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Α green and sustainable metal‐free photochemical protocol for the atom transfer radical addition (ATRA) of carbon tetrabromide onto alkenes was developed. Phenylglyoxylic acid was employed as the photoinitiator to promote the water‐mediated anti‐Markovnikov photochemical addition. A vast variety of alkenes was employed successfully, providing the corresponding products in good to high yields with excellent regioselectivity. The photochemical protocol found an application towards the three‐step synthesis of secondary or tertiary propargylamines starting from alkenes. [ABSTRACT FROM AUTHOR]

Development of catalytic systems using nontoxic natural precursors is the need of the era, and along this line, we have synthesized a new D‐glucose derived ligand (4,6‐O‐ethylidene‐N‐(2‐hydroxy‐4‐(octyloxy)benzylidene)‐β‐D‐glucopyranosylamine) and its dinuclear copper(II) complex. The molecular structure of the complex has been established by single‐crystal X‐ray diffraction studies and detailed noncovalent intermolecular interactions present in it have been explored by Hirshfeld surface analysis. Further, the complex has been used as a catalyst in the enantioselective (87–99 % ee) synthesis of propargylamines in good to excellent yield (82–95 %) via aldehyde‐amines‐alkynes (A3) coupling reaction under solvent‐free condition. The formation of aminal intermediate during the reaction has been confirmed by 1H‐NMR and single‐crystal X‐ray diffraction studies. The catalytic system is reusable without any appreciable loss in the enantioselectivity or product yield. [ABSTRACT FROM AUTHOR]

A base promoted oxidative [4+2] annulation of pyrrole‐2‐carbaldehyde derivatives with o‐hydroxyphenyl propargylamines for the synthesis of highly substituted indolizines has been developed. Using DBN as base, a broad range of 5,6,7‐trisubstituted indolizines have been prepared in good to excellent yields under mild conditions, and many useful functional groups can be tolerated. [ABSTRACT FROM AUTHOR]

ABSTRACT A3 coupling reaction is a multicomponent reaction (MCR) involving aryl aldehydes, phenyl acetylenes and amines to synthesize a variety of biologically active propargylamine derivatives. Herein, we report the preparation of cube‐shaped CuFe2O4 nanoparticles (NPs) via the hydrothermal method in the presence of Lantana camara flower (LCF) extract to use them as catalysts to synthesize propargylamine derivatives. X‐ray diffraction study confirms the formation of CuFe2O4 NPs with cubic spinel structures. In the presence of LCF extract, cube‐shaped CuFe2O4 NPs are formed predominantly irrespective of the type of alkali used as the hydrolyzing agent. However, a mixture of nearly spherical and cube‐shaped particles has been formed in the absence of additives. The synthesized CuFe2O4 NPs exhibit superparamagnetic behaviour and are magnetically ordered. The synthesized cube‐shaped CuFe2O4 NPs exhibit excellent catalytic activity in the A3 coupling reaction between benzaldehyde, piperidine and phenylacetylene to give propargylamine with a yield of 90% under the optimum conditions. The catalyst is highly stable and magnetically retrievable facilitating reusability for up to five cycles without considerable loss of catalytic activity. The protocol is suitable for the synthesis of a diverse range of propargylamine derivatives with moderate to excellent yield. [ABSTRACT FROM AUTHOR]

Copper immobiolized onto the polyvinyl imidazole coated magnetic graphene oxide [MGO@PVimCu(I)] was synthesized and characterized by various analytical methods such as FT-IR, XRD, TGA, TEM, FESEM, VSM and ICP-OES. According to the FE-SEM and TEM results, the size of the snared nanoparticles in the polymer matrix was about 50–90 nm and the surface of the catalyst was rough. The loading percentage of copper onto the polyvinyl imidazole coated MGO was determined to be 17% using ICP-OES, which is far better than the many known metal-based heterogeneous catalysts. In the catalytic activity scrutiny, A3 coupling reaction for the preparation of propargylamines and coupling reaction of aryl halides with nucleophiles were aimed. In the presence of MGO@PVimCu(I), the corresponding products were gained in these reactions with moderate to excellent yields in aqueous medium (50–99%). This method demonstrates several considerable benefits including product yields, the use of various substrates, easy work-up, separation of catalyst by a simple external magnet, reusability of catalyst (at least four cycles), eco-friendliness, and avoidance of using any toxic solvent. The results of this study have shown that this catalyst can be a suitable candidate for other organic transformations. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Allenes, served as highly sought‐after building blocks, are an indispensable component of synthetic chemistry. Their utility in modulating the chemical, physical, and pharmaceutical properties of organic compounds make allenes a desirable choice in various applications. Here, we report a facile method for the atom‐economical synthesis of propargyl allenylamines via an underdeveloped [2,3]‐sigmatropic rearrangement. Our strategy employs easily accessible propargylamines as starting materials, which are first converted into propargyl ammonium salts, followed by a base‐promoted [2,3]‐sigmatropic rearrangement. This one‐pot, two‐step reaction proceeds in the absence of transition metals, displays a very broad scope, and does not require the introduction of the electron‐withdrawing group into the starting materials. [ABSTRACT FROM AUTHOR]

