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

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 r...

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Detalles Bibliográficos
Autores principales: Spedding, Harold, Karuso, Peter, Liu, Fei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6150284/
https://www.ncbi.nlm.nih.gov/pubmed/29088108
http://dx.doi.org/10.3390/molecules22111871
Descripción
Sumario: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.