Missing out on the latest research developments in ... - Sigma-Aldrich

Aldrich
Cyclopropylboronic acid MIDA ester: a useful building block for use in
Suzuki-Miyaura reactions.
VOLUME 11 NUMBER 1 2011 20 2011 11
Asymmetric SSyn
ynth thes es esis is
Catalysis
Ch Chem emic ic ical al BBio
io iolo lo logy g
Organo nome meta ta tall ll llic ic ics
Bu B ilding Block cks
Sy Synt nthe heti ti tic c Re Reag ag agen ents ts
Stab able le IIso
sotopes
St Stockroom m Re Reag ag agen en ents ts
La Labw b are No Note tes

* Thomson Reuters; Journal Citation Reports ® , Science Edition.
<strong>Missing</strong> <strong>out</strong> on
the latest research
developments in
Chemistry?
Aldrichimica Acta is a complimentary quarterly
publication, which has been an international forum for
the frontiers of chemical research for the past 43 years.
Articles, written by chemists from around the world, cover
a variety of topics usually based on a synthetic theme
involving organic, organometallic, bio-organic, or inorganic
chemistry. It has been ranked #1 by Impact Factor in eight
of the past nine years in the fi eld of organic chemistry (<strong>out</strong>
of over 50 similar journals), with an Impact Factor of 18.688
(2009).*
Aldrichimica Acta helps keep you informed of the latest
research methodologies and trends, as well as the related
Aldrich Chemistry products to support them.
Request your FREE copy today
Aldrich.com/acta

Aldrich
Volume 11, Number 1
Sigma-Aldrich Corporation
6000 N. Teutonia Ave.
Milwaukee, WI 53209, USA
Editorial Team
Haydn Boehm, Ph.D.
Wesley Smith
Dean Llanas
Sharbil J. Firsan, Ph.D.
Weimin Qian, Ph.D.
Production Team
Cynthia Skaggs
Carrie Spear
Chris Lein
Tom Beckermann
Christian Hagmann
Denise de Voogd
Chemistry Team
Aaron Thornton, Ph.D.
Daniel Weibel, Ph.D.
Josephine Nakhla, Ph.D.
Matthias Junkers, Ph.D.
Mark Redlich, Ph.D.
Troy Ryba, Ph.D.
Todd Halkoski
Paula Freemantle
Mike Willis
Aldrich ChemFiles Subscriptions
To request your FREE subscription to Aldrich ChemFiles, either
visit our website at: aldrich.com/chemfi les or contact your local
Sigma-Aldrich offi ce (see back cover).
Aldrich ChemFiles Online
Aldrich ChemFiles is also available in PDF format on the Internet at
aldrich.com/chemfi les.
Aldrich Chemistry Products
Aldrich brand products are sold through Sigma-Aldrich, Inc.
Sigma-Aldrich, Inc. warrants that its products conform to the
information contained in this and other Sigma-Aldrich publications.
Purchaser must determine the suitability of the product for its
particular use. See reverse side of invoice or packing slip for additional
terms and conditions of sale. All prices are subject to change
with<strong>out</strong> notice.
To Place Orders or Contact Customer/
Technical Services
Please contact your local Sigma-Aldrich offi ce (see back cover).
Aldrich ChemFiles (ISSN 1933–9658) is a publication of Aldrich
Chemical Co., Inc. Aldrich is a member of the Sigma-Aldrich Group.
© 2011 Sigma-Aldrich Co.
Haydn Boehm, Ph. D.
Global Marketing Manager: Chemical Synthesis
haydn.boehm@sial.com
Introduction 3
Dear Chemists,
Welcome to the fi rst edition of the Aldrich ChemFiles for 2011.
Aldrich ChemFiles is our FREE quarterly newsletter written by
our experts in Product Management and R&D. Our aim is to
keep you keep informed of new Aldrich Chemistry products that facilitate the latest
research methodologies and trends, and allow you to access key starting materials and
reagents more effi ciently.
As well as introducing all the latest innovations across all our product lines, each
2011 edition of Aldrich ChemFiles will be themed to a product line. Aldrich ChemFiles
11.1 focuses on Organometallic Reagents, which is very timely as it aff ords me the
opportunity to welcome Dr. Aaron Thornton as our new Organometallic Reagents
Product Manager. Our cover molecule is cyclopropylboronic acid MIDA ester, which
is a new addition to our ever-growing MIDA boronate portfolio. Aaron also highlights
our latest trifl uoroborates, a complementary strategy to MIDA boronates for selective
Suzuki-Miyaura coupling reactions. This “Organometallics issue” also features our
latest organotin reagents for Stille couplings, as well as TurboGrignards for selective
metallations.
Aldrich ChemFiles 11.1 also introduces our new iridium catalysts (Catalysis),
indoles and thiazoles (Building Blocks), reagents for organometallic chemistry in water
(Synthetic Reagents) and ChemMatrix Resin for solid phase peptide synthesis (Chemical
Biology).
We hope that Aldrich ChemFiles enables you to expand your research toolbox and
advance your chemistry more eff ectively by implementing the latest innovative
synthetic strategies.
Kind Regards,
Haydn Boehm, Ph. D.
Global Marketing Manager: Chemical Synthesis
Table of Contents
Asymmetric Synthesis ...............................................................................................................................4
Catalysis ................................................................................................................................................................8
Chemical Biology ....................................................................................................................................... 10
Organometallic Reagents .................................................................................................................... 14
Building Blocks ............................................................................................................................................ 22
Synthetic Reagents ................................................................................................................................... 24
Stable Isotopes ............................................................................................................................................ 26
Stockroom Reagents ...............................................................................................................................28
Labware Notes .............................................................................................................................................. 30

4
BASF’s ChiPros®: Optically Active Intermediates
on an Industrial Scale
In recent years, single-enantiomer drugs and drug candidates have
become more and more important in the pharmaceutical and agrochemical
industry. Therefore, effi cient methods for the synthesis of small,
homochiral intermediates, which are frequently used as building blocks
for many pharmaceuticals and crop protection agents like herbicides,
fungicides and insecticides, but also resolving agents and chiral auxiliaries,
are of central interest.
With its ChiPros portfolio 1 , BASF off ers a broad and growing range of
chiral amines, alcohols, epoxides and carboxylic acids. The ChiPros toolbox
holds the best-in-class technologies of enzyme-based biocatalysis
including lipases, dehydrogenases, nitrilases, esterases, oxygenases, etc.
In addition, chemical methods such as catalytic asymmetric hydrogenations
and CBS reductions are utilized to further strengthen the technology
portfolio. 2
ChiPros Chiral Amines
Chiral amines play an important role in stereoselective organic synthesis.
They are used directly as resolving agents, building blocks or chiral
auxiliaries. While classically available through racemic resolution with
optically active acids, biotechnological approaches also open a way to
chiral amines. 3 BASF’s optimized lipase-catalyzed r<strong>out</strong>e to optically active
amines (Scheme 1) can be run at a scale of several thousand tons. Due
to the wide range of substrates tolerated by the enzymes, a large variety
of diff erent chiral amines and chiral aminoalcohols are commercially
available.
Aldrich.com
NH 2
CH 3
Lipase
NH 2
CH 3
Scheme 1: Lipase-catalyzed resolution of racemic amines.
Asymmetric Synthesis
Daniel Weibel, Ph.D.
European Market Segment Manager, Chemical Synthesis
daniel.weibel@sial.com
+
O
HN CH 3
CH 3
TO ORDER: Contact your local Sigma-Aldrich offi ce (see back cover), or visit Aldrich.com/chemicalsynthesis.
H 3C
NH 2
NH 2
CH 3
726621
NH2 H3C CH3 H3C CH3
726729
NH2 H3C CH3 H3C CH3
726559
H 2N
NH 2
CH3
NH 2
CH3
OCH 3
NH 2
CH 3
CH 3
F
H 3C
H 3C
Cl
HN
NH 2
O
NH 2
O
NH 2
NH 2
CH 3
CH 3
CH 3
NH 2
NH2
CH 3
NH 2
CH 3
CH3
H 3CO
H 3CO
H 3CO
H 3CO
H 3C
CH 3
Br
727229
727288
NH 2
O
NH 2
NH 2
NH 2
NH 2
NH 2
CH 3
NH 2
NH 2
CH 3
CH 3
CH 3
CH 3
CH 3
Cl
Cl
H 3C
NH2 H3C CH3 CH3 NH2 H3C CH3 CH3 H2N CH3
727164 726494 726591 727156
726486
727148
727024
727172
726532 727105 726680 726524
726796
726583
726915
726710
726516
726664
726826
726540
726974
726907
726850
726648
NH 2
O
NH 2
NH 2
726702
726931
CH3
CH 3
NH 2
726737
NH 2
CH3

H 3C
H 3CO
Br
726893
NH 2
727083
726842
NH 2
726869
NH 2
NH 2
CH 3
ChiPros Chiral Acids
Enantiopure α- and ß-hydroxy acids and esters are versatile building
blocks for the preparation of a wide range of active pharmaceutical
ingredients by incorporating them as esters, amides or ethers, or after
further derivatization, as diols, amino alcohols, thioethers.
Hydroxy acids are accessible via a range of biotransformations, among
them are the stereoselective hydrolysis of the racemic ester precursor or
reduction of the corresponding keto esters. Hydroxynitrile lyase (HNL)
processes catalyze the stereoselective addition of HCN to aldehydes and
ketones yielding single-enantiomeric nitriles. 3 Application of nitrilases or
a combination of nitrile-hydratase plus amidase allows the transformation
of the starting material into the desired enantiomer of the corresponding
acid in a dynamic kinetic resolution fi nally yielding mandelic
acid derivatives.
BASF developed proprietary processes based on dehydrogenases to off er
access to a wide range of α- and ß-hydroxy esters, starting from readily
available keto esters. Due to the large range of enzymes available, both
enantiomers can normally be made. Another established technology is
enzymatic resolution using lipases which only acylate one enantiomer.
Cl OH
CH 3
O
727067
H 3C
CH3 H3C OH
H 3C
NH2 CH3 726605
726885
NH 2
726923
727342
NH 2
CH 3
CH3 H3C NH2
CH3
OH
726990
O
OH
HN
NH 2
CH 3
726818
NH2 CH3 726613
727180
727032
NH 2
CH 3
NH3 O
H3C OH
727350
Br
CH3
H3CO SO 3
CH 3
ChiPros Chiral Alcohols
Ready to scale up? For competitive quotes on larger quantities or custom synthesis, contact your local Sigma-Aldrich offi ce, or visit safcglobal.com.
NH 2
726958
NCO
CH 3
726761
726656
CH 3
NH 2
CH 3
Asymmetric Synthesis 5
Chiral alcohols form a versatile class of chiral synthons, since they can
be incorporated into the API structures directly as esters or ethers. They
can be starting materials for the formation of amines, amides, thiols,
thioethers. In addition, after transforming the hydroxyl function into a
leaving group by way of mesylation, tosylation or trifl ation, they can be
used to form new C–C bonds.
Many manufacturing r<strong>out</strong>es make use of asymmetric hydrogenation
methods. 4 The two most important biocatalytical processes for the formation
of chiral alcohols apply lipases and dehydrogenases, respectively. 3
The latter off ers the advantage that only the requested enantiomer is
obtained. Enzyme-catalyzed acylations using lipases, however, achieve
the resolution of racemic mixtures of alcohols but with an inherent 50
percent maximum yield of the total amount of starting material. One
enantiomer of the racemic mixture remains unchanged while the antipodal
enantiomer is esterifi ed (Scheme 2).
H 3CO
O
O
CH 3
OH
OH
+ CH3 Lipase
CH3 +
R
Scheme 2: Lipase-catalyzed resolution of aryl-substituted alcohols.
R
R
O
O
CH 3
OCH 3
Thanks to a variety of commercial and proprietary enzymes at its disposal,
BASF off ers a wide range of aliphatic and cycloaliphatic and aryl-substituted
single-enantiomer alcohols under the ChiPros brand.
H3C
OH
CH 3
726753 726672
OH
726567
CH 3
H 3C
OH
CH 3
H 3C
OH
727059
CH 3
OH
O
O
727210
CH 3

