Cobalt‐Catalyzed CH Cyanation of Arenes and Heteroarenes

Carboxylate assistance proved to be the key for the success of efficient cobalt(III)‐catalyzed C? H cyanations. Thus, an in situ generated cationic cobalt complex was identified as a versatile catalyst for the site‐selective synthesis of various aromatic and heteroaromatic nitriles with ample substrate scope.     

Copper‐Catalyzed Electrophilic Amination of Heteroarenes and Arenes by CH Zincation

Direct amination of heteroarenes and arenes has been achieved in a one‐pot C? H zincation/copper‐catalyzed electrophilic amination procedure. This amination method provides an efficient and rapid approach to access a diverse range of heteroaromatic and aromatic amines including those previously inaccessible using C? H amination methods. The mild reaction conditions and good functional‐group compatibility demonstrate its great potential for the synthesis of important and complex amines.     

Palladium‐Catalyzed/Norbornene‐Mediated CH Activation/ N‐Tosylhydrazone Insertion Reaction: A Route to Highly Functionalized Vinylarenes

A straightforward method for the synthesis of highly functionalized vinylarenes through palladium‐catalyzed, norbornene‐mediated C?H activation/carbene migratory insertion is described. Extension to a one‐pot procedure is also developed. Furthermore, this method can also be used to generate polysubstituted bicyclic molecules. The reaction proceeds under mild conditions to give the products in satisfactory yields using readily available starting materials. This is a Catellani–Lautens reaction that incorporates different types of coupling partners. Additionally, this reaction is the first to demonstrate the possibility of combining Pd‐catalyzed insertion of diazo compounds and Pd‐catalyzed C?H activation.     

Palladium‐Catalyzed CH Activation and Intermolecular Annulation with Allenes

A new and efficient Pd^II‐catalyzed intermolecular annulation of N‐benzoylsulfonamide with allenes for the synthesis of 3,4‐dihydroisoquinolin‐1(2H)‐ones is reported. This C?H functionalization is compatible with ambient air and moisture, and it can be applied to terminal or internal allenes with di?erent synthetically attractive functional groups. Control experiments and a kinetic isotope effect study are conducted and a plausible mechanism is proposed.     

Heterogeneous Platinum‐Catalyzed CH Perfluoroalkylation of Arenes and Heteroarenes

Fluorinated organic compounds are gaining increasing interest for life science applications. The replacement of hydrogen in arenes or heteroarenes by a perfluoroalkyl group has a profound influence on the physical and biological properties of such building blocks. Here, an operationally simple protocol for the direct C? H perfluoroalkylation of (hetero)arenes with R_fI or R_fBr has been developed, using a robust supported platinum catalyst. The ready availability of the starting materials, the excellent substrate tolerance, and the reusability of the catalyst make this method attractive for the synthesis of a variety of perfluoroalkyl‐substituted aromatic compounds. Preliminary mechanistic studies revealed the formation of radicals to be crucial in the reaction system.     

Carboxylate Assisted Ni‐Catalyzed CH Bond Allylation of Benzamides

A one‐step synthetic method was developed for allylation of benzamides using Ni(COD)₂/RCO₂H and [Ni(μ‐H₂O)(OOCCMe₃)₂(HOOCCMe₃)₂]₂ ( A′ ) catalytic system. Efficient, well‐defined, air and moisture‐stable Ni–pivalate complex was isolated and employed in catalytic allylation. The influence of solvent on product selectivity was also investigated.     

Manganese‐Catalyzed Dehydrogenative [4+2] Annulation of NH Imines and Alkynes by CH/NH Activation

Described herein is a manganese‐catalyzed dehydrogenative [4+2] annulation of N? H imines and alkynes, a reaction providing highly atom‐economical access to diverse isoquinolines. This transformation represents the first example of manganese‐catalyzed C? H activation of imines; the stoichiometric variant of the cyclomanganation was reported in 1971. The redox neutral reaction produces H₂ as the major byproduct and eliminates the need for any oxidants, external ligands, or additives, thus standing out from known isoquinoline synthesis by transition‐metal‐catalyzed C? H activation. Mechanistic studies revealed the five‐membered manganacycle and manganese hydride species as key reaction intermediates in the catalytic cycle.     

Copper(I)‐Catalyzed Alkylation of Polyfluoroarenes through Direct CH Bond Functionalization

The copper(I)‐catalyzed alkylation of electron‐deficient polyfluoroarenes with N‐tosylhydrazones and diazo compounds has been developed. This reaction uses readily available starting materials and is operationally simple, thus representing a practical method for the construction of C(sp²)? C(sp³) bonds with polyfluoroarenes through direct C? H bond functionalization. Mechanistically, copper(I) carbene formation and subsequent migratory insertion are proposed as the key steps in the reaction pathway.     

Copper‐Catalyzed Site‐Selective Intramolecular Amidation of Unactivated C(sp3)H Bonds

The intramolecular dehydrogenative amidation of aliphatic amides, directed by a bidentate ligand, was developed using a copper‐catalyzed sp³ C? H bond functionalization process. The reaction favors predominantly the C? H bonds of β‐methyl groups over the unactivated methylene C? H bonds. Moreover, a preference for activating sp³ C? H bonds of β‐methyl groups, via a five‐membered ring intermediate, over the aromatic sp² C? H bonds was also observed in the cyclometalation step. Additionally, sp³ C? H bonds of unactivated secondary sp³ C? H bonds could be functionalized by favoring the ring carbon atoms over the linear carbon atoms.     

