Acetylenic Esters Research Articles

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.

Carbon-carbon bond forming reactions of acetylenic esters and ketones within frustrated phosphane/borane Lewis pair frameworks.

The three-component reactions of bulky diarylbutenylphosphanes with dimethyl acetylenedicarboxylate (1a) and the strong boron Lewis acid B(C6F5)3 give the ylide-substituted cyclopropane derivatives 26. The acetylenic ester 1a and ketone 1b react with oligomethylene bridged frustrated phosphane/borane Lewis pairs to give the bicyclic C-H insertion/C-C coupling reaction products. The formal carbene products are formed by means of stepwise sequences involving polar intermediate.

Evaluation of WO2014121383 A1: a process for preparation of rufinamide and intermediates

ABSTRACTIntroduction: There is great potential in the synthetic development of rufinamide to treat childhood-onset epilepsy known as Lennox–Gastaut syndrome (LGS).Areas covered: 1,4-disubstituted triazole ring formed by 1,3-dipolar cycloaddition reaction is an important structural motif widely used to construct diverse chemotypes in chemical, biological, and material fields. 1,2,3-triazole ring containing rufinamide, an antiepileptic drug developed by Novartis, is useful in combination with other antiepileptic medicaments for the treatment of childhood-onset epilepsy known as LGS. There are numerous synthetic methods used to construct the rufinamide through 1,3-dipolar cycloaddition. The application claims processes for the preparation of rufinamide and their intermediates. The synthetic strategy covered for the synthesis of rufinamide using activated acetylenic esters. The activation is done using N-hydroxy succinimide, N-hydroxyphthalimide, 1-hydroxy benzotriazole, and 4-nitro phenol.Expert opinion: The manufacturing route appears to follow the regioselective Cu catalyzed cycloaddtion of 2,6-difluro benzyl azide with or without isolated activated acetylenic esters in three steps that provide a good lead for new synthetic strategy for the rufinamide synthesis.

Base-Catalyzed Tandem Cyclization: Diastereoselective Access to the 3,4-Dihydroisoquinolin-2(1H)-one Core

A novel, one-pot reaction for the synthesis of 3,4-dihydroisoquinolin-2(1H)-one derivatives is developed via a base-mediated three-component reaction of ninhydrin, aniline and acetylenic esters. This diastereoselective reaction takes place in methanol at 70 °C under transition-metal-free conditions, and direct construction of the C–N and C–C bonds is readily achieved via tandem cyclization. These cyclic frameworks are resourceful small molecular keys to many natural products.

The Effect of Spatial Hindrance on Stereoselective Synthesis of Real Enaminoesters and Determination of the Relative Stability of the Two E- and Z-Isomers of Hypothetical Enaminoesters

The three-component reactions of isoquinoline and acetylenic esters in the presence of 2-tert-butyl-4-methylphenol has been investigated. The reactions were proceeded smoothly at room temperature without the usage of a catalyst. The structures of the synthesized compounds were characterized by elemental analyses and spectral studies. Also, quantum mechanical calculations were carried out using the ab initio and DFT methods at the HF/6-31G (d,p) and B3LYP/6-31G (d,p) levels of theory to determine the stability of the two E and Z-isomers from both the hypothetical and real reactions between phenantridine or isoquinoline and dimethyl acetylendicarboxylate in the presence of phenol derivatives for the generation of enaminoesters, in both gas phase and solvent media (polar and nonpolar). The results showed that more effective hindrance of any reactants (phenol derivatives, acetylenic esters and phenantridine or isoquinoline) should be considered for the generation of highly stereoselective enaminoester (E-isomer) in real or hypothetical synthesis. To reduce the effect of spatial hindrance on all cases (real or hypothetical synthesis) of E-enaminoester, corresponding to its more stability, the hydrogen atom and phenanthridine (or isoquinoline) moieties were positioned on the side of the double bond within the structure of an enaminoester. The E-isomers were recognized as the preferential form of the highly stable enaminoester and they can be considered as an effective product that has biological activity.

Synthetic strategies towards the carbenoid reactions of ; -acetylenic carbonyls

Catalytic reactions of $\alpha ,\beta $-conjugated carbonyl compounds have been a practical tool towards the synthesis of different useful heterocyclic compounds. Despite the numerous reactions with carbon-carbon double bond conjugated carbonyls, reactions of acetylenic carbonyls are limited. In this study, efficient dioxole synthesis was carried out via acetylenic aldehydes and butadiene formation was preferred over cyclopropene formation via acetylenic esters as different functional groups on these substrates change the product distribution. Both reaction conditions (such as solvent and temperature) and electrophilic structure of metal carbenoids alter the product distribution; acceptor (A), donor-acceptor (DA), and acceptor-acceptor (AA) functionalized diazo compounds yield different product types over different mechanisms.

