Aryl Halides Research Articles

Ni/C-catalyzed aminocarbonylation of aryl halides using DMF as an amine source and o-chlorophenyl formate as a CO surrogate and promoter

We developed Ni/C-catalyzed aminocarbonylation of aryl halide by utilizing DMF and o-chlorophenyl formate to produce tertiary amides. This reaction employed o-chlorophenyl formate (OCPF) as a CO source, and it also acts as a promoter for the selective tertiary amide synthesis. Even under ideal conditions, this newly established approach considerably reduces the generation of homo-coupled biaryl ketone and phenoxy carbonylation byproducts. This protocol shows remarkable activity towards a wide range of aryl halides containing electron-donating and electron-withdrawing functional groups. This methodology represents the moisture-sensitive ligand-free, co-catalyst-free, and heterogeneous recyclable catalyst. The Ni/C catalyst was utilized for up to five consecutive runs. The fresh and recycled Ni/C catalysts were characterized using several techniques, including TEM, SEM, EDX, XRD, and TGA analysis.

Nitrate reduction enables safer aryldiazonium chemistry.

Aryldiazonium salts remain a staple in organic synthesis and are still prepared largely in accord with the protocol developed in the 19th century. Because of the favorable reactivity that often cannot be achieved with other aryl(pseudo)halides, diazonium chemistry continues to grow. Facile extrusion of dinitrogen contributes to the desired reactivity but is also reason for safety concerns. Explosions have occurred since the discovery of these reagents and still result in accidents. In this study, we report a diazonium chemistry paradigm shift based on nitrate reduction using thiosulfate or dihalocuprates as electron donors that avoids diazonium accumulation. Because nitrate reduction is rate-limiting, aryldiazoniums are produced as fleeting intermediates, which results in a safer and often more efficient deaminative halogenation in a single step from anilines.

Palladium-Catalyzed Esterification of Aryl Fluorosulfates with Aryl Formates.

An efficient palladium-catalyzed carbonylation of aryl fluorosulfates with aryl formates for the facile synthesis of esters was developed. The cross-coupling reactions proceeded effectively in the presence of a palladium catalyst, phosphine ligand, and triethylamine in DMF to produce the corresponding esters in moderate to good yields. Of note, functionalities or substituents, such as nitro, cyano, methoxycarbonyl, trifluoromethyl, methylsulfonyl, trifluoromethoxy, fluoro, chloro, bromo, methyl, methoxy, N,N-dimethyl, and [1,3]dioxolyl, were well-tolerated in the reactions, which could be kept for late-stage modification. The reactions employing readily available and relatively robust aryl fluorosulfates as coupling electrophiles could potentially serve as an attractive alternative to traditional cross-couplings with the use of aryl halides and pseudohalides as substrates.

Transition-Metal-Catalyzed Direct Arylation of Ammonia

AbstractIn the past few decades, transition-metal-catalyzed direct amination of aryl halides with ammonia has attracted significant attention from chemists because of its broad substrate scope, good functional group compatibility, and high reaction selectivity. Herein, recent examples of transition-metal-catalyzed syntheses of aniline derivatives starting from aryl halides are reviewed.1 Introduction2 Heat-Driven Transition-Metal-Catalyzed Amination of Aryl Electrophiles2.1 Palladium-Catalyzed Amination2.2 Copper-Catalyzed Amination2.3 Nickel-Catalyzed Amination3 Light-Driven Transition-Metal-Catalyzed Amination of Aryl Electrophiles4 Conclusion and Outlook

Site‐Selective S‐Arylation of 1‐Thiosugars with Aryl Thianthrenium Salts through Copper(I)‐Mediated, Photoredox‐ Catalyzed Reactions

AbstractA process for the synthesis of aryl thioglycosides from the aryl thianthrenium salts and 1‐thiosugars is achieved by copper(I)‐mediated, photoredox‐catalyzed reactions. The desired products could be obtained in 32% to 78% yield after irradiation with 34 W blue light at room temperature. Various functional groups, especially including halogen groups, were well tolerated under standard reaction conditions. This strategy differs conceptually from all previous S‐glycosylations in that thiosugar functionality could be incorporated into complex natural products or drugs at a late stage site‐selectively, which has not been shown via aryl halides and aryldiazonium salts.

Triple Role of Proton Sponge (DMAN) in the Palladium-Catalyzed Direct Stereoselective Synthesis of C-Aryl Glycosides from Glycals.

The triple role of 1,8-bis(dimethylamino)naphthalene (proton sponge) as a reductant, ligand precursor, and organic base in the palladium-catalyzed Heck-type coupling reaction of glycals with aryl iodides affords the rapid and stereoselective synthesis of 2',3'-unsaturated α-C-aryl glycosides in excellent yields. The role of the proton sponge in reducing palladium(II) to (0) has been studied using cyclic voltammetry, UV-vis, HRMS, and other spectroscopic techniques. This is the first example of a palladium proton sponge complex utilized in coupling reactions. The method is observed to be tolerant of various functional groups, as demonstrated by the huge substrate scope. Moreover, the 2',3'-unsaturated α-C-aryl glycosides were also converted to 3-keto-β-C-glycosides under sterically hindered pyridinium salt catalysis via a ring-opening and -closing mechanism.