6
ChiPros Chiral Epoxides
Oxiranes are very valuable building blocks which allow
derivatization:
• by forming C-X bonds (through reactions with alcohols,
ammonia, amines, phenolates etc.)
• or by forming new C–C bonds (through reactions with cyanide,
malonates, allyl silyl reagents, metal-organic reagents, e.g. Mg, Zn,
Li organyls)
There are several alternative r<strong>out</strong>es towards chiral aryl-substituted epoxides,
among them Jacobsen’s asymmetric epoxidation 5 or his hydrolytic
kinetic resolution 6 method, Sharpless’s asymmetric epoxidation 7 using
catalytic titan(IV)- isopropylate/diethyl tartrate complexes and tert-butylhydroperoxide,
complemented by Shi’s reaction 8 using peroxomonosulfate
with a chiral ketone as catalyst, or among the enzymatic methods,
application of epoxide hydrolases, lipases or monooxygenases. The stereoselective
reduction of α-chlorinated acetophenones using dehydrogenases,
however, aff ords a very versatile and more cost-effi cient access
to a wide range of oxiranes, including both enantiomers of styrene oxide
as well as very diff erently substituted phenyl oxiranes (Scheme 3).
Aldrich.com
O O
CH 3
R R
Scheme 3: Stereoselective synthesis of oxiranes.
X
R
OH
X
Base
R
TO ORDER: Contact your local Sigma-Aldrich offi ce (see back cover), or visit Aldrich.com/chemicalsynthesis.
O
O
726508
F
727253
O
Cl
726699
O
O
726834
Aldrich Chemistry is proud to off er ChiPros in small quantities (up to
kilograms). A total of 79 products from the ChiPros portfolio are available
from Aldrich Chemistry, including chiral amines, alcohols, epoxides and
carboxylic acids.
References:
(1) http://www.chipros.com (2) Karl, U.; Simon, A. Chimica Oggi/Chemistry Today 2009,
27, 5. (3) Breuer, M.; Ditrich, K. et al. Angew. Chem. Int. Ed. 2004, 43, 788-824. (4) Blaser, H.
U.; Schmidt, E. Asymmetric Catalysis on Industrial Scale, Wiley-VCH. 2004 (5) Zhang, W.;
Loebach, J. L. et al. J. Am. Chem. Soc. 1990, 112, 2801-2803. (6) White, D. E.; Jacobsen, E. N.
Tetrahedron: Asymmetry 2003, 14, 3633-3638. (7) (a) Katsuki, T.; Sharpless, K. B. J. Am. Chem.
Soc. 1980, 102, 5974-5976. (b) Review: Hüft, E. Top. Curr. Chem. 1993, 164, 63-77.
(8) (a) Wang, Z.-X.; Tu, Y. et al. J. Am. Chem. Soc. 1997, 119, 11224-11235; (b) Ager, D.;
Anderson, K. et al., Org. Proc. Res. Dev. 2007, 11, 44-51; (c) Aldrich Chemfi les 2010, 3, 4-5.
For a complete list of Chiral Building Blocks available from
Aldrich Chemistry, visit Aldrich.com/chiralbb

New Q-Tube Pressure Reactors
Q-Tubes are affordable alternatives to a microwave synthesizer
and feature a safe pressure-release system (patent pending) that
prevents accidental explosions due to overpressurization. Starter
kits contain all items needed for immediate use.
Q-Block Heating Blocks
These anodized-aluminum heating blocks are designed for
use with 12-mL and 35-mL Q-Tubes. The maximum working
temperature is 204 °C. Blocks have a safety locking plate, safety
shield, thermally stable silicone tubing, and an internal cooling
channel for fast cooling (nitrogen, compressed air, or vacuum).
There is also a thermocouple well for accurate temperature
measurement.
Q-Tube Size Cat. No.
12 mL Z567914
35 mL Z567922
Q-Tube Benefi ts:
•
•
•
•
•
•
•
•
Better yield
Cleaner product
Reduced reaction time
Higher reproducibility
Scalability (up to 20 grams)
Safer automatic pressure release
Aff ordability
Maintenance-free
Q-Tube Starter Kits:
Kits contain all items needed for immediate use.
View accessory product listings and technical information
ab<strong>out</strong> Q-Tubes on our website at
sigma-aldrich.com/qtube
Q-Tube Size Cat. No.
12 mL Z567671
35 mL Z567736

8
Ir(I)-Catalyzed C–H
Borylation
Arylboronic acids and esters are invaluable tools for the chemical community.
These powerful reagents are used for a variety of transformations,
most notably the Suzuki-Miyaura cross-coupling reaction. This reaction
is used to selectively construct C–C bonds through the combination of
an organo-boron nucleophile with a suitable aryl, alkenyl, or alkyl halide
or trifl ate. While the Suzuki-Miyaura reaction has become commonplace
within the synthetic community, one limitation of this method is the
limited ability to access the requisite organo-boron species.
Historically, methods for the synthesis for aryl C–B bonds have relied
upon the use of harshly basic reaction conditions or substrates containing
prefunctionalized carbon centers. These shortcomings require that
additional steps must be taken to either protect sensitive functionality
or install the necessary functional handle prior to C–B bond formation
(Scheme 1).
R
X
X = Cl, Br, I
R
DG
H
Aldrich.com
R'MX
R'Li
R
X
Pd(0), Base
HB(OR'')2
or
(OR'') 2B B(OR'')2
R
X = Br, I, OTf
R
R
MX
B(OR'')3
R
B(OR'')2
DG
B(OR'')3
R
DG
Li B(OR'')2
B(OR'') 2
Scheme 1: Classical methods for C–B bond formation.
Harshly basic reaction conditions
Multiple steps and manipulations
Requires prefunctionalized starting materials
The direct formation of aryl C–B bonds from aryl C–H bonds thus represents
a powerful strategy for streamlining the synthesis of these useful
reagents (Scheme 2). 1
R
H [M]
HB(OR'')2
or
(OR'')2B B(OR'')2
R
B(OR'')2
Scheme 2: Metal-catalyzed direct C–H borylation.
Catalysis
Josephine Nakhla, Ph.D.
Market Segment Manager
Organometallics and Catalysis
josephine.nakhla@sial.com
No harsh reagents or reaction conditions
No need for prefunctionalization
Atom economical
TO ORDER: Contact your local Sigma-Aldrich offi ce (see back cover), or visit Aldrich.com/chemicalsynthesis.
Building upon their previous work within the area, 2 Professor John F.
Hartwig has disclosed a method for the direct conversion of aryl C–H
bonds to aryl C–B bonds through the use of an Ir(I) catalyst and B2pin2
(Table 1). 3 This powerful system displays excellent regioselectivity that
can be easily predicted by sterics and leads to the rapid synthesis of
highly useful arylboronic esters.
H 3C
H3CO
R
arene product
CH3
H
H
H
H3C
CH3
H
H3CO
OCH3 OCH3
Cl Cl
Cl
Bpin
Bpin
Bpin
1/2[IrCl(COD)]2/bpy
B2pin2, 80 oC, 16 h.
95 %
83 %
86 %
H Bpin
H3CO H
83 %
Table 1: Ir(I)-Catalyzed aryl C–H borylation.
Cl
R
Bpin
yield arene product yield
H 3C
H3C
H3CO
CH3
CH3
Br
CH3
H 3C
H3C
H3CO
H3CO
This method provides a simple and direct r<strong>out</strong>e to arylboronic esters that
fully avoids the use of harshly basic reaction conditions and does not
require multiple reaction steps and manipulations. Importantly, this reaction
employs catalysts and reagents that are all readily accessible, and
now available from Aldrich.
Reference: (1) Cho, J. Y.; Tse, M. K.; Holmes, D.; Maleczka Jr., R. E.; Smith III, M. R.
Science, 2002, 295, 305 (2) (a) Chen, H.; Hartwig, J. F. Angew. Chem. Int. Ed. Engl. 1999, 38,
3391. (b) Chen, H.; Schlecht, S.; Semple, T. C.; Hartwig, J. F. Science 2000, 287, 1995.
(3) Hartwig, J. F. et al. J. Am. Chem. Soc. 2002, 124, 390. (4) Hartwig, J. F.
et al. Chem. Rev. 2010, 110, 890.
H
H
H
CH3
CH3
Br
Bpin
CH3
Bpin
Bpin
Bpin
58 %
86 %
72 %
73 %

Iridium(I) Catalysts, Bipyridine Ligands, and
Borylation Reagents from Aldrich:
Ir(I) Catalysts Bipyridine Ligands Borylation Reagents
For a complete list of C–H borylation reagents available from Aldrich
Chemistry, please visit Aldrich.com/borylation
Carboranes as Superweak Anions
The chemistry of weakly coordinating anions, or superweak anions,
continues to be actively investigated within many laboratories for a
variety of purposes. These useful molecules often allow for the isolation
of extremely reactive salts of cations, making them applicable to the ever
growing list of chemical tasks that require highly reactive cations. These
uses include the catalytic polymerization of olefi ns, the catalytic formation
of C–C bonds, the manufacture of high-current-density lithium batteries,
and the activation of C–H bonds. Discover how carboranes from Aldrich
can advance your research.
Carboranes from Aldrich:
F
B F
B
B
F
Cl
Ir Ir
Cl
683094
CH3
O
Ir Ir
O
B
CH3
685062
[Ir(COE) 2 Cl] 2
377155
Ir
685011
F
B
B
F
F F F
B
B
F
F B
F
B Cs
B
Cs
B
F
N N
36759 473294
H3C CH3
N N
569593
H3C CH3
N N
513040
H3CO OCH3
N N
536040
t-Bu t-Bu
N N
515477
F
F
B
B
F
B
B
F
B
B
F
B
B
F
F
B
B
F F F
723509 720887
H3C
H3C
H3C
H3C H3C
H3C
H
H
B
B
O O
B B
O O
O
B
O
CH3
CH3
CH3
CH3
655856
O O
B B
O O
473286
O
B
O
188913
O
B
O
518808
F
F
Ready to scale up? For competitive quotes on larger quantities or custom synthesis, contact your local Sigma-Aldrich offi ce, or visit safcglobal.com.
K
K
CH3
CH3
CH3
CH3 O CH3
B
O CH3
Frustrated Lewis Pairs as Hydrogenation
Catalysts
Catalysis
The hydrogenation of organic substrates with molecular hydrogen (H2)
has been used for purposes ranging from the large-scale upgrading of
crude-oil, to the synthesis of fi ne chemicals used in food, agriculture, and
the pharmaceutical industry. While the majority of methods rely on the
use of costly precious metal catalysts, recent work from the lab of Professor
Douglas W. Stephan has illustrated the use of frustrated Lewis pairs
for the same purpose. 1,2 These powerful non-metallic catalysts contain
both Lewis acidic (borane) and Lewis basic (phosphine) moieties that
cannot be quenched internally due to steric constraints. Because of this
unquenched reactivity, these organic catalysts are used to activate a variety
of small molecules, including the heterolytic cleavage of H2, leading to
a powerful catalyst system for the hydrogenation of imines and aziridines
(Scheme 3).
Scheme 3: Frustrated Lewis pairs for the hydrogenation of imines
and aziridines.
Reference: (1) Welch, G. C.; San Juan, R. R.; Masuda, J. D.; Stephan, D. W. Science 2006, 314,
1124. (2) (a) Chase, P. A.; Welch, G. C.; Jurca, T.; Stephan, D. W. Angew. Chem., Int. Ed. 2007,
46, 8050. (b) Chase, P. A.; Welch, G. C.; Jurca, T.; Stephan, D. W. Angew. Chem., Int. Ed. 2007,
46, 9136.
Frustrated Lewis Pairs from Aldrich:
F
F
t-Bu
N
703087 5 mol %
t-Bu
NH
H Ph
5 atm H 2
H Ph
H
98 %
F
F
F F
H
B
F F
F F
F
Ph
F
Ph
N
Ph
F
t-Bu
P
t-Bu
F
H +
703095
5 atm H 2
F
F
For a complete list of Frustrated Lewis pairs available from Aldrich
Chemistry, please visit Aldrich.com/fl p
F
F
F
F
10 mol %
F
BH
F F
F
F
F
F
H3C Ph
NH
H +
F H3C 703087 703095
Ph
Ph
98 %
P
CH 3
CH3 CH3
CH3
9

10
ChemMatrix® Resin – A major advance in solid
phase peptide synthesis
ChemMatrix® is a proprietary, 100% PEG (polyethylene glycol) based
resin from PCAS BioMatrix. It combines the strengths of two major
resin systems — the chemical stability of polystyrene resins and the
superior performance of PEG grafted resins making it the ultimate
choice for the solid supported synthesis of large or hydrophobic
peptides and even proteins.
In the past decades polystyrene resins have been the primary choice for
solid supported peptide synthesis due to their good results in the synthesis
of small peptides. Nevertheless, with the growing amino acid chain
during the synthesis, the tendency of the peptide to form secondary
structures increases. The hydrophobic environment of the polystyrene
resin amplifi es the aggregational behavior of the peptide making the
synthesis of large peptides extremely diffi cult or even impossible. Crude
products of large peptides synthesized on polystyrene resins exhibit a
mixture of deletion sequences and uncompleted fragments. PEG grafted
resins have helped to reach better crude peptide purities by making the
resin more polar and improving the swelling properties in both polar
and unpolar solvents. As a drawback such PEG grafted resins only allow
smaller loadings and are less chemically stable leading to potential leaching
during the cleavage step.
ChemMatrix resin was designed from scratch starting with a new type of
monomer building block. The fi nal polymer resin is built exclusively on
primary ether bonds and therefore exhibits high chemical stability, avoiding
leaching (Figure 1). 1
O
H2N O
H2N O
H2N O
Figure 1: The scaff old of Aminomethyl-ChemMatrix resin is built completely on
chemically stable polyether bonds (left). Microscopic image of ChemMatrix beads
(right).
Aldrich.com
O
O
O
O
O
n
nO
NH2 nO
NH2
O
n
NH2 Chemical Biology
Matthias Junkers, Ph.D.
Product Manager
matthias.junkers@sial.com
TO ORDER: Contact your local Sigma-Aldrich offi ce (see back cover), or visit Aldrich.com/chemicalsynthesis.
At the same time, the increased polarity of the resin allows the use of various
polar solvents, including: water, THF, DMF, methanol and acetonitrile,
in which the resin displays excellent swelling properties (Figure 2). High
swelling properties should be considered during practical use as the wet
ChemMatrix resin will consume considerably more space in the reaction
vessel than conventional polystyrene resins. Typical loading ranges are
between 0.4 and 0.7 mmol/g which is a comparable binding capacity as
polystyrene resins.
Swelling (mL/g)
18
16
14
12
10
8
6
4
2
0
Acetonitrile
DCM
DMF
NMP
DMSO
Methanol
TFA
Water
Figure 2: Swelling properties of ChemMatrix resin compared to
polystyrene resin.
Polystyrene
Aminomethyl-
ChemMatrix
Two recent independent publications give remarkable evidence for
the unmatched performance of ChemMatrix resin. For the synthesis of
HIV–1 protease, a large peptide of 99 amino acids, ChemMatrix resin
was compared directly to polystyrene. 2 As the following chromatograms
clearly show, the desired peptide is the main component of the crude
product using ChemMatrix as the solid support (Figure 3). Polystyrene
resins only deliver crude mixtures preventing the direct, linear synthesis
of long peptides.

