Acetylene derivs cycloaddition, 1,3-dipolar

The thiazofurin acyclic analog 925 was prepared from 924 as shown in the scheme (87H947). 1,3-Dipolar cycloaddition of the acetylenic derivative 927 to the diazo derivative 926 gave the pyrazole 928, whose amidation and debenzylation gave 929 (93MI11). 

Potts and Hsia219 prepared unsaturated 6-oxo-6H-pyrido [ 1,2-a] pyrimidines (165) by the 1,4-dipolar cycloaddition of dipolarophilic acetylene derivatives to pyrimido[l,2-a]pyrimidine betaines (164). 

Cycloaddition of thiazolium azomethine ylides with dialkyl acetylenedicarboxylates 61 provides another approach to pyrrolo[2,1 -bjthiazoles 64 <070L4099>. Quatemization of 2-methylthiothiazole with trimethylsilylmethyl trifluoromethanesulfonate (TMSChkOTf) and subsequent fluoride-induced desilylation of the resulting (trimethylsilyl)methylammonium salt generate the acyclic azomethine ylide 62. This ylide readily participates in 1,3-dipolar cycloadditions with acetylene derivatives 61 to give adducts 63, which undergo spontaneous elimination of methylmercaptan to give the A-fuse cl thiazoles 64. ... 

Reaction of quinazoline with phenacyl bromides and subsequently with dimethyl acetylenedicarboxylate or ethyl propiolate in propylene oxide at ambient temperature gave the pyrrolo[l,2-c]quinazolines 47. The latter are formed in a [3 + 2] dipolar cycloaddition between the quinazolinium ylides 46, generated in situ, and the acetylene derivatives. 

Stereoselective 1,3-dipolar cycloaddition of the azomethine imine 283, obtained by reacting acetaldehyde and the dihydropyrazolo[4,3-d]-pyridazin-4-one 282, with the acetylenic derivative 284 resulted in the construction of the second fused pyrazole ring of 285. Condensation of 282 with the dialdoglucopyranose 286 instead of acetaldehyde gave the aldose azomethine imine 287, which added 284 to give the C-nucleoside 288 carrying two carbohydrate moieties (93FA231) (Scheme 87). 

The most conunon synthetic procedure for the preparation of perfluoroalkylated 1,2,3-triazole derivatives is 1,3-dipolar cycloaddition of azides to diverse unsaturated dipolarophiles containing perfluoroalkyl substituents. Thus, in 1966 Carpenter et al. carried out the cycloaddition of benzyl azide to perfluoroalkyl substituted acetylene derivatives leading to the formation of trifluoro-methyl-l,2,3-triazolines and 1,2,3-triazoles [39]. In this paper a synthesis of l-benzyl-4,5-bistrifluoromethyl-l,2,3-triazole 31 from hexafluoro-2-butyne was described. 

Triazole derivatives are very interesting compounds that can be prepared by 1,3-dipolar cycloadditions between azides and alkynes. Loupy and Palacios reported that electron-deficient acetylenes react with azidoethylphosphonate 209 to form the regioisomeric substituted 1,2,3-triazoles 210 and 211 under microwaves in solvent-free conditions (Scheme 9.65) [114]. This procedure avoids the harsh reaction conditions associated with thermal cycloadditions (toluene under reflux) and the very long reaction times. 

Use of unsubstituted acetylene as a substrate in 1,3-dipolar cycloadditions with azides results in 4,5-unsubstituted triazoles. The reactions have to be carried out under pressure. In an example given in Equation (23) showing synthesis of an antibacterial agent, a solution of azide 1049 in dimethoxyethane is transferred to a pressure bomb that is then charged with acetylene and heated at 90 °C for 12 h to give triazole derivative 1050 in 74% yield <2003BMC35>. 

Reactions of salts of 1,2,3-triazole with electrophiles provide an easy access to 1,2,3-triazol-jV-yl derivatives although, usually mixtures of N-l and N-2 substituted triazoles are obtained that have to be separated (see Section 5.01.5). Another simple method for synthesis of such derivatives is addition of 1,2,3-triazole to carbon-carbon multiple bonds (Section 5.01.5). N-l Substituted 1,2,3-triazoles can be selectively prepared by 1,3-dipolar cycloaddition of acetylene or (trimethylsilyl)acetylene to alkyl or aryl azides (Section 5.01.9). 

