Palladium‐Catalyzed and Hybrid Acids‐Assisted Synthesis of [60]Fulleroazepines in One Pot under Mild Conditions: Annulation of N‐Sulfonyl‐2‐aminobiaryls with [60]Fullerene through Sequential C‐H Bond Activation,C‐C and C‐N Bond Formation

An extraordinarily efficient hybrid acids‐assisted, palladium‐catalyzed and chelating‐group‐assisted C H bond activation of N‐sulfonyl‐2‐aminobiaryls and their annulations with [60]fullerene via sequential C C and C N bond formation at room temperature to afford [60]fulleroazepines is demonstrated. The formation of [60]fulleroazepines is highly regioselective and tolerant to both electron‐withdrawing and electron‐donating groups on the aryl moiety and the reaction gives monofunctionalized fullerenes in good yields (up to 54% isolated yield and 92% based on converted C₆₀).     

Sulfonic Acid‐Catalyzed Autoxidative Carbon‐Carbon Coupling Reaction under Elevated Partial Pressure of Oxygen

An aerobic organocatalytic oxidative C C bond formation reaction of benzylic C H bonds with various C‐nucleophiles is described. The coupling reaction proceeds by simply stirring the substrates under elevated partial pressure of oxygen in the presence of a sulfonic acid catalyst at room temperature. Elevation of the pressure enables the reaction of a broad scope of nucleophile substrates otherwise showing poor reactivity at ambient pressure. The benzylic C H bonds of xanthene, acridanes, isochromane and related heterocycles could be functionalized with nucleophiles including ketones, 1,3‐dicarbonyl compounds and aldehydes. Electron‐rich arenes could be utilized as nucleophiles at elevated temperatures. The reactions are believed to proceed via autoxidation of the benzylic C H bonds to the hydroperoxides and subsequent nucleophilic substitution catalyzed by sulfonic acids.     

Rhodium(III)‐Catalyzed Synthesis of Indole Derivatives From Pyrimidyl‐Substituted Anilines and Diazo Compounds

An efficient method for the synthesis of indole derivatives from readily available pyrimidyl‐substituted anilines and diazo compounds via rhodium(III)‐catalyzed C H bond activation has been developed. This cyclization reaction displays excellent functional group compatibility and regioselectivity, which overcomes some drawbacks of the classical indole synthetic methods and provides a facile approach for the construction of multi‐substituted indole derivatives. The redox‐neutral intermolecular annulation procedure comprises tandem C H bond activation, cyclization, and condensation steps, releasing water and nitrogen as by‐products.

     

Copper‐Catalyzed Cross‐Dehydrogenative Coupling (CDC) of Alkynes and Benzylic C?H Bonds

The activation of benzylic C H bonds and subsequent coupling with terminal alkynes in the presence of 2,3‐dichloro‐5,6‐dicyanoquinone (DDQ) and a catalytic amount of copper(I) triflate is presented. Good to moderate yields of disubstituted alkynes are obtained for this cross‐dehydrogenative coupling (CDC) reaction between a variety of aromatic alkynes and diphenylmethane derivatives.     

Palladium‐Catalyzed Direct Arylations of 1,2,3‐Triazoles with Aryl Chlorides using Conventional Heating

Generally applicable, palladium‐catalyzed direct arylations of 1,2,3‐triazoles with aryl chlorides were accomplished through conventional heating at reaction temperatures of 105–120 °C. Thereby, intra‐ and intermolecular C H bond functionalizations were achieved with a variety of differently substituted chlorides as electrophiles, bearing numerous valuable functional groups.     

Rhodium‐Catalyzed,Three‐Component Reaction of Diazo Compounds with Amines and Azodicarboxylates

A novel, three‐component C N bond forming reaction is described. Reaction of diazo compounds with both azodicarboxylates and arylamines in the presence of dirhodium acetate catalyst gives good yields of the corresponding aminal with high selectivity and, in most cases, N H insertion side products were suppressed. This is the first example of a C N bond formation from the addition of ammonium ylides to azodicarboxylates.     

Ruthenium‐Catalyzed Oxidative Homo‐Coupling of 2‐Arylpyridines

A ruthenium‐catalyzed oxidative homo‐coupling reaction of 2‐arylpyridines via C H activation was developed. The reaction could tolerate various functional groups on both the aryl and the pyridyl rings to afford a series of dimerized products with iron(III) chloride (FeCl₃) as a stoichiometric oxidant. A tentative mechanism was proposed for this oxidative C H/C H homo‐coupling.     

Iron‐Catalyzed Nitrogen‐Directed Coupling of Arene and Aryl Bromides Mediated by Metallic Magnesium

2‐Arylpyridines, 2‐alkenylpyridine, and aromatic imines can be coupled with aryl bromides in the presence of an iron catalyst, metallic magnesium, a diamine ligand and an organic dihalide oxidant at 0 °C. The use of a 1:1 mixture of tetrahydrofuran and 1,4‐dioxane is essential for this C H bond activation reaction. The reaction has wider scope of the substrate compared with the reaction using a separately prepared Grignard reagent, and proceeds with lower catalyst loading (2.5 mol%).     

