Novel synthetic studies of heterocycles containing nitrogen by reductive ring expansion of oximes and their application to synthesis of candidate compounds for clinical studies.

铝还原剂(DIBALH、AlHCl2等)与多种环型和无环型肟的还原重排反应用来买得起各种仲胺。该反应区域选择性地生成了一系列含氮的五元至八元双环杂环或三环杂环化合物，通过分步反应机理实现了三中心过渡态，因为沿本征反应坐标的势能曲线有两个极大值和部分苯阳离子中间体。阐明了取代基迁移的优先顺序，即越富电子的基团优先迁移，得到相应的化合物。介绍了它们在几种候选化合物(AVP拮抗剂、17β-HSD抑制剂、URAT-1抑制剂)的合成研究中的应用。因此，该反应可用于精细化学和药物化学的合成。

The reductive rearrangement of various cyclic and acyclic oximes with aluminum reductants (DIBALH, AlHCl2 etc.) was performed to afford various secondary amines. This reaction regioselectively afforded a variety of five- to eight-membered bicyclic heterocycles or tricyclic heterocycles containing nitrogen neighboring an aromatic ring.The reaction proceeds through a three-centered transition state via a stepwise mechanism, because the potential energy curve along the intrinsic reaction coordinate had two maxima and the partial phenonium cation intermediate. The preference of the migration of a substituent was clarified that the more electron-rich group migrated preferentially to give the corresponding compounds. Their application to synthetic studies of several candidate compounds (AVP antagonist, 17 beta-HSD inhibitor, URAT-1 inhibitor) for clinical studies was demonstrated. Therefore, this reaction could be of practical use for the synthesis of fine chemistry and medicinal chemistry.