Stereochemically Defined C-Substituted glutamic Acids and their Derivatives. 1. An Efficient Asymmetric Synthesis of (2S, 3S)-3-Methyl- and -3-Trifluoromethylpyroglutamic Acids

摘要

An efficient asymmetric synthesis of biologically important (2S, 3S)-3-methyl- and (2S, 3S)-3-trifluoromethylpyroglutamic acid has been developed. The method consists of diastereoselective Michael addition reaction between ethyl crotonate or ethyl 4, 4, 4-trifluorocrotonate and a Ni(II) complex of the chiral non-racemic Schiff base of glycine with (S)-o-[N-(N-benzylprolyl)amino]benzophenone (BPB) followed by decomposition of the addition products by aq. HCl and treatment of the resultant glutamic acid derivatives with NH_4OH to afford the target pyroglutamic acids along with recovery of the chiral auxiliary BPB. The stereochemical outcome of the addition reactions was found to be subjected to kinetic control. A mechanistic rationale for the observed stereochemical preferences is discussed.