Methylenecyclopropane Annulation by Manganese(I)‐Catalyzed Stereoselective C−H/C−C Activation

C−H/C−C functionalizations with methylenecyclopropanes (MCPs) were accomplished with a versatile base‐metal catalyst. A robust manganese(I) complex enabled the expedient annulation of MCPs by synthetically meaningful ketimines to deliver, upon one‐pot hydroarylation, densely substituted polycylic anilines in a step‐economical fashion. Mechanistic studies provided strong support for a facile organometallic C−H manganation, while typical cobalt, ruthenium, rhodium, and palladium catalysts were found completely ineffective.     

Full Selectivity Control in Cobalt(III)‐Catalyzed C−H Alkylations by Switching of the C−H Activation Mechanism

Selectivity control in hydroarylation‐based C−H alkylation has been dominated by steric interactions. A conceptually distinct strategy that exploits the programmed switch in the C−H activation mechanism by means of cobalt catalysis is presented, which sets the stage for convenient C−H alkylations with unactivated alkenes. Detailed mechanistic studies provide compelling evidence for a programmable switch in the C−H activation mechanism from a linear‐selective ligand‐to‐ligand hydrogen transfer to a branched‐selective base‐assisted internal electrophilic‐type substitution.     

Iridium‐Catalyzed Regio‐ and Enantioselective Hydroarylation of Alkenyl Ethers by Olefin Isomerization

Iridium‐catalyzed hydroarylation of alkenyl ethers, such as allylic and homoallylic ethers, by C−H bond activation gave high yields of the corresponding addition products, where the aryl groups were selectively installed at the α‐carbon atom to the alkoxy group. The reaction involves an isomerization of the alkenyl ethers into the corresponding 1‐alkenyl ethers, which then undergo the regio‐ and enantioselective hydroarylation.     

Iridium-Catalyzed Regio- and Enantioselective Hydroarylation of Alkenyl Ethers by Olefin Isomerization

Iridium-catalyzed hydroarylation of alkenyl ethers, such as allylic and homoallylic ethers, by C−H bond activation gave high yields of the corresponding addition products, where the aryl groups were selectively installed at the α-carbon atom to the alkoxy group. The reaction involves an isomerization of the alkenyl ethers into the corresponding 1-alkenyl ethers, which then undergo the regio- and enantioselective hydroarylation.     

Hydroarylation of 2‐Aryloxybut‐1‐en‐3‐ynes via Pd/Acid‐Catalyzed C−H Bond Activation: A Concise Synthesis of 2,3‐Bismethylene‐2,3‐dihydrobenzofurans

An intramolecular exo ‐hydroarylation of 2‐aryloxy‐1,4‐disilylbut‐1‐en‐3‐ynes via ortho ‐C−H bond activation under palladium(0) and acid catalysis was found to give 2,3‐bis(silylmethylidene)‐2,3‐dihydrobenzofurans. The two silyl groups present probably promoted the reaction and played a key role in stabilizing the diene moiety in the product. The products readily led to functionalized condensed cycles by a Diels–Alder reaction.     

Atroposelective Synthesis of C−N Vinylindole Atropisomers by Palladium-Catalyzed Asymmetric Hydroarylation of 1-Alkynylindoles

Transition-metal-catalyzed hydroarylation of unsymmetrical internal alkynes remains challenging because of the difficulty in controlling regioselectivity and stereoselectivity. Moreover, the enantioselective hydroarylation of alkynes using organoboron reagents has not been reported. Herein, we report for the first time that palladium compounds can catalyze the hydroarylation of 1-alkynylindoles with organoborons for the synthesis of chiral C−N atropisomers. A series of rarely reported vinylindole atropisomers was synthesized with excellent regio-, stereo- (Z-selectivity), and enantioselectivity under mild reaction conditions. The ready availability of organoborons and alkynes and the simplicity, high stereoselectivity, and good functional group tolerance of this catalytic system make it highly attractive.     

Cationic Iridium/S‐Me‐BIPAM‐Catalyzed Direct Asymmetric Intermolecular Hydroarylation of Bicycloalkenes

Highly enantioselective cationic iridium‐catalyzed hydroarylation of bicycloalkenes, by carbonyl‐directed C H bond cleavage, was accomplished using a newly synthesized sulfur‐linked bis(phosphoramidite) ligand (S‐Me‐BIPAM). The reaction provides alkylated acetophenone or benzamide derivatives in moderate to excellent yields and good to excellent enantioselectivities. Notably, the hydroarylation reaction of 2‐norbornene with N,N‐dialkylbenzamide proceeds with excellent enantioselectivity (up to 99 % ee) and high selectivity for the mono‐ortho‐alkylation product.     

