Mechanistic insight into the regioselectivity of Pd(ii)-catalyzed C–H functionalization of N-methoxy cinnamamide

Abstract

Computational studies have been applied to gain insight into the mechanism of Pd(II) catalyzed α-C–H functionalization of N-methoxy cinnamamide. The results show that the whole catalytic cycle proceeds via sequential six steps, including (i) catalyst Pd(t-BuNC)₂ oxidation with O₂, (ii) O–H deprotonation, (iii) t-BuNC migratory insertion to the Pd–C bond, (iv) acyl migration, (v) C–H activation and (vi) reductive elimination. The regioselectivity for different C–H activation sites depends on the coordination structures of α-C or β-C to the palladium(II) center. The coordination of α-C to the palladium(II) center shows a regular planar quadrilateral structure, which is stable. However, the β-C coordinating to the palladium(II) center mainly exhibits a distorted quadrilateral structure, which is relatively unstable. Thus, the barrier of α-C–H activation is much lower than that of β-C–H activation. The present results provide a deep understanding of the site-selectivity of C–H activation.