1.00 2.00 3.00 4.00 5.00 6.00 7.00 8.00 9.00 10.00 11.00 12.00
Minutes
1.00 2.00 3.00 4.00 5.00 6.00 7.00 8.00 9.00 10.00 11.00 12.00
Minutes
Figure 3: HPLC chromatograms of HIV–1 protease (99 amino acids) after
78 amino acids. The synthesis on ChemMatrix resin yields the desired peptide
directly with<strong>out</strong> further purifi cation (top) whereas polystyrene
resin only yields a very crude mixture (bottom). 2
7.025
In a second amazing example, Bacsa et al. reported in 2010, the solid
supported, microwave assisted synthesis of the polypeptide Aβ(1–42). 3
Aβ (1–42) plays a crucial role in the pathogenesis of Alzheimer’s disease
in that it forms β–sheet structures and amyloid fi brils which induce
neurotoxicity. Thus, it is a key material needed to further investigate the
molecular mechanisms of Alzheimer’s disease and potential drugs for its
treatment. Due to its aggregational behavior this peptide is highly diffi cult
to synthesize. ChemMatrix resin allows the direct, linear synthesis with a
standard Fmoc/t–Bu synthesis strategy applying DIC/HOBt as a simple
and inexpensive coupling reagent. Except for the coupling of three
racemization sensitive histidine residues which was carried <strong>out</strong> at room
temperature the synthesis was achieved under controlled microwave
conditions at 86 °C. ChemMatrix resin remained completely stable under
these conditions. 4 Finally, Aβ(1–42) was obtained within a 15h overall
processing time in high yield and purity (78% crude yield). 3
Apart from peptide synthesis ChemMatrix resin has also been used successfully
in combinatorial synthesis, 5 for the synthesis of oligonucleotide
derivatives, 6 PNA, 7 asymmetrically substituted phthalocyanines, 8 and
peptide hybrids incorporating non-natural chemical residues. 9
In summary, ChemMatrix overcomes the challenges of synthesizing
longer and more complex therapeutic peptides. Peptides produced with
ChemMatrix have higher purity and can be obtained with better yields.
Peptides that were hitherto achievable only by ligation or recombinant
techniques can now be synthesized directly on solid support.
Ready to scale up? For competitive quotes on larger quantities or custom synthesis, contact your local Sigma-Aldrich offi ce, or visit safcglobal.com.
Chemical Biology
For the synthesis of peptide acids, we recommend using the ChemMatrix
with a HMPB anchor as this resin will provide high crude purity and a
recovery yield of 90–95%. The Wang-ChemMatrix will produce similar
crude peptide purity, but the recovery yield is lower (60–70%). HMPB–ChemMatrix
resins are also off ered preloaded with the most common amino
acids. A number of protocols for the application of ChemMatrix resin have
been published recently in the literature. 10
Features of ChemMatrix Resin
• Exceptional Stability
ChemMatrix resin is made exclusively from primary ether bonds which
are highly chemically stable. No leaching occurs during synthesis and
cleavage.
• High Loading
ChemMatrix resins have a loading of 0.4–0.7 mmol/g.
• Solvent Compatibility
ChemMatrix allows the use of almost any kind of solvent, even water.
High swelling properties of ChemMatrix in water allows high throughput
post-synthetic downstream screening.
• Versatile Choices
ChemMatrix resin is off ered with an extensive range of linkers for
peptide acids, amides and fragments. For peptide synthesis, preloaded
resins are also available for your convenience.
• Demonstrated Superiority
ChemMatrix resin has been fi eld proven for easier and faster development
of long, complex and hydrophobic peptides. The longer, the more
complex or hydrophobic your peptide is, the more improvement you
will see with ChemMatrix.
• Microwave assisted synthesis
No leaching is observed on microwave synthesizers at 80 °C.
References: (1) García-Martin, F.; Albericio, F. Chem. Today 2008, 26, 29. (2) Frutos, S.;
Tulla-Pucha, J.; Albericio, F.; Giralt, E. Intern. J. of Pept. Res. Ther. 2007, 13, 221. (3) Bacsa, B.;
Bösze, S.; Kappe. C. O. J. Org. Chem. 2010, 75, 2103. (4a) Subiros-Funosas, R.; Acosta, G. A.;
El-Faham, A.; Albericio, F. Tet. Lett. 2009, 50, 6200. (4b) Galanis, A. S.; Albericio, F.; Grøtli,
M. Org. Lett. 2009, 11, 4488. (5) Marani, M.M.; Martínez-Ceron, M. C.; Giudicessi, S. L.; de
Oliveira, E.; Côté S.; Erra-Balsells, R.; Albericio, F.; Cascone, O.; Camperi, S. A. J. Comb. Chem.
2009, 11, 146. (6) Mazzini, S.; García-Martin, F.; Alvira, M.; Aviñó, A.; Manning, B.; Albericio, F.;
Eritja, R. Chem. Biodiv. 2008, 5, 209. (7) Fabani, M. M.; Abreu-Goodger, C.; Williams, D.; Lyons,
P. A.; Torres, A. G.; Smith, K. G. C.; Enright, A. J.; Gait, M. J.; Vigorito., E. Nucl. Acids Res. 2010, 38,
4466. (8) Erdem, S. S.; Nesterova, I. V.; Soper, S. A.; Hammer, R. P. J. Org. Chem. 2008, 73, 5003.
(9) Spengler, J.; Ruíz-Rodríguez, J.; Yraola, F.; Royo, M.; Winter, M.; Burger, K.; Albericio. F. J.
Org. Chem. 2008, 73, 2311. (10) García-Ramos Y.; Paradís-Bas, M.; Tulla-Puchea, J.; Albericio, F.
J. Pept. Science 2010, 16, 675.
11

12
ChemMatrix resins
N
H
O
HMPB-CM
727741
N
H
O
Wang-CM
64191
N
H
O
Ramage-CM
Aldrich.com
O
O
O
H2N O
H2N O
H2N O
OH
OCH3
OH
NHFmoc
O
O
O
Aminomethyl CM
68571
nO
NH2
nO
NH2
O NH2
n
N
H
O
O
Rink amide CM
727768
N
H
O
Trityl-OH CM
727776
N
H
O
PAL-CM
727792 727784
OH
O
NHFmoc
OCH3
OCH3
OCH 3
NHFmoc
OCH3
ChemMatrix HMPB preloaded resins
TO ORDER: Contact your local Sigma-Aldrich offi ce (see back cover), or visit Aldrich.com/chemicalsynthesis.
N
H
N
H
N
H
N
H
O
O
O
OCH3
O
NH2
O
H-Gly-HMPB-CM H-Ala-HMPB-CM
O
H-Arg(Pbf)-HMPB-CM
O
O
727806 727822
O
H-Leu-HMPB-CM
O
H-Phe-HMPB-CM
OCH3
O
HN
OCH3
O
OCH3
O
O
NH2
NH
NHPbf
NH2 CH3
CH3
O
N
H
N
H
N
H
O
O
O
O
O
H-Lys(Boc)-HMPB-CM
727849 727865
O
H-Val-HMPB-CM
727814 727830
NH2
O
N H
O
O
H-Pro-HMPB-CM
727857 727873
OCH3
O
OCH3
O
OCH3
O
O
O
BocHN
NH2
NH2
NH2
OCH3
HN
O
O
CH3
CH3
CH3 O
For a complete list of ChemMatrix products available from Aldrich
Chemistry, please visit Aldrich.com/chemmatrix

Custom Packaged Reagents (CPR)
To register for an online ordering
account or to submit inquiries, visit
Discoverycpr.com
Our CPR Service provides a cost eff ective strategy to
procure one to thousands of unique, custom packaged
building blocks and screening compounds for use in
research programs.
CPR is optimized to support several discovery activities:
• The chemist looking to identify and procure sets of building blocks for their high
throughput synthetic reactions
• The chemical biologist or biologist interested in the diversity of the world’s largest
selection of screening compounds
Customized packaging allows you to receive samples in a ready-to-use format, allowing
you to focus on your research rather than spending time weighing <strong>out</strong> building blocks or
tracking down vendors.
CPR from Aldrich provides:
• Widest selection of building blocks, reagents, and screening compounds through
hundreds of managed vendors worldwide
• Internet-based chemical database and procurement functionality
• Custom packaging of over 200,000 off -the-shelf products from global sources
• Availability and pricing in a single quotation with consolidation of invoicing
• Standard or client-supplied custom packaging in vials or plates
• Customized labeling, including 1-D or 2-D barcoding to your specifi cations
Normalization of electronic data with shipment including SD fi le generation
•

14
MIDA Boronates for Suzuki–Miyaura
Cross-Couplings
Aldrich.com
Organometallics
Aaron Thornton, Ph.D.
Product Manager
aaron.thornton@sial.com
Professor Martin Burke and coworkers recently prepared retinal using
key MIDA building block BB1 in iterative Suzuki-Miyaura cross coupling
reactions (Scheme 1). The MIDA unit of BB1 is unreactive under these
conditions, allowing for the selective cross-coupling of BB1 with triene
(1). Subsequent hydrolysis of the MIDA unit of (2) followed by a second
Suzuki-Miyaura reaction provided all-trans-retinal.
H3C
CH3
CH3
B(OH)2
H3C N
BB1
O
B O
Br O O
703478
Pd(OAc)2, SPhos, K3PO4
H3C CH3
CH3
H3C
N
B O
O
O
O
CH3 1 toluene
23 °C, 78%
CH3 2
1. aq. NaOH, THF, 23 °C
CH3 H
2.
Br O
Pd(OAc)2, SPhos, K3PO4, THF
23 °C, 66%
CH3 CH3 H3C
H
CH3
O
CH3
all-trans-retinal
Scheme 1: Iterative Suzuki-Miyaura cross-couplings in the synthesis of
all-trans-retinal.
Reference: Lee, S. J. et al. J. Am. Chem. Soc. 2008, 130, 466.
The many advantages of the MIDA boronate platform include air and
moisture stability, stability under anhydrous cross-coupling conditions,
compatibility with a range of common and harsh reagents, solubility
in various organic solvents, silica gel compatibility, and the ability to
undergo slow release cross-couplings.
MIDA Boronates from Aldrich:
H3C
N
B O O
O O
697311
H3C
H3C
N
B O
O
CH2 O
O
707252
TO ORDER: Contact your local Sigma-Aldrich offi ce (see back cover), or visit Aldrich.com/chemicalsynthesis.
H2C
H2C
H3C
N
B O O
O O
N
B
O
O
O O
H3C
698709 700231
N
B
O
O
O O
H3C
704415
HC
S
N
B
O
O
O O
H3C
708828
For complete list of MIDA boronates available from
Aldrich Chemistry, visit Aldrich.com/mida
Slow-Release of Unstable Boronic Acids from
MIDA Boronates
In addition to attenuated reactivity towards anhydrous cross-coupling
conditions, MIDA boronates also possess the capacity for in situ slowrelease
of boronic acids under aqueous basic conditions (Scheme 2).
Harnessing this phenomenon, boronic acids that are notoriously unstable
can be eff ectively utilized in cross-coupling when employed as MIDA
boronates. While aqueous solutions of NaOH promote the fast hydrolysis
of MIDA boronates to their corresponding boronic acids, the use of aqueous
K3PO4 allows for the slow-release of relatively unstable boronic acids,
preventing decomposition of the organometallic species and improving
overall yields for many Suzuki-Miyaura reactions.
Slow Release of Unstable Boronic Acids
R B
H3C
Pd-catalyst
N
O
O
O
O
mild aqueous base (e.g. K3PO4)
Cl R'
R B(OH)2
Scheme 2: Slow-release of unstable boronic acids from MIDA boronates.
Burke and coworkers examined this slow-release concept by comparing
various freshly prepared boronic acids with their corresponding MIDA
boronates. The study revealed that many boronic acids decompose
signifi cantly via various pathways, including protodeborylation, oxidation,
and polymerization, after just 15 days of benchtop storage under air. On
the other hand, the corresponding MIDA boronates were remarkably
stable, with >95% of each MIDA remaining after ≥60 days of benchtop
storage under air. In addition to complications related to storage, the
overall effi ciency of cross-coupling for these reagents is also impacted
by the nature of the boron unit. For example, while isolated yields are
R R'