In this study, the reaction between 2-(3,5-dimethylpyrazolylmethyl)-5-(dimethylaminomethyl)pyrrole and thiophenol under heating conditions afforded the new ligand 2-(3,5-dimethylpyrazolylmethyl)-5-(phenylthiomethyl)pyrrole 2. The reaction of 2 with meta-chloroperbenzoic acid provided sulfoxide 3 and sulfone 4 group-containing ligands. The reaction of 2 with copper(I) halides provided the binuclear complexes [Cu(μ-X){μ-C4H3N-2-(CH2Me2pz)-5-(CH2SPh)-κ2-S,N}]2 (X = Cl, Br and I, 5–7) in high yields. Conversely, the analogous reaction of 4 with copper(I) halides yielded two types of complexes, three coordinate bi- and mononuclear of the type [Cu(μ-Cl){C4H3N-2-(CH2Me2pz)-5-(CH2SO2Ph)-κ1-N}]28 and [CuX{C4H3N-2-(CH2Me2pz)-5-(CH2SO2Ph)-κ1-N}2], X = Br, 9 and I, 10. When the reaction was carried out in the presence of KPF6, the two-coordinate complex [Cu{C4H3N-2-(CH2Me2pz)-5-(CH2SO2Ph)-κ1-N}2]PF6−11a was isolated, whereas its BF4− analogue 11b was synthesized by the reaction of 8 with AgBF4. The structures of these complexes were determined using single-crystal X-ray crystallography. These copper complexes catalyzed the hydroamination–alkynylation reaction between several secondary amines and alkyl and aryl terminal alkynes. Using 1 mol% of complexes 5–10 as catalysts, both tri- and tetra-substituted propargylamines were isolated. Alternatively, phenylacetylene and different secondary amines afforded the corresponding trisubstituted propargylamines as the major products and alkyl terminal alkynes gave the tetrasubstituted products in excellent yields. In addition, the role of counter anions such as TfO−, PF6−, BF4−, PO43− and Ph4B− on the product selectivity was studied. When fluorinated anions such as TfO−, PF6−, and BF4− were present with the copper complexes, the hydroamination–hydrovinylation product 1-aminodiene 23 was observed, which was not formed with PO43−, Ph4B− or halide ions. Specifically, TfO− and PF6− favored the formation of 23, while BF4− favored the tetrasubstituted product as the major product. This was further supported by the isolated copper(I) complexes containing PF6− and BF4− and by other specific reactions. The peaks for enamines and [LCu]+ species in the HRMS spectra of the reaction mixtures and the isolation of the morpholinium copper(I) salt support the proposed mechanism. [ABSTRACT FROM AUTHOR]

In this research project, we first synthesized the magnetic manganese nanocatalyst by immobilizing the MnCl2 on the surface of magnetic Fe3O4 nanoparticles modified with catechol and piperazine/phenanthroline ligand [Fe3O4@Catechol/PZ-Phen-MnCl2], then we evaluated its catalytic performance in the synthesis of propargyl amines through the A3 and KA2-coupling three-component reactions aromatic aldehydes or ketones, with alkynes, and amines. FT-IR, SEM, TEM, EDX, XRD, TGA, VSM, ICP-OES and elemental mapping analyzes confirmed the successful synthesis of Fe3O4@Catechol/PZ-Phen-MnCl2 nanocatalyst. The results of the coupling reactions confirmed that the Fe3O4@Catechol/PZ-Phen-MnCl2 nanocomposite is a very efficient catalyst for the preparation of various derivatives of propargyl amines. This method has significant features compared to the previous methods, which can be mentioned as follows: synthesis of products with very high efficiency, carrying out the reaction under mild conditions and compatible with the environment, using green and recyclable catalyst, can being applicable to a wide range of substrates and providing NMR analysis for all propargyl amine products. [ABSTRACT FROM AUTHOR]

We present a simple method to prepare diverse benzimidazolium and imidazolium ionic liquids (ILs) from common starting materials imidazole and benzimidazole. These green ILs promote the synthesis of N‐substituted piperazinyl propargylamines via a versatile CuI‐catalyzed coupling of aldehydes, secondary amines, and alkynes under ultrasound. Remarkably, the method works across a broad range of substrates, including diversely substituted aldehydes, heterocycles, cyclic amines, and phenylacetylenes. To understand this versatility, we investigated the influence of IL structure (N‐substitution, anion) on reactivity. Symmetrical long‐chain substituents on the benzimidazolium cation and bromide (Br−) anions led to the most efficient propargylamine formation. This approach offers a sustainable and efficient route to propargylamines with minimal waste and catalyst/IL recyclability over five cycles. [ABSTRACT FROM AUTHOR]

Divergent nitrogen‐containing fused polycyclic ring systems are constructed from simple starting materials via a one‐pot aldehyde‐alkyne‐amine (A3) coupling and intramolecular Diels‐Alder reaction. This domino reaction directly furnishes linear 5/5/5 and 5/5/6, or nonlinear 5/5/6/5, polycyclic rings containing an oxa‐bridged fused 5/5 bicycle and a 1,6‐enyne substructure. One‐step derivation of the oxa‐bridged 5/5 bicycle leads to a polyfunctionalized 5/5 bicycle with tetrahydrofuran fused back‐to‐back to pyrroline or a 6/5 bicycle with the hexahydro‐1H‐isoindole structure, while cycloisomerizing the enyne substructure adds an extra fused 5‐membered ring to afford functionalized linear 5/5/5/5 or 5/5/5/5/5 fused ring systems from selected substrates. In addition, the one‐pot product can be designed so that the alkyne moiety is hydroalkoxylated to form an additional heterocyle in a linear 5/5/5/6 or nonlinear 5/5/6/5/5 ring system. This diversity‐oriented synthetic approach thus allows rapid access to an under‐explored structural space for discovery of new biological or non‐biological activities or functions. [ABSTRACT FROM AUTHOR]

