Aryl Alkynes Research Articles

Evaluating two stages of silicone-containing arylene resin oxidation via experiment and molecular simulation

Silicon-containing aryl acetylene resin (PSA) is a new type of high-temperature resistant resin with excellent oxidation resistance, whereas antioxidant reaction mechanism of PSA resin under ultra-high temperatures still remains unclear. Herein, the oxidation behavior and mechanisms of PSA resin are systematically investigated combining kinetic analysis and ReaxFF molecular dynamics (MD) simulations. Thermogravimetric analysis indicates that the oxidation process of PSA resin undergoes two main steps: oxidative weight gain and oxidative degradation. The Distributed Activation Energy Model (DAEM) is employed for describing oxidation processes and the best-fit one is obtained using genetic algorithms and differential evolution. DAEM model demonstrates that the oxidative weight gain stage is dominated by two virtual reactants and the oxidative degradation stage consists of three virtual reactants. Correspondingly, the observation of MD reaction pathways indicates that oxygen oxidation of unsaturated structures occurs in the initial stage, which results in the formation of PSA resin oxides. Furthermore, cracked pieces react with O2 to generate CO and other chemicals in the second step. The resin matrix's great antioxidation resilience is illustrated by the formation of SiO2. The analysis based on MD simulations exhibits an efficient computational proof with the experiments and DAEM methods. Based on the results, a two-stage reaction mechanism is proposed, which provides important theoretical support for the subsequent study of the oxidation behavior of silica-based resins.

Synthesis of Aryl Thioalkynes Enabled by Electrophilic Sulfenylation of Alkynes and the Following Elimination.

An unexpected deprotonative process of thiirenium ions is presented, which provides a new synthesis of aryl thioalkynes directly from terminal alkynes via the electrophilic activation of the carbon-carbon triple bonds. The conditions are well compatible with various functional-group-substituted aryl alkynes. The direct elimination from the thiirenium ion intermediate, or its tautomer, benzyl vinyl carbocation, is supported by control experiments and labeling reaction.

Bis‐(Aminophenyl)ferrocene ligand for palladium free CuI catalyzed Csp2−Csp cross‐coupling reaction

AbstractTwo new ferrocene based molecules S,S′‐bis(4‐aminophenyl)ferrocene‐1,1'‐bis(carbothioate) (I) and S,S′‐bis(3‐aminophenyl)ferrocene‐1,1'‐bis(carbothioate) (II) have been synthesized via a thioester linkage. The prepared compounds have been successfully applied as ligands for the CuI catalyzed Sonogashira coupling reaction. The ligands are highly effective for the Csp2−Csp coupling between alkyne and iodobenzene and bromobenzene. Corresponding 1,2‐disubstituted alkynes could be synthesized from both aryl and alkyl alkynes in high yield by using catalytic amount of CuI in presence of bis(3‐aminophenyl)ferrocene derivative in dioxane at 50 °C.

Sonogashira coupling reactions with ligand-free heterogeneous nanoporous Pd catalyst

The Sonogashira coupling reaction is one of the most important protocols for the production of aryl alkynes. In order to solve the problems existing in Sonogashira cross-coupling reaction, according to the application of nanoporous palladium in Suzuki and Heck cross-coupling reactions, nanoporous palladium was used as the sustainable catalyst for the Sonogashira cross-coupling reaction. A sustainable catalyst system was tested and optimized without cuprous ion, phosphine ligand, or amine additives. Nanoporous palladium catalyst remained stable over five cycles without significant leaching or loss of catalytic activity, and the desired alkynes were obtained in high yields.

Phosphine-Catalyzed Allylic Alkylation of (Hetero)Aryl Alkynes with Pronucleophiles: Concise Total Synthesis of (±)-Esermethole.

Allylic alkylations are valuable in the construction of versatile carbon-carbon bonds, which are mostly catalyzed by noble transition metals with additional waste byproduct generation. Here, we present the first organophosphine-catalyzed allylic alkylation of (hetero)aryl alkynes with various carbo-nucleophiles. The methodology is highly atom economical and compatible with a wide substrate scope (more than 38 examples). Moreover, the reaction could be easily scaled up, and deuterium labeling experiments have been conducted to elucidate the plausible mechanism. Finally, the protocol has been utilized to achieve the concise total synthesis of natural product (±)-esermethole.

