Reactions of Propiolic Acids

The reaction of propiolic acid or its esters with 2-aminothiazole yields 7H-thiazolo[3.2o]pyTimidine 7-one (109) (Scheme 74) (273), The reaction probably proceeds by initial nucleophilic attack of 2-aminothiazole on the sp C followed by intramolecular addition of ring nitrogen to spC. 

The Sonogashira/decarboxylative Sonogashira reactions of propiolic acid with two kinds of aryl halides give rise to unsymmetric diarylacetylenes (Scheme 4.61) [62]. 

Winterfeldt has shown that the reaction of dimethyl sulfoxide with DMAD gives tetramethyl furantetracarboxylate (345), and it was suggested that this reaction may proceed through the intermediates 342, 343, and.344 (Scheme 52). The reaction of /-butylsulfenic acid with methyl propiolate, however, gives /3v -bis(/ra/is-carbomethoxy)divinyl sulfoxide (348) (Scheme 53). The penicillin S-oxide (349) is known to react with DMAD to give the adduct 352, and this reaction has been assumed to proceed through the sulfenic acid intermediate 350 (Scheme 54). ... 

Despite the uncertainties regarding regiochemistry, the reaction of propiolates with miinchnones has found use in synthesis. Kane and co-workers (84) synthesized the calcium channel activator FPL 64176 (161) using a mtinchnone cycloaddition protocol. Thus, reaction of amino acid 158 with acetic anhydride in the presence of acetylenic dipolarophUe 159 gave pyrrole 160 in 49% yield. Base-induced elimination of the 4-nitrophenethyl protecting group afforded FPL 64176 (161) in 85% yield. 

Generally, the isomeric l,2,4-triazoIo[4,3-a]pyrimidines (such as 18, Section II,B,1) are not formed. Exceptions are found with 3-phenyl-AT (60JOC361) and condensations of propiolic acids and their esters (70CB3266 71CB2702) [and, as minor side reactions, condensations of 3-ketovinylic compounds (83S44)]. 

Vallee, Y. The reaction of propiolate acetylides with nitrones. Synthesis of y-amino-a,/ -ethy-lenic acid derivatives. Tetrahedron Lett. 1997,... 

Diselenetane derivative 39 reacts with elemental selenium in the presence of a catalytic amount of triphenyl-phosphine or triphenylphosphine selenide to give 1,2,4-triselenolane 65 in 37% yield (Scheme 9) <2001TL3881>. The reaction with propiolic acid under reflux conditions in toluene affords selenodioxenone 66 (25%) and trace amounts of compound 67 <2004BCJ1933>. 

Methyl 3-bromopropiolate has been prepared by esterification of 3-bromopropiolic acid with methanol and sulfuric acid for 6 days (75% yield),4 the starting bromo acid being prepared by bromination of propiolic acid with aqueous potassium hypobromite.6 This reaction is particularly delicate to control, giving erratic results. Moreover, direct bromination of methyl propiolate with sodium hypobromite2 could not be reproduced. 

On larger scales (up to 50 grams of propiolic acid) the addition should still be complete within 1 min to allow the internal reaction temperature to rise to 100°C. 

The temperature of the reaction mixture must be raised to the reflux temperature (110°C) immediately after the addition of propiolic acid. 

Danishefsky has exploited his widely utilized silyloxydiene chemistry to complete a formal total synthesis of 90 (Scheme 1.20). By employing the appropriate oxidation levels for both the diene and dienophile, a resorcinyl ester possessing the required differentiation of the phenolic groups was obtained without further oxidative manipulation. To this end, the dianion of propiolic acid was alkylated with l-bromo-7-octene to give acid 98 in 68% yield. Further alkylation with methyl iodide then gave the ester 99. A Diels-Alder reaction with diene 100, a derivative of methyl acetoacetate, and alkyne 99 then furnished an initial phenolic intermediate which was protected as the benzyl ether to afford... 

Interesting results were obtained by reaction of substituted 1,2-dihydro-1,3,5-triazines with esters of acetylenedicarboxylic acid (DMAD) and of propiolic acid.254 In the case of the reaction with DMAD, formation of the different products 175 and 176 has been reported,254 presumably due to differences in the nucleophilicity of the secondary nitrogen atom of the triazines. 

Other reactions studied include reduction of the triple bond of a-acetylenic esters and nitriles by tributyltin hydride in methanol electroreductive cyclization of acetylenic halides at a mercury cathode the trimerization and tetramerization of cyclo-octyne in the presence of various transition metals the kinetics of bromination of alka-l,3-diynes, of permanganate oxidation of acetylenedicarboxylic acid, and of iodination of propiolic acid the participation of the triple bond in reactions of various acetylenes of the general formula (225) and the trimerization of but-2-yne with tolyl-palladium chloride to give a [Pg.48]

Optimization studies revealed that cycloaddilions of cyclic silyl enol ethers with ethyl propiolate (21a), promoted by 2 mol % Tf2NH, occurred at ambient temperature to generate cyclobutenes 22a-C in good yields. Finally, exploratory studies aimed at further optimizing the cyclobutane forming process showed that the organic acid catalyzed cycloaddition reaction could be successfully performed in various solvents, such as toluene, acetonitrile, dichloroethane, and ethyl acetate (Table 4.9). The reactions of propiolate took place even under solvent-free conditions. Although reactions of acrylates normally required careful control of temperature below —40 °C, in ethyl acetate these cycloadditions took place at more conveniently accessed ambient temperatures. 

Vespa orientalis, the Oriental hornet, produces lactone (428) (Scheme 77), which is thought 183) to control some aspects of social behavior. The / -(+)- and 5-(-)-enantiomers (428a and 428b, respectively) were elaborated by Coke and Richon 184) from 1-tridecene (422) via amino-alcohol (424), which was resolved into its enantiomeric forms by resolution of the optically active dibenzoyl tartarates (Scheme 77). Hofmann elimination followed by reaction with propiolic acid dianion (425) and reductive cyclization completed the synthesis. 

The reaction of bromine with (pyrazol-4-yl)acrylic acid and its esters and the subsequent dehydrobromination of the products have been investigated by Finar and Okoh [73JCS(P1)2008]. Attempts to dehydrobrominate bromoacrylic acids (20) to 3-( 1 -phenylpyrazol-4-yl)propiolic acids 22 failed, but were successful when bromoesters 21 were used (Scheme 32). 

The kinetics, products, and stereochemistry of the addition of HC1, HBr, and HI to propiolic acid in water have been studied.28 The addition is predominantly trans to give the cz s-3-haloacrylic acid. Both the rate of addition and the selectivity giving trans-addition increase with the nucleophilicity of the halide in water (i.e., I- > Br > Cl-). The order of reactivity is also consistent with the order of the softness of the nucleophiles. The reaction is first order in propiolic acid and the halide anion. It was proposed that the addition involves two mechanistic pathways a major /ra/z.v-addition via a transient carbanion formed with specific geometry and a minor cO-addition process (Scheme 10.2). 

Reaction of iV-aminoisoindoline 450 with methyl propiolate affords betaine 451 and its treatment with hydrochloric acid gives intermediate chloro derivative 452, which can be cyclized to 453 by treatment with a base or by heating (Scheme 75) <1995LA817>. 

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