Aromatic Trifluoromethylselenolation via Pd-catalyzed C−H functionalization

The synthesis of trifluoromethylselenolated aromatic molecules via an auxiliary-assisted, palladium catalyzed, C−H bonds functionalization with trifluoromethyl tolueneselenosulfonate as reagent is described. The mono- or bis-products can be preferentially formed. Some mechanistic investigations were realized to better understand the reaction. This methodology was also extended to fluoroalkylselenyl groups.     

Pd-Catalyzed Directed Thiocyanation Reaction by C−H Bond Activation

The Pd-catalyzed directed thiocyanation reaction of arenes and heteroarenes by C−H bond activation was achieved. In the presence of an electrophilic SCN source, this original methodology offered an efficient tool to access a panel of functionalized thiocyanated compounds (21 examples, up to 78 % yield). Post-functionalization reactions further demonstrated the synthetic utility of the approach by converting the SCN-containing molecules into value-added scaffolds.     

Design of Chiral NHC-Carboxylates as Potential Ligands for Pd-Catalyzed Enantioselective C−H Activation

Despite numerous efforts, the synthesis of scalemic carbo- and heterocycles through Pd⁰-catalyzed C(sp³)−H activation employing chiral ancillary ligands or chiral bases is still limited. Inspired by the recently reported outstanding performance of IBiox-type NHC ligands and bifunctional ligands in similar transformations, a new class of bifunctional NHC-ligands bearing a pendant carboxylate group was designed. A library of 10 imidazolium-carboxylic acids was obtained in five to six steps from enantiopure l -tert-leucinol. In addition, four well-defined Pd(DMBPA)-NHC palladacycles were synthesized in good to excellent yields from the corresponding imidazolium precursors. These complexes were tested in a prototypical C(sp³)−H arylation reaction, and the most active one afforded the indoline product in low yield but significant enantioselectivity. These new bifunctional NHCs could find broader applications in catalytic enantioselective transformations occurring under milder conditions.     

On-Surface Synthesis of One-Dimensional Carbon-Based Nanostructures via C−X and C−H Activation Reactions

The past decades have witnessed the emergence of low-dimensional carbon-based nanostructures owing to their unique properties and various subsequent applications. It is of fundamental importance to explore ways to achieve atomically precise fabrication of these interesting structures. The newly developed on-surface synthesis approach provides an efficient strategy for this challenging issue, demonstrating the potential of atomically precise preparation of low-dimensional nanostructures. Up to now, the formation of various surface nanostructures, especially carbon-based ones, such as graphene nanoribbons (GNRs), kinds of organic (organometallic) chains and films, have been achieved via on-surface synthesis strategy, in which in-depth understanding of the reaction mechanism has also been explored. This review article will provide a general overview on the formation of one-dimensional carbon-based nanostructures via on-surface synthesis method. In this review, only a part of the on-surface chemical reactions (specifically, C−X (X=Cl, Br, I) and C−H activation reactions) under ultra-high vacuum conditions will be covered.     

Synthesis of Conjugated Polymers via Transition Metal Catalysed C−H Bond Activation

Transition metal catalysed C−H bond activation chemistry has emerged as an exciting and promising approach in organic synthesis. This allows us to synthesize a wider range of functional molecules and conjugated polymers in a more convenient and more atom economical way. The formation of C−C bonds in the construction of pi-conjugated systems, particularly for conjugated polymers, has benefited much from the advances in C−H bond activation chemistry. Compared to conventional transition-metal catalysed cross-coupling polymerization such as Suzuki and Stille cross-coupling, pre-functionalization of aromatic monomers, such as halogenation, borylation and stannylation, is no longer required for direct arylation polymerization (DArP), which involve C−H/C−X cross-coupling, and oxidative direct arylation polymerization (Ox-DArP), which involves C−H/C−H cross-coupling protocols driven by the activation of monomers’ C(sp²)−H bonds. Furthermore, poly(annulation) via C−H bond activation chemistry leads to the formation of unique pi-conjugated moieties as part of the polymeric backbone. This review thus summarises advances to date in the synthesis of conjugated polymers utilizing transition metal catalysed C−H bond activation chemistry. A variety of conjugated polymers via DArP including poly(thiophene), thieno[3,4-c]pyrrole-4,6-dione)-containing, fluorenyl-containing, benzothiadiazole-containing and diketopyrrolopyrrole-containing copolymers, were summarized. Conjugated polymers obtained through Ox-DArP were outlined and compared. Furthermore, poly(annulation) using transition metal catalysed C−H bond activation chemistry was also reviewed. In the last part of this review, difficulties and perspective to make use of transition metal catalysed C−H activation polymerization to prepare conjugated polymers were discussed and commented.     

