Chemical Biology Program , Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 422, New York, New York 10065, United States
School of Chemical Engineering, Shandong University of Technology , Zibo 255049, China.
J Org Chem. 2017 Jan 6;82(1):57-75. doi: 10.1021/acs.joc.6b02053. Epub 2016 Dec 22.
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 PdCl/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.
钯催化的烯丙醇氧化环化反应为环状醚的合成提供了一种便利的方法，但对于三取代烯烃的环化反应，由于竞争的 5 元过渡态构象的能量相似，通常只有很少或没有立体选择性，从而形成四氢呋喃。在此，开发了该反应的一种新变体，其中 PdCl/1,4-苯醌催化剂体系与底物中氢键受体的引入相结合，提高了立体选择性和反应性。环化反应具有 5-endoMarkovnikov 区域选择性。机理和计算研究支持反-氧钯化途径，其中分子内氢键增加了醇的亲核性，并施加构象约束，从而提高了立体选择性。环化反应后是串联的氧化还原接力过程，为进一步衍生化提供了多功能的侧链官能团。