generally low to moderate even when freshly-prepared boronic acids are
employed in Suzuki-Miyaura cross-couplings, employing the corresponding
MIDA boronate results in excellent yields of the desired cross-coupled
products (Table 1).
Entry
1
2
3
4
R B
H3C
R B(OH)2 or
N
O
O
O
O
1 eq 1 eq
A B
R
O
Boc
N
% remaining after benchtop
storage under air
A (15 days) B (>60 days)
7 >95
95
5 >95 a
Ot-Bu
Cl 1 mmol
Pd(OAc)2, SPhos
K3PO4, dioxane:H2O (5:1)
60 °C, 6 h
Boc
N
SO2Ph SO2Ph
N
95
N
a cross coupling conducted at 100 °C
O
C
Ot-Bu
Ot-Bu
Ot-Bu
Ot-Bu
R
C
Ot-Bu
Cross Coupling
Isolated Yield (%)
with A with B
68 94
61 90
79 98
14 93
Table 1: Stability and slow-release cross-coupling studies of MIDA boronates vs.
boronic acids.
MIDA Boronates for Classically Challenging
Suzuki-Miyaura Cross-Couplings
The power of this slow-release concept has been further illustrated by
utilizing various MIDA boronates of which the corresponding boronic
acids have historically exhibited challenges with respect to either storage
or use, including 2-heterocyclic, vinyl and cyclopropyl boronic acids.
Because these organoboron species readily decompose through a variety
of pathways, the effi ciency with which their corresponding MIDA boronates
may be coupled is particularily noteworthy (Table 2).
R B
H3C N
O
O
O
O
Cl R'
Pd(OAc)2, SPhos, K3PO4
dioxane/H2O (5:1), 60 °C, 6 h
R R'
Entry R MIDA R' Cl
Product Isolated Yield (%)
H3C
N
N
N
1
S B O
O
H3C
O
O Cl N
S
N
97
2
Boc
N
N
B O
O
O
O
Cl
O
N
CH3
Boc
N
O
N
CH3
98
H3C 3
N
B O
O
O
O Cl
N NH2
N NH2
76
H3C
N
H3C CH3 H3C CH3
4
B O
O
O
O Cl
CH3
CH3
79
Table 2: Slow-release cross-coupling of MIDA boronates with historically challenging
substrates.
Ready to scale up? For competitive quotes on larger quantities or custom synthesis, contact your local Sigma-Aldrich offi ce, or visit safcglobal.com.
Organometallics
2-Pyridinylboronic Acid MIDA Ester as a Stable
2-Pyridinyl Boron Anion Equivalent
The development of a viable air-stable surrogate for the notoriously
unstable 2-pyridinylboronic acid has been a long-standing challenge
in the fi eld of cross-coupling. This motif is ubiquitous in drug-like small
molecules, and therefore of particular importance to the synthetic community.
While 2-pyridinylboronic acid surrogates exist, their use is often
complicated by air- and moisture-sensitivity as well as their somewhat
variable and impure compositions. In contrast, Burke and coworkers
found that 2-pyridinyl MIDA boronate is isolable, benchtop and chromatography
stable, and under slow-release conditions can be successfully
coupled with a variety of aryl and heteroaryl chlorides (Table 3).
H3C N
N
B O
O
O
O
Cl R
Pd2(dba)3, XPhos, K3PO4
Cu(OAc) 2, K2CO3
DMF/IPA (4:1), 100 °C, 4 h
N R
Entry Cl R Product Isolated Yield (%)
1
2
3
Cl
Cl
Cl
719390
N
N
O
C CH3
CN
N
N
N
N
N
O
C CH3
Table 3: Slow-release cross-coupling of 2-pyridinylboronic acid MIDA ester.
References: (1) Gillis, E. P.; Burke, M. D. Aldrichimica Acta 2009, 131, 17. (2) Knapp, D. M.;
Gillis, E. P.; Burke, M. D. J. Am. Chem. Soc. 2009, 131, 6961.
Pyridinyl MIDA Boronates from Aldrich
Cl
N
N
H3C
N
B
O
O
O O
719390
H3C
N
700908
H3C
N
B O O
O O
N OCH3
701084
B O O
O O
Br
H3CO
N
N
H3C
N
723959
N
B
O
O
O O
H3C
N
702269
H3C
N
723053
B O O
O O
B
O
O
O O
CN
Br
H3CO
For a complete list of MIDA boronates available from
Aldrich Chemistry, visit Aldrich.com/mida
H3C
N
N
72
60
79
H3C
N
B O O
O O
N
704563
H3C
N
703370
H3C
N
699845
B O O
O O
B O O
O O
15

16
Heterocyclic Organotin Reagents for
Stille Coupling
Stille reactions remain one of the most viable methods for the formation
of C–C bonds in organic chemistry. 1 Their use has been highlighted in
various areas, including countless natural product syntheses, material science
applications, and in numerous synthetic methodology studies. The
coupling of imidazolyl stannane 718793 with heterocycle (4) by process
chemists at Pfi zer was reported in 2003 (Scheme 3). 2 This coupling
employed Pd(PPh3)4 as the catalyst and was carried <strong>out</strong> in 67% isolated
yield. Addition/elimination on the resulting functionalized thienopyridine
provided bulk material of the desired VEGFR kinase inhibitor (5). It
is worth noting that of several cross-couplings which were examined,
the Stille coupling employing stannane 718793 was the only reaction
feasible on scales >50g.
Cl
N
S
Aldrich.com
I
CH3
N
SnBu3
N
718793
Pd(PPh3)4 (5 mol%)
DMF, 95 C
40 h, 67%
Cl
N
H3C
S N
N
H3C
t-BuOH/DCE
100 C
4 5
Scheme 3: Stille reaction in the preparation of VEGFR kinase inhibitors (5).
H
N
52%
NH2
H3C
H
N
NH
N
H3C
S N
N
References: (1) Mascitti, Vincent. Stille coupling. Name Reactions for Homologations 2009,
(Pt. 1), 133–162. (2) Ragan, J. A.; Raggon, J. W.; Hill, P. D.; Jones, B. P.; McDermott, R. E.;
Munchhof, M. J.; Marx, M. A.; Casavant, J. M.; Cooper, B. A.; Doty, J. L.; Lu, Y. Org. Proc. Res.
Dev. 2003, 7, 676.
Organotin Reagents from Aldrich:
Bu3Sn SnBu3
S
Bu 3Sn
Bu3Sn N
N
678333 698598
Bu3Sn
Bu3Sn
717703
N
S
H3C
N
Bu3Sn
683930 719366
Bu3Sn
718807
719730 706868 707031
O
O N
706981
N
OCH2CH3
Bu 3Sn
Bu3Sn
N
N
N N
CH3 Cl
Bu3Sn
Bu3Sn
N
Cl N Cl
707813 717630
N
Bu3Sn
N
OCH3
CH3
N
N
TO ORDER: Contact your local Sigma-Aldrich offi ce (see back cover), or visit Aldrich.com/chemicalsynthesis.
Bu 3Sn
N
O
Bu3Sn
638617 642541 706965
Bu 3Sn
N
CH3
Bu3Sn
675679 719501 718793
N
S
N
N
CH3
Br
N
S
Bu3Sn
SnBu3
For a complete list of Organotin Reagents available from
Aldrich Chemistry, visit Aldrich.com/organotin
Selective 1,2-Additions with LaCl3·2LiCl
While the 1,2-addition of Grignard reagents to ketones is undoubtedly
a powerful transformation, oftentimes selectivity issues arising from
competitive alpha-deprotonation detract from the use of these reagents.
Various methods have been developed to address this shortcoming,
including the use of CeCl3 and other Lewis acidic salts. However, because
of the heterogeneous nature of these reagents, it is often diffi cult to
obtain adequate selectivity. With this in mind, the lab of Professor Paul
Knochel has shown that LaCl3•2LiCl (703559) may be used to attenuate
the basicity of Grignard reagents, in turn preventing competitive enolization
side reactions while leading to a powerful method for the selective
1,2-addition of Grignard reagents to ketones. In addition to enolizable
ketones, even sterically hindered ketones, as well as Michael acceptors
and unactivated imines can undergo 1,2-additions selectively to provide
the desired addition products (Table 4). 1
Entry
1
2
EtO2C
3
Grignard
Reagent
i-PrMgCl
MgCl LiCl
N
R1MgCl + R2 Br
Ketone
O
Ph Ph EtO2C
MgCl LiCl
Ph
O
Ph
Product
i-Pr
OH
a Isolated yield of product based on reaction between ketone and Grignard reagent
b Isolated yield of product in the presence of 1.5 eq CeCl3 (Dimitrov Method)
c Isolated yield of product in the presence of 1.0 eq LaCl3 2LiCl
O
R 3
O
0 °C, 10 min-6h
LaCl3 2LiCl
703559
Table 4: LaCl3•2LiCl mediated addition to ketones.
OH
N
R 2
OH
Bn
Bn
Br
OMgCl
R3 R1 N
N
CH3
with
no additives a
with
CeCl3 b
5
72
39 11
35
Yield (%)
__
with
LaCl3 2LiCl c
92
92
81

Subsequent to these initial studies with LaCl3•2LiCl, Knochel and coworkers
reported that sub-stoichiometric quantities of the lanthanide salt are
suffi cient to promote the desired 1,2-addition, as demonstrated by the
addition of i-PrMgCl•LiCl to unactivated imines (Scheme 4). This protocol
is amenable to the use of alkyl, aryl, and heteroaryl Grignard reagents. 2
Ph
N
OMe
+ i-PrMgCl LiCl
LaCl3 2LiCl
(10 mol%)
THF, rt, 12h
HN
Ph i-Pr
Scheme 4: 1,2-Addition of organomagnesium reagents in the presence of catalytic
LaCl3•2LiCl.
Advantages of LaCl3•2LiCl:
• No pretreatment procedures necessary
Easy handling of reagents and reaction setup
• Homogeneous reaction conditions
• Improved selectivity and reactivity providing better yields and
• decreased reaction times
References: (1) Krasovskiy, A.; Kopp, F.; Knochel, P. Angew. Chem. Int. Ed. 2006, 45, 497. (2)
Metzger, A.; Gavryushin, A.; Knochel, P. SynLett 2009, 1433.
For a complete list of selective metallation reagents available from
Aldrich Chemistry, visit Aldrich.com/metallations
Chiral Silacycles for Enantioselective
Allylation and Crotylation Reactions
The asymmetric allylation and crotylation of aldehydes and other carbonyl
compounds remains one of the most fundamental reactions for the
construction of chiral building blocks. While numerous methods for this
challenging task have been examined previously, including the use of
chiral auxiliaries, chiral reagents and catalytic systems, still today a truly
convenient and broadly reaching method remains elusive. With this goal
in mind, the group of Professor James Leighton has developed a versatile
system that has proven to be uniquely eff ective. Leighton and co-workers
have harnessed the power of strained silacycles for use as allylation reagents
with<strong>out</strong> the need for any further catalysts or reagents (Scheme 5).
Me
Ph
Me
N
Si
O Cl
Me
Ph
Me
N
Si
O Cl
Scheme 5: Leighton’s chiral allyl silanes.
H
N
Si
N Cl
H
Br
Br
OMe
84%
H
N
Si
N Cl
H
These bench-stable and non-toxic reagents undergo enantioselective addition
to a range of carbonyl compounds, including aldehydes, ketones,
Ready to scale up? For competitive quotes on larger quantities or custom synthesis, contact your local Sigma-Aldrich offi ce, or visit safcglobal.com.
Br
Br
Organometallics
and hydrazones 1 (Table 5). Notably, all of these reactions are carried <strong>out</strong> at
convenient reaction temperatures with<strong>out</strong> the need for external activating
reagents, thereby simplifying reaction set-up and manipulation.
Me
Ph
Me
N
Si
O Cl
706671
O
OH
+
R H R
R T ( o C) yield % e.e. %
-10
-10
-10
80
59
84
81
78
88
Me
Ph
Me
N
Si
O Cl
706671
R
+
NHBz
N R' NHNHBz
R R' R
R' T ( o C) yield % e.e. %
CH3
CO2Me
Table 5: Enantioselective allylation of various aldehydes and hydrazones with
706671.
In addition to enantioselective allylation reactions, Leighton and
co-workers have extended this concept to the enantioselective crotylation
of carbonyl compounds 2 (Table 6). Importantly, these diamine
derived silacycles are bench-stable crystalline solids, providing the added
benefi t of simple reaction setup and purifi cation.
H
N
Si
N Cl
H
Br
CH 3
CH3
R
R
-10
-10
-10
OH
OH
CH 3
CH 3
Silane R product yield % e.e. %
A
B
A
B
A
B
A
B
A
H
N
Si
N Cl
H
B
or
H 3C
BnO
Br O
+
DBU
o
Br R H CH2Cl2, 0 C
Br
CH 3
CH 3
Table 6: Enantioselective crotylation of aldehydes.
References: (1) (a) Kinnaird, J. W. H.; Ng, P. Y.; Kubota, K.; Wang, X.; Leighton, J. L. J.Am.
Chem. Soc. 2002, 124, 7920. (b) Berger, R.; Duff , K.; Leighton, J. L. J. Am. Chem. Soc. 2004, 126,
5686. (2) Hackman, B. M.; Lombardi, P. J.; Leighton, J. L. Org. Lett. 2004, 23, 4375.
1
2
1
2
1
2
1
2
83
81
70
71
82
83
67
52
1
2
or
97
98
96
97
96
99
95
94
80
59
84
81
78
88
17

