Alkyl Propiolates Research Articles

Domino Approach for the Synthesis of Pyridinium Salts and 1,2,3,8a-Tetrahydroimidazo[1,2-a]pyridines from 2-Imidazolines and Propiolic Acid Esters.

Adducts of 1-alkyl-2-imidazolines and two molecules of alkyl propiolate, possessing an N-propargyl-β-enaminoester fragment, easily undergo a domino reaction to form pyridinium salts with β-(alkylammonio)ethyl group at the nitrogen atom in the presence of 2 equiv of a protic acid. Treatment of the above reaction mixture with a base gives 1,2,3,8a-tetrahydroimidazo[1,2-a]pyridines. Reaction of the latter compounds with acid chlorides affords pyridinium salts with β-(alkylamido)ethyl moiety at the nitrogen atom.

Highly Efficient and Regioselective Synthesis of N‐Acyl Protected 2‐Aminoacrylates through a PPh3‐Catalyzed Reaction of Alkyl Propiolates with Amides

AbstractA simple and convenient strategy for the synthesis of N‐acyl protected 2‐aminoacrylates via PPh3‐catalyzed reaction of alkyl propiolates with amides has been developed. This protocol is rapid and highly regioselective to provide various N‐acyl protected 2‐aminoacrylates in high yields (up to 95 %). The chemical structure of the product was determined by X‐ray single‐crystal structure analysis. In contrast, 3‐sulfonamidoacrylates were obtained by Cs2CO3‐catalyzed reactions of alkyl propiolates with secondary sulfamides. Moreover, synthetic utility of this method was further highlighted in the late‐stage modification of drug molecules.

Diisobutylaluminium hydride mediated efficient synthesis of Morita–Baylis–Hilman adducts through α‐functionalization of alkyl propiolates

AbstractGenerally, oxindole derivatives are biologically important molecules and valuable building blocks in organic synthesis. Herein, we report a diisobutylaluminium hydride mediated efficient one‐pot synthesis of oxindole derivatives using N‐substituted isatins with methyl or ethyl propiolates at lower temperature (−78°C) through Morita‐Baylis‐Hillman (MBH) reaction. Within a short reaction time, a wide range of N‐alkyl or N‐aryl 3‐hydroxy oxindole derivatives (MBH adducts) were easily accessed in excellent yields under mild reaction conditions.

Regio- and Stereoselective One-Pot Synthesis of New Heterocyclic Compounds with Two Selenium Atoms Based on 2-Bromomethyl-1,3-thiaselenole Using Phase Transfer Catalysis

To date, not a single representative of 2,3-dihydro-1,4-thiaselenin-2-yl selenides has been described in the literature. The reaction of 2-bromomethyl-1,3-thiaselenole with potassium selenocyanate at low temperature was accompanied by a rearrangement with ring expansion leading to six-membered 2,3-dihydro-1,4-thiaselenin-2-yl selenocyanate, which was used for the generation of sodium dihydro-1,4-thiaselenin-2-yl selenolate. The latter intermediate was involved in situ in the nucleophilic substitution and addition reactions under phase transfer catalysis conditions. The nucleophilic substitution reactions with alkyl halides gave alkyl, allyl and propargyl 2,3-dihydro-1,4-thiaselenin-2-yl selenides in 93–98% yields. The addition reactions of dihydro-1,4-thiaselenin-2-yl selenolate anion to alkyl acrylates, acrylonitrile and alkyl propiolates proceeded in a regio- and stereoselective fashion affording corresponding functionalized 2,3-dihydro-1,4-thiaselenin-2-yl selenides in 93–98% yields. Thus, the regio- and stereoselective one-pot synthesis of a novel family of 2,3-dihydro-1,4-thiaselenin-2-yl selenides has been developed based 2-bromomethyl-1,3-thiaselenole, potassium selenocyanate, alkyl halides and compound with activated double and triple bonds.

Acetylenic Esters in Organic Synthesis

AbstractActivated acetylenic substrates such as acetylenic esters and alkyl propiolates are very important in organic synthesis. Due to their electron deficiency, these compounds are widely used in combinatorial and multicomponent reactions, enabling the synthesis of a large variety of novel compounds. In addition, these substrates are powerful Michael acceptors and convenient dienophiles and dipolarophiles in Diels–Alder and 1,3-dipolar cycloaddition reactions. The addition of different nucleophiles, primarily phosphorus, nitrogen or sulfur, to the triple bonds of these substrates produces key intermediates, such as Tebby and Huisgen zwitterions, which can lead to designing pathways toward the generation of spirocyclic and polycyclic compounds. This account highlights recent studies on the chemistry of acetylenic esters and their applications in organic synthesis.1 Introduction2 Synthesis of Acyclic and Monocyclic Compounds3 Synthesis of Spirocyclic Compounds4 Synthesis of Polycyclic Compounds5 Conclusion

Copper-catalyzed C-H/N-H annulation of enaminones and alkynyl esters for densely substituted pyrrole synthesis.

