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.     

Rhodium Complexes in P−H Bond Activation Reactions

The feasibility of oxidative addition of the P−H bond of PHPh₂ to a series of rhodium complexes to give mononuclear hydrido-phosphanido complexes has been analyzed. Three main scenarios have been found depending on the nature of the L ligand added to [Rh(Tp)(C₂H₄)(PHPh₂)] (Tp= hydridotris(pyrazolyl)borate): i) clean and quantitative reactions to terminal hydrido-phosphanido complexes [RhTp(H)(PPh₂)(L)] (L=PMe₃, PMe₂Ph and PHPh₂), ii) equilibria between Rh^I and Rh^III species: [RhTp(H)(PPh₂)(L)]⇄[RhTp(PHPh₂)(L)] (L=PMePh₂, PPh₃) and iii) a simple ethylene replacement to give the rhodium(I) complexes [Rh(κ²-Tp)(L)(PHPh₂)] (L=NHCs-type ligands). The position of the P−H oxidative addition–reductive elimination equilibrium is mainly determined by sterics influencing the entropy contribution of the reaction. When ethylene was used as a ligand, the unique rhodaphosphacyclobutane complex [Rh(Tp)(η¹-Et)(κ^C,P-CH₂CH₂PPh₂)] was obtained. DFT calculations revealed that the reaction proceeds through the rate limiting oxidative addition of the P−H bond, followed by a low-barrier sequence of reaction steps involving ethylene insertion into the Rh−H and Rh−P bonds. In addition, oxidative addition of the P−H bond in OPHPh₂ to [Rh(Tp)(C₂H₄)(PHPh₂)] gave the related hydride complex [RhTp(H)(PHPh₂)(POPh₂)], but ethyl complexes resulted from hydride insertion into the Rh−ethylene bond in the reaction with [Rh(Tp)(C₂H₄)₂].     

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.     

Thiourea-Catalyzed C−F Bond Activation: Amination of Benzylic Fluorides

We describe the first thiourea-catalyzed C−F bond activation. The use of a thiourea catalyst and Ti(OiPr)₄ as a fluoride scavenger allows the amination of benzylic fluorides to proceed in moderate to excellent yields. Preliminary results with S- and O-based nucleophiles are also presented. DFT calculations reveal the importance of hydrogen bonds between the catalyst and the fluorine atom of the substrate to lower the activation energy during the transition state.     

Controlling Metal-Oxide Reducibility for Efficient C−H Bond Activation in Hydrocarbons

Knowing the structure of catalytically active species/phases and providing methods for their purposeful generation are two prerequisites for the design of catalysts with desired performance. Herein, we introduce a simple method for precise preparation of supported/bulk catalysts. It utilizes the ability of metal oxides to dissolve and to simultaneously precipitate during their treatment in an aqueous ammonia solution. Applying this method for a conventional VO_x−Al₂O₃ catalyst, the concentration of coordinatively unsaturated Al sites was tuned simply by changing the pH value of the solution. These sites affect the strength of V−O−Al bonds of isolated VO_x species and thus the reducibility of the latter. This method is also applicable for controlling the reducibility of bulk catalysts as demonstrated for a CeO₂−ZrO₂−Al₂O₃ system. The application potential of the developed catalysts was confirmed in the oxidative dehydrogenation of ethylbenzene to styrene with CO₂ and in the non-oxidative propane dehydrogenation to propene. Our approach is extendable to the preparation of any metal oxide catalysts dissolvable in an ammonia solution.     

C−F Bond Activation Mediated by Phosphorus Compounds

The activation and functionalization of C−F bonds has garnered significant attention in the scientific community as a strategy to mitigate toxicity and environmental concerns, as well as provide new pathways to agro- and pharmaceutical chemicals and materials. Although several transition-metal-based systems have been developed for this transformation, the use of main-group compounds remains less explored. In recent years, several strategies for C−F bond activation have focused on the use of phosphorus-based reagents. In this Minireview, an overview of strategies is provided that exploits P^V and P^III-based Lewis acids as well as P^III Lewis bases in frustrated Lewis pair (FLP) protocols for hydrodefluorination, C−C couplings and C−F derivatizations.     

Nickel-Catalyzed Suzuki-Miyaura Cross-Coupling Involving C−O Bond Activation

An efficient Suzuki-Miyaura cross-coupling reaction of ortho-phenoxy-substituted aromatic amides with aryl boronates is described. The use of LiO^tBu is crucial for the success of the reaction. An amidate anion, which is formed through deprotonation of the amide NH bond by LiO^tBu, functions as a directing group to activate a C−O bond.     

