Stereoselective Synthesis of Boc-Protected<i>cis</i>and<i>trans</i>-4-Trifluoromethylprolines by Asymmetric Hydrogenation Reactions

Abstract

Stereocontrolled synthesis of cis and trans-substituted prolines by a divergent approach, leads to the preparation of cis-(4S)- and trans-(4R)-trifluoromethyl-L-proline from hydroxyproline. The key pyrroline intermediates were subjected to hydrogenation (see scheme; A=sterically directed hydrogenation, B=hydroxy-directed hydrogenation; Boc=tert-butoxycarbonyl, TBS=tert-butyldimethylsilyl), to afford products in high diastereomeric excess.