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.

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.

Electro/Ni Dual-Catalyzed Decarboxylative C(sp3)-C(sp2) Cross-Coupling Reactions of Carboxylates and Aryl Bromide.

Paired redox-neutral electrolysis offers an attractive green platform for organic synthesis by avoiding sacrificial oxidants and reductants. Carboxylates are non-toxic, stable, inexpensive, and widely available, making them ideal nucleophiles for C-C cross-coupling reactions. Here, we report the electro/Ni dual-catalyzed redox-neutral decarboxylative C(sp3)-C(sp2) cross-coupling reactions of pristine carboxylates with aryl bromides. At a cathode, a NiII(Ar)(Br) intermediate is formed through the activation of Ar-Br bond by a NiI-bipyridine catalyst and subsequent reduction. At an anode, the carboxylates, including amino acid, benzyl carboxylic acid, and 2-phenoxy propionic acid, undergo oxidative decarboxylation to form carbon-based free radicals. The combination of NiII(Ar)(Br) intermediate and carbon radical results in the formation of C(sp3)-C(sp2) cross-coupling products. The adaptation of this electrosynthesis method to flow synthesis and valuable molecule synthesis was demonstrated. The reaction mechanism was systematically studied through electrochemical voltammetry and density functional theory (DFT) computational studies. The relationships between the electrochemical properties of carboxylates and the reaction selectivity were revealed. The electro/Ni dual-catalyzed cross-coupling reactions described herein expand the chemical space of paired electrochemical C(sp3)-C(sp2) cross-coupling and represent a promising method for the construction of the C(sp3)-C(sp2) bonds because of the ubiquitous carboxylate nucleophiles and the innate scalability and flexibility of electrochemical flow-synthesis technology.

Electro/Ni Dual‐Catalyzed Decarboxylative C(sp3)−C(sp2) Cross‐Coupling Reactions of Carboxylates and Aryl Bromide

AbstractPaired redox‐neutral electrolysis offers an attractive green platform for organic synthesis by avoiding sacrificial oxidants and reductants. Carboxylates are non‐toxic, stable, inexpensive, and widely available, making them ideal nucleophiles for C−C cross‐coupling reactions. Here, we report the electro/Ni dual‐catalyzed redox‐neutral decarboxylative C(sp3)−C(sp2) cross‐coupling reactions of pristine carboxylates with aryl bromides. At a cathode, a NiII(Ar)(Br) intermediate is formed through the activation of Ar−Br bond by a NiI‐bipyridine catalyst and subsequent reduction. At an anode, the carboxylates, including amino acid, benzyl carboxylic acid, and 2‐phenoxy propionic acid, undergo oxidative decarboxylation to form carbon‐based free radicals. The combination of NiII(Ar)(Br) intermediate and carbon radical results in the formation of C(sp3)−C(sp2) cross‐coupling products. The adaptation of this electrosynthesis method to flow synthesis and valuable molecule synthesis was demonstrated. The reaction mechanism was systematically studied through electrochemical voltammetry and density functional theory (DFT) computational studies. The relationships between the electrochemical properties of carboxylates and the reaction selectivity were revealed. The electro/Ni dual‐catalyzed cross‐coupling reactions described herein expand the chemical space of paired electrochemical C(sp3)−C(sp2) cross‐coupling and represent a promising method for the construction of the C(sp3)−C(sp2) bonds because of the ubiquitous carboxylate nucleophiles and the innate scalability and flexibility of electrochemical flow‐synthesis technology.

An Efficient Supported Cu(I) Catalyst for the Amination of Aryl Halides with Sodium Azide

AbstractWe present the synthesis and characterization of a new Cu(I) complex supported on SBA‐15 as a catalyst for preparing anilines from the reaction of aryl halides with sodium azide. The SBA‐15 support was modified by treating it sequentially with (3‐aminopropyl) triethoxysilane (APTES), cyanuric chloride, and 2‐aminothiazole (AT). The modified mesoporous silica, SBA‐15@BAT, was then treated with a CuI solution in acetonitrile to give SBA‐15@BAT‐Cu(I). The catalyst underwent thorough characterization using conventional methods. X‐Ray photoelectron spectroscopy (XPS) analysis corroborated the presence of copper in the +1 oxidation state in the catalyst. The supported Cu(I) complex sufficiently catalyzed the amination reaction of iodo‐, bromo‐, and chloroarenes with NaN3. The catalyst was centrifuged, washed, and applied in the subsequent run. We investigated the effects of various reaction components and parameters to determine the optimal conditions for the reaction. The heterogeneous catalyst exhibited noticeable stability and was reused over seven runs with slight deactivation.

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.

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.