Aromatic Terminal Alkynes Research Articles

Design, Synthesis, Spectroscopic Characterisation and In Vitro Cytostatic Evaluation of Novel Bis(coumarin-1,2,3-triazolyl)benzenes and Hybrid Coumarin-1,2,3-triazolyl-aryl Derivatives.

In this work, a series of novel 1,2,3-triazolyl-coumarin hybrid systems were designed as potential antitumour agents. The structural modification of the coumarin ring was carried out by Cu(I)-catalysed Huisgen 1,3-dipolar cycloaddition of 7-azido-4-methylcoumarin and terminal aromatic alkynes to obtain 1,4-disubstituted 1,2,3-triazolyl-coumarin conjugates 2a–g, bis(1,2,3-triazolyl-coumarin)benzenes 2h–i and coumarin-1,2,3-triazolyl-benzazole hybrids 4a–b. The newly synthesised hybrid molecules were investigated for in vitro antitumour activity against five human cancer cell lines, colon carcinoma HCT116, breast carcinoma MCF-7, lung carcinoma H 460, human T-lymphocyte cells CEM, cervix carcinoma cells HeLa, as well as human dermal microvascular endothelial cells (HMEC-1). Most of these compounds showed moderate to pronounced cytotoxic activity, especially towards MCF-7 cell lines with IC50 = 0.3–32 μM. In addition, compounds 2a–i and 4a–b were studied by UV-Vis absorption and fluorescence spectroscopy and their basic photophysical parameters were determined.

Non-noble Nickel-Modified Covalent Organic Framework for Partial Hydrogenation of Aromatic Terminal Alkynes.

Developing non-noble metal-based catalysts with excellent performance for selective hydrogenation of alkynes under mild reaction conditions is highly desirable but still faces challenges. Herein, a non-noble nickel-modified covalent organic framework (Ni/COF) had been synthesized through a facile post-modified method and followed by reduction at a different temperature under a H2/Ar atmosphere. The as-prepared catalysts were characterized by X-ray diffraction, high-resolution transmission electron microscopy, X-ray photoelectron spectroscopy, Brunauer-Emmett-Teller, and Fourier transforms infrared, and the optimal H350-Ni/COF presents excellent catalytic performance in the semihydrogenation of a series of aromatic terminal alkyne substrates, particularly in the partial hydrogenation of phenylacetylene with nearly full conversion and 85% selectivity toward styrene under mild reaction conditions (10 bar of H2, 100 °C, and 1 h). Moreover, such a catalyst also exhibited satisfying stability after three consecutive cycles.

Glycosyl Triazole Ligand for Temperature-Dependent Competitive Reactions of Cu-Catalyzed Sonogashira Coupling and Glaser Coupling

Glycosyl triazoles have been introduced as efficient ligands for the Cu-catalyzed Sonogashira reaction to overcome the challenges of sideways homocoupling reactions in Cu catalysis in this reaction. The atmospheric oxygen in a sealed tube did not affect the coupling, and no need of complete exclusion of oxygen was experienced in the presence of glycohybrid triazole ligand L3. High product yields were obtained at 130 °C for a variety of substrates including aliphatic and aromatic terminal alkynes and differently substituted aromatic halides including 9-bromo noscapine. In contrast, at room temperature, a very low loading of the L3-Cu catalytic system could produce excellent yields in Glaser coupling including homocoupling and heterocoupling of a variety of aliphatic and aromatic alkynes.

Base promoted CuFe2O4 catalyzed one‐pot synthesis of 3,5‐diaryl‐1H‐pyrazoles

AbstractAvailable synthetic protocols for 3,5‐diaryl‐1H‐pyrazoles generally demand long reaction time. Herein, we are reporting a CuFe2O4 catalyzed synthetic procedure for the same that delivers products in significantly reduced time starting from tosylhydrazones of aromatic aldehydes and terminal alkynes. Under the reaction condition, tosylhydrazone generates diazo compound in situ, which then undergoes [3 + 2] cycloaddition reaction with the terminal alkyne followed by [1,3]‐H shift to deliver the final products in 72%–85% isolated yield. Magnetically active CuFe2O4 nanoparticles can be recovered very easily after the completion of the reaction and can be reused up to fifth cycle without significant loss in its catalytic activity. Operational simplicity of the methodology along with tolerability of various functional groups as well as easy recovery and high reusability of CuFe2O4 nanoparticles make the procedure a practical and handy one for the synthesis of 3,5‐diaryl‐1H‐pyrazoles.

