Three-component Coupling Of Aldehydes Research Articles

A3 polycondensation: A multicomponent step-growth polymerization reaction for the synthesis of polymeric propargylamines

Multicomponent reactions lead to the straightforward synthesis of organic compounds in a one-pot manner. The three-component coupling of aldehydes or ketones with amines and alkynes, commonly known as A3 or KA2 coupling, respectively, is a convenient, highly efficient strategy for the synthesis of propargylamines, a family of compounds with multifaceted chemical behavior. Transferring this multicomponent strategy into the polymer synthesis field can lead to polymers bearing a variety of properties and possible applications. Herein, we report the efficient, straightforward, air tolerant, and sustainable synthesis of various new polymeric propargylamines, in very high to excellent yields. A highly-reactive, earth-abundant, inexpensive, well-defined copper catalyst is employed. An extensive thermal degradation study of the new polymers is also carried out.

N-(Phenylsulfonyl)Benzenesulfonamide: A New Organocatalyst for One-Pot, Solvent-Free Synthesis of Biginelli’s 3,4-Dihydropyrimidine-2(1H)-Thiones

This report describes an efficient method for one-pot, three-component coupling of aldehydes, β-ketoesters/β-diketone, and urea/thiourea catalyzed by N-(phenylsulfonyl)benzene sulfonamide (NPBSA) as efficient organocatalyst to afford the corresponding 3,4-dihydropyrimidine-2(1H)-ones/thiones via Biginelli condensation. Novel catalyst, high yields, quick reaction time, solvent-free environment, simple workup, and the ability to tolerate a variety of functional groups are some of the advantages of the current method, providing economic and environmental benefits. The present work also includes the synthesis of active pharmaceutical ingredient Piperasterol as application of the method.

Synthesis of N-Protected 1-Aminoalkylphosphonium Salts from Amides, Carbamates, Lactams, or Imides.

This report describes the development and optimization of the one-pot method for the synthesis of N-protected 1-aminoalkylphosphonium salts based on the three-component coupling of aldehydes and either amides, carbamates, lactams, imides, or urea in the presence of triarylphosphonium salts. The proposed strategy is very efficient and easy to carry out even on a larger scale (20 g) in any typical laboratory. Most reactions occur at temperatures between 50 and 100 °C in a short time (1–2 h) without requiring any catalyst, and simple workup procedures afford good to excellent yields. The exceptions are condensations with imides, which require much higher temperatures (150–170 °C) and longer reaction times (even 30 h). The possibility of carrying out the synthesis under solvent-free conditions (neat reactions) is also demonstrated. It is especially important for less reactive substrates (imides), and reactions required high temperature (or generally harsher conditions). Finally, we prove the developed one-pot methodology can be successfully applied for the synthesis of structurally diverse N-protected 1-aminoalkylphosphonium salts. Mechanistic studies showed the intermediate products of described couplings are 1-hydroxyalkylphosphonium salts, not N-hydroxyalkylamides, -imides, etc., as initially expected.

BF3·OEt2-catalyzed one-pot three-component access to diarylmethylazides

A direct one-pot access to diarylmethylazides, versatile intermediates, from commercially available starting materials was enabled via three-component coupling of aldehydes, arenes, and TMSN3 in the presence of a catalytic amount of BF3·OEt2.

Biradical o-iminobenzosemiquinonato(1-) complexes of nickel(ii): catalytic activity in three-component coupling of aldehydes, amines and alkynes.

The six-coordinated bis-o-iminosemiquinone complex, NiL2BIS, in which LBIS is the o-iminosemiquinone 1-electron oxidized form of the tridentate o-aminophenol benzoxazole-based ligand H2LBAP, was synthesized and characterized. The crystal structure of the complex reveals octahedral geometry with a NiN4O2 coordination sphere in which Ni(ii) has been surrounded by two tridentate LBIS ligands. This compound exhibits (SNi = 1) with both spin and orbital contribution to the magnetic moment and antiferromagnetic coupling between two electrons on two LBIS ligands which results in a triplet spin ground state (S = 1). The electronic transitions and the electrochemical behavior of this open-shell molecule are presented here, based on experimental observations and theoretical calculations. The electrochemical behavior of NiL2BIS was investigated by cyclic voltammetry and indicates ligand-centered redox processes. Three-component coupling of aldehydes, amines and alkynes (A3-coupling) was studied in the presence of the NiL2BIS complex, and the previously reported four-coordinated bis-o-iminosemiquinone NiL2NIS. Furthermore, among these two o-iminobenzosemiquinonato(1−) complexes of Ni(ii) (NiL2NIS and NiL2BIS), NiL2NIS was found to be an efficient catalyst in A3-coupling at 85 °C under solvent-free conditions and can be recovered and reused for several cycles with a small decrease in activity.

Three-Component Coupling of Aldehydes, 2-Aminopyridines, and Diazo Esters via Rhodium(III)-Catalyzed Imidoyl C-H Activation: Synthesis of Pyrido[1,2- a]pyrimidin-4-ones.

