Cycloaddition reactions 1.2.4- triazolines

The cycloaddition reaction of compound 6 with N-aryl- and N-aralkylazides 23 was also investigated (967(52)7183). Thiadiazabicyclo[3.1.0]hexene derivatives 25 were obtained from the labile triazoline intermediate 24 through nitrogen elimination. This bicyclic system underwent thermal transformation, producing thiadiazine dioxides 26 as the main product together with thiazete dioxides 27 and pyrazoles 28. 

The regioselectivity observed in these reactions can be correlated with the resonance structure shown in Fig. 2. The reaction with electron-rich or electron-poor alkynes leads to intermediates which are the expected on the basis of polarity matching. In Fig. 2 is represented the reaction with an ynone leading to a metalacycle intermediate (formal [4C+2S] cycloadduct) which produces the final products after a reductive elimination and subsequent isomerisation. Also, these reactions can proceed under photochemical conditions. Thus, Campos, Rodriguez et al. reported the cycloaddition reactions of iminocarbene complexes and alkynes [57,58], alkenes [57] and heteroatom-containing double bonds to give 2Ff-pyrrole, 1-pyrroline and triazoline derivatives, respectively [59]. 

The nonsymmetrical quinolizidine 373 was obtained from the acyclic symmetrical precursor 372 by means of a reaction sequence comprising azide formation, intramolecular 1,3-dipolar cycloaddition, thermal triazoline fragmentation to a diazoalkane, and Michael addition individual steps, as shown in Scheme 85 <2005CC4661>. 

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). 

Cycloaddition reactions of dimethyl benzylidenemalonate 262 with azides provide triazolines 263. All compounds 263, except one with R = Ph, are stable in xylene at 110 °C. The phenyl derivative eliminates molecular nitrogen to give dimethyl l,3-diphenylaziridine-2,2-dicarboxylate 264. At elevated temperature, the aziridine system is not... 

Cyclononadiene reacted with aryl azides 91 regioselectively to give triazolines 92 [87]. In the cycloaddition reactions of aryl azides with tetramethylallene (excess), electron-deficient azides afforded better yields of triazolines [88]. 

Substituted l,2,4-triazoline-3,5-diones are excellent dienophiles which react rapidly at room temperature with oxepins, but particularly with the arene oxide valence tautomer. A similar [4+2] cycloaddition reaction between the episulfide tautomer of thiepin (44) and 4-phenyl-l,2,4-triazoline-3,5-dione has been reported (74AG(E)736>. Benzene episulfide (the valence tautomer of thiepin 44) was generated in situ by thermal decomposition of the diepisulfide (151) at 20 °C and trapped as a cycloadduct at the same temperature (equation 34). A 1,3-dipolar cycloaddition reaction between thiepin (152) and diazomethane has been reported (56CB2608). Two possible cycloadduct products are shown since the final structure has not been unequivocally established (equation 35). 

Warrener and co-workers (25) exploited a 1,3-dipolar cycloaddition reaction to synthesize a 7-azanorbomane 124 (Scheme 9.25). The cyclobutene-1,2-diester 121 underwent smooth cycloaddition with benzyl azide to give the triazoline 122, which... 

Several cycloaddition reactions of vinylthiophene and vinylbenzo[6]thiophene are known. 2-Vinylthiophene easily adds 4-phenyI-l,2,4-triazoline-3,5-dione to give (308) (74JA5591). 2-Vinyl-thiophenes also undergo stereospecific cycloaddition with singlet oxygen to produce the corresponding endoperoxides (Scheme 87) (75TL4471). 

The cycloaddition of azides to multiple -ir-bonds is an old and widely used reaction. Organic azides are well known to behave as 1,3-dipoles in thermal cycloaddition reactions.178 The first example of this reaction was observed by Michael in 1893.179 Since then the addition of azide to carbon-carbon double and triple bonds has become the most important synthetic route to 1,2,3-triazoles, -triazolines and their derivatives.180-184 The cycloadditions of simple organic azides with electron-rich dipolarophiles are LUMO controlled.3 Since the larger terminal coefficients are on the unsubstituted nitrogen in the azide and unsubstituted terminus in the dipolarophiles, the 5-substituted A2-triazolines are favored, in agreement with experiment.185-187 Reactions with electron-deficient dipolarophiles are HOMO controlled, and... 

