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

Ruiyuan Xu; Binye Cao; Yibo Wang; Jingyi Zhang; Yuping Huang; Yihan Gao; Wanmei Li

doi:10.1002/cjoc.70244

Chinese Journal of Chemistry ›› 2025, Vol. 43 ›› Issue (23) :3259 -3265. DOI: 10.1002/cjoc.70244

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

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Abstract

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 Csp³-C and Csp³-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.

Keywords

Bicyclo[1.1.1]pentane (BCP) / Csp³-C and Csp³-Y (Y = S/Se/Te) bond formation / Bioisosteres / Photocatalytic multicomponent reaction / ConPET strategy / Chemoselectivity / Difunctionalization / Photocatalysis

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Ruiyuan Xu, Binye Cao, Yibo Wang, Jingyi Zhang, Yuping Huang, Yihan Gao, Wanmei Li. Synthesis of 1-Chalcogen-3-Alkyl Bicyclo[1.1.1]pentanes Enabled by a Photocatalytic Multicomponent Radical Coupling. Chinese Journal of Chemistry, 2025, 43(23): 3259-3265 DOI:10.1002/cjoc.70244