Dynamic kinetic resolution (DKR) is a powerful strategy to construct enantiomerically enriched products. The selectivity of the DKR process depends on the two different rates of interconverting intermediates. Recently, we have discovered the example of a DKR of a geometrical mixture of tetrasubstituted alkenyl olefins derived from α,β-unsaturated aldehydes, resulting in the E-tetrasubstituted alkenyl cyanohydrins.
Density functional theory (DFT) calculations were performed to investigate the mechanistic details of the DKR. The reaction begins with initial deprotonation, leading to the anionic species that forms ion-pair with the sodium cation. We observed that the two stereoisomers show distinct ion-pair structures. The cyano group and the aromatic moiety can stabilize the negative charge of the anionic species. The interaction between the allylic anions and sodium cation reduces the rate of alkylation of one of two isomers and shifts the equilibrium of the E- and Z-olefins to facilitate the DKR. The nature of the alkali metal cation is explored by this work, which is crucial to lowering the barrier for interconversion between two geometrical isomers. The influences of substituents on the viability of the DKR will be discussed.
J. Majhi, B. W. H. Turnbull, H. Ryu, J. Park, M.-H. Baik, and P. A. Evans J. Am. Chem. Soc. 2019, 141, 11770.