Gao Pengcheng, Rahman Md Mahbubur, Zamalloa Alfredo, Feliciano Jessica, Szostak Michal
Department of Chemistry, Rutgers University, 73 Warren Street, Newark, New Jersey 07102, United States.
J Org Chem. 2023 Oct 6;88(19):13371-13391. doi: 10.1021/acs.joc.2c01094. Epub 2022 Sep 2.
Ground-state destabilization of the N-C(O) linkage represents a powerful tool to functionalize the historically inert amide bond. This burgeoning reaction manifold relies on the availability of amide bond precursors that participate in weakening of the n → π* conjugation through N-C twisting, N pyramidalization, and n electronic delocalization. Since 2015, acyl N-C amide bond activation through ground-state destabilization of the amide bond has been achieved by transition-metal-catalyzed oxidative addition of the N-C(O) bond, generation of acyl radicals, and transition-metal-free acyl addition. This Perspective summarizes contributions of our laboratory in the development of new ground-state-destabilized amide precursors enabled by twist and electronic activation of the amide bond and synthetic utility of ground-state-destabilized amides in cross-coupling reactions and acyl addition reactions. The use of ground-state-destabilized amides as electrophiles enables a plethora of previously unknown transformations of the amide bond, such as acyl coupling, decarbonylative coupling, radical coupling, and transition-metal-free coupling to forge new C-C, C-N, C-O, C-S, C-P, and C-B bonds. Structural studies of activated amides and catalytic systems developed in the past decade enable the view of the amide bond to change from the "traditionally inert" to "readily modifiable" functional group with a continuum of reactivity dictated by ground-state destabilization.
N-C(O)键的基态去稳定化是使历史上惰性的酰胺键功能化的有力工具。这种新兴的反应体系依赖于酰胺键前体的可用性，这些前体通过N-C扭曲、N原子的锥形化和n电子离域参与削弱n→π*共轭。自2015年以来，通过过渡金属催化的N-C(O)键氧化加成、酰基自由基的生成以及无过渡金属的酰基加成，实现了通过酰胺键的基态去稳定化对酰基N-C酰胺键的活化。本综述总结了我们实验室在开发通过酰胺键的扭曲和电子活化实现的新型基态去稳定化酰胺前体方面的贡献，以及基态去稳定化酰胺在交叉偶联反应和酰基加成反应中的合成应用。将基态去稳定化的酰胺用作亲电试剂能够实现大量以前未知的酰胺键转化，例如酰基偶联、脱羰偶联、自由基偶联以及无过渡金属偶联，以形成新的C-C、C-N、C-O、C-S、C-P和C-B键。过去十年中对活化酰胺和催化体系的结构研究使人们对酰胺键的看法从“传统上惰性的”官能团转变为“易于修饰的”官能团，其反应活性由基态去稳定化决定。
