Bioinspired Carbon Radical Catalysis

Abstract Carbon radicals are fundamental and pivotal intermediates found in a veritable cornucopia of applications in diverse chemical contexts. Although nature elegantly employs them in enzymes like adenosylcobalamin (AdoCbl) for hydrogen atom transfer catalysis via dynamic cobalt–carbon covalency, their synthetic application in laboratory settings has been stymied by a fundamental paradox: transient radicals form irreversible bonds, while persistent radicals are catalytically inert. Inspired by AdoCbl, we report a catalytic system that circumvents this limitation through the reversible homolysis of a tailored dimer with a dynamic C(sp3)–C(sp3) bond. This mechanism allows the nascent carbon radical to interact reversibly with vinyl cyclopropanes, facilitating subsequent irreversible [3 + 2] reactions with alkenes and the regeneration of active catalyst. The power of this approach is demonstrated in a highly efficient and modular synthesis of cis-cyclopentanes, offering opportunities to rapidly access complex architectures and novel chemical spaces for lead discoveries.