Gold-Catalyzed Alkynylation: Acetylene-Transfer instead of Functionalization

Over the last fifteen years, gold has been raised from the status of an inert noble metal to one of the most-often-used catalysts in synthetic chemistry. The functionalization of the triple bond of alkynes has been especially successful in this respect. In contrast, gold-catalyzed alkynylation reactions only began to emerge in 2007. Since then, three different approaches have been successfully used for this transformation. 1) Gold nanoparticles have been shown to promote catalytic cycles based on the oxidative arylation of aryl halides to give a “palladium-free Sonogashira reaction”. 2) The use of benziodoxol(on)e hypervalent iodine compounds as oxidative alkynylation reagents has allowed the C H functionalization of electron-rich heterocycles under mild conditions with a very broad functional-group tolerance. 3) The use of iodobenzene acetate or Selectfluor as an external oxidant has led to the first alkynylation methods based on direct C H/C H coupling reactions. In only six years, gold-catalyzed alkynylation methods have grown from non-existent to useful synthetic procedures for the synthesis of structurally diverse alkynes. Considering that acetylenes are among the most-important building blocks for applications in synthetic chemistry, chemical biology, and materials science, there is tremendous potential for the further development of gold-catalyzed alkynylation reactions in the future.     

Cooperative Catalysis with Aldehydes and Copper: Development and Application in Aerobic Oxidative C?H Amination at Room Temperature

A conceptually new cooperative catalytic system via a synergistic combination of aldehyde and copper catalysis has been established based on systemic mechanistic studies. This new cooperative catalysis has been successfully applied in the direct aerobic oxidative C H amination of azoles at room temperature, which was previously realized under harsh conditions. Mechanistic studies including isotopic labeling experiments and kinetic isotope effect (KIE) experiments support a reaction pathway that involves formation of an aminal, hydrolysis of the aminal to generate the copper‐amide species, subsequent C H amination and re‐oxidation of copper(I) to copper(II) by oxygen. It not only provides an efficient method to realize the oxidative C H amination of benzoxazoles with free amines at room temperature, but also paves the way for establishing new C N bond formation reactions by using this efficient cooperative catalysis.     

Rhodium‐Catalyzed Oxidative ortho‐Acylation of Aryl Ketone O‐Methyl Oximes with Aryl and Alkyl Aldehydes

The rhodium‐catalyzed oxidative ortho‐acylation of aryl ketone O‐methyl oximes with aryl and alkyl aldehydes via C H bond activation is described. The cross‐coupling reaction exhibits high functional group tolerance and regioselectivity under relatively mild conditions and constitutes a versatile route to a diverse library of diaryl ketones, which are difficult to obtain by the classical Friedel–Crafts acylation. Moreover, this reaction proceeds via an unprecedented Rh‐catalyzed oxidative ortho‐acylation of aryl ketone O‐methyl oximes with highly electron‐deficient aryl aldehydes followed by a direct addition of the second ortho C H bond to aldehydes in a one‐pot reaction, to generate two C C bonds simultaneously.     

Synthesis of Methylene‐Bridge Polyarenes through Palladium‐Catalyzed Activation of Benzylic Carbon‐Hydrogen Bond

In the presence of palladium(II) acetate [Pd(OAc)₂] and an N‐heterocyclic carbene (NHC) ligand, fluorene derivatives can be generated in good to excellent yields from 2‐halo‐2′‐methylbiaryls through the benzylic C H bond activation (14 examples; 81–97% yields). The scope and limitations of this protocol have been examined. A wide range of functional groups, such as alkyl, alkoxy, ester, nitrile, and others, is able to tolerate the reaction conditions herein. The cyclization of an isotope‐labelled biphenyl gave the corresponding product with a primary kinetic isotope effect (k_H/k_D=4.8:1), which indicates that the rate‐determining step of this reaction is the activation of the benzylic C H bond. Moreover, indenofluorenes were also accessed in excellent results from terphenyls (3 examples; 91–92% yields). The cascade reaction of 2,6‐dichloro‐2′‐methylbiphenyl with diphenylacetylene produced 8,9‐diphenyl‐4H‐cyclopenta[def]phenanthrene in 60% yield through the activation of an aryl and a benzylic C H bond.     

Palladium‐Catalyzed Oxidative Intramolecular C?C Bond Formation via Double sp2 C?H Activation between the 2‐Position of Imidazoles and a Benzene Ring

Oxidative intramolecular C C bond formation via double sp² C H activation between the 2‐position of imidazoles and a benzene ring catalyzed by palladium(II) has been developed, which provides an atom‐economical, concise and efficient methodology to synthesize imidazole‐ or benzimidazole‐fused isoquinoline polyheteroaromatic compounds.     

