Cinchona alkaloids are popular organocatalysts because of their excellent availability and diversity. In search of an efficient phase transfer catalyst for the asymmetric intramolecular alkylation in the preparation of a class of drug candidates for the treatment of migraine, the discovery of N,N’-disubstituted cinchona alkaloids was reported by Yasuda and coworkers at Merck in 2014 (Scheme 1).1 In this new generation of phase transfer catalysts, the quinuclidine nitrogen and the quinoline nitrogen are both quaternized. The mechanism and origins of selectivity of the intramolecular alkylation by the doubly quaternized cinchona-based phase transfer catalysts were investigated by performing density functional theory (DFT) calculations in this project. Specifically, we proposed a unified model that synthetic chemists can apply to the design of cinchona catalysts for asymmetric phase transfer transformations. (1) Xiang, B.; Belyk, K. M.; Reamer, R. A.; Yasuda, N. Angew. Chem. Int. Ed. 2014, 53, 8375.

Computational study of the enantioselectivity of an intramolecular alkylation by doubly quaternized cinchona-based phase transfer catalysts

251st National Meeting (2016)

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