Nitrile compounds azide 1,3-dipolar cycloadditions

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). 

Fig. 2.3 shows the core structures of the most important 1,3-dipoles, and what they are all called. As with dienes, they can have electron-donating or withdrawing substituents attached at any of the atoms with a hydrogen atom in the core structure, and these modify the reactivity and selectivity that the dipoles show for different dipolarophiles. Some of the dipoles are stable compounds like ozone and diazomethane, or, suitably substituted, like azides, nitrones, and nitrile oxides. Others, like the ylids, imines, and carbonyl oxides, are reactive intermediates that have to be made in situ. Fig. 2.4 shows some examples of some common 1,3-dipolar cycloadditions, and Fig. 2.5 illustrates two of the many ways in which unstable dipoles can be prepared. 

To use 1,3 dipolar cycloadditions in a retrosynthetic sense, it is necessary to know what 1,3 dipoles are available. The list on pages 319-320 is representative of die more common and useful examples, although many others have been reported. Azides, diazo compounds, and nitrones are normally isolable compounds which can be added to a solution of an olefin. Other 1,3 dipolar species such as nitrile oxides and azomethine ylides are not stable molecules they must be generated in the reaction mixture in the presence of the olefin. As might be expected, many different ways to generate 1,3 dipoles have been developed. 

Disconnection of tetrazoles with a 1,3-dipolar cycloaddition in mind is easy to see once we realize that a nitrile (RCN) is going to be one of the components. It can be done in two ways disconnection of the neutral compound would require hydrazoic acid (HN3) as the dipole but the anion disconnects directly to azide ion. 

The selective synthesis of the 2-allyltetrazoles 55 by the three-component coupling reaction of the cyano compounds 54, allyl methyl carbonate 5b, and trimethylsilyl azide 42 was accomplished in the presence of Pd2(dba)3.CHCl3 and P(2-furyl)3 (Scheme 19) [55,56]. Most probably, the formation of (r)3-allyl)( ]5-tetrazoyl)-palladium complex 56 took place through [3 + 2] dipolar cycloaddition of 7r-allylpalladium azide 44 with the nitrile 54. The complex 56 thus formed would undergo reductive elimination to form the products 55. 

The 1,3-dipolar systems involved in the cycloaddition reaction with cumulenes include azides, nitrile oxides, nitrile imines, nitrones, azomethine imines and diazo compounds. However, some 1,3-dipolar systems are also generated in the reaction of precursors with catalysts. Examples include the reaction of alkylene oxides, alkylene sulfldes and alkylene carbonates with heterocumulenes. Carbon cumulenes also participate as 1,3-dipols in [3+2] cycloaddifion reactions. Examples include thiocarbonyl sulfides, R2C=S=S, and l-aza-2-azoniaallenes. 

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