Open AccessDiastereoselective Synthesis of Highly Substituted Tetrahydrofurans by Pd-Catalyzed Tandem Oxidative Cyclization–Redox Relay Reactions Controlled by Intramolecular Hydrogen Bonding
Author(s) -
Joshua L. Brooks,
Liping Xu,
Olaf Wiest,
Derek S. Tan
Publication year - 2016
Publication title -
journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.2
H-Index - 228
eISSN - 1520-6904
pISSN - 0022-3263
DOI - 10.1021/acs.joc.6b02053
Subject(s) - chemistry , intramolecular force , nucleophile , regioselectivity , redox , catalysis , markovnikov's rule , combinatorial chemistry , reductive elimination , tandem , reactivity (psychology) , hydrogen bond , palladium , photochemistry , medicinal chemistry , stereochemistry , organic chemistry , molecule , medicine , materials science , alternative medicine , pathology , composite material
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 2 /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.