Facile Conversion of α-Amino Acids into α-Amino Phosphonates by Decarboxylative Phosphorylation using Visible-Light Photocatalysis

Abstract

Amino phosphonates exhibit potent inhibitory activity for a wide range of biological processes due to their specific structural and electronic properties, making them important in a plethora of applications, including as enzyme inhibitors, herbicides, antiviral, antibacterial, and antifungal agents. While the traditional synthesis of α-amino phosphonates has relied on the multicomponent Kabachnik-Fields reaction, we herein describe a novel and facile conversion of activated derivatives of α-amino acids directly to their respective α-amino phosphonate counterparts via a decarboxylative radical-polar crossover process enabled by the use of visible-light organophotocatalysis. The novel method shows broad applicability across a range of natural and synthetic amino acids, operates under mild conditions, and has been demonstrated to successfully achieve the late-stage functionalization of drug molecules.

Keywords: Amino Acids; Phosphorylation; Photoredox Catalysis; Radical-Polar Crossover; Reaction Mechanisms.