Enantioselective synthesis of functionalized αα-aminophosphonic acid derivatives

Abstract

An umpolung process for the enantioselective functionalization of α-aminophosphonates with nucleophiles has been developed. This consists in a formal oxidation of tetrasubstituted α-aminophosphonates to α-iminophosphonates followed by an organocatalyzed nucleophilic addition reaction to the imine bond. The optimal enantioselectivity has been reached by studying the effect of the size of the substituent at the phosphonate. Applications for the preparation of tetrasubstituted α-amino α-cyanophosphonates and α-amino β-nitrophosphonates enantiomerically enriched are reported.

Graphical Abstract

Keywords:

• α-Aminophosphonates
• organocatalysis
• nucleophilic addition
• ketimines
• cyanation
• aza-Henry

Acknowledgments

Financial support by Ministerio de Economía, Industria y Competitividad (MINECO, CTQ-2015-67871R) and Gobierno Vasco (GV, IT 992-16) is gratefully acknowledged.