1,2-Dihydroisoquinolines are important compounds due to their biological and medicinal activities, and numerous approaches to their synthesis have been reported. Recently, we reported a facile synthesis of trisubstituted allenamides via N-acetylation followed by DBU-promoted isomerization, where various substituted allenamides were conveniently synthesized from readily available propargylamines with high efficiency. In light of this research background, we focused on the utility of this methodology for the synthesis of substituted 1,2-dihydroisoquinolines. In this study, a palladium-catalyzed cascade cyclization–coupling of trisubstituted allenamides containing a bromoaryl moiety with arylboronic acids is described. When N-acetyl diphenyl-substituted trisubstituted allenamide and phenylboronic acid were treated with 10 mol% of Pd(OAc)2, 20 mol% of P(o-tolyl)3, and 5 equivalents of NaOH in dioxane/H2O (4/1) at 80 °C, the reaction proceeded to afford a substituted 1,2-dihydroisoquinoline. The reaction proceeded via intramolecular cyclization, followed by transmetallation with the arylboronic acid of the resulting allylpalladium intermediate. A variety of highly substituted 1,2-dihydroisoquinolines were concisely obtained using this methodology because the allenamides, as reaction substrates, were prepared from readily available propargylamines in one step. [ABSTRACT FROM AUTHOR]

A novel catalytic route for the direct synthesis of bis-oxazolidino-nedienes from CO2 and propargylic amines is presented. An inexpensive copper catalyst promotes the Glaser coupling and a subsequent double cyclization step. The obtained diene derivatives undergo polymerization in the solid state, showcasing a rare example of spontaneous topochemical polymerization. [ABSTRACT FROM AUTHOR]

In this report, a Cu(II) complex Cu‐L4 containing a new tetradentate benzotriazole‐appended bipyridine ligand was synthesized and characterized fully via spectroscopic and crystallographic techniques. The crystal structure of the complex revealed that the ligand is bound to copper in a tetradentate fashion in a plane and the axial positions are occupied by an anion and a solvent molecule, resulting in a distorted octahedral geometry of the complex in solid‐state. This air‐stable complex was utilized as homogeneous precatalyst for the synthesis of several propargylamine derivatives by 3‐component A3 coupling reactions of aldehydes, amines, and alkynes under aerial atmosphere. [ABSTRACT FROM AUTHOR]

A versatile family of quaternary propargylamines was synthesized employing the KA2 multicomponent reaction, through the single-step coupling of a number of amines, ketones, and terminal alkynes. Sustainable synthetic procedures using transition metal catalysts were employed in all cases. The inhibitory activity of these molecules was evaluated against human monoaminoxidase (hMAO)-A and hMAO-B enzymes and was found to be significant. The IC50 values for hMAO-B range from 152.1 to 164.7 nM while the IC50 values for hMAO-A range from 765.6 to 861.6 nM. Furthermore, these compounds comply with Lipinski's rule of five and exhibit no predicted toxicity. To understand their binding properties with the two target enzymes, key interactions were studied using molecular docking, all-atom molecular dynamics (MD) simulations, and MM/GBSA binding free energy calculations. Overall, herein, the reported family of propargylamines exhibits promise as potential treatments for neurodegenerative disorders, such as Parkinson's disease. Interestingly, this is the first time a propargylamine scaffold bearing an internal alkyne has been reported to show activity against monoaminoxidases. [ABSTRACT FROM AUTHOR]

This study presents a novel approach to modifying copolymers with active azide end-groups through click chemistry, specifically targeting the incorporation of cysteine amino acid. The synthesis commenced with the reaction between cysteine amino acid and propargyl amine, yielding the alkyne-terminated amino acid Boc-Cys(Bnz)-PA compound. Through the click chemistry methodology, the copolymer with active azide ends was modified with alkyne-terminated Cys-PA. Thermal characterization of the copolymers was performed via differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). DSC measurements revealed an increase in glass transition temperature (Tg) from 65 °C to 83 °C upon the modification with cysteine, indicating enhanced thermal stability. However, TGA data suggested a decrease in thermal stability as evidenced by lower initial degradation temperatures for the modified copolymer compared to the unmodified counterpart.The degradation activation energies of the copolymers were estimated using the Flynn-Wall-Ozawa method across various conversion ranges, demonstrating higher thermal degradation activation energy for the modified copolymer compared to the unmodified one. Dielectric behavior analysis conducted at room temperature over a frequency range from 100 Hz to 20 kHz revealed a decreasing trend in dielectric constant and dielectric loss values with increasing frequency for all copolymer structures. The alternating current (AC) conductivities at 30 kHz were calculated as 1.84 × 10−7 S cm−1, and 4.75 × 10−7 S cm−1 for P(VBCl-co-VBN3 0.77) and (P(VBCl-co-(VBN3-click-Cys)0.77), respectively, indicating a frequency-dependent conductivity enhancement with increasing frequency. Overall, the results suggest that these polymeric materials, containing amino acid structures, hold promise as dielectric materials for low-frequency and low-voltage devices such as sensors, owing to their tunable thermal and dielectric properties achieved through click chemistry modification. [ABSTRACT FROM AUTHOR]

