Mechanistic Insights into the Ruthenium-Catalyzed [4 + 1] Annulation of Benzamides and Propargyl Alcohols by DFT Studies

The mechanism of ruthenium-catalyzed [4 + 1] annulation of benzamide and propargyl alcohol has been investigated by density functional theory calculations. The reaction undergoes N–H and C–H deprotonations by a concerted metalation-deprotonation mechanism to afford a 5-membered ruthenacyclic species, which then undergoes ring expansion by alkyne insertion to deliver a 7-membered ring intermediate. Our study focused on how the successive hydrogen migrations take place that remains unclear. The 1,2-proton migration and 1,3-proton transfer from O to C are successively finished by using acetate anion as a shuttle (a stepwise process). In contrast to the experimental proposal that the reaction experiences a Ru­(II)–Ru(0)–Ru­(II) transformation, our study unveiled a Ru­(II)–Ru­(IV)–Ru­(II) transformation in the reaction. In addition, our calculations suggested that the EtO–N bond cleavage rather than the C–H activation is likely to be the rate-determining step for the entire reaction, which is not in contradiction with the experimentally reported kinetic isotope effect values.