Pace Vittorio, Holzer Wolfgang, Meng Guangrong, Shi Shicheng, Lalancette Roger, Szostak Roman, Szostak Michal
Department of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, Althanstrasse 14, Vienna, 1090, Austria.
Department of Chemistry, Rutgers University, 73 Warren Street, Newark, NJ 07102, United States.
Chemistry. 2016 Oct 4;22(41):14494-8. doi: 10.1002/chem.201603543. Epub 2016 Aug 25.
Herein, we show that acyclic amides that have recently enabled a series of elusive transition-metal-catalyzed N-C activation/cross-coupling reactions are highly twisted around the N-C(O) axis by a new destabilization mechanism of the amide bond. A unique effect of the N-glutarimide substituent, leading to uniformly high twist (ca. 90°) irrespective of the steric effect at the carbon side of the amide bond has been found. This represents the first example of a twisted amide that does not bear significant steric hindrance at the α-carbon atom. The (15) N NMR data show linear correlations between electron density at nitrogen and amide bond twist. This study strongly supports the concept of amide bond ground-state twist as a blueprint for activation of amides toward N-C bond cleavage. The new mechanism offers considerable opportunities for organic synthesis and biological processes involving non-planar amide bonds.
在此，我们表明，最近能够实现一系列难以捉摸的过渡金属催化的N-C活化/交叉偶联反应的无环酰胺，通过酰胺键的一种新的去稳定化机制，在N-C(O)轴周围高度扭曲。已发现N-戊二酰亚胺取代基的独特作用，无论酰胺键碳侧的空间效应如何，都会导致均匀的高扭曲（约90°）。这代表了在α-碳原子上没有显著空间位阻的扭曲酰胺的第一个例子。(15)N NMR数据显示氮原子上的电子密度与酰胺键扭曲之间存在线性相关性。这项研究有力地支持了酰胺键基态扭曲的概念，作为酰胺向N-C键裂解活化的蓝图。这种新机制为涉及非平面酰胺键的有机合成和生物过程提供了相当多的机会。
