Synthesis Of Biaryls Research Articles

NHC-Catalyzed Desymmetrization of N-Aryl Maleimides Leading to the Atroposelective Synthesis of N-Aryl Succinimides.

Although the construction of axially chiral C-C bonds leading to the atroposelective synthesis of biaryls and allied compounds are well-known, the related synthesis of compounds bearing axially chiral C-N bonds are relatively rare. Described herein is the N-heterocyclic carbene-catalyzed atroposelective synthesis of N-aryl succinimides having an axially chiral C-N bond via the desymmetrization of N-aryl maleimides. The NHC involved intermolecular Stetter-aldol cascade of dialdehydes with prochiral N-aryl maleimides followed by oxidation afforded N-aryl succinimides in good yields and ee values. Preliminary studies on rotation barrier for the C-N bond, the temperature dependence, and detailed DFT studies on mechanism are also provided.

NHC‐Catalyzed Desymmetrization of N‐Aryl Maleimides Leading to the Atroposelective Synthesis of N‐Aryl Succinimides

AbstractAlthough the construction of axially chiral C−C bonds leading to the atroposelective synthesis of biaryls and allied compounds are well‐known, the related synthesis of compounds bearing axially chiral C−N bonds are relatively rare. Described herein is the N‐heterocyclic carbene‐catalyzed atroposelective synthesis of N‐aryl succinimides having an axially chiral C−N bond via the desymmetrization of N‐aryl maleimides. The NHC involved intermolecular Stetter‐aldol cascade of dialdehydes with prochiral N‐aryl maleimides followed by oxidation afforded N‐aryl succinimides in good yields and ee values. Preliminary studies on rotation barrier for the C−N bond, the temperature dependence, and detailed DFT studies on mechanism are also provided.

Pd(OAc)2-biuret: A highly efficient, low cost and phosphine-free catalyst system for biaryl synthesis under aerobic conditions at room temperature

A highly efficient, less expensive and phosphine-free protocol for the Suzuki-Miyaura cross-coupling reactions of aryl halides and aryl boronic acids in iPrOH-H2O solvent under aerobic conditions has been developed. The results demonstrate that the biuret played a crucial role and making this protocol highly efficient. The Pd(OAc)2-biuret system exhibited superb catalytic activity towards the Suzuki-Miyaura cross-coupling reaction of a wide range of aryl halides with aryl boronic acids at room temperature, giving high yields even under very low catalytic loading. This system offers an attractive alternative to the existing protocols since the reaction proceeds in green solvent at room temperature with working simplicity, shorter reaction time, cost-effectiveness and provides the desired products in high yields. The effect of solvent, base as well as catalyst loading on the cross-coupling reaction of aryl halide with arylboronic acid is also described.

Sustainable and recyclable magnetic nanocatalyst of 1,10-phenanthroline Pd(0) complex in green synthesis of biaryls and tetrazoles using arylboronic acids as versatile substrates

Abstract A magnetic nanocatalyst was purveyed as a heterogeneous recoverable palladium-based catalyst anchored on green, sustainable and phosphine free support. Resulted Fe3O4@SiO2-Phen-Pd(0) nanocatalyst bearing powerful phenanthroline ligand was thoroughly characterized by physicochemical approaches like UV–vis, FT-IR, EDX, XRD, TGA, ICP, VSM, DLS, FESEM, and TEM analyses. After finding trustable data, the obtained magnetic catalyst was considered to be applied in the Suzuki-Miyaura type C-C couplings and getting corresponding tetrazoles using arylboronic acid derivatives as alternate precursors of aromatic halides and stupendous data were observed.

Ligand and Base Free Synthesis of Biaryls from Aryl Halides in Aqueous Media with Recyclable Ti0.97Pd0.03O1.97 Catalyst

Facile protocol for the synthesis of biaryls from aryl halides in presence of magnesium metal without prior formation of organometallic intermediate has been exploited. Irrespective of aqueous medium, Ti0.97Pd0.03O1.97 catalyst supports C–C bond formation reaction in presence of metals rather than dehalogenation without any additives. Homocoupling of 16 different aryl halides furnished corresponding biphenyls in good yield with better functional group tolerance. The recovery of the catalyst was carried out by employing catalyst coated cordierite monolith up to 7th cycle with high yields. A new approach for the cross-coupling reaction is also attempted.

