Theoretical Study on Mechanism of Cinchona Alkaloids Catalyzed Asymmetric Conjugate Addition of Dimethyl Malonate to β-Nitrostyrene

The mechanism and enantioselectivity of the asymmetric conjugate addition of dimethyl malonate to -nitrostyrene catalyzed by cinchona alkaloid QD-4 as organic catalyst are investigated using density function theory and ab initio methods. Six different reaction pathways, corresponding to the different approach modes of -nitrostyrene to dimethyl malonate are considered. Calculations indicate that the reaction process through a dual-activation mechanism, in which the tertiary amine of cinchona alkaloid QD-4 first works as a BrOnsted base to promote the activation of the dimethyl malonate by deprotonation, and then, the hydroxyl group of QD-4 acts as BrOnsted acid to activate the -nitrostyrene. The rate-determining step is the proton transfer process from the tertiary amine of QD-4 to -carbon of -nitrostyrene. The comparison of the mechanisms and energies of the six reaction channels enable us to learn the fact that QD-4 has good catalytic activities for the system, and implies C9OH in QD-4 may not be involved in the activation. These calculation results account well for the observations in experiments. (c) 2014 Wiley Periodicals, Inc.