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Overcoming product inhibition in catalysis of the intramolecular Schmidt reaction
Hashim F Motiwala1, Charlie Fehl, Sze-Wan Li
1Department of Medicinal Chemistry, University of Kansas, Delbert M. Shankel Structural Biology Center, 2034 Becker Drive, West Campus, Lawrence, Kansas 66047, USA.
Abstract:
A method for carrying out the intramolecular Schmidt reaction of alkyl azides and ketones using a substoichiometric amount of catalyst is reported. Following extensive screening, the use of the strong hydrogen-bond-donating solvent hexafluoro-2-propanol was found to be consistent with low catalyst loadings, which ranged from 2.5 mol % for favorable substrates to 25 mol % for more difficult cases. Reaction optimization, broad substrate scope, and preliminary mechanistic studies of this improved version of the reaction are described.
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