4th EucheMs chemistry congress

Poster Session 1
s1050
chem. Listy 106, s587–s1425 (2012)
Poster session 1 - organic chemistry
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BorAte eSter MediAted AMidAtion And
trAnSAMidAtion reACtionS
r. LAniGAn 1 , t. ShePPArd 1
1 University College London, Chemistry, London,
United Kingdom
The formation of an amide bond is an essential
transformation in organic chemistry, the amide bond is found in
25% of known drugs. [1] It is a condensation reaction between a
carboxylic acid and an amine with the elimination of one molecule
of water. Amidation reactions typically require preactivation of
the carboxylic acid as an acid chloride or anhydride, or the use of
coupling reagents, which reduces the efficiency of the reaction.
We have previously shown that tris-(2,2,2-trifluoroethyl) borate
[B(OCH CF ) ] can be used to amidate unactivated carboxylic
2 3 3
acids. [2] We have recently developed a cheaper and more
convenient procedure for the synthesis of B(OCH CF ) from
2 3 3
boric anhydride (£27/kg) instead of boron tribromide (£765/kg) [3]
.
Unlike previous work involving stoichiometric boron
reagents for amidation B(OCH CF ) does not require anhydrous
2 3 3
conditions or an excess of the carboxylic acid or amine for the
reaction to proceed efficiently. A wide range of amides can be
synthesised containing aliphatic, aromatic and heteroaromatic
substituents on both the acid and amine partner. [3] The synthesis
of paracetamol has also been carried out using this methodology.
The products are purified via simple aqueous or solid phase work
up. This method is also useful for the amidation of N-protected
amino acids with both primary and secondary amines. [3]
A formylation method using DMF in the presence of
B(OCH CF ) has also been developed. 2 3 3 3 Trimethoxyboroxine was
investigated as an amidation reagent and displayed similar utility
to B(OCH CF ) . We have carried out an NMR study to elucidate
2 3 3
the reaction mechanism.
references:
1.. C. A. G. N. Montalbetti and V. Falque, V. Tetrahedron,
2005, 61, 10827-10852.
2. P. Starkov and T. D. Sheppard, Org. Biomol. Chem., 2011,
9, 1320-1323.
3. R. M. Lanigan, P. Starkov and T. D. Sheppard, Manuscript
in preparation.
Keywords: Amides; Borates; Boron; Carboxylic acids;
Amines;
4 th EucheMs chemistry congress
P - 0 3 7 8
fLuoroALKyLideneS SyntheSiS froM
BenzothiAzoLyL derivAtiveS
f. LArnAud 1 , e. Pfund 1 , A. GAneSAn 2 , B. LinCLAu 3 ,
t. Lequeux 1
1 Laboratoire de Chimie Moléculaire et Thioorganique, UMR
6507, Caen, France
2 University of East Anglia, School of Pharmacy, Norwich,
United Kingdom
3 University of Southampton, School of Chemistry, Southampton,
United Kingdom
The fluorovinylic moiety has been introduced onto several
bio-active compounds such as vitamins, prostaglandins,
hormones, pheromones and peptide isosteres. However, access to
fluoroalkylidenes is not straightforward and required numerous
steps including functionalization of fluoroacrylates easily obtained
by HWE reaction.
In 2002, our group described the first one step synthesis of
fluoroalkylidene via the modified Julia reaction. Since this report,
our main research deals with the preparation of various alkylated
fluorobenzothiazolylsulfones as new building blocks for the
expeditive synthesis of fluoroalkenes.
For the preparation of alkylfluorosulfones, our strategy is
based on alkylation reactions under Barbier conditions of
benzothiazolylsufonyl fluoroacrylate using alkyl iodides and
alcohols, followed by a decarboxylation process carried out under
Krapcho conditions.
Currently, this approach is applied for on the developement
of new peptidomimetics. Indeed, we already reported the
expeditive synthesis of fluorinated dipeptide analogues using the
modified Julia reaction. Our recent results will be presented.
Keywords: Julia reaction; fluorine; olefination;
Peptidomimetics; alkenes;
AUGUst 26–30, 2012, PrAGUE, cZEcH rEPUbLIc