德国亚琛工业大学Leonori, Daniele团队报道了硝基芳烃脱芳扩环合成多取代氮杂环丁烷。相关研究成果于2024年1月25日发表于国际顶尖学术期刊《自然—化学》。

功能化氮杂环的合成是发现、制造和发展高价值材料不可或缺的一部分。有效的杂环合成策略的可用性往往使特定环系统的频率，相对于生物活性引线的核心结构中的其他环系统有所偏差。例如，虽然六元和五元哌啶和吡咯烷在药物化学库中广泛存在，但七元氮杂环己烷基本上不存在，这留下了相当大的三维化学空间。

该文中，研究人员报道了一种以硝基转化为单线态硝基芳烃为中心，由简单的硝基芳烃通过光化学脱芳扩环制备复杂氮杂环丁烷的策略。这个过程是由蓝光介导的，在室温下发生，并将六元类苯骨架转化为七元环系统。接下来的氢解只需两步就可以生成氮杂环丁烷。研究人员通过合成几种哌啶类药物的氮杂环戊烷类似物，证明了该策略的实用性。

附：英文原文

Title: Synthesis of polysubstituted azepanes by dearomative ring expansion of nitroarenes

Author: Mykura, Rory, Snchez-Bento, Raquel, Matador, Esteban, Duong, Vincent K., Varela, Ana, Angelini, Lucrezia, Carbajo, Rodrigo J., Llaveria, Josep, Ruffoni, Alessandro, Leonori, Daniele

Issue&Volume: 2024-01-25

Abstract: The synthesis of functionalized nitrogen heterocycles is integral to discovering, manufacturing and evolving high-value materials. The availability of effective strategies for heterocycle synthesis often biases the frequency of specific ring systems over others in the core structures of bioactive leads. For example, while the six- and five-membered piperidine and pyrrolidine are widespread in medicinal chemistry libraries, the seven-membered azepane is essentially absent and this leaves open a substantial area of three-dimensional chemical space. Here we report a strategy to prepare complex azepanes from simple nitroarenes by photochemical dearomative ring expansion centred on the conversion of the nitro group into a singlet nitrene. This process is mediated by blue light, occurs at room temperature and transforms the six-membered benzenoid framework into a seven-membered ring system. A following hydrogenolysis provides the azepanes in just two steps. We have demonstrated the utility of the strategy with the synthesis of several azepane analogues of piperidine drugs.

DOI: 10.1038/s41557-023-01429-1

Source: https://www.nature.com/articles/s41557-023-01429-1