Photoredox Phosphonomethylation/Cyclization of Alkenes Enabled by an EDA Complex

Abstract

The phosphonomethyl unit is an important pharmacophore. The ICH2PO(R 1 R 2 ) is a commercially available phosphonomethylation reagent. However, the synthesis of phosphonomethyl substituted cyclic molecules by using ICH2PO(R 1 R 2 ) mainly relies on noble metal catalyzed methods. Herein, the photoredox phosphonomethylation/cyclization of alkenes has been developed. Mechanistically, the electron donor-acceptor (EDA) complex formed in situ between ICH2PO(R 1 R 2 ) and 1,4-diazabicyclo[2.2.2]octane (DABCO) is the key to this reaction. This method does not require photocatalysts, oxidants, or reducing agents, and operates under mild conditions, making it suitable for the late-stage modification of drug molecules.