Synthesis of 2,3,4,5-Tetrahydro-1,5-benzoxazepine Derivatives via Alkoxy Migration Induced by N–O Bond Cleavage of N-Aryl Isoxazolidines

Abstract

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.