Quaternary Ammonium Salts: Catalysts for Hydrosilylation of Alkynes with Hydrosilanes

AbstractMixing i‐PrI and DABCO in solvent EtCN gave two quaternary ammonium salts (QASs) quantitatively, one of which is monocationic (QAS‐1) and the other is dicationic (QAS‐2). These QASs were found to catalyze hydrosilylation of alkynes with hydrosilanes (HAH) without the aid of metal and metalloid catalysts. This organocatalysis can be applied to a variety of alkynes: terminal/internal aryl and alkyl alkynes with/without a functional group. With dihydrosilanes (H2Si), the HAH occurred with high E‐selectivity through syn addition, which was exclusively observed when using terminal alkyl alkynes, irrespective of a hydrosilane used. A scalable HAH is also feasible. The H−Si unit remaining in alkenylsilanes derived from H2Si is available for dehydrogenative alkynylation and N‐heteroarylation under zinc–pyridine catalysis. This synthetic application delivers unique silicon compounds that have, for instance, alkyl, aryl, alkenyl, and alkynyl groups in a single molecule. Mechanistic studies suggested that alkynes activated by QASs irreversibly react with hydrosilanes that become more nucleophilic by the coordination of EtCN. A radical pathway is unlikely. The QAS catalysts can be recovered and reused at least 5 times.

Indium(III)-Catalyzed Benzannulation of 3-Formyl-4-pyrones with Terminal Aryl Alkynes: Regioselective Synthesis of Functionalized Salicylaldehydes with ortho-Terphenyl Frameworks.

An effective and unprecedented In(III)-catalyzed [4 + 2] benzannulation of 3-formyl-4-pyrones with simple arylacetylenes is reported, which enables their conversion into structurally diverse salicylaldehyde-bearing ortho-terphenyl frameworks. This transformation is achieved via an In(III)-catalyzed C-O bond extrusion and proceeds without the requirement for an external oxidant. This protocol directly provides aromatic compounds from 4-pyrones. Isotopic substitution experiments suggest that the reaction proceeds via a stepwise sequence involving the addition of an alkyne to the pyran moiety followed by cyclization, oxidation, decarboxylation, and aromatization. The synthetic utility of this protocol is demonstrated by the transformation of the obtained product into molecules with bisindole, chromene, and oxime moieties.

Peptide‐Hypervalent Iodine Reagent Chimeras: Enabling Peptide Functionalization and Macrocyclization**

AbstractHerein, we report a novel strategy for the modification of peptides based on the introduction of highly reactive hypervalent iodine reagents—ethynylbenziodoxolones (EBXs)—onto peptides. These peptide‐EBXs can be readily accessed, by both solution‐ and solid‐phase peptide synthesis (SPPS). They can be used to couple the peptide to other peptides or a protein through reaction with Cys, leading to thioalkynes in organic solvents and hypervalent iodine adducts in water buffer. Furthermore, a photocatalytic decarboxylative coupling to the C‐terminus of peptides was developed using an organic dye and was also successful in an intramolecular fashion, leading to macrocyclic peptides with unprecedented crosslinking. A rigid linear aryl alkyne linker was essential to achieve high affinity for Keap1 at the Nrf2 binding site with potential protein‐protein interaction inhibition.

Peptide-Hypervalent Iodine Reagent Chimeras: Enabling Peptide Functionalization and Macrocyclization.

Herein, we report a novel strategy for the modification of peptides based on the introduction of highly reactive hypervalent iodine reagents-ethynylbenziodoxolones (EBXs)-onto peptides. These peptide-EBXs can be readily accessed, by both solution- and solid-phase peptide synthesis (SPPS). They can be used to couple the peptide to other peptides or a protein through reaction with Cys, leading to thioalkynes in organic solvents and hypervalent iodine adducts in water buffer. Furthermore, a photocatalytic decarboxylative coupling to the C-terminus of peptides was developed using an organic dye and was also successful in an intramolecular fashion, leading to macrocyclic peptides with unprecedented crosslinking. A rigid linear aryl alkyne linker was essential to achieve high affinity for Keap1 at the Nrf2 binding site with potential protein-protein interaction inhibition.

In situ selective deuterated (hydrogenated) aryl alkynes to alkenes on Pd/Ni(OH)2-nickel foam

The preparation of deuterated alkenes via electrochemistry from a readily available deuterated source has the advantages of mild reaction conditions, sustainability, and cost-effectiveness. Hydrogen isotopic exchange is a simple method to introduce deuterium atoms into molecules without prior functionalization. However, this process typically requires complex ligand catalysts, costly sources of deuterium, and strong bases and acids to activate the robust C-H bonds. The deuterated incorporation sites and their corresponding numbers are difficult to control. In this study, an in-situ electrochemical deuteration system is reported that is based on a Pd/Ni(OH)2 nanoflake catalyst grown on a commercial nickel foam conductive substrate was used as the cathodic working electrode. A room-temperature, one-pot, two-step transformation of 4-ethynylaniline to deuterated 4-vinylanilin was achieved with a conversion rate of up to 96%, selectivity of 98%, and a deuterium ratio of 99% using D2O as the deuterium source. The interaction between Pd and Ni(OH)2-NF promoted the rapid cleavage of D2O during the semi-deuteration of aryl alkynes. The key deuterium and carbon radical intermediates were confirmed using electron paramagnetic resonance spectroscopy. A wide range of substrates and easy access to hydrogenated alkenes highlight the promising applications.

