Copper-catalyzed asymmetric addition of olefin-derived nucleophiles to ketones
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Author(s)
Lu, G.
Liu, P.
Yang, Yang
Perry, Ian
Buchwald, Stephen Leffler
Date Issued
July 2016
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Yang, Y. et al. “Copper-Catalyzed Asymmetric Addition of Olefin-Derived Nucleophiles to Ketones.” Science 353, 6295 (June 2016): 144–150 © 2016 American Association for the Advancement of Science
Version
Author's final manuscript
Abstract
Enantioenriched alcohols found in an array of bioactive natural products and pharmaceutical agents are often synthesized by asymmetric nucleophilic addition to carbonyls. However, this approach generally shows limited functional-group compatibility, requiring the use of preformed organometallic reagents in conjunction with a stoichiometric or substoichiometric amount of chiral controller to deliver optically active alcohols. Herein we report a copper-catalyzed strategy for the stereoselective nucleophilic addition of propargylic and other alkyl groups to ketones, using easily accessible (poly)unsaturated hydrocarbons as latent carbanion equivalents. Our method features the catalytic generation of highly enantioenriched organocopper intermediates and their subsequent diastereoselective addition to ketones, allowing for the effective construction of highly substituted stereochemical dyads with excellent stereocontrol. Moreover, this process is general, scalable, and occurs at ambient temperature.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1126/SCIENCE.AAF7720
