Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, United Kingdom.
GSK Medicines Research Centre, Gunnels Wood Road, Stevenage, Herts SG1 2NY, United Kingdom.
Chem Rev. 2022 May 11;122(9):8181-8260. doi: 10.1021/acs.chemrev.1c00831. Epub 2022 Mar 14.
The chemistry of nitrogen-centered radicals (NCRs) has plentiful applications in organic synthesis, and they continue to expand as our understanding of these reactive species increases. The utility of these reactive intermediates is demonstrated in the recent advances in C-H amination and the (di)amination of alkenes. Synthesis of previously challenging structures can be achieved by efficient functionalization of sp moieties without prefunctionalization, allowing for faster and more streamlined synthesis. This Review addresses the generation, reactivity, and application of NCRs, including, but not limited to, iminyl, aminyl, amidyl, and aminium species. Contributions from early discovery up to the most recent examples have been highlighted, covering radical initiation, thermolysis, photolysis, and, more recently, photoredox catalysis. Radical-mediated intermolecular amination of (hetero)arenes can occur with a variety of complex amine precursors, generating aniline derivatives, an important class of structures for drug discovery and development. Functionalization of olefins is achievable in high anti-Markovnikov regioselectivity and allows access to difunctionalized structures when the intermediate carbon radicals are trapped. Additionally, the reactivity of NCRs can be harnessed for the rapid construction of N-heterocycles such as pyrrolidines, phenanthridines, quinoxalines, and quinazolinones.
氮中心自由基（NCRs）的化学在有机合成中有着广泛的应用，并且随着我们对这些反应性物种的理解不断加深，其应用范围还在不断扩大。这些反应性中间体在 C-H 胺化和烯烃的（二）胺化中的最新进展中得到了证明。通过对 sp 部分进行有效的官能化而无需预官能化，可以实现以前具有挑战性的结构的合成，从而使合成更快、更精简。这篇综述讨论了 NCRs 的生成、反应性和应用，包括但不限于亚胺基、氨基、酰胺基和铵物种。突出强调了从早期发现到最近的例子的贡献，涵盖了自由基引发、热解、光解，以及最近的光还原催化。通过各种复杂的胺前体可以实现（杂）芳环的自由基间胺化，生成苯胺衍生物，这是药物发现和开发的一类重要结构。通过高反马氏规则区域选择性可以实现烯烃的官能化，并且当中间碳自由基被捕获时，可以得到双官能化结构。此外，NCRs 的反应性可以用于快速构建 N-杂环，如吡咯烷、菲啶、喹喔啉和喹唑啉酮。