Rhodium-Catalyzed Alkylation of C−H Bonds in Aromatic Amides with Non-activated 1-Alkenes: The Possible Generation of Carbene Intermediates from Alkenes

The alkylation of C−H bonds (hydroarylation) in aromatic amides with non-activated 1-alkenes using a rhodium catalyst and assisted by an 8-aminoquinoline directing group is reported. The addition of a carboxylic acid is crucial for the success of this reaction. The results of deuterium-labeling experiments indicate that one of deuterium atoms in the alkene is missing, suggesting that the reaction does not proceed through the commonly accepted mechanism for C−H alkylation reactions. Instead the reaction is proposed to proceed through a carbene mechanism. The carbene mechanism is also supported by preliminary DFT calculations.     

Iridium-Catalyzed Remote Site-Switchable Hydroarylation of Alkenes Controlled by Ligands

An iridium-catalyzed remote site-switchable hydroarylation of alkenes was reported, delivering the products functionalized at the subterminal methylene and terminal methyl positions on an alkyl chain controlled by two different ligands, respectively, in good yields and with good to excellent site-selectivities. The catalytic system showed good functional group tolerance and a broad substrate scope, including unactivated and activated alkenes. More importantly, the regioconvergent transformations of mixtures of isomeric alkenes were also successfully realized. The results of the mechanistic studies demonstrate that the reaction undergoes a chain-walking process to give an [Ar−Ir−H] complex of terminal alkene. The subsequent processes proceed through the modified Chalk–Harrod-type mechanism via the migratory insertion of terminal alkene into the Ir−C bond followed by C−H reductive elimination to afford the hydrofunctionalization products site-selectively.     

Nickel(0)‐Catalyzed Hydroarylation of Styrenes and 1,3‐Dienes with Organoboron Compounds

A Ni‐catalyzed hydroarylation of styrenes and 1,3‐dienes with organoboron compounds has been developed. The reaction offers a highly selective approach to diarylalkanes and allylarenes under redox‐neutral conditions. In this hydroarylation reaction, a new strategy that uses the proton of methanol to generate the active catalyst species Ni?H was developed. The Ni‐catalyzed hydroarylation, combined with a Ir‐catalyzed C?H borylation, affords a very efficient and straightforward access to a retinoic acid receptor agonist.     

Dimeric Manganese-Catalyzed Hydroarylation and Hydroalkenylation of Unsaturated Amides

An unprecedented Mn(I)-catalyzed selective hydroarylation and hydroalkenylation of unsaturated amides with commercially available organic boronic acids is reported. Alkenyl boronic acids have been successfully employed for the first time in Mn(I)-catalyzed carbon–carbon bond formation. A wide array of β-alkenylated amide products can be obtained in moderate to good yields, which offers practical access to five- and six-membered lactams. This protocol has predictable regio- and chemoselectivity, excellent functional group compatibility and ease of operation in air, representing a significant step-forward towards manganese-catalyzed C−C coupling.     

Gold‐Catalyzed Formal C−C Bond Insertion Reaction of 2‐Aryl‐2‐diazoesters with 1,3‐Diketones

The transition‐metal‐catalyzed formal C−C bond insertion reaction of diazo compounds with monocarbonyl compounds is well established, but the related reaction of 1,3‐diketones instead gives C−H bond insertion products. Herein, we report a protocol for a gold‐catalyzed formal C−C bond insertion reaction of 2‐aryl‐2‐diazoesters with 1,3‐diketones, which provides efficient access to polycarbonyl compounds with an all‐carbon quaternary center. The aryl ester moiety plays a crucial role in the unusual chemoselectivity, and the addition of a Brønsted acid to the reaction mixture improves the yield of the C−C bond insertion product. A reaction mechanism involving cyclopropanation of a gold carbenoid with an enolate and ring‐opening of the resulting donor–acceptor‐type cyclopropane intermediate is proposed. This mechanism differs from that of the traditional Lewis‐acid‐catalyzed C−C bond insertion reaction of diazo compounds with monocarbonyl compounds, which involves a rearrangement of a zwitterion intermediate as a key step.     

Fluorine Effects on Group Migration via a Rhodium(V) Nitrenoid Intermediate

An unprecedented rhodium(III)‐catalyzed hydroarylation of α,α‐difluoromethylene alkynes with N ‐pivaloxyl aroylamides through sequential C−H activation and aryl migration is detailed herein. A large array of α,α‐difluoromethylene alkynes and N ‐pivaloxyl aryl amides were amenable to this transformation, thus providing a novel synthetic protocol for the construction of difluorinated 2‐alkenyl aniline derivatives in high yields and with excellent regioselectivity. Notably, unique fluorine effects were found to underlie the thus unconventional reaction manifold.     

