
adducts
Considering the good results obtained with alanes in the reaction with sulfonyl
chloride-pyridine adducts, it was of interest to examine the use of Grignard
reagents in the analogous reaction. It was known from the literature that alkynyl
and alkenyl Grignard reagents give homocoupling products when reacted in the
New synthetic approaches to unsaturated sulfones 67

presence of thionyl chloride, 190 whereas alkyl Grignard reagents afford the
corresponding symmetrical sulfoxides and sulfides. Surprisingly, little is reported
on the reaction of Grignard reagents with sulfonyl chlorides. It is reported that this
reaction lacks selectivity, affording mixtures of sulfones, sulfoxides and sulfides,
due to the ability of Grignard reagents to reduce the S=O bond. In this brief
investigation, attention was directed towards the use of alkynyl and aryl Grignard
reagents, in view of their easy preparation and of the synthetic interest of diaryl
and aryl alkynyl sulfones. A preliminary reaction was performed adding pmethoxyphenyl
magnesium bromide to a THF solution of tosyl chloride-pyridine
adduct at room temperature; a satisfactory yield of sulfone (75%) was obtained
(Scheme 3.4).
Me
O
S
O
Cl
Py (1 equiv.)
THF, r.t.
Me
Cl
O
O
S N
MeO
r.t., 30min
68 Chapter 3
MgBr
Me
O O
S
75%
Scheme 3.4: Reaction of tosyl chloride-pyridine complex with p-methoxyphenyl magnesium
bromide
Differently from what reported with alkyl Grignard reagents, the reaction was
quite chemoselective, and no trace of the corresponding sulfide or sulfoxide was
detected in the reaction mixture.
The attention was then directed to other Grignard reagents; alkynyl and other
aryl magnesium halides were employed (Table 3.3).
It is interesting to note that this approach is useful in the synthesis of alkynyl
and aryl sulfones, but it fails when alkyl Grignard reagents are employed; under
these conditions many byproducts are obtained, arising from reduction of the
sulfone and S-S coupling, thus affording the sulfone in very low yields (5-10%).
Despite this limitation, the reaction can be synthetically useful, because it allows a
simple route to alkynyl sulfones, which are obtained in 44-57% yields. These
unexceptional yields are however interesting in view of the simplicity of the
method used. Alkynyl sulfones can be transformed into cis or trans alkenyl
sulfones by means of simple reduction, 69 as already discussed (Section 1.2.1).
OMe

Table 3.3: Reaction of tosyl chloride-pyridine adduct with Grignard reagents
O O
R' S Cl
N
O O Cl
R' S N
RMgBr
THF
r.t., 30min
R' S R
New synthetic approaches to unsaturated sulfones 69
O O
Entry a RMgBr Product Yield(%) b
1
2
3
4
5
MeO
F
Ph
n-Bu
t-Bu
MgBr
MgBr
MgBr
MgBr
MgBr
Me
Me
O
O S
Me
O
O S
O
O S
Me
Me
O O
S
O O
S
a All reactions were performed by quickly adding the Grignard reagent to a
THF solution of tosyl chloride-pyridine adduct at r.t.; b Calculated on the
isolated, chemically pure product; c Conversion was 82%; d Conversion
was 91%; e Conversion was 88%
3.3 Alk-1-enyl sulfones starting from pyridinecomplexed
alanes and sulfonyl chlorides in the
presence of Ph3PO
In the introduction to this chapter, it was pointed out that there were two
possible pathways to sulfones, presumably involving intermediates 30 and 31
(Scheme 3.1); with sulfonyl chloride-pyridine adducts, the reaction was described
in detail in the previous section. It was, however, unlikely that this intermediate
could form a sulfone as byproduct in the sulfoxide formation depicted in Scheme
2.7. It was in fact explained in this chapter that pyridine-complexed alanes fail to
afford sulfones, giving intermediate 25 exclusively.
OMe
F
Ph
Bu-n
Bu-t
75
69 c
44
57 d
50 e

N
(i-Bu) 2Al
1) Pyridine (20 equiv.)
2) TsCl, PPh3O (15%)
CH2Cl2, rfx.
Bu-n
O
O S
70 Chapter 3
Me
Bu-n
+
Me
O
S S
O
19 21
75% 10%
Me
+ N
(i-Bu) 2Al
Cl
Scheme 3.5: Reaction between pyridine-complexed di-i-butyl hex-1-enyl aluminum with tosyl
chloride in the presence of excess pyridine
On the basis of the mechanistic investigation carried out in Section 2.3.3, it is
reasonable to assume that, if intermediate 27 afforded sulfoxides, a similar
reaction could take place for its analogous 31. The possibility of intermediate 31
was supported by recent literature reports 191 which suggest that sulfonyl chlorides
react with Ph3PO in pyridine, to afford the corresponding triphenylphosphine
oxide adduct. In order to evaluate a possible catalytic role of triphenylphosphine
oxide in the formation of sulfones, a reaction was thus performed using pyridinecomplexed
di-i-butyl hex-1-enyl aluminum in the presence of 5% of
triphenylphosphine oxide. The sulfone was isolated in 48% yield, with a
conversion of 51%. The increase of the reaction temperature did not improve
significantly the yield, whereas the use of a large excess (20 molar equivalents) of
pyridine and of 15% of triphenylphosphine oxide, did allow for quantitative
convertion of the sulfonyl chloride into sulfone 19, which was isolated in a 75%
yield. The major side product was S-(p-tolyl)-toluene thio sulfonate 21 (Scheme
3.5).
It must be noted that a large excess of pyridine was necessary to achieve good
yields of sulfones. In fact, low yields (8-12%) of the sulfone and low conversions
(20-25%) were obtained when smaller amounts (two or three equivalents) of
pyridine were employed. This behavior is understandable considering that, as
already stated, pyridine-complexed alanes are completely unreactive toward
unactivated sulfonyl chlorides. Moreover, formation of tosyl chloridetriphenylphosphine
adducts occurs only when an excess of pyridine is present.

(i-Bu) 2Al
N
(i-Bu) 2Al
Cl
R
R
1) Py (excess)
2) ArSO2Cl (i-Bu) 2Al
N
Ar S +
O O
N
O O
+ Ph3PO + S
Ar
R
(i-Bu) 2Al
Ph 3PO
New synthetic approaches to unsaturated sulfones 71
N
R
30
Cl
Ar S O O
Cl
+ O
31
PPh 3
Scheme 3.6: Reaction between pyridine-complexed di-i-butyl alk-1-enyl alanes with sulfonyl
chloride in the presence of excess of pyridine and triphenylphosphine oxide
When insufficient amounts of pyridine are present, all the organometallic
reagent is complexed but much of the sulfonyl chloride remains unactivated, and
low yields are obtained. When a large excess of pyridine is added, only
complexed alane is present in the reaction mixture; in this case
triphenylphosphine oxide substitutes pyridine in compound 30, forming
intermediate 31. The reasonable assumption that direct displacement of chloride
by phosphine oxide is kinetically difficult was verified by means of NMR
analysis: 31 P spectra did not show any change in the chemical shift of
triphenylphosphine oxide upon mixing with tosyl chloride-pyridine complex. The
whole process is depicted in Scheme 3.6.
The Ph3PO-catalyzed synthesis of sulfones represented a valuable approach to
these compounds, and its applicability to the preparation of structurally different
derivatives was investigated. Results obtained with a few representative
organoaluminum compounds are listed in Table 3.4. The nature of the alkyl chain
in β position to the aluminum in the organometallic reagent has no influence on
reactivity; this is remarkably different with what observed in the previously
reported synthesis of sulfones (Section 3.2), and makes this protocol suitable for
the synthesis of structurally diverse derivatives.
Entry 7 in Table 3.4 suggests that this protocol is suitable for the synthesis of
aryl alkyl sulfones, although the presence of Lewis-acid salts (MgCl2) greatly
slows the reaction rate. In this case best yield was in fact achieved only after 92
hours at reflux. Alkyl sulfonyl chlorides fail to afford the corresponding sulfones;

this is likely due to the already mentioned reactivity the hydrogen atoms in α
position to sulfur atom towards bases such as pyridine.
Table 3.4: Alk-1-enyl sulfones starting from pyridine-complexed alanes and
sulfonyl chlorides in the presence of Ph3PO
N
(i-Bu) 2Al
S
R'
Cl
O
+ O
R
Ph3PO CH2Cl2 1h, rfx.
R' S
O O
72 Chapter 3
+
R
N
(i-Bu) 2Al
Cl
Entry a (i-Bu)2AlR R’SO2Cl Product Yield(%) b
O
Hex-n O
1 S
Cl
O
O
Hex-c 2 Me
S
Bu-t 3 Me
S
Cl
O
O
O
Bu-n O
4 S
Cl
Ph 5 Me
S
O
Bu-n O
6 Me S
Cl
7 c
Me
Me
Me
Cl
O
O
Cl
O
O
S
Cl
O
O S
O
O S
Me
O
O S
Me
O
O S
Ph
O
O S
Me
O
O S
Me
O
O S
Hex-n
Hex-c
a All reactions were performed at reflux in CH2Cl2 using a 20/1/0.15
pyridine/alane/Ph3PO ratio; b Calculated on the isolated, chemically pure
product; c The organometallic reagent was prepared in situ starting from AlCl3
and (R,S)-2-methylbutyl magnesium chloride; d Maximum yield was obtained
after 92 hours.
In conclusion, this protocol allows one to synthesize aryl alkenyl sulfones in
good yields (70-76%), using a one-pot procedure; unlike the previously described
reaction, there is no clear dependency of reactivity on the steric bulk at the
Me
Me
Bu-t
Bu-n
Ph
Bu-n
Me
75
70
76
71
70
20
63 d

position β to the aluminum atom. This feature makes the presented reaction quite
suitable for the synthesis of a wide range of products using a straightforward
experimental procedure.
New synthetic approaches to unsaturated sulfones 73

Chapter 4
Reissert-like reactions of dialkyl alk-1-enyl
aluminum-pyridine complexes with acid
chlorides
4.1 Introduction
Heteroaromatic systems are very valuable building blocks in the synthesis of
biologically active compounds, 192,193,194,195 and extensive efforts have been
devoted during the past century to finding efficient methods for the addition of
nucleophiles to quinoline and isoquinoline derivatives. 196,197,198 One of the oldest
protocol in this field is the Reissert reaction, first described in 1905. The reaction
allows the cyanation of quinoline ring in excellent yields; due to its potential, this
protocol has been thoroughly developed. 198,199 In this context, nucleophilic 1,2
addition of organometallic reagents to pyridine derivatives has received
considerable attention; the reactions with lithium derivatives, 200 Grignard
reagents 201,202,203,204 alkenyl stannanes 197,205,206,207,208 and silyl derivatives 209 have
been extensively studied. Applications to the synthesis of natural products 204,210
and liquid crystals 203 have been recorded. Regioselectivity of the reaction often
depends on the nature of the alkylating agent and is sometimes incomplete.
In the previous chapters it was remarked that complexation of dialkyl alk-1enyl
aluminum reagents with nitrogen ligands strongly affects the reactivity of the
alane; it was shown that these complexes present a completely different reactivity
75

from their uncomplexed counterparts, and this observation led to selective and
efficient synthetic routes to unsaturated sulfones and sulfoxides. This
complexation is expected to modulate not only the reactivity of the alane, but also
of the pyridine; it was in fact reported that aluminum-based Lewis acids could
effectively catalyze the Reissert reaction. 199 In the light of these reports, it was
interesting to investigate the reactivity on pyridine-alane complexes with acid
chlorides; two different pathways are conceivable:
1. The reaction could afford unsaturated ketones, by formal substitution of
chlorine atom on the acid chloride with alkenyl chain, with or without the
formation of an intermediate acid chloride-pyridine adduct.
2. The pyridine could be activated toward a Reissert-like reaction.
The second hypothesis was the more intriguing one: indeed, in spite of the
large number of synthetic approaches to the alkenylation of nitrogen bases, the
use of alanes is unprecedented. To verify which of the two pathways may be
operational, some preliminary studies were performed and the results will be
discussed in this chapter.
4.2 Preliminary experiments
A preliminary experiment, involving reaction of acid chlorides with pyridinealane
complexes, was performed in order to acquire some information on the
reactivity of this system. When the di-i-butyl hex-1-enyl aluminum-pyridine
complex 18 was reacted at 0 o C with an equimolar amount of benzoyl chloride 32,
no trace of phenyl 1-(E)-hex-1-en-1-yl ketone was detected; the reaction product
was 1-benzoyl-2-[1-(E)-hex-1-en-1-yl]-1,2-dihydropyridine 33, recovered in a
nearly quantitative (94%) yield (Scheme 4.1).
(i-Bu) 2Al
N
+
O
Cl
CH 2Cl 2
0 o C, 5min N
Bu-n
18 32 33
76 Chapter 4
O
Bu-n + (i-Bu) 2AlCl
Scheme 4.1: Reaction of di-i-butyl hex-1-enyl aluminum/pyridine complex with benzoyl chloride
This result clearly indicated that pyridine was activated towards the addition of
nucleophiles; furthermore, 1,2 addition occurred selectively, thus allowing

formation of a single product. The addition of an alkenyl chain to the pyridine
system by means of dialkyl alk-1-enyl aluminum reagents opened interesting
synthetic possibilities, in particular for the excellent yield and the simple work-up
procedure. Attention was directed to the synthesis of other substrates, in order to
better understand the scope and limitations of the reaction.
4.3 Study of the reaction
The generality of this protocol was evaluated using different acid chlorides and
organo aluminum compounds, obtained from hydroalumination of terminal
alkynes. It is clear from reported data (Table 4.1) that the reaction affords the
desired products in similar yields regardless of the starting alkyne or the acid
chloride employed.
Steric hindrance in the alkenyl chain in position β to the aluminum does not
have any effect on reaction times nor on the yield (entries 1 vs. 3). Furthermore,
both aryl and alkyl acid chlorides can be successfully employed in this protocol,
without any effect on yields and reaction times (entries 1,2,4).
Considering the good results obtained with the simple pyridine system, the
study was widened to more complex systems, such isoquinoline (Scheme 4.2).
(i-Bu) 2Al
N
Bu-n
+
O
Cl
CH 2Cl 2
0 o C, 5min
Bu-n
Reissert-like reactions of dialkyl alk-1-enyl aluminum-pyridine complexes with acid chlorides 77
N
O
Ph
+ Me
Me
34 35
85% 10%
Scheme 4.2: Reaction between isoquinoline-di-i-butyl hex-1-enyl aluminum complex and benzoyl
chloride
A preliminary reaction was carried out under the same experimental conditions
used for pyridine. In this case product 34 was isolated in a satisfactory (85%)
yield, but only partial selectivity was observed, and appreciable amounts (10%) of
the correponding alkylation product 35 were obtained. Compound 34 was,
however, the sole product (93%) when reaction was performed at -20 o C (Scheme
4.3).
N
O
Ph

