Mechanisms of Rhodium(III)-Catalyzed C-H Functionalizations of Benzamides with α,α-Difluoromethylene Alkynes.

The rhodium(III)-catalyzed C-H functionalizations of benzamides with α,α-difluoromethylene alkynes have been investigated by means of density functional theory calculations. The computations show that after the formation of seven-membered rhodacycle via consecutive N-H deprotonation/C-H activation/migratory insertion, a novel redox-neutral process without the engagement of otherwise widely accepted Rh(V) nitrenoid species has been formulated in the hydroarylation reaction. It turns out that the seven-membered rhodacycle undergoes a concerted Lossen rearrangement/migration of OPiv from N to Rh to generate the isocyanate intermediate, from which the ensuing nucleophilic addition of MeOH and protodemetalation lead to the generation of final products. By preventing formation of Rh(V) nitrenoid species, the intriguing role of fluorine substituents in hydroarylation reaction has also been disclosed. Furthermore, the coordination of carbonyl oxygen of OPiv group to the Rh center proves to be crucial for both [4 + 2] annulation and hydroarylation. However, in the case of using directing group with N-OMe, the lack of such assistance would engender a considerable buildup of energy with respect to the transition state, making both [4 + 2] annulation and hydroarylation processes kinetically unfavorable. Accordingly, the alternative [4 + 1] annulation takes place as the most favored pathway via consecutive twofold β-F eliminations.