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Reactions of Alkyl Azides and Ketones as Mediated by Lewis Acids:  Schmidt and Mannich Reactions Using Azide Precursors

Pankaj Desai, Klaas Schildknegt, Konstantinos A. Agrios, Craig Mossman, Gregory L. Milligan and Jeffrey Aubé

*Department of Medicinal Chemistry, University of Kansas, Lawrence, Kansas 66045-2506, Email:

P. Desai, K. Schildknegt, K. A. Agrios, C. Mossman, C. Mossman, G. L. Milligan, J. Aubé, J. Am. Chem. Soc., 2000, 122, 7226-7232.

DOI: 10.1021/ja000490vs

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Lewis acid-promoted reactions of alkyl azides with ketones can afford several products. Cyclohexanones and other cyclic ketones react in the presence of TiCl4 to afford Schmidt-like insertion products, whereas an acid-promoted rearrangement of the azide to an iminium species can occur, mostly with benzylic azides and TfOH; the iminium species can then be trapped by enolates.

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proposed mechanisms

Key Words

ε-lactams, Schmidt reaction

ID: J48-Y2000