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 (E1), which selectively provides the α-C-H activation products (EP as minor product and its C═C rotation isomer ZP' as major product). Three crucial issues are solved: (i) The detailed mechanism leading to ZP' 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 PdL2 (L = t-BuCN) with the C═C bond in EP, followed by the oxidative cyclization/reductive decyclization-assisted C═C double-bond rotation processes resulting in ZP' and regeneration of PdL2. (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, EP is certainly completely generated, while no ZP' formation occurred. Once E1 is used up, EP immediately acts as the partner of the new catalytic cycle and sluggishly evolves into ZP'. A small amount of generated ZP' would reversibly transform to EP 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.