Herein, the copper-catalyzed annulation of enaminones with alkynyl esters for the facile synthesis of different pyrroles with a 2,3,4,5-tetrasubstituted structure has been developed. With Cu(OAc)2 as the only catalyst, the tunable synthesis of 2-vinyl and 2,3-dicarboxyl-functionalized pyrroles has been achieved by using terminal and internal alkynyl esters, respectively. The synthesis of 2-vinyl pyrroles represents the first example accessing 2-vinyl substituted pyrroles via direct cascade reactions involving vinylation and pyrrole ring formation.

Intramolecular Diels‐Alder Reaction of Styrene with Phenoxy‐Acrylate for Construction of Functionalized Naphthalenes

AbstractThe DABCO promoted domino reaction of 1‐(2‐hydroxyphenyl)‐3‐phenylprop‐2‐en‐1‐ones and alkyl propiolate or dialkyl but‐2‐ynedioate in toluene at high temperature resulted in methyl 3‐(2‐hydroxybenzoyl)‐1‐naphthoates or dimethyl 3‐(2‐hydroxybenzoyl)naphthalene‐1,2‐dicarboxylate in moderate to good yields. The hydroxyl group played a crucial rule in the reaction. The reaction mechanism of this formal [4+2] cycloaddition reaction was believed with initially formation of methyl 3‐(2‐cinnamoylphenoxy)acrylate, intramolecular Diels‐Alder reaction, ring‐opening of benzo[b]xanthene and aromatization process.

Efficient Synthesis of a New Family of 2,6-Disulfanyl-9-selenabicyclo[3.3.1]nonanes.

The efficient synthesis of a new family of 2,6-disulfanyl-9-selenabicyclo[3.3.1]nonanes in high yields has been developed based on 9-selenabicyclo[3.3.1]nonane-2,6-dithiolate anion generated from bis-isothiouronium salt of 2,6-dibromo-9-selenabicyclo[3.3.1]nonane. The derivatives of 2,6-disulfanyl-9-selenabicyclo[3.3.1]nonane containing alkyl, allyl and benzyl moieties have been prepared in 90–99% yields by nucleophilic substitution of 9-selenabicyclo[3.3.1]nonane-2,6-dithiolate anion with alkyl, allyl and benzyl halides. The reaction of nucleophilic addition of 9-selenabicyclo[3.3.1]nonane-2,6-dithiolate anion to alkyl propiolates afforded 2,6-di(vinylsulfanyl)-9-selenabicyclo[3.3.1]nonanes. The conditions for regio- and stereoselective addition of 9-selenabicyclo[3.3.1]nonane-2,6-dithiolate anion to a triple bond of alkyl propiolates have been found. To date, not a single representative of 2,6-disulfanyl-9-selenabicyclo[3.3.1]nonanes has been described in the literature.

Switching the reactivity of cyanomethylpyridinium salts in the 1,3-cycloaddition conditions with alkyl propiolates to cyanoindolizines or cyanoazaindolizinyl-indolizines

A particular reactivity of 1-cyanomethylpyridinium salts was revealed in the [3 + 2] cycloaddition conditions with alkyl propiolates. Cycloadducts 3 were obtained in reactions carried out at room temperature while refluxing in CH3CN provided unexpected ethyl or methyl 3-(3-cyanoimidazo[1,2-a]pyridin-2-yl)indolizine-1-carboxylates 4. The structure of the new 2:1 azaindolizine-indolizine adducts was secured by X-ray analysis. Methodological efforts have enabled the adjustment of the reactivity towards the formation of 3-cyanoindolizines 3 or cyanoazaindolizine-indolizines 4. A mechanism for the formation of azaindolizine-indolizines was proposed. A portfolio of rare cyanoindolizines and cyanoazaindolizine-indolizines has been successfully obtained.

Regio- and stereoselective synthesis of new ensembles of diversely functionalized 1,3-thiaselenol-2-ylmethyl selenides by a double rearrangement reaction.

