Terminal Alkynes Research Articles

Furfural: An Efficient Platform Molecule as a CO Surrogate in Palladium Catalysed Synthesis of α, β‐Alkynylamides

AbstractBiomass‐derived furfural was used as a CO surrogate for the first time in the oxidative N‐dealkylation/carbonylation of various aliphatic and cyclic tertiary amines with terminal alkynes to produce alk‐2‐ynamides. This reaction employed O2 as an ideal oxidising agent and used a Pd/C catalyst with KI as an additive in a base free and ligand free condition. Notably, the selective sp3 C−N bond cleavage of tertiary amines led to its potential application as an amine source. The typical and simple route provides another option for producing a broad variety of alk‐2‐ynamide derivatives in environmentally friendly and efficient way under mild conditions. This method also displays notable reusability.

Divergent Synthesis of (E)- and (Z)-Alkenones via Photoredox C(sp3)-H Alkenylation-Dehydrogenation of o-Iodoarylalkanols with Alkynes.

A photoredox C(sp3)-H alkenylation-dehydrogenation of o-iodoarylalkanols with terminal alkynes for the synthesis of (E)- and (Z)-quaternary carbon center-containing pent-4-en-1-ones is described. The stereoselectivity depends on the utilization of alkynes and photocatalysts. While using an organic photocatalyst like 4-DPAIPN manipulates the C(sp3)-H alkenylation-dehydrogenation of o-iodoarylalkanols with arylalkynes to assemble (E)-pent-4-en-1-ones, in the case of an Ir potocatalyst such as Ir(ppy)2(dtbbpy)PF6 the reaction with arylalkynes delivers (Z)-pent-4-en-1-ones. For alkylalkynes, the reaction furnishes (E)-pent-4-en-1-ones exclusively in the presence of 4-DPAIPN or Ir(ppy)2(dtbbpy)PF6.

Bifunctional Ruthenium Catalysts for endo-Selective Cycloisomerization of Nucleophile-Functionalized Terminal Alkynes

Bifunctional Ruthenium Catalysts for <i>endo</i>-Selective Cycloisomerization of Nucleophile-Functionalized Terminal Alkynes

Ni‐Catalyzed [2+2+2] Cycloaddition of Alkynes To Form Arenes and Pyridines at Low Catalyst Loadings

AbstractWe report the Ni‐catalyzed cyclotrimerization of terminal alkynes at very low loadings of catalysts (0.05 mol% for all substrates). The nickel catalyst containing a terphenyl phosphine ligand allows carrying out the reactions at room temperature in only 30 min, providing the arene products as a single regioisomer in most cases. The Ni complex is also competent for the synthesis of polysubstituted pyridines through the cycloadditions of diynes and nitriles at mild temperatures (25 ° or 50 °C) and low Ni loadings (1 mol%). Experimental data and computational studies support the involvement of monoligated PNi species in all fundamental steps of the catalytic cycle.

Photoredox-Catalyzed Multicomponent α-Sulfonylation of Terminal Alkynes.

A generality-oriented and adaptive α-sulfonylation of alkynes via photoinduced multicomponent radical cross-coupling of terminal alkynes with sulfinates and a variety of alcohols, thiophenols, or selenophenols has been explored. This protocol features mild conditions, good functional group tolerability, broad substrate scope, excellent chemo-, site-, and stereoselectivity, and applicability to late-stage functionalization. It provides a modular platform for the synthesis of value-added structurally diverse α-sulfonyl-containing multisubstituted alkenes from simple precursors.

Decarboxylative click cycloaddition: an emerging strategy towards substituted 1,2,3-triazole derivatives.

1,2,3-triazole is a vital structural motif of various drugs and therapeutic leads, as well as a linker for bioconjugation and molecular recognition. Cu-catalysed click cycloaddition of azides with terminal alkynes (CuAAc) is an important reaction to construct the triazole core. In recent years, various decarboxylative click strategies utilizing alkynoic acids as stable surrogates for low boiling or gaseous alkynes have been developed. For instance, propiolic acid, which is easy to transport, is a safe alternative for flammable gaseous acetylene. In this review article, we have covered the recent development in the decarboxylative click cycloaddition of alkynoic acids with azides leading to the synthesis of diversely substituted triazoles, including monosubstituted, 1,4-disubstituted and fully substituted 1,2,3-triazoles. Various aspects such as mechanistic insights and optimization conditions/role of catalyst are highlighted.

