Acetylenedicarboxylic esters cycloaddition

After acetylenedicarboxylates, esters of propiolic acid are the second common group of reagents for 1,3-dipolar cycloaddition with azides. They react fast, and the yields of products are high. However, because the reacting... 

Dipolar Cycloaddition of Azimine with Acetylenedicarboxylic Esters... 

The three-nitrogen azimine 1,3-dipolar system in benzocinnolinium ylides26 undergoes cycloaddition with acetylenedicarboxylic esters to give azomethineimines, presumably derived from the initial A4-triazoline 1,3-cycloadduct by an electrocyclic ring opening (Scheme 8).2 7... 

This reaction can also be regarded as a Michael addition of pyrrole to maleic anhydride. Some substituted pyrroles, however, undergo a [4+2] cycloaddition with acetylene dienophiles, e.g. l-(ethoxycar-bonyl)pyrrole with acetylenedicarboxylic ester [37]. 

Acetic add, frons-cyclohexanediaminetetra-metal complexes, 554 Acetic add, ethylenediaminetetra-in analysis, 522 masking, 558 metal complexes, 554 Acetic acid, iminodi-metal complexes, 554 Acetic acid, nitrilotri-metal complexes titrimetry, 554 Acetoacetic add ethyl ester bromination, 419 Acetone, acetyl-deprotonation metal complexes, 419 metal complexes reactions, 422 Acetone, selenoyl-liquid-liquid extraction, 544 Acetone, thenoyltrifluoro-liquid-liquid extraction, 544 Acetone, trifluorothenoyl-in analysis, 523 Acetonitrile electrochemistry in, 493 exchange reactions, 286 metal complexes hydrolysis, 428 Acetylacetone complexes, 22 liquid-liquid extraction, 543 Acetylacetone, hexafiuorothio-metal complexes gas chromatography, 560 Acetylactone, trifluorothio-metal complexes gas chromatography, 560 Acetylation metal complexes, 421 Acetylenedicarboxylic add dimethyl ester cycloaddition reactions, 458 Acid alizarin black SN metallochromic indicator, 556 Actinoids... 

Heterocyclic o-quinodimethanes are unstable and reactive dienes that must be generated in situ. In solution and in the pre.sence of a dienophile the -quinodimethanes can be intercepted in a Diels-Alder reaction, often in high yield. Most of the dienophiles investigated so far have been electron deficient A-phenylmaleiinide. acrylonitrile, methyl vinyl ketone, acrylate, ftimarate and acetylenedicarboxylic esters are typically used. However, since the objective of most of the work was simply to establish that the o-quinodimethane was being formed, the scope of the reaction has not been adequately explored. The pyridine derived o-quinodimethane 12 has recently been shown to undergo cycloaddition to ethyl vinyl ether (Scheme 2) and to dihydroftiran <96T11889>, and it is thus clear that the scope of the Diels-Alder reaction extends beyond electron deficient alkenes and alkynes. Heterodienophiles (azodicarbonyl compounds and nitrosobenzene) have been added to indole-2,3-quinodimethanes <91T192,S> and this type of hetero Diels-Alder reaction is also potentially of wider application. 

Tanny and Fowler have reported further cycloaddition reactions of homopyrroles with acetylenedicarboxylic ester and other dienophiles. The stereospecificity observed with (720 R = CO Me) and the rate effect of the R substituent appear to be more in line with a concerted than a dipolar mechanism (Scheme 53). 

Several cycloaddition reactions of acetylenedicarboxylic ester with heterocyclic systems proceed via formation of cyclobutenes which undergo subsequent ring-openings and rearrangements. Addition of 1-dimethylaminopropyne to sorbic ester affords the triene (845X possibly via the route shown. ... 

Van Wuytswinkel, G., Verheyde, B., CompernoUe, F. et al. (2000) A convergent synthesis of heterocyclic dendrimers using the 1,3-dipolar cycloaddition reaction of organic azides and acetylenedicarboxylate esters. Journal of the Chemical Society-Perkin Transactions 1, 9,1337. 

Enamino ketones and esters also react with dimethyl acetylenedicarboxylate (67). Again cycloaddition appears to occur and the unstable cyclobutene intermediates rearrange to give insertion of two carbon atoms. 