Cycloaddition reactions of phenyl and tosyl azides to the strained double bond in cyclopropenes have been investigated.170il The reaction products from 3,3-dimethylcyclopropene indicate that the initially formed intermediate is a normal 1,3-dipolar adduct. Tetrachlorocyclopropene yields the primary adducts with several aryl azides. 70b However, cyclopropenedicarboxyl ester gives only unstable triazolines with phenyl and methyl azides.170 ... 

Based on results presented in Scheme 37, Logothetis suggested that the thermal decomposition products from the olefinic azides in the scheme are derived from triazoline intermediates formed by an intramolecular cycloaddition reaction and not by fragmentation of the azido group to a nitrene.100 However, allyl azide and 4-azido-l-pentene do not undergo internal cycloaddition because of the strain in the corresponding triazoline they fail to give aziridines and imines upon thermolysis.100... 

Both i,2-241 242 and 1,4-dihydropyridines243 behave as enamines rather than as dienes244 in cycloaddition reactions with azides bearing electron-withdrawing groups, they provide a route for the preparation of bicycloazir-idines in quantitative yields via thermolysis of the intermediate triazolines (Scheme 60).241-242 The reactions of dienamines have been reviewed.245... 

Olefinic double bonds substituted with one or more electron-withdrawing groups show significant dipolarophilic activity in cycloaddition reactions with organic azides,43,276-278 similar to the electron-rich double bonds of enamines and enol ethers the reactivity is less pronounced in azide additions compared to that observed in diazomethane reactions.7 The first triazolines reported resulted by the action of aryl azides on benzoquinones.1,279-281 As a rule, stereospecific cis additions occur,32 which are usually unidirectional except in the case of methacrylic derivatives67 and certain alkenes bearing... 

Kim and O Shea have reported highly electrophilic additions of 4-substituted l,2,4-triazoline-3,5-diones with substituted alkenes by [2+2] cycloaddition reactions (Equation 33) <2004JA700>. A possible mechanism is depicted in Scheme 38. 

Some hetero double bond systems have been shown to enter [3 + 2] cycloaddition reactions with the mesoionic 1,3-dithiolones. Thus, the mesoionic 1,3-dithiolones (2) react with formaldehyde, prepared in situ by depolymerization of paraformaldehyde, with regiospecific formation of the 2-oxa-6,7-dithiabicyclo[2.2.1]heptanone derivatives (131). The corresponding reaction of (2) with the N=N double bond of dimethyl azodicarboxylate proceeds via cycloaddition yielding (132), and a similar reaction takes place between (2) and 4-phenyl-l,2,4-triazoline-3,5-dione (78CB3171). 

There have been only a few reports of reactions of this type including cycloaddition of dienes 157 with the powerful dienophile 4-phenyl-l,2,4-triazoline-3,5-dione <1996J(P1)2297> and stereoselective cycloaddition of the chiral nitrone 158 with a variety of dipolarophiles <2000JOC7000>. A rare example of intramolecular hetero-Diels-Alder reaction involving a 4-methylene-l,3-oxathiolan-5-one 3 -oxide is provided by the cycloaddition reaction of 159 to give 160 (Equation 42) <1998EJ02733>. 

Triazolines (202) obtained by 1,3-dipolar cycloaddition reactions lose nitrogen on pyrolysis or photolysis to give aziridines (203) in high yields. The isomeric imines (204) are also formed (68X2757). A higher ratio of aziridines (203) to imines (204) results from thermal reaction conditions than from the corresponding photolytic reaction (68x2757). 

The triazolines resulting from the various reaction schemes are predominantly A2-compounds the cycloaddition reactions of azomethinimines and nitrile ylides lead to A3-triazolines. The amidrazones are unique a A3- or A2-system results, depending on the presence or absence of N-2 substitution (84KGS1415). The rare A -compounds are presumed to result from the nonregioselective addition of diazomethane to the imine double bond (72LA9) or by fluorination of 3,6-diamino-s-tetrazine (67USP3326889 70USP3515603). 

Similar cycloaddition reactions of diphenylnitrilimine with pyrrolines and benzopyrroles yield variously substituted fused-ring triazolines 74 and 75 (85AP556). 

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