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A copper(II)-catalyzed protocol to construct trans-configured β-lactams and spirocyclic β-lactams from oximes and methyl propiolate has been developed, which features excellent substrate flexibility and diastereoselectivity (up to >99:1 dr). In situ FT-IR mechanistic experiments support that ketene species might be involved in the formation of β-lactams.

The highly efficient α- and vicinal bis-addition of cyclic imides to methyl propiolate in high yields and β-addition of these imides to α-imidoacrylates in quantitative yields is reported. These reactions offer a simple metal-free method for a gram-scale preparation of practically useful α-imidoacrylates and vicinal bisimides under mild conditions with high atom economy and selectivity.

A new and metal-free approach to the synthesis of substituted 6H-benzo[c]chromenes has been developed. This three-step synthetic sequence starts from variously substituted salicylaldehydes and α,β-unsaturated carbonyl compounds to form the chromene core. The de novo ring-forming key step is based on a highly regioselective intermolecular Diels–Alder cycloaddition between 3-vinyl-2H-chromenes and methyl propiolate, followed by oxidative aromatization of the cyclohexadiene cycloadduct intermediate to obtain the final products in good yields (up to 94% over two steps). A modular and divergent design was followed, including a multicomponent reaction, to maximize the scaffold diversity obtained from our approach. The mechanism, investigated by DFT calculations, was confirmed to be concerted through a slightly asynchronous transition state. Energetic analysis of the transition states which have been found confirmed the experimental results in terms of regioselectivity and reactivity tendencies.

The present study reports on the powerful nematicidal activity of a series of electron-deficient alkynes against the root-knot nematode Meloidogyne incognita (Kofoid and White) Chitwood. Interestingly, we found that the conjugation of electron-withdrawing carbonyl groups to an alkyne triple bond was extremely proficient in inducing nematode paralysis and death. In particular, dimethylacetylenedicarboxylate (10), 3-butyn-2-one (1), and methyl propiolate (4), with EC50/48 h of 1.54 ± 0.16, 2.38 ± 0.31, and 2.83 ± 0.28 mg/L, respectively, were shown to be the best tested compounds. Earlier studies reported on the ability of alkynoic esters and alkynones to induce a chemoselective cysteine modification of unprotected peptides. Thus, also following our previous findings on the impairment of vacuolar-type proton translocating ATPase functionality by activated carbonyl derivatives, we speculate that the formation of a vinyl sulfide linkage might be responsible for the nematicidal activity of the presented electron-deficient alkynes.

International audience; The first example of a silyl gold(I) complex stabilized by an N-heterocyclic carbene (NHC) was synthesised and fully characterized, including crystallographically. The syn insertion of methyl propiolate into the Au-Si bond leading to a vinyl gold complex is reported. As substantiated by X-ray diffraction analysis, the reaction proceeds with opposite regioselectivity compared to that observed previously with phosphine silyl gold(I) complexes.

Reactions of penta-2,4-dienethioamides with acetylenedicarboxylic acid, methyl and ethyl esters, and methyl propiolate were systematically studied, and a number of new 2,3-dihydro-5H-thiazolo[3,2-a...

A new organometallic iodide cluster complex (Bu4N)2[W6I8(C≡C–C(O)OCH3)6] (I), analogous to the previously described (Bu4N)2[Mo6I8(C≡C–C(O)OCH3)6], was obtained by the reaction of (Bu4N)2[W6I14] with silver methyl propiolate AgC≡C–C(O)OCH3. The crystal structure was established for the tetraphenylphosphonium salt (Ph4P)2[W6I8(C≡C–C(O)OCH3)6] (II). According to X-ray diffraction (CIF file CCDC no. 1829205), tungsten atoms in II are coordinated by terminal carbon atoms of methyl propiolate ligands at W–C distances of 2.220(12)–2.268(14) A. The methyl propiolate complexes were characterized by electrospray mass spectrometry, 1H and 13C NMR spectroscopy, elemental analysis, and IR spectroscopy.

Novel polysubstituted pyrrolo[1′,2′:1,2]azocino[4,5-c]quinolines were efficiently synthesized by a one-pot three-component reaction of proline, isatins and chalcones in refluxing methanol and by a sequential domino annulation reaction with methyl propiolate in refluxing acetonitrile. The reaction with isatins without an N-protecting group afforded hexahydropyrrolo[1′,2′:1,2]azocino[4,5-c]quinolines, while the reaction with N-benzylisatins gave octahydropyrrolo[1′,2′:1,2]azocino[4,5-c]quinolones with an additional propiolate unit connecting to a dihydropyridyl ring. The reaction mechanism with domino [3 + 2]cycloaddition, ring-expansion and annulation processes was rationally proposed for the formation of polycyclic products.