Nickel-Catalyzed Markovnikov-Selective Hydrodifluoromethylation of Alkynes Using BrCF2 H.

A Markovnikov-selective hydrodifluoromethylation of alkynes with BrCF2 H via nickel catalysis is described. This protocol proceeds via a migratory insertion of nickel hydride to alkyne followed by a CF2 H-coupling, enabling straightforward access to diverse branched CF2 H-alkenes with high efficiency and exclusive regioselectivity. The mild condition applies to a wide array of aliphatic and aryl alkynes with good functional group compatibility. Mechanistic studies are presented to support the proposed pathway.

Nickel‐Catalyzed Markovnikov‐Selective Hydrodifluoromethylation of Alkynes Using BrCF2H

AbstractA Markovnikov‐selective hydrodifluoromethylation of alkynes with BrCF2H via nickel catalysis is described. This protocol proceeds via a migratory insertion of nickel hydride to alkyne followed by a CF2H‐coupling, enabling straightforward access to diverse branched CF2H‐alkenes with high efficiency and exclusive regioselectivity. The mild condition applies to a wide array of aliphatic and aryl alkynes with good functional group compatibility. Mechanistic studies are presented to support the proposed pathway.

Enantioselective radical cascade cyclization via Ti-catalyzed redox relay

Radical cascade cyclization reactions provide an efficient method for the construction of polycyclic architectures with multiple stereogenic centers. However, achieving enantioselectivity control of this type of reaction is a challenging task. Here, we report an enantioselective cyclization of polyfunctional aryl cyclopropyl ketone and alkyne units, wherein the stereochemical outcome is directed by a chiral Ti(salen) catalyst. This transformation was proposed to proceed via a radical cascade process involving the reductive ring-opening of the cyclopropyl ketone followed by two annulation events entailing cyclization of the ensuing alkyl radical onto the alkyne and subsequent addition of the incipient vinyl radical to the Ti(IV)-enolate.

Precision Deuteration Using Cu-Catalyzed Transfer Hydrodeuteration to Access Small Molecules Deuterated at the Benzylic Position.

A highly regio- and chemoselective Cu-catalyzed aryl alkyne transfer hydrodeuteration to access a diverse scope of aryl alkanes precisely deuterated at the benzylic position is described. The reaction benefits from a high degree of regiocontrol in the alkyne hydrocupration step, leading to the highest selectivities reported to date for an alkyne transfer hydrodeuteration reaction. Only trace isotopic impurities are formed under this protocol, and analysis of an isolated product by molecular rotational resonance spectroscopy confirms that high isotopic purity products can be generated from readily accessible aryl alkyne substrates.

Room-Temperature, Copper-Free, and Amine-Free Sonogashira Reaction in a Green Solvent: Synthesis of Tetraalkynylated Anthracenes and In Vitro Assessment of Their Cytotoxic Potentials.

The multifold Sonogashira coupling of a class of aryl halides with arylacetylene in the presence of an equivalent of Cs2CO3 has been accomplished using a combination of Pd(CH3CN)2Cl2 (0.5 mol %) and cataCXium A (1 mol %) under copper-free and amine-free conditions in a readily available green solvent at room temperature. The protocol was used to transform several aryl halides and alkynes to the corresponding coupled products in good to excellent yields. The rate-determining step is likely to involve the oxidative addition of Ar-X. The green protocol provides access to various valuable polycyclic aromatic hydrocarbons (PAHs) with exciting photophysical properties. Among them, six tetraalkynylated anthracenes have been tested for their anticancer properties on the human triple-negative breast cancer (TNBC) cell line MDA-MB-231 and human dermal fibroblasts (HDFs). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to find out the IC50 concentration and lethal dose. The compounds being intrinsically fluorescent, their cellular localization was checked by live cell fluorescence imaging. 4',6-Diamidino-2-phenylindole (DAPI) and propidium iodide (PI) staining was performed to check apoptosis and necrosis, respectively. All of these studies have shown that anthracene and its derivatives can induce cell death via DNA damage and apoptosis.

