Metal‐ and Reagent‐Free Highly Selective Anodic Cross‐Coupling Reaction of Phenols

The direct oxidative cross‐coupling of phenols is a very challenging transformation, as homo‐coupling is usually strongly preferred. Electrochemical methods circumvent the use of oxidizing reagents or metal catalysts and are therefore highly attractive. Employing electrolytes with a high capacity for hydrogen bonding, such as methanol with formic acid or 1,1,1,3,3,3‐hexafluoro‐2‐propanol, a direct electrolysis in an undivided cell provides mixed 2,2′‐biphenols with high selectivity. This mild method tolerates a variety of moieties, for example, tert‐butyl groups, which are not compatible with other strong electrophilic media but vital for later catalytic applications of the formed products.     

Synthesis of meta‐Terphenyl‐2,2′′‐diols by Anodic C−C Cross‐Coupling Reactions

The anodic C?C cross‐coupling reaction is a versatile synthetic approach to symmetric and non‐symmetric biphenols and arylated phenols. We herein present a metal‐free electrosynthetic method that provides access to symmetric and non‐symmetric meta‐terphenyl‐2,2′′‐diols in good yields and high selectivity. Symmetric derivatives can be obtained by direct electrolysis in an undivided cell. The synthesis of non‐symmetric meta‐terphenyl‐2,2′′‐diols required two electrochemical steps. The reactions are easy to conduct and scalable. The method also features a broad substrate scope, and a large variety of functional groups are tolerated. The target molecules may serve as [OCO]^3? pincer ligands.     

Nitroxyl‐Radical‐Catalyzed Oxidative Coupling of Amides with Silylated Nucleophiles through N‐Halogenation

A nitroxyl‐radical‐catalyzed oxidative coupling reaction between amines with an N‐protecting electron‐withdrawing group (EWG) and silylated nucleophiles was developed to furnish coupling products in high yields, thus opening up new frontiers in organocatalyzed reactions. This reaction proceeded through the activation of N‐halogenated amides by a nitroxyl‐radical catalyst, followed by carbon–carbon coupling with silylated nucleophiles. Studies of the reaction mechanism indicated that the nitroxyl radical activates N‐halogenated amides, which are generated from N‐EWG‐protected amides and a halogenation reagent, to give the corresponding imines.     

Single and Twofold Metal‐ and Reagent‐Free Anodic C−C Cross‐Coupling of Phenols with Thiophenes

The first electrochemical dehydrogenative C−C cross‐coupling of thiophenes with phenols has been realized. This sustainable and very simple to perform anodic coupling reaction enables access to two classes of compounds of significant interest. The scope for electrochemical C−H‐activating cross‐coupling reactions was expanded to sulfur heterocycles. Previously, only various benzoid aromatic systems could be converted, while the application of heterocycles was not successful in the electrochemical C−H‐activating cross‐coupling reaction. Here, reagent‐ and metal‐free reaction conditions offer a sustainable electrochemical pathway that provides an attractive synthetic method to a broad variety of bi‐ and terarylic products based on thiophenes and phenols. This method is easy to conduct in an undivided cell, is scalable, and is inherently safe. The resulting products offer applications in electronic materials or as [OSO]²⁻ pincer‐type ligands.     

Reagent‐ and Metal‐Free Anodic C−C Cross‐Coupling of Aniline Derivatives

The dehydrogenative cross‐coupling of aniline derivatives to 2,2′‐diaminobiaryls is reported. The oxidation is carried out electrochemically, which avoids the use of metals and reagents. A large variety of biphenyldiamines were thus prepared. The best results were obtained when glassy carbon was used as the anode material. The electrosynthetic reaction is easily performed in an undivided cell at slightly elevated temperature. In addition, common amine protecting groups based on carboxylic acids were employed that can be selectively removed under mild conditions after the cross‐coupling, which provides quick and efficient access to important building blocks featuring free amine moieties.     

Synthesis of Chiral Triarylmethanes Bearing All‐Carbon Quaternary Stereocenters: Catalytic Asymmetric Oxidative Cross‐Coupling of 2,2‐Diarylacetonitriles and (Hetero)arenes

A direct and enantioselective oxidative cross‐coupling of racemic 2,2‐diarylacetonitriles with electron‐rich (hetero)arenes has been described, which allows for efficient construction of triarylmethanes bearing all‐carbon quaternary stereocenters with excellent chemo‐ and enantioselectivity. The reaction has an excellent functional group tolerance, and exhibits a broad scope with respect to both 2,2‐diarylacetonitrile and (hetero)arene components. The rich chemistry of the cyano group allows for facile synthesis of other valuable chiral triarylmethanes bearing all‐carbon quaternary centers that are otherwise difficult to access.     

