Intermolecular Cycloaddition Reactions with Azides

Cycloaddition Reactions with Azides for the Synthesis of Tetrazoles 9.7.1 Intermolecular Approaches... 

In the intermolecular reaction of the nitrene that is derived from tosyl azide with benzene, little of the A -tosylazepine (5) is obtained at normal pressures, but the yield is markedly increased when the reaction takes place under a high pressure of nitrogen for example, to 48% at ca 90 atm.In a similar reaction with dimethyl terephthalate, it is suggested that the reaction involves an initial [1,3] cycloaddition of the azide to the aromatic ring to give (6), rather than a nitrene reaction. 

Shea et al. investigated whether strain involved in alkenes affects reactivity and regiochemistry of the intermolecular 1,3-dipolar cycloaddition reaction [14]. Therefore, the addition of picryl azide (18) with a series of mono-and bicyclic olefins including frans-cycloalkenes and bridgehead alkenes was studied (Scheme 5). In the cases of czs-cyclooctene (16) and ci5-cyclononene (17), decomposition of the initially formed cycloadducts 19 and 20 followed... 

The preparation of 85, a structurally diverse analog of carbocyclic ribavarine (86), was reported using an intermolecular 1,3-dipolar cycloaddition reaction of cyclopentyl azide 84 with methyl propiolate [53]. 

For intramolecular 1,3-dipolar cycloadditions, the application of nitrones and nitrile oxides is by far most common. However, in increasing frequency, cases intramolecular reactions of azomethine ylides (76,77,242-246) and azides (247-259) are being reported. The previously described intermolecular approach developed by Harwood and co-workers (76,77) has been extended to also include intramolecular reactions. The reaction of the chiral template 147 with the alkenyl aldehyde 148 led to the formation of the azomethine ylide 149, which underwent an intramolecular 1,3-dipolar cycloaddition to furnish 150 (Scheme 12.49). The reaction was found to proceed with high diastereoselectivity, as only one diaster-eomer of 150 was formed. By a reduction of 150, the proline derivative 151 was obtained. 

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. 

With sodium azide as the trapping reagent, 141 yields cyclic allyl azides, which can immediately undergo an intermolecular 1,3-dipolar cycloaddition with added norbomadi-ene and the adducts eventually cleave off cyclopentadiene in a retro-Diels-Alder reaction to provide triazoles (Scheme 46). Sodium benzenesulflnate can also be nsed as a nncle-ophile. ... 

Recently, Chen and coworkers reported an efficient new method to construct a series of densely functionalized 4,5-dihydro-IH-azepine products 41 from the intermolecular reaction of alkyl azides with propargylic esters. In this approach, sequential reaction of vinyl-gold carbenoids 42 with allqrl azides and formation of vinyl imine intermediates 43 may be involved fScheme 4.14). Then a subsequent formal [4+3] cycloaddition with another molecule of vinyl-gold carbenoid 42 afford the desired azepine 41. 

Aryl-substituted pyridines and pyrimidines have been prepared by 2 - - 2-cycloadditions of alkynyl-substituted pyridines and pyrimidines with electron-rich dienes." The reactions proceed by formation of a bridged cycloadduct and subsequent thermal extrusion of ethylene. The pyridine moiety plays a crucial role for the success of the reaction. 2-Benzoylbenzoyl azides undergo facile cycUzation under acidic conditions to give substituted dibenzo[ / [l,5]-diazocines in good yields. The mechanism of the diazocine synthesis was assumed to proceed by an unprecedented intermolecular 2 - - 2-cyclization. 

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