Photoredox-Catalyzed Allylic Defluorinative Alkoxycarbonylation of Trifluoromethyl Alkenes through Intermolecular Alkoxycarbonyl Radical Addition

The gem-difluoroalkene moiety is an ideal carbonyl bioisostere in medicinal chemistry, but efficient synthesis of beta-gem-difluoroalkene esters remains challenging so far. Herein, we disclose a photoredox-catalyzed allylic defluorinative alkoxycarbonylation of trifluoromethyl alkenes enabled by intermolecular alkoxycarbonyl radical addition. A wide variety of alcohol oxalate derivatives were amenable, affording various beta-gem-difluoroalkene esters with excellent functional group tolerance. Notably, the potential synthetic value of this method is highlighted by successful late-stage modification for bioactive molecules.

Automated summary

A novel method for efficient synthesis of beta-gem-difluoroalkene esters was disclosed in this study. The method involves photoredox-catalyzed allylic defluorinative alkoxycarbonylation of trifluoromethyl alkenes through intermolecular alkoxycarbonyl radical addition, and demonstrates wide reaction adaptability and excellent functional group tolerance. Furthermore, successful late-stage modification of bioactive molecules highlights the synthetic value of this method in medicinal research.