Synthesis of Substituted Oxo-Azepines by Regio- and Diastereoselective Hydroxylation

Abstract

Substituted seven-membered N-heterocycles are prevalent bioactive epitopes and useful synthons for preparing enzyme inhibitors or molecular recognition systems. To fully exploit the chemical properties of this flexible N-heterocycle scaffold, efficient methods for its diverse functionalization are required. Here we utilize the late-stage oxidation of tetrahydroazepines as an approach to access densely functionalized oxo-azepines in a total of 8 steps and ~30% overall yield from commercially available starting materials. Hydroboration of tetrahydroazepines proceeded with diastereoselectivity in a substrate-dependent manner to yield regioisomeric azepanols before their oxidation to the corresponding oxo-azepines. Regioselectivity of the hydroboration step may be improved moderately by a rhodium catalyst, albeit with loss of conversion to a competing hydrogenation pathway. Overall our method allows efficient access to azepanols and oxo-azepines as versatile epitopes and synthons with a high degree of diastereoselectivity and moderate regioselectivity.

Synthesis, Characterization and Biological Screening of Azepine Derivative: 2-hydroxy-1,3-di(naphthalene-2-yl)-1H-benzo[b]azepine-5(4H)one

“…Even azepine based drugs are used for the treatment of Parkinson ' s and Alzheimer ' s diseases since they exhibit anticonvulsant activity and may be used as minor tranquilizers. Some azepine derivatives (Triazepine) affects the central nervous system and exhibit pesticidal and herbicidal activities [10,11]. Due to the unique flexibility of the seven-membered ring, it has received much more attention in both materials and the medicinal industry.…”