Monofluorinated C1 Synthon Strategy for the Construction of Fluoromethylene-Linked Bicyclo[1.1.1]pentane Derivatives

Fluoroalkyl substituted bicyclo[1.1.1]pentanes (BCP) have appeared as an attractive scaffold in drug discovery. Herein, we report on modular construction of fluoromethyele linked BCPs. Fluoroiodomethyl phenyl sulfoxide turned out to be a synthetic equivalent of formal fluoromethylene radical cation synthon, which under metal free, violet light (400 nm) enabled atom-transfer radical addition (ATRA) reaction to [1.1.1]propellane. This simple approach gives access to novel bicyclo[1.1.1]pentane substituted fluoromethyl sulfonium reagents. Electrophilic properties of the sulfonium salt enable nucleophilic displacement under mild conditions and introduction of fluoromethyl bicyclopentyl group to various natural and drug molecules with good functional group tolerance.