Synthesis of pure enantiomers of cis- and trans-3-(trifluoromethyl) pyroglutamic esters

Abstract

The addition of the racemic Schiff base ethyl N-(diphenylmethylene)glycinate ( 2), from glycine ester, to ethyl-4,4,4-trifluorocrotonate gives, according to the experimental conditions, one or two Michael adducts. Acidic hydrolysis gives the cis/trans-3-(trifluoromethyl) pyroglutamates. The enantiomerically pure Schiff base, prepared from chiral 2-hydroxy-3-pinanone and t-butyl glycinate, reacts with trans-ethyl-4,4,4-trifluorocrotonate to produce four diastereoisomers which may be separated and hydrolysed to give enantiomerically pure cis- and trans-3-(trifluoromethyl)pyroglutamate.