In this study, a Cu‐supported amine‐functionalized Fe3O4 nanocatalyst (Fe3O4‐NH2‐Cu) has been synthesized for A3 (amine, aldehyde, and alkyne) coupling reactions. The synthesized nanocatalyst was characterized by PXRD, FT‐IR, FESEM‐EDX, XPS, and VSM analysis. The catalytic action of the synthesized Fe3O4‐NH2‐Cu nanocatalyst was evaluated for A3 coupling reactions, with an excellent product yield of 97% in propargylamine synthesis and 98% in indolizines synthesis, respectively. The substrate scope of the catalyst was validated for various amines, substituted aryl aldehydes, and phenyl acetylene. The uniqueness of the synthesized nanocatalyst is effective performance of the catalyst under solvent‐free conditions and less reaction time for the aforementioned application. With the aid of an external magnet, the catalyst can be easily recovered from the reaction mixture and reused at least for five times without significant loss in catalytic activity, and its structural stability was confirmed by XRD, FT‐IR, and FESEM‐EDX analysis of the recovered catalyst. Overall, it is a green approach to synthesize simple Fe3O4‐NH2‐Cu catalytic system with magnetic recoverability, reusability, and recyclability for A3 coupling reactions under solvent‐free conditions with broad substrate scope. The proposed plausible mechanism is supported by DFT studies. [ABSTRACT FROM AUTHOR]

Chiral cyclohexenylallenes are readily accessed from 1‐enynes, aldehydes and chiral secondary amines in good yields (up to 79 % yield) with excellent enantioselectivities (up to 99 % ee), through CuI catalyzed the formation of chiral propargylamine intermediates. Subsequent Yb(OTf)3 catalyzed [4+2] cycloaddition reaction of cyclohexylallenes with the dienophiles tetracyanoethylene and diethyl acetylenedicarboxylate afforded the corresponding bicyclic products in 69–75 % yield and 84–90 % ee. [ABSTRACT FROM AUTHOR]

This article discusses the use of N-sulfopyridin-1-ium monozinc(II) trichloride ([NSPy]ZnCl3) as a catalyst for the synthesis of propargylamines through the A3 coupling reaction. Propargylamines are important compounds with various biological and pharmaceutical applications. The [NSPy]ZnCl3 catalyst was found to be effective in promoting the reaction under mild conditions, resulting in high yields of propargylamines. The structure of the catalyst was confirmed through spectroscopic and spectrometric analysis. The article provides detailed information on the optimization of reaction conditions and the synthesis of propargylamines using different aldehydes and amines. [Extracted from the article]

A novel heterogeneous catalyst, natural halloysite@Si(CH2)3NH2@Cu(acac)2, was designed and synthesized through the functionalization of the halloysite nano clay surface by 3-aminopropyltriethoxysilane followed by copper acetylacetonate. The catalyst was characterized using various techniques such as FTIR, SEM, EDS, BET, ICP, XRD, TEM, and TGA. The catalytic activity of natural halloysite@Si(CH2)3NH2@Cu(acac)2) was also evaluated for the synthesis of propargylamines using multicomponent A3-coupling reaction of various aldehydes, amines, and phenylacetylene. [ABSTRACT FROM AUTHOR]

A new, straightforward, highly efficient, and mild catalytic protocol for the synthesis of α‐tertiary propargylamines, via the multicomponent KA2 reaction (Ketone‐Amine‐Alkyne), employing well‐defined, sustainable copper(I) complexes bearing N‐heterocyclic carbene ligands, is reported herein. The methodology uses very low catalyst loading under moderate heating to achieve the construction of a wide range of propargylamines in good to excellent yields in very short reaction times. Challenging substrates, including acyclic linear ketones, aromatic ketones, and electron‐poor aromatic alkynes, as well as substrates bearing synthetically valuable functionalities, are well tolerated. [ABSTRACT FROM AUTHOR]

Traditional methods in synthesizing large-scale propargylamines have various limitations such as low reaction temperature, formation of byproducts and requirement of anhydrous reaction conditions. In recent times, a potent alternative for the synthesis of these crucial scaffolds has been identified as A3-coupling processes (aldehydes, amines, and alkynes), which are generally mediated by a suitable transition metal catalyst. For the further development of catalysts for A3-coupling reactions, we have designed and synthesized two new isomeric inverse triazolyl-pyridine ligands (2 and 3) and their Ag(I) complexes (4 and 5). Complexes 4 and 5 are fully characterized using different spectroscopic techniques including molecular structure determination using single crystal X-ray diffraction studies. The activity of both the complexes was tested on an A3-coupling reaction and it was found that both complexes are highly active. The superior reactivity of the newly synthesized complexes in comparison to the known catalysts can be attributed to the particular electronic properties and coordination of the inverse triazolyl-pyridine ligand. [ABSTRACT FROM AUTHOR]

A series of Ag(I) supramolecular organo-aqueous gels have been synthesized in the presence of an amine-rich triazole ligand as a gelator. Judicious choice of the triazole derivative and counter anion allows a desired spatial orientation of the pendant amine functionality to accentuate the gelation ability and autonomous self-healability via hydrogen bonding. In addition, the hydrogen bond donors, i.e. pendant –NH2 groups, offer a critical proximity of counter anions to the Lewis acidic Ag(I) and the reactants for promoting a three component coupling reaction of an aldehyde, a terminal alkyne and an amine, giving expedient access to propargyl amines, with remarkable functional group tolerance for both aromatic and aliphatic aldehydes, and aryl acetylenes. Experiments substantiate the pivotal role of counter anions and H-bonding interactions in the observed preference for propargylamines over the diacetylene by-product. Our catalyst is robust, bench-stable, and recyclable, and demonstrates a catalytic efficiency comparable to or better than those of reported systems. The catalyst was found equally effective for the gram-scale synthesis of propargylamines. Our approach lies at the intersection of metal-based, H-bond-mediated counter anion-tuned catalysis, evincing a potential for the development of purpose-built supramolecular gels for desired catalytic applications in the future. [ABSTRACT FROM AUTHOR]

