Dual-function cinchona alkaloid catalysis: catalytic asymmetric tandem conjugate addition-protonation for the direct creation of nonadjacent stereocenters.
Catalytic tandem asymmetric reactions constitute a powerful strategy for the asymmetric construction of nonadjacent stereocenters in acyclic molecules directly from achiral precursors. In this Communication, we report a highly enantioselective and diastereoselective addition of trisubstituted carbon donors to 2-chloroacrylonitrile catalyzed by bifunctional cinchona alkaloid catalysts. This represents the first asymmetric tandem conjugate addition-protonation with efficient catalytic control of two nonadjacent stereocenters. As demonstrated in a concise and highly stereoselective formal total synthesis of (-)-manzacidin A, this asymmetric tandem reaction establishes a new and versatile catalytic approach for the enantioselective and diastereoselective creation of 1,3-tertiary-quaternary stereocenters.
Department of Chemistry, Brandeis University, Waltham, Massachusetts 02454-9110, USA.
Yi
Y
Wang
Xiaofeng
X
Liu
Li
L
Deng
D000181:Acrylonitrile / Q000031:analogs & derivatives / Q000737:chemistry; D002384:Catalysis; D002930:Cinchona Alkaloids / Q000737:chemistry*; D005609:Free Radicals / Q000737:chemistry; D009570:Nitriles / Q000138:chemical synthesis*; D013237:Stereoisomerism
D002930:Cinchona Alkaloids; D005609:Free Radicals; D009570:Nitriles; C037879:2-chloroacrylonitrile; D000181:Acrylonitrile