Ligand-Enabled Palladium-Catalyzed Through-Space C−H Bond Activation via a Carbopalladation/1,4-Pd Migration/C−H Functionalization Sequence

We report, herein, a palladium-catalyzed cascade comprising carbopalladation, 1,4-Pd-migration and C(sp²)−C(sp²) bond formation to construct a variety of bis-heterocyclic frameworks in a single operational step. The methodology provides a direct approach to introduce an oxadiazole core at a remote location without any functional group obligation, with moderate to good yields.     

Transformations of Aryl Ketones via Ligand-Promoted C−C Bond Activation

The coupling of aromatic electrophiles (aryl halides, aryl ethers, aryl acids, aryl nitriles etc.) with nucleophiles is a core methodology for the synthesis of aryl compounds. Transformations of aryl ketones in an analogous manner via carbon–carbon bond activation could greatly expand the toolbox for the synthesis of aryl compounds due to the abundance of aryl ketones. An exploratory study of this approach is typically based on carbon–carbon cleavage triggered by ring-strain release and chelation assistance, and the products are also limited to a specific structural motif. Here we report a ligand-promoted β-carbon elimination strategy to activate the carbon–carbon bonds, which results in a range of transformations of aryl ketones, leading to useful aryl borates, and also to biaryls, aryl nitriles, and aryl alkenes. The use of a pyridine-oxazoline ligand is crucial for this catalytic transformation. A gram-scale borylation reaction of an aryl ketone via a simple one-pot operation is reported. The potential utility of this strategy is also demonstrated by the late-stage diversification of drug molecules probenecid, adapalene, and desoxyestrone, the fragrance tonalid as well as the natural product apocynin.     

Size Effects in Gas-phase C−H Activation

The gas-phase clusters reaction permits addressing fundamental aspects of the challenges related to C−H activation. The size effect plays a key role in the activation processes as it may substantially affect both the reactivity and selectivity. In this paper, we reviewed the size effect related to the hydrocarbon oxidation by early transition metal oxides and main group metal oxides, methane activation mediated by late transition metals. Based on mass-spectrometry experiments in conjunction with quantum chemical calculations, mechanistic discussions were reviewed to present how and why the size greatly regulates the reactivity and product distribution.     

Cross-Dehydrogenative Coupling Polymerization via C−H Activation for the Synthesis of Conjugated Polymers

Owing to their versatile (opto)electronic properties, conjugated polymers have found application in several organic electronic devices. Cross-coupling reactions such as Stille, Suzuki, Kumada couplings, and direct arylation reactions have proved to be effective for their synthesis. More atom-efficient oxidative direct arylation polymerization has also been reported for making homopolymers. However, growing interest toward donor-acceptor polymers has led to the recent emergence of cross-dehydrogenative coupling (CDC) polymerization to synthesize alternating copolymers without any prefunctionalization of monomers. Metal-catalyzed cross-coupling of two simple arenes via double C−H activation, or of an arene with an alkene via oxidative Heck-type reaction have been used so far for CDC polymerization. In this article, we discuss the development of CDC polymerization protocols along with the relevant small molecule CDC reactions for an improved understanding of these reactions.     

Ruthenium-Catalyzed Activation of Nonpolar C−C Bonds via π-Coordination-Enabled Aromatization

Activation of C−C bonds allows editing of molecular skeletons, but methods for selective activation of nonpolar C−C bonds in the absence of a chelation effect or a driving force derived from opening of a strained ring are scarce. Herein, we report a method for ruthenium-catalyzed activation of nonpolar C−C bonds of pro-aromatic compounds by means of π-coordination-enabled aromatization. This method was effective for cleavage of C−C(alkyl) and C−C(aryl) bonds and for ring-opening of spirocyclic compounds, providing an array of benzene-ring-containing products. The isolation of a methyl ruthenium complex intermediate supports a mechanism involving ruthenium-mediated C−C bond cleavage.     

