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

Abstract

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 TiCl 4 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.

Iron(III)‐Catalyzed Tandem Sequential Methanol Oxidation/Aldol Coupling

“…[22a] 2b, [3e] 2c, [29] 6, [19] 7b, [30] 9, [26] were in accordance to published data, 2e was fully characterized.…”

To Protonate or Alkylate? Stereoselective Brønsted Acid Catalysis of CC Bond Formation Using Diazoalkanes

“…Azides can suffer similar protonative decomposition pathways, [53] and the acid-stimulated rearrangement of electron-rich azides to Schiff bases is the basis for a number of efficient reactions. [54] In 2004, we reported the Brønsted acid promoted azide/olefin route to aziridine derivatives (Scheme 14). [19] Additionally, unsaturated imide substrates bearing a participating oxygen atom yield to formal aminohydroxylation when activated by Brønsted acid toward electron-rich azide compounds (Scheme 14).…”

Cerium Chloride (CeCl3·7H2O) as a highly efficient catalyst for one-pot Three-Component Mannich reaction

“…15 The conventional catalyst for the synthesis of β-amino carbonyl compounds of aldehydes, ketones and amines involve mainly organic and mineral acids like proline, [16][17][18] acetic acid, 19 p-dodecyl benzene sulfonic acid 20 and other Lewis acids. 21,22 They often suffer the drawbacks of long reaction times, harsh reaction conditions, toxicity and difficulty in product isolation. While searching for economical and better catalyst, we thought its worthwhile to perform a controlled reaction for one-pot threecomponent Mannich reaction catalyzed by cerium(III) chloride heptahydrate (CeCl 3…”