1,3-dipolar cycloaddition carbon-nitrogen bond formation

It is well known that alkyl azides also behave as 1,3-dipoles in intramolecular thermal cycloaddition reactions. The formation of two carbon-nitrogen bonds leads to triazolines, which are usually not stable. They decompose after the loss of nitrogen to aziridines, diazo compounds, and heterocyclic imines. There are a limited number of examples reported in which the triazoline was isolated [15]. The dipolar cycloaddition methodology has been extremely useful for the synthesis of many natural products with interesting biological activities [16], In recent years, the cycloaddition approach has allowed many successful syntheses of complex molecules which would be difficult to obtain by different routes. For instance, Cha and co-workers developed a general approach to functionalized indolizidine and pyrrolizidine alkaloids such as (-i-)-crotanecine [17] and (-)-slaframine [18]. The key step of the enantioselective synthesis of (-)-swainsonine (41), starting from 36, involves the construction of the bicyclic imine 38 by an intramolecular 1,3-dipolar cycloaddition of an azide derived from tosylate 36, as shown in Scheme 6 [ 19). 

Erba et al. (102) observed a novel formation of pyrrole imines 181 from the 1,3-dipolar cycloaddition of mtinchnones 179 and 5-amino-l-aryl-4,5-dihydro-4-methylene-1,2,3-triazoles 180 (Table 10.4). Treatment with benzaldehyde yielded 3-formylpyrroles (182). The reaction presumably involves loss of carbon dioxide, nitrogen, and morpholine from the initial cycloadduct. Unsymmetrical mtinchnones behave regioselectively and furnish products derived from bonding between C(2) of... 

The 1,3-dipolar cycloaddition of nitrones to alkenes has been shown to be very useful in the field of synthesis of alkaloids. The reaction is normally efficient and the inherent features of carbon-carbon bond formation, oxygen transfer and nitrogen incorporation have been joined by high regioselectivity and even stereoselectivity (79ACR396). The... 

Electrophilic carbenes and carbenoids can readily react with the nitrogen atom of a carbon-nitrogen multiple bond to effect immonium (cycloimmon-ium) or nitrile ylide formation. 1,3-Dipolar cycloaddition of these ylides... 

Tethering the alkene to the carbon atom of the nitrone allows the preparation of cw-l,2-disubstituted cycloalkanes such as 212. Examples in which the alkene is tethered to the nitrogen atom of the nitrone are also common. Thus, addition of formaldehyde to the hydroxylamine 213 promoted formation of the intermediate nitrone and hence the cycloadduct 214 (3.140). " Subsequent transformations led to the alkaloid luciduline. This synthesis illustrates a useful feature of the 1,3-dipolar cycloaddition reaction of nitrones, in that it provides an alternative to the Mannich reaction as a route to (3-amino-ketones, via reductive cleavage of the N-0 bond in the isoxazolidine and oxidation of the 1,3-amino-alcohol product. In another example of such an intramolecular cycloaddition reaction, the bridged bicyclic product 217, used in a synthesis of indolizidine 209B, was formed by addition of an aldehyde to the hydroxylamine 215, followed by heating the intermediate nitrone 216 (3.141).142... 

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