A computational study on ruthenium-catalyzed [4 + 1] annulation via C–H activation: the origin of selectivity and the role of the internal oxidizing group

Abstract

We report a density functional theory study on ruthenium-catalyzed [4 + 1] annulation of benzamides with propargyl alcohols via C–H activation. The plausible catalytic cycles involve N–H deprotonation, C–H activation, alkyne insertion, β-H elimination, enol–keto tautomerism, oxidative addition, C–N reductive elimination, protonation, and catalyst recovery. Importantly, the preference of the [4 + 1] annulation over the [4 + 2] annulation is discussed in detail. Alkynes bearing a β-H group and a hydroxyl group are necessary for β-H elimination and enol–keto tautomerism, which lead to the formation of a [4 + 1] product. In contrast, alkynes without a β-H group or a hydroxyl group could only lead to [4 + 2] annulation. Additionally, this article addresses the key role of the internal oxidizing group, which is responsible for converting Ru^II into Ru^IV and thus favoring the following C–N reductive elimination. Hence, the studied mechanism of [4 + 1] annulation is a novel Ru^II/IV/II pathway rather than a Ru^II/0/II pathway.