1,2,3 triazole 1,3-dipolar cycloaddition reactions

Azidofurazans and -furoxans undergo dipolar cycloaddition reactions with unsaturated compounds, in some cases regiospecifically. Thus, reaction of 3-amino-4-azidofurazan with l-morpholinyl-2-nitroethene (toluene, reflux, 70 hours) gives 4-nitro-l,2,3-triazole 204 in 87% yield (99MI1, 000KGS406). Cycloaddition of the same azide to alkynes was accomplished by formation of a mixture of position isomers 205 and 206. Regiospecific addition was observed only in singular cases... 

The 1,3-dipolar cycloaddition reactions to unsaturated carbon-carbon bonds have been known for quite some time and have become an important part of strategies for organic synthesis of many compounds (Smith and March, 2007). The 1,3-dipolar compounds that participate in this reaction include many of those that can be drawn having charged resonance hybrid structures, such as azides, diazoalkanes, nitriles, azomethine ylides, and aziridines, among others. The heterocyclic ring structures formed as the result of this reaction typically are triazoline, triazole, or pyrrolidine derivatives. In all cases, the product is a 5-membered heterocycle that contains components of both reactants and occurs with a reduction in the total bond unsaturation. In addition, this type of cycloaddition reaction can be done using carbon-carbon double bonds or triple bonds (alkynes). 

The 1,3-dipolar cycloaddition reaction of l,2-0-isopropylidene-a-D-xylopentodialdo-l,4-furanose oxime 262 with 3-(2-propynylthio)-l/f-l,2,4-triazole affords 3,4-bis-(l,2-0-isopropylidene-a-D-threofuranos 4-yl)-l,2,5-oxadiazole-2-oxide 263 as a main product (Scheme 68) <2000CHC393>. Synthesis of 3,4-bis(alkylamino)-l,2,5-oxadiazoles 265... 

Scheme 7.1 Click chemistry synthesis of 1,4-disubstituted-l,2,3-triazoles by a 1,3-dipolar cycloaddition reaction of organic azides with terminal acetylenes.

Diazo-substituted 1,2,3-triazoles undergo regiospecific dipolar cycloaddition reactions with electron-rich unsaturated compounds. Thus, 4-diazo-5-phenyl-4//-1,2,3-triazole (272, R = Ph) reacts with 1 -morpholinyl-2-nitroethene (273) in CH2CI2 at 20 °C by a net 1,7-cycloaddition and elimination of morpholine to give the product (274) (Scheme 53). 4-Diazo-5-cyano-4/f-1,2,3-triazole (272, R = CN) similarly adds to phenylacetylene to form compound (275) <87JOC5538>. 

Since the discovery of triazole formation from phenyl azide and dimethyl acetylenedicarboxylate in 1893, synthetic applications of azides as 1,3-dipoles for the construction of heterocychc frameworks and core structures of natural products have progressed steadily. As the 1,3-dipolar cycloaddition of azides was comprehensively reviewed in the 1984 edition of this book (2), in this chapter we recount developments of 1,3-dipolar cycloaddition reactions of azides from 1984 to 2000, with an emphasis on the synthesis of not only heterocycles but also complex natural products, intermediates, and analogues. 

TABLE 10.4. 1,3-DIPOLAR CYCLOADDITION REACTIONS OF MUNCHNONES AND METHYLENE TRIAZOLES ... 

Palladium catalyzed cyclization of l-iodo-2-((propa-l,2-dienyloxy)methyl)benzene 150 occurs with concomitant anion incorporation to furnish 4-substituted-l//-isochromenes 151 (Scheme 49) <1998TL435, 2000J(P1)3799>. In the presence of norbornadiene 152, the initially formed azide can undergo a further 1,3-dipolar cycloaddition reaction and fragmentation to give l-((l//-isochromen-4-yl)methyl)-l//-l,2,3-triazole 153 (Scheme 49) <1998TL435, 2001T7729>. 

Pyrrolo[3,4-dipolar cycloaddition reactions, lose nitrogen under mild conditions to give aziridines (71), cyclopropanes (73) and phosphiranes (75), respectively. Ar... 

Diazo-substituted 1,2,3-triazoles undergo regiospecific dipolar cycloaddition reactions with electron-rich unsaturated compounds. Thus, 4-diazo-5-phenyl-4//-l,2,3-triazole 410 reacts with l-morpholinyl-2-nitroethene by a net 1,7-cycloaddition and elimination of morpholine to give the product 411. 

Stoddart and co-workers have developed a variety of elegant stoppering strategies for dibenzylammonium-derived pseudorotaxanes. The 1,2,3-triazole stoppers present in [2]rotaxane 131 and [3]rotaxane 132 were generated by 1,3-dipolar cycloaddition reactions between bis(azidomethyl)-substituted cation and dication axles in the presence of di- z -butyl acetylenedicarboxylate <1996CEJ729, 1996TL6217>. 

The triazole-linked 3 -5 thymidine dimmer (xv) has been synthesized by utilizing the 1,3-dipolar cycloaddition reaction under microwave irradiation [28]. 

Dipolar cycloaddition of polyethylene glycol-supported azide with various dipolarophiles followed by acidic cleavage afforded 4- and 5-substituted-1,2,3-triazoles 05T4983>. Trimethylsilyl-directed 1,3-dipolar cycloaddition reactions in the solid-phase synthesis of 1,2,3-triazoles have been developed <05OL1469>. 

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