Mechanistic Studies Lead to Dramatically Improved Reaction Conditions for the Cu-Catalyzed Asymmetric Hydroamination of Olefins
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Mechanistic studies.pdf
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1.46 MB
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Author(s)
Bandar, Jeffrey
Pirnot, Michael T
Buchwald, Stephen Leffler
Date Issued
November 2015
Journal
Journal of the American Chemical Society
Publisher
American Chemical Society (ACS)
Citation
Bandar, Jeffrey S., Michael T. Pirnot, and Stephen L. Buchwald. “Mechanistic Studies Lead to Dramatically Improved Reaction Conditions for the Cu-Catalyzed Asymmetric Hydroamination of Olefins.” Journal of the American Chemical Society 137.46 (2015): 14812–14818. © 2015 American Chemical Society
Version
Final published version
Abstract
Enantioselective copper(I) hydride (CuH)-catalyzed hydroamination has undergone significant development over the past several years. To gain a general understanding of the factors governing these reactions, kinetic and spectroscopic studies were performed on the CuH-catalyzed hydroamination of styrene. Reaction profile analysis, rate order assessment, and Hammett studies indicate that the turnover-limiting step is regeneration of the CuH catalyst by reaction with a silane, with a phosphine-ligated copper(I) benzoate as the catalyst resting state. Spectroscopic, electrospray ionization mass spectrometry, and nonlinear effect studies are consistent with a monomeric active catalyst. With this insight, targeted reagent optimization led to the development of an optimized protocol with an operationally simple setup (ligated copper(II) precatalyst, open to air) and short reaction times (<30 min). This improved protocol is amenable to a diverse range of alkene and alkyne substrate classes.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1021/jacs.5b10219
