Synthesis of 2,3,4,5-Tetrahydro-1,5-benzoxazepine Derivatives <i>via</i> Alkoxy Migration Induced by N–O Bond Cleavage of <i>N</i>-Aryl Isoxazolidines
2,3,4,5-Tetrahydro-1,5-benzoxazepine derivatives constitute an important class of heterocycles frequently found in pharmaceuticals. In this study, we developed an efficient and practical synthetic method for the construction of 2,3,4,5-tetrahydro-1,5-benzoxazepine cores starting from N-aryl isoxazolidines. The key step involves Lewis acid–mediated alkoxy migration induced by N–O bond cleavage using aluminum chloride, providing the desired heterocyclic scaffolds in good yields. This method offers a new route to access 2,3,4,5-tetrahydro-1,5-benzoxazepine frameworks and expands the utility of N-aryl isoxazolidines in heterocycle synthesis.
Authors
- Yoshimitsu Hashimoto (ORCID: https://orcid.org/0000-0002-2868-901X)
- Hitomi Chiaki
- 田村修
- Nobuyoshi Morita
- Kosaku Tanaka III
- Motoko Nishidate
Institutions
- Hokkaido University (JP)
- Showa Pharmaceutical University (JP)
Publication Details
- Journal
- Chemical and Pharmaceutical Bulletin
- Published
- 2026-06-18
- DOI
- https://doi.org/10.1248/cpb.c26-00150
- Primary Topic
- Synthesis and pharmacology of benzodiazepine derivatives
- Type
- article
- Field-Weighted Citation Impact
- 0.00