Biaryl Construction Based on Nickel-Catalyzed C–O Bond Activation

AbstractNickel-catalyzed carbon–oxygen bond activation is one of the most powerful strategies for the direct construction of various biaryl compounds. Under nickel catalysis, efficiently produced and naturally abundant arenol-based electrophiles can be activated and coupled with different aryl nucleophiles, including nucleophiles containing magnesium, zinc, boron, etc., to produce biaryl structural units. This Account summarizes recent progress on biaryl synthesis via nickel-catalyzed C–O bond activation.1 Introduction2 Coupling of Arenols and Arenol Derivatives with Aryl Magnesium Reagents3 Coupling of Arenols and Arenol Derivatives with Aryl Zinc Reagents4 Coupling of Arenols and Arenol Derivatives with Aryl Boron Reagents5 Others6 Conclusion

Decorated palladium nanoparticles on chitosan/δ-FeOOH microspheres: A highly active and recyclable catalyst for Suzuki coupling reaction and cyanation of aryl halides

In this study, an eco-friendly and low cost magnetic nanocomposite consisting of chitosan/δ-FeOOH microspheres (CS/δ-FeOOH) was fabricated as a stabilizer by using a simple method. Pd nanoparticles (Pd NPs) were decorated on the designed CS/δ-FeOOH, and the resulting Pd NPs@CS/δ-FeOOH microspheres were employed as a heterogeneous catalyst in the construction of biaryl and benzonitriles. Pd NPs@CS/δ-FeOOH microspheres efficiently catalyzed the conversion of aryl iodides and bromides to the desired biaryls within 3 h. Moreover, Pd NPs@CS/δ-FeOOH microspheres showed high catalytic potential against synthesis of benzonitriles by providing yields up to of 99% within 4 h. More importantly, it was proved that Pd NPs@CS/δ-FeOOH microspheres were able to be easily recycled and reused up to eight runs for both reactions. This study reveals that Pd NPs@CS/δ-FeOOH microspheres are useful and recyclable nanocatalysts, which catalyze the synthesis of biaryl and benzonitriles with good reaction yields.

Pd-catalyzed oxidative homocoupling of arylboronic acids in WEPA: A sustainable access to symmetrical biaryls under added base and ligand-free ambient conditions

Symmetrical and unsymmetrical biaryls comprises a diverse class of biologically eloquent organic compounds. We herein report, a quick and eco-friendly protocol for the synthesis of biaryls by an oxidative (aerobic) homocoupling of arylboronic acids (ABAs) using Pd(OAc)2 in water extract of pomogranate ash (WEPA) as an efficient agro-waste(bio)-derived aqueous (basic) media. The reactions were executed at ambient aerobic conditions in the absence of external base and ligand to result symmetrical biaryls in excellent yields. The use of renewable media with an effective exploitation of waste, short reaction times, excellent yields of products, easy separation of the products, unnecessating the external base, oxidant, ligand or volatile organic solvents and ambient reaction conditions are the vital insights of the present protocol.

Sustainable Synthesis of Biaryls Using Silica Supported Ferrocene Appended N-Heterocyclic Carbene-Palladium Complex

A novel silica supported ferrocene appended N-heterocyclic carbene-palladium complex (SilFemBenzNHC@Pd) has been prepared and characterized by using fourier transform infrared (FT-IR), fourier transform Raman (FT-Raman), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and energy dispersive X-ray analysis (EDX). This novel complex served as a robust heterogeneous catalyst for the synthesis of biaryls via homocoupling of aryl boronic acids under base-free conditions in water. Recyclability experiments were executed successfully for six successive runs.

Electron-transfer oxidation of Organo-cuprates with Benzophenone: Synthesis of Biaryls

A mild and simple way to synthesize Biaryls from aryl bromides via formation of organo-cuprate complexes has been developed. The Organo-cuprates {Ar2CuMgBr.Mg(I)Br}, generated from Arylmagnesium bromide and half equivalent of copper(I) iodide in dry THF at lower temperature under nitrogen, underwent electron-transfer oxidation with an aryl ketone benzophenone producing homo-coupled Biaryls in moderate yields. Aryl bromides either with electron-donating or with electron-withdrawing substituents were smoothly transformed into the corresponding Biaryls through formation of aryl Grignard reagents and Organo-cuprate complexes in a one pot reaction under this electron-transfer oxidation procedure.

