Difunctionalisation of arenes and heteroarenes by directed metallation and sulfoxide-magnesium exchange

The aryl sulfoxide moiety allows an expedient two‐step difunctionalisation of readily available diaryl sulfoxides. Highly functionalised 1,2,4‐trisubstituted arenes and difunctionalised heteroarenes (furans, thiophenes, benzofurans and pyridines) were prepared in a two‐step sequence, triggered by an aryl sulfoxide group. In the first step, the sulfoxide moiety acts as a metallation‐directing group, allowing smooth ortho‐magnesiation with TMPMgCl ? LiCl (TMP=tetramethylpiperidine). After a quenching reaction with an electrophile, the resulting sulfoxide is converted into a second magnesium reagent with iPrMgCl ? LiCl (sulfoxide–magnesium exchange), which can be trapped with various electrophiles. Highly chemoselective TMPMgCl ? LiCl and iPrMgCl ? LiCl are compatible with a broad range of functional groups (e.g., F, Cl, CF₃, CN, CO₂tBu, alkynyl, ethers, thioethers). Large‐scale reactions (25–40 mmol) and the preparation of fully functionalised furans and thiophenes are also reported.     

Microwave‐Assisted Cross‐Coupling for the Construction of Diaryl Sulfides

The construction of diaryl sulfides through the cross‐coupling of aryl iodides and thiols in microwave heating is described. By using this method, a variety of diaryl sulfides can be prepared in a mild condition and in high yields. Deactivated 4‐nitrothiophenol was effective to afford the product in 94% yield. Sterically hindered ortho‐substituted aryl iodides or thiophenols provided diaryl sulfides effectively by this microwave‐assisted coupling reaction.     

Efficient Copper(I)‐Catalyzed S‐Arylation of KSCN with Aryl Halides in PEG‐400

A simple and efficient protocol for CuI‐catalyzed C? S bond formation of aryl halides with KSCN to symmetrical diaryl sulfides was reported in PEG‐400 without any other additives. A variety of aryl halides were converted to the corresponding diaryl sulfides in good to excellent yields. The present procedure tolerated a variety of functional groups and the steric hindrance of ortho‐substituents on aryl halides did not affect the outcome.     

Methenamine as an Efficient Ligand for Copper‐catalyzed Coupling of Phenols with Aryl Halides

Employing methenamine as a new supporting ligand, the copper‐catalyzed coupling reactions of aryl bromides or aryl iodides with various phenols successfully proceeded in good yields under mild conditions. A series of diaryl ethers were obtained with excellent yields in the presence of K₃PO₄ and copper(I) salt.     

2‐Aryl‐4‐azido‐3‐(bromo/iodo)quinolines as substrates for the synthesis of primary 4‐amino‐2,3‐disubstituted quinoline derivatives

Staudinger reaction of the 2‐aryl‐4‐azido‐3‐bromoquinolines and 2‐aryl‐4‐azido‐3‐iodoquinolines with triphenyl phosphine in refluxing tetrahydrofuran afforded series of 2‐aryl‐3‐halogeno‐4‐(triphenylphosphoranylideneamino)quinolines. The latter were, in turn, hydrolyzed to the corresponding primary 4‐amino‐2‐aryl‐3‐(bromo/iodo)quinolines using 80% acetic acid under reflux. Tetrakis(triphenylphosphine)‐palladium(O)‐catalyzed Suzuki reaction of the 2‐aryl‐3‐iodo‐4‐(triphenylphosphoranylideneamino)‐quinolines with phenylboronic acid in dimethyl formamide in the presence of 2 M K₂CO₃ followed by hydrolysis of the incipient 2,3‐diaryl‐4‐(triphenylphosphoranylideneamino)quinolines with 80% acetic acid afforded the 4‐amino‐2,3‐diarylquinolines.     

Experimental Evidence of Intramolecular CAr–H···O=C Hydrogen Bonds in the Structure of (Diaryl)tetrahydrofuranones Using Spectroscopic Tools

The occurrence of bifurcate H‐bonds C_Ar–H···O=C in the structure of (diaryl)‐tetrahydrofuranones was experimentally demonstrated using different methods and techniques. The consistent increasing spin–spin coupling constants ¹J(C,H) of the ortho‐H‐atoms and low‐field shift of v_C=O in IR spectra of 2,2‐(diaryl)tetrahydrofuran‐3(2H)‐ones relative to their 5,5‐diaryl counterparts, as well as pronounced dependence of the ortho‐C–H H‐atoms chemical shifts on the temperature and solvent polarity along with X‐ray diffraction analysis data unambiguously point to the existence of weak C_Ar–H···O=C H‐bonds in these molecules.     

