Origins of chemoselectivity of Rh(III)-Catalyzed C–H activation of N-(pivaloyloxy)benzamide: Insights from density functional theory calculations.

Abstract An unprecedented Rh(III)-catalyzed C–H activation of N -(pivaloyloxy)benzamide was recently reported by Feng et al. In this transformation, the substituent on the alkyne controls the chemoselectivity (annulation or hydroarylation). Given the importance of this novel strategy, we performed a density functional theory study to clarify the origins of the experimentally observed chemoselectivity. The results of our calculations showed that the conventional annulation of N -(pivaloyloxy)benzamide with an alkynone was kinetically favored, whereas the hydroarylation of α,α-difluoromethylene alkynes was kinetically favored. We found that the inductive effect of a fluorine substituent on the alkyne polarizes the Rh–C bond, and this facilitates the protonation step. Our calculations also explain the experimentally observed regioselectivity, which mainly arises from the interaction energy. Graphical abstract Image 1 Highlights • Origin of substituent-controled chemoselectivity (annulation or hydroarylation) was clarified. • Experimentally observed regioselectivity was explained. • Fluorine substituents in alkyne play an essential role in diverting the reaction sequence from the conventional pathway. • Protonation of the alkenyl group precedes formation of a Rh(V) nitrenoid intermediate. [ABSTRACT FROM AUTHOR]