Aryl Halides Research Articles

CuI/Oxalamide-Catalyzed Coupling Reaction of (Hetero)aryl Halides with Sodium Nitrite.

The N,N'-bis(thiophen-2-ylmethyl)oxalamide (BTMO) was found to be an effective ligand for Cu-catalyzed ipso-nitration of (hetero)aryl halides (Br, I), making the coupling reaction with sodium nitrite proceed smoothly at 100-120 °C with 1-5 mol % CuI and BTMO. Electron-rich substrates were the best coupling partners to give the desired coupling products in good to excellent yields at 100 °C. Electron-neutral substrates required heating at 120 °C to get complete conversion, while rather low conversions were observed in the case of electron-poor (hetero)aryl bromides.

Regioselective C6‐Arylation of Thieno[3,2‐c]pyrazole Heterocycles with Aryl Iodides

Efficient and regioselective C6‐arylation of thieno[3,2‐c]pyrazoles with aryl iodides as coupling partners has been developed. This strategy was performed in the presence of Pd(OAc)2 as catalyst in combination with AgOTf as an oxidant and TFA in dimethylacetamide. In all experiments, only the C6‐arylated thieno[3,2‐c]pyrazole was isolated since its C5‐regioisomer was not observed, indicating the high regioselectivity of this approach. The catalytic system used is compatible with a variety of 3‐functionalized thieno[3,2‐c]pyrazoles and iodoaryl electrophiles, providing access to novel 3,6‐disubstituted thieno[3,2‐c]pyrazoles in moderate to good yields.

Efficient solar-driven interfacial evaporation using conjugated microporous polymer networks synthesized from Buchwald–Hartwig coupling

Solar-driven interfacial evaporation (SDIE) has been considered as an effective and sustainable technology to purify water. To optimize heat localization and regulate water-existing forms via developing excellent photothermal materials is a key strategy to enhance SDIE performance. Herein, three novel conjugated microporous polymer networks (namely PBPs) were readily synthesized via Buchwald-Hartwig coupling between aryl bromides and p-phenylenediamine. Under 1 sun irradiation, the pure PBP-He without any additives delivered an excellent water evaporation of 1.18 and 0.96 kg · m−2 · h−1 using pure water, nature seawater as water source, respectively, and the corresponding energy conversion efficiency was up to 81.1 % and 65.7 %. An ever-enhanced SDIE performance was found in the PBPs networks with increased amine-linked sites density. The study provided a promising CMPs-based photothermal conversion platform for water purification, photothermal therapy, and photothermal sterilization, etc.

Synthesis of amide functionlized bidentate NHC-Pd complex for application as catalyst in Suzuki‐Miyaura cross-coupling, in distilled water, under mild reaction conditions

An amide functionlized bidentate NHC-Pd complex was successfully prepared by a facile solvothermal methodology from a bridged bis-benzimidazolium chloride and K2PdCl4. The new bidentate NHC-Pd complex has been effectively applied as catalyst in Suzuki-Miyaura cross-coupling reactions of aryl halides with arylboronic acids in distilled water (yields up to 99.0%). The bridged bis-benzimidazolium ligand from the Pd complex, bearing the amide functional groups on the nitrogen atom, showed to distinctly influence the electronic and steric effects on the catalytic process. The potential of application of the new NHC-Pd catalyst in diverse CC bond forming processes, working under environmentally friendly conditions, is further outlined.

Anion exchange membranes derived from poly(ionic liquid) of poly(bis-piperidinium) and polybenzimidazole blends

