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.