18
Chiral Allyl and Crotylsilanes:
Me
Ph
H
N
Si
N Cl
H
704725
Me
N
Si
O Cl
706671
For a complete list of allylation reagents available from
Aldrich Chemistry, visit Aldrich.com/allylations
Selective Metalations using i-PrMgCl·LiCl and
s-BuMgCl·LiCl
While halogen-metal exchange reactions are among the most common
methods for preparing reactive organometallic reagents, Li-halogen
exchange reactions typically require low temperatures and off er limited
compatibility with other functionalities. On the other hand, Mg-halogen
exchange reactions require higher temperatures and are often prone to
elimination side reactions. To address these issues, Knochel and coworkers
have found that the use of salt additives increase both the rate and
the effi ciency of this Mg-halogen exchange reaction. The most eff ective
reagents are generated with R-MgCl (R = i-Pr, s-Butyl) and 1.0 equiv
of LiCl. The increased reactivity of these aptly named TurboGrignards
may be due to the breakup of polymeric aggregates known to exist in
classical solutions of Grignard reagents. TurboGrignards allow for the
conversion of a variety of functionalized and highly sensitive substrates,
including those containing CO2R, CN, OMe, and halogen moieties, to
their corresponding functionalized organometallic derivatives. While rate
enhancements are observed with TurboGrignards, this increased reactivity
does not have a negative impact on the overall scope of the reaction,
permitting transformations to occur in the presence of a broad range of
functional groups (Table 7). 1
Aldrich.com
Br
Br
Me
Ph
H
N
Si
N Cl
H
705098
Me
N
Si
O Cl
719056
Br
Br
H
N
Si
N Cl
H
733075
Br
CH3
Br
H
N
Si
N Cl
H
733199
TO ORDER: Contact your local Sigma-Aldrich offi ce (see back cover), or visit Aldrich.com/chemicalsynthesis.
Br
CH3
Br
Entry
1
2
i-PrMgCl LiCl
Br 656984
(TurboGrignard)
FG
THF, -15 °C to 25 °C
or heteroaryl halide
FG = CO2R', CN, OMe, halogen
FG
MgCl LiCl
Reagent
Electrophile Product
i-PrO O
O
O
MgCl LiCl
PhCHO
Br
N
MgCl LiCl
Allyl Bromide
N MgCl LiCl
PhCHO
3
S
aThe halogen-metal exchange was conducted in THF/DMPU.
bGrignard was transmetalated with CuCN 2LiCl before addition of E.
Br
E
FG
N
OH
N
Ph
S
E
Ph 80 a
Allyl
Isolated
Yield
Table 7: Aryl/heteroaryl Grignard reagents prepared using i-PrMgCl·LiCl and reactions
with electrophiles.
Advantages of TurboGrignards:
• Increased functional group compatibility
• Mild reaction conditions
• Minimal side reactions
• Allows for the large-scale production of reactive
Grignard reagents
References: (1) Krasovskiy, A.; Knochel, P. Angew. Chem. Int. Ed. 2004, 43, 3333.
(2) P. Knochel, E P 1582 524 A1.
TurboGrignard Reagents from Aldrich:
H3C
CH3
MgCl . LiCl
656984
For more information on these new reagents, visit
Aldrich.com/metalations
Sold in collaboration with
H3C
CH3
MgCl . LiCl
703486
93 b
87

Organotrifl uoroborates as Coupling
Partners in Suzuki-Miyaura Reactions
Suzuki-Miyaura cross-coupling reactions are some of the most common
methods for the formation of C–C bonds in organic chemistry. The use of
organotrifl uoroborate salts as boronic acid surrogates has lead to signifi -
cant advancement in the fi eld of Suzuki-Miyaura reactions. Trifl uoroborates
exhibit excellent functional group tolerance and stability towards
1, 2
common reagents, in turn leading to a truly versatile class of reagents.
Our platform of trifl uoroborate salts is continually growing, with new
product introductions occurring regularly.
Benefi ts of Organotrifl uoroborates:
• Stable tetracoordinate species
Less prone to protodeboronation
• Air-and moisture-stable
•
Potassium Vinyltrifl uoroborate as a Versatile
Dianion Precursor
Molander and co-workers have developed a powerful strategy for the
production of a unique 1,2-dianion equivalent using potassium vinyltrifl
uoroborate. 1 This useful organotrifl uoroborate undergoes selective
hydroboration with 9-BBN to generate (3), a 1,2-dianion equivalent that
can then undergo a variety of selective transformations (Scheme 6).
9-BBN
BF3K
Potassium vinyltrifluoroborate
655228
B
3
BF3K
Scheme 6: Hydroborated intermediate (3) as a 1,2-dianion equivalent.
Ready to scale up? For competitive quotes on larger quantities or custom synthesis, contact your local Sigma-Aldrich offi ce, or visit safcglobal.com.
Organometallics
This versatile 1,2-dianion equivalent undergoes sequential Suzuki-Miyaura
cross-coupling with a range of organic electrophiles, including aryl-,
heteroaryl-, and alkenyl halides (Table 8).
BF 3K
1.) 9-BBN
2.) Pd(OAc)2, DavePhos, KF,
R' Br
3.) RuPhos, K2CO3,toluene/H2O R'' Br
R'-Br R''-Br yield %
OMe
MeO Br
OMe
MeO Br
OMe
MeO Br
H
O
Me
O Cl
Me
Me
Br
Br OMe
N
Cl S O
Br
Br
N
N
N
H
Br OMe
MeO
MeO
MeO
Table 8: Sequential Suzuki-Miyaura cross-couplings to build molecular complexity
from potassium vinyltrifl uoroborate.
Me
H
O
OMe
OMe
Me
OMe
Me
O
N
N
S
R'
OMe
N
O
H
N
OMe
References: Molander. G. A.; Sandrock, D. L. Org. Lett. 2009, 11, 2369.
Alkenyl Potassium Trifl uoroborates from Aldrich:
BF3K
655228
H3C
BF3K
CH3 720682
Br
684937
BF3K
CH3
H3C
BF3K
CH3
720933
H3CO
H3C
683590
BF3K
CH3
BF3K
720747
R''
CH 3
82
84
74
60
80
BF3K
723916
19

20
Ni-Catalyzed Cross-Coupling of
Heteroaryltrifl uoroborates with Unactivated
Alkyl Halides
Recently the lab of Professor Gary Molander disclosed a method for the
eff ective cross-coupling of air and moisture stable heteroaryltrifl uoroborates
with unactivated alkyl halides. 3 While previous methods for
this same transformation have been developed, still today a number of
shortcomings remain. Most notable is the need for excess organoboron
coupling partner, and the limited scope of organoboron reagents that
can be used for this transformation (generally restricted to aryl boronic
acids only). To address these issues, Molander has taken advantage of
the increased stability of organotrifl uoroborates as well as the increased
reactivity of Ni catalysts. Under the optimized conditions a range of
heteroaryltrifl uoroborates can be coupled effi ciently with both alkyl
bromides and iodides (Table 9).
N
Aldrich.com
BF3K
O
or
NiBr .
2 glyme (10 mol %)
BF3K + Alkyl X
(X = Br, I)
bathophenanthroline (10 mol %)
LiHMDS (3 eq), s-BuOH
Cl
BnO
Alkyl-X
O
O
Br
Br
I
yield % Alkyl-X yield %
A, 80
B, 76
A, 76
B, 78
A, 84
B, 63
Br
I
Br
Alkyl
O
A or
Alkyl
B
A, 67
B, 68
A, 63
B, 68
A, 60
B, 71
Table 9: Cross-coupling of 2-benzofuranyl- and 4-pyridinyltrifl uoroborates with
various alkyl halides.
References: (1) Molander, G. A.; Ellis, N. Acc. Chem. Res. 2007, 40, 275.
(2) Molander, G. A.; Figueroa, R. Aldrichimica Acta 2005, 38, 49. (3) Molander, G. A.;
Argintaru, O. A.; Aron, I.; Dreher, S. D. Org. Lett. 2010, 24, 5783.
N
Heteroaryltrifl uoroborates from Aldrich:
TO ORDER: Contact your local Sigma-Aldrich offi ce (see back cover), or visit Aldrich.com/chemicalsynthesis.
N
N
H
BF3K
711144
KF3B
N
N
O
722588
BF3K
N
Boc
719420
KF3B
KF3B
N
711098
706116
S
717509
N
N
O
N
BF3K
N
BF3K
711101
BF3K
H3C CH3 S
711136
Br
F
N
717517
N
BF3K
BF3K
717487
For a complete list of organotrifl uoroborates available from Aldrich
Chemistry, visit Aldrich.com/tfb

Nano-layers of metals, semiconducting and dielectric materials are
crucial components of modern electronic devices, high-effi ciency
solar panels, memory systems, computer chips and a broad variety of
high-performance tools.
The technique of choice for depositing nano-fi lms on various surfaces
is Atomic Layer Deposition (ALD), which uses consecutive chemical
reactions on a material’s surface to create nanostructures with
predetermined thickness and chemical composition (Figure 1).
Aldrich Materials Science off ers high-quality precursors for ALD safely
packaged in steel cylinders suitable for use with a variety of
deposition systems.
We continue to expand our portfolio of ALD precursors to include
new materials. For an updated list of our deposition precursors, please
visit aldrich.com/ald
Materials Science
Precursors for Atomic Layer Deposition
High-Tech Solutions for Your Research Needs
Precursors Packaged for Deposition Systems
Atomic
No. Description Molecular Formula Form Prod. No.
Water packaged for use in
deposition systems
H 2O liquid 697125
13 Trimethylaluminum (CH 3) 3Al liquid 663301
14 (3-Aminopropyl)triethoxysilane H 2N(CH 2) 3Si(OC 2H 5) 3 liquid 706493
14 Silicon tetrachloride SiCl 4 liquid 688509
14 Tris(tert-butoxy)silanol ((CH 3) 3CO) 3SiOH solid 697281
14 Tris(tert-pentoxy)silanol (CH 3CH 2C(CH 3) 2O) 3SiOH liquid 697303
22 Tetrakis(diethylamido)titanium(IV) [(C 2H5) 2N] 4Ti liquid 725536
22 Tetrakis(dimethylamido)
titanium(IV)
[(CH 3) 2N] 4Ti liquid 669008
22 Titanium tetrachloride TiCl 4 liquid 697079
22 Titanium(IV) isopropoxide Ti[OCH(CH 3) 2] 4 liquid 687502
30 Diethylzinc (C 2H 5) 2Zn liquid 668729
31 Triethylgallium (C 3H 2) 3Ga liquid 730726
31 Trimethylgallium Ga(CH 3) 3 liquid 730734
39 Tris[N,N-bis(trimethylsilyl)amide]
yttrium
40 Bis(methyl-η5-cyclo-pentadienyl)
methoxymethylzirconium
[[(CH 3) 3Si] 2N] 3Y solid 702021
Zr(CH 3C 5H 4) 2CH 3OCH 3 liquid 725471
(a)
(b)
Figure 1. Schematic of the ALD method based on sequential, self-limiting
surface reactions.
Atomic
No. Description Molecular Formula Form Prod. No.
40 Tetrakis(dimethylamido)
zirconium(IV)
40 Tetrakis(ethylmethylamido)
zirconium(IV)
44 Bis(ethylcyclopentadienyl)
ruthenium(II)
72 Bis(methyl-η5-cyclopentadienyl)
dimethylhafnium
72 Bis(methyl-η5-cyclopentadienyl)
methoxymethylhafnium
72 Tetrakis(dimethylamido)
hafnium(IV)
72 Tetrakis(ethylmethylamido)
hafnium(IV)
73 Tris(diethylamido)(tertbutylimido)tantalum(V)
74 Bis(tert-butylimino)
bis(dimethylamino)tungsten(VI)
78 Trimethyl(methylcyclopentadienyl)platinum(IV)
For additional vapor deposition precursors prepacked in cylinders, please contact us by email at matsci@sial.com
[(CH 3) 2N] 4Zr solid 669016
C 12H 32N 4Zr liquid 725528
C 7H 9RuC 7H 9 liquid 679798
Hf[C 5H 4(CH 3)] 2(CH 3) 2 solid 725501
HfCH 3(OCH 3)[C 5H 4(CH 3)] 2 liquid 725498
[(CH 3) 2N] 4Hf lowmelting
solid
666610
[(CH 3)(C 2H 5)N] 4Hf liquid 725544
(CH 3) 3CNTa(N(C 2H 5) 2) 3 liquid 668990
((CH 3) 3CN) 2W(N(CH 3) 2) 2 liquid 668885
C 5H 4CH 3Pt(CH 3) 3
lowmelting
solid
697540