In numerous synthetic studies,9" 6 100 it has been demonstrated that porphyrins react at the chromophore periphery in cycloaddition reactions, rearrangements, conjugative additions and substitution reactions to yield interesting porphyrin derivatives. Thus, metal-free protoporphyrin IX dimethyl ester reacts in Diels-Alder reactions108a b with dienophilcs like ethenetetra-carbonitrile and acetylenedicarboxylates at the diene structural parts to yield, according to the reaction conditions, the corresponding monoadducts 2 and 3 (see also Section 1.2.) and bisadducts 1 (see also Section 1.4.), respectively. 

Esters of acetylenedicarboxylic acid 1023 are commercially readily available, are very reactive as dipolarophiles, and the carboxylic groups in products of their reactions can be easily converted to many other functionalities. Therefore, they are often the first choice as substrates for 1,3-dipolar cycloaddition to azides 1024 (Huisgen reaction). The reactions are carried out at room or elevated temperature, and the yields of 1,2,3-triazoles 1025 are usually high to quantitative (Equation 22). Several products obtained in this way are presented as structures 1026-1034. Some details about the reactions leading to these products are given in Table 10. 

Acetylenedicarboxylic acid esters and related activated alkynes are routinely used as dipolarophiles for diazo dipoles. Recent examples include the use of diazo compounds 20 (49), 23 (51), and 24 (52) (Scheme 8.7), 25 (56) (Scheme 8.8), diazoacetaldehyde dimethylacetal (41) (which after cycloaddition and deprotection gave the corresponding pyrazole-3-carbaldehyde), ethyl 3-diazopyruvate (270), p-tolyl-trifluoromethyldiazomethane (271), bis(trifluoromethyl)diazomethane (272), and diazomethylenephosphoranes (60). 

The synthesis of the heterocyclic dendrimer 181 was based on the intermolecular 1,3-dipolar cycloaddition of the azide 180 with acetylenedicarboxylic acid and its esters (39) (Scheme 9.39). 

We were not able to obtain any cycloadduct from unactivated 2-azadienes 139 and esters of acetylenedicarboxylic acid. However, we found that 139 did cycloadd to typical electron-poor dienophiles such as esters of azodicarboxylic acid and tetracyanoethylene (Scheme 62). Thus, diethyl and diisopropyl azodicarboxylates underwent a concerted [4 + 2] cycloaddition with 139 to afford in a stereoselective manner triazines 278 in 85-90% yield (86CC1179). The minor reaction-rate variations observed with the solvent polarity excluded zwitterionic intermediates on the other hand, AS was calculated to be 48.1 cal K 1 mol-1 in CC14, a value which is in the range of a concerted [4 + 2] cycloaddition. Azadienes 139 again reacted at room temperature with the cyclic azo derivative 4-phenyl-1,2,4-triazoline-3,5-dione, leading stereoselectively to bicyclic derivatives 279... 

Wittig reactions with pyrrole-2-aldehyde led to the esters (79) which were cyclisized to 3a-azaazulen-4-ones (80).104,105 4-Methylene-3a-aza-azulenes (81) have been obtained from 80 with stabilized phos-phoranes.36 Reaction of dimethyl acetylenedicarboxylate with 81 could not be achieved. A similar cycloaddition was successful in the synthesis of cycl[3,3,3]azines (2) (Section V). 

The cycloaddition chemistry of pyridones (695) is quite analogous to that of the a-pyrones (79CC1091). Pyridones will react under high pressure conditions with acetylenedicarboxylic acid esters to furnish cycloadducts (696) which when heated expel a molecule of an isocyanate to yield substituted aromatics (697 Scheme 163). 

Developments in aziridine chemistry, including the synthetic applications of their cycloadditions, have recently been reviewed by Lown and Matsumoto.35-37 Many investigators have added aziridines to acetylenic esters. Russian workers38 treated aziridine in the cold with various esters and then heated the mixtures to 40°-60° for 3 hours. They obtained 59% of compound 16 with EP, and 71 % of 17 with EPP, no stereochemistry being defined. Diethyl acetylenedicarboxylate gave 24% of the maleate 18 (R = Et) and 16% of the fumarate 19 (R = Et). 

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