Diastereoselective Synthesis of Highly Substituted Tetrahydrofurans by Pd-Catalyzed Tandem Oxidative Cyclization–Redox Relay Reactions Controlled by Intramolecular Hydrogen Bonding

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• 作者：Joshua L. BrooksLiping Xu ; Olaf Wiest ; Derek S. Tan
• 刊名：Journal of Organic Chemistry
• 出版年：2017
• 出版时间：January 6, 2017
• 年：2017
• 卷：82
• 期：1
• 页码：57-75
• 全文大小：738K
• ISSN：1520-6904

文摘

Palladium-catalyzed oxidative cyclization of alkenols provides a convenient entry into cyclic ethers but typically proceeds with little or no diastereoselectivity for cyclization of trisubstituted olefins to form tetrahydrofurans due to the similar energies of competing 5-membered transition-state conformations. Herein, a new variant of this reaction has been developed in which a PdCl₂/1,4-benzoquinone catalyst system coupled with introduction of a hydrogen-bond acceptor in the substrate enhances both diastereoselectivity and reactivity. Cyclization occurs with 5-exo Markovnikov regioselectivity. Mechanistic and computational studies support an anti-oxypalladation pathway in which intramolecular hydrogen bonding increases the nucleophilicity of the alcohol and enforces conformational constraints that enhance diastereoselectivity. The cyclization is followed by a tandem redox-relay process that provides versatile side-chain functionalities for further derivatization.