title: Computational insight into the cooperative role of non-covalent interactions in the aza-Henry reaction catalyzed by quinine derivatives: mechanism and enantioselectivity.
abstract: Density functional theory (DFT) calculations were performed to elucidate the mechanism and the origin of the high enantioselectivity of the aza-Henry reaction of isatin-derived N-Boc ketimine catalyzed by a quinine-derived catalyst (QN). The C-C bond formation step is found to be both the rate-determining and the stereo-controlled step. The results revealed the important role of the phenolic OH group in pre-organizing the complex of nitromethane and QN and stabilizing the in situ-generated nitronate and protonated QN. Three possible activation modes for C-C bond formation involving different coordination patterns of catalyst and substrates were studied, and it was found that both the ion pair-hydrogen bonding mode and the Brønsted acid-hydrogen bonding mode are viable, with the latter slightly preferred for the real catalytic system. The calculated enantiomeric excess (ee) favouring the S enantiomer is in good agreement with the experimental result. The high reactivity and enantioselectivity can be ascribed to the cooperative role of the multiple non-covalent interactions, including classical and non-classical H bonding as well as anionπ interactions. These results also highlight the importance of the inclusion of dispersion correction for achieving a reasonable agreement between theory and experiment for the current reaction.
authors.affiliation: Institute of Theoretical and Computational Chemistry, Key Laboratory of Mesoscopic Chemistry of MOE, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210093, P. R. China. zxchen@nju.edu.cn and School of Pharmacy, Xuzhou Medical University, No. 209, Tongshan Road, Xuzhou, 221004, P. R. China.
authors.forename: Yunsheng
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Shanghai Key Laboratory of Green Chemistry and Chemical Processes, East China Normal University, 3663 N. Zhongshan Road, Shanghai, 200062, P. R. China.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory of Green Chemistry and Chemical Processes, East China Normal University, 3663 N. Zhongshan Road, Shanghai, 200062, P. R. China.
authors.forename: Zhongyan
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Shanghai Key Laboratory of Green Chemistry and Chemical Processes, East China Normal University, 3663 N. Zhongshan Road, Shanghai, 200062, P. R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Institute of Theoretical and Computational Chemistry, Key Laboratory of Mesoscopic Chemistry of MOE, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210093, P. R. China. zxchen@nju.edu.cn.
authors.forename: Zhao-Xu
authors.initials: ZX
authors.lastname: Chen