Anion exchange membranes (AEMs) play a critical role in various environmentally friendly electrochemical energy conversion and storage devices such fuel cells, water electrolysis and flow batteries. Recently, AEMs based on ether-free ionomers or ionenes have attracted much attention due to their excellent alkaline stabilities, however normally suffering from multiple-step synthetic procedure, post-functionalization and the use of precious metal catalysts. In this study, we develop a facile method to synthesize bis-piperidinium main-chain poly(ionic liquid)s devoid of ether linkages through the nucleophilic reaction between a bis-piperidine monomer of 4,4′-trimethylene bis(1-methyl-piperidine) and various bifunctional alkyl or aryl bromides. Seven poly(ionic liquid)s of poly(bis-alkyl piperidinium) are subsequently blended with polybenzimidazole (PBI) to give mechanically robust and dimensionally stable AEMs. The membrane performances are readily adjusted by changing the chemical structure of poly(bis-alkyl piperidinium)s. The membrane based on the poly(bis-alkyl piperidinium) containing a flexible butylidene spacer chain achieves the highest Br- conductivity of 67 mS cm−1 at 80 °C, tensile strength of around 13 MPa at room temperature, and a superior alkaline stability in 1 mol/L KOH at 60 °C during 1250 h. Density functional theory calculations further support the enhanced alkaline stability of the piperidinium cation with alkyl group compared with the one with benzyl group.

Photoinduced Pd-Catalyzed Enantioselective Carboamination of Dienes via Aliphatic C-H Bond Elaboration.

Three-component diene carboaminations offer a potent means to access synthetically valuable allylic amines with rapid molecular complexity escalation. The existing literature primarily discloses racemic examples, necessitating the use of halides/pseudohalides as substrates. This paper introduces a photoinduced Pd-catalyzed enantioselective three-component carboamination of aryl-substituted 1,3-dienes, leveraging aliphatic C-H bonds for rapid synthesis. The reaction employs 10 mol % of chiral palladium catalyst and an excess aryl bromide as the HAT reagent. This approach yields diverse chiral allylamines with moderate to excellent enantioselectivities. Notably, it stands as the first instance of an asymmetric three-component diene carboamination reaction, directly utilizing abundant C(sp3)-H bearing partners, such as toluene-type substrates, ethers, amines, esters, and ketones. The protocol exhibits versatility across amines, encompassing aliphatic, aromatic, primary, and secondary derivatives. This method could serve as a versatile platform for stereoselective incorporation of various nucleophiles, dienes, and C(sp3)-H bearing partners.

Selective Arylation of RNA 2′‐OH Groups via SNAr Reaction with Trialkylammonium Heterocycles

Small‐molecule reactions at the 2′‐OH groups of RNA enable useful applications for transcriptome technology and biology. To date, all reactions have involved carbonyl acylation and mechanistically related sulfonylation, limiting the types of modifications and properties that can be achieved. Here we report that electron‐deficient heteroaryl species selectively react with 2′‐OH groups of RNA in water via SNAr chemistry. In particular, trialkyl‐ammonium (TAA)‐activated aromatic heterocycles, prepared in one step from aryl chloride precursors, give high conversions to aryl ether adducts with RNAs in aqueous buffer in ~2‐3 h. Remarkably, a TAA triazine previously used only for reaction with carboxylic acids, shows unprecedented selectivity for RNA over water, reacting rapidly with 2′‐OH groups while exhibiting a half‐life in water of >10 days. We further show that a triazine aryl species can be used as a probe at trace‐level yields to map RNA structure in vitro. Finally, we prepare a number of functionalized trialkylammonium triazine reagents and show that they can be used to covalently label RNA efficiently for use in vitro and in living cells. This direct arylation chemistry offers a simple and distinct structural scaffold for post‐synthetic RNA modification, with the potential for utility in multiple applications in transcriptome research.

Selective Arylation of RNA 2'-OH Groups via SNAr Reaction with Trialkylammonium Heterocycles.

