Control of Diastereoselectivity in Tandem Asymmetric Reactions Generating Nonadjacent Stereocenters with Bifunctional Catalysis by Cinchona Alkaloids

We report the manipulation of hydrogen-bonding-based cooperative catalysis to control the diastereoselectivity for a tandem asymmetric reaction creating two nonadjacent stereocenters. This ability to control both the enantioselectivity and diastereoselectivity allows, for the first time, the direct and stereoselective construction of 1,3-tertiary−quaternary stereocenters in any of the possible four configurations from the same prochiral precursors with catalytic control. The synthetic consequence of such catalyst-controlled construction of nonadjacent stereocenters is illustrated by the asymmetric synthesis of manzacidin C by using the same reaction sequence that was previously applied to the total synthesis of manzacidin A.