Mechanism of Rhodium(III)-Catalyzed C-H Activation/Annulation of Aromatic Amide with α-Allenol: A Computational Study.

With the help of DFT calculations, the reaction mechanisms of the rhodium(III)-catalyzed C-H activation/annulation between aromatic amide and α-allenol leading to the formation of isoindolinone have been theoretically investigated. Our calculated results show that the catalytic cycle consists of four stages: N-H deprotonation and C-H activation (Stage I), allene insertion, rearrangement and isomerization (Stage II), β-H elimination and enol-keto tautomerism (Stage III), and catalyst regeneration resulting in the five-membered ring product (Stage IV). For stage IV, besides the reaction paths proposed by the experimentalists, i.e., the insertion and reductive elimination (labeled as path a) and the reductive elimination and hydroamination (labeled as path b), an alternative path which involves C-N and C-H reductive eliminations (labeled as path c) was proposed and examined. The computational results show that the newly established path c is more energetically favorable than the reaction paths proposed by the experimentalists (paths a and b). The allene (non-terminal double bond) insertion step contributes to the rate-determining step with an overall activation free energy of 24.6 kcal/mol. Our study is beneficial for a better comprehension of the reaction mechanisms and provides a significant suggestion for further development of similar reactions.