Small-molecule reactions at the 2'-OH groups of RNA enable useful applications for transcriptome technology and biology. To date, all reactions have involved carbonyl acylation and mechanistically related sulfonylation, limiting the types of modifications and properties that can be achieved. Here we report that electron-deficient heteroaryl species selectively react with 2'-OH groups of RNA in water via SNAr chemistry. In particular, trialkyl-ammonium (TAA)-activated aromatic heterocycles, prepared in one step from aryl chloride precursors, give high conversions to aryl ether adducts with RNAs in aqueous buffer in ~2-3 h. Remarkably, a TAA triazine previously used only for reaction with carboxylic acids, shows unprecedented selectivity for RNA over water, reacting rapidly with 2'-OH groups while exhibiting a half-life in water of >10 days. We further show that a triazine aryl species can be used as a probe at trace-level yields to map RNA structure in vitro. Finally, we prepare a number of functionalized trialkylammonium triazine reagents and show that they can be used to covalently label RNA efficiently for use in vitro and in living cells. This direct arylation chemistry offers a simple and distinct structural scaffold for post-synthetic RNA modification, with potential utility in multiple applications in transcriptome research.

NOVEL SYNTHETIC INVESTIGATION IN THE FIELD OF INDOLO[2,3-B]QUINOXALINE RING CONTAINING TETRACYCLIC AND PENTACYCLIC HETEROCYCLES

A series of seven new indolo[2,3-b]quinoxaline ring containing compounds were efficiently synthesized in three different pathways. In the first case, the relevant pentacyclic systems (3,4) were received by the condensation reaction between 7-acetyl-1,5,6,7-tetrahydropyrrolo[3,2-f]indole-2,3-dione and o-phenylenediamine in glacial acetic acid. In the second case, tetracyclic indolo[2,3-b]qui-no¬xa¬li¬ne derivatives (7, 8a-d) were synthesised by a one-pot approach using Pd-catalyzed Sonogashira-hagihara C-C cross-coupling reaction between various terminal acetylenes and 9-iodo-6H-indo¬lo¬[2,3-b]quinoxaline in presence of various Pd catalysts. The third pathway is based on the Cu-catalyzed modified Ullmann protocol. The appropriate indolo-quinoxaline derivative (9) was successfully syn¬the¬sized by arylamination, using benzylamine (as a nucleophile) and 6-benzyl-9-iodo-6H-indolo[2,3-b]qui¬no¬xaline as an aryl halide. The reaction was performed in DMF in the presence of CuI.

C–O, C–S, and C–P Coupling of Aryl Halides by a Ni(II)-Incorporated Covalent Organic Framework

C–O, C–S, and C–P Coupling of Aryl Halides by a Ni(II)-Incorporated Covalent Organic Framework

Substitution Effects in Aryl Halides and Amides into the Reaction Mechanism of Ullmann-Type Coupling Reactions.

In this article, we present a comprehensive computational investigation into the reaction mechanism of N-arylation of substituted aryl halides through Ullmann-type coupling reactions. Our computational findings, obtained through DFT ωB97X-D/6-311G(d,p) and ωB97X-D/LanL2DZ calculations, reveal a direct relation between the previously reported experimental reaction yields and the activation energy of haloarene activation, which constitutes the rate-limiting step in the overall coupling process. A detailed analysis of the reaction mechanism employing the Activation Strain Model indicates that the strain in the substituted iodoanilines is the primary contributor to the energy barrier, representing an average of 80% of the total strain energy. Additional analysis based on conceptual Density Functional Theory (DFT) suggests that the nucleophilicity of the nitrogen in the lactam is directly linked to the activation energies. These results provide valuable insights into the factors influencing energetic barriers and, consequently, reaction yields. These insights enable the rational modification of reactants to optimize the N-arylation process.

Palladium(II)-Catalyzed Tandem γ-C(sp2)-H Arylation and Cyclization for the Construction of Natural Product-Like Polycyclic Fused ortho-Quinone Scaffolds.

Here, we report a novel strategy for the direct construction of polycyclic fused ortho-quinone scaffolds through palladium(II)-catalyzed tandem γ-C(sp2)-H arylation and cyclization of arylglyoxals with aryl iodides. This transformation features unique tandem transient directing of γ-C(sp2)-H arylation and cyclization reaction mode, broad substrate scope, especially for the aromatic substrates containing oxygen and sulfur atoms, and avoiding the common issue of aromatization due to the construction of the hexatomic ring.

