Propiolic ester, reaction with

The reaction of 1,2,3-triazolium-l-aminides 3 with propiolate esters led to fluorescent 2,5-dihydro-1,2,3-triazine derivatives 4 in one pot, involving a Huisgen cycloaddition followed by a sequence of rearrangements <06JOC5679 06TL1721>. These reactions can be carried out in acetone, in water, or under solvent-free conditions. 

The intermolecular reaction of phenols with propiolic esters occurs in the presence of a Pd(OAc)2 catalyst to afford coumarin derivatives directly.48,48a An exclusive formation of 5,6,7-trimethoxy-4-phenylcoumarin is observed in the Pd(OAc)2-catalyzed reaction of 3,4,5-trimethoxyphenol with ethyl phenylpropiolate in TFA (Equation (46)). Coumarin derivatives are obtained in high yields in the cases of electron-rich phenols, such as 3,4-methylenedioxyphenol, 3-methoxyphenol, 2-naphthol, and 3,5-dimethylphenol. A similar direct route to coumarin derivatives is accomplished by the reaction of phenols with propiolic acids (Equation (47)).49 A similar reaction proceeds in formic acid at room temperature for the synthesis of coumarins.50,50a Interestingly, Pd(0), rather than Pd(n), is involved in this reaction. 

It is also possible to carry out a substrate-controlled reaction with aldehydes in an asymmetric way by starting with an acetylene bearing an optically active ester group, as shown in Eq. 9.8 [22]. The titanium—acetylene complexes derived from silyl propiolates having a camphor-derived auxiliary react with aldehydes with excellent diastereoselectivity. The reaction thus offers a convenient entry to optically active Baylis—Hillman-type allyl alcohols bearing a substituent (3 to the acrylate group, which have hitherto proved difficult to prepare by the Baylis—Hillman reaction itself. 

Witulski and Alayrac reported the synthesis of clausine C (clauszoline-L) (101) by a rhodium-catalyzed alkyne cyclotrimerization of diyne 1014 and propiolic ester 635 (561). Analogous to the hyellazole (245) synthesis (see Scheme 5.75), the diyne precursor 1014 required for this key cyclotrimerization reaction was obtained starting from readily available 2-iodo-5-methoxyaniline. Using Wilkinson s catalyst, [RhClfPPhsls], crossed-alkyne cyclotrimerization of 1014 and 635 led to N-tosylclausine C (1015) in 78% yield in an isomeric ratio of 3.8 1. Finally, deprotection of the tosyl group with TBAF in refluxing TFIF afforded clausine C (clauszoline-L) (101) (561) (Scheme 5.147). 

Wilson and Tebby have studied the reaction of triphenylphosphine with different acetylenic esters in alcohol medium and have shown that /3-alkoxyvinylphosphonium ylides and vinyl ethers are formed through the alcoholysis of vinyl phosphonium intermediates. Thus, triphenylphosphine reacts with DMAD in methanol to give the phosphorane (432) [Eq. (62)]. The reaction with propiolic esters, on the... 

The 4-phospha-1,3-butadiene 77/80 serves as an effective synthon for the unknown H-substituted nitrile ylide 79 in [3+ 2]-cycloaddition reactions with a range of electron-poor dipolarophUes (e.g., reaction with DMAD gave 78 in 80% yield). Similar yields were also obtained using methyl propiolate, azodicaboxylic esters, ethyl acrylate, and acrylonitrile (39). The reactant was generated under very mild conditions from 75 as shown below. 

Similarly, cyclization of 3-amino-l, 2,4-triazoles (65) with methyl propio-late or methyl phenylpropiolate gave a mixture of the l,2,4-triazolo[4,3-a]pyrimidin-7-ones 97 and the l,2,4-triazolo[l,5-a]pyrimidin-7-ones 98 (70CB3266 71CB2702). In addition, methyl tram-3-(3-amino-l,2,4-triazol-l-yl)acrylates (99) were also obtained. Production of the 1,2,4-triazolopy-rimidines 97 and 98 started by condensation of the ester function with the amino group of 65, followed by cycloaddition of the triazole N4 or N1 of the two tautomeric intermediates 96a and 96b, respectively, onto the carbon-carbon triple bond of the side chain. In contrast, formation of the triazolyl acrylates 99 took place through addition only of the triazole N1 onto the propiolate carbon-carbon triple bond. The relative amounts of products were found to depend on the reaction conditions (temperature, solvent, and time) (70CB3266) (Scheme 42). 