Transformations of 2-methyl-1-phenylethynyl-1,2,3,4-tetrahydroisoquinoline resulting from the action of activated alkynes in trifluoroethanol and hexafluoroisopropanol were studied. In reactions with dimethyl acetylenedicarboxylate, 6-phenylethynyl-substituted benzazocines were prepared, while methyl 4-benzyl-5-(2-ethenylphenyl)-1-methyl-1H-pyrrole-3-carboxylate and benzo[d][3]-azacyclodeca[4,6,7]triene with the allene fragment, respectively, were isolated in reactions with methyl propiolate and acetylacetylene in addition to the corresponding benzazocines. As a rule, in hexafluoroisopropanol, the yields of azocines are higher. In reaction with acetylacetylene in dichloromethane, 1-(2-acetylvinyl)-1-phenylethynyltetrahydroisoquinoline is formed in high yield.

Ferrocenyl methyl ketone reacts with aromatic aldehydes yielding 1-ferrocenyl-3-aryl-propenones (chalcones), which upon treatment with Lawesson’s reagent (LR) are converted to the corresponding thiochalcones. The latter enter the thia-Diels–Alder reaction with acetylenic dienophiles (DMAD and methyl propiolate) to give ferrocenyl-substituted 4H-thiopyrans. In the case of methyl propiolate, the formation of the six-membered ring occurs with complete regioselectivity.

A simple approach to a series of 2,4a,7,7a-tetrahydro-1H-cyclopenta[c]pyridines was proposed on the basis of the amino-Claisen rearrangement of readily accessible 2-azabicyclo[2.2.1]hept-5-enes under the action of dialkyl acetylenedicarboxylates, methyl propiolate or propiolamide. The rearrangement is highly diastereoselective and leads to the formation of only one isomer with cis-annulation of the five- and six-membered rings in satisfactory yields. Using the developed method, close analogs of the altemicidin and SB-203207 cores were synthesized.

1-Tetrazolyl-substituted tetrahydro-β-carbolines undergo a reaction with activated alkynes (acetylacetylene, methyl propiolate, and dimethyl acetylenedicarboxylate) over 4–8 days in MeOH or 1 day in CF3CH2OH with the formation of multicomponent mixtures, from which spiro[indole-3,4'-pyridines] were isolated chromatographically. Additionally, two azocino[5,4-b]indoles were isolated from methyl propiolate and acetylacetylene reactions.

A metal-free highly efficient synthesis of a wide range of 4-propenyl 1,4-DHPs from pyridines, methyl propiolate, and aromatic acids is described. The reactions are conducted under convenient conditions and provide products with excellent regioselectivity in good to excellent yields, with broad substrate scope.

With 2-(trimethylsilyl)aryl triflates as aryne precursors, an unprecedented three-component carboarylation reaction of unactivated imines with arynes and carbon nucleophiles has been developed to access a variety of functionalized tertiary amines under transition metal-free conditions. Suitable carbon nucleophiles include chloroform, acetonitrile, and methyl propiolate.

A short route toward aromatic cassane diterpenes from labdane terpenoids has been developed. In the key step, the aromatic ring with the oxygenated function at C-12 and the characteristic carbon group at C-14 of the target compounds is elaborated via a Diels-Alder/aromatization sequence of a furanosesquiterpene and methyl propiolate. On this basis, the synthesis of the proposed structure of benthaminin 1 from trans-communic acid has been achieved. The physical properties of the synthetic compound are somewhat different from those reported for the natural product.

The excellent catalytic effect on methyl propiolate addition to a wide range of aromatic and aliphatic aldehydes promoted by inexpensive and commercially available BINOL-based ligand is reported. The catalyst systems showed high yields and excellent enantioselectivities for aromatic aldehydes, and excellent yields and high enantioselectivities for aliphatic aldehydes.

Three-component reactions of cotarnine chloride with silver acetylides and methyl propiolate or ethynyl methyl ketone in acetonitrile, as well as two-component reactions of 5-phenylethynyl-substituted tetrahydro[1,3]dioxolo[4,5-g]isoquinoline with alkynes in various solvents were studied. Performing them in 2,2,2-trifluoroethanol as the solvent, 10-phenylethynyl-substituted tetrahydro[1,3]dioxolo[4,5-i]-[3]benzazocines were obtained in good yields.