The reaction of isoalantolactone with primary amines or piperazine proceeds under mild conditions with high stereoselectivity to give 11,13-isoalantolactone dimers connected by an alkyldiamine or piperazine linker. The reaction of isoalantolactone with propargylamine hydrochloride afforded the corresponding 13-propargylamino-11,13-dihydroisoalantolactone or 13-propargylamino-N-bis(11,13-dihydroisoalantolactone). The synthesized propargylamines showed high activity in the Cu-catalyzed cycloaddition with organic azides. The newly synthesized compounds with a bis-eudesman structure were found to exhibit antibacterial activity against strains of Staphylococcus aureus, Bacillus cereus, and Escherichia coli. [ABSTRACT FROM AUTHOR]

Reactions between enamine analogues and terminal alkynes were explored. Copper(I) complex of 1,10‐phenanthroline catalyzed these reactions to generate a diastereoselective propargylamines via C−C bond formation. In the presence of Zn2+, the chiral propargylamines converted into the β‐allenoates with an excellent yield and enantioselectivity achieved up to 99 %. Models of synthesized propargylamines were used for molecular docking and dynamic simulations, which indicate that this class of molecules shows promise for anti‐neurodegenerative activity. [ABSTRACT FROM AUTHOR]

A versatile family of quaternary propargylamines was synthesized employing the KA2 multicomponent reaction, through the single-step coupling of a number of amines, ketones, and terminal alkynes. Sustainable synthetic procedures using transition metal catalysts were employed in all cases. The inhibitory activity of these molecules was evaluated against human monoaminoxidase (hMAO)-A and hMAO-B enzymes and was found to be significant. The IC50 values for hMAO-B range from 152.1 to 164.7 nM while the IC50 values for hMAO-A range from 765.6 to 861.6 nM. Furthermore, these compounds comply with Lipinski’s rule of five and exhibit no predicted toxicity. To understand their binding properties with the two target enzymes, key interactions were studied using molecular docking, all-atom molecular dynamics (MD) simulations, and MM/GBSA binding free energy calculations. Overall, herein, the reported family of propargylamines exhibits promise as potential treatments for neurodegenerative disorders, such as Parkinson’s disease. Interestingly, this is the first time a propargylamine scaffold bearing an internal alkyne has been reported to show activity against monoaminoxidases.

The cooperative activity of two proximal metal ions is well-known to exhibit highly efficient and synergistic catalytic activities in living organisms. Owing to this knowledge, tandem Cu–Zn systems have been widely used to catalyze a diversity of chemical transformations. This report describes the use of CuI and zinc dust as a sustainable tandem catalyst for the preparation of propargylamines via a three-component coupling reaction under neat conditions. This reaction proceeds at low temperature, and produces good yields with a number of aliphatic and aromatic aldehydes. The reactivity of a number of amines and alkynes has also been explored under these reaction conditions, resulting in 33 fully characterized compounds prepared in the process. Among the ketones tested during this study, only cyclohexanone was able to produce the expected product in a decent yield. The catalytic system reported here represents one of the sustainable approaches to the preparation of propargylamines, as it involves the use of naturally abundant metals as a tandem catalyst, at a low temperature and under neat conditions.

Synthetic A3-coupling represents an efficient and environmentally convenient procedure for the production of propargylamines, relevant intermediates for the preparation of pharmacologically active substances. Gold(I) complexes of general formula NHC-Au-X have been synthesized, characterized, and tested in the A3-coupling reaction of benzaldehyde, piperidine and phenylacetylene on varying the anionic fragment X as halogenide (Cl, Br, I), acetate (OAc), hexafluorophosphate (PF6) or phenylacetylide (-C≡CPh), with 5-dichloro[N-methyl, N’(2-hydroxy-2-phenyl)ethyl imidazole-2-ylidene as NHC ligand. The kinetic profiles were interpreted with DFT (Density Functional Theory) studies on bond dissociation energies (BDE) of the counterion as well as on the relative stability of the neutral NHC-Au-X complexes with respect to their ionic forms [Au(NHC)2]+[AuX2]−.

A facile enantioselective alkynylation of cyclic ketimines attached to a neutral functional group utilizing the dual Cu(I)‐CPA catalysis is described. The strategy of the alkynylation of 2‐aryl‐3H‐indol‐3‐one directly to chiral propargylic amines containing indolin‐3‐one moiety in good yields and enantioselectivities. Moreover, gram‐scale synthesis of chiral propargylamines based C2‐quaternary indolin‐3‐ones was performed. The synthetic applications were confirmed by transformations of the products with no decrease in the yield and enantioselectivity. [ABSTRACT FROM AUTHOR]

Developing new organic reactions with excellent atom economy and high selectivity is significant and urgent. Herein, by ingeniously regulating the reaction conditions, highly selective transformations of propargylamines have been successfully implemented. The palladium-catalyzed cyclization of propargylamines generates a series of functionalized quinoline heterocycles, while the base-promoted isomerization of propargylamines affords diverse 1-azadienes. Both reactions have good functional group tolerance, mild conditions, excellent atom economy and high yields of up to 93%. More importantly, these quinoline heterocycles and 1-azadienes could be flexibly transformed into valuable compounds, illustrating the validity and practicability of the propargylamine-based highly selective reactions. [ABSTRACT FROM AUTHOR]