Palladium‐Catalyzed Intramolecular Reductive Cross‐Coupling of Csp2Csp3 Bond Formation

A Pd‐catalyzed efficient reductive cross‐coupling reaction without metallic reductant to construct a Csp²?Csp³ bond has been reported. A Pd^IV complex was proposed to be a key intermediate, which subsequently went through double oxidative addition and double reductive elimination to produce the cross‐coupling products by involving Pd^0/II/IV in one transformation. The oxidative addition from Pd^II to Pd^IV was partially demonstrated to be a radical process by self‐oxidation of substrate without additional oxidants. Furthermore, the solvent was proved to be the reductant for this transformation through XPS analysis.     

1,3‐Diethynylallenes: Carbon‐Rich Modules for Three‐Dimensional Acetylenic Scaffolding

Regioselective Pd⁰‐catalyzed cross‐coupling of substrates, which bear bispropargylic leaving groups with silyl‐protected alkynes, has provided access to a variety of 1,3‐diethynylallenes, a new family of modules for three‐dimensional acetylenic scaffolding. In enantiomerically pure form, these C‐rich building blocks could provide access – by oxidative oligomerization – to a fascinating new class of helical oligomers and polymers with all‐carbon backbones (Fig. 2). In the first of two routes, a bispropargylic epoxide underwent ring opening during S_n 2′‐type cross‐coupling, and the resulting alkoxide was silyl‐protected, providing 1,3‐diethynylallenes (±)‐ 8 , (±)‐ 12 (Scheme 3), and (±)‐ 15 (Scheme 5). A more general approach involved bispropargylic carbonates or esters as substrates (Scheme 6–8), and this route was applied to the preparation of a series of 1,3‐diethynylallenes to investigate how their overall stability against undesirable [2+2] cycloaddition is affected by the nature of the substituents at the allene moiety. The investigation showed that the 1,3‐diethynylallene chromophore is stable against [2+2] cycloaddition only when protected by steric bulk and when additional π‐electron delocalization is avoided. The regioselectivity of the cross‐coupling to the bispropargylic substrates is entirely controlled by steric factors: attack occurs at the alkyne moiety bearing the smaller substituent (Schemes 9 and 10). Oxidative Hay coupling of the terminally mono‐deprotected 1,3‐diethynylallene (±)‐ 49 afforded the first dimer 50 , probably as a mixture of two diastereoisomers (Scheme 12). Attempts to prepare a silyl‐protected tetraethynylallene by the new methodology failed (Scheme 13). Control experiments (Schemes 14–16) showed that the Pd⁰‐catalyzed cross‐coupling to butadiyne moieties in the synthesis of this still‐elusive chromophore requires forcing conditions under which rapid [2+2] cycloaddition of the initial product cannot be avoided.     

Synthesis of Novel Chiral Biphenylamine Ligand 6,6'‐Dimethoxy‐2,2′‐diaminobiphenyl

A new chiral ligand 6,6′‐dimethoxy‐2,2′‐diaminobiphenyl was successfully prepared from 3‐nitrophenol via iodination, Ullmann coupling, and reduction. The resolving reagent (2R, 3R)‐ or (2S,3S)‐2,3‐di (phenylaminocarbonyl)tartaric acid was prepared from commercially available tartaric acid in large scale and was used to resolve the racemic 6,6′‐dimethoxy‐2,2′‐diaminobiphenyl. The chiral 6,6′‐ dimethoxy‐2,2′‐diaminobiphenyl obtained was proved to be enantiomerically pure.     

Highly selective oxidative cross‐coupling polymerization with copper(I)‐bisoxazoline catalysts

The asymmetric oxidative coupling polymerization of methyl 6,6′‐dihydroxy‐2,2′‐binaphthalene‐7‐carboxylate with the copper‐diamine catalysts under an O₂ atmosphere was carried out. As is the case with the CuCl‐2,2′‐(S)‐isopropylidenbis(4‐phenyl‐2‐oxazoline) [(S)IPhO] catalyst, a polymer with a high cross‐coupling selectivity of 96% was obtained in 71% yield, whose THF‐soluble part had a number‐average molecular weight of 4.5 × 10³. To estimate the enantioselectivity with respect to the cross‐coupling linkage in the obtained polymer, the model asymmetric oxidative cross‐coupling reaction with CuCl‐(S)IPhO was also conducted, and the products showed a 94% cross‐coupling selectivity and enantioselectivity of 31% ee (S). © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 6287–6294, 2005     

