Enantioselective construction of highly substituted pyrrolidines by palladium-catalyzed asymmetric [3+2] cycloaddition of trimethylenemethane with ketimines.
The transition-metal catalyzed trimethylenemethane [3+2] cycloaddition provides a direct route to functionalized heterocycles. Herein, we describe a protocol for the reaction between 1-cyano-2-((trimethylsilyl)methyl)allyl acetate and a series of ketimines to generate highly substituted pyrrolidines. This methodology showcases a catalytic, asymmetric addition of a carbon nucleophile to ketimines, examples of which are still rare. The corresponding pyrrolidines were obtained in excellent yields and selectivities making use of our novel phosphoramidite ligands L2-L3.
Trost
Barry M
BM
Department of Chemistry, Stanford University, Stanford, California 94305-5080, USA. bmtrost@stanford.edu
Silverman
Steven M
SM
D002384:Catalysis; D007097:Imines / Q000737:chemistry*; D008697:Methane / Q000031:analogs & derivatives* / Q000737:chemistry; D009570:Nitriles / Q000737:chemistry*; D010165:Palladium / Q000737:chemistry*; D011759:Pyrrolidines / Q000737:chemistry*; D013237:Stereoisomerism; D013379:Substrate Specificity
D007097:Imines; D009570:Nitriles; D011759:Pyrrolidines; C542835:ketimine; C522820:trimethylenemethane; D010165:Palladium; D008697:Methane