Abstract:
Enhanced effectiveness of pharmaceuticals and agrochemicals is the most sought-after
attribute in the field of enantioselective synthesis of chiral molecules where single enantiomer
(R or S) is required, for which asymmetric catalysis is an attractive way. The synthesis of
enantiomerically pure compounds in traditional way is difficult, costly and time-consuming
process involving the running of long columns which create a lot of waste that causes water
pollution. The selectivity of products are equally depends upon the catalyst and conditions of
the reaction which makes the task harder for selecting and finding new catalytic system.
Present work deals with the development of six families of chiral ligands libraries for rapid
recognition of the best system, by using combinatorial chemistry, during hydrogenation of
ketones, a starting material and as intermediate in a number of pharmaceutical processes. The
ligands were both generated in situ and in pure form for the comparison of results and were
obtained by simple condensation, providing one of the starting materials being chiral. Six
families namely; bisimine, diamine, aminal, imine, iminophosphine and oxazoline were
synthesized and tested in presence of Zn(II), Rh(I) and Rh(III) by using
polymethylhydrosiloxane (PMHS), diphenylsilane and formic acid/sodium formate as
hydrogen donor species for transfer hydrogenation during synthesis of selective chiral
alcohols from achiral acetophenone. Overall 1566 catalytic systems were developed and
subsequently tested and the yield and enantiomeric excesses were found by using 1H NMR
and chiral High Performance Liquid Chromatography (HPLC) respectively with more than
90% ee and 99% conversion as the best result for imine and aminal ligands. It has been
proven that ligands synthesized in-situ gave comparable and almost same results to purified
version with best reproducibility.