Table 4.1: Reaction of pyridinated organoalanes with acid chlorides
N
(i-Bu) 2Al
O Cl
+
R'
R
CH 2Cl 2
0 o C, 5min
78 Chapter 4
R'
N
O
R + (i-Bu) 2AlCl
Entry a (i-Bu)2AlR R’COCl Product Yield(%) b
1 Bu-n Cl
2
Bu-n
O
Me
3 Bu-t Cl
4
Bu-n
O
O
Cl
O
Cl
a All reactions were performed in CH2Cl2 at 0 o C; b Calculated on the
isolated, chemically pure product
Different ligands as well as acid chlorides were employed to prepare a wider
range of targets (Table 4.2). It is evident that the nature of the acid chloride
employed does not affect the reaction. Furthermore, the applicability of this
reaction seems to be very broad: both alkynyl and alkenyl aluminum reagents are
reactive under the reported conditions (entries 2,3), and it is possible to obtain, in
satisfactory yields, even products bearing groups potentially reactive towards
alanes (entry 4).
(i-Bu) 2Al
N
Et
Et
+
O
Cl
n-Bu
n-Bu
t-Bu
n-Bu
CH 2Cl 2
-20 o C, 5min
O
O
O
O
N
N
N
N
Bu-n
N
36
55%
O
Ph
94
94
94
90
+
(i-Bu) 2AlCl
Scheme 4.3: Reaction of di-i-butyl 1’-ethylbut-1-enyl aluminum-isoquinoline complex with
benzoyl chloride

The major limitation emerging from this study is represented by the results
obtained employing α-substituted alkenyl alanes. In this case the sole product
isolated was 36, arising from a reduction of the aromatic system (Scheme 4.3).
Table 4.2: Reaction of alane-isoquinoline complexes with acid halides
Entry a (i-Bu)2AlR RCOCl Product Yield(%) b
1
Bu-n
O
Me
2 Bu-n Cl
3 Bu-n Cl
O
Bu-n 4 Me
O Cl
5 Bu-n Cl (CH 2) 8 Cl
6 Bu-n Br
O
Br
7 Bu-n Cl
O
Cl
O
O
O
O
O
Cl
N Bu-n
Reissert-like reactions of dialkyl alk-1-enyl aluminum-pyridine complexes with acid chlorides 79
n-Bu
n-Bu
n-Bu
n-Bu
O
N
N
O
O
O
O
N O
O
N (CH 2) 8 N
Me
n-Bu Bu-n
n-Bu
N
O O
a
All reactions were performed in CH2Cl2 solution at 0 o C; b Calculated on the
isolated, chemically pure product.
It is known that 2,3-dihydro-1H-imidazole derivatives are often obtained by
complex or low-yielding approaches, which limits the availability of these
compounds. 211,212,213 On the contrary, use of an N-acyl imidazole as ligand to the
organoalane would afford these products with a simple and straightforward
procedure. A preliminary reaction was carried out on N-benzoyl imidazole 37,
which after complexation with di-i-butyl hex-1-enyl aluminum to form
intermediate 38 was reacted with benzoyl chloride. The reaction afforded the (E)-
Bu-n
N
O
n-Bu
N
Br
93
93
92
60
54
55
58

2-hex-1’-enyl-1,3-dibenzoyl-2,3-dihydroimidazole 39 in good (68%) yield,
(Scheme 4.4), thus demonstrating that this methodology is easily applicable to the
synthesis of 2,3-dihydro imidazole derivatives.
O
N
N
Ph
(i-Bu) 2Al
Bu-n
(i-Bu) 2Al
N
Bu-n
Ph Cl
CH2Cl2 -20 oC, 5min
2) H3O +
1)
80 Chapter 4
N
Ph
O
O
Ph
O
N N
37 38
39
Scheme 4.4: Application of our new reaction to an imidazole derivative
68%
Bu-n
Finally, a more complex reaction sequence was examined, which involved
formation of a tricyclic derivative. Nitrogen-containing tricyclic systems are
valuable in the synthesis of natural and bioactive products, but their synthesis is
often difficult to achieve; in view of the flexibility of the reaction under study,
extension to the synthesis of tricyclic derivatives seemed possible. 214,215,216
Indeed, 8-trimethyl silyloxy quinoline 40, obtained from 8-hydroxyquinoline and
trimethyl silyl chloride, could be employed as ligand in this reaction and
complexed with (E) di-i-butyl hex-1-enyl aluminum to form intermediate 41
(Scheme 4.5); bromo acetyl bromide was added at -20 o C, and upon warming to
room temperature the labile intermediate 42 was obtained. a Compound 42
cyclized both thermally and in the presence of KF or NaOH under phase-transfer
conditions to afford 5-[(E)-hex-1’-enyl]-2H-[1,4]oxazino[2,3,4-ij]quinolin-3(5H)one
43. Closely related compounds have been investigated 214 in view of their
microbiocidal 215 and fungicidal 216 activity. The efficient synthesis of 43 bodes
well for the convenient preparation of a host of synthetically related derivatives.
a Compound 42 was too labile to record appropriate 1 H and 13 C NMR spectra. It was however
possible to obtain the following GC-MS spectrum: 423 (M .+ 1, 9), 421(8), 406(7), 343(18),
342(67), 328(7), 301(28), 300(100), 285(9), 284(37), 258(14), 242(15), 240(22), 218(67), 202(92),
186(7), 172(21), 142(4), 128(3), 73(26)
O
Ph

Me 3SiO
O
N
O
N
43
80%
Bu-n
(i-Bu) 2Al
(i-Bu) 2Al
Me 3SiO
Reissert-like reactions of dialkyl alk-1-enyl aluminum-pyridine complexes with acid chlorides 81
Bu-n
40 41
KF
Et 2O/H 2O
r.t., 45min
Br
Br
Me 3SiO
O
Br
42
N
CH 2Cl 2
-20 o C to r.t.
20min
O
N
Bu-n
Bu-n
Scheme 4.5: Synthesis of a tricyclic system by alkenylation and subsequent deprotection of
substituted quinoline ring
4.4 Mechanistic considerations
Although a mechanistic study has not been performed on this reaction, some
reasonable hypotheses can be advanced; the most reasonable reaction mechanism
involves the formation of an acid chloride-heterocycle adduct, and subsequent
transfer of the unsaturated chain from the alane to the position α to the nitrogen
atom; to account for the tendency of alanes to form stable complexes with Lewis
bases, intermediate 44 is proposed (Scheme 4.6). This intermediate, similar to
compound 25 described in Scheme 2.11, is unstable and spontaneously reacts to
afford the products.
N
(i-Bu) 2Al
R
O
R' X
CH2Cl2 Cl
(i-Bu) 2Al
O
R' N
44
R
(i-Bu) 2Al
O
R' N
Scheme 4.6: Plausible reaction pathway between heteroaromatic nitrogen ligand-acid chloride
complexes and di-i-butyl alk-1-enyl alanes.
Cl
R

In support of this hypothesis, di-i-butyl hex-1-enyl aluminum was reacted with
preformed pyridine-benzoyl chloride complex (Scheme 4.7, path a) and
isoquinoline-benzoyl chloride complex (Scheme 4.7, path b). The expected
product were obtained in lower yields than those obtained with complexed alanes,
(Table 4.1, entry 1 and Table 4.2, entry 2 respectively); this suggests the
mechanism is more subtle than one involving the uncomplexed alane and the
acylated pyridine, indicating that perhaps slow decomplexation of the pyridinealane
complex is a key factor in a successful reaction.
O
Cl
+
O Cl
+
Ph
CH2Cl2 0 o O
N
C, 5min
N
Cl
CH2Cl2 0 o N
C, 5min
Cl
Ph
N O
(i-Bu) 2Al
(i-Bu) 2Al
82 Chapter 4
n-Bu
n-Bu
70%
N
25%
N
O
O
+
Ph
+
Ph
Side
products
Scheme 4.7: Reaction between benzoyl chloride-heteroaromatic nitrogen ligand and di-i-butyl hex-
1-enyl aluminum
In conclusion, reaction of heteroaromatic nitrogen systems/alane complexes
with acid halides affords products arising from the addition of the alkenyl chain in
position 2 of the heteroaromatic ring; products are obtained in excellent yields,
with simple work-up procedures. This protocol is amenable to the preparation of
many synthetically useful intermediates; in particular, synthesis of (E)-2-hex-1’enyl-1,3-dibenzoyl-2,3-dihydroimidazole
39 and of the tricyclic product 5-[(E)hex-1’-enyl]-2H-[1,4]oxazino[2,3,4-ij]quinolin-3(5H)-one
43 has been achieved
in high yields; this last compound is of potential interest, due to its close
relationship with derivatives having fungicidal and herbicidal activity. It has to be
pointed out that, as already seen for the preparation of sulfones and sulfoxides,
and as usual in the chemistry of dialkyl alk-1-enyl aluminum reagents, products
are always obtained as single isomer, because the geometry of the double bond is
retained during the transfer.
Bu-n
Bu-n
N
12%
O
Ph

Chapter 5
Conclusions
The main goal of this work was the development of new synthetic routes to
alk-1-enyl sulfoxides and sulfones. As already stated, these compounds are very
valuable as building blocks and chiral auxiliaries in organic synthesis, due to their
peculiar stereoelectronic properties, which allow excellent diastereo- or
enantiocontrol even on remote reaction centers.
The current approaches to these derivatives, described in Chapter 1, are
however not always efficient, and for this reason new approaches are desirable.
Surprisingly, among the reported routes to sulfones and sulfoxides, use of dialkyl
alk-1-enyl aluminum reagents was almost completely unexplored, in contrast with
what reported on other alkenyl organometallic reagents. Considering that dialkyl
alkenyl aluminum reagents are easily obtained by hydroalumination of alanes, our
attention was directed to these easily available reagents.
The first attempts were performed using the modification of a procedure
reported in the 1960s by Reinheckel (Section 2.2). In this approach, an aluminum
sulfinate was prepared from a sulfonyl chloride and Et3Al. Subsequent addition of
the suitable dialkyl alkenyl aluminum in hexane solution afforded the pure
sulfoxide. The reaction was tested on several alkynes and sulfonyl chlorides, and
no appreciable dependence on the nature of the substrates employed was found
(Scheme 5.1).
83

R
O
S
+
OAlEt2 O
O O CH
S AlEt 2Cl2 + 3 S
R Cl
r.t. R OAlEt2 (i-Bu) 2Al
(i-Bu) 2Al
R'
Hexane, rfx.
5h
R'
R
72-75%
84 Chapter 5
O
/ RSO 2Cl 1.5/1
S
R'
+ EtCl
(i-Bu) 2Al O +
AlEt2 Scheme 5.1: Modification of Reinheckel protocol applied to the synthesis of alk-1-enyl
sulfoxides
Although the reaction seemed reasonably efficient, it was necessary to employ
1.5 molar equivalents of the alane in order to achieve a good yield of sulfoxide;
this resulted in a rather poor yield with respect to the starting organo metallic
reagent. Any attempt to improve the yields failed, thus limiting the synthetic
applicability of this reaction.
A different approach was adopted in the synthesis of sulfoxides, starting from
pyridine-complexed alanes (Section 2.3.2). Ph3P was chosen as reducing agent,
and acceptable yields of sulfoxide were obtained. The reaction was improved by
studying the effect of temperature, solvents and ratio between reagents, by means
of a chemiometric analysis; this led to optimized reaction conditions (Scheme
5.2).
N
(i-Bu) 2Al
R
+
S
Ar
Cl
O
O
N
(i-Bu) 2Al
PPh 3
CH 2Cl 2
0 o C, 5min
R
O
Ar S
70-94%
R
/ ArSO 2Cl/Ph 3P 1/0.92/1.35
+ Ph 3PO +
N
(i-Bu) 2Al
Cl
Scheme 5.2: Synthesis of alk-1-enyl sulfoxides from pyridine-alanes complexes, sulfonyl
chlorides and Ph3P.
Preliminary mechanistic investigations were performed on this reaction
(Section 2.3.3); in particular, NMR analysis of the reaction intermediates, and
reactions performed with benzene sulfinyl chloride, allowed to propose a
rationale. This hypothesis, although not fully demonstrated, explains all the
experimental evidence available.
The study of the synthesis of alk-1-enyl sulfones took first into consideration
the reactivity of sulfonyl chloride-pyridine complex with unsolvated alanes

(Section 3.2). It was found that good to excellent conversions can be achieved
when a fast addition of the alane to the sulfonyl chloride-pyridine complex was
performed (Scheme 5.3). Conversions and yields seemed to depend on the steric
hindrance of the residue present on the alkenyl chain.
O O
R' S Cl
N
O O Cl
R' S N
(i-Bu) 2Al
+ N
(i-Bu) 2Al
Cl
Conclusions 85
R
CH 2Cl 2, r.t., 5min
R' S
O O
40-90%
Scheme 5.3: Synthesis of alk-1-enyl sulfones starting from TsCl-Py complex and
uncomplexed alanes.
Further investigations showed that the less than quantitative conversion was
likely due to the complexation of pyridine with unreacted dialkyl alkenyl
aluminum; this hypothesis was confirmed by NMR analysis performed on the
reaction mixtures. Addition of copper chloride as pyridine complexant led to
better yields (Section 3.2.2).
In order to achieve more general results, a different approach was studied
which employed Ph3PO as catalyst. In this case, pyridine-alane complexes gave
best results, allowing the synthesis of aryl alkenyl sulfones in good yields (Section
3.3).
N
(i-Bu) 2Al
R
+
S
Ar
Cl
O
O
Ph3PO CH2Cl2 rfx., 1h
Ar S
O O
70-76%
+
R
R
N
(i-Bu) 2Al
Cl
Scheme 5.4: Synthesis of alk-1-enyl sulfones from pyridine-alane complexes and sulfonyl
chlorides in the presence of Ph3PO
This procedure gave similar results regardless of the chain transferred (Scheme
5.4).
Although the synthesis of aryl alkynyl and diaryl sulfones was not a goal of
this work, a brief investigation was performed on their preparation; acetylenic and
aryl Grignard reagents, whose synthesis is particularly easy, were tested. In these
cases acceptable, even though rather erratic, yields were obtained (Section 3.2.3).
Considering the good and unexpected results obtained in the previously
summarized rections, as last part of this work, the reactivity of di-i-butyl alk-1enyl
aluminum-pyridine complexes towards compounds different from sulfonyl

chlorides was tested (Chapter 4). It was found that N-acyl-2-alk-1’-enyl-2Hdihydropyridine
derivatives were formed in nearly quantitative yields upon
addition of acid chlorides under very mild reaction conditions (Scheme 5.5).
N
(i-Bu) 2Al
R
+
O
R'
Cl
CH 2Cl 2
0 o C, 5min
86 Chapter 5
R'
N
O
90-94%
+ (i-Bu) 2AlCl
R
Scheme 5.5: Synthesis of N-acyl-2-alk-1’-enyl-2H-dihydropyridine and dihydroisoquinoline
derivatives by reaction of acid chlorides with complexed alanes
This protocol afforded synthetically interesting derivatives and was extended to
benzoyl imidazole and 8-trimethylsilyloxyquinoline. In all cases the reaction
afforded the desired compounds in excellent yields, without any trace of
byproducts.

