Lankelma Marianne, Olivares Astrid M, de Bruin Bas
Van 't Hoff Institute for Molecular Sciences (HIMS), Homogeneous, Supramolecular & Bio-Inspired Catalysis, University of Amsterdam, Science Park 904, 1098 XH, Amsterdam, The Netherlands.
Department of Chemistry, University of Rochester, 404 Hutchison Hall, Rochester, NY, 14627-0216, USA.
Chemistry. 2019 Apr 17;25(22):5658-5663. doi: 10.1002/chem.201900587. Epub 2019 Apr 1.
Radical cyclization via cobalt(III)-carbene radical intermediates is a powerful method for the synthesis of (hetero)cyclic structures. Building on the recently reported synthesis of five-membered N-heterocyclic pyrrolidines catalyzed by Co porphyrins, the [Co(TPP)]-catalyzed formation of useful six-membered N-heterocyclic piperidines directly from linear aldehydes is presented herein. The piperidines were obtained in overall high yields, with linear alkenes being formed as side products in small amounts. A DFT study was performed to gain a deeper mechanistic understanding of the cobalt(II)-porphyrin-catalyzed formation of pyrrolidines, piperidines, and linear alkenes. The calculations showed that the alkenes are unlikely to be formed through an expected 1,2-hydrogen-atom transfer to the carbene carbon. Instead, the calculations were consistent with a pathway involving benzyl-radical formation followed by radical-rebound ring closure to form the piperidines. Competitive 1,5-hydrogen-atom transfer from the β-position to the benzyl radical explained the formation of linear alkenes as side products.
通过钴（III）-卡宾自由基中间体进行的自由基环化反应是合成（杂）环结构的一种有效方法。基于最近报道的钴卟啉催化合成五元氮杂环吡咯烷，本文介绍了由[Co（TPP）]催化直接从直链醛合成有用的六元氮杂环哌啶的方法。哌啶的总收率较高，少量直链烯烃作为副产物生成。进行了密度泛函理论（DFT）研究，以更深入地了解钴（II）-卟啉催化形成吡咯烷、哌啶和直链烯烃的机理。计算结果表明，烯烃不太可能通过预期的1,2-氢原子转移到卡宾碳上形成。相反，计算结果与一条涉及苄基自由基形成，随后通过自由基反弹闭环形成哌啶的途径一致。从β位到苄基自由基的竞争性1,5-氢原子转移解释了直链烯烃作为副产物的形成。