Bazı Piridin-Sübstitüe-Bis-1,2,4-Triazol Türevleri Üzerine Hesaplamalı Bir Çalışma ve Katalitik Aktivitelerinin İncelenmesi

In this work were specified catalytic activity of pyridine-substituted-bis-1,2,4-triazole (PBTT) derivative ligands 5,5′-(pyridine-2,5-diyl)bis(4-ethyl-4H-1,2,4-triazole-3-thiol) (L1) and 5,5′-(pyridine-2,5-diyl)bis(4-phenyl-4H-1,2,4-triazole-3-thiol) (L2) in biaryl synthesis in situ-reaction condition. Catalytic activities are determined in terms of conversion percentages to derivatives of biaryl of aryl bromides by GC-MS. The highest catalytic effect for L1 ligand was measured as 61% with 4-bromobenzaldehyde. Apart from catalytic activity studies, some structural properties of related ligands were discussed by computational methods. As a result, the ground state geometries, frontier molecular orbitals (FMOs) and also the maps of molecular electrostatic potential (MEP) of L1 and L2 ligands were obtained using DFT/B3LYP/6-31+G(d) calculations. Additionally, the global reactivity descriptors were reached using the FMOs calculations.

Anchored Pd(0) Nanoparticles on Synthetic Talc for the Synthesis of Biaryls and a Precursor of Angiotensin II Inhibitors

AbstractThe palladium-catalyzed Suzuki–Miyaura cross-coupling reaction is one of the most important and efficient reactions to prepare a variety of organic compounds, including biaryls. Despite the overwhelming number of reports related to this topic, some methodological difficulties persist in terms of catalyst handling, recovery, and reuse, as well as the reaction media. This work reports the rational design of new, efficient, cost-effective, and reusable palladium catalysts supported on synthetic talc for the Suzuki–Miyaura reaction. From the results, key points were identified: both designed catalysts accelerated the reaction in EtOH and an open-flask setup, affording moderate to excellent yields within a short time (e.g., 30 min) even for deactivated aryl halides; the protocol can be applied to a great number of both cross-coupling partners, showing an excellent functional group tolerance; the catalysts can be recovered and reused without significant loss of activity. This protocol was used for the synthesis of a precursor of angiotensin II inhibitors such as valsartan, losartan, irbesartan, and telmisartan.

Enantioselective Synthesis of Atropisomeric Biaryls using Biaryl 2,5‐Diphenylphospholanes as Ligands for Palladium‐Catalysed Suzuki‐Miyaura Reactions

AbstractHere we describe the development of biaryl 2,5‐diphenylphospholanes as a new class of C2‐symmetric, monodentate ligands for asymmetric Suzuki‐Miyaura (ASM) reactions. Screening of a series of exemplary phospholanes led to the identification of two ligands that were used to prepare a range of atropisomeric biaryl and heterobiaryl products with good to excellent levels of enantioselectivity (up to 97:3 e.r.) under mild conditions. DFT studies suggest that the formation of a constraining ligand pocket and coordination of one of the biaryl methoxy groups in the optimised ligands to the metal centre is crucial for restricting conformational freedom in the bond‐forming step.magnified image

Shape-selective C–H activation of aromatics to biarylic compounds using molecular palladium in zeolites

The selective activation of inert C–H bonds has emerged as a promising tool for avoiding the use of wasteful traditional coupling reactions. Oxidative coupling of simple aromatics allows for a cost-effective synthesis of biaryls. However, utilization of this technology is severely hampered by poor regioselectivity and by the limited stability of state-of-the-art homogeneous Pd catalysts. Here, we show that confinement of cationic Pd in the pores of a zeolite allows for the shape-selective C–H activation of simple aromatics without a functional handle or electronic bias. For instance, out of six possible isomers, 4,4′-bitolyl is produced with high shape selectivity (80%) in oxidative toluene coupling on Pd-Beta. Not only is a robust, heterogeneous catalytic system obtained, but this concept is also set to control the selectivity in transition-metal-catalysed arene C–H activation through spatial confinement in zeolite pores. Controlling the regioselectivity in the coupling of simple aromatics is challenging. Now, para–para selectivity is achieved during the aerobic dehydrogenative homocoupling of arenes through a shape-selective catalyst based on molecular palladium confined within the framework of zeolite materials.