Part III
Experimental section

Chapter 6
Experimental section
6.1 Chemicals and instruments
6.1.1 Purification of solvents and reagents
All the solvents employed were purified and dried immediately before use.
Tetrahydrofuran (THF) was stirred in the presence of KOH for 12 h, then refluxed
on, and distilled from, sodium and LiAlH4 subsequently. 217 Diethyl ether and
hexane were refluxed on, and distilled from, sodium and LiAlH4. 217
Dichloromethane (CH2Cl2) was refluxed on, and distilled from, P2O5. 217 Pyridine
was refluxed on, and distilled from, potassium hydroxide (KOH), then stored in
the dark under N2 atmosphere. 217 Tosyl chloride was purified by estraction in a
Soxhlet apparatus, using benzene as solvent. Alkynes were distilled immediately
before use. Quinoline and isoquinoline were purified by distillation.
Trimethylsilyl chloride was distilled immediately before use. Triethyl aluminum
was purified by distillation (b.p. 51 o C/0.1 mmHg). The Grignard reagents
employed were available in the laboratory and were used after titration.
6.1.2 Instruments
Gas chromatographic analyses were performed on a Perkin-Elmer 8500 or on a
Perkin-Elmer Clarus 500 gas chromatograph, equipped with a split-splitless
injector and a FID detector, using a capillary column ZB-1 (15 m*0.25 mm, film
thickness 0.25 μm), and He as carrier gas. NMR spectra were recorded on a
Varian Gemini NMR spectrometer, at the frequencies of 200 MHz ( 1 H) and 50
89

MHz ( 13 C) respectively, using TMS and CDCl3 as internal standard, unless
otherwise stated. Mass spectra were recorded on an Agilent 5995A spectrometer,
interfaced with an Agilent 5980 gas chromatograph, equipped with a split-splitless
injector and a ZB-1 column (30 m*0.25 mm, film thickness 0.25 μm), using He as
carrier gas.
6.2 Synthesis of the starting reagents
6.2.1 Synthesis of di-i-butyl aluminum hydride (DIBAL-H)
As previously reported, triisobutyl aluminum (50 ml), was transferred via
cannula into a three-necked flask equipped with a condenser and a magnetic
stirrer, dried and maintained under N2 atmosphere. The reaction mixture was
slowly heated to 130 o C, and the apparatus was placed under vacuum (18 mmHg).
After 6h the product was transferred under inert atmosphere into a distillation
apparatus and distilled under vacuum (b.p. 86 o C/0.1 mmHg). The purified
product was maintained under N2.
6.2.2 Synthesis of benzenesulfinyl chloride
A 250 ml, two-necked flask equipped with a reflux condenser and a magnetic
stirrer was dried and placed under a N2 atmosphere. Freshly distilled thionyl
chloride (50 ml) was added; 21.473 g (139.9 mmol) of sodium benzenesulfinate
were cautiously added in small portions to the stirred reaction mixture. The
reaction mixture was stirred for 2h, and filtered under inert atmosphere. When the
exothermic reaction ceased, the excess of thionyl chloride was removed under
vacuum and the residue was washed several times with anhydrous diethyl ether.
The crude reaction product was transferred into a distillation apparatus.
Distillation at reduced pressure (85-90 o C/0.05 mmHg) afforded 13.45 g (64%) of
product.
6.2.3 Synthesis of 1-N-benzoyl imidazole
According to a reported procedure, 218 a 50 ml three-necked flask,
equipped with a reflux condenser and a magnetic stirrer, dried
and placed under N2 atmosphere, was filled with 1.74 ml (15
mmol) of benzoyl chloride and 25 ml of dry THF. The reaction
mixture was cooled to 0 o O
N
N
C, and imidazole (2.04 g, 30 mmol), dissolved in 25 ml
of dry THF, was added dropwise during 10 minutes. After the appearance of an
90 Chapter 6

abundant white precipitate, the mixture was stirred for additional 3h, then filtered.
The clear ethereal solution was quickly washed with 100 ml of cold water and
dried over Na2SO4. After removal of the solvent at reduced pressure, 2.008 g
(11.7 mmol, 78%) of chemically pure product were recovered, as a colorless
liquid; GC-MS (m/z, I%): 172 (M .+ , 21), 105 (100), 95 (14), 77(32), 65(8); 1 H
NMR: 7.15 (d, J=0.6 Hz, 1H), 7.5-7.85 (m, 6H), 8.08 (s, 1H); 13 C NMR: 118.1,
129.0, 129.8, 130.9, 132.0, 133.6, 138.2, 166.1.
6.2.4 Synthesis of 8-trimethylsilyloxyquinoline
Analogously to what previously reported, 219 a two-necked flask
equipped with a magnetic stirrer and a reflux condenser,
maintained under inert atmosphere, was successively charged
with 50 ml of dry CH2Cl2, 4.785 g (33 mmol) of 8hydroxyquinoline,
2.357 g of imidazole (34.65 mmol), and 4.62
ml (36.3 mmol) of trimethylsilyl chloride. The mixture was stirred overnight, then
diethyl ether (100 ml) was added; the resulting suspension was filtered through
synthered glass. The organic layer was dried over Na2SO4 and the solvent
evaporated under reduced pressure (18 mmHg), affording the chemically pure
product as a yellowish oil (6.323 g, 88%); GC-MS (m/z, I%): 216 (M .+ , 3), 204
(5), 203 (20), 202 (100), 186(2), 172 (34), 142 (4), 128 (5), 101 (5), 94 (4); 1 H
NMR: 0.2 (s, 9H), 7.21 (dd, J=7.2 Hz, J’= 1.4 Hz, 1H), 7.36 (dd, J=8.2 Hz, J’=1.4
Hz, 1H), 7.45 (dd, J=4.2 Hz, J’=4.4 Hz, 1H), 7.48 (dd, J=4.2 Hz, J’=0.9 Hz, 1H),
8.18 (dd, J=8Hz, J’=0.9 Hz, 1H), 8.81 (dd, J=4.4 Hz, J’=1.4 Hz, 1H); 13 Me3Si O
N
C NMR:
5.4, 110.4, 118.0, 121.9, 127.9, 128.7, 136.3, 138.4, 148.1, 152.4..
6.3 General procedures
General procedures for the previously described reactions are here reported.
Characterization of the synthesized products are reported in Section 6.4.
6.3.1 Hydroalumination of alkynes
In a typical run, a 100 ml three-necked flask equipped with reflux condenser,
magnetic stirrer and dropping funnel, dried and maintained under N2, was
successively charged with 20 ml of dry hexane and 4.4 mmol of the appropriate
alkyne. The solution was cooled to 0 o C and 4.0 mmol of DIBAL-H in 5 ml of dry
hexane were added dropwise through the dropping funnel. The mixture was
Experimental section 91

efluxed until a complete conversion (GLC) of the reagent was achieved (usually
after 6h), then allowed to cool to room temperature. The resulting alane was
employed in the subsequent reactions without further purification.
6.3.2 Synthesis of unsolvated dialkyl alk-1-ynyl alanes
In a typical run, a three-necked flask equipped with a reflux condenser, a
magnetic stirrer and a dropping funnel, mantained under N2, was charged with 4.0
mmol of the appropriate alkyne dissolved in 20 ml of dry hexane. The reaction
mixture was cooled to -20 o C and then added dropwise of butyllithium (4.0 mmol)
in 5 ml of hexane. After stirring for 30min, the resulting white suspension was
warmed to 0 o C and 4.0 mmol of Et2AlCl were added to the reaction mixture.
After 30 min the homogeneous solution was allowed to warm at room temperature
and the resulting organoalane was employed in the subsequent reactions without
further purification.
6.3.3 Synthesis of alk-1-enyl sulfoxides via aluminum sulfinates
In a typical run, a three-necked flask dried and maintained under N2, equipped
with a magnetic stirrer, a reflux condenser and a dropping funnel, was charged
with 2.0 mmol of the appropriate sulfonyl chloride dissolved in 3 ml of dry
CH2Cl2. The solution was cautiously added of 0.27 ml (2.0 mmol) of triethyl
aluminum in 5 ml of dry CH2Cl2. After the exothermic reaction ceased, the
solution was allowed to cool to room temperature, then diluted with 20 ml of dry
hexane and 3 mmol of the appropriate di-i-butyl alk-1-enyl alane, prepared
according to the procedure described in Section 6.3.1. The reaction mixture was
refluxed for 5 hours, then cooled and siphoned onto a short column of silica gel.
After elution with 200 ml of CH2Cl2 and drying on anhydrous Na2SO4, removal of
the solvent at reduced pressure afforded the chemically pure sulfoxide.
6.3.4 Synthesis of aryl alk-1-enyl sulfoxides using pyridinated
organo alanes
In a typical run, a three-necked flask, equipped with a reflux condenser, a
dropping funnel and a magnetic stirrer, was thoroughly dried and placed under N2.
The appropriate alane (2.0 mmol), prepared according to Section 6.3.1, was
introduced. The hexane was removed at reduced pressure, and CH2Cl2 (20 ml)
was added. Pyridine (0.16 ml, 2.0 mmol) was added to the organometallic reagent,
and the resulting bright yellow solution was cooled to 0 o C; tosyl chloride (0.350
g, 1.84 mmol) and triphenylphospine (707 mg, 2.7 mmol) were quickly
92 Chapter 6

introduced in the reaction flask. After stirring for 15 min the solution was allowed
to warm to room temperature, siphoned onto a short column of silica gel and
eluted with 200 ml of CH2Cl2. After removal of the solvent at reduced pressure,
the product was further purified by flash chromatography.
6.3.5 Synthesis of unsaturated sulfoxides from unsolvated alanes
and benzenesulfinyl chloride in the presence of Ph3PO
In a typical run, a three necked flask, equipped with a reflux condenser, a
dropping funnel and a magnetic stirrer, dried and maintained under a N2, was
charged with benzenesulfinyl chloride (3 mmol) dissolved in 10 ml of dry
CH2Cl2; Ph3PO (1.5 mmol) was then added to the stirred solution. The reaction
mixture was cooled to 0 o C, and 3.3 mmol of the appropriate organoalane was
quickly introduced through the dropping funnel. After stirring for 1 h at 0 o C, the
solution was syphoned onto a short column of silica gel, and eluted with 200 ml of
CH2Cl2. The solution was dried with anhydrous Na2SO4 and the solvent was
removed at reduced pressure. The product was further purified by flash
chromatography.
6.3.6 Synthesis of alk-1-enyl sulfones from sulfonyl chlorides and
pyridine-coordinated alanes in the presence of Ph3PO
In a typical reaction, a three-necked flask, equipped with a reflux condenser, a
dropping funnel and a magnetic stirrer was dried and charged with 2.0 mmol of
the appropriate alane, prepared according to Section 6.3.1. The solvent was
removed at reduced pressure and CH2Cl2 (20 ml) and pyridine (2.0 mmol) were
added to the organometallic reagent. A catalytic amount (0.3 mmol) of Ph3PO and
tosyl chloride (1.8 mmol) were added to the resulting bright yellow solution. The
reaction mixture was refluxed for 1 h, cooled and hydrolyzed with the addition of
an aqueous solution (1% v/v) of H2SO4. After extraction with CH2Cl2, the organic
layer was dried on Na2SO4 and the solvent was removed at reduced pressure (18
mmHg). The product was further purified by flash chromatography.
6.3.7 Synthesis of alk-1-enyl sulfones using sulfonyl chloridepyridine
complexes and uncomplexed alanes
In a typical reaction, a three-necked flask equipped with reflux condenser,
dropping funnel and magnetic stirrer was thoroughly dried and maintained under
N2; the flask was charged with tosyl chloride (0.381 g, 2.0 mmol) CH2Cl2 (20 ml)
and pyridine (0.16 ml, 2 mmol). The solution was stirred for 30 min, and very
Experimental section 93

quickly (10 seconds) added of a CH2Cl2 solution (10 ml) of the appropriate
dialkyl alk-1-enyl alane (2.0 mmol). After stirring for 4 h the reaction mixture was
hydrolyzed with an aqueous solution of H2SO4 (1%), extracted with CH2Cl2 and
dried on anhydrous Na2SO4. After removal of the solvent at reduced pressure (18
mmHg) the product was further purified by flash chromatography.
6.3.8 Synthesis of alk-1-enyl sulfones using sulfonyl chloridepyridine
complexes and uncomplexed alanes in the
presence of CuCl
In a typical run, tosyl chloride (2.0 mmol) and CH2Cl2 (20 ml) were introduced
under N2 into a dry three-necked flask equipped with reflux condenser, dropping
funnel and magnetic stirrer.After addition of pyridine (0.16 ml, 2.0 mmol) to the
reaction mixture, the solution was stirred for 30 min. The appropriate dialkyl alk-
1-enyl alane, dissolved in CH2Cl2, was quickly added to the reaction mixture. The
solution was stirred at room temperature until the conversion was stationary
(usually overnight), and the appropriate amount of CuCl (1.0-2.0 mmol) was
added to the reaction mixture. The resulting blue solution was stirred at room
temperature until the maximum conversion was achieved, then hydrolyzed with
an aqueous solution (1%) of H2SO4. After extraction with CH2Cl2, the organic
layer was dried over Na2SO4. The solvent was removed at reduced pressure (18
mmHg) and the crude product was further purified by flash chromatography.
6.3.9 Synthesis of unsaturated sulfones using sulfonyl chloridepyridine
complexes and Grignard reagents
In a typical run, tosyl chloride (4.5 mmol) and dry THF (20 ml) were
introduced under N2 in a dry three-necked flask equipped with reflux condenser,
dropping funnel and magnetic stirrer. Pyridine (0.36 ml, 4.5 mmol) was added,
and the solution was stirred for 30 min; the Grignard reagent was quickly added
through the dropping funnel, and the solution was stirred overnight. After
hydrolysis (1% aq. H2SO4) the mixture was extracted with Et2O and dried over
anhydrous Na2SO4. After removal of the solvent at reduced pressure the crude
product was further purified by flash chromatography.
6.3.10 Synthesis of alkenylated 2H-dihydropyridine and 2Hdihydroisoquinoline
derivatives
In a typical reaction, a two-necked flask equipped with reflux condenser,
magnetic stirrer and dropping funnel was thoroughly dried; the appropriate alane
94 Chapter 6

(3.0 mmol), prepared according to Section 6.3.1 or 6.3.2, was introduced under
N2; hexane was removed at reduced pressure (18 mmHg) and CH2Cl2 (20 ml) and
the appropriate heteroaromatic substrate was added. The solution was cooled to 0
or -20 o C (depending on the nature of the nitrogen ligand) and the acid halide (2.7
mmol) was quickly added. After stirring for 30 min the reaction mixture was
siphoned onto a short column of silica gel and eluted with 200 ml of CH2Cl2. The
solution was dried over anhydrous Na2SO4 and the solvent was removed at
reduced pressure (18 mmHg). The crude product was purified by flash
chromatography.
6.3.11 Cyclization of 1-(2-bromoacetyl)-2-(hex-1-enyl)-8trimethylsilyloxy-2H-dihydroquinoline
A flask was charged with 30 ml of an aqueous solution of KF (5% w/v); a
solution of the crude intermediate 42 in Et2O (30 ml) was added, and the mixture
was vigorously stirred at r.t. until complete conversion of the product (GLC) was
achieved (45 min). The organic layer was then separated, washed with water and
dried. After evaporation of the solvent at reduced pressure the analytically pure 43
was recovered.
Experimental section 95

