Cycloaddition reactions azides

Akritopoulou-Zanze I, Gracias V, Djuric SW (2004) A versatile synthesis of fused triazolo derivatives by sequential Ugi/alkyne-azide cycloaddition reactions. Tetrahedron Lett 45 8439-8441... 

Fig. 10.13. Hammett plots of cycloaddition rates of substituted aryl azides with nucleophiUc, electrophilic, and unsubstituted alkenes showing the ambiphilic character of the azide cycloaddition. Reaction with maleic anhydride (electrophilic) is favored by donor substituents. Reaction with pyrroUdinocy-clohexene (nucleophilic) is favored by acceptor substituents.

A straightforward synthesis of fused dihydrotriazolo[l,5-Q ]pyrazinones and triazolobenzodiazepines by sequential Ugi/alkyne-azide cycloaddition reactions was recently demonstrated by Djuric et al. [55]. The couphng of the Ugi multi-component reaction with the intramolecular alkyne-azide cycloaddition provides access to highly functionaUzed heterocyclic ring systems in just two steps. 

Mechanistic investigations of copper(I)-catalysed alkyne—azide cycloaddition reactions to form 1,2,3-triazoles 12THC(28)1. 

Shelbourne M, Chen X, Brown T, El-Sagheer AH (2011) Fast copper-free click DNA ligation by the ring-strain promoted alkyne-azide cycloaddition reaction. Chem Commun 47(22) 6257-6259. doi 10.1039/clccl0743g... 

Mechanistic Investigations of Copper(I)-Catalysed Alkyne-Azide Cycloaddition Reactions... 

Chapter 1, Mechanistic Investigations of Copper(I)-Catalysed Alkyne-Azide Cycloaddition Reactions , by Buckley and Heaney is concerned with various mechanistic interpretations of thermal and metal-catalyzed reactions of organic azides and aUcynes, which result in the formation of 1,2,3-triazoles. 

In 2011, Wang and coworkers developed the regioselective organocatalytic enamide-azide cycloaddition reaction for the synthesis of 1,4,5-trisubstituted... 

Sulfonium ylides may be added to C N double bonds to yield aziridines in a formal [1 -t-2]-cycloaddition. Alkyl azides are decomposed upon heating or irradiating to yield ni-trenes, which may also undergo [ 1 + 2 -cycloaddition reactions to yield highly strained hetero-cycles (A.G. Hortmann, 1972). 

Dipolar cycloaddition reactions with azides, imines, and nitrile oxides afford synthetic routes to nitrogen-containing heterocycles (25—30). 

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... 

Similarly, the regiospecific 1,3-dipolar cycloaddition reaction of 1-methyl-1,2-dihydropyridines 41 with cyanogen azide (50a) and selected organic azides 50c and 50g afforded 2-methyl-2,7-diazabicyclo[4.1.0]hept-4-enes 57, which can be elaborated to 1-methyl-l,2,5,6-tetrahydropyridylidene-2-cyanamide (58) and 1-methyl-2-piperidylidenes 59a-d (85CJC2362). 

The authors have also elaborated a microwave-enhanced one-pot procedure [90] for the Huisgen 1,3-dipolar cycloaddition reaction. In a typical procedure, a pyrazinone with a triple bond connected to the core via C - O linkage, was reacted with a suitable benzylic bromide and NaNs in presence of the Cu(I) catalyst in a t Bu0H/H20 system under microwave irradiation (Scheme 26). The cycloaddition was found to proceed cleanly and with full regioselectivity. As the azide is generated in situ, this procedure avoids the isolation and purification of hazardous azides, which is especially important when handling the ahphatic ones, which are known to be toxic and explosive in nature. 

The NHCs have been used as ligands of different metal catalysts (i.e. copper, nickel, gold, cobalt, palladium, rhodium) in a wide range of cycloaddition reactions such as [4-1-2] (see Section 5.6), [3h-2], [2h-2h-2] and others. These NHC-metal catalysts have allowed reactions to occur at lower temperature and pressure. Furthermore, some NHC-TM catalysts even promote previously unknown reactions. One of the most popular reactions to generate 1,2,3-triazoles is the 1,3-dipolar Huisgen cycloaddition (reaction between azides and alkynes) [8]. Lately, this [3h-2] cycloaddition reaction has been aided by different [Cu(NHC)JX complexes [9]. The reactions between electron-rich, electron-poor and/or hindered alkynes 16 and azides 17 in the presence of low NHC-copper 18-20 loadings (in some cases even ppm amounts were used) afforded the 1,2,3-triazoles 21 regioselectively (Scheme 5.5 Table 5.2). 

Cycloaddition Reactions with Mesityl Azide, Diphenyldiazomethane, Isocyanides, and Benzonitrile... 

Surprisingly, in contrast to the reaction of the Si=P bond with mesityl azide, the reaction of 15a with diphenyldiazomethane resulted in the formation of the [2+l]-cycloadduct 35 (Scheme S).38 The bonding situation in 35 (Fig. 11) may be described in terms of a 7r-complex, by employing the Dewar-Chatt-Duncanson model, in which the Si=P bond acts as v donor and acceptor at the same time (Scheme 9). The corresponding [2+31-cycloaddition product 36 was generated only on thermal activation of 35. 

Gramlich PME, Wirges CT, Manetto A, Carell T (2008) Postsynthetic DNA modification through the copper-catalyzed azide-alkyne cycloaddition reaction. Angew Chem Int Ed... 

Some cycloaddition reactions of 4 are summarized in Scheme 1. This shows that silylene 4 undergoes reactions with nitriles [14], phosphaalkynes [15], silyl azides [16], diazabutadienes [17], 2,2 -bipyridyl and its derivatives [18, 19], a-ketoimines [19], and pyridine-2-aldimines [19]. 

The pyrido[l,2-tf][l,3,5]triazine-2,4(3//)-dione derivative 89 was obtained in a cycloaddition reaction of diphenyl-methyl isocyanate 90 with 2-pyridyl isocyanate 91 derived from the corresponding acyl azide via Curtius rearrangement <2002ARK438>. Compound 89 was also synthesized by the reaction of diphenylacetyl chloride 118 and picolinyl azide 116a in the presence of triethylamine (Scheme 11) <2002ARK438>. ... 

Benzocyclobutene, when generated by oxidation of its iron tricarbonyl complex, can function as the dipolarophile in 1,3-dipolar cycloaddition reactions with arylnitrile oxides (Scheme 113).177 Unfortunately the synthetic versatility of this type of process is limited because of the unreactivity of other 1,3-dipolar species such as phenyl azide, benzonitrile N-phenylimide, and a-(p-tolyl)benzylidenamine N-oxide.177... 

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