Zhang Jin, Zhang Pei, Shao Lei, Wang Ruihong, Ma Yangmin, Szostak Michal
College of Chemistry and Chemical Engineering, Key Laboratory of Chemical Additives for China National Light Industry, Shaanxi University of Science and Technology, Xi'an, Shaanxi, 710021, China.
Institute of Frontier Science and Technology Transfer, Shaanxi University of Science and Technology, Xi'an, Shaanxi, 710021, China.
Angew Chem Int Ed Engl. 2022 Feb 7;61(7):e202114146. doi: 10.1002/anie.202114146. Epub 2021 Dec 29.
Although cross-coupling reactions of amides by selective N-C cleavage are one of the most powerful and burgeoning areas in organic synthesis due to the ubiquity of amide bonds, the development of mechanochemical, solid-state methods remains a major challenge. Herein, we report the first mechanochemical strategy for highly chemoselective, solvent-free palladium-catalyzed cross-coupling of amides by N-C bond activation. The method is conducted in the absence of external heating, for short reaction time and shows excellent chemoselectivity for σ N-C bond activation. The reaction shows excellent functional group tolerance and can be applied to late-stage functionalization of complex APIs and sequential orthogonal cross-couplings exploiting double solventless solid-state methods. The results extend mechanochemical reaction environments to advance the chemical repertoire of N-C bond interconversions to solid-state environmentally friendly mechanochemical methods.
尽管由于酰胺键的普遍性，通过选择性N-C裂解进行的酰胺交叉偶联反应是有机合成中最强大且新兴的领域之一，但机械化学固态方法的发展仍然是一项重大挑战。在此，我们报道了首个通过N-C键活化实现高化学选择性、无溶剂钯催化酰胺交叉偶联的机械化学策略。该方法在无外部加热的情况下进行，反应时间短，对σ N-C键活化表现出优异的化学选择性。该反应具有出色的官能团耐受性，可应用于复杂活性药物成分的后期官能团化以及利用双无溶剂固态方法进行的连续正交交叉偶联。这些结果扩展了机械化学反应环境，将N-C键相互转化的化学方法拓展到固态环境友好型机械化学方法。