Palladium‐Catalyzed Direct CH Functionalization of Benzoquinone

A direct Pd‐catalyzed C? H functionalization of benzoquinone (BQ) can be controlled to give either mono‐ or disubstituted BQ, including the installation of two different groups in a one‐pot procedure. BQ can now be directly functionalized with aryl, heteroaryl, cycloalkyl, and cycloalkene groups and, moreover, the reaction is conducted in environmentally benign water or acetone as solvents.     

Copper‐Catalyzed Trifluoromethylation of Internal Olefinic CH Bonds: Efficient Routes to Trifluoromethylated Tetrasubstituted Olefins and N‐Heterocycles

The functionalization of internal olefins has been a challenging task in organic synthesis. Efficient Cu^II‐catalyzed trifluoromethylation of internal olefins, that is, α‐oxoketene dithioacetals, has been achieved by using Cu(OH)₂ as a catalyst and TMSCF₃ as a trifluoromethylating reagent. The push–pull effect from the polarized olefin substrates facilitates the internal olefinic C?H trifluoromethylation. Cyclic and acyclic dithioalkyl α‐oxoketene acetals were used as the substrates and various substituents were tolerated. The internal olefinic C?H bond cleavage was not involved in the rate‐determining step, and a mechanism that involves radicals is proposed based on a TEMPO‐quenching experiment of the trifluoromethylation reaction. Further derivatization of the resultant CF₃ olefins led to multifunctionalized tetrasubstituted CF₃ olefins and trifluoromethylated N‐heterocycles.     

Mechanistic Study on Rh‐Catalyzed Stereoselective CC/CH Activation of tert‐Cyclobutanols

A mechanistic study was performed on the Rh‐catalyzed stereoselective C?C/C?H activation of tert‐cyclobutanols. The present study corroborated the previous proposal that the reaction occurs by metalation, β‐C elimination, 1,4‐Rh transfer, C?O insertion, and a final catalyst‐regeneration step. The rate‐determining step was found to be the 1,4‐Rh transfer step, whereas the stereoselectivity‐determining step did not correspond to any of the aforementioned steps. It was found that both the thermodynamic stability of the product of the β‐C elimination and the kinetic feasibility of the 1,4‐Rh transfer and C?O insertion steps made important contributions. In other words, three steps (i.e., β‐C elimination, 1,4‐Rh transfer, and C?O insertion) were found to be important in determining the configurations of the two quaternary stereocenters.     

Silver‐Mediated Oxidative Aliphatic CH Trifluoromethylthiolation

The first example of a practical and direct trifluoromethylthiolation reaction of unactivated aliphatic C? H bonds employs a silver‐based reagent. The reaction is operationally simple, scalable, and proceeds under aqueous conditions in air. Furthermore, its broad scope and good functional‐group compatibility were demonstrated by applying this method to the selective trifluoromethylthiolation of natural products and natural‐product derivatives.     

Rhodium‐Catalyzed Directed Sulfenylation of Arene CH Bonds

The rhodium‐catalyzed intermolecular direct C?H thiolation of arenes with aryl and alkyl disulfides was developed for the first time to provide a convenient route to aryl thioethers. This strategy is compatible with many different directing groups and exhibits excellent functional group tolerance. More significantly, mono‐ or dithiolation can be selectively achieved, thus providing a straightforward way for selective preparation of aryl thioethers and dithioethers.     

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.     

The Cross‐Dehydrogenative Coupling of CH Bonds: A Versatile Strategy for CC Bond Formations

Over the last decade, substantial research has led to the introduction of an impressive number of efficient procedures which allow the selective construction of C? C bonds by directly connecting two different C? H bonds under oxidative conditions. Common to these methodologies is the generation of the reactive intermediates in situ by activation of both C? H bonds. This strategy was introduced by the group of Li as cross‐dehydrogenative coupling (CDC) and discloses waste‐minimized synthetic alternatives to classic coupling procedures which rely on the use of prefunctionalized starting materials. This Review highlights the recent progress in the field of cross‐dehydrogenative C? C formations and provides a comprehensive overview on existing procedures and employed methodologies.     

Iridium‐Catalyzed Enantioselective CH Alkylation of Ferrocenes with Alkenes Using Chiral Diene Ligands

The first catalytic and enantioselective C? H alkylation of ferrocene derivatives with various alkenes was achieved. A cationic iridium complex, having a chiral diene ligand, and an isoquinolyl moiety as a directing group are essential for regioselective and enantioselective C? H bond activation.     

Palladium‐Catalyzed CH Activation of N‐Allyl Imines: Regioselective Allylic Alkylations to Deliver Substituted Aza‐1,3‐Dienes

A new mode of activation of an imine via a rare aza‐substituted π‐allyl complex is described. Palladium‐catalyzed C(sp³)? H activation of the N‐allyl imine and the subsequent nucleophilic attack by the α‐alkyl cyanoester produced the 1‐aza‐1,3‐diene as the sole regioisomer. In contrast, nucleophilic attack by the α‐aryl cyanoester exclusively delivered the 2‐aza‐1,3‐diene, which was employed in an inverse‐electron‐demand Diels–Alder reaction for heterobiaryl synthesis.