Nickel-Mediated Trifluoromethylation of Phenol Derivatives by Aryl C−O Bond Activation

The increasing pharmaceutical importance of trifluoromethylarenes has stimulated the development of more efficient trifluoromethylation reactions. Tremendous efforts have focused on copper- and palladium-mediated/catalyzed trifluoromethylation of aryl halides. In contrast, no general method exists for the conversion of widely available inert electrophiles, such as phenol derivatives, into the corresponding trifluoromethylated arenes. Reported herein is a practical nickel-mediated trifluoromethylation of phenol derivatives with readily available trimethyl(trifluoromethyl)silane (TMSCF₃). The strategy relies on PMe₃-promoted oxidative addition and transmetalation, and CCl₃CN-induced reductive elimination. The broad utility of this transformation has been demonstrated through the direct incorporation of trifluoromethyl into aromatic and heteroaromatic systems, including biorelevant compounds.     

Redox-Induced Oxidative C−C Bond Cleavage of 2,2′-Pyridil in Diruthenium Complexes

In the recent years, there has been an emerging research interest in the domain of C−C bond-cleavage reactions. The present contribution deals with the redox-mediated dioxygen activation and C−C bond cleavage in a diruthenium complex [(acac)₂Ru^II(μ-L1)Ru^II(acac)₂], 1 (acac=acetylacetonate) incorporating 2,2′-pyridil (L1) as the bridging ligand. The above process leads to a C−C-cleaved monomeric product [(acac)₂Ru^III(pic⁻)], 2 (pic⁻=piconilate). Intriguingly, similar diastereomeric complexes [(acac)₂Ru^II(μ-L2)Ru^II(acac)₂], meso (ΔΛ): 3 a and rac (ΔΔ/ΛΛ): 3 b , involving an analogous diimine bridge (L2=N1,N2-diphenyl-1,2-di(pyridin-2-yl)ethane-1,2-diimine), were stable towards such oxidative transformations. Electrochemical and spectroelectrochemical studies, in combination, establish the potential non-innocent feature of the 2,2′-Pyridil (L1) and its derivative (L2) both in oxidation and reduction processes. Additionally, theoretical calculations have been employed to verify the redox states and their behavior. Furthermore, transition state (TS) calculations at the M06L/6-31G*/LANL2DZ level of theory together with detailed kinetic studies outline a putative mechanism for the selective transformation of 1 → 2 involving the formation of an intermediate bearing peroxide linkage to complex 1 .     

Carbon Monoxide Activation by a Molecular Aluminium Imide: C−O Bond Cleavage and C−C Bond Formation

Anionic molecular imide complexes of aluminium are accessible via a rational synthetic approach involving the reactions of organo azides with a potassium aluminyl reagent. In the case of K₂[( NON )Al(NDipp)]₂ ( NON =4,5-bis(2,6-diisopropylanilido)-2,7-di-tert-butyl-9,9-dimethyl-xanthene; Dipp=2,6-diisopropylphenyl) structural characterization by X-ray crystallography reveals a short Al−N distance, which is thought primarily to be due to the low coordinate nature of the nitrogen centre. The Al−N unit is highly polar, and capable of the activation of relatively inert chemical bonds, such as those found in dihydrogen and carbon monoxide. In the case of CO, uptake of two molecules of the substrate leads to C−C coupling and C≡O bond cleavage. Thermodynamically, this is driven, at least in part, by Al−O bond formation. Mechanistically, a combination of quantum chemical and experimental observations suggests that the reaction proceeds via exchange of the NR and O substituents through intermediates featuring an aluminium-bound isocyanate fragment.     

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.     

Photoredox-Catalyzed Isomerization of Highly Substituted Allylic Alcohols by C−H Bond Activation

Photoredox-catalyzed isomerization of γ-carbonyl-substituted allylic alcohols to their corresponding carbonyl compounds was achieved for the first time by C−H bond activation. This catalytic redox-neutral process resulted in the synthesis of 1,4-dicarbonyl compounds. Notably, allylic alcohols bearing tetrasubstituted olefins can also be transformed into their corresponding carbonyl compounds. Density functional theory calculations show that the carbonyl group at the γ-position of allylic alcohols are beneficial to the formation of their corresponding allylic alcohol radicals with high vertical electron affinity, which contributes to the completion of the photoredox catalytic cycle.     

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.     

C−H Bond Activation by Iridium(III) and Iridium(IV) Oxo Complexes

Oxidation of an iridium(III) oxo precursor enabled the structural, spectroscopic, and quantum-chemical characterization of the first well-defined iridium(IV) oxo complex. Side-by-side examination of the proton-coupled electron transfer thermochemistry revealed similar driving forces for the isostructural oxo complexes in two redox states due to compensating contributions from H⁺ and e⁻ transfer. However, C−H activation of dihydroanthracene revealed significant hydrogen tunneling for the distinctly more basic iridium(III) oxo complex. Our findings complement the growing body of data that relate tunneling to ground state properties as predictors for the selectivity of C−H bond activation.     

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.     