6.4 Characterization of the products synthesized
Physical and spectroscopic characterizations are reported for each isolated
product. The following data are reported: eluting mixture employed in the flash
chromatography when used, physical state, mass spectrum, 1 H NMR and 13 C
NMR spectrum, infrared spectrum (neat).
6.4.1 Alk-1-enyl and alk-1-ynyl sulfoxides
(E) Phenyl hex-1-enyl sulfoxide
O Bu-n
S
Hexane/Ethyl acetate 75/25; yellowish oil; GC-MS (m/z, I%):
208 (M .+ , 14), 192 (36), 160 (60), 149 (52) 117 (100), 111 (66)
104 (57) 91 (21), 78 (36); 1 H NMR: 0.89 (t, J=7.2 Hz, 3H),
1.25-1.50 (m, 4H), 2.23 (dtd, J=7.0 Hz, J =6.5 Hz, J =1.4 Hz,
2H), 6.23 (dt, J=15.0 Hz, J =1.4 Hz, 1H), 6.62 (dt, J=15.0 Hz, J
=7.2 Hz, 1H), 7.45-7.65 (m, 5H); 13 C NMR: 13.4, 21.7, 29.7, 31.3, 124.0, 128.9,
130.4, 134.5, 141.2, 143.8; IR (cm -1 ): 2954, 2921, 2855, 1627, 1466, 1444, 1377,
1077, 1038, 960, 916, 745, 683.
(E) Phenyl cyclohexylethenyl sulfoxide
Hexane/Ethyl acetate 75/25; yellowish oil; GC-MS (m/z, I%):
234 (M .+ , 5), 219 (18), 218 (100), 186 (18), 136 (36), 109 (71),
67 (63); 1 H NMR: 1.0-1.2 (m, 5H), 1.5-1.8 (m, 5H), 2.10 (m,
1H), 6.10 (dd, J=15.4 Hz, J =1.1 Hz, 1H), 6.51 (dd, J=15.4 Hz,
J =6.2 Hz, 1H), 7.4-7.6 (m, 5H); 13 C NMR: 25.5, 25.7, 31.5,
40.25, 124.4, 129.2, 130.7, 132.8, 144.15, 146.4; IR (cm -1 O
S
Hex-c
): 3023, 2921, 2855,
2657, 1622, 1594, 1446, 1397, 1083, 1048, 1021, 967, 811, 770, 624.
(E) Phenyl oct-1-enyl sulfoxide
O Hex-n
S
Hexane/Ethyl acetate 75/25; yellowish oil; GC-MS (m/z,
I%): 236 (M .+ , 10), 219 (28), 188 (47), 149 (18), 117 (96),
110 (50), 91 (27), 78 (31), 77 (23); 1 H NMR: 0.87 (t, J=6.6
Hz, 3H), 1.20-1-60 (m, 8H), 2.22 (dtd, J=6.6 Hz, J’=7.0 Hz,
J”=1.1 Hz, 2H), 6.23 (dt, J=15.3 Hz, J’=1.5 Hz, 1H), 6.62
96 Chapter 6

(dt, J= 15.3 Hz, J’=6.6 Hz), 7.45-7.65 (m, 5H); 13 C NMR: 13.8, 22.3, 27.8, 28.5,
31.3, 31.8, 124.2, 129.0, 130.6, 134.7, 141.3, 144.0; IR (cm -1 ): 2956, 2911, 2844,
1622, 1461, 1439, 1078, 1039, 956, 744, 683.
(E) Phenyl 3,3-dimethylbut-1-enyl sulfoxide
O Bu-t
S
Hexane/Ethyl acetate 75/25; yellowish oil; GC-MS (m/z, I%):
208 (M .+ , 19), 177 (17), 160 (41), 145 (100), 110 (31), 77 (24);
1 H NMR: 1.09 (s, 9H), 6.14 (d, J=15.3 Hz, 1H), 6.62 (d, J=15.3
Hz, 1H), 7.45-7.65 (m, 5H); 13 C NMR: 21.8, 26.0, 31.5, 127.8,
128.9, 130.1, 138.2, 144.3, 151.4; IR (cm -1 ): 2954, 2921, 2855,
1627, 1466, 1444, 1377, 1077, 1038, 960, 916, 745, 683.
(E) 4’-Methylphenyl hex-1-enyl sulfoxide
O Bu-n
S
Me
Hexane/Ethyl acetate 75/25; yellowish oil; GC-MS (m/z, I%):
222 (M .+ , 5), 206 (11), 174 (67), 131 (100), 123 (29), 91 (29); 1 H
NMR: 0.88 (t, J=7.0 Hz, 3H), 1.2-1.5 (m, 4H), 2.22 (dtd, J=7.0
Hz, J =6.6 Hz, J =1.5 Hz, 2H), 2.4 (s, 3H), 6.2 (dt, J= 15.0 Hz, J
=1.5 Hz, 1H), 6.59 (dt, J=15.0 Hz, J =7.0 Hz, 1H), 7.3-7.5 (m,
4H); 13 C NMR: 14.0, 21.6, 22.3, 30.4, 31.9, 124.8, 130.2, 135.3,
141.2, 141.4, 141.5; IR (cm -1 ): 2944, 2922, 2856, 1628, 1589, 1494, 1450, 1078,
1044, 961, 806.
(E) 4’-Methylphenyl oct-1-enyl sulfoxide
O Hex-n
S
Me
Hexane/Ethyl acetate 75/25; yellowish oil; GC-MS (m/z, I%):
250 (M .+ , 4), 234 (30), 202 (56), 163 (29), 131 (100), 124 (49),
118 (51), 105 (18), 91 (36), 77 (9); 1 H NMR: 0.86 (t, J=6.6,
3H), 1.2-1.5 (m, 8H), 2.21 (dtd, J=6.2, J’=7.0, J”=1.4, 2H), 2.40
(s, 3H), 6.20 (dt, J=15.4, J’=1.4, 1H), 6.59 (dt, J=15.4, J’=7.0,
1H), 7.26-7.35 (m, 2H), 7.46-7.54 (m, 2H); 13 C NMR: 13.9,
21.2, 22.4, 27.9, 28.5, 31.3, 31.8, 124.4, 129.8, 134.8, 140.9, 141.5; IR (cm -1 ):
2956, 2911, 2844, 1628, 1489, 1456, 1300, 1089, 1044, 1011, 956, 806, 617.
Experimental section 97

(E) 4’- Methylphenyl 3,3-dimethylbut-1-yl sulfoxide
O Bu-t
S
Me
Hexane/Ethyl acetate 75/25; yellowish oil; GC-MS (m/z, I%):
222, (M .+ , 2), 206 (6), 191 (11), 174 (53), 159 (100), 137 (17),
123 (26), 91 (25), 77 (8), 65 (14), 57 (16); 1 H NMR: 1.16 (s,
9H), 2.49 (s, 3H), 6.11 (d, J=15.4, 1H), 6.60 (d, J=15.4, 1H),
7.23-7.32 (m, 2H), 7.42-7.52 (m, 2H); 13 C NMR: 21.6, 29.0,
34.4, 124.9, 130.2, 131.3, 141.4, 141.5, 151.0; IR (cm -1 ): 2956,
2856, 1617, 1589, 1494, 1461, 1361, 1261, 1078, 1044, 967, 811.
(E) 4’- Methylphenyl 2-cyclohexyl ethenyl sulfoxide
O Hex-c
S
Me
Hexane/Ethyl acetate 75/25; yellowish oil; GC-MS (m/z, I%):
1 H NMR: 1.1-1.4 (m, 5H), 1.6-1.9 (m, 5H), 2.1-2.2 (m, 1H),
2.40 (s, 3H), 6.15 (dd, J=15.0, J’=1.1, 1H), 6.56 (dd, J=15.0,
J’=6.6, 1H), 7.27-7.33 (m, 2H), 7.46-7.53 (m, 2H); 13 C NMR:
21.6, 25.9, 26.0, 32.0, 40.5, 124.8, 130.2, 133.3, 141.4, 141.5,
146.0; IR (cm -1 ): 3021, 2925, 2851, 2667, 1622, 1595, 1448,
1398, 1083, 1048, 1015, 964, 810, 773, 622.
(E) Methyl hex-1-enyl sulfoxide
O Bu-n
S
Me
Hexane/Ethyl acetate 40/60; yellowish oil; GC-MS (m/z, I%):
146 (M .+ , 49), 129 (11), 117 (12), 103 (10), 81 (51), 55 (100),
41 (72); 1 H NMR: 0.91 (t, J=7 Hz, 3H), 1.25-1.55 (m, 4H),
2.24 (dtd, J=7.0 Hz, J = 6.4 Hz, J =1.5 Hz, 2H), 2.60 (s, 3H), 6.27 (dt, J=15.0 Hz,
J =1.5 Hz, 1H), 6.49 (dt, J=15.0 Hz, J =6.6 Hz, 1H); 13 C NMR: 14.0, 22.4, 30.4,
31.9, 41.0, 134.2, 141.2; IR (cm -1 ): 2944, 2911, 2856, 1628, 1467, 1417, 1038,
961, 717, 683.
(E) 4’-Methylphenyl 4-phenylbut-1-enyl sulfoxide
Hexane/Ethyl acetate 75/25; white solid m.p. 49-50 o C; GC-
MS (m/z, I%): 284 (M .+ , 3), 268 (46), 236 (100), 225 (15),
193 (99), 185 (62), 178 (40), 165 (23), 152 (71), 141 (14),
115 (16), 77 (7), 55 (12), 41 (16); 1 H NMR: 2.49 (s, 3H),
2.63 (dtd, J=7, J =7.4, J =1, 2H), 2.87 (t, J=7.2, 2H), 6.28
(dt, J=15.4, J =1, 1H), 6.69 (dt, J=15.4, J =7.4, 1H), 7.2-7.55 (m, 9H); 13 O
S
Ph
Me
C NMR:
21.7, 33.8, 34.6, 125.0, 126.5, 128.7, 128.8, 130.3, 136.0, 139.5, 140.7, 141.1,
98 Chapter 6

141.6; IR (cm -1 ): 3011, 2911, 2844, 1622, 1594, 1489, 1450, 1433, 1189, 1146,
1083, 1039, 950, 806, 722, 694.
(E) 4’-Biphenyl hex-1-enyl sulfoxide
Hexane/Ethyl acetate 75/25; yellowish oil; GC-MS (m/z,
I%): 270 (M .+ , 1), 254 (5), 222 (17), 163 (21), 131 (110), 123
(14), 91 (73), 77 (10), 65 (16); 1 H NMR: 0.99 (t, J=6.6, 3H),
1.3-1.6 (m, 4H), 2.34 (dtd, J=6.6, J =6, J =1.4, 2H), 6.36 (dt,
J=15.4, J =1.4, 1H), 6.74 (dt, J=15.4, J =6.6, 1H), 7.45-7.60
(m, 4H), 7.65-7.90 (m, 5H); 13 C NMR: 14.1, 22.4, 24.0, 26.1, 30.4, 30.6, 32.0,
125.3, 127.5, 128.3, 128.4, 129.2, 134.9, 140.0, 142.1, 143.0, 144.2; C, 76.01; IR
(cm -1 O
S
Bu-n
Ph
): 3033, 2955, 2922, 2856, 1622, 1589, 1478, 1444, 1389, 1317, 1139, 1089,
1044, 1000, 833, 761, 691.
Phenyl hex-1-ynyl sulfoxide
Hexane/Ethyl acetate 70/30; yellowish oil; GC-MS (m/z,
I%): 206 (M .+ , 6), 190 (17), 163 (22), 157 (20), 143 (56), 129
(71), 121 (16), 115 (100), 103 (35), 91 (20), 81 (28), 77 (46),
71 (16), 51 (32); 1 H NMR: 0.97(t, J= 7 Hz, 3H), 1.4-1.7 (m,
4H), 2.50 (t, J= 7 Hz, 2H), 7.58-7.66 (m, 3H), 7.84-7.92 (m,
2H); 13 C NMR: 13.6, 19.6, 22.1, 29.7, 76.9, 106.3, 125.1, 129.7, 131.7, 144.6; IR
(cm -1 Bu-n
O
S
): 3056, 2956, 2922, 2856, 2167, 1461, 1439, 1378, 1317, 1133, 1083, 1050,
878, 744, 683.
Phenyl 3,3- dimethylbut-1-ynyl sulfoxide
Hexane/Ethyl acetate 80/20; yellowish oil; GC-MS (m/z, I%):
206 (M .+ , 4), 191 (100), 175 (13), 150 (24), 143 (96), 128
(45), 121 (17), 115 (24), 105 (24), 97(10), 77 (35), 65 (10),
57 (16), 51 (22); 1 H NMR: 1.33 (s, 9H), 7.58-7.61 (m, 3H),
7.83-7.89 (m, 2H); 13 C NMR: 15.8, 30.1, 78.0, 113.3, 125.3,
129.7, 131.8, 132.3; IR (cm -1 Bu-t
O
S
): 3062, 2950, 2929, 2843, 2157, 1469, 1448, 1307,
1122, 1091, 1034, 746, 678.
Experimental section 99

Phenyl hex-5-en-1-ynyl sulfoxide
Hexane/Ethyl acetate 80/20; yellowish oil; GC-MS (m/z, I%):
204 (M .+ ,3), 187 (7), 161 (6), 155 (27), 147 (12), 141 (17), 128
(17), 115 (100), 103 (17), 91 (15), 77 (30), 65 (8), 51 (18); 1 H
NMR: 2.10 (td, J=7 Hz, J’=1.1 Hz, 2H), 2.32(td, J=7 Hz,
J’=1.5 Hz, 2H), 4.94(dd, J=9.8 Hz, J’=2.2 Hz, 1H), 5.05 (dd,
J=13.5 Hz, J’=2.2 Hz, 1H), 5.86 (ddt, J=13.5 Hz, J’=9.8 Hz, J”=1.5 Hz, 1H), 7.6-
7.8 (m, 5H); 13 C NMR: 19.6, 31.6, 78.9, 105.1, 116.6, 125.0, 129.5, 131.6, 135.6,
144.5; IR (cm -1 O
S
): 3067, 2967, 2922, 2356, 2178, 1722, 1639, 1481, 1439, 1378,
1228, 1089, 1050, 916, 750, 683.
100 Chapter 6

6.4.2 Unsaturated sulfones
(E) 4’-Methylphenyl hex-1-enyl sulfone
Hexane/Ethyl acetate 80/20; yellowish oil; GC-MS (m/z, I%):
238 (M .+ ,42), 223 (2), 209 (100), 157 (50), 139 (59), 91 (54),
82 (33), 67 (30); 1 H NMR: 0.89 (t, J=7.3 Hz, 3H), 1.2-1.4 (m,
4H), 2.22 (dtd, J=6.7 Hz, J’=6.7 Hz, J”=1.5 Hz, 2.43 (s, 3 Hz),
6.29 (dt, J=15 Hz, J’=1.5 Hz, 1H), 6.96 (dt, J=15 Hz, 6.7 Hz,
1H), 7.32 (d, J=7.7 Hz, 2H), 7.75 (d, J=7.7 Hz, 2H); 13 C NMR:
13.9, 21.8, 22.3, 29.9, 31.4, 127.8, 130.9, 136.5, 138.1, 144.3, 146.8; IR (cm -1 O
O S
Bu-n
Me
):
3044, 2956, 2922, 2867, 2344, 1628, 1594, 1456, 1317, 1283, 1144, 1083, 972,
833, 811, 655.
(E) Phenyl oct-1-enyl sulfone
Hexane/Ethyl acetate 80/20; yellowish oil; GC-MS (m/z,
I%): 236 (M .+ , 10), 219 (28), 207 (17), 188 (47), 149 (17),
126 (22), 124 (53), 117 (96), 110 (50), 104 (100), 91 (26), 78
(30), 69 (16), 55 (30), 41 (27); 1 H NMR: 0.86 (t, J=6.6 Hz,
3H), 1.2-1.5 (m, 8H), 2.22 (dtd, J=7.3 Hz, J’=7.4 Hz, J”=1.6
Hz, 2H), 6.23 (dt, J=15.4 Hz, J’=1.5 Hz, 1H), 6.62 (dt, J=15.4 Hz, J’=6.6 Hz, 1H),
7.4-7.7 (m, 5H); 13 C NMR: 13.8, 22.3, 27.8, 28.5, 31.3, 31.8, 124.2, 129.1, 130.6,
134.7, 141.3, 144.0; IR (cm -1 O
Hex-n
O S
): 3084, 2950, 2912, 2873, 2337, 1623, 1593, 1458,
1312, 1287, 1146, 978, 807.
(E) 4’-Methylphenyl 3,3-dimethylbut-1-enyl sulfone
Hexane/Ethyl acetate 80/20; yellowish oil; GC-MS (m/z, I%):
238 (M .+ , 3), 223 (1), 157 (8), 139 (31), 91 (20), 83 (100), 67
(16), 55 (26); 1 H NMR: 1.08 (s, 9H), 2.44 (s, 3H), 6.18 (d, J=15
Hz, 1H), 6.92 (d, J=15 Hz, 1H), 7.33 (d, J=8.1 Hz, 2H), 7.75 (d,
J=8.1 Hz, 2H); 13 C NMR: 21.8, 28.6, 34.3, 127.8, 130.1, 136.3,
144.3, 150.1, 156.1; IR (cm -1 O
O
S
Bu-t
Me
): 2967, 2856, 2356, 1617, 1594,
1461, 1361, 1311, 1289, 1178, 1139, 1093, 978, 917, 833, 806, 756.
Experimental section 101