Aryne Multicomponent Reactions by Directed C−H Activation

Arylation via ortho C−H activation by the aid of directing groups has been explored recently by many researchers. Herein, a palladium-catalyzed C−H arylation using 8-aminoquinoline as a bidentate directing group has been developed. The reaction furnishes only C−H arylation, unlike previous methods where cyclization to corresponding isoquinolones is observed. More interestingly, sequential C−H functionalization was observed when methylacrylate and acrylonitrile was added; this led to C−H olefination with the aryl group, which was installed from the aryne precursor.     

Nickel-Catalyzed Reductive Allyl−Aryl Cross-Electrophile Coupling via Allylic C−F Bond Activation

Nickel-catalyzed reductive cross-coupling of allylic difluorides with aryl iodides was achieved via allylic C−F bond activation. Based on this protocol, a series of γ-arylated monofluoroalkenes were synthesized in moderate to high yields with high Z-selectivities. Mechanistic studies suggest that the C−I bonds of the aryl iodides and the C−F bonds of the allylic difluorides were cleaved via oxidative addition and β-fluorine elimination, respectively, where the oxidative addition of less reactive C−F bonds was avoided to permit their transformation.     

Selective Labeling of Peptides with o-Carboranes via Manganese(I)-Catalyzed C−H Activation

A robust method for the selective labeling of peptides via manganese(I) catalysis was devised to achieve the C-2 alkenylation of tryptophan containing peptides with 1-ethynyl-o-carboranes. The manganese-catalyzed C−H activation was accomplished with high catalytic efficiency, and featured low toxicity, high functional group tolerance and excellent E-stereoselectivity. This approach unravels a promising tool for the assembly of o-carborane with structurally complex peptides of relevance to applications in boron neutron capture therapy.     

Divergent Coupling of Benzocyclobutenones with Indoles via C−H and C−C Activations

Highly selective divergent coupling reactions of benzocyclobutenones and indoles, in which the chemoselectivity is controlled by catalysts, are reported herein. The substrates undergo C2(indole)–C8(benzocyclobutenone) coupling to produce benzylated indoles and benzo[b]carbazoles in the Ni- and Ru-catalyzed reactions. A completely different selectivity pattern C2(indole)–C2(benzocyclobutenone) coupling to form arylated indoles is observed in the Rh-catalyzed reaction. Preliminary mechanistic studies suggest C−H and C−C activations in the reaction pathway. Synthetic utility of this protocol is demonstrated by the selective synthesis of three different types of carbazoles from the representative products.     

Catalyst Deactivation During Rhodium Complex-Catalyzed Propargylic C−H Activation

Detailed mechanistic investigations on our previously reported synthesis of branched allylic esters by the rhodium complex-catalyzed propargylic C−H activation have been carried out. Based on initial mechanistic studies, we present herein more detailed investigations of the reaction mechanism. For this, various analytical (NMR, X-ray crystal structure analysis, Raman) and kinetic methods were used to characterize the formation of intermediates under the reaction conditions. The knowledge obtained by this was used to further optimize the previous conditions and generate a more active catalytic system.     

Synthesis of Heptagon-Containing Polyarenes by Catalytic C−H Activation

Nanocarbons incorporating non-hexagonal aromatic rings - such as five-, seven-, and eight-membered rings - have various intriguing physical properties such as curved structures, unique one-dimensional packing, and promising magnetic, optical, and conductivity properties. Herein, we report an efficient synthetic approach to polycyclic aromatics containing seven-membered rings via a palladium-catalyzed intramolecular Ar−H/Ar−Br coupling. In addition to all-hydrocarbon scaffolds, heteroatom-embedded heptagon-containing polyarenes can be efficiently constructed with this method. Rhodium- and palladium-catalyzed sequential six- and seven-membered ring formations also afford complex heptagon-containing molecular nanocarbons from readily available arylacetylenes and biphenyl boronic acids. Detailed mechanistic analysis by DFT calculations showed the feasibility of seven-membered ring formation by a concerted metalation-deprotonation mechanism. This reaction can serve as a template for the synthesis of a wide range of seven-membered ring-containing molecular nanocarbons.     