22
Indoles and Indole Isosteres
Substituted indoles have frequently been referred to as “privileged structures”
since they are capable of binding to multiple receptors with high
affi nity, and thus have applications across a wide range of therapeutic
areas. 1 However, recent publications often demonstrate the need for a
researcher to attenuate or amplify the activity of their target compound
with<strong>out</strong> altering the steric bulk of the structure; thus, isosteres of the indole
ring have proven very valuable to synthetic and medicinal chemists.
The azaindole and indazole moieties diff er only by the addition of an
extra ring nitrogen, and thus exhibit excellent potential as bioisosteres
of the indole ring system. Although more rare in nature, interest in these
structures has surged over the past decade and they comprise essential
subunits in many pharmaceutically relevant compounds. 2,3 Indazoles
have been widely reported to display signifi cant activity as antifungals,
anti-infl ammatory agents, antiarrhythmic agents, analgesics, and nitric
oxide synthase inhibitors. 2a Of the various azaindoles, 7-azaindoles are of
particular interest because of their ability to mimic purines in their roles
as hydrogen-bonding partners. Similarly, imidazopyridines have proven
eff ective as purine mimics in several recent studies. 4
When two ring nitrogens are added to the indole subunit, it results in
7-deazapurines, an important class of compounds found in a wide variety
of biological niches. Various ribonucleosides containing 7-deazapurines
demonstrate a broad spectrum of biological activity, even at
nanomolar concentrations. 5
Aldrich is pleased to off er a wide variety of these useful building blocks
for your research.
New Indoles
H 2N
Br O
N
H
O
For a complete list of indoles from Aldrich Chemistry, visit
Aldrich.com/indole
Aldrich.com
N
H
CH 3
H 3CO
H 3CO
F 3C
733040 723789 716529
N
H
724718 724378
Building Blocks
Mark Redlich
Product Manager
mark.redlich@sial.com
N
H
O
H
N
H
CH 3
New Azaindoles
For a complete list of azaindoles available from
Aldrich Chemistry, visit Aldrich.com/azaindole
New Indazoles
For a complete list of indazoles available from
Aldrich Chemistry, visit Aldrich.com/indazole
New Imidazopyridines
NH2 N
N
TO ORDER: Contact your local Sigma-Aldrich offi ce (see back cover), or visit Aldrich.com/chemicalsynthesis.
N
Br
N
H
Br
N
N
685755 721050 732141
For a complete list of imidazopyridines available from
Aldrich Chemistry, visit Aldrich.com/imidazopyridine
New Purines and Deazapurines
CH3 H3CO N
H3C Si O N
N
H
CH3 732168 707953 723770
Br
N
N
H
N
N
CH3 717525 717215
N
NH 2
N
N H
Cl
722332 717592
N
Br
NH2 H
N
N
N
For a complete list of purines and deazapurines available from Aldrich
Chemistry, visit Aldrich.com/purine
Br
N
N
N
H

Thiazoles
Thiazoles have been frequently discovered as a vital component of novel
and structurally diverse natural products that exhibit a wide variety of
biological activities. Their presence in peptides, their ability to bind to
proteins, DNA, and RNA, as well as the exceptional range of antitumor,
antiviral, and antibiotic activities of thiazole-containing compounds have
directed numerous synthetic studies and new applications. The thiazole
ring has been identifi ed as a central feature of myriad natural products,
and synthetic variants have been pursued by pharmaceutical companies
due to their signifi cant activity. 6
Additionally, thiazoles are important features of various peptides and
pseudopeptides that function as potent antineoplastic agents, 7 or have
demonstrated signifi cant cytotoxicity or antibiotic properties. 8 Thiazoles
can also serve as a protected formyl group that can be liberated in the
late stages of a complex natural product synthesis. 9
New Thiazoles
Br
N
t-Bu
S
Boc
N
H
N
S Br
723649 724122 722375
H 3C
S
N
NH2
H 3C
For a complete list of thiazoles available from
Aldrich Chemistry, visit Aldrich.com/thiazole
Other New Building Blocks
Br
O
717851 717258
OH
Cl Br
718076
729442
N
N
H
O
725293
NH 2
O
OCH 3
O CH 3
N OH
NH2
Boc N
HO
O
CH 3
723282
722316
O
722340
O
H
N Boc
O
N N
CH3
OH
CH3
S
N
N
O
N
H
H 3C
O
HO
O
722464
O
O
721530
722359
H 3C
O
O CH 3
N N
CH3
724890 722367 724149
OH
H3CO NH 2
O
Ready to scale up? For competitive quotes on larger quantities or custom synthesis, contact your local Sigma-Aldrich offi ce, or visit safcglobal.com.
CH 3
OH
O
S Cl
O
Cl NO2
S
N
NH 2
Other New Building Blocks — cont'd
H 3CO
Cl
722073
722022
725048
O 2N
720321
O
S
O
NO 2
O H
N
Boc
N
N
N
O
NH 2
NH 2
N
N
O
727598
724254
OH
Cl
NH2
O
O
H
N
Boc
Cl
H 3CO
H
N CH3
715646
O
N
N
N
720844
N
720917
714372
H 3C
O
Building Blocks
N
CH3 724165
697966
719722
730343
For a comprehensive list of Building Blocks available form Aldrich
Chemistry, visit Aldrich.com/bb
Cl
References: (1) Horton, D. A. et al. Chem. Rev. 2003, 103, 893 and references therein.
(2) Recent reviews of indazoles: a) Schmidt, A. et al. Eur. J. Org. Chem. 2008, 4073. (b)
Cerecetto, H. et al. Mini-Rev. Med. Chem. 2005, 5, 869. (c) Stadlbauer, W.; Camp, N. In
Science of Synthesis: Houben-Weyl Methods of Molecular Transformations; Bellus, D., Ley,
S. V., Noyori, R., Regitz, M., Schaumann, E., Shinkai, E., Thomas, E. J., Trost, B. M., Reider, P.
J., Eds.; Thieme: Stuttgart, Germany, 2002; Vol. 12, p 227. (3) Recent reviews of azaindoles:
(a) Popowycz, F. et al. Tetrahedron 2007, 63, 1031. (b) Popowycz, F. et al. Tetrahedron
2007, 63, 8689. (c) Song, J. J. et al. Chem. Soc. Rev. 2007, 36, 1120. (4) Huang, W.-S. et al.
J. Med. Chem. 2010, 53, 4701. (b) Buckley, G. M. et al. Bioorg. Med. Chem. Lett. 2008, 18,
3656. (c) Buckley, G. M. et al. Bioorg. Med. Chem. Lett. 2008, 18, 3291. (5) (a) Suhadolnik,
R. J. Pyrrolopyrimidine Nucleosides in Nucleoside Antibiotics; Wiley-Interscience: New York,
1970; 298 and references therein. (b) Kasai, H. et al. Biochemistry 1975, 14, 4198. (c) Nauš,
P. et al. J. Med. Chem. 2010, 53, 460. (6) Jin, Z. Nat. Prod. Rep., 2005, 22, 196. (7) Pettit, G. R.
et al. J. Am. Chem. Soc. 1987, 109, 6883. (8) (a) Davidson, B. S. Chem. Rev. 1993, 93, 1771.
(b) Fusetani, N.; Matsunaga, S. Chem. Rev. 1993, 93, 1793. (c) Wipf, P. Chem. Rev. 1995, 95,
2115. (d) Aulakh, V. S.; Ciufolini, M. A. J. Org. Chem. 2009, 74, 5750. (9) Dondoni, A.; Marra,
A. Chem. Rev. 2004, 104, 2557.
N
N
Cl
CF 3
N
722243
694770
O
O
N
Cl
H
Cl
O
O
O
CH 3
H
N CH 3
Br
N
Br N Br
F
N
N
S
NH2
O
722251
724157
O
S Cl
O
23

24
Cross-Couplings in Water
Conducting transition metal-catalyzed cross-coupling chemistry in water
instead of organic solvent has a number of potential benefi ts in terms of
cost, environmental impact, safety, and impurity profi les. Increasing focus
on the “green-ness” of chemical processes has further promoted recent
developments in this fi eld. The actual means of implementing reactions
in water, however, especially at room temperature and for water-insoluble
organic substrates, has not always been clear. One solution that has
been applied to a broad range of transition metal-catalyzed processes is
the use of small amounts of a nanomicelle-forming amphiphile in water,
which provides a lipophilic medium in which cross-coupling reactions
can take place.
Micellar Catalysis
Aldrich.com
Synthetic Reagents
Troy Ryba, Ph.D.
Product Manager
troy.ryba@sial.com
TPGS–750–M: Second Generation Amphiphile for Organometallic Chemistry in Water @ RT
Beginning in 2008, Lipshutz et al. published a series of papers demonstrating
the viability of surfactant promoted, transition metal-catalyzed
chemistry in water at room temperature. Using a variety of commercially
available surfactants, a number of palladium- and ruthenium-catalyzed
processes were found to be amenable to mild, room temperature reactions
in water. Products can be recovered from the aqueous phase using
standard extraction procedures and in high isolated yields.
TPGS–750–M: A Second Generation
Amphiphile
TO ORDER: Contact your local Sigma-Aldrich offi ce (see back cover), or visit Aldrich.com/chemicalsynthesis.
Lipshutz and co-workers have recently developed a second
generation technology to their original PTS-enabling surfactant based
on a polyoxyethanyl-α-tocopheryl succinate derivative, TPGS-750-M
(733857) (Figure 1). This designer surfactant is composed of a lipophilic
α-tocopherol moiety and a hydrophilic PEG-750-M chain, joined by an
inexpensive succinic acid linker, and spontaneously forms micelles upon
dissolution in water. The balance and composition of TPGS-750-M’s
lipophilic and hydrophilic components has been tailored to promote a
broader array of chemistry in water more effi ciently than that seen in PTS.
Furthermore, this new, more practical surfactant can be readily substituted
for older amphiphiles, usually with equal or greater
effi ciency in terms of both yield and reaction times.
Figure 1: TPGS–750–M.
3
O
O
O
O
O
O
O Me
16
*Special thanks to Professor Bruce Lipshutz, Zarko V. Boskovic and Alex R. Abela of
University of California, Santa Barbara for contributing this article on TPGS-750-M.

Olefi n Metathesis
Employing the second generation Grubbs catalyst (2 mol %) a variety of
lypophillic substrates successfully undergo ring-closing or cross-metathesis
in water at room temperature to produce high isolated yields of the
desired products (Scheme 1). Reactions were conducted in 2.5% TPGS-
750-M/water, with yields equal to or slightly better than those performed
using various other surfactant-water combinations.
OTBS
N
Ts
Scheme 1: Selected olefi n metathesis.
O
O
Grubbs-2 (2 mol %)
2.5% TPGS-750-M, water
22 o C, 12 h
Grubbs-2 (2 mol %)
2.5% TPGS-750-M, water
22 o C, 12 h
O
OTBS
91%
N
Ts
88%
Pd-Catalyzed Cross-Coupling Reactions
A variety of widely used palladium-catalyzed cross-coupling reactions can
now be run under mild room temperature conditions in water with TPGS-
750-M, using a variety of commercially available palladium complexes
and ligands. These transformations, including Suzuki-Miyaura, Sonogashira,
Buchwald-Hartwig aminations, and Heck, are amongst the most
heavily used bond forming reactions, both industrially and academically
(Scheme 2).
I
Br
Br
+
+
B(OH) 2
OMe
Br NH 2
+
OMe +
2 mol % Pd(dtbpf)Cl2
Et3N (3 equiv)
2% TPGS-750-M, water
20 °C, 24 h
3% TPGS-750-M, water
22 o PdCl2(CH3CN)2 (1 mol %)
X-Phos (2.5 mol %)
Et3N (2 eq.)
C, 21 h
[(allyl)PdCl] 2 (0.5 mol %)
Takasago's cBRIDP (2 mol %)
KOH (1.5 equiv)
2% TPGS-750-M, water
22 o C, 19 h
(PtBu3)2Pd (2 mol %)
Et3N (3 equiv)
5% TPGS-750-M, water
22 o C, 12 h
Scheme 2: Selected Pd-catalyzed cross coupling reactions.
Operationally extremely simple Suzuki-Miyaura reactions using micellar
catalysis and bis(di-tert-butylphosphino)ferrocene palladium chloride
complex provide access to highly sterically congested substrates at room
temperature using triethylamine as base.
O
88%
99%
H
N
93%
Ready to scale up? For competitive quotes on larger quantities or custom synthesis, contact your local Sigma-Aldrich offi ce, or visit safcglobal.com.
OMe
95%
OMe
Synthetic Reagents
Sonogashira reactions and Buchwald-Hartwig aminations are also
amenable to reaction in water with TPGS-750-M using the palladium
chloride/X-Phos combination in the former, and allyl palladium chloride/cBRIDP
in the latter (Figure 2).
Figure 2: Selected ligand examples.
Heck cross-couplings with aryl iodides can be successfully performed
using Pd(P(t-Bu)3)2 as the palladium source in the bulk aqueous environment
containing TPGS-750-M (5 wt. %), obviating the need for high
temperatures commonly associated with Heck reactions.
Zinc-mediated Negishi-like couplings between aryl and alkyl
halides can be performed in aqueous TPGS-750-M (Scheme 3).
Under these conditions, typically highly moisture sensitive organozinc
halides are formed in situ from an alkyl halide and zinc dust, and react
with an aryl halide under palladium catalysis. With the aid of a surfactant
and a stabilizing ligand for RZnX, such as tetramethylethylenediamine
(TMEDA), this entire process takes place in water, leading to a
variety of primary and secondary alkyl-substituted aromatics. The choice
of catalyst is crucial for the success of the reaction; Pd(Amphos)2Cl2
(Bis(di-tert-butyl (4-dimethylaminophenyl)phosphine) palladium(II)
chloride) was found to be the optimal catalyst.
Scheme 3: Selected Negishi-like cross-coupling example.
C–H Activation Reactions
Cationic palladium in combination with stoichiometric oxidant benzoquinone
and silver nitrate successfully catalyzes ortho-functionalization
of a variety of aryl acetamides in water at room temperature using this
amphiphile (Scheme 4).
Scheme 4: Selected C–H activation reaction.
H
OMe
Br
H
N
O
i-Pr
+
EtO2C
+
i-Pr
PCy2 i-Pr
Reference: Lipshutz, B. H.; Ghorai, S. Aldrichimica Acta 2008, 41, 59.
For more information on TPGS–750–M, visit
Aldrich.com/tpgs750m
Ph
Ph
Me
X-Phos cBRIDP
638064
O
Br
On-Bu
P(t-Bu)2
685151
0.5% Pd(Amphos)2Cl2
TMEDA (1 equiv)
Zn dust (3 equiv)
2% TPGS-750-M, water, rt
EtO2C
[Pd(MeCN)4](BF4)2 (10 mol %)
BQ, AgNO3
2% TPGS-750-M, water, rt
OMe
80%
CO2n-Bu
H
N
83%
O
25