A series of ionic liquids were synthesized and their synergetic effects on the Cu catalyzed one-pot A3 coupling reactions were investigated for the synthesis of propargylamines. The results showed that the combined catalytic system based on ionic liquid [MEA][H2PO4] and CuI had excellent catalytic activity and selectivity for the target propargylamines, a series aromatic aldehyde with electro-withdrawing and donating groups and heteroaromatic aldehyde could all reach good to excellent isolated yields. This catalytic system benefit from mild reaction conditions and simple operation procedures, no volatile organic solvents and other additives were involved, and no inert gas protection were needed. In addition, the ionic liquid utilized in this work was easy to be prepared and its utilization made the catalytic system recyclable. All of these superiorities made this catalytic system efficient and eco-friendly for the synthesis of propargylamines. [ABSTRACT FROM AUTHOR]

The reaction of propargylamines with isothiocyanates results in the selective formation of iminothiazolidines, aminothiazolines or mixed thiazolidine–thiourea compounds under mild conditions. It has been observed that secondary propargylamines lead to the selective formation of cyclic 2-amino-2-thiazoline derivatives, while primary propargylamines form iminothiazoline species. In addition, these cyclic thiazoline derivatives can further react with an excess of isothiocyanate to give rise to thiazolidine–thiourea compounds. These species can also be achieved by reaction of propargylamines with isothiocynates in a molar ratio of 1 : 2. Coordination studies of these heterocyclic species towards silver and gold with different stoichiometries have been carried out and complexes of the type [ML(PPh3)]OTf, [ML2]OTf (M = Ag, Au) or [Au(C6F5)L] have been synthesised. Preliminary studies of the cytotoxic activity in lung cancer cells have also been performed in both ligands and complexes, showing that although the ligands do not exhibit anticancer activity, their coordination to metals, especially silver, greatly enhances the cytotoxic activity. [ABSTRACT FROM AUTHOR]

Silica-grafted DBU-supported NiCl2 complex, 1-(3-((3-(silica-trioxysilyl) propyl) amino) propyl) azepan-2-one nickel chloride (SiO2@DBU-NiCl2), has been designed and synthesized by multistep approach and characterized by FT-IR, XRD, EDS, FE-SEM, TGA and XPS. Catalytic activity of SiO2@DBU-NiCl2 has been explored for A3 coupling of terminal alkynes, aldehydes and secondary amines resulting in excellent yields (up to 97%). Special features of present protocol are high TONs (625–1212) and TOFs (52–404), low catalyst loading (0.08 mol %), solvent-free conditions, facile recyclability and reusability of the catalyst (up to 5 times). [ABSTRACT FROM AUTHOR]

A well-dispersed magnetically separable copper nanocatalyst via the immobilization of copper (II) complex on the surface of silica-coated magnetic nanoparticles functionalized with di(pyridin-2-yl)amine as ligand. After the fabrication of the Fe3O4@SiO2-di(pyridin-2-yl)amine-Cu, the structure of this nanomaterial was fully characterized by a number of spectroscopic techniques including FT-IR, SEM, TEM, EDS, XRD, TGA,VSM, AAS, and ICP-AES. This nanocomposite was found to be an efficient and versatile catalyst for A3-synthesis of propargylamines and C-S cross-coupling of thiophenols with aryl iodides. The presence of Fe3O4@SiO2-di(pyridin-2-yl)amine-Cu catalyst was very vital because the reactions was failed in the absence of this nanomaterial. After the reaction, the catalyst was easily separated by external magnetic effect and reused for several runs with consistent catalytic activity without any detectable leaching. [ABSTRACT FROM AUTHOR]

After choosing the best catalyst, the model reaction was carried out on 1 mmol scale with different amounts of catalyst, and 0.025 g of the catalyst was determined as a sufficient amount (Table 1, entries 4-6). Utilizing the optimized reaction conditions, aromatic aldehydes containing electron-donating and electron-withdrawing groups, together with aliphatic and heterocyclic aldehydes, were applied for the synthesis of propargylamines through the one-pot A SP 3 sp coupling reaction. Copper is an efficient, cheap, readily-available and lower toxicity catalyst which provides favorable reactivity for the A SP 3 sp coupling Mannich reaction.[[26], [28]] On the other hand, despite the effectiveness of homogeneous transition metal catalysis methods, they have some serious problems, especially from the viewpoint of recovery and reusability of the catalyst. [Extracted from the article]

The stereoselective synthesis of several secondary propargylamines by the copper-promoted A3-coupling reaction of aliphatic and aromatic aldehydes with phenylacetylene and (R)-(+)-phenylethylamine is here reported. Two different synthetic methodologies have been investigated in this study, involving CuSO4 /NaI and -CeCl3 ·7H2 O/CuI promoting systems. The reported methodologies were compared in terms of efficiency, diastereoselectivity, and toxicity, both showing advantages with respect to the current methodologies. The relative configurations of each of the obtained propargylamines, previously unknown in the literature, were assigned by comparison of the1 H NMR experimental chemical shifts with those theoretically predicted via the DFT-GIAO method. [ABSTRACT FROM AUTHOR]

