Dipolarophiles acetylenic

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). 

A triazole crosslinked polymer can be formed by the cycloaddition of an azide end-capped polymer with dipolarophile acetylenic curing agent [31]. 

Oxazolium oxides, which can be generated by cyclization of a-amido acids, give pyrroles on reaction with acetylenic dipolarophiles.144 These reactions proceed by formation of oxazolium oxide intermediates. The bicyclic adduct can then undergo a concerted (retro 4 + 2) decarboxylation. 

During the course of a study of the cycloaddition of azidomethyldiethylphospho-nate with acetylenes and enamines leading to alkyltriazoles under solvent-free conditions we observed that specific effects can be involved, depending on the nature of the substituents on the dipolarophiles [50] (Eq. (7) and Tab. 3.4). 

The 2,5-dihydro-l,3,4-thiadiazole 79 reacts with a range of acetylenic dipolarophiles to afford the 2,5-dihydrothio-phenes 80 in 25-75% yields (Equation 19) <2002HCA451>. The thermal extrusion of dinitrogen from the thiadia-zole affords a thiocarbonyl ylide, which reacts with the dipolarophiles to form the thiophenes. 

Yields from 1,3-dipolar addition reactions with pyridinium ylides are enhanced by the addition of phase-transfer catalysts [60]. The ylides are produced in situ under basic two-phase conditions and react at room temperature with acetylenic dipolarophiles. 

Mesoionic 4-amino-l,2,3,5-thiatriazoles constitute the only class of mesoionic 1,2,3,5-thiatriazoles known. They are prepared by the reaction of l-amino-l-methyl-3-phenylguanidine with approximately 2 equivalents of thionyl chloride with pyridine as solvent (88ACS(B)63>. They are obtained as the yellow 1 1 pyridine complexes (17). The dark-violet mesoionic 1,2,3,5-thiatriazole (18) was liberated on treatment with aqueous potassium carbonate (Scheme 3). The structure is established on the basis of elemental analysis and spectroscopic data. In particular, the IR spectrum is devoid of NH absorptions. Compound (18) exhibits a long-wavelength absorption at 463 nm in methanol. When mixed with an equivalent amount of pyridinium chloride, complex (17) is formed and the absorption shifts to 350 mn. The mesoionic thiatriazoles are sensitive towards mineral acids and aqueous base and although reaction takes place with 1,3-dipolarophiles such as dimethyl acetylene-dicarboxylate, a mixture of products were obtained which were not identified. 

The cycloaddition reactions of 2-phenyloxazol-4(5H)-one with acetylenic dipolarophiles has been briefly reported. " The formation of 2-phenylfurans may well involve a tautomerism analogous to that exhibited by azlactones (76 77). 

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. ... 

The ring fused pyrroles 480 have been prepared by in situ trapping of the meso-ionic l,3-oxazol-5-ones (479) with alkynes. This 1,3-dipolar cycloaddition was found to be regiospecific when phenyl acetylene was used as 1,3-dipolarophile, the only products being 480, R = H or MeO, R = Ph, R2 =... 

Numerous reactions of acetylenic esters are reported in the literature, and many of these lead to heterocyclic compounds. Acetylenic esters undergo very facile addition reactions with several nucleophiles and also they participate as dipolarophiles in 1,3-dipolar cycloadditions, and as... 

Repetition of the reaction with DEAD as the dipolarophile furnished the desired cycloadduct 55 in 48% yield, but with 25% yield of the enamide 56 also being isolated. This was rationalized by invoking decomposition of the ylide precursor 57 to the (trimethylsilylmethyl)silyl amine 58, which undergoes subsequent addition to the highly reactive acetylene (Scheme 3.14). 

Alkene dipolarophiles such as diethyl fumarate were shown to be somewhat less reactive than electron poor acetylenes (9), but were effective for the formation of dihydrofuran derivatives (Scheme 4.7). 

Harwood and co-workers (105) utihzed a phenyloxazine-3-one as a chiral derived template for cycloaddition (Scheme 4.50). An oxazinone template can be formed from phenylglycinol as the template precursor. The diazoamide needed for cycloaddition was generated by addition of diazomalonyl chloride, trimethyl-dioxane-4-one, or succinimidyl diazoacetate, providing the ester, acetyl, or hydrogen R group of the diazoamide 198. After addition of rhodium acetate, A-methylmaleimide was used as the dipolarophile to provide a product that predominantly adds from the less hindered a-face of the template in an endo fashion. The cycloaddition also provided some of the adduct that approaches from the p-face as well. p-Face addition also occurred with complete exo-selectivity. Mono- and disubstituted acetylenic compounds were added as well, providing similar cycloadducts. 

