Alkyl propiolate

Quaternarization of 43 with phenacyl bromide produced the corresponding salt 51 that was reacted with several triple-bond-containing dipolarophiles (Scheme 4), such as dimethyl acetylenedicarboxylate (DMAD) or alkyl propiolates to give tricyclic compounds 52, 53 and 54, 55. Compound 51 reacted also with acrylonitrile as dipolaro-phile in MeCN/K2C03 to give the cycloadduct 56 as a mixture of diasteroisomers. 

Better yields may be obtained from vinylpyridines and alkyl propiolates, as can be seen from the conversion of 36 to the cycl[3,2,2]-azine (lw).41 Reaction of a-(bismethylthio)methylene-2-pyridineaceto-nitrile and ethyl bromoacetate using triethylamine afforded the indolizine derivative (37). Dimethyl l-carbamoyl-2-methylthiocycl-[3,2,2]azine-3,4-dicarboxylate (Iz) was synthesized by allowing dimethyl acetylenedicarboxylate to react with indolizine derivative 38, which was obtained by decarboxylation of 37 using sulfuric acid in presence of palladium-on-charcoal as catalyst [Eq. (6)].42... 

Dihydro-1,3-thiazine derivatives (208) and (210) are prepared by the addition of alkyl propiolates to thioureas and dithiocarbamic acids respectively. In the latter case it is necessary to cyclize the initial products (209) with acetic anhydride (Scheme 96) (70AJC51). Ring expansion of isothiazolium chlorides (211) by the action of potassium cyanide provides a route to imine derivatives (212 Scheme 97) (79TL1281). 

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. 

Keywords benzaldehyde, alkyl propiolate, primary amine, cyclocondensation, microwave irradiation, 1,4-dihydropyridine... 

The benzaldehyde derivative 1 (4 mmol), alkyl propiolate 2 (8 mmol), primary amine 3 (4 mmol), and 2 g silica gel were mixed thoroughly in a mortar. Then tlie reaction mixture was transferred to a beaker and irradiated with microwaves for 4 min. The progress of reaction was monitored by TLC. The mixture was extracted widi 3x30 mL CHC13, filtered, and the solvent was removed by a rotary evaporator under reduced pressure. Further purification by recrystallization gave die desired pure products 4. 

In the reaction of 2-(hexahydropyrimidin-2-ylidene)cycloalkanone 247 and alkyl propiolate for 20-40 hours, after addition and cis-trans isomerization, the spiro intermediates 248 suffered ring cleavage by the attack of a molecule of alcohol to give alkyl 6-oxo-1,2,3,4-tetrahydro-6//-pyrido[ 1,2-a]pyrimidine-9-alkanoates 249 (Scheme 19) (87CB1803, 87TL1527). 

Tetrasubstituted pyrroles could be obtained by skeletal rearrangement of 1,3-oxazolidines, a reaction that is substantially accelerated by microwave irradiation. Dielectric heating of a 1,3-oxazolidine 7, absorbed on silica gel (1 g silica gel/mmol) for 5 min in a household MW oven (900 W power) cleanly afforded the 1,2,3,4-tetrasubstituted pyrrole 8 in 78% yield, thus reducing the reaction time from hours to minutes (Scheme 5) [24], 1,3-Oxazolidines are accessible in one-pot, two-step, solvent-free domino processes (see also Sect. 2.6). The first domino process, a multi-component reaction (MCR) between 2 equivalents of alkyl propiolate and 1 equivalent of aldehyde furnished enol ethers 9 (Scheme 5). Subsequent microwave-accelerated solvent-free reactions of enol ethers 9 with primary amines on silica support afforded intermediate 1,3-oxazolidines, which in situ rearranged to the tetrasubstituted pyrroles (2nd domino process). Performed in a one-pot format, these... 

Stable phosphorus ylides (50) and (51) have been prepared from the reaction of electron-deficient acetylenic esters, such as dialkyl acetylenedicarboxylates or alkyl propiolates and triphenylphosphine in the presence of 3-chlorotetrahyd-rofuran-2,4-dione (Scheme 10). These reactions are thought to proceed via vinylphosphonium salt intermediates which undergo Michael addition with the conjugate base of the CH-acid. Similar methodology has been used to prepare phosphonium ylide (52) from triphenylphosphine, isatin (indoline-2,3-dione) and dimethyl acetylenedicarboxylate. " ... 

Michael addition of imidazole (1) and benzimidazole (5) to alkyl propiolate (2) can be promoted by KIO montmorillonite clay affording alkyl 3-(imidazol-l-yl)acrylate (3) and alkyl 3-(benzimidazol-l-yl)acrylates (6), respectively. Michael adduct of 2-mercaptobenz-imidazole (8) undergoes cyclization in the presence of clay catalyst to 4-oxo-4H-[ 1,3]thiazino[3,2-a]benzimidazole (9). 

Table 1. Reaction of imidazole (1) with alkyl propiolate (2)...

The mixture of (benz)imidazoles (0.01 mole), alkyl propiolate (0.01-0.02 mole), KIO montmorillonite (Aldrich, 2-4 g), and toluene (50-100 ml) was stirred at 110 °C for 1 -7 hours. The clay was filtered off from the hot reaction mixture and washed with CHCI3 (50 ml). The combined filtrate was evaporated and the crude product was analyzed by H-NMR spectroscopy (200 MHz). The products were purified or separated by crystallization or column chromatography. 

The biselectrophilic reactivity motif of alkynones is also present in 3-substituted alkyl propiolates 2. Utilizing the previously described Michael addition/cyclocondensation approach with various binucleophiles allows the introduction of oxo/hydroxyl substituents to the heterocycle. An example of the concept is the copper(I)-catalyzed carboxylation of terminal alkynes, which allows the convenient synthesis of 3-substituted alkyl propiolates 2 a by trapping the intermediary carboxylate with methyl iodide. This one-pot procedure can be expanded to a three-component process by adding binucleophiles such as amidines 36 and hydrazines 20 to furnish the corresponding 2,6-disubstituted pyrimidin-4(3fl)-ones 54 and 1,5-disubsti-tuted 3-hydroxypyrazoles 55 in a one-pot fashion. The incorporation of nontoxic, abundant and economical carbon dioxide provides an environmentally benign access to interesting heterocyclic structures (Scheme 33) (2014ASC(356)3135). 

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