Azides cycloadditions

An intramolecular version of an azide cycloaddition of 221 and 222 provided cyclopropylimines 224 and 225 via formation of triazoline 223 followed by extrusion of nitrogen with concomitant 1,2-hydrogen shift (Scheme 36) [58], The cyclization was found to be solvent dependent polar solvents such as DMF gave the best yields, whereas benzene gave several side products. 

Campidelli et al. have synthesized interesting linear and hyperbranched porphyrin polymers from CNTs via copper-catalyzed alkyne-azide cycloaddition (CuAAC) [122], Zinc porphyrin monomers containing an azide group and one or three alkyne groups were synthesized and chemically bound to alkyne functionalized SWCNTs via CuAAC. Depending upon the number of alkyne functionalities either linear (single alkyne) or dendrimer-like (triple alkyne) porphyrin polymers were produced (Fig. 5.9) [122],... 

CuAAC copper catalysed alkyne-azide cycloaddition... 

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... 

Further disadvantage of the alkyne-azide cycloaddition is the lack of regiospecificity. On the other hand, cycloadditions of azides to alkenes are, in most cases, regioselective and afford 1,5-disubstituted triazolines . Therefore, the regioselective cycloaddition of an azide to an alkene, followed by aromatization (see Section 4.01.5.3.1) is an alternative method for the synthesis of 1,2,3-triazoles. 

Following reports of efficient Cu(I)-catalyzed alkyne/azide cycloaddition on solid phase and in solution by Meldal [42] and Sharpless [43], respectively, the formerly obscure Huisgen reaction soared to prominence as a versatile tool for covalent chemical ligation. The so-called click reaction can be catalyzed by a number of copper sources in a variety of media (Equation 9.14). 

The 1,3-dipolar cycloaddition of azides combined with further synthetic transformations is a highly useful reaction for the synthesis of heterocycles and natural products. Even though the chemistry of azide cycloadditions has been known for... 

Azide cycloaddition to electron-deficient dipolarophiles is normally HOMO-dipole LUMO-dipolaro-phile controlled, whereas the reverse is true for electron-rich dipolarophiles. Products with an electron-deficient group at the 5-position or an election-rich group at the 4-position are favored electronically in intramolecular cycloadditions, steric constraints can be expected to outweigh these considerations. 

Intramolecular azide cycloaddition to an alkyne produces a triazole. Triazoles are typically much more stable than triazolines and are most often directly isolable. Thus, azide (213) cyclized in 89% yield to a triazole (Scheme 65).118 The azido enyne (214) presents an interesting case intramolecular cycloaddition... 

Click chemistry also found applications in peptides and peptidomimetics. Alkyne-azide cycloaddition between two peptide strands provided an efficient convergent synthesis of triazole ring-based P-tum mimics <07CC3069>. The synthesis of a-substituted prolines has been accomplished by microwave-assisted Huisgen 1,3-dipolar cycloaddition between azides and orthogonally protected a-propynyl proline in the presence of Cu(I) sulfate <07SL2882>. The synthesis of new trifluoromethyl peptidomimetics with a triazole moiety has been reported <07TL8360>. 

The reaction of azides with 1,3-dienes affords vinyl aziridines (through nitrene or azide cycloaddition), which can be converted to dihydropyrroles. It is also possible that dihydropyrroles are directly produced from azidodienes. 

The intramolecular azide cycloaddition has also been used in approaches to the aspidosperma alkaloids <2004TL919, 20050BC213>. The cycloaddition of 123 proceeds directly to aziridine 124 in 80% yield (Equation 28) <2004TL919>. This is an interesting transformation in that none of the initially formed triazoline is observed and because of the high regioselectivity of the addition. A conceptually related approach to the synthesis of cephalotaxine has also been reported <1997TL4347>. 

An example of an azide cycloaddition to an open-chain enamino ester (292) has also been reported giving (293) (76BSF2025). 4-Acyl-l,2,3-triazoles (249) have been obtained in fair yield by the reaction of the phenyl azide with a-keto vinyl chlorides (sszoBisee). 

Extension of diis methodology to nitrogenous compounds (Scheme 53) has been implemented via azide cycloadditions to dienes as a facile means of synthesis of functionalized pyrrolizidines. Recently a [2 -I- 3] methodology was developed (Scheme 54) that promises to have wide tqrplicability in the synthesis of cyclopentanoids, bridged systems and dihydrofurans. ... 

---