Imines formed in situ from 2-aminopyridines and aldehydes undergo Rh(III)-catalyzed imidoyl C-H activation and coupling with diazo esters to give pyrido[1,2- a]pyrimidin-4-ones. Aromatic and enolizable aliphatic aldehydes were both effective substrates, and a broad range of functional groups were incorporated at different sites on the heterocyclic products. In addition, methoxy and dimethylamino functionalities could be directly installed on the pyrimidine ring by employing trimethyl orthoformate or N, N-dimethylformamide dimethyl acetal in place of the aldehyde, respectively.

Three-Component Coupling of Aldehydes, Aminopyrazoles, and Sulfoxonium Ylides via Rhodium(III)-Catalyzed Imidoyl C-H Activation: Synthesis of Pyrazolo[1,5- a]pyrimidines.

An efficient, three-component strategy for Rh(III)-catalyzed annulation of readily available 3-aminopyrazoles, aldehydes, and sulfoxonium ylides to give diverse pyrazolo[1,5- a]pyrimidines is disclosed. The reactions were performed under straightforward benchtop conditions using microwave heating with short reaction times. Good yields were obtained for many substituted aminopyrazoles and a very large variety of aromatic and heteroaromatic aldehydes, including those incorporating electron-withdrawing, electron-donating, basic nitrogen, halide and acidic functionality. Ester and methoxy functionalities could also be directly installed on the pyrimidine ring by employing ethyl glyoxylate and trimethyl orthoformate in place of the aldehyde, respectively. In addition, a range of sulfoxonium ylides provided products in good yields to establish that aryl, heteroaryl, and branched and unbranched alkyl substituents can be introduced with this reagent. Finally, the first use of a formyl sulfoxonium ylide in a chemical transformation enabled the preparation of products with only a single substituent on the pyrimidine ring as introduced by the aldehyde coupling partner. For the formyl ylide, a one-pot, stepwise reaction sequence was used to prevent competitive condensation of the formyl group with the aminopyrazole.

Efficient Gold(I) Acyclic Diaminocarbenes for the Synthesis of Propargylamines and Indolizines.

Mononuclear gold(I) acyclic diaminocarbenes (ADCs) were prepared by the reaction of 1,2-cyclohexanediamine with the corresponding isocyanide complexes [AuCl(CNR)] (R = Cy, tBu). The three-component coupling of aldehydes, amines, and alkynes was investigated by using these gold(I) ADC complexes. The new gold(I) metal complexes are highly efficient catalysts for the synthesis of propargylamines and indolizines in the absence of solvent and in mild conditions. This method affords the corresponding final products with excellent yields in short reaction times. Additionally, chiral gold(I) complexes with ADCs have been prepared and tried in the enantioselective synthesis of propargylamines.

Visible-light-promoted organic-dye-catalyzed three-component coupling of aldehydes, hydrazines and bromodifluorinated reagents

α,α-Difluoroketone hydrazones have been synthesised from readily available aldehydes, hydrazines, and bromodifluorinated reagents via visible-light photoredox catalysis.

Gold nanoparticles supported on mercaptoethanol directly bonded to MCM-41: An efficient catalyst for the synthesis of propargylamines

Mercaptofunctionalized MCM-41 (MCM-SH) was obtained via reaction of MCM-chloride with mercaptoethanol. Then, gold nanoparticles supported on MCM-SH (Au@HS-MCM nanocomposite) were prepared by chemical reduction of HAuCl4 by NaBH4. The obtained catalyst was used as an effective and reusable heterogeneous catalyst in three-component coupling of aldehydes, alkynes, and amines (A3-coupling) in water. The catalyst could be recovered and reused several times without a significant loss of activity.

One-pot, three-component approach to the synthesis of 3,4,5-trisubstituted pyrazoles.

An operationally simple and high yielding protocol for the synthesis of polyfunctional pyrazoles has been developed through one-pot, three-component coupling of aldehydes, 1,3-dicarbonyls, and diazo compounds as well as tosyl hydrazones. The reaction proceeds through a tandem Knoevenagel condensation, 1,3-dipolar cycloaddition, and transition metal-free oxidative aromatization reaction sequence utilizing molecular oxygen as a green oxidant. The scope of the reaction was studied by varying the aldehyde, 1,3-dicarbonyl, and diazo component individually.

Tandem Prins/Wagner/Ritter process for the stereoselective synthesis of (3-oxabicyclo[4.2.0]octanyl)amide and (1-(5-aryltetrahydrofuran-3-yl)cyclobutyl)amide derivatives.

Three-component coupling of aldehydes, vinylcyclopropyl carbinols, and nitriles in the presence of 10 mol% TMSOTf at -40 to 0 °C in dichloromethane affords a novel class of (3-oxabicyclo[4.2.0]octanyl)amides in high yields with excellent selectivity, whereas (1-vinylcyclobutyl)methanol provides the corresponding (1-(5-aryltetrahydrofuran-3-yl)cyclobutyl)amides under similar conditions. This is the first report on the synthesis of oxabicycles through a sequential Prins/Wagner/Ritter process.