Homotropic Cooperativity in Iron-Catalyzed Alkyne Cyclotrimerizations.

Enhancing catalytic activity through synergic effects is a current challenge in homogeneous catalysis. In addition to the well-established metal-metal and metal-ligand cooperation, we showcase here an example of self-activation by the substrate in controlling the catalytic activity of the two-coordinate iron complex [Fe(2,6-Xyl2C6H3)2] (1, Xyl = 2,6-Me2C6H3). This behavior was observed for aryl acetylenes in their regioselective cyclotrimerization to 1,2,4-(aryl)-benzenes. Two kinetically distinct regimes are observed dependent upon the substrate-to-catalyst ratio ([RC≡CH]0/[1]0), referred to as the low ([RC≡CH]0/[1]0 < 40) and high ([RC≡CH]0/[1]0 > 40) regimes. Both showed sigmoidal kinetic response, with positive Hill indices of 1.85 and 3.62, respectively, and nonlinear Lineweaver-Burk replots with an upward curvature, which supports positive substrate cooperativity. Moreover, two alkyne molecules participate in the low regime, whereas up to four are involved in the high regime. The second-order rate dependence on 1 indicates that binuclear complexes are the catalytically competent species in both regimes, with that in the high one being 6 times faster than that involved in the low one. Moreover, Eyring plot analyses revealed two different catalytic cycles, with a rate-determining step more endergonic in the low regime than in the high one, but with a more ordered transition state in the high regime than in the low one.

Rhodium-Catalyzed Asymmetric Annulation of Unactivated Alkynes with 3-(ortho-Boronated Aryl) Conjugated Enones: Enantioselective Synthesis of 2,3-Disubstituted Indenes

A rhodium-catalyzed tandem arylation/cyclization reaction of 3-(ortho-boronated aryl) conjugated enones with unactivated alkynes is reported. By using a rhodium(I)/chiral-diene complex as the catalyst, the protocol was processed smoothly to provide various 2,3-disubstituted indene compounds in high yields with excellent regioselectivities and enantioselectivities. The approach outlined herein is appealing, as simple diarylalkynes, diakylalkynes, and alkyl(aryl)alkynes are the starting materials.

Stereoselective Synthesis of Tetraarylethylenes Enabled by Reductive anti-1,2-Dimetallation of Alkynes.

Tetraarylethylenes (TAEs) have been gaining attention from various scientific disciplines for their characteristic chemical and physical properties. From the synthetic perspective, however, efficient methods for the selective synthesis of different isomers of TAEs are still underdeveloped. Here, we report the regio- and stereoselective synthesis of TAEs by means of sodium-promoted reductive anti-1,2-dimagnesiation of alkynes. Subsequent transmetallation to zinc generates trans-1,2-dizincioalkenes, which underwent the stereoselective arylation under a palladium catalysis to afford a variety of TAEs that had been difficult to prepare according to the conventional procedures. In addition, the present method accommodates not only diarylacetylenes but also alkyl aryl acetylenes and thus enables to synthesize a wide range of all-carbon tetrasubstituted alkenes.

Arylation of Terminal Alkynes: Transition-Metal-Free Sonogashira-Type Coupling for the Construction of C(sp)-C(sp2) Bonds.

Alkynes are attractive synthons for organic chemistry. Despite the prevalence of transition-metal-catalyzed Sonogashira reactions, a transition-metal-free version of the arylation of terminal alkynes is elusive. Herein, we report an efficient transition-metal-free Sonogashira-type coupling reaction for the one-pot arylation of alkynes to construct C(sp)-C(sp2) bonds from a tetracoordinate boron intermediate with NIS as a mediator. With its high efficiency, wide substrate range, and good functional group tolerance, this method is further supported by the gram-scale synthesis and subsequent modification of complex molecules.

Environmentally benign synthesis of 2,4-diarylquinolines under metal- & solvent-free conditions

The synthesis of 2,4-diarylquinolines is reported by employing arylamine, aryl aldehyde, and aryl acetylene using 30 mol% p-toluenesulfonic acid monohydrate (p-TSA·H2O) as a catalyst at 110 °C temperature under solvent-free conditions via a one-pot three-component reaction. The salient features of the present protocol are the nonrequirement of a metal catalyst, additive, solvent, and inert atmospheric reaction conditions, good yield, substrate scope, and shorter reaction time. Using 30 mol% p-toluenesulfonic acid monohydrate (p-TSA·H2O) as a catalyst in solvent-free conditions has made the three-component reaction efficient enough to form 2,4-diarylquinoline without the involvement of any heavy metal catalyst or additives.