Phosphonate NOPP-Enabled Enantioselective Radical Cyanophosphonation of Alkenes

Abstract

The catalytic cyanophosphonation of alkene feedstocks is a powerful method for introducing phosphonates and cyano into organic molecules. Herein, we report the development of a phosphonate reagent, O-phthalimidebenzyl phosphonate (NOPP), and their application in the photocatalytic, highly enantioselective cyanophosphonation of alkenes through a dual photoredox and copper-catalyzed three-component cross-coupling with TMSCN to the synthesis of structurally diverse racemic and chiral β-cyano phosphonates. The utilization of NOPP, characterized by the weaker reduction potential, is crucial for suppressing side reactions and promoting the effective cyanophosphonation. This operationally simple and scalable modular protocol efficiently facilitates the cyanophosphonation of extensive substrates, including styrenes, acrylates, acrylamides, and complex medicinally relevant alkenes, all while demonstrating impressive functional group tolerance, representing the phosphonate radical mediated asymmetric difunctionalization of alkenes and providing an appealing approach for the synthesis of β-chiral alkyl phosphonates.