Regioselective Metal‐ and Reagent‐Free Arylation of Benzothiophenes by Dehydrogenative Electrosynthesis

A novel strategy for the synthesis of biaryls consisting of a benzothiophene and a phenol moiety is reported. These heterobiaryls are of utmost interest for pharmaceutical, biological, and high‐performance optoelectronic applications. The metal‐ and reagent‐free, electrosynthetic, and highly efficient method enables the generation of 2‐ and 3‐(hydroxyphenyl)benzo[b]thiophenes in a regioselective fashion. The described one‐step synthesis is easy to conduct, scalable, and inherently safe. The products are afforded in high yields of up to 88 % and with exquisite selectivity. The reaction also features a broad scope and tolerates a large variety of functional groups.     

Synthesis of biaryls via decarboxylative Pd-catalyzed cross-coupling reaction

[reaction: see text] A simple and efficient route to biaryls via Pd-catalyzed decarboxylative cross-couplings of arene carboxylic acids and aryl iodides is reported. The PdCl2/AsPh3 catalytic system in the presence of Ag2CO3 in DMSO was found to be particularly efficient to perform this transformation. This reaction can be extended to the synthesis of various biaryls, including sterically hindered biaryls, with yields ranging from 58% to 90%.     

Biaryl synthesis via decarboxylative Pd-catalyzed reactions of arenecarboxylic acids and diaryliodonium triflates

A novel simple and efficient synthesis of biaryls via a Pd-catalyzed decarboxylative cross-coupling reaction of arenecarboxylic acids and diaryliodonium triflates is described. The PdCl2/DPEphos catalytic system in the presence of Ag2CO3 in DMSO was found to be the most efficient. Various biaryls, including sterically hindered biaryls, were synthesized with yields ranging from 37 to 85%.     

Pd(OAc)2/PPh3-Catalyzed Desulfonylative Homocoupling of Arylsulfonyl Chlorides

The Pd‐catalyzed homodimerization with respect to arylsulfonyl chlorides as an efficient method for the synthesis of biaryls has been developed. This desulfonylative reaction which was performed at reflux in 1,4‐dioxane for 4 h under air afforded the desired products in good to excellent yields.     

Desulfinative palladium‐catalyzed cross‐coupling of arylsulfonyl hydrazides with aryl bromides under air

A highly efficient and mild palladium‐catalyzed cross‐coupling of arylsulfonyl hydrazides and aryl bromides for the selective synthesis of unsymmetrical biaryls has been developed. This methodology has the advantages of easily accessible starting materials, functional group tolerance and a wide range of substrates, which provide rapid access to biaryls derivatives. In this protocol, abundant and stable aryl bromides serve as the aryl sources by coupling reaction of the aryl group generated from arylsulfonyl hydrazides via in situ release of nitrogen and sulfur dioxide. No external oxidants or acids are needed for this kind of transformation.     

Gold‐Catalyzed Direct Oxidative Arylation with Boron Coupling Partners

An efficient synthesis of biaryls through a gold‐catalyzed oxidative cross‐coupling of arenes with strong electron‐deprived aryl boronates is presented herein. Regio‐ and chemocontrol are achieved by the selective activation of these coupling partners by gold at different oxidation states. Under reaction conditions devoid of basic additives or directing groups, the role of acetato ligand as an internal base has been revealed as a key parameter for expanding the reaction scope in these transformations.     

Heterogeneous Rhodium‐Catalyzed Aerobic Oxidative Dehydrogenative Cross‐Coupling: Nonsymmetrical Biaryl Amines

The first heterogeneously catalyzed oxidative dehydrogenative cross‐coupling of aryl amines is reported herein. 2‐Naphthylamine analogues were reacted with various electron‐rich arenes using a heterogeneous Rh/C catalyst under mild aerobic conditions, thus affording nonsymmetrical biaryl amines in excellent yields with high selectivities. This reaction provides a mild, operationally simple, and efficient approach for the synthesis of biaryls which are important to pharmaceutical and materials chemistry.     

Desulfinylative Pd-catalyzed coupling reaction of arenediazonium salt with aryl sulfinates to give unsymmetrical biaryls

An efficient route for the synthesis of unsymmetrical biaryls was developed via palladium catalyzed reaction of arenediazonium salts and aryl sulfinates under inert atmosphere. This synthesis involves cascade processes. Tetrabutylammonium iodide was used as an iodide source for in situ formation of aryl iodide, followed by desulfinylative cross-coupling reaction between aryl sulfinates and aryl iodides. A wide range of biaryls were selectively prepared in one pot from simple substrates in good to excellent yields.     

