Unusual Tethering Effects in the Schmidt Reaction of Hydroxyalkyl Azides with Ketones:  Cation−π and Steric Stabilization of a Pseudoaxial Phenyl Group

The Lewis acid-promoted reactions of chiral 2-aryl-3-azido-1-propanols with 4-substituted cyclohexanones lead to iminium ethers and ultimately caprolactams (following a hydrolysis step). In this study, it is shown that these reactions afford variable ratios of products, depending on the electronic n...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2003-11, Vol.125 (46), p.13948-13949
Main Authors: Katz, Christopher E, Aubé, Jeffrey
Format: Article
Language:English
Subjects:
Azides - chemical synthesis
Azides - chemistry
Chemical reactivity
Chemistry
Cyclohexanones - chemistry
Exact sciences and technology
Lactams - chemical synthesis
Lactams - chemistry
Molecular Conformation
Organic chemistry
Reactivity and mechanisms
Stereoisomerism
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Summary:The Lewis acid-promoted reactions of chiral 2-aryl-3-azido-1-propanols with 4-substituted cyclohexanones lead to iminium ethers and ultimately caprolactams (following a hydrolysis step). In this study, it is shown that these reactions afford variable ratios of products, depending on the electronic nature of the phenyl group. These results are interpreted in the context of a cation−π stabilizing effect in the product-determining reaction intermediate. Remarkably, the best selectivity was obtained when an azidopropanol reagent containing a quaternary center was used; a control experiment showed that the high selectivity observed in this result depended upon the free rotation of the pseudoaxial aromatic group in the intermediate that affords the major product.
ISSN:0002-7863
1520-5126
DOI:10.1021/ja0382361