Highly diastereoselective lithiation and substitution of an (S)-prolinyl thiocarbamate via sterically homogeneous lithio(thiocarbamate): Synthesis of enantiomerically pure prolinethiols

Abstract

Highly diastereoselective lithiation-substitution reactions of an (S)-proline derived S-alkyl thiocarbamate was accomplished. The configuration of the predominant alkyllithium species and the stereochemical course of the electrophilic substitution reactions are deduced by a combination of X-ray crystal structure analysis, NMR spectroscopic studies, deuteration/dedeuteration experiments, and quantum chemical calculations. The lithium intermediate (S,S)-9 was found to be kinetically and thermodynamically favoured, whereas (S,R)-9 rapidly epimerizes. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA.