Synthesis of α,β-Functionalized Phosphinic Acid Derivatives

Abstract

The diastereoselective synthesis of α,β-functionalized phosphinates was examined through hydrophosphinylation of α-oxy aldehydes and α-amino aldehydes. When reactions of phosphinic nucleophile with α-oxy aldehydes or α-amino aldehydes were carried out in the presence of catalytic amount of PhOLi or AlLibis(binaphthoxide) (ALB), anti-β-substituted α-hydroxyphosphinates were formed with high diastereoselectivity. The product was transformed into β-amino-α-hydroxy(methoxycarbonylmethyl)phosphinic acid, which would be applicable as a building block for peptidic transition state analogue inhibitors of protease. The hydrophosphinylation product was also converted into N-Boc-aziridine phosphinate.