N-Heterocyclic Selone-Catalyzed [2σ + 2π] Cycloaddition of Bicyclo[1.1.0]butanes via Photoredox Radical Buffer.

The development of Fsp3-rich bioisosteres for meta-substituted benzenes remains a significant challenge in medicinal chemistry. We herein disclose novel redox-active N-heterocyclic selone (NHS) catalysts that enable a radical-catalyzed [2σ + 2π] cycloaddition platform, providing direct access to 1,3-bicyclohexane, a geometrically congruent bioisostere for meta-substituted benzene. This method enables efficient radical-mediated cycloaddition of vinyl-bicyclobutanes (V-BCBs) with diverse alkenes, achieving high yields (up to 99%) and broad substrate compatibility (47 examples) with a low catalyst loading (1 mol %). Mechanistic studies and DFT calculations confirm the generation of the NHC-stabilized selenium-centered radical (C6·+) via a radical buffer strategy under blue-light irradiation. Downstream manipulation and the expedient synthesis of an Fsp3-rich analogue of the anticancer drug Sonidegib substantiate the synthetic versatility of our catalytic platform.