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 β‐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 β‐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 Brønsted base to promote the activation of the dimethyl malonate by deprotonation, and then, the hydroxyl group of QD‐4 acts as Brønsted acid to activate the β‐nitrostyrene. The rate‐determining step is the proton transfer process from the tertiary amine of QD‐4 to α‐carbon of β‐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 C9? OH in QD‐4 may not be involved in the activation. These calculation results account well for the observations in experiments. © 2014 Wiley Periodicals, Inc.