Asymmetric Schmidt Reaction of Hydroxyalkyl Azides with Ketones

An asymmetric equivalent of the Schmidt reaction permits stereocontrol in ring expansions of symmetrical cyclohexanones. The procedure involves the reaction of chiral 1,2- and 1,3-hydroxyalkyl azides with ketones under acid catalysis; the initial reaction affords an iminium ether that can be subsequ...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2003-07, Vol.125 (26), p.7914-7922
Main Authors: Sahasrabudhe, Kiran, Gracias, Vijaya, Furness, Kelly, Smith, Brenton T, Katz, Christopher E, Reddy, D. Srinivasa, Aubé, Jeffrey
Format: Article
Language:English
Subjects:
Azides - chemical synthesis
Azides - chemistry
Chemistry
Cyclohexanones - chemistry
Exact sciences and technology
Ketones - chemistry
Kinetics and mechanisms
Lactams - chemical synthesis
Lactams - chemistry
Models, Molecular
Organic chemistry
Reactivity and mechanisms
Stereoisomerism
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Summary:An asymmetric equivalent of the Schmidt reaction permits stereocontrol in ring expansions of symmetrical cyclohexanones. The procedure involves the reaction of chiral 1,2- and 1,3-hydroxyalkyl azides with ketones under acid catalysis; the initial reaction affords an iminium ether that can be subsequently opened with base. A systematic study of this reaction is reported, in which ketone substrates, chiral hydroxyalkyl azides, and reaction conditions are varied. Selectivities as high as ca. 98:2 are possible for the synthesis of substituted caprolactams, with up to 1,7-stereoselection involved in the overall process. The fact that either possible migrating carbon is electronically identical provides an unusual opportunity to study a ring-expansion reaction controlled entirely by stereoelectronic factors. The mechanism of the reaction and the source of its stereoselectivity are also discussed.
ISSN:0002-7863
1520-5126
DOI:10.1021/ja0348896