A Synthesis of Novel Perinaphthenones from Acetylenic Esters and Acenaphthoquinone–Malononitrile Adduct in the Presence of Triphenylphosphine

A facile protocol involving Tebby zwitterions (PPh3-acetylenic esters) and the Knoevenagel condensation product of acenaphthylene-1,2-dione with malononitrile or ethyl cyanoacetate for the selective synthesis of a new series of perinaphthenone derivatives is described. Triphenylphosphine plays a catalytic role in these transformations. The structure of a typical product was confirmed by X-ray crystallography. The merits of this method include high yields of products, good atom economy, and a metal-free catalyst.

A Convenient Synthesis of Functionalized 2,3-Diazaspiro[4.4]nona-1,6,8-trienes

A convenient Michael addition/cyclization sequence of alkyl isocyanide–acetylenic ester zwitterionic adducts with various pyrazolone derivatives, leading to the formation of dialkyl 6-(alkylamino)-1-methyl-4-oxo-3-phenyl-9-aryl-2,3-diazaspiro[4.4]nona-1,6,8-triene-7,8-dicarboxylates in moderate to good yields, is described. The structure of the target compounds was confirmed by an X-ray diffraction study.

Semi-synthesis, antibacterial and antifungal activities of three novel thiazolidin-4-one by essential oil of Anethum graveolens seeds as starting material

The three novel compounds of thiazolidin-4-one were synthesized by the reaction of essential oil of Anethum graveolens seeds (containing carvone) with thiosemicarbazide and acetylenic esters. The essential oil of A. graveolens seeds were analyzed by GC–MS after extraction that were containing high amount of carvone (37%). Carvonethiosemicarbazone was produced by the reaction of carvone with thiosemicarbazide that this compound in the reaction with acetylenic esters produced thiazolidin-4-one derivatives. The synthetic compounds 6a–c was confirmed by FT-IR, 1H-NMR, 13C-NMR and mass spectral data. Antimicrobial and antifungal activities of the synthetic compounds were assessed against 9 Gram-positive and 7 Gram-negative pathogenic bacteria as well as three fungal strains. The activities were reported as inhibition zone diameter, minimum inhibitory concentration, minimum bactericidal concentration and minimum fungicidal concentration values.

Synthesis of 2-Selanylidene-1,9A-Dihydro-2H-Pyrido[1,2-A]Pyrimidine Derivatives

The reactive intermediate produced in the reaction between pyridines and acetylenic esters was trapped by aryl isoselenocyanates to afford 2-selanylidene-1,9a-dihydro-2H-pyrido[1,2-a]pyrimidine derivatives in good yields.

Regioselective four-component synthesis of new tetrazolo[1,5-a]quinoline-based 2-amino-1,4-dihydropyridine and pyridin-2(1H)-one derivatives using nano-ZnO catalysis.

Four-component reaction between primary amines, dialkylacetylendicarboxylates, tetrazolo[1,5-a] quinoline-4-carbaldehyde and ethyl-2-cyanoacetate in the presence of 1,4-diaza-bicyclo[2.2.2]octane and zinc oxide nanoparticles results to the regioselective production of new tetrazolo[1,5-a]quinoline-based 2-amino-1,4-dihydropyridine or pyridin-2(1H)-one derivatives in good to high yields. The selectivity of the catalyzed reaction toward the generation of the dihydropyridine or pyridin-2(1H)-one derivatives was found to be strongly dependent on the size of the alkyl groups in the ester moieties of the acetylenic esters. According to single-crystal X-ray diffraction and NMR studies, the pyridin-2(1H)-one derivatives involve a restricted rotation around the C-C bond connecting the tetrazoloquinoline and dihydropyridinone cyclic systems.

One-Pot Multicomponent Mechanosynthesis of Polysubstituted trans-2,3-Dihydropyrroles and Pyrroles from Amines, Alkyne Esters, and Chalcones.

An efficient and practical one-pot multicomponent reaction of amines with alkyne esters and chalcones promoted by I2/PhI(OAc)2 has been developed under solvent-free ball-milling conditions to afford a variety of polysubstituted trans-2,3-dihydropyrroles in moderate to good yields. The present method features a short reaction time, mild reaction conditions, broad substrate scope, and feasibility of large-scale synthesis. Intriguingly, this protocol can also furnish the corresponding synthetically more attractive pyrroles with the addition of an oxidant in a one-pot way.

Synthesis of 3,4,5-substituted furan-2(5H)-ones using Al-doped ZnO nanostructure

Al-doped ZnO nanostructures were prepared via a simple precipitation method and were characterized by several techniques including XRD, TEM, EDX, UV–Vis, and DLS. All XRD patterns show the hexagonal single-phase structure of pure and Al-doped ZnO nanopowders without impurity. The samples consist of particles with average sizes ranging from 53 to 60 nm measured by DLS technique. Next, the catalytic activity of pure and Al-doped ZnO nanopowders was investigated in terms of synthesis of 3,4,5-substituted furan-2(5H)-one derivatives using the three-component reaction of aldehydes, aromatic amines, and acetylenic esters. This procedure has advantages such as high yields, simple methodology, and easy work-up.

