Vinyl azides cycloaddition reactions

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). 

Vinyl sulfones can function as acetylene equivalents through the elimination of sulfinic acid. Reck and coworkers prepared a series of vinyl sulfones for cycloaddition reactions with azides to prepare 1,2,3-triazole derivatives to be incorporated into new oxazolidinone antibacterial agents. Included in the series was the cycloaddition of l-fluoro-l-(phenylsulfonyl)ethylene with the oxizolidinone 156 to give, after elimination of phenylsulfonic acid, a 28% yield of a 1 7 mixture of the regioisomeric 4-and 5-fluorotriazoles (157 and 158) (Fig. 3.91). 

The 1,3-dipolarophiles participating in the [3+2] cycloaddition reaction with azides include carbon-carbon multiple bonds, such as alkynes, olefins, vinyl ethers and ketene acetals, but addition across C=N multiple bonds, such as in nitriles and isocyanates, C=S and P=C bonds is also observed. The yields observed for many of these reactions approach quantitative. 

The intramolecular [3+2] cycloaddition reaction of azides to olefin tethers is also observed. For example, vinyl-substituted biphenyl azide 69 undergoes the reaction on standing at room temperature to give the 1,2,3-triazoline 70 in quantitative yield . ... 

We became interested in this area of chemistry because we wished to prepare some new and highly electrophilic 2//-azirines with potential for use as dienophiles in the Diels-Alder reaction. Vinyl azides appeared to be the most promising precursors. Previously there had been only one report of the cycloaddition of 2H-azirines to a simple diene (cyclopentadiene) although highly activated dienes such as tetraphenylcyclopentadie-none and 1,3-diphenylisobenzofuran had been used to intercept some transient 2H-azirines. Our investigations led to the preparation of several new 2ff-azirines. Cycloaddition reactions with these provided access to some novel fused-ring aziridines. An outline of the results is included in Sections 6.2 and 6.3. 

Aryl and vinyl nitriles have been prepared very efficiently from the corresponding bromides by palladium-catalyzed reactions under microwaves. This energy source has been employed for the conversion of these nitriles into aryl and vinyl tetrazoles by cycloaddition reactions with sodium azide (Scheme 9.66). The direct transformation of aryl halides to the aryl tetrazoles in a one pot procedure could be accomplished both in solution and on a solid support [115], The reactions were complete in a few minutes, a reaction time considerably shorter than those previously reported for the thermal reactions. The cydoadditions were performed with sodium azide and ammonium chloride in DMF and, although no explosion occurred in the development of this work, the authors point out the necessity of taking adequate precautions against this eventuality. 

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 formation of 34 from 33 in the reaction of Scheme 42 is explained by a rapid intramolecular cycloaddition of the initially formed vinyl azide followed by loss of nitrogen.200... 

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. 

Hassner and co-workers have shown that the intramolecular azide-alkene cycloaddition reactions of azido vinyl j8-lactams primarily lead to cis fused triazolines. The triazoline 61, fused to a 6-membered ring, was formed exclusively as the cis-fused isomer and decomposed on treatment with silica gel to imine 66. On the other hand, the 8-membered ring fused triazoline 63 which was isolated as a cis trans mixture, on exposme to sUica, produced only aziri-... 

Later, Narasaka and coworkers reported that the scope of this transformation could be substantially improved with the use of Mn(III) catalysis [313]. These new reaction conditions allowed highly efficient employment of differently substituted simple non-activated alkyl-, aryl-, hetaryl- and even cydic vinyl azides 328 (Scheme 8.117). In addition, previously unreactive 1,3-diketones 33S could serve as feasible 1,3-dicarbonyl components in this formal [3 + 2] cycloaddition reaction, affording 2,3,5-tri-and 2,3,4,5-tetra-substituted pyrroles 336 in moderate to excellent yields... 

Also, bis-alkylthiocarbene undergoes the [4+1] cycloaddition reaction with a suitably substituted indol isocyanate to give the [4+1] cycloadduct in 72 % yield. This approach was utilized in the total synthesis of (+) phenserin . Numerous examples of vinyl isocyanates, generated from the corresponding carbonyl azides, in the presence of bis-alkylthiocarbene precursors afford the [4+1] cycloadducts, often in high yields . ... 

At the latest during the last two decades, it turned out that vinyl azides are not only compounds for experts in organic chemistry but also very useful and general tools in synthetic chemistry. Although these azides are known for about hundred years, efficient approaches, developed in the last 45 years, were necessary to supply the starting materials, which have been utilized to show the versatility of vinyl azides. This is demonstrated by reactions induced by thermolysis, photolysis, cycloaddition, or attack by electrophiles or... 

Just like the aryl azides 2, the vinyl azides 11 are more reactive in their cycloadditions with active methylene compounds than are alkyl azides. In 1970, Alfred Hassner et al. developed a general synthetic approach to 1-vinyl-1,2,3-triazoles 12 and 14, (Scheme 4.4) [6] by the cycloaddition of active methylene compounds 10 or 13 with vinyl azides 11 (or their precursors, the P-haloalkyl azides), in the presence of 1 equiv. of an alkoxide (NaOMe). Decarboxylation of the l- dnyl-5-substituted l,2,3-triazole-4-carboxylic acids 14 synthesized from the reaction of ethyl acetoacetate or ethyl benzoylacetate with vinyl and P-haloalkyl azides led to 1-vinyl-5-substituted 1,2,3-triazoles in almost quantitative yield [6]. 

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