A Combined IM-MS/DFT Study on [Pd( MPAA)]-Catalyzed Enantioselective C-H Activation: Relay of Chirality through a Rigid Framework

A combined ion-mobility mass spectrometry (IMMS) 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.