Copper-catalyzed asymmetric addition of olefin-derived nucleophiles to ketones.
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.
Department of Chemistry, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.
Yang
Y
Yang
Department of Chemistry, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.
Ian B
IB
Perry
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Gang
G
Lu
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA. pengliu@pitt.edu sbuchwal@mit.edu.
Peng
P
Liu
Department of Chemistry, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA. pengliu@pitt.edu sbuchwal@mit.edu.
Stephen L
SL
Buchwald