Reaction with acetylenic dipolarophiles represents an efficient method for the preparation of 2,5-dUiydrothiophenes. These products can be either isolated or directly converted to thiophene derivatives by dehydration procedures. The most frequently used dipolarophile is dimethyl acetylenedicarboxylate (DMAD), which easily combines with thiocarbonyl yhdes generated by the extrusion of nitrogen from 2,5-dihydro-1,3,4-thiadiazoles (8,25,28,36,41,92,94,152). Other methods involve the desUylation (31,53,129) protocol as well as the reaction with 1,3-dithiohum-4-olates and l,3-thiazolium-4-olates (153-158). Cycloaddition of (5)-methylides formed by the N2-extmsion or desilylation method leads to stable 2,5-dUiydrothiophenes of type 98 and 99. In contrast, bicyclic cycloadducts of type 100 usually decompose to give thiophene (101) or pyridine derivatives (102) (Scheme 5.37). 

Reactions of thiocarbonyl ylides with nitriles are scarce. Simple nitriles do not undergo bimolecular cycloaddition (171). There is, however, a single example of an intramolecular case that was reported by Potts and Dery (24c,62). By analogy to the intramolecular cycloaddition with acetylenic dipolarophiles (Scheme 5.40), the primary product derived from the reaction of a thiocarbonyl ylide with a nitrile group undergoes a subsequent elimination of phenylisocyanate to give the fused 1,3-thiazole (131). 

Confirmation was provided by the observation that the species produced by the photolysis of two different carbene sources (88 and 89) in acetonitrile and by photolysis of the azirine 92 all had the same strong absorption band at 390 nm and all reacted with acrylonitrile at the same rate (fc=4.6 x 10 Af s" ). Rate constants were also measured for its reaction with a range of substituted alkenes, methanol and ferf-butanol. Laser flash photolysis work on the photolysis of 9-diazothioxan-threne in acetonitrile also produced a new band attributed the nitrile ylide 87 (47). The first alkyl-substituted example, acetonitrilio methylide (95), was produced in a similar way by the photolysis of diazomethane or diazirine in acetonitrile (20,21). This species showed a strong absorption at 280 nm and was trapped with a variety of electron-deficient olefinic and acetylenic dipolarophiles to give the expected cycloadducts (e.g., 96 and 97) in high yields. When diazomethane was used as the precursor, the reaction was carried out at —40 °C to minimize the rate of its cycloaddition to the dipolarophile. In the reactions with unsymmetrical dipolarophiles such as acrylonitrile, methyl acrylate, or methyl propiolate, the ratio of regioisomers was found to be 1 1. 

Freeze and Norris (34) reported the 1,3-dipolar cycloaddition of 5-azido-5-deoxy-l,2-0-isopropylidene-D-xylofiiranose (164) with acetylenic dipolarophiles to give the triazoles 165 (Scheme 9.34). This process was subsequently extended using the soluble polymer-supported azide (166) to produce the corresponding triazoles 167 in 50-95% yield. Dipolarophiles present in large excess facilitated the cycloaddition of the polymer-supported azide 166. Purification of the triazole 167 was achieved by filtration. 

Hlasta and Ackerman (72) reported a synthesis of the triazoles 379, related to the human leuokocyte elastase inhibitor WIN 62225 (380), based on an inter-molecular 1,3-dipolar cycloaddition of the azide 378 with alkynes (Scheme 9.72). They also investigated in detail the effect of steric and electronic factors on the regioselectivity of the cycloaddition reaction. (Azidomethyl)benzisothiazolone (378) underwent smooth 1,3-dipolar cycloaddition with various disubstituted acetylenes to give the corresponding triazoles (379) in 37-84% yields. Electron-deficient acetylenic dipolarophiles reacted more rapidly with the azide to give the respective triazoles. 

Maier and Schoffling (37) extended this intramolecular isomiinchnone cycloaddition to a synthesis of fused furans by employing an alkyne dipolarophile (Scheme 10.9). Thus, the diazo acetylenes (66) are smoothly converted to furans (69) via isomtinchnones (67) with catalytic rhodium acetate. 

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). 

An example of 2,4,6-triphenylpyrylium-3-olate (65 R = R = R = Ph, R = H) reacting as a 1,3-dipole was first provided by Suld and Price who obtained a maleic anhydride adduct (C25HigO5). Subsequently, an extensive study of the cycloadditions of this species has been published by Potts, Elliott, and Sorm. With acetylenic dipolarophiles, compound 65 (R = R = R = Ph, R = H) gives 1 1 adducts that have the general structure 74 and that isomerize to 6-benzoyl-2,4-cyclohexadienones (76) upon thermolysis. This thermal rearrangement (74 -> 76) has been interpreted in terms of an intermediate ketene 75. The 2,3-double bond of adduct 74 (R = Ph) is reduced by catalytic hydrogenation. Potential synthetic value of these cycloadducts (74) is demonstrated by the conversion of compound 74 (R = Ph) to l,2,3,4,6-pentaphenylcyclohepta-I,3,5-triene (79 R= Ph) via the alcohol 78 (Scheme 1). ... 

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