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.

官能化氮杂环的合成对于发现、制造和开发高价值材料至关重要。有效的杂环合成策略的可用性通常会使生物活性先导核心结构中特定环系统的频率偏向于其他环系统。例如，虽然六元和五元哌啶和吡咯烷广泛存在于药物化学库中，但七元氮杂环庚烷基本上不存在，这留下了很大的三维化学空间区域。在这里，我们报告了一种通过光化学脱芳环扩展从简单硝基芳烃制备复杂氮杂环庚烷的策略，该策略以硝基基团转化为单线态氮烯为中心。该过程由蓝光介导，在室温下发生，并将六元苯环框架转变为七元环系统。随后的氢解只需两步即可提供氮杂环庚烷。我们通过合成几种哌啶药物的氮杂环庚烷类似物证明了该策略的实用性。