Synthesis of Biaryls via Decarbonylative Nickel-Catalyzed Suzuki-Miyaura Cross-Coupling of Aryl Anhydrides.

Transition metal-catalyzed cross-couplings have been widely employed in the synthesis of many important molecules in synthetic chemistry for the construction of diverse C-C bonds. Conventional cross-coupling reactions require active electrophilic coupling partners, such as organohalides or sulfonates, which are not environmentally friendly enough. Herein, we disclose the first nickel-catalyzed Suzuki-Miyaura cross-coupling of aryl anhydrides and arylboronic acids for the synthesis of biaryls in a decarbonylation manner. The reaction tolerates a wide range of electron-withdrawing, electron-neutral, and electron-donating substituents in this process.

Ligand‐Free Iron‐Catalyzed Homo‐Coupling of Aryllithium Reagents

AbstractThe synthesis of symmetric biaryls via the iron‐catalyzed homo‐coupling of aryllithium reagents was developed under a mild condition, in the absence of ligand, with wide range of scope, and in good yields. Investigation on reaction concentration and practical utility of this environmentally friendly procedure also indicates a promising application outlook.

Para‐Selective Arylation of Arenes: A Direct Route to Biaryls by Norbornene Relay Palladation

AbstractBiaryl compounds are extremely important structural motifs in natural products, biologically active components and pharmaceuticals. Selective synthesis of biaryls by distinguishing the subtle reactivity difference of distal arene C−H bonds are significantly challenging. Herein, we describe para‐selective C−H arylation, which is acheived by a unique combination of a meta‐directing group and norbornene as a transient mediator. Upon direct meta‐C−H palladation, one‐bond relay palladation occurs in presence of norbornene and subsequently para‐C−H arylation is achieved for sulfonates, phosphonates and phenols bearing 2,6‐disubstitution patterns. The protocol is amenable to electron‐deficient aryl iodides. Multisubstituted arenes and phenols are obtained by postsynthetic modification of the products. The protocol allows the synthesis of hexa‐substituted benzene by sequential selective distal C−H functionalization.

Para-Selective Arylation of Arenes: A Direct Route to Biaryls by Norbornene Relay Palladation.

Biaryl compounds are extremely important structural motifs in natural products, biologically active components and pharmaceuticals. Selective synthesis of biaryls by distinguishing the subtle reactivity difference of distal arene C-H bonds are significantly challenging. Herein, we describe para-selective C-H arylation, which is acheived by a unique combination of a meta-directing group and norbornene as a transient mediator. Upon direct meta-C-H palladation, one-bond relay palladation occurs in presence of norbornene and subsequently para-C-H arylation is achieved for sulfonates, phosphonates and phenols bearing 2,6-disubstitution patterns. The protocol is amenable to electron-deficient aryl iodides. Multisubstituted arenes and phenols are obtained by postsynthetic modification of the products. The protocol allows the synthesis of hexa-substituted benzene by sequential selective distal C-H functionalization.

New Nanomagnetic Heterogeneous Cobalt Catalyst for the Synthesis of Aryl Nitriles and Biaryls.

Cobalt nanoparticles immobilized on magnetic chitosan (Fe3O4@CS-Co) have been prepared. They were identified using various techniques such as Fourier-transform infrared spectroscopy, X-ray diffraction, field emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, transmission electron microscopy, thermogravimetric analysis, vibrating sample magnetometry, X-ray photoelectron spectroscopy, and inductively coupled plasma atomic emission spectroscopy analysis and applied efficiently as a cobalt catalyst in the cyanation and fluoride-/palladium-free Hiyama reactions of different types of aryl halides employing K4[Fe(CN)6]·3H2O and triethoxyphenylsilane, respectively. After each reaction, the catalyst was isolated and reused for the second run. The catalytic activity of the catalyst was not lost apparently even after five runs. No considerable changes in its chemical structure and morphology were observed. It is worth to note that in this paper, the cobalt catalyst has been used for the first time for the cyanation of aryl halides.

Enantioselective Biaryl Synthesis Enabled by Electrochemical Nickel Catalysis

Enantioselective Biaryl Synthesis Enabled by Electrochemical Nickel Catalysis