Graphene‐Oxide‐Catalyzed Direct CH−CH‐Type Cross‐Coupling: The Intrinsic Catalytic Activities of Zigzag Edges

The development of graphene oxide (GO)‐based materials for C?C cross‐coupling represents a significant advance in carbocatalysis. Although GO has been used widely in various catalytic reactions, the scope of reactions reported is quite narrow, and the relationships between the type of functional groups present and the specific activity of the GO are not well understood. Herein, we explore CH?CH‐type cross‐coupling of xanthenes with arenes using GO as real carbocatalysts, and not as stoichiometric reactants. Mechanistic studies involving molecular analogues, as well as trapped intermediates, were carried out to probe the active sites, which were traced to quinone‐type functionalities as well as the zigzag edges in GO materials. GO‐catalyzed cross‐dehydrogenative coupling is operationally simple, shows reusability over multiple cycles, can be conducted in air, and exhibits good functional group tolerance.     

Synthesis of All‐Carbon Disubstituted Bicyclo[1.1.1]pentanes by Iron‐Catalyzed Kumada Cross‐Coupling

1,3‐Disubstituted bicyclo[1.1.1]pentanes (BCPs) are important motifs in drug design as surrogates for p‐substituted arenes and alkynes. Access to all‐carbon disubstituted BCPs via cross‐coupling has to date been limited to use of the BCP as the organometallic component, which restricts scope due to the harsh conditions typically required for the synthesis of metallated BCPs. Here we report a general method to access 1,3‐C‐disubstituted BCPs from 1‐iodo‐bicyclo[1.1.1]pentanes (iodo‐BCPs) by direct iron‐catalyzed cross‐coupling with aryl and heteroaryl Grignard reagents. This chemistry represents the first general use of iodo‐BCPs as electrophiles in cross‐coupling, and the first Kumada coupling of tertiary iodides. Benefiting from short reaction times, mild conditions, and broad scope of the coupling partners, it enables the synthesis of a wide range of 1,3‐C‐disubstituted BCPs including various drug analogues.     

Visible‐Light‐Induced Nickel‐Catalyzed Negishi Cross‐Couplings by Exogenous‐Photosensitizer‐Free Photocatalysis

The merging of photoredox and transition‐metal catalysis has become one of the most attractive approaches for carbon–carbon bond formation. Such reactions require the use of two organo‐transition‐metal species, one of which acts as a photosensitizer and the other one as a cross‐coupling catalyst. We report herein an exogenous‐photosensitizer‐free photocatalytic process for the formation of carbon–carbon bonds by direct acceleration of the well‐known nickel‐catalyzed Negishi cross‐coupling that is based on the use of two naturally abundant metals. This finding will open new avenues in cross‐coupling chemistry that involve the direct visible‐light absorption of organometallic catalytic complexes.     

Pd(0)‐Catalyzed Cu(I)‐Thiophene‐2‐carboxylate‐mediated Cross‐Coupling of Heteroaromatic Thioethers and Boronic Acids—First Liebeskind–Srogl Reaction in Water

The first example of a Liebeskind–Srogl cross‐coupling reaction in water as sole reaction solvent is reported. 2‐(Methylthio)pyridine and 2‐(methylthio)benzothiazole were reacted in the presence of a Pd(0) catalyst and copper(I) thiophene‐2‐carboxylate with a series of arylboronic acids. These cross coupling reactions in water proceeded well with electron‐rich boronic acids and gave comparable yields to literature examples using organic solvents. Electron‐poor boronic acids gave somewhat lower yields in aqueous medium.     

Transition‐Metal‐Free BF3‐Mediated Oxidative and Non‐Oxidative Cross‐Coupling of Pyridines

We report a BF₃‐mediated direct alkynylation of pyridines at C(2) by using a variety of alkynyllithium reagents (oxidative cross‐coupling). Moreover, we have developed a novel transition‐metal‐free cross‐coupling method between alkylmagnesium reagents and 4‐substituted pyridines, such as isonicotinonitrile and 4‐chloropyridine, by employing BF₃?OEt₂ as a promoter. The combination of these methods enabled us to efficiently prepare a range of di‐, tri‐, and tetrasubstituted pyridines.     

