Asymmetric biomimetic transamination of α-keto phosphonates enabled by chiral pyridoxamines and synergistic solvent

Chiral α-aminophosphonate derivatives are recognized as valuable compounds in both medicine and organic chemistry. Biomimetic transamination of α-keto phosphonates represents one of the most efficient strategies for accessing these pharmaceutically relevant molecules. However, establishing a general amine-transfer platform that directly delivers N-unprotected chiral α-aminophosphonates remains challenging. We report an asymmetric transamination of α-keto phosphonates catalyzed by a chiral pyridoxamine catalyst, which efficiently affords a diverse range of chiral α-aminophosphonates with up to 86% yield and 98% ee. This methodology provides a straightforward approach to biologically active α-aminophosphonic acid derivatives. Mechanistic studies, supported by DFT calculations, reveal that trifluoroethanol plays a critical role in determining the enantioselectivity and stabilizing the transition states of the rate-limiting step. Chiral α-aminophosphonate derivatives are recognized as valuable compounds in both medicine and organic chemistry, but establishing a general amine-transfer platform that directly delivers N-unprotected chiral α-aminophosphonates remains challenging. Here, the authors report an asymmetric transamination of α-keto phosphonates catalyzed by a chiral pyridoxamine catalyst, which efficiently affords a diverse range of chiral α-aminophosphonates.