Dual C(sp3 )-H Bond Functionalization of N-Heterocycles through Sequential Visible-Light Photocatalyzed Dehydrogenation/[2+2] Cycloaddition Reactions.

Herein we describe a mild method for the dual C(sp3 )-H bond functionalization of saturated nitrogen-containing heterocycles through a sequential visible-light photocatalyzed dehydrogenation/[2+2] cycloaddition procedure. As a complementary approach to the well-established use of iminium ion and α-amino radical intermediates, the elusive cyclic enamine intermediates were effectively generated by photoredox catalysis under mild conditions and efficiently captured by acetylene esters to form a wide array of bicyclic amino acid derivatives, thus enabling the simultaneous functionalization of two vicinal C(sp3 )-H bonds.

Dual C(sp3)−H Bond Functionalization of N‐Heterocycles through Sequential Visible‐Light Photocatalyzed Dehydrogenation/[2+2] Cycloaddition Reactions

AbstractHerein we describe a mild method for the dual C(sp3)−H bond functionalization of saturated nitrogen‐containing heterocycles through a sequential visible‐light photocatalyzed dehydrogenation/[2+2] cycloaddition procedure. As a complementary approach to the well‐established use of iminium ion and α‐amino radical intermediates, the elusive cyclic enamine intermediates were effectively generated by photoredox catalysis under mild conditions and efficiently captured by acetylene esters to form a wide array of bicyclic amino acid derivatives, thus enabling the simultaneous functionalization of two vicinal C(sp3)−H bonds.

Synthesis of 3-(quinolin-2-yl)indolizines through iodine-mediated sp3C–H functionalization of azaarenes

ABSTRACTAn efficient approach toward C–H bond activation using iodine-mediated sp3C–H bond functionalization for the synthesis of dialkyl 3-(quinolin-2-yl)indolizine-1,2-dicarboxylates and dialkyl 3-(quinolin-2-yl)pyrrolo[2,1-a]isoquinoline-1,2-dicarboxylates through 1,3-dipolar cycloaddition reaction of nitrogen ylides with acetylenic esters is described.

Synthesis of Functionalized γ-Spiroiminolactones through a One-Pot Three-Component Reaction of Isocyanides, Acetylenic Esters, and 6H-Indeno[1,2-b]pyrido[3,2-e]pyrazin-6-one

ABSTRACTA new and efficient isocyanide-based one-pot multi-component reaction has been described for the synthesis of novel ?-spiroiminolactone derivatives. Products were obtained by a three-component condensation reaction between isocyanides with acetylenic esters which was trapped with 6H-indeno[1,2-b]pyrido[3,2-e]pyrazin-6-one (aromatic ketone) in CH2Cl2 without use of any catalyst or activator in excellent yields.

Synthesis of Acetylenic Amides with Propyllactam Moieties by In Situ DBU or DBN Ring-Opening Rearrangement in the Presence of Acetylenic Esters

DBN (1,5-diazabicyclo[4.3.0]non-5-ene) and DBU (1,8-diaza­bicyclo[5.4.0]undec-7-ene) react with methyl esters of acetylenic acids and excess water (the reactant molar ratio 1:1, in aqueous MeCN, at 20–25 °C, for 48 h) to afford acetylenic amides with pyrrolidone and caprolactam moieties in 89–100% yields. The synthesis involves amines formed in situ from the cyclic amidines, which further react with acetylenic esters.

Acetylenic Ester Promoted Tandem Ring Opening of Dienyl Thiazolidin-4-ones and Cyclizations: A Facile and Chemoselective Synthesis of Functionalized Pyridine-2-carboxylates

Acetylenic ester promoted ring opening of dienyl-thiazolidin-4-ones and subsequent electrocyclization affords 5-phenyl-6-aryl pyridine-2-carboxylates in good to excellent yields.

Ester Synthesis in Water: Mycobacterium smegmatis Acyl Transferase for Kinetic Resolutions

AbstractThe acyl transferase from Mycobacterium smegmatis (MsAcT) catalyses transesterification reactions in aqueous media because of its hydrophobic active site. Aliphatic cyanohydrin and alkyne esters can be synthesised in water with excellent and strikingly opposite enantioselectivity [(R);E>37 and (S);E>100, respectively]. When using this enzyme, the undesired hydrolysis of the acyl donor is an important factor to take into account. Finally, the choice of acyl donor can significantly influence the obtained enantiomeric excesses.magnified image