Nitrenes from vinyl azides

Although vinylnitrenes are not involved in the formation of 2ff-azirines from vinyl azides, such nitrenes must be invoked in order to explain the further reactions of the azirines (Scheme 2). Thermal or photochemical ring opening of the azirine to a nitrene, and subsequent 1,2-shifts explain the formation of ketenimines and benzyl cyanides. A competing electrocycliza-tion of the nitrene onto a phenyl substituent in the /(-position leads to the... 

The photoreactions of azides can in most cases be rationalized in terms of initial loss of nitrogen with the formation of nitrenes which undergo rearrangement, insertion or addition reactions. Further examples of rearrangement of the nitrenes derived from vinyl azides to 2H-azirines have been reported ... 

Photogenerated nitrenes can undergo cycloaddition with alkenes intermolecular reaction leads to aziridine products (5.38), and intramolecular reaction in vinyl azides gives azirines (5.39). The bicyclic azirine from phenyl azide has not been isolated, but it is the intermediate that best accounts for the formation of a substituted azepine when this azide is irradiated in the presence of a secondary amine (5.401. 

The question as to whether the thermal azirine formation proceeds through a vinyl nitrene intermediate or by a concerted mechanism is not as yet resolved. A nitrene intermediate seems most probable on the basis of its similarity with cyclopropene formation from alkenylcarbenesM>> and because either thermal or photochemical decomposition of vinyl azides yields die azirines (Table XI). 

The base-catalyzed condensation of a-azido esters and ketones with aromatic aldehydes has recently been developed as a new vinyl azide synthesis.42,43 The yields range from moderate to excellent in some cases. The thermal decomposition of ethyl a-azidocinnamate (87) in xylene gives only 2-ethoxycarbonylindole (88).44 The unstable 2-ethoxycarbonyl-3-phenyl-l-azirine could be detected if the thermolysis was carried out at a lower temperature. This fact indicates that the 1-azirine is probably an intermediate leading to the indole, although the intermediacy of the vinyl nitrene could not be established. This result is similar to that observed by Isomura et al. on the pyrolysis of terminal vinyl azides.27,28... 

The mechanism of azirine formation has been discussed by L abbe.20 A priori, the three paths shown in Scheme 1 can be considered. From a comparison of the activation parameters27 for vinyl azide decomposition ( a 26-30 kcal/mol, AS - 3 to + 5 eu) with those for aryl azides (Ea 35-39, AS 18) it appears that the nitrene pathway a can be excluded, but a clear choice between paths b and c cannot be made at this time.20... 

Nitrene insertion. A nitrene insertion reaction is central to many syntheses of pyridoacridine alkaloids and their analogues. For example, Labarca et al. [87JCS(P1)927] have reported a three-step synthesis of a pyridoacridine 169 starting from 2-methoxyacridine-9-carboxaldehyde 165 (Scheme 26). Cyclization of the vinyl azide 166 by thermolysis is believed to involve a nitrene insertion reaction, to give either 167 or 168. 

The dediazoniation of the vinyl azide proceeds via vinyl nitrene. A variant of this synthesis enables the preparation of 3-(dialkylamino)-2//-azirines starting from A,7V-disubstituted acid amides [15] ... 

Few examples of azirine synthesis via enaminones are found in the literature, as azirines tend to undergo further reactions to give more stable compounds. One important method is the vinyl azide-olefin cycloaddition where the azides can be considered as derivatives of enaminones. The chemistry of this unique reaction has been reviewed (75AGE775). A recent example is included in Scheme 17, in which intramolecular cycloadditions of vinyl azides 53 furnish azirines 54 (87CB2003). In a similar reaction, the aziridinoindoies 56 are synthesized from 55 by insertion of the azide-derived nitrene into the olefinic bond (89H2029). 

In some instances the vinyl azide does not undergo the conversion to the 2/f-azirine and instead yields a nitrene, which adds to alkenes and dienes. This is seen with the azide 653 which, on irradiation through Pyrex, affords the corresponding nitrene that adds to alkenes stereospecifically to yield aziridines. Stereo specific addition to dienes is exemplified by the irradiation of the quinone azide 654 in the presence of trans,trans-hQX3,-2,4-diene. Aziridines do not result from this process and instead the stereoisomeric indole derivatives 655 and 656 are obtained. This process has been developed as a route to... 

Another conceptually unique approach in alkene aziridination has come from Johnston s labs. These workers shrewdly identified organic azides as nitrene equivalents when these compounds are in the amide anion/diazonium resonance form. Thus, when a range of azides were treated with triflic acid and methyl vinyl ketone at 0 °C, the corresponding aziridines were obtained, in synthetically useful yields. In the absence of the Bronsted acid catalyst, cycloaddition is observed, producing triazolines. The method may also be adapted, through the use of unsaturated imi-des as substrates, to give anti-aminooxazolidinones (Scheme 4.25) [32]. 

The reaction of azides with 1,3-dienes affords vinyl aziridines (through nitrene or azide cycloaddition), which can be converted to dihydropyrroles. It is also possible that dihydropyrroles are directly produced from azidodienes. 

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