The reaction of 2-(bromomethyl)-1,3-thiaselenole with potassium selenocyanate proceeded via a rearrangement with ring expansion, leading to a six-membered 2,3-dihydro-1,4-thiaselenin-2-yl selenocyanate (kinetic product) which in turn underwent rearrangement with ring contraction to a 1,3-thiaselenol-2-ylmethyl selenocyanate (thermodynamic product). These rearrangements occurred by a nucleophilic attack of the selenocyanate anion at two different carbon atoms of the seleniranium intermediate. The efficient regioselective synthesis of alkyl, allyl, 2-propynyl, benzyl, 4-fluorobenzyl, and 2-pyridinylmethyl 1,3-thiaselenol-2-ylmethyl selenides was developed based on the generation of sodium 1,3-thiaselenol-2-ylmethylselenolate from 1,3-thiaselenol-2-ylmethyl selenocyanate or bis(1,3-thiaselenol-2-ylmethyl) diselenide followed by nucleophilic substitution reactions. Sodium 1,3-thiaselenol-2-ylmethylselenolate underwent nucleophilic addition to alkyl propiolates in a regio- and stereoselective manner affording 1,3-thiaselenol-2-ylmethyl vinyl selenides in high yields predominantly with Z-configuration. Not a single representative of the 1,3-thiaselenol-2-ylmethyl selenide scaffold has been previously described in the literature.

Biaryl and atropisomeric biaryl aldehyde synthesis by one-step, metal-free benzannulation of aryl enals and propiolates

The metal-free benzannulation reactions of alkyl propiolates and aryl enals have been developed for biaryl and atropisomeric biaryl aldehyde synthesis.

Mild and Efficient Synthesis of Polysubstituted Phthalimides and Piperidines Catalyzed by DABCO

Polysubstituted phthalimide derivatives have been isolated in excellent yield from the addition reaction between acetoacetanilide and dialkyl acetylenedicarboxylates by using DABCO as an efficient basic catalyst in EtOH at room temperature. This procedure led to the formation of new phthalimide derivative in the presence of di-tert-butylacetylendicarboxylate as acetylenic ester. The methodology has also been applied successfully for the synthesis of novel piperidine substitutes via the simple reaction between acetoacetanilide and alkyl propiolates. These reactions have some advantages such as not only the process is eco-friendly but also the yields are good and the work-up is simple.

Synthesis of functionalized 1,2-dihydroisoquinolines via one-pot reactions of isoquinoline, alkyl propiolate, and thiazolidin-2,4-dione

The reactive zwitterionic intermediates, generated from addition of isoquinoline to alkyl propiolates, react with thiazolidin-2,4-dione to afford 3-[1-(2,4-dioxothiazolidin-3-yl)isoquinolin-2(1 H)-yl]acrylates in good yields. Using (Z)-5-arylidenethiazolidine-2,4-diones as the NH-acidic component leads to 3-{1-[( Z)-5-benzylidene-2,4-dioxothiazolidin-3-yl] isoquinolin-2(1 H)-yl}acrylates in moderate to good yields in the absence of any catalysts under mild reaction conditions. The reaction between quinoline, ethyl propiolate, and thiazolidin-2,4-dione leads to ethyl 3-[2-(2,4-dioxothiazolidin-3-yl) quinolin-1(2 H)-yl]acrylate.

Pyridine‐Based Organocatalysts for Regioselective syn‐1,2‐Silaboration of Terminal Alkynes and Allenes

AbstractAn organocatalytic silaboration of terminal alkynes and allenes was established using pyridine‐based catalysts. In the presence of 4‐cyanopyridine (1–2 mol%), alkyl propiolates underwent regio‐ and stereoselective addition of silylboronic esters in toluene at 135 °C to afford (Z)‐3‐boryl‐2‐silylacrylates in good yields. 2,6‐Dichloro‐4,4′‐bipyridine and 4‐(3,5‐dichlorophenyl)pyridine also exhibited high catalyst efficiency for the 1,2‐silaboration of ethyl propiolate, whereas 1,1‐silaboration was induced by P(n‐Bu)3, t‐BuOK, and ICy to afford ethyl 3‐boryl‐3‐silylacrylates as Z/E mixtures. The silaboration of ethynylbenzenes and terminal allenes was also catalyzed by 4‐cyanopyridine to afford (Z)‐β‐boryl‐α‐silylstyrenes and β‐borylallylsilanes in a regioselective manner.

Proposed Mechanism for the High-Yield Polymerization of Oxyethyl Propiolates with Rh Complex Catalyst Using the Density Functional Theory Method.

