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

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 alpha-amino phosphonates has relied on the multicomponent Kabachnik-Fields reaction, we herein describe a novel and facile conversion of activated derivatives of alpha-amino acids directly to their respective alpha-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.

Automated summary

Amino phosphonates are highly effective inhibitors in various biological processes due to their unique structural and electronic properties. They find numerous applications as enzyme inhibitors, herbicides, antiviral, antibacterial, and antifungal agents. This study presents a novel and convenient method utilizing visible-light organophotocatalysis to convert activated derivatives of alpha-amino acids directly into their respective alpha-amino phosphonate counterparts, demonstrating broad applicability, mild reaction conditions, and successful late-stage functionalization of drug molecules.