Regioselective Transition‐Metal‐Free Allyl–Allyl Cross‐Couplings

Readily prepared allylic zinc halides undergo S_N2‐type substitutions with allylic bromides in a 1:1 mixture of THF and DMPU providing 1,5‐dienes regioselectively. The allylic zinc species reacts at the most branched end (γ‐position) of the allylic system furnishing exclusively γ,α′‐allyl–allyl cross‐coupling products. Remarkably, the double bond stereochemistry of the allylic halide is maintained during the cross‐coupling process. Also several functional groups (ester, nitrile) are tolerated. This cross‐coupling of allylic zinc reagents can be extended to propargylic and benzylic halides. DFT calculations show the importance of lithium chloride in this substitution.     

PdII‐Catalyzed Domino Heterocyclization/Cross‐Coupling of α‐Allenols and α‐Allenic Esters: Efficient Preparation of Functionalized Buta‐1,3‐dienyl Dihydrofurans

A mild, palladium(II)‐catalyzed reaction of α‐allenols with α‐allenic esters in a heterocyclization/cross‐coupling sequence, applicable to a wide range of substitution patterns, has been developed for the preparation of 2,3,4‐trifunctionalized 2,5‐dihydrofurans. Our studies indicate high levels of chemo‐ and regiocontrol. The possibility of using optically active substrates as well as substrates of increased steric demand, such as tertiary α‐allenols, makes this novel sequence of heterocyclization/cross‐coupling an attractive method in organic synthesis. The current mechanistic hypothesis invokes a regiocontrolled palladium(II)‐mediated intramolecular oxypalladation of the free allenol component, that then undergoes a cross‐coupling reaction with the allenic ester partner, followed by a trans‐β‐deacyloxypalladation with concomitant regeneration of the Pd^II species.     

Source of Selectivity in Oxidative Cross‐Coupling of Aryls by Solvent Effect of 1,1,1,3,3,3‐Hexafluoropropan‐2‐ol

Solvents such as 1,1,1,3,3,3‐hexafluoroisopropanol (HFIP) with a high capacity for donating hydrogen bonds generate solvates that enter into selective cross‐coupling reactions of aryls upon oxidation. When electric current is employed for oxidation, reagent effects can be excluded and a decoupling of nucleophilicity from oxidation potential can be achieved. The addition of water or methanol to the electrolyte allows a shift of oxidation potentials in a specific range, creating suitable systems for selective anodic cross‐coupling reactions. The shift in the redox potentials depends on the substitution pattern of the substrate employed. The concept has been expanded from arene–phenol to phenol–phenol as well as phenol–aniline cross‐coupling. This driving force for selectivity in oxidative coupling might also explain previous findings using HFIP and hypervalent iodine reagents.     

Nickel/Photoredox‐Catalyzed Asymmetric Reductive Cross‐Coupling of Racemic α‐Chloro Esters with Aryl Iodides

A unique nickel/organic photoredox co‐catalyzed asymmetric reductive cross‐coupling between α‐chloro esters and aryl iodides is developed. This cross‐electrophile coupling reaction employs an organic reductant (Hantzsch ester), whereas most reductive cross‐coupling reactions use stoichiometric metals. A diverse array of valuable α‐aryl esters is formed under these conditions with high enantioselectivities (up to 94 %) and good yields (up to 88 %). α‐Aryl esters represent an important family of nonsteroidal anti‐inflammatory drugs. This novel synergistic strategy expands the scope of Ni‐catalyzed reductive asymmetric cross‐coupling reactions.     

Silicon‐Based Cross‐Coupling Reactions in the Total Synthesis of Natural Products

Unlike other variants of transition‐metal‐catalyzed cross‐coupling reactions, those based on organosilicon donors have not been used extensively in natural product synthesis. However, recent advances such as: 1) the development of mild reaction conditions, 2) the expansion of substrate scope, 3) the development of methods to stereoselectively and efficiently introduce the silicon‐containing moiety, 4) the development of a large number of sequential processes, and 5) the advent of bifunctional bis(silyl) linchpin reagents, signify the coming of age of silicon‐based cross‐coupling reactions. The following case studies illustrate how silicon‐based cross‐coupling reactions play a strategic role in constructing carbon–carbon bonds in selected target molecules.     