26
Stable Isotope Labeled
Reagents from ISOTEC®
Stable isotope containing compounds are used in a variety of applications
including tracers in clinical studies, 1 labeled amino acids for use in
protein quantifi cation 2 and standards for metabolic research. 3 Historically,
the introduction of stable isotopes has been a diffi cult, time consuming
and costly process requiring the specialized skill of a stable isotope
chemist. The reagents below were designed to introduce stable isotopes
using standard chemical procedures.
13 C Labeled Olefi nation Reagents
The 13 C labeled olefi nation reagents 4 were developed to simplify the
labeling process by providing a set of substrates ready to be incorporated
into precedented chemical syntheses. 5 These olefi nation reagents
provide access to a fi xed 13 C label within the alkene as well as site-variable
deuterium incorporation (Scheme 1). This methodology effi ciently
provides a densely labeled compound ready for further functionalization.
O O
S
Ph 13CH
Aldrich.com
CH2
O O
Ph
S
13C
R
R'
K2CO3, CH2O
K2CO3, CD2O
H2O/DMSO
D2O/DMSO O O O
K2CO3, CH2O
S P D2O/DMSO
13CH2 OEt
Ph
OEt
1. K2CO3
H2O/DMSO
2. RI, 3. R'CHO
Scheme 1: Olefi nation reagents labeling strategies.
K 2CO3, CD2O
H 2O/DMSO
O O
Ph
S
13C
D
D D
O O
Ph
S
13C
D
CH2 O O
S
Ph 13CH
The availability of all three sulfur oxidation states allows control of the
reaction conditions including base type and strength as well as access to
a preferred sulfur removal strategy. 6 By providing access to mild reaction
conditions, fewer compatibility issues arise between reaction conditions,
olefi nation reagent and substrate.
New 13 C Labeled Olefi nation Reagents
Ph
O
S P
13CH2 OEt
OEt
Ph
O
S P
13CH2 OEt
OEt
O O O
Ph
S P
13CH2 OEt
OEt
715832 715824
715816
O
Stable Isotopes
Lisa Roth, Ph.D.
Product Manager
lisa.roth@sial.com
D
D
TO ORDER: Contact your local Sigma-Aldrich offi ce (see back cover), or visit Aldrich.com/chemicalsynthesis.
D and/or 13 C Labeled 1,3–Dithiane
Unlabeled 1,3–Dithiane is a versatile reagent able to act as an acyl anion
equivalent when submitted to Corey-Seebach reaction conditions. 7
This well known chemistry can also be carried <strong>out</strong> when 1,3–Dithiane
is labeled at the 2 position providing labeled and protected aldehydes,
ketones, α-hydroxyketones, 1,2–diketones and α-keto acid derivatives.
Deprotection can be facilitated using standard methods to give the
appropriately labeled substrates (Scheme 2). 8
Scheme 2: 1,3–Dithiane for the introduction of D and/or 13 C.
New Labeled D and/or 13 C 1,3–Dithiane
S
13 H
C
H
S
716111
S
13 D
C
D
S
716073
References: (1) Brown, L. D.; Cheung, A.; Harwood, J. E. F.; Battaglia, F. C.; J. Nut. 2009,
139, 1649. (2) Hanke, S.; Besir, H.; Oesterhelt, D.; Mann, M.; J. Proteome. Res. 2008, 7, 1118.
(3) Li, C.; Hill, R.W.; Jones, A. D.; J. Chrom. B 2010, 878, 1809. (4) Licensed from Highlands
Stable Isotopes Corp. (5) a) Capela, R.; Oliveira, R.; Gonçalves, L. M.; Domingos, A; Gut, J.;
Rosenthal, P. J.; Lopes, F.; Moreira, R.; Biorg. Med. Chem. Lett. 2009, 19, 3229. (b) Verissimo,
E.; Berry, N.; Gibbons, P.; Cristiano, M. L. S.; Rosenthal, P. J.; Gut, J.; Ward, S. A.; O’Neill, P. M.;
Biorg. Med. Chem. Lett. 2008, 18, 4210. (6) a) Beye, G. E.; Ward, D. E.; J. Am. Chem. Soc. 2010,
132, 7210. (b) Pellissier, H.; Tetrahedron 2006, 62, 5559. (7) a) Seebach, D.; Corey, E. J.; J. Org.
Chem. 1975, 40, 231. (b) Mundy, P. B.; Ellerd, M. G.; Favaloro, F. G., Jr.; Name Reactions and
Reagents in Organic Synthesis, 2nd ed.; Wiley & Sons: New York, 2005; p 186, 745. (8) Wutz, P.
G. M.; Greene, T. W.; Protection for the Carbonyl Group, Greene’s Protective Groups in Organic
Synthesis, 4th ed.; Wiley & Sons: New York, 2007; p 482.
For more information on these products avaliable from
Aldrich Chemistry, visit Aldrich.com/sinext
or contact:
S
13 R
C
S R
R = H or D
O
O OH
13C R R' O
O
13C R R'
13C R
OH 13C R
R'
O
O
Stable Isotope Technical Services
Phone: (937) 859-1808
(800) 448-9760 (US and Canada)
Fax: (937) 859-4878
E-mail: isosales@sial.com

Unlock a smarter, greener laboratory
Visit our Greener Alternatives Web portal at sigma-aldrich.com/green to learn how you can
reduce your lab’s environmental impact–with<strong>out</strong> compromising the quality of your data
or research. Come see how Sigma-Aldrich® is meeting the research community’s needs
for products and services which can signifi cantly lessen environmental impact. Put our
commitment to environmental sustainability to work in your lab.
Greener Products
Browse greener alternatives.
Programs and Services
Discover solutions designed to reduce the environmental impact of your lab.
Learning Center
Resources and links to information on environmental sustainability.
Greener
Alternatives
Check <strong>out</strong> our Web portal to find <strong>out</strong> ab<strong>out</strong>
our Greener Products and Programs
For more information on our
Greener Alternatives, Programs
and Services, visit
sigma-aldrich.com/green

28
Aldrich NMR Solvents
Challenge Us... and see why our Quality is
Unsurpassed!
High quality NMR solvents are essential for satisfying the most rigorous
demands of NMR-based research and analyses. At Aldrich, we are passionate
ab<strong>out</strong> providing this high level of quality to our customers and
work continuously to meet these requirements. We off er the widest
range of NMR solvents with the highest isotopic enrichment available
along with excellent chemical purity. We consistently review and improve
our methods for solvent purifi cation and for the reduction of water
content in our already high quality NMR solvents. All of our NMR solvents
undergo thorough quality control testing during the manufacturing and
packaging processes to verify that the product quality is preserved.
Use and Handling of NMR Solvents
Most deuterated NMR solvents readily absorb moisture. To minimize the chance of
water contamination, use carefully dried NMR tubes and handle NMR solvents in a
dry atmosphere.
How to Obtain a Nearly Moisture-free Surface
1. Dry glassware at ~150 °C for 24 hours and cool under an inert atmosphere.
2. Rinse the NMR tube with the deuterated solvent prior to preparing the sample.
This allows for a complete exchange of protons from any residual moisture on
the glass surface.
3. For less demanding applications, a nitrogen blanket over the sample preparation
setup may be adequate.
How to Avoid Sources of Impurities and Chemical Residues
1. Use clean, dry glassware and PTFE accessories.
2. Use a vortex mixer instead of shaking the tube contents. The latter action can
introduce contaminants from the NMR tube cap.
3. Residual chemical vapor from equipment can be a source of impurities;
residual acetone in pipette bulbs is a common example.
Aldrich.com
Stockroom Reagents
Todd Halkoski
Market Segment Manager
Solvents
todd.halkoski@sial.com
TO ORDER: Contact your local Sigma-Aldrich offi ce (see back cover), or visit Aldrich.com/chemicalsynthesis.
Aldrich also off ers unparalleled convenience and service. Our awardwinning
website allows for quick product searching, easy ordering, and a
wealth of valuable tools and information to aid your research eff orts. We
also off er on-site stocking programs for NMR solvents so they are available
to you for immediate use. If you have technical questions, you can feel
comfortable knowing our knowledgeable and well-trained technical
service specialists can answer your toughest questions.
Try our NMR Solvents today to see their high quality
for yourself.
For a complete listing of all NMR-related products and information,
visit Aldrich.com/nmr
How to Remove Solvent Residue
1. Protonated solvent residue can be removed by co-evaporation.
2. Use a small quantity of the desired deuterated solvent, a brief high vacuum
drying (5–10 min), and then prepare the NMR sample.
3. Solvents such as chloroform-d, benzene-d6, and toluene-d8, also remove
residual water azeotropically.
How to Avoid TMS Evaporation
1. Extended storage of TMS-containing solvents can lead to some loss of TMS.
Storing these solvents in Sure/Seal bottles virtually eliminates such a loss. *
2. Purchase TMS-containing solvents in single-use ampules.
* To dispense the product from Sure/Seal bottle or septum vials, use standard
syringe needle techniques. For details and recommended procedures, please refer
to Aldrich Technical Bulletin AL-134 or visit our Web site at Aldrich.com.

Specialty NMR Solvents
Aldrich off ers a wide range of high purity deuterated solvents for the
NMR community. In addition, we also off er various specialty solvents for
more demanding applications. Whether you need the highest enriched
deuterium oxide available, or solvents with a reduced HOD peak, we
have what you need.
“Special HOH” Solvents
When customers requested NMR solvents with a suppressed HOD peak
we listened, and developed NMR solvents called “Special HOH”. These
solvents have an HOD peak which is less than 1% of the HOH peak, to
minimize potential exchange with an analyte. “Special HOH” solvents also
meet our standard water specifi cation for NMR solvents.
1 H-NMR Spectrum of DMSO-d6 “Special HOH”
Acetonitrile-d3, 99.8 atom % D, "Special HOH"
699543-10G glass bottle 10 g
699543-25G glass bottle 25 g
699543-50G glass bottle 50 g
Dimethyl sulfoxide-d6, 99.9 atom % D, "Special HOH"
612324-25G glass bottle 25 g
612324-50G glass bottle 50 g
612324-100G glass bottle 100 g
716731-10x0.75ML ampule 10 x 0.75 mL
716731-10ML serum vial 10 mL
716731-50ML serum vial 50 mL
Data acquired on a Varian 400 MHz instrument.
11.5 11.0 10.5 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 –0.5
ppm
HOH
3.3
ppm
HOD
DMSO-d6
residual peak
2.5 2.4
ppm
Anhydrous NMR Solvents
Ready to scale up? For competitive quotes on larger quantities or custom synthesis, contact your local Sigma-Aldrich offi ce, or visit safcglobal.com.
Stockroom Reagents
When water content is of paramount concern, try our anhydrous
solvents that contain reduced levels of water.
Acetonitrile-d 3, 99.8 atom % D, Anhydrous (water < 10 ppm)
569550-10X1ML ampule 10 x 1 mL
Benzene-d 6, 99.6 atom % D, Anhydrous (water < 10 ppm)
570680-50G glass bottle 50 g
Chloroform-d, 99.8 atom % D, Anhydrous (water < 10 ppm)
570699-50G glass bottle 50 g
Dimethyl sulfoxide-d 6, 99.9 atom % D, Anhydrous (water < 50 ppm)
570672-50G glass bottle 50 g
569585-5X1ML ampule 5 x 1 mL
569585-10X1ML ampule 10 x 1 mL
Methanol-d 4, 99.8 atom % D, Anhydrous (water < 50 ppm)
570729-50G glass bottle 50 g
569534-5X1ML ampule 5 x 1 mL
569534-10X1ML ampule 10 x 1 mL
Toluene-d 8, 99.6 atom % D, Anhydrous (water < 10 ppm)
570710-50G glass bottle 50 g
“Extra” Enriched D 2O
With an enrichment of 99.994 atom % D, this is the highest enriched
deuterium oxide available.
Deuterium oxide, Extra, 99.994 atom % D
613398-10G serum bottle 10 g
613398-50G serum bottle 50 g
For additional information visit us at Aldrich.com/nmr
or contact:
Stable Isotope Technical Services
Phone: (937) 859-1808
(800) 448-9760 (US and Canada)
Fax: (937) 859-4878
E-mail: isosales@sial.com
29

