Dual-function cinchona alkaloid catalysis: Catalytic asymmetric tandem conjugate addition-protonation for the direct creation of nonadjacent stereocenters

ORGN 23

Li Deng, deng@brandeis.edu, YI Wang, and Xiaofeng Liu. Chemistry Department, Brandeis University, 415 South Street, Waltham, MA 02454
Catalytic tandem asymmetric reactions constitute a powerful strategy for the asymmetric construction of non-adjacent stereocenters in acyclic molecules directly from achiral precursors. In this talk, we present a highly enantioselective and diastereoselective addition of trisubstituted carbon donors to 2-chloroacrylonitrile catalyzed by bifunctional cinchona alkaloid catalysts. The reactions of a variety of sterically and electronically different Michael donors could provide the 1,4-adducts in 4:1-25:1 dr and up to 99% ee. This represents the first asymmetric tandem conjugate addition-protonation with efficient catalytic control of two non-adjacent stereocenters. As demonstrated in a concise and highly stereoselective formal total synthesis of (-)-manzacidin A in this talk, this asymmetric tandem reaction establishes a new and versatile catalytic approach for the enantioselective and diastereoselective creation of 1,3-tertiary-quaternary stereocenters.