Rapid Assembly of Diversely Functionalized Spiroindenes by a Three‐Component Palladium‐Catalyzed C−H Amination/Phenol Dearomatization Domino Reaction

A novel palladium‐catalyzed three‐component reaction of phenol‐derived biaryls with N‐benzoyloxyamines and norbornadiene (NBD) has been developed for the assembly of highly functionalized spiroindenes. This domino process was realized through NBD‐assisted C−H amination and phenol dearomatization by forming one C−N bond and two C−C bonds in a single step. Preliminary studies indicated that asymmetric control of this transformation was feasible with chiral ligands. Moreover, the potential synthetic utility of this methodology was highlighted by a series of further transformations.     

CuBr/proline‐catalyzed cross‐coupling of unactivated benzene with aryl halides

Direct C? H arylation of unactivated benzene with aryl halides was achieved using a readily available copper catalyst. The reaction was carried out at 80 °C, using CuBr as catalyst, proline as ligand and t‐BuOK as base. This radical cross‐coupling reaction between unactivated benzene and aryl iodides proceeds via homolytic aromatic substitution and offers an efficient method for the synthesis of various biaryls in good to excellent yields. Copyright © 2015 John Wiley & Sons, Ltd.     

Diels-Alder approach to tetra-ortho-substituted biaryls employing propargylic tertiary alcohols as dienophiles

The efficient synthesis of a series of tetra-ortho-substituted biaryls is described utilizing a Diels-Alder reaction between propargylic tertiary alcohols and cyclic oxygenated dienes. The successful resolution of one of the biaryls is achieved through derivatization with menthyl chloroformate followed by crystallization. The menthyl carbamate is cleaved under basic conditions to reveal enantiomerically pure biaryl compounds.     

Single‐step oxidative homocoupling of aryl Grignard reagents via Co(II), Ni(II) and Cu(II) Complexes under air

A simple catalytic system of direct synthesis for the symmetrical biaryls using catalytic amounts of Co(II), Ni(II) and Cu(II) complexes has been developed. The reaction system involves in situ synthesis of Grignard reagents. The complexes, containing bidentate Schiff base and dmit (2‐thioxo‐1,3‐dithiole‐4,5‐dithiolate) ligands, were compatible with diverse functionalities and afford a high yield of biaryls in a single step, proving to be promising catalysts in homocoupling reactions. Atmospheric oxygen is used as an oxidant which renders a green, simple and economical catalytic route. Copyright © 2014 John Wiley & Sons, Ltd.     

Enantiodivergent Atroposelective Synthesis of Chiral Biaryls by Asymmetric Transfer Hydrogenation: Chiral Phosphoric Acid Catalyzed Dynamic Kinetic Resolution

Reported herein is an enantiodivergent synthesis of chiral biaryls by a chiral phosphoric acid catalyzed asymmetric transfer hydrogenation reaction. Upon treatment of biaryl lactols with aromatic amines and a Hantzsch ester in the presence of chiral phosphoric acid, dynamic kinetic resolution (DKR) involving a reductive amination reaction proceeded smoothly to furnish both R and S isomers of chiral biaryls with excellent enantioselectivities by proper choice of hydroxyaniline derivative. This trend was observed in wide variety of substrates, and various chiral biphenyl and phenyl naphthyl adducts were synthesized with satisfactory enantioselectivities in enantiodivergent fashion. The enantiodivergent synthesis of synthetically challenging, chiral o‐tetrasubstituted biaryls were also accomplished, and suggests high synthetic potential of the present method.     

Dearomatization of Biaryls through Polarity Mismatched Radical Spirocyclization

Dearomatization reactions involving radical cyclizations can facilitate the synthesis of complex polycyclic systems that find applications in medicinal chemistry and natural product synthesis. Here we employ redox-neutral photocatalysis to affect a radical spirocyclization that transforms biaryls into spirocyclic cyclohexadienones under mild reaction conditions. In a departure from previously reported methods, our work demonstrates the polarity mismatched addition of a nucleophilic radical to an electron rich arene, and allows the regioselective synthesis of 2,4- or 2,5-cyclohexadienones with broad functional group tolerance. By transforming biaryls into spirocycles, our methodology accesses underexplored three-dimensional chemical space, and provides an efficient means of creating quaternary spirocenters that we apply to the first synthesis of the cytotoxic plant metabolite denobilone A.     