Carbodicarbene‐Stibenium Ion‐Mediated Functionalization of C(sp3)−H and C(sp)−H Bonds

AbstractMain‐group element‐mediated C−H activation remains experimentally challenging and the development of clear concepts and design principles has been limited by the increased reactivity of relevant complexes, especially for the heavier elements. Herein, we report that the stibenium ion [(pyCDC)Sb][NTf2]3 (1) (pyCDC=bis‐pyridyl carbodicarbene; NTf2=bis(trifluoromethanesulfonyl)imide) reacts with acetonitrile in the presence of the base 2,6‐di‐tert‐butylpyridine to enable C(sp3)−H bond breaking to generate the stiba‐methylene nitrile complex [(pyCDC)Sb(CH2CN)][NTf2]2 (2). Kinetic analyses were performed to elucidate the rate dependence for all the substrates involved in the reaction. Computational studies suggest that C−H activation proceeds via a mechanism in which acetonitrile first coordinates to the Sb center through the nitrogen atom in a κ1 fashion, thereby weakening the C−H bond which can then be deprotonated by base in solution. Further, we show that 1 reacts with terminal alkynes in the presence of 2,6‐di‐tert‐butylpyridine to enable C(sp)−H bond breaking to form stiba‐alkynyl adducts of the type [(pyCDC)Sb(CCR)][NTf2]2 (3 a–f). Compound 1 shows excellent specificity for the activation of the terminal C(sp)−H bond even across alkynes with diverse functionality. The resulting stiba‐methylene nitrile and stiba‐alkynyl adducts react with elemental iodine (I2) to produce iodoacetonitrile and iodoalkynes, while regenerating an Sb trication.

Anti-Selective Carboacylation of Alkynes via Photoredox/Nickel Dual Catalysis.

Here, we report an intermolecular carboacylation of terminal alkynes with tertiary and secondary alkyltrifluoroborates as well as acyl chlorides via photoredox/nickel dual catalysis, affording a varity of stereodefined trisubstituted enones in good to excellent yields and E stereoselectivity, through a radical relay process. This redox-neutral protocol exhibits excellent functional group tolerance, exclusive regio- and stereoselectivity, and broad compatibility with various acyl chlorides and alkyltrifluoroborates.

Investigating the in vitro Anticancer Potential and Phytochemical Constituents of Cheilanthes hirta Swartz Plant Extracts

Cancer, a complex group of diseases characterized by uncontrolled cell growth, remains a leading cause of death worldwide, accounting for approximately 10 million deaths in 2020. Despite advancements in chemotherapy and targeted therapies, survival rates have not significantly improved, necessitating the exploration of novel anticancer agents. This study investigates the in vitro anticancer potential and phytochemical constituents of Cheilanthes hirta Swartz, a fern known for its medicinal properties. The plant was collected from KwaZulu Natal, South Africa and extracts were prepared using water, ethanol and methanol. The phytochemical and FTIR screening were carried out using standard procedure and anticancer activities of the extracts were assessed against prostate (PC-3 and DU-145), human T-lymphocytes (SKU-T) and gastric (AGS) cancer cell lines using the MTT assay. The phytochemical screening revealed the presence of tannins, terpenoids, saponins, flavonoids, cardiac glycosides, anthraquinones, phlobatannins, alkaloids and steroids. FTIR spectroscopy identified the functional groups such as hydroxyl, carboxylic acid, terminal alkynes, ketones, phenols and phosphate ions. The cytotoxicity results showed that the ethanol extract exhibited the most potent antiproliferative effects on prostate cancer cell lines, while the aqueous extract had the strongest effect on the gastric cancer cells. This study highlights the potential of C. hirta as a source of bioactive compounds for anticancer drug development, however, further investigation into its mechanisms of action and therapeutic efficacy is needed.

