Lactams, from acyl azides

The dimerization appears to be a characteristic of triplet nitrenes, since it occurs on sensitization by such compounds as benzophe-none. When 2-azidobiphenyl is irradiated in Ihe presence of a triplet quencher (penta-I,3-diene to inhibit the formation o( an azocompound, the main product iscarbazole (5.36), which is formed by internal insertion into an aromatic C—H bond. Other nitrenes may also participate in intramolecular insertion, and this allows lactams to be formed from acyl azides (5.37). 

In synthetic target molecules esters, lactones, amides, and lactams are the most common carboxylic acid derivatives. In order to synthesize them from carboxylic acids one has generally to produce an activated acid derivative, and an enormous variety of activating reagents is known, mostly developed for peptide syntheses (M. Bodanszky, 1976). In actual syntheses of complex esters and amides, however, only a small selection of these remedies is used, and we shall mention only generally applicable methods. The classic means of activating carboxyl groups arc the acyl azide method of Curtius and the acyl chloride method of Emil Fischer. 

A third approach to 3-amino-/3-lactams is by Curtius rearrangement of the corresponding acyl azides. These are readily prepared from r-butyl carbazides, available via photochemical ring contraction of 3-diazopyrrolidine-2,4-diones in the presence of f-butyl carbazate (c/. Section 5.09.3.3.2). Thus treatment of (201) with trifluoroacetic acid followed by diazotiz-ation gives the acyl azide (202) which, in thermolysis in benzene and subsequent interception of the resulting isocyanate with r-butanol, yields the protected 3-amino-/3-lactam (203) (73JCS(P1)2907). 

Dehydration. This reagent is useful for synthesis of acyl azides from carboxylic acids, NaCN, and pyridine, with tetrabutylammomum bromide as catalyst (75-95% yield). In combination with pyridine, it effects dehydration of oximes to nitriles in 80-90% yield, P-Lactams can be prepared directly in 40-75 )t yield from carboxylic acids and imines with the reagent (1 equiv,) and triethylamine (excess). In general, a mixture of cis- and rra/j5-azetidinones is formed. 

The use of acylnitiene cyclizations in the synthesis of diteipene alkaloids goes back to the early 1960s, and although much of the early work has been reviewed, selected examples are included here. The acyl azide (19), readily prepared from podocarpic acid, was irradiated to give the 8-lactam (20 20%), which has the azabicyclononane ring system of the diteipene alkaloids such as atisine. ... 

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