Mechanistic Insights on the Ruthenium-Catalyzed Hydrogenation of Amides - C-N vs. C-O Cleavage

Ruthenium-catalyzed amide hydrogenation was thoroughly explored by means of DFT calculations. All the plausible pathways, including those involving the amide or imine tautomer, were assessed. The classical C-O cleavage and the recently reported C-N cleavage were compared by employing a bipyridyl-based Ru-II pincer complex as catalyst in the calculations. The study reveals that C-O cleavage can be achieved directly over the amide substrate or its imine tautomer, since the computed pathways show analogous energy barriers. In addition, the mechanism for the novel C-N cleavage was elucidated by modeling all the reasonable intermediates and transition structures. The computed energy barrier is lower than that for C-O cleavage by more than 10 kcalmol(-1), thus explaining the observed selectivity. The key role of the aromatization/dearomatization processes during the transformation is also disclosed.