Photoredox-Catalyzed Cyclopropanation via Ligated Boryl Radical-Mediated Nonstabilized Carbene Formation

Abstract

The [2 + 1] cycloaddition of carbenes with alkenes is widely regarded as one of the most straightforward strategies for synthesizing cyclopropanes, which are ubiquitous motifs in pharmaceuticals. A significant challenge in cyclopropanation reactions is managing the high reactivity and inherent safety risks associated with the use of diazo compounds, particularly alkyl-substituted variants, as carbene precursors. Leveraging metallaphotoredox catalysis, we report the development of a method for ligated boryl radical-mediated generation of nonstabilized metal carbenes directly from aliphatic aldehydes. Employing B₂cat₂ as the activating agent for the carbonyl group, this approach enables the direct use of alkyl aldehydes as nonstabilized carbene precursors, eliminating the need for substrate prefunctionalization. This protocol features mild conditions, broad substrate scope (>88 examples), and good functional group tolerance, demonstrating its applicability in diverse cyclopropanation and σ-bond insertion reactions. Preliminary mechanistic studies have been also performed to elucidate the reaction pathway.