Pd‐catalyzed Desulfitative reaction of Aryltrifluoroborates with sodium Arenesulfinates in water

An efficient procedure for the synthesis of biaryls was catalyzed by Pd(CH₃CN)₄(BF₄)₂ is reported. This Pd‐catalyzed cross‐coupling reaction of aryltrifluoroborates with sodium arenesulfinates was developed under mild and environmentally benign conditions, in water without any ligand or additive. The reaction gave a range of structurally diverse unsymmetrical bi‐aryl molecules with excellent yields, in which the byproduct was sulfur dioxide. It is worth noting that this protocol is also applicable to many heterocyclic aromatics such as thiophene, furan, pyridine, quinoline, isoquinoline and indole.     

Synthesis of Axially Chiral Biaryls through Sulfoxide‐Directed Asymmetric Mild C?H Activation and Dynamic Kinetic Resolution

A mild and robust direct C H functionalization strategy has been applied to the synthesis of axially chiral biaryls. Such an efficient and stereoselective transformation occurs through an original dynamic kinetic resolution pathway enabling the conversion of diastereomeric mixtures of non‐prefunctionalized substrates into atropisomerically pure, highly substituted biaryl scaffolds. The main feature of this transformation is the use of an enantiopure sulfoxide as both chiral auxiliary and traceless directing group. The potential of newly synthesized biaryls as valuable building blocks is further illustrated.     

Synthesis of Axially Chiral Biaryls through Sulfoxide‐Directed Asymmetric Mild CH Activation and Dynamic Kinetic Resolution

A mild and robust direct C? H functionalization strategy has been applied to the synthesis of axially chiral biaryls. Such an efficient and stereoselective transformation occurs through an original dynamic kinetic resolution pathway enabling the conversion of diastereomeric mixtures of non‐prefunctionalized substrates into atropisomerically pure, highly substituted biaryl scaffolds. The main feature of this transformation is the use of an enantiopure sulfoxide as both chiral auxiliary and traceless directing group. The potential of newly synthesized biaryls as valuable building blocks is further illustrated.     

Cascades of Interrupted Pummerer Reaction‐Sigmatropic Rearrangement

A new class of Pummerer chemistry has emerged as a powerful tool in organic synthesis. The new technology consists of a beautiful cascade of an interrupted Pummerer reaction and the subsequent [3,3] sigmatropic rearrangement. The interrupted Pummerer reactions of alkenyl or aryl sulfoxides with unsaturated nucleophiles such as allylic silanes, ketones, and phenols provide sulfonium intermediates, which are ready to undergo smooth charge‐accelerated [3,3] sigmatropic rearrangement with excellent to exclusive regioselectivity. Some of the transformations proceed with transient loss of aromaticity. The reactions afforded five‐membered heterocycles, benzofurans, and biaryls of importance, depending on the sulfoxides and nucleophiles used. The reactions are unique and game‐changing because they are efficient, robust, redox‐neutral, regioselective, and metal‐free, which perfectly fits the need of modern organic synthesis. This chemistry also underscores the synthetic potential of organosulfur chemistry.     

Ni-Catalyzed Cross Coupling of Aryl Grignard Reagents with Aryl Halides in a Nonpolar Solvent and an Efficient Synthesis of Biaryls Under Neat Conditions

This study details Ni-catalyzed cross coupling of aryl Grignard reagents with aryl halides in toluene, a nonpolar solvent with a high boiling point. The reaction was applied for the synthesis of various biaryls in good yields without the introduction of a large steric ligand. The Kumada-Tamao-Corriu(KTC) reaction in toluene was then successfully modified to proceed under neat conditions for the efficient syntheses of symmetrical biaryls, particularly in large-scale preparations. Unactivated aryl chlorides show higher reactivity than aryl bromides, particularly under neat conditions. Mechanistic investigations suggest a radical procedure for the catalytic cycle, and the origin of the radical intermediates being aryl halides.     

Amine‐Catalyzed Direct Photoarylation of Unactivated Arenes

Constructing biaryls through direct aromatic C? H functionalization of unactivated arenes has become a popular topic in organic chemistry. Many efficient methods have been developed. In this Communication, a direct arylation of unactivated arenes with a broad range of aryl iodides is reported. This reaction proceeds through a new type of amine‐catalyzed single electron transfer initiated radical coupling procedure to form biaryls in high yields under UV irradiation at room temperature. Only 20 mol% of TMEDA is used as the catalyst. No other additives are required for this transformation, thus avoiding the use of toxic transition metal catalysts, strong bases, or large amounts of other organic additives. This greener protocol provides a new strategy to achieve direct aromatic C? H functionalization and offers a new example of cost‐effective and environmentally benign access to biaryls.