Catalytic Behavior of NHC–Silver Complexes in the Carboxylation of Terminal Alkynes with CO2

A number of N-heterocyclic carbene–silver compounds (NHCs)AgX were tested in the direct carboxylation of terminal alkynes using carbon dioxide as the C1 carbon feedstock. The reactions proceed at a pressure of 1 atm of CO2 at room temperature, in the presence of Cs2CO3, and using silver–NHC complexes as catalysts. Thus, phenylacetylene and several alkynes are converted to the corresponding propiolic acids in good to high conversions. The activity of the catalysts is strongly influenced by the substituents on the NHC backbone and the nature of the counterion. Specifically, the most active compound exhibits iodide as the counterion and is stabilized by a benzimidazole derivative. After 24 h of reaction, a quantitative conversion is obtained utilizing DMF as the solvent and phenylacetylene as the substrate.

Copper Catalysts Anchored on Cysteine-Functionalized Polydopamine-Coated Magnetite Particles: A Versatile Platform for Enhanced Coupling Reactions.

Cysteine plays a crucial role in the development of an efficient copper-catalyst system, where its thiol group serves as a strong anchoring site for metal coordination. By immobilizing copper onto cysteine-modified, polydopamine-coated magnetite particles, this advanced catalytic platform exhibits exceptional stability and catalytic activity. Chemical modification of the polydopamine (PDA) surface with cysteine enhances copper salt immobilization, leading to the formation of the Fe3O4@PDA-Cys@Cu platform. This system was evaluated in palladium-free, copper-catalyzed Sonogashira coupling reactions, effectively catalyzing the coupling of terminal acetylenes with aryl halides. Additionally, the Fe3O4@PDA-Cys@Cu platform was employed in click reactions, confirming the enhanced catalytic efficiency due to increased copper content. The reusability of the platform was further investigated, demonstrating improved performance, especially in recyclability tests in click reaction, making it a promising candidate for sustainable heterogeneous catalysis.

A Sustainable Approach for Palladium and Phosphane‐Free Sonogashira Type Cross‐Coupling of 2‐Chloroquinoline with Terminal Alkynes

AbstractAn efficient and cost‐effective Cu (I) mediated protocol for the C(sp2)–C(sp) cross‐coupling of 3‐chalcone‐2‐chloroquinoline with terminal alkynes has been disclosed by optimizing a wide range of catalysts, ligands, base, and solvents. This approach conveniently assembles various alkynylated hybrids with excellent to moderate yields. Appropriate functional group tolerance and significant mechanistic pathway with mild reaction conditions well‐justified this synthetic transformation more sustainable towards the greener exploration.

Sterically Hindered Derivatives of Pentacene and Octafluoropentacene.

6,13-Diethynylpentacene derivatives with sterically bulky substituents (Tr*, tris(3,5-di-tert-butylphenyl)methyl groups) appended to the ethynyl moieties at the 6- and 13-positions have been synthesized, as well as derivatives with electron-withdrawing fluorine groups on the 1,2,3,4,8,9,10,11-positions. These molecules are designed to investigate relationships between steric and electronic effects on the stability of pentacene toward endoperoxide formation via reaction with photosensitized oxygen in solution under ambient light (i. e., 'laboratory' conditions). It is evident from the study that stabilization through changes to the electronic characteristics of pentacene are more effective than the incorporation of sterically bulky groups at the acetylenic termini. Selected pentacene derivatives have been made into binary, amorphous films with the fullerene derivative PCBM to investigate the stability imparted by substituents against cycloaddition reactions. Overall, the introduction of steric protection through the incorporation of Tr* groups is not an efficient strategy for enhancing the persistence of pentacenes. Stabilization through fluorination proves successful for extending the lifetime of the pentacene derivatives by an order of magnitude in solution. Notably, the persistence of pentacene derivatives in solution can also be enhanced through the use of ethereal solvents stabilized with butylated hydroxy toluene (BHT) and/or an increased number of trialkylsilyl groups as substituents.