Reversible Alkylation of Dimedone with Aldehyde: A Neglected Way for Maximizing Selectivity of Three‐Component Reactions of Dimedone and an Aldehyde

The selectivity of a three‐component electrophilic reaction of an aldehyde with dimedone and another carbon‐based nucleophile could be improved by a reversible alkylation procedure, which involves formation, breaking and regeneration of C C bonds. In the presence of iron(III) chloride and triphenylphosphine, an analogous C C bond breaking can be observed in the reaction of 2,3,4,9‐tetrahydro‐9‐(2‐hydroxy‐4,4‐dimethyl‐6‐oxo‐1‐cyclohexen‐1‐yl)‐3,3‐dimethyl‐1H‐xanthen‐1‐one, in which the fragment of dimedone was replaced by a carbon‐based nucleophile. Inspired by this observation, some three‐component reactions of salicyldehyde and dimedone were successfully developed by using iron(III) chloride and triphenylphosphine (PPh₃) as catalyst. PPh₃ plays the role of hydrogen bond acceptor, which confers a good flexibility of the substrate by weakening the intramolecular hydrogen bond, allowing thus an easy interaction of the substrate with iron(III) chloride catalyst.     

Pd‐Catalyzed ortho‐Selective Oxidative Coupling of Halogenated Acetanilides with Acrylates

Coupling of different halogenated acetanilides with acrylates using Pd‐catalyzed ortho‐selective C H bond activation is reported. The yields of coupled products are low to high depending on the substrate. In general, arenes with electron‐rich substituents like methoxy and methyl groups gave higher yields of the coupled products. The presence of the halogen substituent did not interfere with the activation process under these conditions     

Copper‐Catalyzed Cascade Reactions of Substituted 4‐Iodopyrazolecarbaldehydes with 1,2‐Phenylenediamines and 2‐Aminophenols

A new approach for the synthesis of novel annulated‐pyrazoles is presented. This protocol includes an intermolecular condensation followed by a copper‐mediated intramolecular C N or C O coupling reaction. The method is applied to a range of substituted 4‐iodopyrazolecarbaldehydes which react with 1,2‐phenylenediamines or 2‐aminophenols to yield substituted 2,4‐ or 1,4‐dihydrobenzo[b]pyrazolo[4,3‐e][1,4]diazepines or substituted‐2H‐ or 1H‐benzo[b]pyrazolo[3,4‐f][1,4]oxazepines, respectively.     

Regioselective Access to Sultam Motifs through Cobalt‐Catalyzed Annulation of Aryl Sulfonamides and Alkynes using an 8‐Aminoquinoline Directing Group

The use of cobalt as catalyst in direct C H activation protocols as a replacement for more expensive second row transition metals is currently attracting significant attention. Herein we disclose a facile cobalt‐catalyzed C H functionalization route towards sultam motifs through annulation of easily prepared aryl sulfonamides and alkynes using 8‐aminoquinoline as a directing group. The reaction shows broad substrate scope with products obtained in a highly regioselective manner in good to excellent isolated yields. Mechanistic insights suggest the formation of a Co(III)‐aryl key species via a rate‐determining arene C H activation during the annulation reaction.

     

Multiple Roles of the Pyrimidyl Group in the Rhodium‐Catalyzed Regioselective Synthesis and Functionalization of Indole‐3‐carboxylic Acid Esters

A regioselective synthesis of indole‐3‐carboxylic acid esters from anilines and diazo compounds has been realized by making use of the pyrimidyl group‐assisted rhodium‐catalyzed C H activation and C N bond formation. The reaction proceeds under mild conditions, exhibits good functional group tolerance and scalability. Reutilization of the pyrimidyl directing group in the resulting products provided an efficient strategy for further C‐7 functionalization of indoles. Moreover, the pyrimidyl moiety could be readily removed as a leaving group to offer various free N H indoles.

     

C?C Bond Formation via C?H Activation and C?N Bond Formation via Oxidative Amination Catalyzed by Palladium‐ Polyoxometalate Nanomaterials Using Dioxygen as the Terminal Oxidant

An efficient heterogeneous palladium‐polyoxometalate catalyst with the formula Pd‐H₆PV₃Mo₉O₄₀/C has been successfully developed for carbon‐carbon (C C) bond formation via carbon‐hydrogen (C H) activation and carbon‐nitrogen (C N) bond formation via oxidative amination using oxygen as the terminal oxidant. The coupling processes are simple, and use relatively mild conditions to form the desired products. In addition, less waste is generated as no additional reagents such as organic/inorganic oxidants are required, and water is the only by‐product generated.     

Copper‐Catalyzed Intermolecular Amination of Acidic Aryl C?H Bonds with Primary Aromatic Amines

A copper‐catalyzed intermolecular aerobic oxidative C H bond amination of various polyfluorobenzenes with an array of primary aromatic amines was achieved for the first time. The reactivity of the polyfluorobenzenes was observed to depend on the acidity of C H bonds. Under similar reaction conditions, the C H bond amination of azoles also occurred.