Mechanistic Study of Palladium-Catalyzed Chemoselective C(sp3)-H Activation of Carbamoyl Chloride

A theoretical study has been carried out on the palladium-catalyzed C(sp(3))-H activation/amidation reaction of carbamoyl chloride precursors (Takemoto, Y. et al. Angew. Chem. Int. Ed. 2012, 51, 2763). In Takemoto's reaction, although the C(sp(2))-H bond of naphthalene was present in the substrate, the benzylic C(sp(3))-H bond was activated exclusively. Mechanistic calculations have been performed on the two possible pathways: the C(sp(3))-H activation/amidation pathway (Path-sp(3)) and the C(sp(2))-H activation/ainidation pathway (Path-sp(2)). Calculation results show that both paths include three steps: oxidative addition (via the mono-phosphine mechanism), C-H activation involving the PivNHO(-) anion (via the CMD mechanism), and final reductive elimination. The calculations indicate that the Path-sp(3) mechanism is kinetically favored, and the C(sp(3))-H amidated product is predicted to be the main product. This conclusion is consistent with Takemoto's experimental observations. The rate-determining step of Path-sp(3) is the oxidative addition step, and the C(sp(3))-H bond activation step determines the selectivity. Further examination on the origin of the selective C(sp(3))-H activation shows that the higher acidity of the benzylic C(sp(3))-H (in comparison to the naphthalene C(sp(2))-H in this system) is the main reason for the chemoselectivity. The additive might promote the reaction by forming a more soluble organic base (PivNHOCs) via reaction with Cs2CO3.