title: Diastereoselective Synthesis of Highly Substituted Tetrahydrofurans by Pd-Catalyzed Tandem Oxidative Cyclization-Redox Relay Reactions Controlled by Intramolecular Hydrogen Bonding.
abstract: 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.
authors.affiliation: Chemical Biology Program , Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 422, New York, New York 10065, United States
authors.forename: Joshua L
authors.identifier: 0000-0002-9404-8173
authors.initials: JL
authors.lastname: Brooks
authors.affiliation: School of Chemical Engineering, Shandong University of Technology , Zibo 255049, China.|Lab of Computational Chemistry and Drug Design, Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School , Shenzhen 518055, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Xu
authors.affiliation: Lab of Computational Chemistry and Drug Design, Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School , Shenzhen 518055, China.|Department of Chemistry and Biochemistry, University of Notre Dame , Notre Dame, Indiana 46556, United States.
authors.forename: Olaf
authors.identifier: 0000-0001-9316-7720
authors.initials: O
authors.lastname: Wiest
authors.affiliation: Chemical Biology Program , Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 422, New York, New York 10065, United States|Tri-Institutional Research Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 422, New York, New York 10065, United States
authors.forename: Derek S
authors.initials: DS
authors.lastname: Tan
mesh_terms: D002384:Catalysis; D003500:Cyclization; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry; D006860:Hydrogen Bonding; D008968:Molecular Conformation; D010084:Oxidation-Reduction; D010165:Palladium / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D005663:Furans; D010165:Palladium; C008756:palladium chloride