Streamlining the synthesis of amides using Nickel-based nanocatalysts

The synthesis of amides is a key technology for the preparation of fine and bulk chemicals in industry, as well as the manufacture of a plethora of daily life products. Furthermore, it constitutes a central bond-forming methodology for organic synthesis and provides the basis for the preparation of numerous biomolecules. Here, we present a robust methodology for amide synthesis compared to traditional amidation reactions: the reductive amidation of esters with nitro compounds under additives-free conditions. In the presence of a specific heterogeneous nickel-based catalyst a wide range of amides bearing different functional groups can be selectively prepared in a more step-economy way compared to previous syntheses. The potential value of this protocol is highlighted by the synthesis of drugs, as well as late-stage modifications of bioactive compounds. Based on control experiments, material characterizations, and DFT computations, we suggest metallic nickel and low-valent Ti-species to be crucial factors that makes this direct amide synthesis possible.

Jie Gao, Rui Ma, Fairoosa Poovan, Lan Zhang, Hanan Atia, Narayana V. Kalevaru, Wenjing Sun, Sebastian Wohlrab, Denis A. Chusov, Ning Wang, Rajenahally V. Jagadeesh, Matthias Beller