Pinho e Melo et al. (89) employed an intramolecular miinchnone cycloaddition to constmct several l/7-pyrrolo[l,2-c]thiazole derivatives from N-acylthiazolidines and acetic anhydride. Martinelli and co-workers (90,91) employed an intramolecular miinchnone cycloaddition to craft a series of 4-keto, 5,6,7-tetrahydroindoles (168-171) in two steps. The requisite acetylenic precursors were prepared from glutaric anhydride (or 3-methylglutaric anhydride). The overall sequence is illustrated for the synthesis of 168. An electrophilic acetylenic unit appears to be necessary for successful intramolecular 1,3-dipolar cycloaddition. 

Dumitrascu and co-workers (52) transformed 4-halosydnones into 5-halopyr-azoles by cycloaddition with DMAD and methyl propiolate followed by retro-Diels-Alder loss of CO2. Turnbull and co-workers (194) reported that the cycloadditions of 3-phenylsydnone with DMAD and diethyl acetylenedicarboxylate to form pyrazoles can be achieved in supercritical carbon dioxide. Nan ya et al. (195) studied this sydnone in its reaction with 2-methylbenzoquinone to afford the expected isomeric indazole-4,7-diones. Interestingly, Sasaki et al. (196) found that 3-phenylsydnone effects the conversion of l,4-dihydronaphthalene-l,4-imines to isoindoles, presumably by consecutive loss of carbon dioxide and A-phenylpyrazole from the primary cycloadduct. Ranganathan et al. (197-199) studied dipolar cycloadditions with the sydnone 298 derived from A-nitrosoproline (Scheme 10.43). Both acetylenic and olefinic dipolarophiles react with 298. In... 

Avalos and co-workers (220-228) extensively investigated the 1,3-dipolar cycloaddition chemistry of 2-aminothioisomiinchnones with both acetylenic and olefinic dipolarophiles. For example, sugar derivatives of the mesoionic imi-dazo[2,l-Z7]thiazolium-3-olate system react regioselectively with a variety of acetylenic dipolarophiles [DMAD, diethyl azodicarboxylate (DEAD), methyl propiolate, ethyl phenylpropiolate] to give the corresponding imidazo[l,2-a]pyr-idin-4-ones (e.g., 323) following sulfur extrusion from the not isolable cycloadducts (220). Similarly, these thioisomtinchnones react with diethyl azodicarboxylate and arylisocyanates in the expected fashion (221), and also with aryl aldehydes to form episulfides (222). 

Zinc chloride-doped natural phosphate was shown to have catalytic behavior in the 1,3-dipolar cycloadditions of nucleoside acetylenes with azides to form triazolonucleosides <99SC1057>. A soluble polymer-supported 1,3-dipolar cycloaddition of carbohydrate-derived 1,2,3-triazoles has been reported <99H(51)1807>. 2-Styrylchromones and sodium azide were employed in the synthesis of 4(5)-aryl-5(4)-(2-chromonyl)-1,2,3-triazoles <99H(51)481>. Lead(IV) acetate oxidation of mixed bis-aroyl hydrazones of biacetyl led to l-(a-aroyloxyarylideneamino)-3,5-dimethyl-l,2,3-triazoles <99H(51)599>. Reaction of 1-amino-3-methylbenzimidazolium chloride with lead(fV) acetate afforded l-methyl-l/f-benzotriazole <99BML961>. Hydrogenation reactions of some [l,2,3]triazolo[l,5-a]pyridines, [l,2,3]triazolo[l,5-a]quinolines, and [l,2,3]triazolo[l,5-a]isoquinolines were studied <99T12881>. 

Kobayashi et a/.392 have studied the 1,4-dipolar cycloadditions of DMAD to enaminodithiocarboxylates derived from dihydroquinolines. Addition of acetylene to 351 gave the spirocycloadduct 352 which did... 

Diazomethane is an electron-rich 1,3-dipole, and it therefore engages in Sustmann type I 1,3-dipolar cycloadditions. In other words, diazomethane reacts with acceptor-substituted alkenes or alkynes (e. g., acrylic acid esters and their derivatives) much faster than with ethene or acetylene (Figure 15.36). Diazomethane often reacts with unsymmetrical electron-deficient... 

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