Abstract
A mechanistic study of the isothiourea-catalyzed enantioselective [2,3]-rearrangement of allylic ammonium ylides is described. Reaction kinetic analyses using 19F 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 by 13C and 15N 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.
Original language | English |
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Pages (from-to) | 4366-4375 |
Number of pages | 10 |
Journal | Journal of the American Chemical Society |
Volume | 139 |
Issue number | 12 |
Early online date | 23 Feb 2017 |
DOIs | |
Publication status | Published - 29 Mar 2017 |
Funding
The research leading to these results (T.H.W., J.E.T., G.C.L.-J., and A.D.S.) has received funding from the ERC under the European Union's Seventh Framework Programme (FP7/2007-2013)/E.R.C. Grant Agreement Nos. 279850 and 340163. A.D.S. thanks the Royal Society for a Wolfson Research Merit Award. We also thank the EPSRC UK National Mass Spectrometry Facility at Swansea University. P.H.-Y.C. is the Bert and Emelyn Christensen Professor and gratefully acknowledges financial support from the Stone Family of OSU. Financial support from the National Science Foundation (NSF) (CHE-1352663) is acknowledged. D.M.W. acknowledges the Bruce Graham and Johnson Fellowships of OSU. A.C.B. acknowledges the Johnson Fellowship of OSU. D.M.W., A.C.B., R.C.J., and P.H.-Y.C. also acknowledge computing infrastructure in part provided by the NSF Phase-2 CCI, Center for Sustainable Materials Chemistry (CHE-1102637).
ASJC Scopus subject areas
- Catalysis
- General Chemistry
- Biochemistry
- Colloid and Surface Chemistry