Cycloaddition, 1,3-dipolar 1.2.3- triazoline ring

The interaction of diazomethane with 1-azirines was the first example of a 1,3-dipolar cycloaddition with this ring system (64JOC3049, 68JOC4316). 1,3-Dipolar addition produces the triazoline adduct (87). This material can exist in equilibrium with its valence tautomer (88), and allylic azides (89) and (90) can be produced from these triazolines by ring cleavage. 

In the first step, formyl ketone 14a reacts via its enol form 14b with tosyl azide in a 1,3-dipolar cycloaddition yielding intermediate 15. Its triazoline ring resolves into the a-diazo ketone 4 and 7V-formyl tosyl amide. 

N-Condensed 1,2,3-triazoline ring by 1,3-dipolar cycloaddition Double ring closure... 

The overall pathway for the conversion of the unsaturated azido ether 281 to 2,5-dihydrooxazoles 282 involves first formation of the dipolar cycloaddition product 287, which thermolyzes to oxazoline 282 or is converted by silica gel to oxazolinoaziridine 288. While thermolysis or acid-catalyzed decomposition of triazolines to a mixture of imine and aziridine is well-documented [71,73], this chemoselective decomposition, depending on whether thermolysis or exposure to silica gel is used, is unprecedented. It is postulated that acidic surface sites on silica catalyze the triazoline decomposition via an intermediate resembling 289, which prefers to close to an aziridine 288. On the other hand, thermolysis of 287 may proceed via 290 (or the corresponding diradical) in which hydrogen migration is favored over ring closure. 

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 three-nitrogen azimine 1,3-dipolar system in benzocinnolinium ylides26 undergoes cycloaddition with acetylenedicarboxylic esters to give azomethineimines, presumably derived from the initial A4-triazoline 1,3-cycloadduct by an electrocyclic ring opening (Scheme 8).2 7... 

The protected glucose derivative 165 was transformed by an intramolecular 1,3-dipolar cycloaddition of the azide to the allyl function, affording a fused 1,2,3-triazole 166 after in situ oxidation. The other stereoisomer gave under the same conditions aziridine 167, probably after ring opening of the intermediate 1,2,3-triazoline (Scheme 26) <2004T4959>. 

The dipolar cycloaddition of an alkyl azide with an alkene to form an aziridine has been exploited in the total synthesis of the alkaloid ( )-aspidospermidine <20050BC213>. Enone 353 was prepared in 11 steps from 3-ethoxycyclohexenone and coupled to 2-iodo nitrobenzene under Ullman cross-coupling conditions. The acetate group of 354 was hydrolyzed and the resulting alcohol converted to an azide using standard conditions in 75% overall yield. The cycloaddition of the azide with the enone was conducted in refluxing benzene for 3 days. The fused-ring aziridine 355 was the only product isolated. None of the initial dipolar cycloadduct triazoline was observed. The... 

D-Xylose has been converted to (25)-3-(indol-3-yl)propane-l,2-diol 237 by two different routes, one involving direct Fischer indolization of 238. The dibenzyl-dithioacetal 239 was elaborated to the fused triazoline 240 following reaction with MCPBA. Initial oxidation was followed by elimination of acetic acid allowing intramolecular 1,3-dipolar cycloaddition reaction to construct the triazole ring. The bicyclic iV,S -acetals 242 and 241 were prepared by reaction of the 2,3-0-isopropylidene-D-ribofuranose with 2-aminoethane thiol followed by Mitsunobu reaction. These products are considered analogues of castanosper-mine and australine. ... 

The addition of a 1,3-dipole to an alkene for the synthesis of five-membered rings is a classic reaction in organic chemistry and is used for the preparation of molecules of fimdamental importance. The 1,3-dipolar - mostly stereospecific - cycloaddition of an azide 1 with an alkene 2 leads to the formation of a triazoline 3 (Scheme 1). 

Mechanistically, these processes involve Lewis-acid activation of the enone, subsequent 1,3-dipolar cycloaddition of the enone with azide, and ring opening of the nnstable triazoline (Scheme 7.30). In the case of exocyclic enaminone formation, antiperiplanar arrangement of the methylene gronp (path a) with the diazoninm ion facilitated ring contraction a 1,3-H shift nltimately provided product via path a. On the other hand, migration of an axially oriented R gronp led to the observed endocyclic enaminones (path b). 

The synthesis of triazoles by 1,3-dipolar cycloaddition between azides and alkynes has been extensively studied recently with numerous synthetic applications in the field of click chemistry. However, the Huisgen cycloaddition between azides 39 and alkenes 40 (Scheme 41.9) although less studied offers interesting opportunities for the stereoselective formation of C N bonds in the context of natural products synthesis. The triazolines 41 thus formed are in fact good precursors of aziridines via ring contraction and expulsion of N2. 

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