Visible light-induced gem-difluoroallylation of [1.1.1]propellane to access gem-difluoroallylic bicyclo[1.1.1]pentanes

Abstract

Bicyclo[1.1.1]pentanes (BCPs) represent an important compound class often used as linear spacer units to enhance pharmacokinetic profiles in modern drug design. Herein, we report a cascade multicomponent reaction to synthesize gem-difluoroallylic bicyclo[1.1.1]pentanes via visible light-induced defluorinative gem-difluoroallylation of [1.1.1]propellane. In this methodology, sulfonyl radicals generated from sodium arylsulfinates added to [1.1.1]propellane to form BCP radicals were then trapped by α-trifluoromethyl alkenes to form gem-difluoroallylic bicyclo[1.1.1]pentanes. Importantly, our methodology is characterized by mild reaction conditions, wide reactant scope, and suitable functional group tolerance.