Base-Promoted One-Pot Synthesis of Pyridine Derivatives via Aromatic Alkyne Annulation Using Benzamides as Nitrogen Source.

In the presence of Cs2CO3, the first simple, efficient, and one-pot procedure for the synthesis of 3,5-diaryl pyridines via a variety of aromatic terminal alkynes with benzamides as the nitrogen source in sulfolane is described. The formation of pyridine derivatives accompanies the outcome of 1,3-diaryl propenes, which are also useful intermediates in organic synthesis. Thus, pyridine ring results from a formal [2+2+1+1] cyclocondensation of three alkynes with benzamides, and one of the alkynes provides one carbon, whilst benzamides provide a nitrogen source only. A new transformation of alkynes as well as new utility of benzamide are found in this work.

Rhodium-Catalyzed Anti-Markovnikov Hydroamination of Aliphatic and Aromatic Terminal Alkynes with Aliphatic Primary Amines.

Anti-Markovnikov hydroamination of both aliphatic and aromatic terminal alkynes with primary amines was achieved using an 8-quinolinolato rhodium catalyst to form aldimines and enamines in high yields. This catalytic system realized high functional group tolerance including hydroxy, bromo, cyano, and thioester groups.

Selective Manganese-Catalyzed Dimerization and Cross-Coupling of Terminal Alkynes.

Herein, efficient manganese-catalyzed dimerization of terminal alkynes to afford 1,3-enynes is described. This reaction is atom economic, implementing an inexpensive, earth-abundant nonprecious metal catalyst. The precatalyst is the bench-stable alkyl bisphosphine Mn(I) complex fac-[Mn(dippe)(CO)3(CH2CH2CH3)]. The catalytic process is initiated by migratory insertion of a CO ligand into the Mn–alkyl bond to yield an acyl intermediate that undergoes rapid C–H bond cleavage of alkyne, forming an active Mn(I) acetylide catalyst [Mn(dippe)(CO)2(C≡CPh)(η2-HC≡CPh)] together with liberated butanal. A range of aromatic and aliphatic terminal alkynes were efficiently and selectively converted into head-to-head Z-1,3-enynes and head-to-tail gem-1,3-enynes, respectively, in good to excellent yields. Moreover, cross-coupling of aromatic and aliphatic alkynes selectively yields head-to-tail gem-1,3-enynes. In all cases, the reactions were performed at 70 °C with a catalyst loading of 1–2 mol %. A mechanism based on density functional theory (DFT) calculations is presented.

Amidoxime fibers-copper–catalyzed cross-dehydrogenative coupling of N,N-dimethylanilines and aromatic terminal alkynes

A heterogeneous Cu(II)-AOFs catalyst, Cu(II) supported on amidoxime fibers (AOFs), is successfully applied to the cross-dehydrogenative coupling of aromatic terminal alkynes and N,N-dimethylanilines to form propargylamines. The Cu(II)-AOFs catalyst shows high catalytic activity with the yields of the corresponding propargylamines reaching 90% at 70 °C for 4 h without the protection of an inert gas. The Cu(II)-AOFs coordinate with the imine ion intermediate generated during the reaction, making the coupling facile. X-ray photoelectron spectrometer, scanning electron microscope, and energy dispersive X-ray spectroscopy results show that Cu(II) successfully coordinates with N and O atoms on the surface of the fibers with the mutual conversion between monovalent and divalent Cu in the Cu-AOFs being the catalytically active center. The catalyst can be recycled more than four times, and the catalytic activity is not obviously reduced. This process represents a new pathway for the formation of propargylamines using a Cu(II)-AOFs catalyst.

Synthesis of N-perfluoroalkyl-3,4-disubstituted pyrroles by rhodium-catalyzed transannulation of N-fluoroalkyl-1,2,3-triazoles with terminal alkynes.

The rhodium-catalyzed transannulation of N-perfluoroalkyl-1,2,3-triazoles with aromatic and aliphatic terminal alkynes under microwave heating conditions afforded N-perfluoroalkyl-3,4-disubstituted pyrroles (major products) and N-fluoroalkyl-2,4-disubstituted pyrroles (minor products). The observed selectivities in the case of the reactions with aliphatic alkynes were high.