(E) 4’-Methylphenyl 2-cyclohexylethenyl sulfone
Hexane/Ethyl acetate 80/20; yellowish oil; GC-MS (m/z,
I%): 264 (M .+ , 11), 207 (5), 183 (24), 157 (16), 139 (26), 109
(100), 91 (33), 79 (29), 67 (53); 1 H NMR: 1.1-1.3 (m, 5H),
1.65-1.85 (m, 5H), 2.1-2.2 (m, 1H), 2.43 (s, 3H), 6.22 (dd,
J=15.5 Hz, J’=1.5 Hz, 1H), 6.92 (dd, J=15.5 Hz, J’=6.2 Hz,
1H), 7.32 (d, J=8.1 Hz, 2H), 7.74 (d, J=8.1 Hz, 2H); 13 C
NMR: 21.8, 28.6, 34.3, 38.4, 127.0, 127.8, 130.1, 138.1, 144.4, 156.1; IR (cm -1 O
O S
Hex-c
Me
):
2922, 2844, 1627, 1594, 1444, 1322, 1294, 1277, 1138, 1083, 972, 833, 811, 667,
544.
(E) 4’-Methylphenyl 4-phenylbut-1-enyl sulfone
Hexane/Ethyl acetate 80/20; white solid m.p. 42-45 o C; GC-MS
(m/z, I%): 285 (1), 157 (2), 130 (40), 115 (3), 91 (100), 77 (3),
65 (10); 1 H NMR: 2.46 (s, 3H), 2.63 (dtt, J=7.0 Hz, J’=6.9 Hz,
J”=1.5 Hz, 2H), 2.86 (t, J=7.0 Hz, 2H), 6.37 (dt, J=15.0 Hz,
J’=1.5 Hz, 1H), 7.06 (dt, J=15.0 Hz, J’= 6.9 Hz, 1H), 7.15-7.45
(m, 7H), 7.95 (dt, J=8.4 Hz, J’=1.8 Hz, 2H); 13 C NMR: 21.6,
33.1, 33.9, 126.4, 127.6, 128.4, 128.6, 129.9, 131.4, 137.7, 140.1, 144.2, 145.4; IR
(cm -1 O
O S
Ph
Me
): 2934, 2827, 1632, 1600, 1450, 1318, 1290, 1270, 1130, 1067, 982, 843,
801, 672, 538.
(E) Methyl hex-1-enyl sulfone
Hexane/Ethyl acetate 50/50; yellowish oil; GC-MS (m/z, I%):
162 (M .+ , 100), 143 (21), 125 (8), 111 (43), 97 (76), 83 (51), 69
(93), 55 (97), 41 (40); 1 H NMR: 0.99 (t, J=6.9, 3H), 1.3-1-6 (m,
4H), 2.34 (dtd, J=6.6 Hz, J’=6.6 Hz, J”=1.5 Hz, 2H), 2.99 (s,
3H), 6.44 (dt, J=14.8 Hz, J’=1.5 Hz, 1H), 7.02 (dt, J=14.8 Hz, J’=6.6 Hz, 1H); 13 C
NMR: 14.0, 22.4, 29.9, 31.3, 43.1, 129.6, 149.0; IR (cm -1 O
Bu-n
O S
Me
): 2956, 2922, 2856,
2344, 1633, 1461, 1305, 1283, 1128, 967, 817.
(E) 4’-Biphenyl hex-1-enyl sulfone
Hexane/Ethyl acetate 80/20; yellowish oil; GC-MS (m/z, I%):
300 (M .+ , 100), 271 (5), 245 (5), 217 10), 201 (80), 169 (67),
152 (79), 141 (16); 1 O
O S
Bu-n
H NMR: 0.98 (t, J=7 Hz, 3H), 1.3-1.6 (m,
4H), 2.34 (dtd, J=6.6 Hz, J’=7 Hz, J”= 1.5 Hz, 2Hz), 6.44 (dt,
Ph
102 Chapter 6

J=15 Hz, J’=1.5 Hz, 1H), 7.11 (dt, J=15 Hz, J’=6.6 Hz, 1H), 7.5-7.6 (m, 3 H),
7.65-7.75 (m, 2H), 7.8-7.85 (m, 2H), 7.95-8.05 (m, 2H); 13 C NMR: 14.0, 22.4,
29.9, 31.5, 127.6, 128.1, 128.3, 128.8, 129.3, 130.7, 139.5, 139.6, 146.4, 147.5; IR
(cm -1 ): 3033, 2922, 2355, 1622, 1594, 1500, 1450, 1405, 1322, 1283, 1144, 1073,
956, 811, 750, 700, 657, 570, 528.
(R,S)-(E) 4’-Methylphenyl 2-methylbutyl sulfone
Hexane/Ethyl acetate 80/20; yellowish oil; GC-MS (m/z, I%):
207 (2), 173 (22), 155 (72), 91 (79), 70 (100); 1 H NMR: 0.90 (t,
J=7.3 Hz, 3H), 0.96 (d, J=6.5 Hz, 3H), 1.2-1.3 (m, 2H), 1.3-1.4
(m, 1H), 3.88 (dd, J=9.2 Hz, J’=6.2 Hz, 1H), 3.97 (dd, J=9.2 Hz,
J’=6.2 Hz, 1H), 7.42 (d, J=8 Hz, 2H), 7.87 (d, J=8Hz, 2H); 13 C
NMR: 11.2, 16.2, 21.9, 25.7, 34.6, 75.1, 127.3, 128.1, 130.0,
130.5; IR (cm -1 O
O S
Et
Me
Me
): 2956, 2922, 2867, 2356, 1594, 1461, 2478, 1189, 1172, 1094,
961, 844, 811, 783, 661.
(E) 4’-Methylphenyl hex-1-ynyl sulfone
Hexane/Ethyl acetate 80/20; yellowish oil; GC-MS
(m/z, I%): 236 (40), 194 (43), 155 (49), 139 (88), 129
(43), 107 (28), 91 (100), 79 (49), 65 (50), 53 (18), 41
(25); 1 H NMR: 0.86 (t, J=7.0 Hz, 3H), 1.2-1.6 (m, 4H),
2.34 (t, J=7.3 Hz, 2H), 2.44 (s, 3H), 7.35 (d, J=7.5 Hz, 2H), 7.86 (d, J=7.5 Hz,
2H); 13 C NMR: 13.4, 18.6, 21.6, 21.9, 29.0, 78.4, 97.4, 127.1, 130.0, 139.3, 145.2;
IR (cm -1 O O
S
Bu-n
Me
): 2955, 2867, 2356, 2200, 1594, 1461, 1327, 1156, 1089, 811, 700, 672.
(E) 4’-Methylphenyl 3,3-dimethylbut-1-ynyl sulfone
Hexane/Ethyl acetate 80/20; white solid m.p. 43-45 o C; GC-MS
(m/z, I%): 236 (M .+ , 49), 157 (36), 139 (53), 115 (10), 91 (28),
81 (100), 65 (28), 53 (17), 41 (17); 1 H NMR: 1.25 (s, 9H), 2.48
(s, 3H), 7.37 (d, J=7.5 Hz, 2H), 7.89 (d, J=7.5 Hz, 2H); 13 C
NMR: 21.6, 27.9, 29.3, 78.1, 103.5, 127.0, 130.0, 139.3, 145.1;
IR (cm -1 O
O S
Bu-t
Ph
): 2974, 2931, 2870, 2211, 2174, 1595, 1492, 1475,
1456, 1356, 1318, 1253, 1188, 1176, 1147, 1086, 1006, 917, 815, 777, 670.
Experimental section 103

(E) 4’-Methylphenyl 4-phenyl-but-1-ynyl sulfone
Hexane/Ethyl acetate 80/20; yellowish oil; GC-MS (m/z, I%):
284 (M .+ , 1), 283 (3), 249 (3), 219 (5), 204 (9), 128 (36), 117
(5), 91 (100), 77 (5), 65 (15); 1 H NMR: 2.49 (s, 3H), 2.66 (t,
J=6.3 Hz, 2H), 2.86 (t, J=6.3 Hz, 2H), 7.1-7.2 (m, 2H), 7.2-
7.3 (m, 3H), 7.37 (d, J=8 Hz, 2H), 7.85 (d, J=8 Hz, 2H); 13 C
NMR: 21.2, 21.8, 33.2, 79.3, 96.3, 126.9, 127.4, 128.5, 128.7,
130.0, 139.1, 139.2, 145.3; IR (cm -1 O
O S Ph
Me
): 3086, 3062, 3029,
2927, 2865, 2200, 1596, 1494, 1454, 1328, 1304, 1185, 1159, 1089, 1050, 1017,
814, 750, 705, 678, 618.
(E) 4-Methylphenyl 4’-methoxyphenyl sulfone
Hexane/Ethyl acetate 80/20; yellowish oil; GC-MS (m/z,
I%): 262 (M .+ , 71), 230 (3), 207 (4), 183 (7), 171 (4), 155
(77), 139 (14), 123 (100), 107 (8), 91 (17), 77 (17), 65 (17);
1
H NMR: 2.39 (s, 3H), 3.84 (s, 3H), 6.96 (d, 8.2 Hz, 2H),
7.28 (d, 8.2 Hz, 2H), 7.81 (d, 8.2 Hz, 2H), 7.87 (d, 8.2 Hz,
2H); 13 C NMR: 21.6, 55.7, 114.6, 127.4, 128.4, 129.8, 129.9,
133.6, 139.5, 143.7; IR (cm -1 OMe
O
O S
Me
): 3096, 3068, 2972, 2938,
2925, 2837, 2537, 1916, 1596, 1578, 1495, 1456, 1413, 1319, 1299, 1264, 1183,
1151, 1106, 1072, 1019, 831, 802, 708, 680, 634, 562, 548.
(E) 4-Methylphenyl 3’-fluorophenyl sulfone
Hexane/Ethyl acetate 80/20; white solid m.p. 88-90 o C; GC-
MS (m/z, I%): 250 (88), 183 (6), 170 (6), 139 (79), 107
(100), 95 (18), 91 (65), 77 (23), 65 (28), 51 (7); 1 H NMR:
2.43 (s, 3H), 7.2-7.4 (m, 3H), 7.49 (td, J=8.1 Hz, J’=5.1 Hz,
1H), 7.63 (td, J=2.2 Hz, J’=8.1 Hz, 1H), 7.74 (td, J=1.1 Hz,
J’=8.1 Hz, 1H), 7.84 (d, J=8.0 Hz, 2H); 13 C NMR: 21.7,
114.7, 115.2, 120.1, 120.6, 123.3, 123.4, 127.9, 130.2, 131.1,
131.3; IR (cm -1 O
O S F
Me
): 3064, 2962, 2943, 2820, 2530, 1922, 1604, 1582, 1440, 1319,
1254, 1200, 1100, 1078, 1023, 700, 630.
104 Chapter 6

6.4.3 Dihydropyridine and dihydroquinoline derivatives
1-Benzoyl-2-[(1E)-hex-1-en-1-yl]-1,2-dihydropyridine
Hexane/Ethyl acetate 85/15; yellowish oil; GC-MS (m/z,
I%): 267 (M .+ , 7), 224 (1), 210 (2), 184 (18), 162 (22), 132
(1), 118 (3), 105 (100), 77 (32); 1 H NMR: 0.88 (t, J= 7.0
Hz, 3H), 1.2-1.4 (m, 4H), 2.03 (dtd, J=7.0 Hz, J’=6.6 Hz,
J”=1.0 Hz, 2H), 5.25 (bt, J=7.0 Hz, 1H), 5.5-5.8 (m, 3H),
6.03 (dd, J=9.2 Hz, J’=5.4 Hz, 1H), 6.30 (bs, 1H), 7.4-7.7
(m, 5H); 13 C NMR: 14.1, 22.4, 31.4, 32.1, 51.4, 109.1, 121.7, 123.1, 125.6, 128.6,
129.2, 130.7, 133.5, 135.1; IR (cm -1 N Bu-n
O
): 3061, 3030, 2956, 2928, 2871, 2859, 1719,
1637, 1578, 1530, 1489, 1448, 1413, 1358, 1263, 1109, 1071, 1027, 970, 790,
755, 712.
1-Pentanoyl-2-[(1E)-hex-1-en-1-yl]-1,2-dihydropyridine
Hexane/Ethyl acetate 85/15; yellowish oil; GC-MS (m/z,
I%): 247 (M .+ , 14), 218 (1), 204 (1), 190 (3), 162 (40), 132
(2), 120 (16), 106 (11), 93 (4), 80 (100), 67 (2), 57 (10); 1 H
NMR: 0.90 (t, J=7 Hz, 3H), 0.93 (t, J=7 Hz, 3H), 1.2-1.4 (m,
4H), 1.55-1-75 (m, 4H), 1.97 (dt, J=7.0 Hz, J’=6.6 Hz, 2H),
2.41 (td, J=7.7 Hz, J’= 0.9 Hz, 2H), 4.92 (m, 1H), 5.2-5.7 (m, 4H), 5.95 (dd, J=8.4
Hz, J’= 5.5 Hz, 1H), 6.49 (d, J=7.7 Hz, 1H); 13 C NMR: 14.1, 22.4, 22.7, 27.1,
31.4, 32.0, 33.3, 51.5, 107.2, 121.2, 123.7, 124.7, 126.0, 133.2, 171.9; IR (cm -1 n-Bu O
n-Bu N
):
3023, 2957, 2930, 2871, 1672, 1625, 1569, 1491, 1456, 1412, 1379, 1290, 1218,
1105, 966, 920, 775, 752.
1-Benzoyl-2-[3,3-dimethyl-(1E)-but-1-en-1-yl]-1,2-dihydropyridine
Hexane/Ethyl acetate 85/15; yellowish oil; GC-MS (m/z,
I%): 267 (M .+ , 7), 224 (2), 184 (22), 162 (5), 131 (15), 118
(14), 105 (100), 77 (38), 55 (6); 1 H NMR: 0.91 (s, 9H), 5.28
(bd, J=7.0 Hz, 1H), 5.5-5.8 (m, 3H), 5.98 (dd, J=9.0 Hz,
J’=5.6 Hz, 1H), 6.35 (bs, 1H), 7.4-7.7 (m, 5H); 13 C NMR:
23.0, 31.4, 51.8, 109.0, 121.6, 123.3, 125.5, 128.7, 129.2, 130.2, 133.4, 135.0; IR
(cm -1 N Bu-t
O Ph
): 3058, 3027, 2960, 2930, 2864, 2845, 1725, 1638, 1585, 1532, 1484, 1450,
1412, 1314, 1262, 1111, 1073, 1024, 967, 787, 754, 711.
Experimental section 105