Influence of the Flexibility of Nickel PCP-Pincer Complexes on C−H and P−C Bond Activation and Ethylene Reactivity: A Combined Experimental and Theoretical Investigation

Using a pincer platform based on a bridgehead NHC donor with functional side arms, the combined effect of increased flexibility in six-membered pyrimidine-type heterocycles compared to the more often studied five-membered imidazole, and rigidity of phosphane side arms was examined. The unique features observed include: 1) the reaction of the azolium C_sp2−H bond with [Ni(cod)₂] affording a carbanionic ligand in [NiCl(PC_sp3^HP)] ( 8 ) rather than a carbene; 2) its transformation into the NHC, hydrido complex [NiH(PC^NHCP)]PF₆ ( 9 ) upon halide abstraction; 3) ethylene insertion into the Ni−H bond of the latter and ethyl migration to the N−C−N carbon atom of the heterocycle in [Ni(PC^EtP)]PF₆ ( 10 ); and 4) an unprecedented C−P bond activation transforming the P−C^NHC−P pincer ligand of 8 in a C−C^NHC−P pincer and a terminal phosphanido ligand in [Ni(PPh₂)(CC^NHCP)] ( 15 ). The data are supported by nine crystal structure determinations and theoretical calculations provided insights into the mechanisms of these transformations, which are relevant to stoichiometric and catalytic steps of general interest.     

Electrosynthetic C−O Bond Activation in Alcohols and Alcohol Derivatives

Alcohols and their derivatives are ubiquitous and versatile motifs in organic synthesis. Deoxygenative transformations of these compounds are often challenging due to the thermodynamic penalty associated with the cleavage of the C−O bond. However, electrochemically driven redox events have been shown to facilitate the C−O bond cleavage in alcohols and their derivatives either through direct electron transfer or through the use of electron transfer mediators and electroactive catalysts. Herein, a comprehensive overview of preparative electrochemically mediated protocols for C−O bond activation and functionalization is detailed, including direct and indirect electrosynthetic methods, as well as photoelectrochemical strategies.     

Enantioselective Cleavage of Cyclobutanols Through Ir-Catalyzed C−C Bond Activation: Mechanistic and Synthetic Aspects

The Ir-catalyzed conversion of prochiral tert-cyclobutanols to β-methyl-substituted ketones proceeds under comparably mild conditions in toluene (45–110 °C) and is particularly suited for the enantioselective desymmetrization of β-oxy-substituted substrates to give products with a quaternary chirality center with up to 95 % ee using DTBM-SegPhos as a chiral ligand. Deuteration experiments and kinetic isotope effect measurements revealed major mechanistic differences to related Rh^I-catalyzed transformations. Supported by DFT calculations we propose the initial formation of an Ir^III hydride intermediate, which then undergoes a β-C elimination (C−C bond activation) prior to reductive C−H elimination. The computational model also allows the prediction of the stereochemical outcome. The Ir-catalyzed cyclobutanol cleavage is broadly applicable but fails for substrates bearing strongly coordinating groups. The method is of particular value for the stereo-controlled synthesis of substituted chromanes related to the tocopherols and other natural products.     

Intermolecular Carbophosphination of Alkynes with Phosphole Oxides via Ni−Al Bimetal-Catalyzed C−P Bond Activation

Intermolecular carbophosphination reaction of alkynes or alkenes with unreactive C−P bonds remains an elusive challenge. Herein, we used a Ni−Al bimetallic catalyst to realize an intermolecular carbophosphination reaction of alkynes with 5-membered phosphole oxides, providing a series of 7-membered phosphepines in up to 94 % yield.     

Photocatalyzed Hydrogen Atom Transfer Degradation of Vinyl Polymers: Cleavage of a Backbone C−C Bond Triggered by Radical Activation of a C−H Bond in a Pendant

In this work, we achieved a triggering degradation of polymers composed of carbon-carbon (C−C) bonded backbone without relying on introduction of labile heteroatom-based bond. The crucial point for the achievement is using vinyl ether (VE) as a comonomer in radical copolymerization of (meth)acrylate for introduction of the carbon-hydrogen (C−H) bonds active for photocatalyzed hydrogen atom transfer (HAT) as triggers in the pendant. Interestingly, methyl methacrylate (MMA)-n-butyl vinyl ether (NBVE) copolymer underwent degradation in acetonitrile in the presence of benzophenone (Ph₂CO) under UV irradiation at 80 °C. The degradation did not take place, when any one of UV, Ph₂CO, heat, and NBVE unit was removed or HAT-active solvent such as toluene and 1,4-dioxane was used. These control experiments strongly supported the HAT-triggering degradation. Furthermore, the degradation behaviors of the copolymers with other vinyl ethers such as tert-butyl vinyl ether and methyl isopropenyl ether indicated that the C−H bond neighboring to oxygen on the pendant is mainly responsible for the trigger leading to degradation. The HAT-triggering degradation was also demonstrated even with the acrylate-based copolymer.