Reactions of alkyl azides and ketones as mediated by Lewis acids:: Schmidt and Mannich reactions using azide precursors

The Lewis acid-promoted reactions of alkyl azides with ketones can afford several products. Chief among these result from a Schmidt-like insertion of the azide into the carbon-carbon bond adjacent to the carbonyl group. Alternatively, an acid-promoted rearrangement of the azide to an iminium species can occur, mostly with benzylic azides; the iminium species can then be trapped by the enol of the carbonyl compound in a variation of the Mannich reaction. The scope of each of these reactions, the dependence of the observed products upon azide and ketone structure, and the nature of acid promotion are discussed. In broad strokes, cyclohexanones and other cyclic ketones react in the presence of TiCl4 to afford insertion products, whereas the Mannich route predominates when benzyl azide and triflic acid are used. The features that lead to each reaction type and possible mechanistic implications are discussed.