Epoxidation over Semipinacol Rearrangement via Photocopper Catalysis for Oxa-Spirocycle Synthesis

Spirocycles serve as pivotal three-dimensional bioisosteres for flat scaffolds in drug discovery, offering enhanced structural diversity and physicochemical properties. We report a visible-light-induced, copper-catalyzed alkylative epoxidation of 1-vinylcyclobutanols and their derivatives, enabling the direct construction of oxa-spirocycles from unactivated alkyl halides as alkyl radical precursors. The success of this transformation depends on the right redox potential of in-situ-generated Cu(II) species, which stabilizes the radical intermediate while preventing its over-oxidation to a carbocation. This critical control suppresses the competing semipinacol rearrangement pathway, selectively delivering valuable oxa-spirocyclic compounds.