1-Napht-1-oyl-2-[(1E)-hex-1-en-1-yl]-1,2-dihydropyridine
Hexane/Ethyl acetate 85/15; yellowish oil; GC-MS (m/z,
I%): 317 (M .+ , 3), 289 (1), 260 (1), 234 (2), 232 (2), 219
(1), 162 (15), 156 (17), 155 (100), 127 (47), 118 (2), 101
(2), 91 (1), 77 (3); 1 H NMR: 0.91 (t, J= 7.0 Hz, 3H), 1.2-1.4
(m, 4H), 2.10 (dtd, J=7.1 Hz, J’=6.7 Hz, J”=1.1 Hz, 2H),
5.27 (bt, J=7.1 Hz, 1H), 5.5-5.8 (m, 3H), 6.07 (dd, J=9.2
Hz,J’=5.4 Hz, 1H), 6.30 (bs, 1H), 7.4-7.8 (m, 6H), 9.05 (dd,
J=8.4 Hz, J’=1.1 Hz, 1H); 13 C NMR 14.1, 22.4, 31.4, 32.1, 51.4, 109.1, 120.3,
121.7, 123.1, 125.6, 128.6, 129.2, 130.7, 131.1, 132.4, 133.1, 133.5, 134.7, 135.1;
IR (cm -1 N
O Bu-n
): 3048, 2956, 2928, 2870, 2858, 1713, 1635, 1592, 1579, 1509, 1463,
1414, 1351, 1255, 1214, 1196, 1132, 1027, 970, 780, 737, 634.
2-Pentanoyl-1-[(1E)-hex-1-yn-1-yl]-1,2-dihydro isoquinoline
Hexane/Ethyl acetate 85/15; yellowish oil; GC-MS (m/z,
I%): 297 (M .+ ,18), 282 (7), 275 (9), 268 (45), 254(25), 240
(7), 230 (8), 214 (32), 212(14), 195(18), 168 (39), 154 (3),
129 (12), 85 (4); 1 H NMR: 0.90 (t, J= 7 Hz, 3H), 0.99 (t,
J=6.9 Hz, 3H), 1.3-1.6 (m, 8H), 2.01 (t, J= 6.8 Hz, 2H), 2.35
(td, J=7.1 Hz, J’=6.9 Hz, 2H), 5.52 (dt, J=14.1, J’=7 Hz,
1H), 5.98 (bd, 1H), 6.1-6.8 (m, 4H), 7.5-7.8 (m, 3H); 13 C NMR: 12.9, 13.5, 18.4,
19.0, 21.5, 22.4, 31.2, 32.3, 47.0, 110.2, 125.9, 127.6, 128.9, 129.4, 130.0, 131.2,
131.7, 134.3, 135.5, 169.2; IR (cm -1 N Bu-n
O Bu-n
): 3067, 2958, 2917, 2215, 1772, 1661, 1618
1583, 1451, 1337, 1260, 1241, 1163, 1102, 921, 752, 722, 685.
2-Benzoyl-1-[(1E)-hex-1-yn-1-yl]-1,2-dihydro isoquinoline
Hexane/Ethyl acetate 85/15; yellowish oil; GC-MS (m/z,
I%): 317 (M .+ ,15), 288 (5), 275 (18), 274 (22), 260 (37),
242 (4), 230 (13), 212 (25), 168 (21), 154 (1), 129 (17),
105 (100), 83 (19) 77 (56); 1 H NMR: 0.96 (t, J= 7 Hz, 3H),
1.3-1.6 (m, 4H), 2.27 (td, J=7 Hz, J’=6.9 Hz, 2H), 5.48 (dt,
J=13.8, J’=6.9 Hz, 1H), 6.10 (bd, 1H), 6.2-6.8 (m, 4H),
7.2-7.4 (m, 5H), 7.5-7.8 (m, 3H); 13 C NMR: 13.5, 19.0, 22.4, 31.2, 47.0, 110.2,
125.9, 126.2, 127.6, 128.2, 128.9, 129.4, 129.7, 130.0, 131.1, 131.7, 134.3, 135.5,
169.2; IR (cm -1 N Bu-n
O Ph
): 3056, 2946, 2929, 2223, 1784, 1673, 1629 1573, 1444, 1343,
1265, 1238, 1159, 1098, 910, 760, 729, 699.
106 Chapter 6

2-Benzoyl-1-[(1E)-hex-1-yn-1-yl]-1,2-dihydro isoquinoline
Hexane/Ethyl acetate 85/15; yellowish oil; GC-MS (m/z,
I%): 315 (M .+ ,14), 286 (7), 273 (13), 272 (24), 258 (21),
244 (9), 230 (4), 210 (33), 180 (5), 168 (12), 154 (4), 129
(10), 105 (100), 77 (45); 1 H NMR: 0.92 (t, J= 7 Hz, 3H),
1.3-1.6 (m, 4H), 2.20 (td, J=7 Hz, J’=0.2 Hz, 2H), 6.07
(bd, 1H), 6.4-6.8 (m, 3H), 7.2-7.4 (m, 5H), 7.5-7.8 (m,
3H); 13 C NMR: 13.8, 18.7, 22.1, 30.7, 47.2, 78.4, 84.7, 110.3, 125.4, 126.4, 127.9,
128.5, 128.7, 129.0, 129.3, 131.3, 131.6, 134.3, 135.6, 169.0; IR (cm -1 N
Bu-n
Ph O
): 3061,
2957, 2931, 2216, 1773, 1664, 1625 1569, 1455, 1349, 1272, 1231, 1154, 1102,
919, 773, 726, 701.
Methyl 1-[(E)-hex-1-enyl]isoquinolin-2(1H)-carboxilate
Hexane/Ethyl acetate 80/20; yellowish oil GC-MS (m/z, I%):
271 (M .+ , 20), 214 (2), 188 (100), 168 (5), 156 (1), 144 (25),
129 (8), 115 (5), 103 (6), 77 (2), 59 (3); 1 H NMR: 0.83 (t,
J=7.3, 3H), 1.2-1.4 (m, 4H), 1.93 (bdt, J= 6.2 Hz, J’=6.6 Hz,
2H), 3.82 (s, 3H), 5.4-5.55 (m, 2H), 5.75-5.9 (m, 2H), 6.75-
6.95 (m, 1H), 7.0-7.25 (m, 4H); 13 C NMR: 13.9, 22.2, 31.2
31.7, 53.2, 57.3(broad), 108.3, 124.8, 126.1, 126.7, 127.0, 127.7, 128.0, 130.4,
131.7, 132.1; IR (cm -1 n-Bu
O
N O
Me
): 2955, 2927, 2871, 2856, 1718, 1633, 1571, 1456, 1441,
1413, 1352, 1235, 1193, 1121, 1101, 968, 923, 771.
1,10-Bis-1-[(E)-hex-1-enyl]isoquinolin-2(1H)-yldecan-1,10-dione
Hexane/Ethyl acetate 85/15; yellowish oil; GC-MS (m/z,
I%): could not be recorded due to the low volatility of the
product; 1 H NMR: 0.8-0.9 (m, 6H), 1.1-1.5 (m, 8H), 1.6-
1.8 (m, 8H), 1.92 (dt, J=5.8 Hz, J’=5.6 Hz, 4H), 2.2-2.6
(m, 4H), 5.3-5.5 (m, 2H), 5.8-6.0 (m, 2H), 5.84 (d,
J=12.1 Hz, 2H), 5.88 (d, J=12.1 Hz, 2H), 6.15-6.2 (bd,
2H), 6.65 (d, J= 12.4 Hz, 2H), 6.69 (d, J= 12.4 Hz, 2H), 7.0-7.3 (m, 8H), 7.6-8.1
(m, 2H); 13 C NMR: 13.9, 22.2, 24.9, 29.2, 31.7, 34.1, 44.5, 54.9, 109.9, 124.7,
126.0, 126.7, 127.3, 127.7, 129.8, 130.2, 131.1, 132.4, 132.6, 171.2; IR (cm -1 n-Bu
O
N (CH2) 4
2
):
3062, 3018, 2946, 2921, 2864, 2852, 1724, 1664, 1613, 1578, 1562, 1449, 1405,
1352, 1286, 1227, 1157, 1113, 925, 754, 712, 685.
Experimental section 107

1,2-Bis2-1-[(E)-hex-1-enyl]isoquinolin-2(1H)-ylbenzene dione
Hexane/Ethyl acetate 85/15; yellowish oil GC-MS (m/z, I%):
could not be obtained due to the low volatility of the product;
1
H NMR: 0.84 (m, 6H), 1.1-1.3 (m, 8H), 1.8-2.0 (m, 4H),
5.3-5.6 (m, 4H), 5.6-5.8 (m, 2H), 6.1-6.2 (m, 2H), 6.4-6.6
(m, 2H), 6.9-7.3 (m, 8H), 7.3-7.8 (m, 8H); 13 C NMR: 14.0,
22.2, 31.2, 31.7, 55.5, 109.4, 124.9, 125.8, 127.2, 127.7,
128.1, 128.5, 128.7, 129.8, 130.1, 132.0, 132.3, 134.8, 167.5;
IR (cm -1 n-Bu N
O
O
n-Bu N
): 3058, 3023, 2956, 2927, 2870, 2857, 1720, 1660,
1625, 1595, 1569, 1489, 1455, 1413, 1359, 1290, 1234,
1198, 1157, 1118, 1090, 967, 919, 774, 749, 722, 709, 695.
2-(2-Bromoetanoyl)-1-[(1E)-hex-1-en-1-yl]-1,2-dihydro isoquinoline
Hexane/Ethyl acetate 80/20; yellowish oil GC-MS (m/z,
I%): 334 (12), 333 (12), 254 (33), 252 (38), 250 (39), 212
(9), 196 (3), 182 (3), 168 (14), 156(4), 154 (4), 143 (6), 130
(100), 115 (7), 102 (5), 89 (1), 77 (3); 1 H NMR: 0.86 (t, J=
7.0, 3H), 1.2-1.4 (m, 4H), 1.9-2.05 (m, 2H), 3.98 (d, J= 0.3
Hz, 2H), 5.46 (dd, J=3.3 Hz, J’=1.5 Hz, 1H), 5.58 (m, 1H),
6.03 (d, J=7.7 Hz, 1H), 6.13 (m, 1H), 6.69 (dd, J=7.7 Hz, J’=1 Hz, 1H), 7.1-7.35
(m, 4H); 13 C NMR: 13.9, 22.2, 25.6, 31.1, 31.7, 55.5, 111.7, 123.9, 125.2, 126.4,
127.0, 127.8, 127.9, 129.6, 132.5, 133.0, 164.3; IR (cm -1 n-Bu
O
N
Br
): 2960, 2930, 2865,
2850, 1707, 1621, 1561, 1432, 1423, 1408, 1360, 1231, 1187, 1112, 1098, 972,
920, 765.
1,3-Dibenzoyl-2-[(1E)-hex-1-en-1-yl]-2,3-dihydro-1H imidazole
Hexane/Ethyl acetate 80/20; white waxy solid m.p. 29-31
o .+
C; GC-MS (m/z, I%): 360 (M , 6), 277 (3), 255 (4),
195(1), 145 (6), 105 (100), 77 (24); 1 H NMR: 0.89 (m, 3H),
1.2-1.6 (m, 4H), 1.9-2.1 (m, 2H), 5.5 (m, 1H), 6.0-6.4 (m,
2H), 6.5-6.9 (m, 2H), 7.2-7.6 (m, 10H); 13 C NMR: 13.9,
22.2, 27.0, 30.8, 31.6, 114.8 (broad), 122.5, 127.8, 128.7,
131.1, 168.2. IR (cm -1 Ph
O
N
N
Ph
O
Bu-n
): 3143, 3060, 2956, 2928, 2870, 2857, 1651, 1645, 1578,
1447, 1387, 1347, 1276, 1151, 1076, 968, 862, 787, 718, 701.
108 Chapter 6

5-((E)-Hex-1-enyl)-2H-[1,4]-oxazino-[2,3,4-ij]-quinolin-3(5H)-one
Yellowish oil GC-MS (m/z, I%): 269 (M .+ ,38), 252 (2),
240 (9), 227 (19), 212 (14), 198 (12), 186 (99), 167 (6),
158 (100), 128 (28), 115 (6), 101 (5), 89 (5), 77 (7); 1 H
NMR: 0.86 (t, J=7.3 Hz, 3H), 1.1-1.4 (m, 4H), 1.98 (dt,
J=6.6 Hz, J’=7.3 Hz, 2H), 4.48 (d, J=15 Hz, 1H), 4.72 (d,
J=15 Hz, 1H), 5.45 (dd, J=15 Hz, J’= 6.6 Hz, 1H), 5.6-5.8 (m, 2H), 5.86 (dd, J=10
Hz, J’=5.5 Hz, 1H), 6.47 (d, J=10 Hz, 1H), 6.75-7.0 (m, 3H); 13 C NMR: 14.0,
22.3, 31.1, 31.8, 51.7, 68.0, 116.6, 120.8, 122.8, 123.3, 123.7, 125.9, 126.1, 134.2,
144.5, 163.9; IR (cm -1 O Bu-n
O
N
): 3045, 2957, 2927, 2871, 2857, 1688, 1580, 1477, 1386,
1358, 1311, 1277, 1252, 1181, 1085, 1055, 1035, 967, 802, 726, 705.
Experimental section 109

6.4.4 NMR studies of di-i-butyl hex-1-enyl alane derivatives
All the above reported spectra were recorded on a Varian Infinity spectrometer,
at the frequency of 300 MHz for 1 H NMR and 75 MHz for 13 C NMR, using C6D6
solutions. All signals are referred to the frequency of residual signal of the solvent
set exactly at 2134.36 Hz. Chemical shift are expressed in Hertz.
Tosyl chloride
Pyridine
1
H NMR: 503 (s, 3H), 1936 (d, J=8 Hz, 2H), 2258 (d, J=8 Hz,
2H); 13 C NMR: 21.0, 126.9, 129.9, 142.0, 146.1.
1
H NMR: 2002 (m, 2H), 2101 (tt, J=7 Hz, J’=2 Hz, 1H), 2543 (m, 2H);
13
C NMR: 123.4, 135.2, 150.1.
4-(N,N-Dimethyl)-amino pyridine (DMAP)
1
H NMR: 664 (s, 6H), 1824 (d, J=7 Hz, 2H), 2523 (d, J=7 Hz,
2H).
Di-i-butyl hex-1-enyl aluminum-DMAP complex and pyridine
Me
Me
N
O O
S
Cl
Me
N N
Me
Me
N
N
Al
(i-Bu) 2
Bu-n
1 H NMR: 165 (d, J=7 Hz, 4H), 276 (t, J=7 Hz, 3H),
392 (s, 12H), 390-482 (m, 4H), 622 (s, 6H), 678 (m,
2H), 723 (m, 2H), 1746 (d, J=7 Hz, 2H), 1941 (dt,
J=20 Hz, J’=1.5 Hz, 1H), 2001 (dt, J=20 Hz, J’=6 Hz,
1H), 2099 (tt, J=7 Hz, J’=2 Hz, 1H), 2469 (d, J=8 Hz,
2H), 2541 (d, J=7 Hz, 2H).
110 Chapter 6

