Visible-Light-Mediated Dearomative Cyclopropanation of Benzo-Heterocycles via Energy Transfer

Visible-light photocatalysis is increasingly recognized as an effective and sustainable approach for the activation of otherwise poorly reactive organic molecules.1 In this work, we describe the first energy-transfer-mediated dearomative cyclopropanation of benzo-heterocycles, providing rapid access to highly strained cyclopropane-fused polycyclic systems in an atom-economical fashion.2,3 These motifs are particularly relevant because they are frequently found in natural products and biologically active compounds such as Lundurine B, Brimarafenib, and Lifirafenib. Mechanistic investigations suggest an EnT activation pathway involving neutral diradical intermediates and a radical cascade terminating in an unusual intramolecular 3-exo-trig cyclization. Interestingly, the generated α-cyclopropyl radical undergoes cyclization rather than the expected ring opening, enabling the efficient formation of complex three-dimensional scaffolds from simple benzo-heterocyclic precursors. The transformation delivers 22 unprecedented cyclopropane-fused products with good to excellent diastereoselectivity, forming up to four new C–C bonds and six stereocentres in a single step.4