Stable mesoporous Fe/TiO2 nanoparticles: A recoverable catalyst for solvent-free synthesis of propargylamine via C[sbnd]H activation

Fe-doped mesoporous metal oxides (Fe/MO2, M=Si and Ti) were synthesized with particle size in the range of 10–15nm via modified sol–gel method. The Fe modified SiO2 and TiO2 have proved to be very efficient catalysts in three-component coupling of aldehydes, alkynes and amines for the solvent-free synthesis of proargylamines. Among the two Fe-doped metal oxide catalysts, Fe/TiO2 gives 94% propargylamine yield at 245W microwave power for few minutes under solvent free condition and found to be a better catalyst. With a Fe/TiO2 heterogeneous catalyst and in the absence of solvent, the proposed process for propargylamine synthesis is green and environmentally benign protocol.

Cu(II) salen complex catalyzed synthesis of propargylamines by a three-component coupling reaction

A one pot three-component coupling reaction of phenylacetylene, aldehyde, and amine derivatives in the presence of Cu(II) Salen complex as an efficient heterogeneous catalyst under solvent-free conditions is reported. The catalyst displayed high activity and afforded the corresponding propargylamines in good to excellent yields. This method provides a wide range of substrate applicability. The catalyst was reused several times without significant loss of its catalytic activity. A Cu(II) salen complex showed excellent catalytic activity toward the synthesis of propargylamines through the three-component coupling of aldehydes, amines, and phenylacetylene. Highlights are excellent yields, short reaction times, and a recyclable catalyst.

Regioselective synthesis of 6-aryl-benzo[h][1,2,4]-triazolo[5,1-b]quinazoline-7,8-diones as potent antitumoral agents

Three-component coupling of aldehyde, 2-hydroxy-1,4-naphthoquinone and 3-amino-1,2,4-triazole has been achieved using a catalytic amount of sulfamic acid under solvent free conditions to produce a novel series of 6-aryl-benzo[h][1,2,4]-triazolo[5,1-b]quinazoline-7,8-dione derivatives in good yields and with high regioselectivity. These compounds are found to exhibit potent antitumoral properties.

One-Pot and Solvent-Free Synthesis of 1,4-Dihydropyridines and 3,4-Dihydropyrimidine-2-ones Using New Synthetic Recyclable Catalyst via Biginelli and Hantzsch Reactions

Pyridine dicarboxylic acid guanidine–cobalt complex (PDAG-Co) (3) catalyzes one-pot, three-component coupling of aldehydes, β-dicarbonyl compounds, and ammonium acetate to afford the corresponding 1,4-dihydropyridines (1,4-DHPs) via Hantzsch reaction. 3,4-Dihydropyrimidine-2-ones (3,4-DHPMs) and their sulfur analogs are also synthesized under the same conditions via Biginelli condensation protocol. The catalyst is reusable at least five times, highly efficient, easily prepared, and used under mild reaction conditions. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view free supplemental file.

CuI-nanoparticles-catalyzed one-pot synthesis of benzo[b]furans via three-component coupling of aldehydes, amines and alkyne

A novel application of copper iodide nanoparticles as an efficient catalyst has been developed for the synthesis of 2,3-disubstituted benzo[b]furan derivatives via three-component coupling of aldehydes, secondary amines and alkyne. The method presented is green, effective, inexpensive and satisfactory to give the products in high yields and short reaction times by the use of novel nanoscale materials.

Three‐Component Coupling of Aldehydes, Amines, and Alkynes Catalyzed by Oxidized Copper Nanoparticles on Titania

AbstractCopper nanoparticles (mainly as Cu2O) on titania have been shown to catalyze the multicomponent synthesis of propargylamines from aldehydes, amines, and alkynes (A3 coupling) effectively at 70 °C under solvent‐free conditions. Both aromatic and aliphatic aldehydes and alkynes have been combined with secondary amines to provide a wide range of propargylamines in moderate to excellent yields. Two examples of ketone/amine/alkyne (KA2) coupling are also included. The catalyst is easy to prepare, reusable at a low copper loading (0.5 mol‐%), and exhibits higher catalytic activity than some commercially available copper sources. Some mechanistic aspects of the reaction have also been examined, which have unveiled the participation of copper(I) acetylides in a heterogeneous process.

Indium(III) chloride catalyzed three-component coupling reaction: A novel synthesis of 2-substituted aryl(indolyl)kojic acid derivatives as potent antifungal and antibacterial agents

Three-component coupling of aldehyde, indole and kojic acid has been achieved using a catalytic amount of InCl(3) under solvent free conditions to produce a novel series of 2-substituted aryl(indolyl)kojic acid derivatives in good yields and with high selectivity. These compounds are found to exhibit potent antifungal properties.

An efficient and facile one-pot synthesis of propargylamines by three-component coupling of aldehydes, amines, and alkynes via C–H activation catalyzed by NiCl 2

NiCl 2 was found to be a highly efficient and effective catalyst for the one-pot three-component (A 3) coupling of aldehydes, amines, and alkynes to produce propargylamines in nearly quantitative yields. Structurally divergent aldehydes, amines, and alkynes were converted into the corresponding propargylamines. No co-catalyst or activator is needed and water is the only byproduct of this novel protocol.