Cobalt(III) Halide Metal-Organic Frameworks Drive Catalytic Halogen Exchange.

The selective halogenation of complex (hetero)aromatic systems is a critical yet challenging transformation that is relevant to medicinal chemistry, agriculture, and biomedical imaging. However, current methods are limited by toxic reagents, expensive homogeneous second- and third-row transition metal catalysts, or poor substrate tolerance. Herein, we demonstrate that porous metal-organic frameworks (MOFs) containing terminal Co(III) halide sites represent a rare and general class of heterogeneous catalysts for the controlled installation of chlorine and fluorine centers into electron-deficient (hetero)aryl bromides using simple metal halide salts. Mechanistic studies support that these halogen exchange (halex) reactions proceed via redox-neutral nucleophilic aromatic substitution (SNAr) at the Co(III) sites. The MOF-based halex catalysts are recyclable, enable green halogenation with minimal waste generation, and facilitate halex in a continuous flow. Our findings represent the first example of SNAr catalysis using MOFs, expanding the lexicon of synthetic transformations enabled by these materials.

Arylative Ring Expansion of 3‐Vinylazetidin‐3‐Ols and 3‐Vinyloxetan‐3‐Ols to Dihydrofurans by Dual Palladium and Acid Catalysis

AbstractIn contrast to the well‐studied 1‐vinylcyclobutanols, the reactivity of 3‐vinylazetidin‐3‐ols 1 and 3‐vinyloxetan‐3‐ols 2 under transition metal catalysis remains largely unexplored. We report herein their unique reactivity under dual palladium and acid catalysis. In the presence of a catalytic amount of Pd(OAc)2(PPh3)2, AgTFA and triflic acid, the reaction of 1 or 2 with aryl iodides affords 2,3,4‐trisubstituted dihydrofurans, which are valuable heterocycles in organic synthesis. Mechanistic studies reveal that this arylative ring‐expansion reaction proceeds via a domino process involving Heck arylation of alkene, acid‐catalyzed transposition of allylic alcohol and ring opening of the azetidine/oxetane by an internal hydroxyl group.

Arylative Ring Expansion of 3-Vinylazetidin-3-Ols and 3-Vinyloxetan-3-Ols to Dihydrofurans by Dual Palladium and Acid Catalysis.

In contrast to the well-studied 1-vinylcyclobutanols, the reactivity of 3-vinylazetidin-3-ols 1 and 3-vinyloxetan-3-ols 2 under transition metal catalysis remains largely unexplored. We report herein their unique reactivity under dual palladium and acid catalysis. In the presence of a catalytic amount of Pd(OAc)2(PPh3)2, AgTFA and triflic acid, the reaction of 1 or 2 with aryl iodides affords 2,3,4-trisubstituted dihydrofurans, which are valuable heterocycles in organic synthesis. Mechanistic studies reveal that this arylative ring-expansion reaction proceeds via a domino process involving Heck arylation of alkene, acid-catalyzed transposition of allylic alcohol and ring opening of the azetidine/oxetane by an internal hydroxyl group.

Water-Promoted Mild and General Michaelis-Arbuzov Reaction of Triaryl Phosphites and Aryl Iodides by Palladium Catalysis.

A Pd-catalyzed relatively general Michaelis-Arbuzov reaction of triaryl phosphites and aryl iodides for preparing useful aryl phosphonates was developed. Interestingly, water can greatly facilitate the reaction through a water-participating phosphonium intermediate rearrangement process, which also makes the reaction conditions rather mild. In comparison with the known methods, this reaction is milder and more general, as it exhibits excellent functional group tolerance, can be applied to various triaryl phosphites and aryl iodides, and can be extended to aryl phosphonites and phosphinites. A gram-scale reaction with a low catalyst loading also revealed its practicality and potential in large-scale preparation.

Palladium-Catalyzed Atroposelective Suzuki-Miyaura Coupling to Construct Axially Chiral Tetra-Substituted α-Boryl Styrenes.