Homolytic C−H Bond Activation by Phosphine−Quinone-Based Radical Ion Pairs

Herein, we present the formation of transient radical ion pairs (RIPs) by single-electron transfer (SET) in phosphine−quinone systems and explore their potential for the activation of C−H bonds. PMes₃ (Mes=2,4,6-Me₃C₆H₂) reacts with DDQ (2,3-dichloro-5,6-dicyano-1,4-benzoquinone) with formation of the P−O bonded zwitterionic adduct Mes₃P−DDQ ( 1 ), while the reaction with the sterically more crowded PTip₃ (Tip=2,4,6-iPr₃C₆H₂) afforded C−H bond activation product Tip₂P(H)(2-[CMe₂(DDQ)]-4,6-iPr₂-C₆H₂) ( 2 ). UV/Vis and EPR spectroscopic studies showed that the latter reaction proceeds via initial SET, forming RIP [PTip₃]⋅⁺[DDQ]⋅⁻, and subsequent homolytic C−H bond activation, which was supported by DFT calculations. The isolation of analogous products, Tip₂P(H)(2-[CMe₂{TCQ−B(C₆F₅)₃}]-4,6-iPr₂-C₆H₂) ( 4 , TCQ=tetrachloro-1,4-benzoquinone) and Tip₂P(H)(2-[CMe₂{oQ^tBu−B(C₆F₅)₃}]-4,6-iPr₂-C₆H₂) ( 8 , oQ^tBu=3,5-di-tert-butyl-1,2-benzoquinone), from reactions of PTip₃ with Lewis-acid activated quinones, TCQ−B(C₆F₅)₃ and oQ^tBu−B(C₆F₅)₃, respectively, further supports the proposed radical mechanism. As such, this study presents key mechanistic insights into the homolytic C−H bond activation by the synergistic action of radical ion pairs.     

Catalytic C−C/C−H Bond Activation Relay for Synthesis of Fluorescent Naphthoquinolizinium Salts

Herein, we report the design and synthesis of a series of novel cationic nitrogen-embedded polyaromatic hydrocarbons with a planar geometry. The synthetic pathway is based on catalytic C−C/C−H bond activation relay that enabled preparation of regioselectively 5,6,10,11-tetrasubstituted naphtho[2,1,8-ija]quinolizinium salts bearing various types of substituents. Single-crystal X-ray analyses of selected compounds confirmed planarity of the quinolizinium core. Most of the prepared compounds exhibited strong fluorescence (Φ_s up to >99 %) ranging from 420–600 nm depending on the substitution pattern. According to DFT calculations LUMO is always distributed over the quinolizinium framework regardless of the attached substituents, whereas delocalization of HOMO is related to the substitution pattern. Electrochemical measurements show irreversible reduction of all compounds, which is supported by the calculated location of LUMO orbitals.     

C―H Activation

<正>Conventional syntheses of organic chemicals rely mostly on reactions between various reactive functional groups and reagents. Mechanistically, they are dominated by the involvement of highly reactive intermediates such as carbocations, carbanions, radicals and carbenes. Due to the high dissociation energy and low acidity of common C―H bonds,     

Chiral Catalysts for Pd0-Catalyzed Enantioselective C−H Activation

In the past few decades, processes that involve transition-metal catalysis have represented a major part of the synthetic chemist′s toolbox. Recently, the interest has shifted from the well-established cross-coupling reactions to C−H bond functionalization, thus making it a current frontier of transition-metal-catalyzed reactions. Constant progress in this field has led to the discovery of enantioselective methods to generate and control various types of stereogenic elements, thereby demonstrating its high value to generate scalemic chiral molecules. The present review is dedicated to enantioselective Pd⁰-catalyzed C−H activation, which may be considered as an evolution of Pd⁰-catalyzed cross-couplings, with a focus on the different chiral ligands and catalysts that enable these transformations.