Alkynoic acids/esters

Yamanaka and co-workers (74) effected the 1,3-dipolar cycloaddition between miinchnones 134 and polyfluoro-2-alkynoic acid esters to afford the corresponding 4-(polyfluoroalkyl)pyrrole-3-carboxylates (135). The reaction proceeds rapidly at low temperature and the various miinchnones (134) were generated from 1,3-oxazolium perchlorates 133 using the method of Boyd and Wright (6,7). Under... 

Unlike the cases of alkenes, Wacker-type intermolecular oxypalladation reactions of alkynes have not been extensively investigated, although their intramolecular cyclization reactions have been developed into synthetically useful procedures (Sects. V3.2). In principle, they can proceed by a few alternative paths shown for the cases of terminal alkynes in Scheme 14. In reality, however, alkynyl C—H activation by Pd to give alkynylpalladium derivatives shown in Scheme 3 may well be the dominant path, as suggested by the carbonylative oxidation of terminal alkynes to give alkynoic acid esters shown in Scheme 15. Oxidative dimerization of alkynes is a potentially serious side reaction. Further systematic investigation of this fundamentally important process appears to be highly desirable. 

Funabild K, Ishihara T, Yamanaka H (1995) An efficient and convenient synthesis of 4-polyfluoroalkylated pyrrole-3-carboxylates through 1,3-dipolar cycloaddition reaction of polyfluoro-2-alkynoic acid esters with munchnones. J Fluor Chem 71 5-7... 

The regioselective anti-Markovnikov addition of benzoic acid to phenyl-acetylene has also been carried out with success at 111 °C in the presence of ruthenium complexes containing a tris(pyrazolyl)borate (Tp) ligand [RuCl(Tp)(cod), RuCl(Tp)(pyridine), RuCl(Tp)(N,N,Ar,AT-tetramethylethyl-enediamine )] with a stereoselectivity in favour of the (E)-enol ester isomer [22]. The o-enynyl complex Ru(Tp)[PhC=C(Ph)C=CPh](PMe/-Pr2) (C) efficiently catalyses the regioselective cyclization of a,cu-alkynoic acids to give en-docyclic enol lactones [23] (Eq. 2). 

Several other transannular lactonizations and reductions have been reported to proceed in high overall yields. Also other acid derivatives, such as amides and esters, cyclize to form lactones. Alkynoic acids have been lactonized to y-alkylidene-y-lactones in good yield, e.g. the conversion of (31) to (32 equation 29). Unfortunately the vinyl selenide product can isomerize from ( ) to (Z) in a secondary process. Analogous lactam formation is also known. Unsaturated amides, when cyclized with benzenese-lenenyl halides, produce good yields of lactams or iminolactones depending upon the alkene utilized. The amide (33) cyclizes to the iminolactone (34), producing a mixture of stereoisomers (65 35 Scheme 5). The amide (35) is cyclized to lactam (36) in moderate yield. 

When the anions of these acids are good leaving groups, elimination from their enol esters can be readily induced by comparatively weak bases. This is the case for p-bromobenzenesulphonates and triflates. Thus decarboxylative elimination from enol sulphonates 28 furnishes good yields of 2-alkynoic acids (equation 88), when R... 

Alkaline decomposition of 4,4-dihalopyrazolinones with aqueous alkali at 0-10 °C affords 2-alkynoic acids in good yields. The starting materials are obtained from the corresponding p-keto esters as illustrated in equation (114). Phenylpropiolic acid... 

Isomerizations. A convenient method for the conversion of alkynes to conjugated dienes is by treatment with Ph P. The synthetic application is shown in the preparation of 2,4-alkadienols from 2-alkynoic acids involving esterification with pentafluorophenol, isomerization with PhjP (PhMe, 50°), and reduction with DIBAL-H. Even propargyl bromide can be isomerized to give 1-bromopropadiene, albeit in 29% yield. Conjugated alkadienoic esters and amides are obtained in one step from the pentafluorophenyl alkynoates on reaction with alcohols and amines, respectively, after treatment with catalytic amount of PhjP. 

Addition reaction. Hydroarylation of 2-alkynoic acids and esters occur on their treatment with ArH and PtCl2-AgOTf in TFA at room temperature. ... 

Activated acetylenic compounds, for example esters RC=CC02R" undergo cycloadditions to adenosine derivatives to yield two possible products (3, 4), depending on the conditions or reaction. The derivatives of 2-alkynoic acids undergo a regiospecific and stereospecific hydroacetoxylation reaction, catalysed by palladium acetate, as shown in reaction 2. ... 

Azide is one of the easiest functional groups to reduce with heterogeneous Pd catalyst and H2. Thus, even with the less active Lindlar s catalyst, azides can readily be reduced to amines. Reduction of azido alkynoate ester 84 using Lindlar s catalyst produced cis-alkenylaminocarboxylic acid ester 85 in 86% yield (Scheme 30). ... 

The Stille adduct of 2-bromothiophene and l-ethoxy-2-tributyl-n-stannylethene or 1-ethoxy-l-tri-n-butylstannylethene is a masked thienyl aldehyde or a masked ketone, respectively [77-80]. Vinylstannane 93, derived exclusively as the -isomer from hydrostannation of bis(trimethyl-silyl)propargyl amine (92), was coupled with 2-bromothiophene to form ( )-cinnamyl amine 94 upon acidic hydrolysis [81, 82], In another case, stereoisomerically pure phenyl ( )-2-tributylstannyl-2-alkenoate 95, arising from Pd-mediated hydrostannation of phenyl ( )-2-alkynoate, was joined with 2-iodothiophene to deliver the stereodefmed trisubstituted a,p-unsaturated ester 96 [83, 84],... 

Suitably protected amino acids (112) (cysteine, serine, and lysine) have been added via the side-chain heteroatom (S, O, and N, respectively) to conjugated alkynones, alkynoic ester and alkynoic amide (113). The expected heterosubstituted vinyl product (114) was formed in each case, mainly as the ii-isomer. In an accompanying paper, this type of addition was applied to the derivatives of fluorescein, 7-hydroxycoumarin, Sudan 1, and dansyl chloride with linker arms containing a conjugated terminal alkyne. 

A regioselective cyclization of pent-4-ynoic acid is catalyzed by a TpRu complex 825. The anti-Markovnikov 3,4-dihydropyran-2-one product is exclusively formed in excellent yield (Equation 339) <2001CC2324>. Similarly, alkynoic esters 826 undergo ICl-promoted iodolactonizations to afford 5-iodo-3,4-dihydropyran-2-ones in moderate yield (Equation 340) <2003JOC10175>. 

R = H or alkyl, the thiolate salts 27 are formed but no elimination takes place because of the low acidity of the hydrogen . Dialkylsulphide elimination from dialkylsulphonium methyl sulphates of -oxocarboxylic acids proceeds readily with aqueous alkali at 0 °C to furnish predominantly high yields of alkynoic esters (equation 86)" . Very recently intramolecular thiol eliminations (i.e. ring openings)... 

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