Compounds with propargylamine moiety are useful synthetic precursors of several important classes of nitrogen-containing heterocycles. The title compound, methyl (2E)-3-[3-benzyl-2-(3-methoxy-3-oxoprop-1-yn-1-yl)-2-(1-naphthyl)imidazolidine-1-yl]acrylate, has been prepared by domino-reaction, employing easily available 1-benzyl-2-(1-naphthyl)-4,5-dihydro-1H-imidazole and methyl propiolate in a high 92% yield. The structure of title compound was determined using 1H-NMR, 13C-NMR, UV, FT-IR and HRMS (High-Resolution Mass Spectrometry).

[Formula: see text]-Enaminoesters were generated in situ by the reaction of aliphatic or aromatic primary amines to electron-deficient alkynes, dimethyl acetylenedicarboxylate, and methyl propiolate. [Formula: see text]-Enaminoesters thus formed were reacted with 1-adamantanamine and formaldehyde in methanol to give novel molecular hybrids: dimethyl 3-((3s,5s,7s)-adamantan-1-yl)-1-(alkyl/aralkyl/aryl)-1,2,3,4-tetrahydropyrimidine-5,6-dicarboxylates (5a-j) and methyl 3-((3s,5s,7s)-adamantan-1-yl)-1-(alkyl/aralkyl/aryl)-1,2,3,4-tetrahydropyrimidine-5-carboxylates (9a-j). The structures of the molecular hybrids have been established based on the spectral and analytical data. Structural confirmation of the products was done by X-ray crystallography of 5d as a representative product of the series.

Three-component reactions of tetrahydropyrrolo[1,2-a][1,4]benzodiazepines with methyl propiolate or acetylacetylene and СН, NH, SH, and ОН acids were studied in various solvents. The reaction direction is assumed to depend on the nucleophilicity of anion, formed through deprotonation of acid by the anionic center of initial Michael-type zwitterion.

A powerful, novel approach to meroterpenes conicol, epiconicol and didehydroconicol has been achieved via a key step Diels–Alder reaction of ( E )-3-methyl-1-(2′,5′-dimethoxyphenyl)buta-1,3-diene as diene with methyl vinyl ketone, methyl acrylate or methyl propiolate as dienophiles. Activation by high pressure (9 kbar) or by the use of Lewis acid catalysts, allows the Diels–Alder reaction to proceed in excellent yield and diastereoselectively to form cyclohexenyl-benzene cycloadducts, which are useful precursors for conicols. The successful total syntheses of conicol, epiconicol and didehydroconicol, are described.

A novel method for the assembly of multisubstitued dihydropyridines has been developed starting from methyl propiolate and propargylamines. The reactions were efficiently catalyzed by AuPPh3Cl to get high regioselectivity and high yields. And alternatively, since propargylamines could be easily derived by the CuCl-mediated addition of methyl propiolate to imines, the reactions could be carried out as a sequential three-component model.

2-(Chloromethyl)-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4(3Н)-ones reacted with acetylenedicarboxylate ester, methyl propiolate or acetylacetylene, forming mixtures of 2-(chloromethyl)-5,6,7,10-tetrahydropyrimido[5',4':4,5]thieno[3,2-d]azocin-4(3Н)-ones and 2'-chloromethyl-6'-methylidene-2,3-dihydro-1Н-spiro[pyrido[4,5']thieno[2,3-d]pyrimidin]-4'(3'H)-ones in various ratios. Analogous products were also obtained in the reaction of 2-(methoxymethyl) derivative with methyl propiolate, while using 2-[(morpholin-4-yl)-methyl] derivative in a similar reaction led to the formation of a more complex product mixture.

The three-component reactions of α,β-unsaturated N-arylaldimines, dimethyl acetylenedicarboxylate (methyl propiolate) and isatylidene malononitriles in dry acetonitrile at room temperature afforded polysubstituted spiro[indoline-3,4′-pyridines] in good yields and with high diastereoselectivity. Under similar reaction conditions, the corresponding functionalized spiro[indene-2,4′-pyridines] were also obtained from the three-component reactions containing 2-(1,3-dioxo-1H-inden-2(3H)-ylidene)malononitrile.

A reaction of selenofenchone with propiolic acid in refluxing chloroform produced 1,3-oxaselenin-6-one, which further reacted with acid to afford the ring-opened product. A reaction of 1,3-oxathiin-6-one prepared from thiofenchone with trifluoroacetic acid gave a Wagner–Meerwein rearranged product. In the presence of AlCl3, thiofenchone reacted with methyl propiolate to afford the corresponding rearranged ester.

The Biginelli reaction of methyl propiolate and of methyl 3-diethylaminoacrylate has yielded a novel series of 6-unsubstituted 3,4-dihydropyrimidin-2(1H)-ones. The successie oxidation of the pyrimidine ring, chlorination of the 2-oxo group, and substitution of the chlorine atom by an aromatic amine give previously unknown 2-(arylamino)pyrimidines. 2-Oxo- and 2-(arylamino)pyrimidine-5-carboxylic acids have been obtained.

