College of Chemistry and Chemical Engineering, Key Laboratory of Chemical Additives for China National Light Industry, Shaanxi University of Science and Technology, Xi'an 710021, China.
Department of Chemistry, Rutgers University, 73 Warren Street, Newark, NJ 07102, USA.
Org Biomol Chem. 2022 Aug 3;20(30):5981-5988. doi: 10.1039/d2ob00412g.
Thioamides are 'single-atom' isosteres of amide bonds that have found broad applications in organic synthesis, biochemistry and drug discovery. In this themed issue, we present a general strategy for activation of N-C(S) thioamide bonds by ground-state-destabilization. This concept is outlined in the context of a full study on transamidation of thioamides with nucleophilic amines, and relies on (1) site-selective -activation of the thioamide bond to decrease resonance and (2) highly chemoselective nucleophilic acyl addition to the thioamide CS bond. The follow-up collapse of the tetrahedral intermediate is favored by the electronic properties of the amine leaving group. The ground-state-destabilization concept of thioamides enables weakening of the N-C(S) bond and rationally modifies the properties of valuable thioamide isosteres for the development of new methods in organic synthesis. We fully expect that in analogy to the burgeoning field of destabilized amides introduced by our group in 2015, the amide bond ground-state-destabilization activation concept will find broad applications in various facets of chemical science, including metal-free, metal-catalyzed and metal-promoted reaction pathways.
硫代酰胺是酰胺键的“单原子等排体”，在有机合成、生物化学和药物发现中有着广泛的应用。在本期主题中，我们提出了一种通过基态失稳来激活 N-C(S)硫代酰胺键的通用策略。这一概念是在对硫代酰胺与亲核胺的 transamidation 的全面研究背景下提出的，依赖于 (1) 硫代酰胺键的选择性 - 活化以降低共振，以及 (2) 对硫代酰胺 CS 键的高化学选择性亲核酰基加成。胺离去基团的电子性质有利于四面体中间体的后续崩塌。硫代酰胺的基态失稳概念能够削弱 N-C(S)键，并合理地修饰有价值的硫代酰胺等排物的性质，从而为有机合成中的新方法的发展提供思路。我们完全期望，与我们小组在 2015 年引入的不稳定酰胺领域的蓬勃发展类似，酰胺键基态失稳激活概念将在化学科学的各个方面得到广泛应用，包括无金属、金属催化和金属促进的反应途径。