Based on the coordination properties of carboxylates in carboxymethylcellulose (CMC) and metal ions, we have prepared microscale Cu‐based carboxymethylcellulose fibers (Cu(II)/CMC) by extruding the CMC‐Na solution into a Cu(II) ions coagulation bath. We found that the as‐obtained microscale Cu(II)/CMC fibers are well suitable for the in situ growth of the copper terephthalate (Cu(BDC)) MOFs directly from the coordinated Cu(II) sites enriched on the surface of fibers (Cu(BDC)@Cu(II)/CMC) in the terephthalic acid solution. The composition and structure of Cu(BDC)@Cu(II)/CMC composite fibers were verified using various FTIR, XRD, SEM, EDX, elemental mapping, XPS, TGA, and BET tools. The characterized data revealed that well‐defined Cu(BDC) particles were distributed uniformly on the surface of the microscale Cu‐based fibers. The resulting Cu(BDC)@Cu(II)/CMC fibers were used as an effective and retrievable heterogeneous catalyst for the aldehyde‐alkyne‐amine (A3) coupling reactions. The superior catalytic activity is attributed to the excellent dispersion and stability of the Cu(BDC) MOFs crystallites containing the numerous active Cu(II) sites on the microscale fibers. In addition, the microscale fibrous catalyst can be conveniently retrieved with tweezers after each cycle and reused at least six times without a significant drop in its activity. [ABSTRACT FROM AUTHOR]

[Display omitted] An efficient and green protocol for the A3 coupling reaction of aldehyde, amine and alkyne involves the use of copper nanoparticles and β-cyclodextrin in water. The copper nanoparticles are generated in situ by reduction with green and cheap sodium hydroxymethanesulfinate (rongalite) while β-cyclodextrin serves as a stabilizing agent and a phase-transfer catalyst. [ABSTRACT FROM AUTHOR]

Vitamin B1 is successfully used as an N-heterocyclic carbene ligand for the facile and high-yielding synthesis of a water soluble monodentate NHC-gold(I) complex, which efficiently catalyses an aldehyde-alkyne-amine (A3) coupling reaction in open air under solvent-free conditions or in water. [ABSTRACT FROM AUTHOR]

In this paper, we shown that copper(II) complex supported on the surface of magnetic nanoparticles modified with 2-methoxy-1-phenylethan-1-imine (Fe3O4@SiO2-MPI-Cu(II) nanocatalyst) is an efficient nanocatalyst for synthesis of propargylamines and diaryl sulfides. The copper-nanomagnetic catalyst was fully characterized by FT-IR spectroscopy, SEM, TEM, BET, EDX, TGA, XRD, VSM, ICP-OES spectroscopic techniques. The Fe3O4@SiO2-MPI-Cu(II) nanocomposite exhibited high catalytic activity in the synthesis of propargyl amines and diaryl sulfides. The Fe3O4@SiO2-MPI-Cu(II) nanocatalyst was readily recovered by simple magnetic decantation and can be reused seven cycles without considerable loss in catalytic activity. [ABSTRACT FROM AUTHOR]

The first ZnCl2-catalyzed alkynylation of aldimines with tetra(phenylethynyl)tin was achieved under solvent-free conditions. The present methodology provides propargylamines in 38–62% yields. [ABSTRACT FROM AUTHOR]

Pd/Cu‐catalyzed cross‐coupling of propargylamines with aromatic acyl chlorides (PdCl2, CuI, Ph3P, 40–45 °C) provides α‐aryl(hetaryl)aminoacetylenic ketones in a yield of up to 97%. The latter undergo cyclization to 1,2,5‐triaryl(hetaryl)‐1,2‐dihydro‐3H‐pyrrol‐3‐ones in up to 93% yield after the treatment with KOH or Et2NH (40–55 °C, aqueous ethanol). The one‐pot synthesis of the pyrrol‐3‐ones (in up to 62% yields) by consecutive treatment of the above propargylamines with acyl chlorides (PdCl2/CuI/Ph3P) and a base (KOH) in aqueous ethanol has been also developed. [ABSTRACT FROM AUTHOR]

A highly efficient heterogeneous copper(I)-catalyzed decarboxylative C–C coupling of α-amino acids with various carbon nucleophiles has been developed that proceeds smoothly in toluene at 110 °C by using an 2-aminoethylamino-modified SBA-15-supported copper(I) bromide complex as the catalyst and di-tert-butyl peroxide as the oxidant and provides a novel and practical approach for the synthesis of diverse propargylamines, indolyl pyrrolidines and piperidines, and β-nitroamines in good yields. The new heterogeneous copper(I) catalyst can be facilely prepared from commercially easily available and inexpensive reagents via a simple procedure, and exhibits a slightly higher catalytic activity than homogeneous CuBr/TMEDA system and can be recycled at least 8 times without any apparent loss of catalytic efficiency. A recyclable copper(I)-catalyzed decarboxylative C–C coupling of α-amino acids with various carbon nucleophiles has been developed by using an SBA-15-supported copper(I) bromide complex as the catalyst, providing a novel and practical approach for the synthesis of diverse propargylamines, indolyl pyrrolidines and piperidines, and β-nitroamines. [ABSTRACT FROM AUTHOR]

A novel and green magnetic nanocatalyst were synthesized by anchoring silver (I) to (2-iminomethyl)pyridine moiety. The prepared nanocatalyst was identified by different techniques, such as FT-IR, XRD, SEM, EDX, VSM, and TGA analyses. The nanocatalyst exhibited significant catalytic activity and recoverability in a three-component coupling reaction of aldehyde, amine, and terminal alkyne to produce a variety of propargylmines. This impactful method furnished the desired products under mild reaction conditions, in excellent yield (91–98%) and lower reaction time (25–45 min). The nanocatalyst was easily recovered by an external magnet and reused in10 consecutive cycles without a considerable decrease in its activity and selectivity. [ABSTRACT FROM AUTHOR]

