Efficient Nitrogen Ring-Expansion Process Facilitated by in Situ

J. Am. Chem. SOC. 1995,117, 8047-8048

Efficient Nitrogen Ring-Expansion Process Facilitated by in Situ Hemiketal Formation. An Asymmetric Schmidt Reaction

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Scheme 1

Vijaya Gracias, Gregory L. Milligan, and Jeffrey Aub6*

1

Department of Medicinal Chemistry, University of Kansas Lawrence, Kansas 66045-2506 Received April 19, 1995

We recently reported an intramolecular version of the Schmidt reaction' in which hydrazoic acid was replaced by an alkyl azide connected to the reactive ketone.2 This is an unusual example of intramolecularity because the analogous H+-promoted intermolecular reaction does not succeed at alL3 Given the potential utility of a general method for the intermolecular insertion of an N-alkyl group adjacent to a ketone, other conditions to effect the direct reaction of ketones with alkyl azides were examined. Of several Lewis acids tried, only TiCL was e f f e ~ t i v e . ~ However, this reaction tumed out to be severely limited, with poor (