Other preparations of 2-iminothiazolidin-4-ones which are discussed in the review by Brown139 utilize the reactions of thiourea with a-hydroxy acids,146 ethyl diazoacetate,73 glycidic esters,74,147 cinnamic acid,148 unsaturated diacids (fumaric, maleic, and citraconic) or their esters or imides,149-152 and propiolic esters.153,154 There has been considerable controversy in the literature surrounding the propiolic ester synthesis since many workers have proposed that the products are 1,3-thiazines (see Section IV, B, 1). The pertinent papers in this controversy have been summarized by Cain and Warrener.155 Nagase158 has recently settled the argument in favor of the 2-iminothiazolidin-4-... 

Michael adducts are also formed from the reactions of pyrroles with ethyl propiolate and with but-l-yn-3-one. In addition to the expected acrylic ester, 1-methylpyrrole also yields ethyl 3,3-bis(l-methyl-2-pyrrolyl)propanoate in its reaction with ethyl propiolate (67MI30500, 67MI30501), whilst if both a -positions of the pyrrole ring are unsubstituted, a twofold Michael addition with but-l-yn-3-one occurs to give the 2,5-disubstituted pyrrole (76JHC1145). 

Propiolic esters combine readily with pyridines to give first a zwitter-ion of type 95, but the only recorded case of subsequent addition of a second mole of the ester to give a quinolizine is with 6-methylphenan-thridine (see Section V,M). Zwitterion 95 usually abstracts a proton from either another molecule of alkyl propiolate or an alternative proton donor, and further reactions ensue. Some of the reactions are very difficult to reproduce and are very dependent on trace impurities and yield complex mixtures. 

Sydnones behave as 1,3-dipolar systems and undergo addition reactions with various dipolarophiles. Huisgen, Grashey, Gotthardt, and Schmidt503,504 were the first to react acetylenic esters with sydnones and obtained pyrazoles e.g., 71 with DMAD (1 hour, 120°, in xylene) gave 99% of the pyrazole 73. These reactions have also been carried out with propiolic and phenylpropiolic esters, and their kinetics have been studied.505... 

Radical cyclization with iodine atom transfer of a highly functionalized propiolic ester 103 using dibenzoyl peroxide as an initiator gave the a-methylene-y-butyrolactone 104 in good yield [95T11257]. The relative stereochemistry at carbon atoms 4 and 5 are established during the reaction. The intermediate 104 has been converted to the anti-tumor agent (-)-methylenolactocin 105. 

M. F. Czarniecki (13) also has examined the ferrocene ester (II) carrying a propiolic acid sidechain. This also fits very well, since the somewhat shorter distance involved with an acetylene makes up for the zig-zag arrangement of an olefin. He finds that the acceleration of reaction of this acetylenic p-nitrophenyl ester on reaction with cyclodextrin under our conditions is 100,000-fold, close to that for the... 

Acetylenedicarboxylic ester, propiolic esters and dicyanoacetylene react with unactivated ene components below 200 Isobutene undergoes ene reactions with dimethyl acetylenedicarboxylate... 

Benzamidinc combines with 2-amino-3-phenacyl-l,3,4-oxadiazolium bromides to give l-acylamino-2-benzimidoylamino-4-arylimidazolcs. Yields arc only moderate (14-43%), but the reaction works for a variety of 4-arylimidazoles f22. Reactions of /V-methyl-JV-(JV -phenylbenzimidoyl)amino-acetonitrile (13) under acidic conditions lead to imidazolium salts which have amino (14) or amido (15) groups in the 4-position (Scheme 2.2.6). The 4-amino salt (14) undergoes Dimroth rcaaangement to the 4-phenylaminoimidazole (16) direct conversion of (13) into (16) also occurs in warm alkali [8]. A Claisen rearrangement of the adduct (17), which forms from interaction of an arylamidoxime and a propiolate ester, provides a method... 

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