Cyclopropanation of unactivated alkenes with diazo compounds enables facile synthesis of challenging cyclopropanes and late-stage sesquiterpene modification.

Cyclopropanes are prevalent motifs in pharmaceuticals and natural products; however, the construction of complex cyclopropanes remains a longstanding issue owing to low intrinsic reactivity and steric congestion. Herein, we report a visible-light-mediated cyclopropanation of unactivated alkenes with diazo compounds via an energy-transfer (EnT) pathway. This protocol provides direct access to a range of cyclopropanes, including spirocyclic, fused and those bearing quaternary carbon centers. Notably, a broad spectrum of unactivated alkenes-spanning endocyclic, bridged, polysubstituted, and terminal systems, along with diverse diazo reagents-are well tolerated, underscoring the generality of the method. The practicality is demonstrated by gram-scale synthesis and late-stage modification of natural products such as valencene, β-caryophyllene and flavanone. Moreover, in a preliminary in vitro assay, the caryophyllene oxide derivative exhibits promising anti-atopic dermatitis activity, showing nearly twice as high inhibition of CCL17 and CCL22 compared to its precursor, while exhibiting no detectable cytotoxicity. Finally, mechanistic studies support the involvement of triplet carbene species. These findings highlight the potential of this photochemical strategy for the rapid construction of challenging cyclopropanes and its utility in the development of bioactive natural product analogues.