Di-i-butyl hex-1-enyl aluminum
i-Bu
Al
i-Bu
1 H NMR: 111 (d, J=7 Hz, 4H), 227 (t, J=7 Hz), 330.3 (s,
12H, ), 345-390 (m, 4H), 601 (m, 2H), 629 (m, 2H), 1770 (dt,
J=20Hz, J’=1.5Hz, 1H), 2242 (dt, J=20Hz, J’=6Hz, 1H); 13 C
NMR: 13.7, 22.4, 26.8, 28.3, 29.4, 40.3, 126.3, 186.2.
Di-i-butyl hex-1-enyl aluminum-pyridine complex
N
Al
i-Bu 2
Bu-n
Bu-n
1 H NMR: 126 (d, J=7 Hz, 4H), 269 (t, J=7 Hz, 3H), 364 (s,
12H), 405-480 (m, 4H), 646 (m, 2H), 708 (m, 2H), 1895 (dt,
J=20 Hz, J’=1.5 Hz, 1H), 1935 (dt, J=20 Hz, J’=6 Hz, 1H),
1940 (m, 2H), 2038 (tt, J=7 Hz, J’=2 Hz, 1H), 2513 (m, 2H);
13 C NMR: 14.2, 22.7, 27.3, 28.7, 32.0, 39.6, 124.0, 124.1,
137.4, 148.7, 149.2.
Di-i-butyl hex-1-enyl aluminum-pyridine complex and tosyl chloride
(i-Bu) 2Al
O O
Ar S N
Bu-n
Cl
1
H NMR: 117 (d, J=7 Hz, 4H), 265 (t, J=7 Hz, 3H), 364 (s,
12H), 390-465 (m, 4H), 522 (s, 3H), 636 (m, 2H), 699 (m,
2H), 1884 (dt, J=20 Hz, J’=1.5 Hz, 1H), 1929 (dt, J=20 Hz,
J’=6 Hz, 1H), 1950 (m, 2H), 1959 (d, J=8 Hz, 2H), 2061 (tt,
J=7 Hz, J’=2 Hz, 1H), 2263 (d, J=8 Hz, 2H), 2514 (m, 2H);
13
C NMR: 14.2, 21.1, 22.7, 27.3, 28.7, 28.7, 32.0, 39.6,
124.3, 126.9, 130.0, 137.9, 141.9, 146.3, 148.5, 149.1.
Experimental section 111

Bibliography
1 Donaldson, R. E.; Fuchs, P. L. J. Am. Chem. Soc. 103(8), 2108 (1981).
2
Fuchs, P. L., Braish, T. F. Chem. Rev. 86, 903 (1986).
3
Nayera, C.; Yus, M. Tetrahedron 55, 10547 (1999).
4
Fabre, J.-L.; Julia, M.; Verpeaux, J.-N. Bull. Soc. Chim. Fr. (5), 762 (1985).
5
Trost, B. M.; Ghadiri, M. R. J. Am. Chem. Soc. 108(5), 1098 (1986).
6
Trost, B. M.; Schmuff, N. R.; Miller, M. J. J. Am. Chem. Soc. 102(18), 5979 (1980).
7
Lofstrom, C. M. G.; Ericsson, A. M.; Bourrinet, L.; Juntunen, S. K.; Backvall, J. E. J. Org.
Chem. 60(12), 3586 (1995).
8
Baudin, J. B.; Hareau, G.; Julia, S. A.; Ruel, O. Tetrahedron Lett. 32(9), 1175 (1991).
9 Charette, A. B.; Berthelette, C.; St-Martin, D. Tetrahedron Lett. 42, 5149 (2001).
10
Guijarro, D.; Yus, M. Tetrahedron Lett. 35(18), 2965 (1994).
11
Pospisil, J.; Pospisil, T.; Marko, I. E. Org. Lett. 7, 2373 (2005).
12
Park, E. S.; Hwan, S.; Lee, J. H.; Rhee, H. J.; Yoon, C. M. Synthesis , 3499 (2005).
13 Pospisil, J.; Marko, I. E. Tetrahedron Lett. 47, 5933 (2006).
14 Pummerer, R. Ber. 42, 2282 (1909).
15 Wilson, G.; Edwin, J.; Albert, R. J. Org. Chem. 38(12), 2160 (1973).
16 Posner, G. H.; Hulce, M.; Mallamo, J. P.; Drexler, S. A.; Clardy, J. J. Org. Chem. 46(25),
5244 (1981).
17 Trost, B. M.; Salzmann, T. N. J. Am. Chem. Soc. 95(20), 6840 (1973).
18 Ottenheijm, H. C. J.; Liskamp, R. M. J.; van Nispen, S. P. J. M.; Boots, H. A. Tijhuis, M. W.
J. Org. Chem. 46(2), 3273 (1981).
19 Hutton, C. A.; White, J. M. Tetrahedron Lett. 38(9), 1643 (1997).
20 Houpis, I. N.; Molina, A.; Dorziotis, I.; Reamer, R. A.; Volante, R. P.; Reider, P. J.
Tetrahedron Lett. 38(41), 7131 (1997).
21 Carreno, M.C. Chem. Rev. 95, 1717 (1995).
22
Pellissier, H. Tetrahedron 62, 5559 (2006).
23
Mandai, T.; Yanagi, T.; Araki, K.; Morisaki Y.; Kawada M.; Otera J. J. Am. Chem. Soc. 106,
3670 (1984).
24
Yoshida, K.; Hayashi, T. J. Am. Chem. Soc. 125, 2872 (2003).
25
Otera, J.; Misawa, H.; Sugimoto, K. J. Org. Chem. 51(20), 3830 (1986).
26
Keck, G. E.; Savin, K. A.; Weglarz, M. A. J. Org. Chem. 60(10), 3194 (1995).
27
Alonso, I.; Carretero, J. C.; Garrido, J. L.; Magro, V.; Pedregal, C. J. Org. Chem. 62(17), 5682
(1997).
28
Block, E.; Jeon, H. R.; Zhang, S.-Z.; Dikarev, E. V. Org. Lett. 6(3), 437 (2004).
29
Yoshimatsu, M.; Kawahigashi, M.; Hondab, E.; Kataoka, T. J. Chem. Soc., Perkin Trans. 1 ,
695 (1997).
30
Kim, S. H.; Jin, Z.; Ma, S.; Fuchs, P. L. Tetrahedron Lett. 36(23), 4013 (1995).
113

31
Yoshimatsu, M.; Hayashi, M.; Tanabe, G.; Muraoka, O. Tetrahedron Lett. 37(24), 4161
(1996).
32
Hardinger, S. A.; Fuchs, P. L. J. Org. Chem. 52(13), 2739 (1987).
33
Back, T. G.; Nakajima, K. J. Org. Chem. 65(15), 4543 (2000).
34
Costa, A; Najera, C.; Sansano, J. M. J. Org. Chem. 67(15), 5216 (2002).
35
Back, T. G.; Parvez, M.; Wulff, J. E. J. Org. Chem. 68(6), 2223 (2003).
36
Back, T. G.; Parvez, M.; Zhai, H. J. Org. Chem. 68(24), 9389 (2003).
37
Back, T. G.; Hamilton, M. D. Org. Lett. 4(10), 1779 (2002).
38
Mauleon, P.; Carretero, J. C. Org. Lett. 6(18), 3195 (2004).
39
Ogura, K.; Takeda, M.; Xie, J. R.; Akazomea, M.; Matsumotoa, S. Tetrahedron Lett. 42, 1923
(2001).
40
Trost, B. M.; Ghadiri, M. R. J. Am. Chem. Soc. 106, 7260 (1984).
41 Theobald, P. G.; Okamura, W. H. J. Org. Chem. 55(2), 741 (1990).
42 Alonso, I.; Carretero, J. C. J. Org. Chem. 66(12), 4453 (2001).
43 Satoh, T.; Sugiyama, S.; Kamide, Y.; Ota, H. Tetrahedron 59, 4327 (2003).
44 Maezaki, N.; Sawamoto, H.; Yuyama, S.; Yoshigami, R.; Suzuki, T.; Izumi, M.; Ohishi, H.;
Tanaka, T. J. Org. Chem. 69(19), 6335 (2004).
45 Capozzi, M. A. M.; Cardellicchio, C. N. F. Eur. J. Org. Chem. , 1855 (2004).
46 Backvall, J.-E.; Chinchilla; R. Najera; C.; Yus M. Chem. Rev. 98, 2291 (1998).
47 Schank, K. The Chemistry of sulfones and sulfoxides.
48 Vayssie, S., Elias, H. Angew. Chem., Int. Ed. Engl. 37(15), 2088 (1988).
49 Sato, K.; Hyodo, M.; Aoki, M.; Zheng, X. Q.; Noyori, R. Tetrahedron 57(13), 2469 (2001).
50 Back, T. G. Tetrahedron 57, 5263 (2001).
51 Truce, W. E.; Hill, H. E.; Boudakian, M. M. J. Am. Chem. Soc. 78, 2760 (1956).
52
Russell, G.; Ochrymowycz, L. A. J. Org. Chem. 36(6), 2106 (1970).
53
Hopkins, P. B.; Fuchs, P. L. J. Org. Chem. 43(6), 1208 (1978).
54
Backer, H. J.; Strating, J. Recl. Trav. Chim. Pays-Bas 73, 565 (1954).
55
Corlay, H.; Lewis, R. T.; Motherwell, W. B.; Shipman, M. Tetrahedron 51, 3303 (1995).
56
Jeong, I. H.; Chung, W. J. Bull. Korean Chem. Soc. 20(7), 768 (1999).
57
Xu, L.; Cheng, J.; Trudell, M. L. J. Org. Chem. 68(13), 5388 (2003).
58
Trost, B. M.; Curran, D. P. Tetrahedron Lett. 22, 1287 (2004).
59
Trost, B. M.; Braslau, R. J. Org. Chem. 53(3), 532 (1988).
60
Baciocchi, E.; Gerini, M. F.; Lapi, A. J. Org. Chem. 69, 3586 (2004).
61
Sankia, A. K.; Pathakb, T. Tetrahedron 59, 7203 (2003).
62
Michrowska, A.; Bieniek, M.; Kim, M.; Klajn, R.; Grela, K. Tetrahedron 59, 4525 (2003).
63 Kabalka, G. W.; Guchhait, S. K. Tetrahedron Lett. 45, 4021 (2004).
64 Fiandanese, V.; Marchese, G.; Naso, F. Tetrahedron Lett. 19(51), 5131 (1978).
65 Meijer, J.; Vermeer, P. Recl. Trav. Chim. Pays-Bas 94, 14 (1975).
66 Kleijn, H.; Vermeer, P. J. Org. Chem. 50, 5143 (1985).
67 Ryu, I.; Matsumoto, K.; Kameyama, Y.; Ando, M.; Kusumoto, N.; Ogawa, A.; Kambe, N.;
Murai, S.; Sonoda, N. J. Am. Chem. Soc. 115, 12330 (1993).
68 Eisch, J. J.; Behrooz, M.; Dua, S. K. J. Organomet. Chem. 285, 121 (1985).
114 Bibliography

69 Huang, X.; Duan, D.-H. J. Chem. Soc., Chem. Commun. , 1741 (1999).
70
Huang, X.; Duan, D.; Zheng, W. J. Org. Chem. 68(5), 1958 (2003).
71
Huang, X.; Xie, M. J. Org. Chem. 67(25), 8895 (2002).
72
Huang, X.; Xie, M. Org. Lett. 4(8), 1331 (2002).
73
Clasby, M. C.; Craig, D.; Jaxa-Chamiec, A. A.; Lai, J. Y. Q.; Marsh, A.; Slawin, A. M. Z.;
White, A. J. P.; Williams, D. J. Tetrahedron 52, 4769 (1996).
74
Truce, W. E.; Klein, H. G.; Kruse, R. B. J. Am. Chem. Soc. 83, 4636 (1961).
75 Xiang, J. S.; Mahadevan, A.; Fuchs, P. L. J. Am. Chem. Soc. 118(18), 4284 (1996).
76 Snider, B. B.; Kirk, T. C.; Roush, D. M.; Gonzalez, D. J. Org. Chem. 45, 5015 (1980).
77
Labadie S. S. J. Org. Chem. 54, 2496 (1989).
78
Russell, G. A.; Herold, L. L. J. Org. Chem. 50(7), 1037 (1985).
79
Dubbaka, S. R.; Vogel, P. J. Am. Chem. Soc. 125(50), 15292 (2003).
80
Dubbaka, S. R.; Vogel, P. Org. Lett. 6(1), 95 (2004).
81
Cho, C.-H.; Yun, H.-S.; Park, K. J. Org. Chem. 68(8), 3017 (2003).
82
Duan, D.-H.; Huang, X. Synlett (3), 317 (1999).
83
Cacchi, S.; Fabrizi, G.; Goggiamani, A.; Parisi, L. M.; Bernini, R. J. Org. Chem. 69(17), 5608
(2004).
84
Suzuki, H.; Abe, H. Tetrahedron Lett. 37(21), 3717 (1996).
85 Hershberger, J.; Russell, G. A. Synthesis , 475 (1980).
86 Truce, W.; Wolf, G. C. J. Org. Chem. 36(13), 1727 (1971).
87 Amiel, Y. J. Org. Chem. 36(24), 3691 (1971).
88 Pillot, J.P.; Dunoguic, J.; Calas, R. Synthesis , 469 (1977).
89
Amiel, Y. J. Org. Chem. 36(24), 3697 (1971).
90
Truce, W. E.; Goralski, C. T.; Christensen, L. W.; Bavry, R. H. J. Org. Chem. 35(12), 4217
(1970).
91
Amiel, Y. J. Org. Chem. 39(26), 3867 (1974).
92 Amiel, Y. Tetrahedron Lett. 12(8), 661 (1971).
93 Back, T. G.; Collins, S.; Kerr, R. G. J. Org. Chem. 48, 3077 (1983).
94 Back, T. G.; Collins, S.; Gokhale, U.; Law, K.-W. J. Org. Chem. 48, 4776 (1983).
95 Miura, T.; Kobayashi, M. J . Chem. Soc., Chem. Commun. , 438 (1982).
96 Back, T. G.; Collins, S.; Krishna, M. V.; Law, K.-W. J. Org. Chem. 52(19), 4258 (1987).
97 Back, G. T.; Lai, E. K. Y.; Muralidharan, K. R. J. Org. Chem. 55, 4595 (1990).
98 Watanabe, S.-I.; Yamamoto, K.; Itagaki, Y.; Iwamura, T.; Iwama, T.; Kataoka, T.; Tanabe, G.;
Muraoka, O. J. Chem. Soc., Perkin Trans. 1 , 239 (2001).
99 Gundermann, K. D. Angew. Chem., Int. Ed. Engl. 2, 674 (1963).
100 Mueller, W. H. Angew. Chem., Int. Ed. Engl. 8, 482 (1969).
101 Truce, W. E.; Goralsky, C. T. J. Org. Chem. 36(17), 3697 (1971).
102 Asscher, M.; Vofsi, D. J. Chem. Soc. , 4962 (1964).
103 Burger, J.J.; Chen, T. B. R. A.; De Waard, E. R.; Huisman, H. O. Tetrahedron 36, 723 (1980).
104 Liu, L. K.; Chi, Y.; Jen, K.-Y. J. Org. Chem. 45, 406 (1980).
105 Nair V., Augustine, A., Suja, T. D. Synthesis , 2259 (2002).
106 Simpkins, N. S. Tetrahedron Lett. 28(9), 989 (1987).
Bibliography 115

