Sydnones 1,3-dipolar cycloadditions

Table 4 1,3-Dipolar cycloaddition of propargyl esters 86 to sydnone 85 (Scheme 3) <2006H1007, 2006SL901 >...

The Weintraub reaction was revisited to form additional members of the series of diazatetracycloundecanes by tandem 1,3-dipolar cycloaddition of sydnones and 1,5-cyclooctadiene (Equation 11) <1996JHC719>. 

Arylsydnone-4-carbonitrile oxides, which are generated in situ by thermal dehydrochlorination of the corresponding hydroximic acid chlorides, undergo 1,3-dipolar cycloadditions with sydnone-4-carbonitriles to give 3-aryl-4-[5-(3-arylsydnonyl)-l,2,4-oxadiazol-3- yl]sydnones 228 (392). 

Photochemical cycloaddition reactions between sydnones (1) and 1,3-dipolarophiles take place to give products which are different from, but isomeric with, the thermal 1,3-dipolar cycloaddition products. These results are directly interpreted in terms of reactions between the 1,3-dipolarophiles and Ae nit mine (316). The photochemical reactions between sydnones and the following 1,3-dipolarophiles have been reported dicyclopentadiene, dimethyl acetylene dicarboxylate, dimethyl maleate, dimethyl fumarate, indene, carbon dioxide, and carbon disulfide. ... 

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... 

Nan ya et al. (93,94) also reported the reaction of sydnones with Al-methyl- and N-phenylmaleimides. Gribble and Hirth (206) extended the work of Weintraub (207) on the tandem dipolar cycloaddition of sydnones with 1,5-cyclooctadiene to afford diazatetracycloundecanes 305. 

Dipolar cycloaddition of sydnones with 1-aryl-3,3,3-trifluoropropynes is a general synthesis of 4-trifluoromethylpyrazoles (93JHC365). 

Dipolar cycloaddition of sydnones with benzocyclobutene yield 3/7-2,3-benzodiazepines, e.g. (434). 

Mesoionic compounds have been known for many years and have been extensively utilized as substrates in 1,3-dipolar cycloadditions.158-160 Of the known mesoionic heterocycles, munchnones and sydnones have generated the most interest in recent years. These heterocyclic dipoles contain a mesoionic aromatic system i.e. 206) which can only be depicted with polar resonance structures.158 Although sydnones were extensively investigated after their initial discoveiy in 1935,160 their 1,3-dipolar character was not recognized until the azomethine imine system was spotted in the middle structure of (206). C-Methyl-N-phenylsydnone (206) combines with ethyl phenylpropiolate to give the tetrasub-... 

Huisgen and coworkers have also described the cycloaddition behavior of the munchnones , unstable mesoionic A2-oxazolium 5-oxides with azomethine ylide character.166 Their reactions closely parallel those of the related sydnones. These mesoionic dipoles are readily prepared by cyclodehydration of N-acyl amino acids (216) with reagents such as acetic anhydride. The reaction of munchnones with alkynic dipolarophiles constitutes a pyrrole synthesis of broad scope.158-160 1,3-Dipolar cycloaddition of alkynes to the A2-oxazolium 5-oxide (217), followed by cycloreversion of carbon dioxide from the initially formed adduct (218), gives pyrrole derivative (219 Scheme 51) in good yield. Cycloaddition studies of munchnones with other dipolarophiles have resulted in practical, unique syntheses of numerous functionalized monocyclic and ring-annulated heterocycles.167-169... 

This type of preparation of 1,2-diazepines has been reported earlier involving the dipolar cycloaddition of sydnones with benzocyclobutene <1996CHEC-II(9)113>. This method could be further exploited by the use of the correct hydrazone derivative (1,3-electrophile, nucleophile) with a,/3-unsaturated ketone (1,4-electrophile, nucleophile) for the synthesis of 1,2-diazepines. 

Thermal reactions and 1,3-dipolar cycloaddition reactions Thermally mesoionic oxatriazoles are relatively stable. Heating of (85) in tolane (97) at 200 °C for 20 d in the presence of LiCl induces C02 fragmentation and formation of cycloadduct (99) in 37% yield. There is no bimolecular reaction as found in the case of the sydnones and isosydnones (equation 56) (68CB536). 

The cycloaddition of isomiinchnones with acetylenic dipolarophiles followed by the extrusion of an alkyl or aryl isocyanate (RNCO) has proven to be an effective method for the synthesis of substituted furans. The Ibata group investigated the bimolecular 1,3-dipolar-cycloaddition of aryl-substituted isomiinchnones with a number of acetylenic dipolarophiles [50]. Aryl diazoimides of type 1 were heated in the presence of a catalytic amount of Cu(acac)2 and the appropriate acetylenic dipolarophile. Formation of the substituted furan was found to be temperature-dependent higher temperatures (ca. 120°C) were needed for complete conversion to the furan. It was reasoned that the extrusion of methyl isocyanate was not as facile as the loss of carbon dioxide from sydnones and miinchnones [50]. 

This is exactly what has been observed for the cycloaddition reactions of sydnones 6.336 with all three kinds of dipolarophile. An intermediate is produced in the first instance with the general structure 6.337 this loses carbon dioxide in a retro 1,3-dipolar cycloaddition, followed by tautomerism giving the 3-substituted pyrazolines 6.338 as the major products.860... 

Phenylsydnone is the prototype of that class of mesoionic compounds called sydnones. On acidic hydrolysis it produces phenylhydrazine, whereas basic hydrolysis regenerates N-nitroso-N-phenylglycine. This sydnone undergoes a variety of electrophilic substitutions,3,4 8-19 including mercuration n-13,16 and formylation,19 with an ease comparable to thiophene, and a number of 1,3-dipolar cycloadditions with numerous alkenes,18 18 alkynes,17 and quinones8 to form, with loss of carbon dioxide, a variety of pyrazole derivatives. 

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