• Pd–impregnated LDHs were ecofriendly synthesized from aluminum salt cake. • Propargylamines were synthesized solvent – free using Pd–LDHs as catalyst. • The Pd–nial catalyst showed the best results in A3–coupling reaction. • Optimum reaction conditions were: catalyst dosage 30 mg, 5 h and 80 °C. • Good catalytic behavior of Pd–nial catalyst. Several Al3+–based LDHs with different divalent cations have been synthesized by coprecipitation from aluminum salt slag and have been impregnated with Pd. After their characterization by PXRD, FT–IR, thermal analysis, N 2 adsorption–desorption isotherms at –196 °C and electron microscopy (SEM and TEM), they were used as heterogeneous catalysts in the A3–coupling reaction (benzaldehyde + morpholine + phenylacetylene) to produce propargylamines. The catalyst that showed the best results was NiAl–Pd and the optimal reaction conditions were: catalyst dose 30 mg, temperature 80 °C and reaction time 6 h. In addition, this catalyst showed a good cyclic behavior, retaining a catalytic activity higher than 80 % after 4 cycles. [Display omitted] [ABSTRACT FROM AUTHOR]

• Realize selective C−N bond cleavage of tertiary amines and C−C bond formation. • Using alkynes for in situ activation of amines. • Regioselectivity in catalytic propargylic substitution. • Broaden the application of propargylamine in coupling reactions. The development of general approaches for the regioselective construction of propargylic derivatives from propargylic electrophiles remains a formidable challenge in synthetic chemistry. Enabled by the newly developed propiolate-enabled C−N activation, we disclosed an efficient palladium-catalyzed deaminative Hiyama coupling of propargylamines with aryl silanes under microwave irradiation. Various structurally diverse propargyl derivatives are produced in good to excellent yields, utilizing propargylamines as propargylic electrophiles in which C−N bond was activated by in situ formed propargylic ammonium salts. The salient features of this protocol include readily or easily available feedstock, broad substrate scope, single-step preparation, and high regioselectivity. Table of Contents Entry. [Display omitted] [ABSTRACT FROM AUTHOR]

• Copper and silver mediated Aldehyde−Amine−Acetylene (A3) Coupling yielded propargylamines in good to excellent yields (24–89 %). • A metal-bound acetylide species is identified as a key catalytic species by mass spectrometric studies. • DFT studies provide mechanistic insights about the Aldehyde−Amine−Acetylene (A3) Coupling. • The electronic structure and bonding characteristics of the copper (1 – 2) a and the silver (1 – 2) b complexes were investigated using steric map plots, 13C NMR and other computational analyses, indicating a robust concurrence with the experimental data. • Through DFT analysis, the suggested mechanistic pathway reveals that the A3 coupling reaction catalysis is governed by a rate-determining C–C coupling step. The copper (1 – 2) a and the silver (1 – 2) b complexes of the super bulky N-heterocyclic carbene (NHC) variants namely, [1,3-{2,4,6-(Ph 2 CH) 3 C 6 H 2 } 2 -imidazol-2-ylidene]MX [where, M = Cu; X = Cl (1a), Br (2a): M = Ag; X = Cl (1b), Br (2b)] effectively facilitated the A3 coupling reaction of diverse amine, aldehyde, and acetylene substrates yielding a wide array of propargylamines in moderate to good (ca. 24−89 %) yields. A metal bound acetylide species, [1,3-{2,4,6-(Ph 2 CH) 3 C 6 H 2 } 2 -imidazol-2-ylidene]M(C CPh) [where, M = Cu (A), Ag (B)] has been identified as a key catalytic species by mass spectrometric studies. The Density functional theory (DFT) studies further revealed the rate-limiting step as the formation of the C-C coupling transition state (TS2) from the silver-acetylide species (Int2). The super bulky ligand framework plays a pivotal role in this step by anchoring the protonated Schiff's base imine in the vicinity of the alkyne through several non-covalent-interactions, including a strong C–H•••O interaction, thereby reducing the corresponding kinetic barrier leading to an efficient catalytic transformation as reflected in the high propargylamine yields. Furthermore, the catalytic utility of the coupling reaction was further extended by synthesising pargyline, which is a monoamine oxidase B (MAO-B) inhibitor drug molecule, in a one-pot manner and that to in a gram-scale synthesis. Super bulky N−heterocyclic carbene complexes of Cu(I), Ag(I), efficiently catalyzed propargylamine synthesis by Aldehyde-Amine-Acetylene (A3) coupling via a catalytically active metal acetylide species. [Display omitted] [ABSTRACT FROM AUTHOR]

A metal‐free cascade annulation of propagylamines with amidines for divergent synthesis of polysubstituted imidazoles and 4‐alkenylquinazolines has been developed. The reaction is believed to proceed by sequential 1,4‐conjugate addition of amidines to propargylamines, 5‐exo‐dig annulation/aromatization to form the polysubstituted imidazoles, and nucleophilic addition/elimination/aromatization to quinazoline skeleton. In this reaction, a broad range of electron‐rich, electron‐neutral, and electron‐deficient propagylamines react well with amidines to give polysubstituted imidazoles and 4‐alkenylquinazolines in 53–93% yields. Moreover, the utility of this method was showcased by gram‐scale experiments and synthetic transformations of the product. [ABSTRACT FROM AUTHOR]