Mechanistic Unveiling of C═C Double-Bond Rotation and Origins of Regioselectivity and Product E/Z Selectivity of Pd-Catalyzed Olefinic C-H Functionalization of (E)-N-Methoxy Cinnamamide.

Density functional theory (DFT) calculations have been performed to study the Pd-catalyzed C-H functionalization of (E)-N-methoxy cinnamamide (1), which selectively provides the α-C-H activation products (P as minor product and its C═C rotation isomer P' as major product). Three crucial issues are solved: (i) The detailed mechanism leading to P' is one issue. The computational analyses of the mechanisms proposed in previously experimental and theoretical literature do not seem to be consistent with the experimental findings due to the high barriers involved. Alternatively, we present a novel oxidation/reduction-promoted mechanism featuring the Pd(0) → Pd(II) → Pd(0) transformation. The newly proposed mechanism involves the initial coordination of the active catalyst PdL (L = t-BuCN) with the C═C bond in P, followed by the oxidative cyclization/reductive decyclization-assisted C═C double-bond rotation processes resulting in P' and regeneration of PdL. (ii) The origin of the product E/Z selectivity is the second issue. On the basis of the calculated results, it is found that, at the initial stage of the reaction, P is certainly completely generated, while no P' formation occurred. Once 1 is used up, P immediately acts as the partner of the new catalytic cycle and sluggishly evolves into P'. A small amount of generated P' would reversibly transform to P due to the higher barrier involved. (iii) The intrinsic reasons for the regioselectivity are the third issue. The calculated results indicate that the regioselectivity for α-C-H activation is mainly attributed to the stronger electrostatic attraction between the α-C and the metal center.