In this study, poly(oxyethyl propiolate)s (POP)s featuring various oxyethylene derivatives are synthesized using a [Rh(norbornadiene)Cl]2 catalyst. In particular, POPs featuring the normal oxyethylene chain in the side-chain exhibit excellent yields and high molecular weights in methanol and N,N-dimethylformamide at 40 °C, compared with poly(n-alkyl propiolate)s (PnAP)s. The high reactivity of the oxyethyl propiolate (OP) monomers is clarified by considering the time dependences of the polymerization yields of OPs and alkyl propiolates (Aps). Furthermore, the monomer structure and intermediate conformation of the Rh complex are optimized using Density Function theory (DFT) methods (B3LYP/6-31G** and B3LYP/LANL2DZ) and a polymerization mechanism is proposed.

Highly Regio- and Stereoselective Hydrogermylation of Fluorinated Alkyl Propiolate

The selective introduction of fluoroalkylated vinylmetals in controlled strategies is a challenging process for many chemists. This study reports the highly regio- and stereoselective synthesis of functionalized vinylgermanes bearing a perfluoroalkyl group from per­fluoroalkylated acetylenic esters via AlCl3-catalyzed hydrogermylation. Regio- and stereoselectivity are highly dependent on the nature of the catalyst and the nature of the fluoroalkyl group of alkyne.

Construction of Unique Eight- or Nine-Membered Polyheterocyclic Systems via Multicomponent Reaction of l-Proline, Alkyl Propiolate, and Isatin.

The multicomponent reaction of l-proline, isatins, and excess of methyl propiolates in methanol unexpectedly afforded 2-(oxoindolin-3-ylidene)propylidene)pyrrolidin-1-yl)acrylates in good yields, and the products subsequently converted to unique nine-membered pyrrolo[1',2':1,9]azonino[6,5,4- cd]indoles in the presence of p-TsOH. Furthermore, the multicomponent reaction of l-proline, N-benzylisatins, and excess alkyl propiolates in refluxing chloroform unprecedentedly resulted in eight-membered azocino[1,2- a]benzo[ c][1,5]diazocines as the main product. The molecular structures of the polyheterocyclic compounds were confirmed by determination of 19 single crystal structures. The reaction mechanism was believed to contain the sequential 1,3-dipolar cycloaddition, addition of cyclic tertiary amine to excess of propiolate, and fascinating ring opening as well as rearrangement process. The N-substituent on isatins played a critical role in the different reaction patterns.

Alkyl Propiolates Participated [3+2] Annulation for the Switchable Synthesis of 1,5‐ and 1,4‐Disubstituted 1,2,3‐Triazoles Containing Ester Side Chain

AbstractBy means of a featured enamine activation, the alkyl propiolates have been successfully employed in the [3+2] annulation for the synthesis of 1,2,3‐triazoles. The synthesis of both 1,4‐ as well as the hardly available 1,5‐disubstituted 1,2,3‐triazoles can be selectively accessed by using tosyl azide and tosyl hydrazine as nitrogen source, respectively.

Three-Component Reaction of 4-Methylpyridine with Alkyl Propiolates and Secondary Phosphine Chalcogenides

The reaction between 4-methylpyridine, alkyl propiolates, and secondary phosphine oxides proceeded as N-vinylation-C-phosphorylation with stereo- and regioselective formation of (E)-N-ethenyl-C2- phosphoryl-1,2-dihydropyridines [when using bis(2-phenylethyl)phosphine oxide] or (E)-N-ethenyl-C4- phosphoryl-1,4-dihydropyridines (when using diphenylphosphine oxide). The process occurred at 60–62°C within 3 h to give functional dihydropyridines in 40–82% yield. Under similar conditions, bis(2-phenylethyl) phosphine sulfide and selenide reacted with alkyl propiolates preferably by nucleophilic PH-monoaddition at the triple bond.

Regioselective intramolecular annulations of ambident β-enamino esters: A diversity-oriented synthesis of nitrogen-containing privileged molecules

Diversity-oriented, regioselective, intramolecular annulation of β-enamino esters is described under solvent-free, calcium-catalysis. 2-aminoaryl ketones and alkyl propiolates undergone a [4+2] annulation to yield substituted quinolines; with an excess of alkyl propiolates, benzodiazepines were formed via a [4+2+1] annulation. We also described a one-pot, 3-component synthesis of quinoline derivatives via a [4+2+2] annulation. Interestingly, 2-aminoaryl ketones undergone a self-condensation [4+4] and gave the dibenzodiazocines.