NiII, PdII and PtII pincer complexes of 2-(diphenylphosphanyl)-N-(2-(diphenyl-phosphanyl)benzyl)benzamide: synthesis, reactivity and catalytic studies.

In this article, the synthesis of bis(phosphine), o-Ph2PC6H4C(O)N(H)CH2C6H4PPh2-o (1) (hereafter referred to as "PCNHCP" and its anionic form as "PCNCP") and its group 10 metal chemistry and catalytic studies are described. PCNHCP (1) on reaction with NiCl2(DME) and PdCl2(COD) afforded pincer complexes, [MCl{(PCNCP)κ3-P,N,P}] (M = Ni, 2; Pd, 3). A similar reaction of 1 with PtCl2(COD) yielded a chelate complex, [PtCl2{(PCNHCP)κ2-P,P}] (4), which on further treatment with LiHMDS produced the 1,2-azaphospholene-phosphine complex, [PtCl(Ph){(o-P(Ph)C6H4CONCH2C6H4PPh2-o)κ2-P,P}] (5) via P-C/P-N bond metathesis. Passing dry HCl gas through the solution of 5 resulted in benzene elimination to form [PtCl2{(o-P(Ph)C6H4CONCH2C6H4PPh2-o)κ2-P,P}] (6). Treatment of 1 with PtCl2(COD) and Pt(Cl)(Me)(COD) in the presence of a base resulted in pincer complexes [PtX{(PCNCP)κ3-P,N,P}] (X = Cl, 7; Me, 8). Nickel complex 2 catalyzed the Suzuki-Miyaura cross coupling reaction between bromobenzene and phenyl boronic acid to give the corresponding biphenyls in good yield. The platinum complex 5 showed good catalytic activity towards regio- and stereoselective hydroboration of terminal alkynes. Both the catalytic reactions were performed under mild reaction conditions with a very low catalyst loading.

Halogenase-Assisted Alkyne/Aryl Bromide Sonogashira Coupling for Ribosomally Synthesized Peptides.

We describe the enzymatic bromination of ribosomally synthesized peptides and develop protocols for Sonogashira coupling of peptidic aryl bromides with a panel of alkynes. Using this workflow, entirely new chemical handles are introduced onto ribosomal peptides, including but not limited to terminal alkynes, which enable further diversification via alkyne-azide click chemistry. Regiospecific enzymatic installation of the aryl bromide circumvents genetic code expansion and passivation of other reactive handles on the peptide chain, representing the applicability of biocatalysts in peptide modification chemistry.

Post-synthetic modification of Zr-based metal organic framework by schiff base zinc complex for catalytic applications in a click reaction

A novel nanocatalyst, denoted as UiO-66/Sal-ZnCl2, has been synthesized and systematically characterized employing a range of analytical techniques, including Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), thermogravimetric analysis (TGA), Brunauer–Emmett–Teller (BET) surface area analysis, and inductively coupled plasma (ICP) analysis. The comprehensive analyses collectively affirm the effective coordination of zinc chloride onto the functionalized UiO-66. Subsequently, the catalytic efficacy of UiO-66/Sal-ZnCl2 was assessed in a one-pot, three-component click reaction involving terminal alkynes, alkyl halides, and sodium azide, conducted in an aqueous medium. The catalyst demonstrated remarkable catalytic activity, showcasing the capability to facilitate the reaction with high yields and exceptional regioselectivity. Noteworthy attributes of this nanocatalyst and the method include its elevated efficiency, recyclability, convenient product workup, and, significantly, the utilization of a sustainable solvent medium. The synthesis, characterization, and catalytic performance of this catalyst collectively contribute to its potential as an innovative and reusable nanocatalyst for diverse synthetic transformations.

UiO-67 MOF-Encapsulated NHC-Based Single-Site Copper Catalyst and Its Application in Regioselective Borylation of Terminal Alkynes.

