Asymmetric Strecker-Type Reaction of alpha-Aryl Ketones. Synthesis of (S)-alphaM4CPG, (S)-MPPG, (S)-AIDA, and (S)-APICA, the Antagonists of Metabotropic Glutamate Receptors.

Dawei Ma, Hongqi Tian, Guixiang Zou

Index: J. Org. Chem. 64(1) , 120-125, (1999)

Full Text: HTML

Abstract

Heating a mixture of alpha-aryl ketone with (R)-phenylglycinol produces a mixture of imine and 1,3-dioxazolidine. Treatment of this mixture with trimethylsilyl cyanide followed by transformation of nitrile to ester gives Strecker-type reaction products. The diastereoselectivity of the generated alpha-amino esters is from 2/1 to 7/1, and the (R,S)isomer is found as the major product. The (R,S) and (R,R)isomers can be separated by conversion to their N-Cbz or cyclization derivatives. Using this methodology, four antagonists of metabotropic glutamate receptors, (S)-alphaM4CPG, (S)-MPPG, (S)-AIDA, and (S)-APICA, are synthesized.