The three-component reaction of 4-phenyl-, p-methoxyphenyl-, and thienylpyrrolo[1,2-a][1,4]benzo-diazepines with methyl propiolate and indole in dichloromethane proceeds through opening of the diazepine ring. The major transformation products isolated are substituted pyrroles, namely, 1-(2-aminomethylphenyl)-5-(arylmethyl)-2-(indol-1(3)-yl)pyrroles and 1-(2-aminomethylphenyl)-2-aryl-(indol-3-yl)-methylpyrroles.

In the presence of zinc chloride, the in situ generated β-enamino ester from the reaction of morpholine, piperidine and pyrrolidine with methyl propiolate reacted, with aromatic aldehydes and thiourea in ethanol resulting in the functionalized tetrahydropyrimidin-2-thiones in satisfactory yields and with good diastereoselectivity. When aromatic aldehydes bearing electron-withdrawing group were used in the reaction, the 4-hydroxytetrahydropyrimidin-2-thione derivatives were obtained as the main product.

The p -toluenesulfonic acid catalyzed Povarov reaction of isatin-3-imines with β-enamino esters, which were generated in situ from the reaction of arylamines and methyl propiolate in eth­anol, afforded the polysubstituted spiro[indoline-3,2′-quinolines] in high yields and with high diastereoselectivity.

Polysubstituted 3-arylaminoacrylate and tetrahydropyrimidin-2-one derivatives could be selectively produced from the one-pot domino reaction of arylamines, methyl propiolate, aromatic aldehydes, and urea in ethanol in the presence of $$\hbox {FeCl}_{3}$$ as catalyst. Under similar reactions secondary amines such as morpholine and piperidine predominately afford tetrahydropyrimidin-2-one derivatives in good yields.

The one-pot sequential reaction of arylamines, methyl propiolate and 2-aryl-3-nitrochromenes without any catalyst in refluxing ethanol afforded the polysubstituted 3-(3-nitro-2-phenylchroman-4-yl)-3-arylaminoacrylates in good yields and with high diastereoselectivity. Reaction mechanism was believed involving the initial formation of β-enamino ester and sequential Michael addition.

The reaction of [Mo6I14]2– with methyl propiolate HC≡CC(O)OMe in the presence of Ag+ and Et3N yielded the new luminescent complex [Mo6I8(C≡CC(O)OMe)6]2–, the first fully organometallic complex in the family of octahedral {M6X8} clusters. The cluster was crystallized as tetraphenylphosphonium salt and characterized by X-ray single-crystal diffraction and elemental analyses, mass spectrometry, 13C NMR, UV–vis, and luminescence spectroscopies.

It was shown that 2,3,4,5-tetrahydro-1,4-benzoxazepines were cleaved at the N–C(5) bond under the action of activated alkynes in methanol, forming o-(methoxyethyl)- and o-(methoxybenzyl)-phenyl(aminoethyl) ethers. The cleavage rate depended on the electronic effects of the substituents at the C-5 atom. Thiazepine ring expansion in tetrahydro-1,4-benzothiazepine was achieved for the first time via reaction with methyl propiolate to give a benzothiazonine.

The reactions of methyl propiolate and ethyl buta-2,3-dienoate with cyclohexanone induced by SmI2 occurred either at α- or β-position to yield different products depending on with or without a proton source. The synthesis of terpenic acid was demonstrated using this reaction.

An interaction of 1,2-dialkyldiaziridine and 1,2,3-trialkyldiaziridine with methyl propiolate was studied both in organic solvent (MeCN, CH2Cl2, C6H6) and in ionic liquids. Earlier unknown linear structures, in which three molecules of methyl propiolate were suited to one diaziridine molecule (adducts 1 : 3), were obtained in MeCN. The diaziridine ring expansion products 1,2,3,4-tetrahydropyrimidine derivatives (adducts 1 : 2) and, along with them in some cases, the same linear structures were obtained in ionic liquids. A mechanism of reactions found was offered. The regioselectivity of reactions was supposed to determine by the structure of substituents in initial diaziridines. This conclusion was supported by quantum chemical calculations.

The excellent catalytic effect on methyl propiolate addition to a wide range of aromatic and aliphatic aldehydes promoted by inexpensive and commercially available BINOL-based ligand is reported. The catalyst systems showed high yields and excellent enantioselectivities for aromatic aldehydes, and excellent yields and high enantioselectivities for aliphatic aldehydes.

