Efficient N‐Heterocyclic Carbene/Ruthenium Catalytic Systems for the Alcohol Amidation with Amines: Involvement of Poly‐Carbene Complexes?

The atom‐economic direct amidation of alcohols with amines has been recently highlighted as an attractive and promising transformation. Among the versatile reported catalytic systems, in situ generated N‐heterocyclic carbene (NHC)/ruthenium (Ru) catalytic systems have demonstrated their advantages such as easy operation and use of commercial Ru compounds. However, the existing catalyst loadings are relatively high, and additional insights for the in situ catalyst generation are still not well‐documented. In this work, a variety of benzimidazole‐based NHC precursors were initially synthesized. Through the screening of various NHC precursors and other reaction conditions, active in situ catalytic systems were discovered for the efficient amide synthesis. Notably, the catalyst loading is as low as 0.5 mol %. Furthermore, additional experiments were performed to validate the rationale for the superiority of the current catalytic systems over our previous system. It was observed that the ligand structure is one of the reasons for the higher activity. In addition, the higher ratio of the NHC precursor/[Ru] is another important factor for the improvement. Further HR‐MS analysis identified the formation of two mono‐NHC‐Ru species as major species and two Ru species bearing multiple NHC ligands as minor species. Hopefully, the efficient and readily‐accessible catalytic systems reported herein could demonstrate great potential for further practical applications.