Asymmetric synthesis of β-hydroxy-α-amino phosphonic acid derivatives via organocatalytic direct aldol reaction of α-isothiocyanato phosphonates with aldehydes

Abstract

α-Isothiocyanato phosphonates are first used as nucleophiles to react with aldehydes for the asymmetric synthesis of β-hydroxy-α-amino phosphonic acid derivatives. The process is catalyzed by a quinine-derived thiourea via cascade aldol/cyclization reaction, affording a wide range of protected β-hydroxy-α-amino phosphonates containing adjacent quaternary-tertiary stereocenters in up to 93% yield, up to 81% ee, and >99:1 dr. This work represents the first example of α-isothiocyanato phosphonates serving as nucleophiles that are used in the catalytic asymmetric synthesis.