Room temperature suzuki cross‐coupling polymerizations of aryl dihalides and aryldiboronic acid/acid esters with t‐Bu3P‐coordinated 2‐phenylaniline‐based palladacycle complex as the precatalyst

Room temperature Suzuki cross‐coupling polymerization of aryl dibromides/diiodides with aryldiboronic acids/acid esters with t‐Bu₃P‐coordinated 2‐phenylaniline‐based palladacycle complex, [2′‐(amino‐kN)[1,1′‐biphenyl]‐2‐yl‐kC]chloro(tri‐t‐butylphosphine)palladium, as a general precatalyst is described. Such room temperature Suzuki cross‐coupling polymerization is achieved by employing six equivalents or more of the base and affords polymers within an hour, with the yields and the molecular weights in general comparable to or higher than reported results that required higher reaction temperature and/or longer polymerization time. Our study provides a general catalyst system for the room temperature Suzuki cross‐coupling polymerization of aryl dibromides/diiodides with aryldiboronic acids/acid esters and paves the road for the investigation of employing other monodentate ligand‐coordinated palladacycle complexes including other electron‐rich monophosphine‐coordinated ones for room temperature cross‐coupling polymerizations. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1606–1611     

Copper‐Polymer Nanocomposite Catalyst for Synthesis of 1,4‐Diphenylbutadiyne‐1,3

A new catalyst for cross‐coupling synthesis of 1,4‐diphenylbutadiyne‐1,3 was prepared by thermolysis of copper(II) poly‐5‐vinyltetrazolate. It presents heterogeneous catalyst, in which copper nanoparticles are supported on polymeric matrix surface. The catalyst is recovered, recycled, and shows high catalytic activity in cross‐coupling synthesis of 1,4‐diphenylbutadiyne‐1,3. The reaction proceeds in aerobic conditions at room temperature in the presence of pyridine.     

Transition‐Metal‐Free Oxidative Cross‐Coupling of Tetraarylborates to Biaryls Using Organic Oxidants

Readily prepared tetraarylborates undergo selective (cross)‐coupling through oxidation with Bobbitt's salt to give symmetric and unsymmetric biaryls. The organic oxoammonium salt can be used either as a stoichiometric oxidant or as a catalyst in combination with in situ generated NO₂ and molecular oxygen as the terminal oxidant. For selected cases, oxidative coupling is also possible with NO₂/O₂ without any additional nitroxide‐based cocatalyst. Transition‐metal‐free catalytic oxidative ligand cross‐coupling of tetraarylborates is unprecedented and the introduced method provides access to various biaryl and heterobiaryl systems.     

Iron‐Catalyzed Cross‐Coupling of Alkenyl Acetates

Stable C O linkages are generally unreactive in cross‐coupling reactions which mostly employ more electrophilic halides or activated esters (triflates, tosylates). Acetates are cheap and easily accessible electrophiles but have not been used in cross‐couplings because the strong C O bond and high propensity to engage in unwanted acetylation and deprotonation. Reported herein is a selective iron‐catalyzed cross‐coupling of diverse alkenyl acetates, and it operates under mild reaction conditions (0 °C, 2 h) with a ligand‐free catalyst (1–2 mol %).     

Practical Iron‐ and Cobalt‐Catalyzed Cross‐Coupling Reactions between N‐Heterocyclic Halides and Aryl or Heteroaryl Magnesium Reagents

The reaction scope of iron‐ and cobalt‐catalyzed cross‐coupling reactions in the presence of isoquinoline (quinoline) in the solvent mixture tBuOMe/THF has been further investigated. Various 2‐halogenated pyridine, pyrimidine, and triazine derivatives were arylated under these mild conditions in excellent yields. The presence of isoquinoline allows us to perform Fe‐catalyzed cross‐coupling reactions between 6‐chloroquinoline and aryl magnesium reagents. Furthermore, it was found that the use of 10 % N,N‐dimethylquinoline‐8‐amine increases the yields of some Co‐catalyzed cross‐coupling reactions with chloropyridines bearing electron‐withdrawing substituents.     

Cobalt‐Catalyzed Cross‐Coupling of 3‐ and 4‐Iodopiperidines with Grignard Reagents

A cobalt‐catalyzed cross‐coupling between 3‐ and 4‐iodopiperidines and Grignard reagents is disclosed. The reaction is an efficient, cheap, chemoselective, and flexible way to functionalize piperidines. This coupling was used as the key step to realize a short synthesis of (±)‐preclamol. Some mechanistic investigations were conducted that highlight the formation of radical intermediates.     