Co(iii)-catalysed regioselective linear C(8)–H olefination of isoquinolone with terminal aromatic and aliphatic alkynes

A regioselective C8 linear olefination of isoquinoline-1H-2-one with terminal (aromatic and aliphatic) alkynes is reported under Co(iii) catalysis.

Dimethylzinc-mediated enantioselective addition of terminal alkynes to 1,2-diketones using perhydro-1,3-benzoxazines as ligands

A conformationally restricted perhydro-1,3-benzoxazine derived from (-)-8-aminomenthol behaves as a good chiral ligand in the dimethylzinc-mediated enantioselective monoaddition of aromatic and aliphatic terminal alkynes to 1,2-diketones. The corresponding α-hydroxyketones were obtained in good yields with high enantioselectivities starting from both aromatic and aliphatic 1,2-diketones. The alkynylation of unsymmetrical 1,2-diketones with electronically different substituents also proceeds with high regio- and enantioselectivity. This reaction provides a practical method to synthesize ketones bearing a chiral tertiary propargylic alcohol.

Theoretical insight into the different reactivities of aliphatic and aromatic terminal alkynes towards homopropargyl alcohols via Au(I) catalysis

Au(I)-catalyzed intermolecular condensations between terminal alkynes and homopropargyl alcohols were reported as an effective strategy for the synthesis of hydrooxepine skeletons. It was found that only aliphatic terminal alkynes furnish the desired product in high yields (84%), in contrast to very low yields (<5%) with aromatic terminal alkynes. This work aims at understanding the different reactivities of aliphatic and aromatic terminal alkynes by performing DFT calculations. The results show that the reaction of the aliphatic terminal alkyne occurs via the intermolecular-addition-first mechanism, while that of the aromatic terminal alkyne proceeds via the intramolecular-cyclization-first mechanism. The overall barrier is 21.7 kcal/mol for the reaction of the former and 27.3 kcal/mol for that of the latter, rationalizing the experimental observation. The poorer reactivity of the aromatic terminal alkyne is attributed to the weaker electrophilicity of the proximal carbon in phenylacelene resulted from the conjugative effect between phenyl and alkynyl group.

Regio- and Enantioselective Allylic Alkylation of Terminal Alkynes by Synergistic Rh/Cu Catalysis.

A highly branch- and enantioselective 1,4-enynes synthesis from readily available terminal alkynes and racemic allylic carbonates by Sonogashira type synergistic Rh and Cu catalysis under neutral conditions has been developed. Aliphatic and aromatic terminal alkynes with various functional groups could be used directly. An inner-sphere reductive elimination C(sp)-C(sp3) bond formation mechanism is supported by the stoichiometric reaction.

Copper-catalyzed thiolation of terminal aromatic alkynes to access alkynyl disulfides

A copper-catalyzed thiolation of terminal aromatic alkynes by disulfur transfer to access alkynyl disulfides was developed. Different types of products were afforded due to the steric hindrance of dithiolsulfonates. Some important compounds, such as fully substituted triazoles and pyrene-gemcitabine conjugate were prepared by this new approach.

9-Borobicyclo[3.3.1]nonane-Catalyzed Hydroboration of Terminal Aromatic Alkynes with Pinacolborane

Organoboron compounds are extensively used in organic synthesis. The alkenylboronic acid pinacol esters formed from the hydroboration reaction of alkynes with pinacolborane are stable, easy to handle, and useful in many synthetic transformations. However, pinacolborane lacks the reactivity necessary to undergo facile hydroboration reaction with terminal aromatic alkynes. 9-Borobicyclo[3.3.1]nonane (9-BBN) can be used to catalyze the hydroboration reaction of phenylacetylene with pinacolborane. The hydroboration reaction parameters and product purification conditions were evaluated to maximize the yield of (E)-2-phenylethenylboronic acid pinacol ester. It was found that the optimal reaction conditions for the 9-BBN-catalyzed hydroboration of phenylacetylene with pinacolborane were: phenylacetylene (1.0 equiv), pinacolborane (1.2 equiv), 9-BBN (20 mol%), and THF [0.2] at 65 °C. The compatibility of these reaction conditions with p-substituted terminal aromatic alkynes bearing electronically diverse groups was studied. Moderate to good yield (49–76%) of the hydroboration products were isolated after purification by liquid-liquid extraction and flash chromatography. KEYWORDS: Organic Synthesis; Catalysis; Methods Development; Hydroboration; Reaction Optimization; Alkenylboronic Ester; Alkyne; Pinacolborane; 9-Borobicyclo[3.3.1]nonane

