Synthesis of 1‐Chalcogen‐3‐Alkyl Bicyclo[1.1.1]pentanes Enabled by a Photocatalytic Multicomponent Radical Coupling

Comprehensive Summary Current methods to access aryl/alkyl thiol‐substituted bicyclo[1.1.1]pentane (BCP) derivatives (valuable bioisosteres for thiophenols/ thioethers) remain underdeveloped. Herein, we report a photocatalytic multicomponent reaction via consecutive photoinduced electron transfer (ConPET) to enable simultaneous C sp 3 ‐C and C sp 3 ‐Y (Y = S, Se, Te) bond formation on [1.1.1]pentanes. This strategy delivers diverse alkyl halides (Cl, Br, I; primary, secondary, tertiary). Late‐stage derivatization of drug molecules ( e.g ., aspirin, methylprednisolone) and oxidations to sulfoxides/sulfones demonstrate synthetic versatility. Mechanistic studies support a radical relay pathway initiated by ConPET‐mediated alkyl radical generation. The method establishes a robust platform for constructing chalcogen‐rich BCP bioisosteres, addressing a critical gap in medicinal chemistry and offering significant potential for drug discovery.