Propiolic acid, ethyl ester

Ethyl propiolate Propiolic acid, ethyl ester (8) 2-Propynoic acid, ethyl ester (9) (623-47-2)... 

Treatment of aziridinyl ketone 18 with propiolic acid ethyl ester 58 leads to two regioisomeric pyrroles 59 and 60 [76] (Scheme 1.15). The reaction of ketone... 

A. (Z)-2,3-Dibromo-2-propenoic acid ethyl ester.2 Ethyl propiolate (9.01 g.91.8 mmol) and carbon tetrachloride (75 mL) are added in sequence to a 250-mL, round-bottomed flask equipped with a Teflon-coated magnetic stirring bar (Note 1). The flask is fitted with a 30-mL pressure equalizing addition funnel to which elemental bromine... 

The procedure outlined above describes the selective, retentive, p-coupling of (Z)-2,3-dibromopropenoic acid ethyl ester with (trimethylsilyl)acetylene employing the palladium-modified version of the Castro-Stephens reaction.4 5 The dibromide starting material is readily available by bromination of ethyl propiolate (Procedure A), as described by Trippett and Hall.2 The coupling product has been shown to be a versatile precursor for the synthesis of variously substituted enynes and enediynes. For example, a second acetylene may be introduced into the a-position under modified coupling conditions. Alternatively, reduction of the ester with diisobutylaluminum hydride and protection of the resultant alcohol with tert-butyldiphenylsilyl chloride affords a vinyl bromide that can be metalated and trapped with various electrophiles. These procedures have been used on the gram and multigram scale.5... 

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 acid, 58,43 Propionaldehyde, 58, 80, 82 Propionic acid, 2-iodo-3-mtro-, ethyl ester, 56, 65... 

Other preparations of 2-iminothiazolidin-4-ones which are discussed in the review by Brown utilize the reactions of thiourea with a-hydroxy acids,ethyl diazoacetate,glycidic esters, - cinnamic acid, unsaturated diacids (fumaric, maleic, and citraconic) or their esters or imides, and propiolic esters. 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. Nagase has recently settled the argument in favor of the 2-iminothiazolidin-4-... 

Other synthons for 1,3-dicarbonyl compounds that have been successfully applied include p-chloro-a,P-unsaturated ketones and aldehydes, P-dimethylamino-a,P-unsaturated ketones (easily obtained from ketones by reaction with DMFDMA), P-alkoxy-enones"" and vinyl-amidinium salts."" Alkynyl-ketones react with 5-alkyl-isothioureas, giving 2-alkylthio-pyrimidines" and propiolic acid reacts with urea to give uracil directly in about 50% yield. "" 1,3-Keto-esters with formamidine produce 4-pyrimidinones"" and C-substituted formamidines with ethyl cyanoacetate give 2-substituted-6-amino -pyrimidinones. In analogy, pyrimidines fused to other rings, for example as in quinazolines, can be made from ortho-aminonitriles " and in general, from P-enamino esters. ... 

As is true for hydrostannation, acetylenes are also more reactive than the olefins toward hydroplumbation. Acetylenedicarboxylic acid dimethyl ester and ethyl propiolate 152) add Bu3PbH at — 50° C (used as a pure substance, or made in situ from organotin hydrides) spontaneously and without side reactions. Me3PbH adds in the same smooth manner to cyanoacetylene and methyl propiolate 165). Phenylacetylene reacts under the same conditions but in a side reaction Pb is precipitated and H2 evolves. After a short while starting materials disappear if excess of lead hydride is used. The IR spectrum shows absorption at 990 cm , which is in accordance with a trans adduct 152,194). 

Various functionalized alkynes can be submitted to carbocupration reactions, such as alkoxyalkynes,150 alkynyl carbamates,151 acetylenic orthoesters,152 and thioalkynes.153 The carbocupration of orthoesters, for example, 204, has been used to prepare a-substituted esters of the type 206 by acidic hydrolysis of the adduct 205 (Scheme 51).152 This allows the formation of regioisomers that are not accessible by copper-mediated addition to acetylenic esters. A stereoselective synthesis of trisubstituted alkenes has been described by Normant et al.lSd> starting from phenylthio-acetylene 207. Carbocupration with lithium di- -butylcuprate affords the intermediate 208 which, upon addition of /z-butyllithium, undergoes a 1,2-metalate rearrangement to the vinylcuprate 209. The latter can be trapped with various electrophiles, for example, ethyl propiolate, providing product 210 with complete regio- and stereocontrol. 

The oxidation of the chiral ferrocenyl vinyl selenides, prepared from the optically active diferrocenyl diselenides and ethyl propiolate derivatives, with 1 molar equivalent of MCPBA under various conditions afforded the corresponding chiral selenoxides. The chiral selenoxides suffered in situ selenoxide elimination to afford the axially chiral allenecarboxyUc esters in moderate chemical yields with high enantioselectivities (Scheme 10). Typical results are shown in Table 5. The reaction temperature had a remarkable effect upon stereoselectivity and the lower temperature gave better results. The addition of molecular sieves (4 A) to the reaction system improved the stereoselectivity. Dichlo-romethane was revealed to be the solvent of choice. In other words, reaction conditions to suppress the racemization of a diastereomeric selenoxide intermediate were required. Asymmetric selenoxide elimination provides a new method for the preparation of the chiral allenecarboxyUc esters which have so far been prepared by optical resolution of the corresponding racemic acids. 

Michael additions between the thioamido ester (200) and alkyl-3-methyl-2-oxobut-3-enoates (201) in the presence of an acid gives the thiazines (202) (Equation (24)) <88SC1043>, and in yet another variation on this theme ethyl propiolate (203) and 7V-phenylthiourea can be cyclocondensed to yield... 

The cyclization of 4-substituted 5-hexenyl iodides proceeds well, leading to cyclopentylz-inc iodides that can be trapped with various electrophiles such as 3-iodo-2-cyclohexenone, iodine, acid chlorides, allylic halides, and ethyl propiolate (carbocupration) (Scheme 1) Various substitution patterns allow a successful cyclization. Also, a range of functional groups like esters or nitriles are tolerated in the ring closure (Scheme 8). 

---