N-Heterocyclic carbenes (NHCs) act as versatile ligand backbones due to their strong σ-donation and π-acceptance properties. However, the encapsulation of NHC-coinage metal complexes in a metal-organic framework (MOF) to utilize them in organic catalysis is rare. In this work, an NHC-coordinated CuBr (NHC = Bn2Im; 1,3-dibenzyl-imidazol-2-ylidene) complex was encapsulated in UiO-67 MOF ((Bn2Im)2CuBr@UiO-67) and further utilized toward the regioselective protoboration of terminal alkynes. (Bn2Im)2CuBr@UiO-67 was found to show superior catalytic performance in aiding the protoboration of terminal alkynes, with a very high turnover frequency (TOF) of 14333.3 h-1, much higher than those of many other reported copper-based heterogeneous catalysts. Our catalyst also retained excellent catalytic efficiency for up to five cycles for the above-mentioned process. The newly synthesized (Bn2Im)2CuBr@UiO-67 and the recovered catalyst post-catalysis were characterized using various analytical techniques, including powder X-ray diffraction (PXRD), IR spectroscopy, field-emission scanning electron microscopy (FESEM), high-resolution transmission electron microscopy (HRTEM), and X-ray photoelectron spectroscopy (XPS).

Asymmetric Total Synthesis of Naturally Occurring (R)-2'-Methoxydihydroartemidin, (R)-(E)-3'-Hydroxyartemidin, and Its Structural Congeners: Method Optimization and Mechanistic Analysis.

Asymmetric total synthesis of naturally occurring 3-substituted isocoumarins, 2'-methoxydihydroartemidin, (E)-3'-hydroxyartemidin, and two structural congeners is reported in this article. Enantiopure 3-alkylisocoumarin core present in those target molecules was accessed through an atom-economical and regiodefined 6-endo-dig cyclization from properly substituted 2-halobenzoic acids and chiral terminal alkynes through ligand-free Cu(I) catalysis. A detailed mechanistic investigation was carried out through control experiments, and density functional theory (DFT) analysis reveals that solvent directed a non-Sonogashira pathway through direct insertion of alkyne through a regiodefined way is operating. The synthesized 3-alkylisocoumarins are synthetically manipulated into various small molecular entities.

4+1] Heteroannulation to Form 1‐Pyrrolines through Alder‐Ene Reaction of in situ Generated Ynimines: Development and Application in Total Synthesis of Borrecapine

AbstractWe report in this paper a novel Cu‐catalyzed synthesis of polysubstituted 1‐pyrrolines. The reaction of β,γ‐unsaturated oxime esters 4 with terminal alkynes 5 in the presence of a catalytic amount of Cu(OAc)2 and 2,2′‐biquinoline affords the corresponding 1,6‐enynimines, which undergo a highly stereoselective Alder‐ene reaction to afford 1‐pyrrolines with concomitant generation of a quaternary carbon and a 2‐azadiene motif. It represents an unusual [4+1] heteroannulation reaction wherein terminal alkynes act as a one carbon donor and are 1,1‐difunctionalized. Mechanistic studies suggest that the allylic hydrogen trans to the oxime ester main chain is selectively transferred to the electron‐rich alkyne during the pericyclic reaction. The resulting 1‐pyrrolines undergo facile acid‐catalyzed regioselective Wagner–Meerwein rearrangement to provide 2H‐pyrroles in excellent yields. The 2H‐pyrroles are also accessible from 4 and 5 in a one‐pot manner without isolation of the 1‐pyrrolines. Leveraging this heteroannulation reaction as a key step, the first total synthesis of borrecapine, a 2,3,3,5‐tetrasubstituted pyrrolidine, is accomplished.

Continuous Flow Synthesis of Five‐Membered N‐Heterocycles by Ynone System

In this study, we devised a practical and effective method for synthesizing ynones from terminal alkynes and anhydride utilizing a continuous flow apparatus at ambient temperature. Moreover, we coupled the ynones with hydrazines, and hydroxylamine hydrochloride to synthesize pyrazole and isoxazole derivatives. This protocol's unique characteristics include a metal‐free approach, mild reaction conditions, a short residence time, and a wide range of functional group tolerance. Sustainable strategies are most useful and affordable than conventional benchtop approaches.