Mechanistic insights and stereoselectivity in Ni(II)-catalyzed asymmetric [3 + 2]/[3 + 3] cycloaddition reactions of donor-acceptor cyclopropanes: A DFT study

Density functional theory (DFT) was employed to investigate the reaction mechanisms and stereoselectivity of Ni(II)-catalyzed nonracemic donor-acceptor cyclopropane (DAC) [3 + 2]/[3 + 3] cycloaddition reactions with imine, triazine, and nitrone substrates. The results indicate that the overall reaction for all three substrates consists of two main steps: (1) nucleophilic attack of the substrate on the nonracemic DAC, and (2) C-C cyclization of the resulting key intermediate to form either five- or six-membered rings. For imine and triazine, the most favorable reaction pathway involves direct nucleophilic attack followed by cyclization, while for nitrone, the reaction proceeds via racemization to form an alkene intermediate, which then undergoes cyclization. Computational analysis reveals that the of the diastereoselectivity nucleophilic attack step is primarily controlled by distortion energy, whereas the enantioselectivity of the cyclization step is governed by interaction energy. Global reactivity index (GRI) analysis shows that imine exhibits the highest nucleophilicity with the lowest activation energy, while nitrone displays the weakest nucleophilicity and the highest activation energy. This theoretical study provides new insights into predicting reaction pathways and rationalizing the selective features of related cyclization reactions.