107 Sengupta, S.; Sarma, D. S.; Mondal, S. Tetrahedron: Asym. 9, 2311 (1998).
108 Katritzky, A. R.; Abdel-Fattah, A. A. A.; Wang, M. J. Org. Chem. 68(4), 1443 (2003).
109 Back, T. G.; Collins, S. J. Org. Chem. 46, 3249 (1981).
110 Gancarz, R. A.; Kice, J. L. J. Org. Chem. 46, 4899 (1981).
111 Paquette, L. A.; Crouse, G. D. J. Org. Chem. 48, 141 (1981).
112 Sas, W. J. Chem. Soc., Chem. Commun. , 862 (1984).
113 Posner, G.; Brunelle, D. J. J. Org. Chem. 37(22), 3547 (1972).
114 Reith, B. A.; Strating, J.; van Leusen, A. M. J. Org. Chem. 39(18), 2728 (1974).
115 Jang, W. B.; Jeon, H. J.; Oh, D. Y. Synth. Comm. 28(7), 1253 (1998).
116 Lee, J. W.; Oh, D. Y. Synth. Comm. 20(2), 273 (1990).
117
Lee, J. W.; Kim, T. H.; Oh, D. Y. Synth. Comm. 19(15), 2633 (1989).
118
Cuvigny, T.; Penhoat, C. H.; Julia, M. Tetrahedron 42(19), 5329 (1986).
119
Yoshimatsu, M.; Oh-Ishi, K.; Tanabe, G.; Muraoka, O. J. Chem. Soc., Perkin trans. 1 , 1413
(2002).
120
Shen, Y.; Wang, G.; Sun, J. J. Chem. Soc., Perkin Trans. 1 , 519 (2001).
121 Tanikaga, R.; Tamura, T.; Nozaki, Y.; Kaji, A. J. Chem. Soc., Chem. Commun. , 87 (1984).
122 Seshapathi, M.; Naidu, R.; Reddy, D. B. Bull. Soc. Chem. Jpn. 48(3), 1091 (1975).
123 Baliah, V.; Seshapathirao, M. J. Org. Chem. 24(3), 867 (1959).
124 Happer, D. A. R.; Steenson, B. E. Synthesis , 806 (1980).
125
Mohamed Zahouily, M.; Salah, M.; Bennazha, J.; Rayadha, A.; Sebti, S. Tetrahedron Lett. 44,
3255 (2003).
126
Harpp, D. N.; Vines, S. M.; Montillier, J. P.; Chan, T. H. J. Org. Chem. 41(25), 3987 (1976).
127 Indrarsena, T. R.; Rajender, S. V. Chem. Comm. , 471 (1997).
128
Vayssie, S.; Elias, H. Angew. Chem., Int. Ed. Engl. 37(15), 2088 (1998).
129
Paul J. Kropp, P. J.; Breton, G. W.; Fields, J. D.; Tung, J. C.; Loomis, B. L. J. Am. Chem. Soc.
122(18), 4280 (2000).
130
Bravo, A.; Dordi, B.; Fontana, F.; Minisci, F. J. Org. Chem. 66(9), 3232 (2001).
131 Legros, J.; Bolm, C. Angew. Chem., Int. Ed. Eng. 43, 4225 (2004).
132 Sun, J.; Zhu, C.; Dai, Z.; Xang, M.; Pan, Y.; Hu, H. J. Org. Chem. 69, 8500 (2004).
133
Bordwell, F. G.; Bout, P. J. J. Am. Chem. Soc. 59, 717 (1957).
134
Ford-Moore, A. H. J. Chem. Soc. , 2126 (1949).
135
Richmonn, L. S. S.; O’Sullivan, W. I. J. Chem. Soc., Perkin Trans. 1 , 1194 (1980).
136 Richmonn, L. S. S.; O’Sullivan, W. I. J. Chem. Soc., Chem. Commun. , 1012 (1976).
137 Verboom, W.; Sukhai, R. S.; Meijer, J. Synthesis , 47 (1979).
138
Muller, A. L.; Virtanen, A. I. Acta Chem. Scand. 80(20), 1163 (1966).
139
Ando, W.; Haniu, Y.; Takata, T. Tetrahedron 42, 1989 (1986).
140
Evans, D. A.; Brygan, C. A.;Sims, C. L. J. Am. Chem. Soc. 94, 2891 (1972).
141
Haszeldine, R. N.; Rigby, R. B.; Tipping, A. E. J. Chem. Soc., Perkin Trans. 1 , 676 (1973).
142
Zhong, P.; Huanga, X.; Ping-Guoa, M. Tetrahedron 56, 8921 (2000).
143
Maezaki, N.; Yagi, S.; Yoshigami, R.; Maeda, J.; Suzuki, T.; Ohsawa, S.; Tsukamoto, K.;
Tanaka, T. J. Org. Chem. 68(14), 5550 (2003).
116 Bibliography

144
Maezaki, N.; Sawamoto, H.; Suzuki, T.; Yoshigami, R.; Tanaka, T. J. Org. Chem. 69(24),
8387 (2004).
145
Kosugi, H.; Kitaoka, M.; Tagami, K.; Takahashi, A.; Uda, H. J. Org. Chem. 52(6), 1078
(1987).
146
Paley, R. S.; Weers, H. L.; Fernandez, P. Tetrahedron Lett. 36(21), 3605 (1995).
147 Hori, I.; Oishi, T. Tetrahedron Lett. 20, 4087 (1979).
148 Truce, W. E.; Lusch, M. J. J. Org. Chem. 39(21), 3174 (1974).
149 Truce, W. E.; Luschl, M. J. J. Org. Chem. 43(11), 2252 (1978).
150 Gilman, H; Robinson, J.; Beaber, N. J. Am. Chem Soc. 48, 2715 (1926).
151 Andersen, K. K. Tetrahedron Lett. 3(3), 93 (1962).
152 Solladié, G.; Hutt, J.; Girardin, A. Synthesis (2), 173 (1987).
153
Louis, C.; Hootel, C. Tetrahedron: Asym. 8(1), 109 (1997).
154
Posner, G. H.; Tang, P.-W. J. Org. Chem. 43(21), 4131 (1978).
155
Fernandez, I.; Khiar, N.; Llera, J. M.; Alcudia, F. J. Org. Chem. 57(25), 6789 (1992).
156 Strickler, R. R.; Schwan, A. L. Tetrahedron: Asym. 10, 4065 (1999).
157 Watanabe, Y.; Mase, N.; Tateyama, M.-A. Toru, T. Tetrahedron: Asym. 10, 737 (1999).
158
Huang, X.; Zhong, P.; Guo, M.-P. J. Organomet. Chem. 603, 249 (2000).
159
Baudin, J.-B.; Julia, S. A.; Wang, Y. Synlett , 911 (1992).
160
Brauman, J. I.; Bryson, J. A.; Kahl, D. C.; Nelson, N. J. J. Am. Chem. Soc. 92(22), 6679
(1970).
161
Mikolajczyk, M.; Grzejszczak, S.; Midura, W.; Zatorski, A. Synthesis , 278 (1975).
162 Mikolajczyk, M.; Grzejszczak, S.; Zatorski, A. J. Org. Chem. 40, 1979 (1975).
163 Craig, D.; Daniels, K.; Marsh, A.; Rainford, D.; Smith, A. M. Synlett , 531 (1990).
164 Mikolajczyk, M.; Perlikowska, J.; Omelanczuk, J.; Cristau, H.-J.; Perraud-Darcy, A. Synlett ,
913 (1991).
165 Mikolajczyk, M.; Perlikowska, W.; Omelanczuk, J.; Cristau, H.-J.; Perraud-Darcy, A. J. Org.
Chem. 63(26), 9716 (1998).
166 Almog, J.; Weissman, B. A. Synthesis , 164 (1973).
167 Otten, P. A.; Davies, H. M.; van Steenis, J. H.; Gorter, S.; van der Gen, A. Tetrahedron
53(30), 10527 (1997).
168 Otten, P. A.; Davies, H. M.; van der Gen, A. Tetrahedron Lett. 36(5), 781 (1995).
169
Guerrero-de la Rosa, V.; Ordofiez, M.; Alcudia, F.; Llera, J. M. Tetrahedron Lett. 36(27),
4889 (1995).
170
Solladie, G.; Ruiz, P.; Colobert, F.; Carreno, M. C.; Ruano, J. G. Synthesis , 1011 (1991).
171 Segorbe, M. M.; Adrio, J.; Carretero, J. C. Tetrahedron Lett. 41, 1983 (2000).
172
Herrmann, J. L.; Richman, J. E.; Wepplo, P. J.; Schlessinger, R. H. Tetrahedron Lett. 14(47),
4707 (1973).
173
Solladie, G.; Maugein, N.; Morreno, I.; Almario, A.; Carreno, M. C.; Garcia-Luano, J. L.
Tetrahedron Lett. 33(32), 4561 (1992).
174
Carey, F. A.; Hernandez, O. J. Org. Chem. 38(15), 2670 (1973).
175 Huang, X.; Zhong, P.; Guo, M.-P. J. Organom. Chem. 603(2), 249 (2000).
176 Zhong, P.; Guo, M.-P.; Huang, X. Journal of Chemical Research, Synopses (12), 588 (2000).
177 Zhong, P.; Guo, M.-P.; Huang, X. Synth. Comm. 31(4), 615 (2001).
Bibliography 117

178
Reinheckel, H; Jahnke, D. Abhandlungen der Deutschen Akademie der Wissenschaften zu
Berlin, Klasse fuer Chemie, Geologie und Biologie, , 67 (1967).
179
Reinheckel, H.; Haage, K.; Jahnke, D.;. Organometallic Chemistry Reviews, Section A:
Subject Reviews 4, 47 (1969).
180
Reinheckel, H.; Jahnke, D. Chem. Ber. 99, 1718 (1966).
181
Ziegler, K.; Gellert, H. G.; Lehmkuhl, H.; Pfohl, W.; Zosel, K. Ann. Chem. 629, 1 (1960).
182
Lehto, E. A.; Shirley, D. A. J. Org. Chem., 22, 1254 (1957)
183
Field, L.; Grunwald, F. A. J. Org. Chem., 16, 946 (1951)
184
Christophe, F. J.; Blanchet, M.; Bonin, M.; Micouin, L. Org. Lett. 6(14), 2333 (2004).
185 Henrickson, C. H.; Nykerx, K. M.; Eyman, D. P. Inorg. Chem. 7(5), 1028 (1968).
186 Henricksox, C. H.; Duffy, D.; Eyman, D. P. Inorg. Chem. 7(5), 1047 (1968).
187 Schwartz, G. L.; Dehn, W. M. J. Am. Chem. Soc. 39, 2444 (1917)
188 Seifert, E.; Abramo, L.; Thelin, B.; Nystrom, A.; Pettersen, J.; Bergman, R. Chemom. Intel.
Lab. Syst. 42, 3-40 (1998)
189 Opitz, G.; Mohl, H. R. Angew. Chem., Int. Ed. Eng. 8(1), 73 (1969).
190 Uchida, A.; Nakazawa T.; Kondo, I.; Iwata, N.; Matsuda, S. J. Org. Chem. 37(23), 3749
(1972).
191 Higashi, F.; Ikeda, E. Macrom. Rapid Comm. 21(18), 1306 (2000).
192 Theeraladanon, C.; Arisawa, M.; Nishida A.; Nakagawa, M. Tetrahedron 60, 3017 (2004).
193 Williamson, N. M.; Ward, A. D. Tetrahedron 61, 155 (2005).
194 Comins, D. L.; Joseph, S. P.; Zhang, Y. M. Tetrahedron Lett. 37(6), 793 (1996).
195 Arisawa, M.; Theeraladanon, C.; Nishida, A.; Nakagawa, M. Tetrahedron Lett. 42, 8029
(2001).
196 Ichikawa, E.; Suzuki, M.; Yabu, K.; Albert, M.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc.
126(38), 11808 (2004).
197 Boger, D. L.; Christine, E.; Brotherton, C. E.; Panek, J. S.; Yohannes, D. J. Org. Chem.
49(21), 4056 (1984).
198 Akib, K.; Nakatani, M.; Wada, M.; Yamamoto, Y. J. Org. Chem. 50(1), 63 (1985).
199
Takamura, M.; Funabashi, K.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc. 123(28), 6801
(2001).
200
Alexakis, A.; Amiot, F. Tetrahedron: Asym. 13, 2117 (2002).
201
Hoesl, C. E.; Maurus, M.; Pabel, J.; Polborn, K.; Wanner, K. T. Tetrahedron 58, 6757 (2002).
202 Comins, D. L.; Abdullah, A. H. J. Org. Chem. 47(22), 4315 (1982).
203 Chia,W.-L.; Shen, S.-W.; Lin, H.-C. Tetrahedron Lett. 42, 2177 (2001).
204
Comins, D. L.; Myoung, Y. C. J. Org. Chem. 55, 292 (1990).
205
Hilgeroth, A.; Voigt, B. Heterocycles 60(10), 2223 (2003).
206
Yamaguchi, R.; Otsuji, A.; Utimoto, K. J. Am. Chem. Soc. 110(7), 2186 (1988).
207 Yamaguchi, R.; Moriyasu, M.; Yoshioka, M.; Kawanisi, M. J. Org. Chem. 50(2), 287 (1985).
208
Yamaguchi, R.; Moriyasu, M.; Yoshioka, M.; Kawanisi, M. J. Org. Chem. 53(15), 3507
(1988).
209
Yamaguchi, R.; Nakayasu, T.; Hatano, B.; Nagura, T.; Kozima, S.; Fujita, K.-I. Tetrahedron
57, 109 (2001).
210
Bennasar, M.-L.; Roca, T.; Monerris, M. J. Org. Chem. 69(3), 752 (2004).
118 Bibliography

211 Plath, M. W.; Scharf, H.-D.; Raabe, G.; Kruger, C. Synthesis (10), 951 (1990).
212 Coldham, I.; Houdayer, P. M. A.; Judkins, R. A.; Witty, D. R. Synlett (11), 1109 (1996).
213 Coldham, I.; Houdayer, P. M. A.; Judkins, R. A.; Witty, D. R. Synthesis (10), 1463 (1998).
214
Techer, H.; Pesson, M.; Lavergne, M. Compt. Rend. 269(10), 564 (1969).
215
Sturm, E. (1979). United States Patent US 4,133,954, 9.01.1979.
216
Naumann, K.; Scheinpflug, H.; Rosslenbroich, H.-L.; Paul, V. (1985). United States Patent US
4,537,888, 27.08.1985, German Patent DE 3234529, 17.09.1982.
217 nd
Perrin, D. D.; Armarego, W. L. F. Purification of laboratory chemicals. Pergamon press, 2
edition, (1983).
218 Zaramell, S.; Stramberg, R. Y. E. Eur. J. Org. Chem. , 2633 (2002).
219 Jotterand, N.; Pearce, D. A.; Imperiali, B. J. Org. Chem. 66, 3224 (2001).
Bibliography 119