Stereo- and regioselective synthesis of polysubstituted chiral 1,4-oxazepanes.
J Org Chem
; 78(3): 872-85, 2013 Feb 01.
Article
em En
| MEDLINE
| ID: mdl-23305339
ABSTRACT
The number of cyclic molecular scaffolds available to medicinal chemists remains limited, and simple structures such as oxazepanes are still made using multistep procedures, including a number of protection/deprotection steps and purifications. We report herein an expedient and efficient synthesis of chiral polysubstituted oxazepanes. The developed method relies on a regio- and stereoselective 7-endo cyclization through haloetherification. Mechanistic studies using a combination of computations and experiments confirmed the expected role of the asymmetry of the chiral bromonium intermediate on the haloetherification regioselectivity. Computations also suggested that the bromonium intermediate is formed with no transition state; hence, the stereoselectivity is controlled primarily by the conformation of the substrate. Applied to a set of 16 substrates, tetra- and pentasubstituted oxazepanes were prepared with good yields and moderate to excellent regio- and stereoselectivities.
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Base de dados:
MEDLINE
Assunto principal:
Oxazepinas
/
Éteres
Idioma:
En
Revista:
J Org Chem
Ano de publicação:
2013
Tipo de documento:
Article