A Heterogeneous‐Catalyst‐Based,Microwave‐Assisted Protocol for the Synthesis of 2,2′‐Bipyridines

A new method of preparing 2,2′‐bipyridines with short reaction times by using microwave assistance and heterogeneous catalysts has been developed. With a Negishi‐like protocol, it was found that Ni/Al₂O₃–SiO₂ afforded 2,2′‐bipyridine products in up to 86 % yield in 1 h. Palladium supported on alumina also provided yields of 2,2′‐bipyridines comparable to those seen for homogeneous PEPPSI^TM (1,3‐diisopropylimidazol‐2‐ylidene)(3‐chloropyridyl)palladium(II)dichloride) and tetrakis(triphenylphosphanyl)palladium complexes.     

Bipyridine‐Modulated Palladium‐Catalyzed Oxidative Heck‐Type Reactions of Arylboronic Acids with Olefins

We have demonstrated that 4,4′‐dimethyl 2,2′‐bipyridine as ligand for Pd(II) catalysts was very efficient for oxidative Heck‐type coupling reaction of arylboronic acids with olefins in DMA or CH₃CN under atm air at 80 °C. The presence of chelated bipyridine ligand isindispensable to achieve high reaction yields and to suppress the formation of biphenyl as homocoupled byproduct.     

A highly efficient heterogeneous montmorillonite K‐10‐supported palladium catalyst for Suzuki–Miyaura cross‐coupling reaction in aqueous medium

A heterogeneous montmorillonite K‐10‐supported palladium triphenylphosphine catalyst is reported for the Suzuki–Miyaura cross‐coupling reaction at room temperature. A library of electronically diverse aryl bromides and arylboronic acids underwent the cross‐coupling reaction at very good rates in aqueous solvent. The reusability of the catalyst was also examined and it was found to be effective up to three catalytic cycles. Copyright © 2014 John Wiley & Sons, Ltd.     

1,4‐Addition of Bis(iodozincio)methane to α,β‐Unsaturated Ketones: Chemical and Theoretical/Computational Studies

1,4‐Addition of bis(iodozincio)methane to simple α,β‐unsaturated ketones does not proceed well; the reaction is slightly endothermic according to DFT calculations. In the presence of chlorotrimethylsilane, the reaction proceeded efficiently to afford a silyl enol ether of β‐zinciomethyl ketone. The C? Zn bond of the silyl enol ether could be used in a cross‐coupling reaction to form another C? C bond in a one‐pot reaction. In contrast, 1,4‐addition of the dizinc reagent to enones carrying an acyloxy group proceeded very efficiently without any additive. In this case, the product was a 1,3‐diketone, which was generated in a novel tandem reaction. A theoretical/computational study indicates that the whole reaction pathway is exothermic, and that two zinc atoms of bis(iodozincio)methane accelerate each step cooperatively as effective Lewis acids.     

Copper‐Catalyzed Arylation of Remote C(sp3)−H Bonds in Carboxamides and Sulfonamides

Reported herein is an unprecedented copper‐catalyzed arylation of remote C(sp³)?H bonds. Stirring a trifluorotoluene solution of either N‐fluorocarboxamides or N‐fluorosulfonamides and arylboronic acids in the presence of a catalytic amount of copper(II) trifluoroacetylacetonate, 2,2′‐bipyridine, and sodium tert‐butoxide afforded the γ‐ and δ‐C(sp³)?H arylated carboxamides and sulfonamides, respectively, in good to high yields. Mechanistic studies indicate that the reaction might proceed through an amidyl radical generation, 1,5‐hydrogen atom transfer (HAT), and copper‐catalyzed cross‐coupling of the resulting carbon radical with arylboronic acids.     

Synthese und Molekülstrukturen von N‐substituierten Diethylgallium‐2‐pyridylmethylamiden

