硫代酰胺
化学
化学选择性
组合化学
过渡金属
立体化学
有机化学
催化作用
作者
Guangchen Li,Yang-Yang Xing,Hui Zhao,Jin Zhang,Xin Hong,Michal Szostak
标识
DOI:10.1002/anie.202200144
摘要
Thioamides represent highly valuable isosteric in the strictest sense "single-atom substitution" analogues of amides that have found broad applications in chemistry and biology. A long-standing challenge is the direct transamidation of thioamides, a process which would convert one thioamide bond (R-C(S)-NR1 R2 ) into another (R-C(S)-NR3 N4 ). Herein, we report the first general method for the direct transamidation of thioamides by highly chemoselective N-C(S) transacylation. The method relies on site-selective N-tert-butoxycarbonyl activation of 2° and 1° thioamides, resulting in ground-state-destabilization of thioamides, thus enabling to rationally manipulate nucleophilic addition to the thioamide bond. This method showcases a remarkably broad scope including late-stage functionalization (>100 examples). We further present extensive DFT studies that provide insight into the chemoselectivity and provide guidelines for the development of transamidation methods of the thioamide bond.
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