Stereocontrolled Synthesis of Alpha-aminophosphinic Acid Derivatives

Abstract

A new and efficient method was developed for a stereocontrolled synthesis of a-aminophosphinic acid derivatives, which were useful intermediates for biologically active aminophosphinyl peptides, starting with a-amino-H-phosphinates possessing defined relative configuration. The method was based upon stereospecific Michael addition of a-amino-H-phosphinates to acrylates, affording adducts with retention of phosphorous chirality, followed by diastereoselective alkylation of their corresponding lithium enolates. The diastereoselectivty depended upon steric factor of protective group on the nitrogen atom. Excellent selectivity (>17:1) was observed using a trisyl group as the nitrogen protective group. The feature of this method is a high diastereoselectivity partially controlled by the asymmetric center at the phosphorus atom.