30
Inert Atmosphere Glove-Boxes
Sigma-Aldrich® off ers a wide range of Plas-Labs glove boxes for most
oxygen and moisture-sensitive applications .
The boxes are manufactured with a clear, one piece acrylic top and a
molded base section. Gaskets are double layered for a reliable, airtight
seal. The 8 in. ports with ambidextrous Hypalon® glove with SS O-rings
give easy access to all parts of the glove box. The transparent transfer
chamber has an adjustable vacuum gauge.
Nitrogen Dry Box
The Plas-Labs nitrogen Dry Box is a completely enclosed chamber
designed for working in nitrogen, argon and plasma-type atmospheres
and ideal for handling oxygen sensitive materials.
• Two vacuum/pressure pumps to speed purging.
• Fluorescent light system with illuminated controls
•
Single-station model - Internal H×W×D - 26 in.×41 in.×26 in.
Drying train removal with<strong>out</strong> disturbing internal atmosphere
Z562920 AC input 120 V
Z563285 AC input 240 V, Euro plug
Z562939 AC input 240 V, UK plug
Multi-station model - Internal H×W×D - 28 in.×60 in.×38 in.
Z562947 AC input 120 V
Z563293 AC input 240 V, Euro plug
Z562955 AC input 240 V, UK plug
Aldrich.com
Labware Notes
Paula Freemantle
Product Manager
labware@sial.com
Basic Glove Box
The Plas-Labs Basic glove
boxes are engineered to
fi t general laboratory isolation
applications. They
can be easily modifi ed
for specifi c uses and are
very handy for isolating
sensitive research studies
from a hostile exterior
environment.
TO ORDER: Contact your local Sigma-Aldrich offi ce (see back cover), or visit Aldrich.com/chemicalsynthesis.
These economical units are compact, portable, lightweight and
self-contained.
• Three tier suspended clear acrylic shelves
White leveling tray for transferring the transfer chamber.
• Four purge valves
• Multiple electrical <strong>out</strong>let strip
•
Single-station model - Internal H×W×D - 26 in.×41 in.×28 in.
Z563013 AC input 120 V
Z563307 AC input 240 V, Euro plug
Z563021 AC input 240 V, UK plug
Multi-station model - Internal H×W×D - 28 in. × 60 in. × 38 in.
Z563048 AC input 120 V
Z563315 AC input 240 V, Euro plug
Z563056 AC input 240 V, UK plug

Eliminating Static
from Glove Boxes
Static in plastic glove boxes
and bags can be a problem in
many applications. The antistatic
ionizer from Plas-Labs
is an eff ective way to eliminate
all static charges within 36
inches (90 cm) of unit.
• Ion balance adjustment
Compact footprint
• Virtually maintenance free
•
Z563064 120 V
Z563072 240 V, UK plug
Z563323 240 V, Euro plug
For more information ab<strong>out</strong> these products or to place an order visit
Aldrich.com
The AtmosBag
An Economical Solution for
Controlled
Atmosphere Applications.
AtmosBag is a fl exible, infl atable
polyethylene chamber with built-in
gloves that lets you work in a totally
isolated and controlled environment.
Our customers use it for a
wide variety of applications from
providing an emergency isolation environment for inspecting unknown
materials to the transfer of air- and moisture-sensitive materials when
sampling or weighing. AtmosBag even permits weighing operations
inside a fume hood for added safety. Air currents that would interfere with
weighing are eliminated inside of AtmosBag.
Z106089 Two-hand, non-sterile, size L, Tape-seal
Z108405 Four-hand, non-sterile, Tape-seal
Z112828 Two-hand, non-sterile, size M, Tape-seal
Z112836 Two-hand, non-sterile, size S, Tape-seal
Z118354 Two-hand, sterile, size L, Tape-seal
Z118362 Two-hand, sterile, size M, Tape-seal
Z118370 Two-hand, sterile, size S, Tape-seal
Z530204 Two-hand, size S, Zipper-lock
Z530212 Two-hand, size M, Zipper-lock
Z530220 Two-hand, size L, Zipper-lock
Z555525 Four-hand, Zipper-lock
Full details can be found in our Technical Bulletin AL 211 which can be
downloaded from Aldrich.com
NMR Tube Holders
Unbreakable, NMR tube carrier
provides protection for
the tube and lab personnel
when transporting samples.
Ready to scale up? For competitive quotes on larger quantities or custom synthesis, contact your local Sigma-Aldrich offi ce, or visit safcglobal.com.
Labware Notes
The clear, shatter-resistant
polycarbonate case allows
for visual sample identifi cation
and inspection prior
to opening. Natural rubber
plugs on both ends of the
case provide impact absorption
if accidentally dropped. NMR tubes are held securely in place inside
the PC case by the bottom loading rubber plug. Carrier holds one 5 mm
diameter tube, 7 or 8 in. L.
Z567078-5EA
News and Innovation
Chemrus® Disposable Filter Funnels
Convenient and inexpensive, these disposable fi lter funnels have
polypropylene bodies with tapered stems that fi t 7/10 joints with<strong>out</strong>
seals. The funnels are available in two styles, Buchner and Hirsch,
and a choice of 10 micron polyethylene frit, Celite, or perforated
plate for use with fi lter paper.
Maximum use temperature is 110 °C. Order vacuum adapters, fi lter
paper, vials and 20–400 to 24–400 vial connector separately not
given below.
Cat. No. Style Filter type Capacity (mL)
Z679798 Buchner PE frit, 10 micron 18
Z679801 Buchner PE frit, 10 micron 40
Z679828 Buchner PE frit, 10 micron 110
Z679860 Buchner Celite® (0.5g) 18
Z679860 Buchner Celite® (1.5g) 40
Z679836 Hirsch Perforated Plate 20
Z679844 Hirsch Perforated Plate 60
31

Sigma-Aldrich
3050 Spruce Street
St. Louis, MO 63103 USA
Sigma-Aldrich ® Worldwide Offices
Argentina
Free Tel: 0810 888 7446
Tel: (+54) 11 4556 1472
Fax: (+54) 11 4552 1698
Australia
Free Tel: 1800 800 097
Free Fax: 1800 800 096
Tel: (+61) 2 9841 0555
Fax: (+61) 2 9841 0500
Austria
Tel: (+43) 1 605 81 10
Fax: (+43) 1 605 81 20
Belgium
Free Tel: 0800 14747
Free Fax: 0800 14745
Tel: (+32) 3 899 13 01
Fax: (+32) 3 899 13 11
Brazil
Free Tel: 0800 701 7425
Tel: (+55) 11 3732 3100
Fax: (+55) 11 5522 9895
Canada
Free Tel: 1800 565 1400
Free Fax: 1800 265 3858
Tel: (+1) 905 829 9500
Fax: (+1) 905 829 9292
Chile
Tel: (+56) 2 495 7395
Fax: (+56) 2 495 7396
China
Free Tel: 800 819 3336
Tel: (+86) 21 6141 5566
Fax: (+86) 21 6141 5567
Czech Republic
Tel: (+420) 246 003 200
Fax: (+420) 246 003 291
Enabling Science to
Improve the Quality of Life
Denmark
Tel: (+45) 43 56 59 00
Fax: (+45) 43 56 59 05
Finland
Tel: (+358) 9 350 9250
Fax: (+358) 9 350 92555
France
Free Tel: 0800 211 408
Free Fax: 0800 031 052
Tel: (+33) 474 82 28 88
Fax: (+33) 474 95 68 08
Germany
Free Tel: 0800 51 55 000
Free Fax: 0800 64 90 000
Tel: (+49) 89 6513 0
Fax: (+49) 89 6513 1160
Hungary
Ingyenes telefonszám: 06 80 355 355
Ingyenes fax szám: 06 80 344 344
Tel: (+36) 1 235 9063
Fax: (+36) 1 269 6470
India
Telephone
Bangalore: (+91) 80 6621 9400
New Delhi: (+91) 11 4358 8000
Mumbai: (+91) 22 4087 2364
Hyderabad: (+91) 40 4015 5488
Kolkata: (+91) 33 4013 8000
Fax
Bangalore: (+91) 80 6621 9550
New Delhi: (+91) 11 4358 8001
Mumbai: (+91) 22 2579 7589
Hyderabad: (+91) 40 4015 5466
Kolkata: (+91) 33 4013 8016
Ireland
Free Tel: 1800 200 888
Free Fax: 1800 600 222
Tel: (+353) 402 20370
Fax: (+ 353) 402 20375
Israel
Free Tel: 1 800 70 2222
Tel: (+972) 8 948 4100
Fax: (+972) 8 948 4200
Italy
Free Tel: 800 827 018
Tel: (+39) 02 3341 7310
Fax: (+39) 02 3801 0737
Japan
Tel: (+81) 3 5796 7300
Fax: (+81) 3 5796 7315
Korea
Free Tel: (+82) 80 023 7111
Free Fax: (+82) 80 023 8111
Tel: (+82) 31 329 9000
Fax: (+82) 31 329 9090
Malaysia
Tel: (+60) 3 5635 3321
Fax: (+60) 3 5635 4116
Mexico
Free Tel: 01 800 007 5300
Free Fax: 01 800 712 9920
Tel: (+52) 722 276 1600
Fax: (+52) 722 276 1601
The Netherlands
Free Tel: 0800 022 9088
Free Fax: 0800 022 9089
Tel: (+31) 78 620 5411
Fax: (+31) 78 620 5421
New Zealand
Free Tel: 0800 936 666
Free Fax: 0800 937 777
Tel: (+61) 2 9841 0555
Fax: (+61) 2 9841 0500
Norway
Tel: (+47) 23 17 60 00
Fax: (+47) 23 17 60 10
Poland
Tel: (+48) 61 829 01 00
Fax: (+48) 61 829 01 20
Portugal
Free Tel: 800 202 180
Free Fax: 800 202 178
Tel: (+351) 21 924 2555
Fax: (+351) 21 924 2610
Russia
Tel: (+7) 495 621 5828
Fax: (+7) 495 621 6037
Singapore
Tel: (+65) 6779 1200
Fax: (+65) 6779 1822
Slovakia
Tel: (+421) 255 571 562
Fax: (+421) 255 571 564
S<strong>out</strong>h Africa
Free Tel: 0800 1100 75
Free Fax: 0800 1100 79
Tel: (+27) 11 979 1188
Fax: (+27) 11 979 1119
Spain
Free Tel: 900 101 376
Free Fax: 900 102 028
Tel: (+34) 91 661 99 77
Fax: (+34) 91 661 96 42
Order/Customer Service (800) 325-3010 Fax (800) 325-5052
Technical Service (800) 325-5832 sigma-aldrich.com/techservice
Development/Custom Manufacturing Inquiries (800) 244-1173
Safety-related Information sigma-aldrich.com/safetycenter
©2011 Sigma-Aldrich Co. All rights reserved. SIGMA, SAFC, SIGMA-ALDRICH, ALDRICH, and SUPELCO are registered trademarks of Sigma-Aldrich Biotechnology L.P. FLUKA is a registered
trademark of Fluka GmbH. Isotec, Sure/Seal and AtmosBag are trademarks of Sigma-Aldrich Biotechnology L.P. Journal Citation Reports is a registered trademark of Thomson Reuters. Hypalon is
a registered trademark of E.I. du Pont de Nemours & Co., Inc. Celite is a registered trademark of Celite Corp. ChiPros is a registered trademark of BASF SE. ChemMatrix is a registered trademark of
Matrix Innovations Inc. Chemrus is a registered trademark of Xiaogao Liu and Jianjian Cai. Q-Tube and Q-Block are trademarks of Q Labtech LLC. Plas-Labs is a trademark of Plas Labs, Inc.
Sigma brand products are sold through Sigma-Aldrich, Inc. Sigma-Aldrich, Inc. warrants that its products conform to the information contained in this and other Sigma-Aldrich publications.
Purchaser must determine the suitability of the product(s) for their particular use. Additional terms and conditions may apply. Please see reverse side of the invoice or packing slip.
Sweden
Tel: (+46) 8 742 4200
Fax: (+46) 8 742 4243
Switzerland
Free Tel: 0800 80 00 80
Free Fax: 0800 80 00 81
Tel: (+41) 81 755 2828
Fax: (+41) 81 755 2815
United Kingdom
Free Tel: 0800 717 181
Free Fax: 0800 378 785
Tel: (+44) 1747 833 000
Fax: (+44) 1747 833 313
United States
Toll-Free: 800 325 3010
Toll-Free Fax: 800 325 5052
Tel: (+1) 314 771 5765
Fax: (+1) 314 771 5757
Vietnam
Tel: (+84) 3516 2810
Fax: (+84) 6258 4238
Internet
sigma-aldrich.com
World Headquarters
3050 Spruce St.
St. Louis, MO 63103
(314) 771-5765
sigma-aldrich.com
NJO
75210-510265
1011