Stereochemically defined C-substituted glutamic acids and their derivatives. 1. An efficient asymmetric synthesis of (2S,3S)-3-methyl- and -3-trifluoromethylpyroglutamic acids

An efficient asymmetric synthesis of biologically important (2S,3S)-3-methy l- and (2S,3S)-3-trifluoromethylpyroglutamic acid has been developed. We me thod consists of diastereoselective Michael addition reaction between ethyl crotonate or ethyl 4,4,4-trifluorocrotonate and a Ni(II) complex of the ch iral non-racemic Schiff base of glycine with (S)-o-[N-(N-benzylprolyl)amino ]benzophenone (BPB) followed by decomposition of the addition products by a q. HCl and treatment of the resultant glutamic acid derivatives with NH4OH to afford the target pyroglutamic acids along with recovery of the chiral a uxiliary BPB. The stereochemical outcome of the addition reactions was foun d to be subjected to kinetic control. A mechanistic rationale for the obser ved stereochemical preferences is discussed. (C) 1999 Elsevier Science Ltd. All rights reserved.