title: Catalytic Enantioselective [2,3]-Rearrangements of Allylic Ammonium Ylides: A Mechanistic and Computational Study.
abstract: A mechanistic study of the isothiourea-catalyzed enantioselective [2,3]-rearrangement of allylic ammonium ylides is described. Reaction kinetic analyses using19F NMR and density functional theory computations have elucidated a reaction profile and allowed identification of the catalyst resting state and turnover-rate limiting step. A catalytically relevant catalyst-substrate adduct has been observed, and its constitution elucidated unambiguously by13C and15N isotopic labeling. Isotopic entrainment has shown the observed catalyst-substrate adduct to be a genuine intermediate on the productive cycle toward catalysis. The influence of HOBt as an additive upon the reaction, catalyst resting state, and turnover-rate limiting step has been examined. Crossover experiments have probed the reversibility of each of the proposed steps of the catalytic cycle. Computations were also used to elucidate the origins of stereocontrol, with a 1,5-S···O interaction and the catalyst stereodirecting group providing transition structure rigidification and enantioselectivity, while preference for cation-π interactions over C-H···π is responsible for diastereoselectivity.
authors.affiliation: EaStCHEM, School of Chemistry, University of St Andrews , North Haugh, St. Andrews, KY16 9ST, U.K.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: West
authors.affiliation: Department of Chemistry, Oregon State University , 153 Gilbert Hall, Corvallis, Oregon 97333, United States.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Walden
authors.affiliation: EaStCHEM, School of Chemistry, University of St Andrews , North Haugh, St. Andrews, KY16 9ST, U.K.
authors.forename: James E
authors.initials: JE
authors.lastname: Taylor
authors.affiliation: Department of Chemistry, Oregon State University , 153 Gilbert Hall, Corvallis, Oregon 97333, United States.
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Brueckner
authors.affiliation: Department of Chemistry, Oregon State University , 153 Gilbert Hall, Corvallis, Oregon 97333, United States.
authors.forename: Ryne C
authors.identifier: 0000-0002-6606-9401
authors.initials: RC
authors.lastname: Johnston
authors.affiliation: Department of Chemistry, Oregon State University , 153 Gilbert Hall, Corvallis, Oregon 97333, United States.
authors.forename: Paul Ha-Yeon
authors.initials: PH
authors.lastname: Cheong
authors.affiliation: EaStCHEM, School of Chemistry, University of Edinburgh , Joseph Black Building, David Brewster Road, Edinburgh, EH9 3FJ, U.K.
authors.forename: Guy C
authors.identifier: 0000-0003-2128-6864
authors.initials: GC
authors.lastname: Lloyd-Jones
authors.affiliation: EaStCHEM, School of Chemistry, University of St Andrews , North Haugh, St. Andrews, KY16 9ST, U.K.
authors.forename: Andrew D
authors.identifier: 0000-0002-2104-7313
authors.initials: AD
authors.lastname: Smith