Stereocontrol through Synergistic Catalysis in the Enantioselective α-Alkenylation of Aldehyde: A Computational Study

We describe the computational study of an interesting class of reactions involving synergistic action of chiral amine and Cu catalyst. The stereoselectivity-determining step of the enantioselective α-alkenylation of aldehyde has been investigated using the density functional theory methods to gain insight into the origin of the product selectivity. We found that the catalytic activation of reactants in the form of enamine and alkenyl Cu(III) intermediates significantly reduces the activation barrier of the addition step through an improved interaction between these two intermediates at the transition state (referred as enamine and Cu catalyst fragments of the transition state in the text). The transition-state stabilization through interaction between catalytic fragments, as demonstrated by the interaction/distortion model, clearly outperforms destabilization incurred due to the distortion of catalytic fragments and hence is recognized as a major factor contributing to the high stereoselectivity of reacti...