Theoretical study on the mechanism and selectivity of asymmetric cycloaddition reactions of 3-vinylindole catalyzed by chiral N,N'-dioxide-Ni(II) complex

Abstract

The mechanism and selectivity of the asymmetric cycloaddition reactions of 3-vinylindole towards methyleneindolinone (Diels–Alder reaction) or ketimine (aza-Diels–Alder reaction) were investigated theoretically by DFT and ONIOM methods. The non-catalytic DA reaction occurred in a two-stage one-step mechanism with the energy barriers of 17.0–29.6kcalmol−1. Reactivity index analysis indicated that the cycloaddition tended to occur by the most nucleophilic terminal C4 center in 3-vinylindole and the most electrophilic Cβ center in methyleneindolinone with lower activation energies, which accounted for the regioseletivity observed in experiment. For non-catalytic reactions, the slightly exo-preference stemmed from the stabilizing π-π stacking of two indole rings in substrates. In the presence of chiral N,N'-dioxide-Ni(II) complex, the bulky ortho-iPr group in aniline of ligand provided sufficient steric shielding around dienophile from the si-face attack in Diels–Alder reaction or re-face attack in aza-Diels–Alder reaction by diene, resulting in predominant products with excellent enantioselectivity (the favorable re-face attack in Diels–Alder reaction or si-face attack in aza-Diels–Alder reaction). A “pocket-like” chiral cavity constructed by chiral catalyst enhanced exo-diastereofacial selectivity significantly by maximizing the overlap of the two indole rings of substrates to avoid unfavorable steric repulsion between indole ring of 3-vinylindole and chiral ligand. Compared with catalytic aza-Diels–Alder reaction of 3-vinylindole and ketimine, the improved catalytic activity of chiral N,N'-dioxide-Ni(II) catalyst in Diels–Alder reaction of 3-vinylindole with methyleneindolinone contributed to the high turnover frequency (TOF=1.05×106s−1). These results were in good agreement with experimental observations.