title: A combined IM-MS/DFT study on [Pd(MPAA)]-catalyzed enantioselective C-H activation: relay of chirality through a rigid framework.
abstract: A combined ion-mobility mass spectrometry (IM-MS) and DFT study has been employed to investigate the mechanism and the origin of selectivity of palladium/mono-N-protected amino acid (MPAA)-catalyzed enantioselective CH activation reactions of several prochiral substrates. We captured the [Pd(MPAA)(substrate)] complex at different stages, and demonstrated that the CH bond can be activated in the absence of an external base. DFT studies lead to the establishment of a significantly modified relay mechanism invoking a key conformational effect to account for the origin of enantioselectivity. This relay mechanism successfully accounts for the enantioselectivity for all the relevant reactions reported. The enantioselectivity originates from the rigid square-planar Pd coordination in the CH activation transition state: Bidentate MPAA and substrate coordination.
authors.affiliation: Lab of Computational Chemistry and Drug Design, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen 518055 (P.R. China).
authors.forename: Gui-Juan
authors.initials: GJ
authors.lastname: Cheng
authors.affiliation: Lab of Computational Chemistry and Drug Design, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen 518055 (P.R. China).
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.affiliation: Lab of Computational Chemistry and Drug Design, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen 518055 (P.R. China).
authors.forename: Tian-Yu
authors.initials: TY
authors.lastname: Sun
authors.affiliation: Lab of Computational Chemistry and Drug Design, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen 518055 (P.R. China). zhangxh@pkusz.edu.cn.
authors.forename: Xinhao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, The Scripps Research Institute, California 92037 (USA). yu200@scripps.edu.
authors.forename: Jin-Quan
authors.initials: JQ
authors.lastname: Yu
authors.affiliation: Lab of Computational Chemistry and Drug Design, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen 518055 (P.R. China). wuyd@pkusz.edu.cn.|College of Chemistry, Peking University, Beijing 100871 (P.R. China). wuyd@pkusz.edu.cn.
authors.forename: Yun-Dong
authors.initials: YD
authors.lastname: Wu
keywords: CH activation; amino acids; asymmetric catalysis; density functional calculations; enantioselectivity; mass spectrometry