Diels-Alder reactions of a range of 1-(alkoxy/alkyl/halogen-substituted phenyl)buta-1,3-dienes with methyl propiolate carried out in a green ethanolic medium under 9 kbar pressure were investigated. The use of high pressure as activating method of the Diels-Alder reactions allows efficient and regioselective generation of a series of cyclohexadienyl-benzene cycloadducts that are oxidized to the corresponding biaryls. The alkoxy/alkyl/halogen-substituted biaryls produced are useful precursors for accessing substituted 6H-benzo[c]chromen-6-ones and the cannabinols family.

A novel domino reaction of tetrahydrobenzofuro[3,2-c] or [2,3-c]pyridines with dimethylacetylene dicarboxylate (DMAD) or methyl propiolate (MP) resulted in the formation of spirobenzofuranpyridines in moderate yields. The spirobenzofuran derivatives reported may be considered analogs of the antifungal drug griseofulvin.

3-Ethylhexahydropyrazino[3,2,1-jk]carbazole is converted into hexahydro[1,4]diazocino[7,8,1-jk]carbazoles by the action of methyl propiolate and acetylacetylene in acetonitrile and into 1-methoxy9-(β-vinylethylamino)ethylcarbazoles by the action of acetylenedicarboxylic ester and methyl propiolate in methanol. 3-Benzyl-substituted pyrazinocarbazole does not react with alkynes.

In this study, a new, green analytical method is proposed for the determination of N-acetylcysteine (NAC) in pharmaceutical formulations. The analyte was separated from the samples matrix using a 100% aqueous mobile phase [0.05% v/v CH3COOH+1 mmol L−1 ethylenediaminetetraacetic acid (EDTA) in water] and a suitable analytical column (Prevail reversed phase column). Detection was carried out at 285nm after on-line post-column derivatization (PCD) with methyl-propiolate (MP) in alkaline medium. Method development included both chromatographic and reaction parameters, while validation was based on international recommendations. The developed analytical scheme excludes the use of organic modifiers from all steps of pretreatment/analysis and offers adequate figures of merit for the quality control (assay and content uniformity) of NAC-containing formulations.

Postsynthetic strategy based on organic coupling reactions has been explored for the synthesis of novel coordination complexes with larger dimensions. A discrete coordination species with a paddlewheel motif, dicopper(II) tetracarboxylate Cu2(OOC-C6H4-N3)4(quinoline)2 (SBU1), was covalently modified with methyl propiolate via “Click” reaction to generate a new coordination compound Cu2(OOC-C6H4-C2N3H-COOCH3)4·(quinoline)2 (1). The combination of single-crystal X-ray diffraction, diffusion NMR and ESR has confirmed the success of covalently modifying SBU1 and the retention of the structural integrity after the postsynthetic modification.

An efficient synthetic method for the densely substituted 3-arylaminoacrylates was successfully developed via the one-pot reaction of arylamines, methyl propiolate, aromatic aldehydes, and active methylene compounds such as pivaloylacetonitrile, 1,3-cyclopentanedione, and 4-hydroxycoumarin. The key step of the reaction was believed to involve the formation of a β-enamino ester and a sequential Michael addition to the in situ formed arylidene dicarbonyl compound.

It has been established that 2-R-4-oxotetrahydropyrido[4,3-d]pyrimidines, under the action of activated alkynes in methanol, form a mixture of 2-R-4-oxohexahydropyrimido[4,5-d]azocines and products of decomposition of the tetrahydropyridine ring, the 2-R-5-methoxymethyl-4-oxo-6-vinylaminoethyl-pyrimidines. Tetrahydropyrido[3,4-d]pyrimidine, isomeric at the junction of the pyrimidine and tetrahydropyridine rings, forms only the corresponding pyrimido[5,4-d]azocine, the product of expansion, under the action of methyl propiolate.

The kinetic study of the alcaline hydrolysis of methyl acrylate and propiolate, in acetone 70% — water 30%, have been made. The rate of hydrolysis of methyl propiolate is to fast to be measured: at‐12° the reaction is finished in less than 4 minutes. In the case of methyl acrylate the Arrhenius parameters are: E=12,9 Kcal./mole log PZ=8,27. Copyright © 1955 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim

A convenient and efficient one-pot sequence has been developed for the synthesis of C-carbamoyl-1,2,3-triazoles from alkyl bromide using (i) sodium azide, (ii) methyl propiolate and copper iodide, and (iii) amines, zirconium tert-butoxide, and 1-hydroxybenzotriazole, under microwave irradiation. The sequential reactions in one-pot provided the desired C-carbamoyl-1,2,3-triazoles in excellent yields.