Asymmetric Desymmetrization via Metal‐Free C−F Bond Activation: Synthesis of 3,5‐Diaryl‐5‐fluoromethyloxazolidin‐2‐ones with Quaternary Carbon Centers

We disclose the first asymmetric activation of a non‐activated aliphatic C?F bond in which a conceptually new desymmetrization of 1,3‐difluorides by silicon‐induced selective C?F bond scission is a key step. The combination of a cinchona alkaloid based chiral ammonium bifluoride catalyst and N,O‐bis(trimethylsilyl)acetoamide (BSA) as the silicon reagent enabled the efficient catalytic cycle of asymmetric C_sp3?F bond cleavage under mild conditions with high enantioselectivities. The ortho effect of the aryl group at the prostereogenic center is remarkable. This concept was applied for the asymmetric synthesis of promising agrochemical compounds, 3,5‐diaryl‐5‐fluoromethyloxazolidin‐2‐ones bearing a quaternary carbon center.     

Chemo‐ and Regioselective Hydrogenolysis of Diaryl Ether C−O Bonds by a Robust Heterogeneous Ni/C Catalyst: Applications to the Cleavage of Complex Lignin‐Related Fragments

We report the chemo‐ and regioselective hydrogenolysis of the C?O bonds in di‐ortho‐substituted diaryl ethers under the catalysis of a supported nickel catalyst. The catalyst comprises heterogeneous nickel particles supported on activated carbon and furnishes arenes and phenols in high yields without hydrogenation. The high thermal stability of the embedded metal particles allows C?O bond cleavage to occur in highly substituted diaryl ether units akin to those in lignin. Preliminary mechanistic experiments show that this catalyst undergoes sintering less readily than previously reported catalyst particles that form from a solution of [Ni(cod)₂].     

Dehydrogenative Carbon–Carbon Bond Formation Using Alkynyloxy Moieties as Hydrogen‐Accepting Directing Groups

In the presence of a catalyst system consisting of Pd(OAc)₂, PCy₃, and Zn(OAc)₂, the reaction of alkynyl aryl ethers with bicycloalkenes, α,ß‐unsaturated esters, or heteroarenes results in the site‐selective cleavage of two C? H bonds followed by the formation of C? C bonds. In all cases, the alkynyloxy group acts as a directing group for the activation of an ortho C? H bond and as a hydrogen acceptor, thus rendering the use of additives such as an oxidant or base unnecessary.     

Synthesis of Cyclic and Acyclic ortho-Aryloxy Diaryliodonium Salts for Chemoselective Functionalizations

Two regioselective, high-yielding one-pot routes to oxygen-bridged cyclic diaryliodonium salts and ortho-aryloxy-substituted acyclic diaryliodonium salts are presented. Starting from easily available ortho-iodo diaryl ethers, complete selectivity in formation of either the cyclic or acyclic product could be achieved by varying the reaction conditions. The complimentary reactivities of these novel ortho-oxygenated iodonium salts were demonstrated through a series of chemoselective arylations under metal-catalyzed and metal-free conditions, to deliver a range of novel, ortho-functionalized diaryl ether derivatives.     

Synthesis of 2,3‐Diaryl‐3H‐pyrrolo[2,3‐c]pyridin‐3‐ol Derivatives by the Reaction of Aryl(3‐isocyanopyridin‐4‐yl)methanones with Aryl Grignard Reagents

The reaction of aryl(3‐isocyanopyridin‐4‐yl)methanones 1 , easily prepared from commercially available pyridin‐3‐amine, with aryl Grignard reagents gave, after aqueous workup, 2,3‐diaryl‐3H‐pyrrolo[2,3‐c]pyridin‐3‐ols 2 . These rather unstable alcohols were O‐acylated with Ac₂O in pyridine in the presence of a catalytic amount of 4‐(dimethylamino)pyridine (DMAP) to afford the corresponding 2,3‐diaryl‐3H‐pyrrolo[2,3‐c]pyridin‐3‐yl acetates 3 in relatively good yields.     

Intramolecular Metal‐Free Oxidative Aryl–Aryl Coupling: An Unusual Hypervalent‐Iodine‐Mediated Rearrangement of 2‐Substituted N‐Phenylbenzamides

Hypervalent‐iodine‐mediated oxidative coupling of the two aryl groups in either 2‐acylamino‐N‐phenyl‐benzamides or 2‐hydroxy‐N‐phenylbenzamides, with concomitant insertion of the ortho‐substituted N or O atom into the tether, has been described for the first time. This unusual metal‐free rearrangement reaction involves an oxidative C(sp²)? C(sp²) aryl–aryl bond formation, cleavage of a C(sp²)? C(O) bond, and a lactamization/lactonization. Furthermore, unsymmetrical diaryl compounds can be easily obtained by removing the tether within the cyclized product.     

Microwave‐Assisted Construction of Diaryl Ethers Directly from Arylmethanesulfonates as Convenient Latent Phenols with Aryl Halides

The microwave‐assisted synthesis of diaryl ethers directly from aryl halides and arylmethanesulfonates, which as latent phenols obviate a deprotection step prior to the S_NAr reaction, in the presence of Cs₂CO₃ is described. The reaction time was very short (6–9 min), and good to excellent yields (53–90%) with the wide substrate scope were achieved without any catalyst.     

