Cycloaddition of sydnones

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>. 

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). 

The products derived from intermolecular cycloaddition of sydnones readily lose carbon dioxide. If the original cycloaddition is carried out on a diene, the resulting azomethine imine intermediate can be trapped intramolecularly. Thus, 1,5-cyclooctadiene cycloadded to a sydnone to afford the cycloadduct (168).78b It is theorized that the intermolecular monocycloadduct (169) was formed, lost carbon dioxide, and cycloadded as a cyclic azomethine imine to the remaining C—C double bond. Conjugated dienes have been shown to undergo a similar sequence.87... 

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. 

While thermal cycloadditions of sydnones with acetylenes are well known, the photolysis of sydnone in the presence of acetylenes gives different products (Scheme 19).53... 

The dipolar cycloaddition of sydnones (l,2,3-oxadiazolidin-5-one derivatives) (108) with benzocyclobutene (109) has been used to synthesize 3 f-2,3-benzodiazepines (110). This synthesis involves a cycloaddition-extrusion-ring-expansion sequence, and with other mesionic compounds, for example the thiazolium-4-olate (111), primary cydoadducts (112) were isolated (Scheme 13)... 

A-Unsubstituted pyrazoles have been obtained via resin-bound sydnones (Scheme 11.17). ° Sydnones are mesoionic compounds that react as azomethine im-ine-type 1,3-dipoles in 1,3-dipolar cycloaddition. The cycloaddition of sydnones with electron-withdrawing alkynes gave pyrazoles. 2-Methoxy-substituted resin acted as a... 

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

Phenylsydnone 89 is not restricted to [3+2] cycloaddition. Reaction of sydnone 89 and its derivatives with the substituted azete 90 gives isomeric l//-triazepines after extrusion of carbon dioxide (Equation 8). 

Photolysis of the triazepine products produces 2,2-dimethylpropanenitrile and the corresponding pyrazole in quantitative yield <1997BSF927>. Reaction of sydnone 89 with fulvene 91 proceeds by [ji4s + jt6s]-cycloaddition followed by spontaneous loss of carbon dioxide and a molecule of dimethylamine or acetic acid from the pseudo-azulene , cyclopentaMpyridazine 92 (Equation 9) <1996CC1011, 1997T9921>. 

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). 

The addition to alkenes normally leads to unstable adducts that lose carbon dioxide under the reaction conditions. The intramolecular cycloaddition of the sydnone (30) takes place at room temperature, however (Equation (5)) and the cycloadduct (31) has been characterized <86HCA927>. The unstable species formed by the loss of carbon dioxide are also azomethine ylides. It is therefore possible for a second 1,3-dipolar addition to take place, as illustrated in Scheme 6 for the reaction of 3-phenylsydnone with Al-phenylmaleimide <86TL317,92JA8414>. This 2 1 addition has been used as the basis of a synthesis of polyimides. Imides of the type (32) were used as the dipolarophiles and their reaction with 3-phenylsydnone gave linear polymers <87MM726>. 

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... 

Ollis, and Ramsden520 treated 99, 100 and 101 with neat EPP and obtained the pyrazole 103 and the phenylpropiolic ester dimer 104, but no 105. A comparative study was carried out with phenylacetylene. When 100 was heated with DM AD in dioxane, 25% of the pyrazole 106 was obtained. These authors have concluded that the cycloaddition of alkynes to isosydnones is analogous to that of sydnones but the reactions are slower and the cycloadducts are obtained in lower yields. 

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... 

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... 

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