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

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journal contribution
posted on 12.08.2013, 00:00 by Qi Zhang, Hai-Zhu Yu, Yao Fu
A theoretical study has been carried out on the palladium-catalyzed C­(sp3)–H activation/amidation reaction of carbamoyl chloride precursors (Takemoto, Y. Angew. Chem. Int. Ed. 2012, 51, 2763 ). In Takemoto’s reaction, although the C­(sp2)–H bond of naphthalene was present in the substrate, the benzylic C­(sp3)–H bond was activated exclusively. Mechanistic calculations have been performed on the two possible pathways: the C­(sp3)–H activation/amidation pathway (Path-sp3) and the C­(sp2)–H activation/amidation pathway (Path-sp2). 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-sp3 mechanism is kinetically favored, and the C­(sp3)–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-sp3 is the oxidative addition step, and the C­(sp3)–H bond activation step determines the selectivity. Further examination on the origin of the selective C­(sp3)–H activation shows that the higher acidity of the benzylic C­(sp3)–H (in comparison to the naphthalene C­(sp2)–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.