3- propiolate esters

The regioselectivity of the reaction appears to be determined by a balance of electronic and steric factors. For acrylate and propiolate esters, the carb-oxylate group is found preferentially at C3 of the carbazole product[6-8]. Interestingly, a 4-methyl substituent seems to reinforce the preference for the EW group to appear at C3 (compare Entries 4 and 5 in Table 16.2). For disubstituted acetylenic dicnophiles, there is a preference for the EW group to be at C2 of the carbazole ring[6]. This is reinforced by additional steric bulk in the other substituent[6,9]. 

Acetylenic esters react well witli copper-zinc compounds. Propiolic esters are especially reacive [83], but otier acetylenecarboxylic acid derivabves suci as di-nietliyl acetylenedicarboxylate or propiolaniide 118 undergo biglily stereoselecive cis addition (Scienie 2.47) [46]. 

Apart from Cu1, Zn11 salts or Zn metal were also shown to be effective, thus bringing forward an alternative efficient protocol (36) which may be useful for the applications in which the contamination of products by Cu cannot be tolerated. Such protocols can also be advantageous in cross-coupling with acetylenes bearing electron-withdrawing substituents, such as propiolate esters,115 which usually give unsatisfactory results under the standard conditions. 

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. 

Propiolic acids. The ylide derived from 1 converts aldehydes into propiolic esters or the acids in 50-70% yield. 

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... 

Acyloxyacrylates are conveniently prepared through the catalyzed addition of carboxylic acids to propiolic esters. Thus, the addition of acetic acid (iron salt) to methyl propiolate yields methyl 3-acetoxyacrylate. Similar additions have been observed with benzoic acid to give the corresponding acrylic esters. 

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-... 

Lown and Matsumoto51 added DEAD and EP to the 2-(2 -thienyl)-aziridine 48 and obtained results similar to those described already. Hence cis- and trans-48 with propiolic ester gave only the pyrrole 49, whereas DMAD gave mostly compound 50 with some 51. 

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. 

Methyl 2-pyridylacetate in ether with MP yields a mixture of 106, 107, and 108 which could be formed through a zwitterion corresponding to 95,296 and 109. The 1-propanoyl derivative of 109 is obtained from l-(2-pyridyl)butan-2-one. However, ethyl 2-pyridylacetate with phenyl-propiolic esters apparently gave only 110, and, if sodium methoxide was... 

The addition of propiolic esters to substituted 2-aminopyridines has been examined by three groups.303-305 The most recent study305 is definitive. The 1 2 molar adduct was first303 thought to be 132 but is, in fact,305 130, which cyclizes to 131. In two cases,305 compounds with structure 132 were obtained, and the NMR spectra for all these adducts were compared. 

Treatment of the pyrimidinimines 228 with propiolic ester gave 229.345 The authors state that 230 was expected because of the lower electron density at C-2, but spectroscopic data provided convincing evidence for the alternative structure. 

Addition of propiolic esters to 3-aminobenzisoxazole (1) gave a mixture of 2 and 3.471... 

The addition of DMAD, DEAD, and propiolic ester to 2-amino-1,3,4-oxadiazoles (95) led to the Michael adducts 96, which were cyclized to 5-oxo-1,3,4-oxadiazolo[3,2-a]pyrimidines (97). The alternative mode of addition leading to 98 was not observed. The structures were assigned spectroscopically.817... 

The addition of DMAD to 2-aminothiazole (25) gave 26, whereas propiolic ester gave 27, 28 and 29, all derived by Michael-type additions.549 Dunwell and Evans550,551 have also added acetylenic esters to 2-amino- (and 2-amino-4-methyl)thiazole and obtained 26 and 27 from DMAD and EP, and similar compounds from tetrolic and phenyl-propiolic esters. By independent synthesis, these compounds were shown not to have the isomeric structures derived by initial addition to the exocyclic nitrogen. 

Aminotriazolo[l,5-a]pyridine (63) on treatment with propiolic ester gave 64.606... 

An alternative route to the dianionic ynolato complex is from propiolic ester complexes and excess organolithium reagents (21, 26, 27) ... 

Condensation of propiolic esters with alkenes.2 Methyl propiolate or tetrolate, when activated by complcxation with the C5H5Fe(CO)2 cation (Fp+), condense with alkenes to form cyclobutenes, 1,3-dienes, and lactones. The type of products formed depend on the structure of the alkene. 1,2-Disubstituted alkenes yield cyclobutenes and 1,3-dienes mainly, whereas 1,1-disubstiluted or trisubstituted alkenes form mainly lactones. 

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