Page 65 - Catalysts for Fine Chemical Synthesis Vol 1 - Robert & Poignant

Catalysts for Fine Chemical Synthesis: Hydrolysis, Oxidation and Reduction. Volume 1
Edited by Stan M Roberts and Geraldine Poignant
Copyright  2002 John Wiley & Sons, Ltd.
ISBN: 0-471-98123-0

2 General Information

Before conducting an asymmetric synthesis, one needs to ensure that one is able
to separate both enantiomers of the desired compound. The racemate (RS, 50%
of each enantiomer) needs to be synthesized in order to study the different
possibilities of differentiating each enantiomer.
Two enantiomers can be differentiated by their retention time (R f ) during
chromatography on a chiral support, for example, using High Pressure Liquid
Chromatography (HPLC) or Gas Chromatography (GC) over a chiral column.
They can also be separated by derivatization with an homochiral auxiliary,
affording the corresponding diastereomers. As the two diastereomers can have
1
different chemical shifts in NMR spectra, their analysis by H-, 13 C- or 19 F-
NMR spectroscopy represents a useful method for the determination of the
enantiomeric excess. (R)-(‡)-a-methoxy-a-(trifluoromethyl)phenylacetic acid
or its (S)-(ÿ)-enantiomer (MTPA, Mosher acid) is used in the following chap-
ters to determine the enantiomeric excess (e.g. of allylic alcohols). Chemical
shift reagents such as [europium(III)-tris[3-(heptafluoropropylhydromethy-
lene)-d-camphorate]] (Eu(hfc) 3 ) can also be used to assess the ratio in a mixture
of enantiomers. Each method needs to be performed on the racemic compound
in order to find the conditions to separate the two enantiomers.
For experiments conducted in Liverpool GC was performed on a Shimadzu
GC-14A gas chromatograph using a SE30 capillary column with the injector
and detector set to 250 8C; chiral GC was performed with chiral capillary
columns (Lipodex 1 E and C as indicated) with the injector and detector set
to 250 8C. HPLC was performed on a Gilson chromatograph equipped with
chiral columns Daicel Chiralpack 1 AD and OD (wavelength 254 nm).
NMR spectra were recorded on Bruker AC200 spectrometers; unless indi-
cated otherwise deuteriated chloroform was used as solvent and tetramethylsi-
lane as internal reference. Chemical shifts (d) are given in ppm. The following
abbreviations were used to define the multiplicities; s, singlet; d, doublet; t,
triplet; q, quartet; m, multiplet; br, broad; coupling constants (J) are measured
in Hertz (Hz). IR spectra were recorded on a Nicolet Magna-550 FTIR