Copper-Catalyzed Cyclization\nand Alkene Transposition\nCascade Enables a Modular Synthesis of Complex Spirocyclic Ethers

Complexity-generating reactions that access three-dimensional\nproducts\nfrom simple starting materials offer substantial value for drug discovery.\nWhile oxygen-containing heterocycles frequently feature unique, nonaromatic\narchitectures such as spirocyclic rings, exploration of these chemical\nspaces is limited by conventional synthetic approaches. Herein, we\nreport a copper-catalyzed annulation and alkene transposition cascade\nreaction that enables a modular preparation of complex, spirocyclic\nethers from readily available alkenol substrates via a copper-catalyzed\nannulation and transannular 1,5-hydrogen atom transfer-mediated C–H\nfunctionalization. Our transformation displays a broad substrate scope,\nshows excellent heteroatom compatibility, and readily constructs spirocycles\nof varying ring sizes. The wider synthetic utility of this method\nis highlighted by numerous product diversifications and a short synthesis\nof the all-carbon framework of spirotenuipesine A. We anticipate that\nthis transformation can significantly streamline access to a privileged\nclass of three-dimensional oxygen-containing heterocycles and will\nfind broad application in natural product synthesis.