Palladium-catalyzed Suzuki-Miyaura (SM) coupling is a valuable method for forming C─C bonds, including those between aryl moieties. However, achieving atroposelective synthesis of axially chiral styrenes via SM coupling remains challenging. In this study, a palladium-catalyzed atroposelective Suzuki-Miyaura coupling between gem-diborylalkenes and aryl halides is presented. Using the monophosphine ligand Me-BI-DIME (L2), a range of axially chiral tetra-substituted acyclic styrenes with high yields and excellent enantioselectivities are successfully synthesized. Control experiments reveal that the gem-diboryl group significantly influences the product enantioselectivities and the coupling prefers to occur at sites with lower steric hindrance. Additionally, the alkenyl boronate group in the products proves versatile, allowing for various transformations while maintaining high optical purities.

Electrochemical Nickel‐Catalyzed Hydrogenation

AbstractOlefin hydrogenation is one of the most important transformations in organic synthesis. Electrochemical transition metal‐catalyzed hydrogenation is an attractive approach to replace the dangerous hydrogen gas with electrons and protons. However, this reaction poses major challenges due to rapid hydrogen evolution reaction (HER) of metal‐hydride species that outcompetes alkene hydrogenation step, and facile deposition of the metal catalyst at the electrode that stalls reaction. Here we report an economical and efficient strategy to achieve high selectivity for hydrogenation reactivity over the well‐established HER. Using an inexpensive and bench‐stable nickel salt as the catalyst, this mild reaction features outstanding substrate generality and functional group compatibility, and distinct chemoselectivity. In addition, hydrodebromination of alkyl and aryl bromides could be realized using the same reaction system with a different ligand, and high chemoselectivity between hydrogenation and hydrodebromination could be achieved through ligand selection. The practicability of our method has been demonstrated by the success of large‐scale synthesis using catalytic amount of electrolyte and a minimal amount of solvent. Cyclic voltammetry and kinetic studies were performed, which support a NiII/0 catalytic cycle and the pre‐coordination of the substrate to the nickel center.

Electrochemical Nickel-Catalyzed Hydrogenation.

Olefin hydrogenation is one of the most important transformations in organic synthesis. Electrochemical transition metal-catalyzed hydrogenation is an attractive approach to replace the dangerous hydrogen gas with electrons and protons. However, this reaction poses major challenges due to rapid hydrogen evolution reaction (HER) of metal-hydride species that outcompetes alkene hydrogenation step, and facile deposition of the metal catalyst at the electrode that stalls reaction. Here we report an economical and efficient strategy to achieve high selectivity for hydrogenation reactivity over the well-established HER. Using an inexpensive and bench-stable nickel salt as the catalyst, this mild reaction features outstanding substrate generality and functional group compatibility, and distinct chemoselectivity. In addition, hydrodebromination of alkyl and aryl bromides could be realized using the same reaction system with a different ligand, and high chemoselectivity between hydrogenation and hydrodebromination could be achieved through ligand selection. The practicability of our method has been demonstrated by the success of large-scale synthesis using catalytic amount of electrolyte and a minimal amount of solvent. Cyclic voltammetry and kinetic studies were performed, which support a NiII/0 catalytic cycle and the pre-coordination of the substrate to the nickel center.

Ligand‐Free Copper(0)‐Catalyzed C−S Ullmann‐Type Cross‐Coupling Reaction: S‐Arylation of 5,4‐Disubstituted 2,4‐Dihydro‐3H‐1,2,4‐triazole‐3‐thiones

AbstractWe investigated the S‐arylation of 5,4‐disubstituted 2,4‐dihydro‐3H‐1,2,4‐triazole‐3‐thiones under ligand‐free Cu(0) catalysis employing Ullmann‐type reaction conditions. We determined optimal reaction conditions and assessed the impact of substituents in the arylating agent on the reaction progress. Notably, the presence of an electron‐withdrawing group (EWG) in the aryl halide facilitated the reaction even without a catalyst. In particular, an EWG in the para position of the aromatic ring exerted a directing effect on the leaving group, regardless of the halogen present.