Sustainable Catalysis: Rational Pd Loading on MIL‐101Cr‐NH2 for More Efficient and Recyclable Suzuki–Miyaura Reactions

Palladium nanoparticles have been immobilized into an amino‐functionalized metal–organic framework (MOF), MIL‐101Cr‐NH₂, to form Pd@MIL‐101Cr‐NH₂. Four materials with different loadings of palladium have been prepared (denoted as 4‐, 8‐, 12‐, and 16 wt %Pd@MIL‐101Cr‐NH₂). The effects of catalyst loading and the size and distribution of the Pd nanoparticles on the catalytic performance have been studied. The catalysts were characterized by using scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier‐transform infrared (FTIR) spectroscopy, powder X‐ray diffraction (PXRD), N₂‐sorption isotherms, elemental analysis, and thermogravimetric analysis (TGA). To better characterize the palladium nanoparticles and their distribution in MIL‐101Cr‐NH₂, electron tomography was employed to reconstruct the 3D volume of 8 wt %Pd@MIL‐101Cr‐NH₂ particles. The pair distribution functions (PDFs) of the samples were extracted from total scattering experiments using high‐energy X‐rays (60 keV). The catalytic activity of the four MOF materials with different loadings of palladium nanoparticles was studied in the Suzuki–Miyaura cross‐coupling reaction. The best catalytic performance was obtained with the MOF that contained 8 wt % palladium nanoparticles. The metallic palladium nanoparticles were homogeneously distributed, with an average size of 2.6 nm. Excellent yields were obtained for a wide scope of substrates under remarkably mild conditions (water, aerobic conditions, room temperature, catalyst loading as low as 0.15 mol %). The material can be recycled at least 10 times without alteration of its catalytic properties.     

Mechanistic Origin of Cross‐Coupling Selectivity in Ni‐Catalysed Tishchenko Reactions

Mechanistic studies have been performed for the recently developed, Ni‐catalysed selective cross‐coupling reaction between aryl and alkyl aldehydes. A mono‐carbonyl activation (MCA) mechanism (in which one of the carbonyl groups is activated by oxidative addition) was found to be the most favourable pathway, and the rate‐determining step is oxidative addition. Analysing the origin of the observed cross‐coupling selectivity, we found the most favourable carbonyl activation step requires both coordination of the aryl aldehyde and oxidative addition of the alkyl aldehyde. Therefore, the stronger π‐accepting ability of the aryl aldehyde (relative to alkyl aldehyde) and the ease of oxidative addition of the alkyl aldehyde (relative to aryl aldehyde) are responsible for the cross‐coupling selectivity.     

Stereospecific synthesis of a family of novel (E)‐2‐aryl‐1‐silylalka‐1,4‐dienes or (E)‐4‐aryl‐5‐silylpenta‐1,2,4‐trienes via a cross‐coupling of (Z)‐silyl(stannyl)ethenes with allyl halides or propargyl bromide

Stereospecific synthesis of a family of novel (E)‐2‐aryl‐1‐silylalka‐1,4‐dienes or (E)‐4‐aryl‐5‐silylpenta‐1,2,4‐trienes via a cross‐coupling of (Z)‐silyl(stannyl)ethenes with allyl halides or propargyl bromide is described. In the reaction with allyl bromide, either a Pd(dba)₂? CuI combination (dba, dibenzylideneacetone) in DMF or copper(I) iodide in DMSO–THF readily catalyzes or mediates the coupling reaction of (Z)‐silyl(stannyl)ethenes at room temperature, producing novel vinylsilanes bearing an allyl group β to silicon with cis ‐disposition in good yields. Allyl chlorides as halides can be used in the CuI‐mediated reaction. CuI alone much more effectively mediates the cross‐coupling reaction with propargyl bromide in DMSO–THF at room temperature compared with a Pd(dba)₂? CuI combination catalysis in DMF, providing novel stereodefined vinylsilanes bearing an allenyl group β to silicon with cis ‐disposition in good yields. Copyright © 2008 John Wiley & Sons, Ltd.     

Palladium‐catalysed Suzuki reaction of aryl chlorides in aqueous media using 1,3‐dialkylimidazolidin‐2‐ylidene ligands

A highly effective, easy to handle and environmentally benign process for palladium‐mediated Suzuki cross‐coupling is developed. The in situ prepared three‐component system Pd(OAc)₂–1,3‐bis(alkyl)imidazolinium chlorides (2a–f) and Cs₂CO₃ catalyses quantitatively the Suzuki cross‐coupling of deactivated aryl chlorides. Copyright © 2005 John Wiley & Sons, Ltd.