TY - JOUR
T1 - Copper-Catalyzed Cyclization and Alkene Transposition Cascade Enables a Modular Synthesis of Complex Spirocyclic Ethers
AU - Wei, Wan Xu
AU - Kuang, Yangjin
AU - Tomanik, Martin
N1 - Publisher Copyright:
© 2024 The Authors. Published by American Chemical Society.
PY - 2024
Y1 - 2024
N2 - Complexity-generating reactions that access three-dimensional products from simple starting materials offer substantial value for drug discovery. While oxygen-containing heterocycles frequently feature unique, nonaromatic architectures such as spirocyclic rings, exploration of these chemical spaces is limited by conventional synthetic approaches. Herein, we report a copper-catalyzed annulation and alkene transposition cascade reaction that enables a modular preparation of complex, spirocyclic ethers from readily available alkenol substrates via a copper-catalyzed annulation and transannular 1,5-hydrogen atom transfer-mediated C-H functionalization. Our transformation displays a broad substrate scope, shows excellent heteroatom compatibility, and readily constructs spirocycles of varying ring sizes. The wider synthetic utility of this method is highlighted by numerous product diversifications and a short synthesis of the all-carbon framework of spirotenuipesine A. We anticipate that this transformation can significantly streamline access to a privileged class of three-dimensional oxygen-containing heterocycles and will find broad application in natural product synthesis.
AB - Complexity-generating reactions that access three-dimensional products from simple starting materials offer substantial value for drug discovery. While oxygen-containing heterocycles frequently feature unique, nonaromatic architectures such as spirocyclic rings, exploration of these chemical spaces is limited by conventional synthetic approaches. Herein, we report a copper-catalyzed annulation and alkene transposition cascade reaction that enables a modular preparation of complex, spirocyclic ethers from readily available alkenol substrates via a copper-catalyzed annulation and transannular 1,5-hydrogen atom transfer-mediated C-H functionalization. Our transformation displays a broad substrate scope, shows excellent heteroatom compatibility, and readily constructs spirocycles of varying ring sizes. The wider synthetic utility of this method is highlighted by numerous product diversifications and a short synthesis of the all-carbon framework of spirotenuipesine A. We anticipate that this transformation can significantly streamline access to a privileged class of three-dimensional oxygen-containing heterocycles and will find broad application in natural product synthesis.
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U2 - 10.1021/jacs.4c14418
DO - 10.1021/jacs.4c14418
M3 - Article
AN - SCOPUS:85212770738
SN - 0002-7863
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
ER -