Synthesis of Diaryl Ethers Through the Copper-Catalyzed Arylation of Phenols with Aryl Iodides Using KF/Al2O3

An efficient synthesis of diaryl ethers by the copper-catalyzed arylation of phenols with a variety of aryl iodide susing KF/Al₂O₃ as a suitable base and CuI and 1,3 diphenyl-1,3 propandione as the catalyst is described.     

Fluorinated Phenanthrenes as Aryne Precursors: PAH Synthesis Based on Domino Ring Assembly Using 1,1‐Difluoroallenes

On treatment with the catalyst InBr₃, 1,1‐difluoroallenes that bear a cyclopentene moiety and an aryl group underwent domino ring assembly in the presence or absence of N‐bromosuccinimide or N‐iodosuccinimide to afford aryne precursors such as three‐ringed ortho‐fluoro(halo)phenanthrenes, four‐ringed ortho‐fluoro(halo)tetraphenes, ortho‐fluoro(halo)chrysenes and fluoro[4]helicenes. Metalation of the aryne precursors followed by elimination of the fluoride resulted in the unprecedented systematic generation of arynes bearing π‐extended systems. Diels?Alder reactions of these arynes with isobenzofurans afforded the corresponding cycloadducts whose reductive aromatisation in an SnCl₂/HBr system furnished fully aromatised benzotriphenylenes. In addition, oxidative aryl?aryl coupling (the Scholl reaction) of these benzotriphenylenes facilitated the synthesis of ‘half HBCs’ (hexabenzocoronenes).     

A Catalyst‐Controlled Aerobic Coupling of ortho‐Quinones and Phenols Applied to the Synthesis of Aryl Ethers

ortho‐Quinones are underutilized six‐carbon‐atom building blocks. We herein describe an approach for controlling their reactivity with copper that gives rise to a catalytic aerobic cross‐coupling with phenols. The resulting aryl ethers are generated in high yield across a broad substrate scope under mild conditions. This method represents a unique example where the covalent modification of an ortho‐quinone is catalyzed by a transition metal, creating new opportunities for their utilization in synthesis.     

Ligand‐free palladium‐catalyzed tandem pathways for the synthesis of 4,4‐diarylbutanones and 4,4‐diaryl‐3‐butenones under microwave conditions

Two efficient Pd‐catalyzed tandem pathways for the synthesis of 4,4‐diaryl‐2‐butanones and 4,4‐diaryl‐3‐buten‐2‐ones were elaborated. The first step in both procedures was the Heck coupling of methyl vinyl ketone (MVK) and various aryl iodides leading to 4‐aryl‐3‐buten‐2‐one with the yield of up to 92% in 1 hr. The second step performed with the same catalyst and a new portion of aryl iodide in the presence K₂CO₃ as a base produced 4,4‐diaryl‐3‐buten‐2‐ones in high yield. Reaction selectivity changed completely to saturated 4,4‐diaryl‐2‐butanones, reductive Heck products, when a tertiary amine was used instead of K₂CO₃. Due to the application of microwave irradiation (MW), the desired products were obtained in high yield in a short time (4 hr), using 0.5 mol% of the Pd (OAc)₂ catalyst without additional ligands.     

The ortho‐Difluoroalkylation of Aryliodanes with Enol Silyl Ethers: Rearrangement Enabled by a Fluorine Effect

Presented herein is an intriguing effect of fluorine, and it allows difluoroenol silyl ethers to couple with aryliodanes in a redox‐neutral manner to afford ortho‐iodo difluoroalkylated arenes. The remaining iodide group provides a versatile platform for converting the products into various valuable difluoroalkylated arenes. The reaction shows excellent functional‐group compatibility and broad substrate scope. A DFT mechanistic study suggests that the fluorine effect facilitates a subtle nucleophilic attack of the oxygen atom of enol silyl ethers onto aryliodanes, therefore leading to a rearrangement.     

Chiral Ammonium Betaine‐Catalyzed Highly Stereoselective Aza‐Henry Reaction of α‐Aryl Nitromethanes with Aromatic N‐Boc Imines

A highly stereoselective aza‐Henry reaction of α‐aryl nitromethanes with aromatic N‐Boc imines was established by using C₁‐symmetric chiral ammonium betaine as a bifunctional organic base catalyst. Various substituted aryl groups for both imines and nitromethanes were tolerated in the reaction, and a series of precursors for the synthesis of unsymmetrical anti‐1,2‐diaryl ethylenediamines was provided.     

An efficient BINAM-copper(II) catalyzed Ullmann-type synthesis of diaryl ethers

A wide range of diaryl ethers are synthesized from the corresponding aryl iodides and phenols through Ullmann type coupling reactions in the presence of a catalytic amount of easily available BINAM-Cu(OTf)₂ complex under mild reaction conditions. Less reactive aryl bromides have also been shown to react with phenols under identical reaction conditions to give good yields of the diaryl ethers without increasing the reaction temperature and time.