Metal Insertion into C−C Bonds in Solution

What kind of ligated metal center is necessary for insertion into the “hidden” C−C bond? How can one tune the metal center for C−C bond activation by variation of the steric and electronic properties of ligands? What are the possible mechanisms of C−C bond activation in various reaction systems? A systematic look at the available data on C−C bond activation in solution provides some answers to these questions.     

Selective α‐Oxyamination and Hydroxylation of Aliphatic Amides

Compared to the α‐functionalization of aldehydes, ketones, even esters, the direct α‐modification of amides is still a challenge because of the low acidity of α‐CH groups. The α‐functionalization of N−H (primary and secondary) amides, containing both an unactived α‐C−H bond and a competitively active N−H bond, remains elusive. Shown herein is the general and efficient oxidative α‐oxyamination and hydroxylation of aliphatic amides including secondary N−H amides. This transition‐metal‐free chemistry with high chemoselectivity provides an efficient approach to α‐hydroxy amides. This oxidative protocol significantly enables the selective functionalization of inert α‐C−H bonds with the complete preservation of active N−H bond.     

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.     

para‐Selective C−H Borylation of (Hetero)Arenes by Cooperative Iridium/Aluminum Catalysis

para ‐Selective C−H borylation of benzamides and pyridines has been achieved by cooperative iridium/aluminum catalysis. A combination of iridium catalysts commonly employed for arene C−H borylation and bulky aluminum‐based Lewis acid catalysts provides an unprecedented strategy for controlling the regioselectivity of C−H borylation to give variously substituted (hetero)arylboronates, which are versatile synthetic intermediates for complex multi‐substituted aromatic compounds.     

Reductive Coupling of Acrylates with Ketones and Ketimines by a Nickel‐Catalyzed Transfer‐Hydrogenative Strategy

Nickel‐catalyzed coupling of benzyl acrylates with activated ketones and imines provides γ‐butyrolactones and lactams, respectively. The benzyl alcohol byproduct released during the lactonization/lactamization event is relayed to the next cycle where it serves as the reductant for C−C bond formation. This strategy represents a conceptually unique approach to transfer‐hydrogenative C−C bond formation, thus providing examples of reductive heterocyclizations where hydrogen embedded within an alcohol leaving group facilitates turnover.     

Recent Progress in Application of Graphene Supported Metal Nanoparticles in C−C and C−X Coupling Reactions

The carbon‐carbon and carbon‐heteroatom bonds catalytic formation is among the most significant reactions in organic synthesis which extensively applied for synthesis of natural products, heterocycles, dendrimers, biologically active molecules and useful compounds. This review provides the latest advances in the preparation of graphene supported metal nanoparticles and their application in the catalytic formation of both carbon‐carbon (C−C) and carbon‐heteroatom (C−X) bonds including the Suzuki, Heck, Hiyama, Ullmann, Buchwald and Sonogashira coupling reactions. Numerous examples are given concerning the use of these catalysts in C−C and C−X coupling reactions along with the reliable and simple preparation methods of these catalysts, their characterization and catalytic properties and also the recycling possibilities.     

Ruthenium-Catalyzed Hydroarylation of Methylenecyclopropanes through CH Bond Cleavage: Scope and Mechanism

Intermolecular hydroarylation reactions of highly strained methylenecyclopropanes 2-phenylmethylenecyclopropane (1), 2,2-diphenylmethylenecyclopropane (2), methylenespiropentane (3), bicyclopropylidene (4), (dicyclopropylmethylene)cyclopropane (5), and benzhydrylidenecyclopropane (6) through C?H bond functionalization of 2-phenylpyridine (7?a) and other arenes with directing groups were studied. The reaction was very sensitive to the substitution on the methylenecyclopropanes. Although these transformations involved (cyclopropylcarbinyl)-metal intermediates, substrates 1 and 4 furnished anti-Markovnikov hydroarylation products with complete conservation of all cyclopropane rings in 11-93?% yield, whereas starting materials 3 and 5 were inert toward hydroarylation. Methylenecyclopropane 6 formed the products of formal hydroarylation reactions of the longest distal C?C bond in the methylenecyclopropane moiety in high yield, and hydrocarbon 2 afforded mixtures of hydroarylated products in low yields with a predominance of compounds that retained the cyclopropane unit. As byproducts, Diels-Alder cycloadducts and self-reorganization products were obtained in several cases from substrates 1-3 and 5. The structures of the most important new products have been unambiguously determined by X-ray diffraction analyses. On the basis of the results of hydroarylation experiments with isotopically labeled 7?a-[D(5) ], a plausible mechanistic rationale and a catalytic cycle for these unusual ruthenium-catalyzed hydroarylation reactions have been proposed. Arene-tethered ruthenium-phosphane complex 53, either isolated from the reaction mixture or independently prepared, did not show any catalytic activity.