Practical Synthesis of Boc-Protected <i>cis</i>-4-Trifluoromethyl and <i>cis</i>-4-Difluoromethyl-<scp>l</scp>- prolines

Abstract

A short, efficient, and diastereomerically pure synthesis of N-Boc-cis-4-trifluoromethyl-L-proline (7) and N-Boc-cis-4-difluoromethyl-L-proline (9) from N-Boc-4-oxo-L-proline (4) is described. The reaction of 4 with Me(3)SiCF(3) and the conversion of the carbonyl group of 4 into the difluoromethylene group are the key steps for the synthesis of 7 and 9, respectively.