Synthesis and Molekular Structures of N‐substituted Diethylgallium‐2‐pyridylmethylamides (2‐Pyridylmethyl)(tert‐butyldimethylsilyl)amine ( 1a ) and (2‐pyridylmethyl)‐di(tert‐butyl)silylamine ( 1b ) form with triethylgallane the corresponding red adducts 2a and 2b via an additional nitrogen‐gallium bond. These oily compounds decompose during distillation. Heating under reflux in toluene leads to the elimination of ethane and the formation of the red oils of [(2‐pyridylmethyl)(tert‐butyldimethylsilyl)amido]diethylgallane ( 3a ) and [(2‐pyridylmethyl)‐di(tert‐butyl)silylamido]diethylgallane ( 3b ). In order to investigate the thermal stability solvent‐free 3a is heated up to 400 °C. The elimination of ethane is observed again and the C‐C coupling product N, N′‐Bis(diethylgallyl)‐1, 2‐dipyridyl‐1, 2‐bis(tert‐butyldimethylsilyl)amido]ethan ( 4 ) is found in the residue. Substitution of the silyl substituents by another 2‐pyridylmethyl group and the reaction of this bis(2‐pyridylmethyl)amine with GaEt₃ yield triethylgallane‐diethylgallium‐bis(2‐pyridylmethyl)amide ( 5 ). The metalation product adds immediately another equivalent of triethylgallane regardless of the stoichiometry. The reaction of GaEt₃ with 2‐pyridylmethanol gives quantitatively colorless 2‐pyridylmethanolato diethylgallane ( 6 ).     

Palladium‐Catalyzed Construction of Heteroatom‐Containing π‐Conjugated Systems by Intramolecular Oxidative CH/CH Coupling Reaction

Synthesis of heteroatom‐containing ladder‐type π‐conjugated molecules was successfully achieved via a palladium‐catalyzed intramolecular oxidative C?H/C?H cross‐coupling reaction. This reaction provides a variety of π‐conjugated molecules bearing heteroatoms, such as nitrogen, oxygen, phosphorus, and sulfur atoms, and a carbonyl group. The π‐conjugated molecules were synthesized efficiently, even in gram scale, and larger π‐conjugated molecules were also obtained by a double C?H/C?H cross‐coupling reaction and successive oxidative cycloaromatization.     

Cobalt‐Catalyzed Oxidative C−H/C−H Cross‐Coupling between Two Heteroarenes

The first example of cobalt‐catalyzed oxidative C?H/C?H cross‐coupling between two heteroarenes is reported, which exhibits a broad substrate scope and a high tolerance level for sensitive functional groups. When the amount of Co(OAc)₂?4 H₂O is reduced from 6.0 to 0.5 mol %, an excellent yield is still obtained at an elevated temperature with a prolonged reaction time. The method can be extended to the reaction between an arene and a heteroarene. It is worth noting that the Ag₂CO₃ oxidant is renewable. Preliminary mechanistic studies by radical trapping experiments, hydrogen/deuterium exchange experiments, kinetic isotope effect, electron paramagnetic resonance (EPR), and high resolution mass spectrometry (HRMS) suggest that a single electron transfer (SET) pathway is operative, which is distinctly different from the dual C?H bond activation pathway that the well‐described oxidative C?H/C?H cross‐coupling reactions between two heteroarenes typically undergo.     

Oxidative C−H/C−H Cross‐Coupling Reactions between N‐Acylanilines and Benzamides Enabled by a Cp*‐Free RhCl3/TFA Catalytic System

By making use of a dual‐chelation‐assisted strategy, a completely regiocontrolled oxidative C?H/C?H cross‐coupling reaction between an N‐acylaniline and a benzamide has been accomplished for the first time. This process constitutes a step‐economic and highly efficient pathway to 2‐amino‐2′‐carboxybiaryl scaffolds from readily available substrates. A Cp*‐free RhCl₃/TFA catalytic system was developed to replace the [Cp*RhCl₂]₂/AgSbF₆ system generally used in oxidative C?H/C?H cross‐coupling reactions between two (hetero)arenes (Cp*=pentamethylcyclopentadienyl, TFA=trifluoroacetic acid). The RhCl₃/TFA system avoids the use of the expensive Cp* ligand and AgSbF₆. As an illustrative example, the procedure developed herein greatly streamlines the total synthesis of the naturally occurring benzo[c]phenanthridine alkaloid oxynitidine, which was accomplished in excellent overall yield.     

Single‐Electron‐Transfer‐Induced Coupling of Arylzinc Reagents with Aryl and Alkenyl Halides

Arylzinc reagents, prepared from aryl halides/zinc powder or aryl Grignard reagents/zinc chloride, were found to undergo coupling with aryl and alkenyl halides without the aid of transition‐metal catalysis to give biaryls and styrene derivatives, respectively. In this context, we have already reported the corresponding reaction using aryl Grignard reagents instead of arylzinc reagents. Compared with the Grignard cross‐coupling, the present reaction features high functional‐group tolerance, whereby electrophilic groups such as alkoxycarbonyl and cyano groups are compatible as substituents on both the arylzinc reagents and the aryl halides. Aryl halides receive a single electron and thereby become activated as the corresponding anion radicals, which react with arylzinc reagents, thus leading to the cross‐coupling products.