Dimerization of Aromatic Terminal Alkynes Featuring Hydrophilic Functional Groups under Ruthenium and Acid Promoted Catalysis. Competitive Alkyne Hydration upon Substituent Effect

AbstractThe self‐coupling (hydroalkynylation) process of aromatic terminal alkynes RC6H4C≡CH to give dimeric 1,4‐diaryl‐1‐en‐3‐yne products (trans‐RC6H4C≡CCH=CHC6H4R) is catalyzed by the complex [{RuCl(μ‐Cl)(η6‐p‐cymene)}2] with sodium acetate co‐catalyst dissolved in neat acetic acid, the reaction proceeding with high trans‐stereoselectivity under mild conditions (r.t.) even for substrates with protic or polar substituent groups (e. g. R=3‐OH, 4‐CH2OH, 4‐NHAc, ‐CHO, 4‐tetra‐O‐acetyl‐β‐D‐glucopyranoside). In presence of strongly electron donating arene substituents, NMe2 and NH2, the triple bond is activated toward exclusive triple bond hydration by reaction with acetic acid at room temperature also in absence of the ruthenium catalyst.

Cu(I) Catalyzed 1,3-Dipolar Click Synthesis of S-Heterocyclic 1,2,3-Triazole Derivatives, Their Antibacterial Activity

A novel series of 1,2,3-triazoles is synthesized by 1,3-dipolar cycloaddition of aromatic azides and terminal alkynes containing 1,2,4-triazole/1,3,4-oxadiazole in presence of Cu(I) catalyst in aqueous medium. The compounds are characterized by spectral and analytical data. The novel triazoles demonstrate moderate to excellent antibacterial activity and good docking score.

Palladium/Copper-Catalyzed Denitrogenative Alkylidenation and ortho-Alkynylation Reaction of 1,2,3-Benzotriazin-4(3H)-ones.

An efficient palladium-catalyzed approach to access various functionalized (Z)-3-benzylidene-isoindoline-1-ones and (Z)-3-benzylidene(imino)isobenzofuranones via a denitrogenative tandem alkynylation/cyclization reaction of 1,2,3-benzotriazin-4(3H)-ones with aromatic terminal alkynes is described. Furthermore, a denitrogenative ortho-alkynylation reaction of 1,2,3-benzotriazinones with aliphatic terminal alkynes is also developed. The reaction proceeds through a five-membered azapalladacyclic intermediate with the extrusion of a nitrogen molecule. The significance of the reaction is also demonstrated by a one-pot synthesis of (Z)-3-benzylideneisobenzofuran-1(3H)-one derivatives in good to high yields.

Copper Aluminate Spinel in Click Chemistry: An Efficient Heterogeneous Nanocatalyst for the Highly Regioselective Synthesis of Triazoles in Water

An expeditious protocol for the one-pot synthesis of 1,4-disubstituted (β-hydroxy)-1,2,3-triazoles in an aqueous medium has been developed using copper aluminate nanoparticles. This heterogeneous catalytic system was found to drive a multicomponent click reaction between organic azides (generated in situ from epoxides or halides) and terminal aliphatic or aromatic alkynes in up to 96% yield without the need for a reducing agent. Structurally diverse 1,2,3-triazoles were synthesized in good to excellent yields, and the catalyst could be easily separated by simple filtration, recycled, and reused in six subsequent cycles.

MnCl2‐Mediated Carbonylative Sonogashira Coupling of Aryl Iodides and Aromatic Terminal Alkynes by Using CO

AbstractA new, simple, and efficient synthetic protocol has been developed for Carbonylative Sonogashira Coupling (CSC) with aryl iodides, aromatic terminal alkynes, and CO (2 atm) by using manganese chloride (MnCl2) as a catalyst. This method has shown a good‐to‐excellent yield of the desired products. Additionally, it was found to have ensured the synthesis of 2‐substituted flavones.