Carbon-carbon Bond Activation Research Articles

Temperature-Dependent Divergent Cyclopentadiene Synthesis through Cobalt-Catalyzed C-C Activation of Cyclopropenes.

We report a temperature-dependent divergent approach to synthesize multisubstituted cyclopentadienes through cobalt-catalyzed carbon-carbon (C-C) bond activation of cyclopropenes and ring expansion with internal alkynes. By employing different heating procedures, two cyclopentadiene substitution isomers were efficiently and selectively constructed. This reaction does not require preactivation of the metal catalyst or additional reducing reagents. Preliminary mechanistic investigations suggest that the key steps are oxidative addition of the cyclopropene to cobalt catalyst, followed by alkyne insertion and 1,5-ester shift.

Palladium-Catalyzed Directed Carbon-Carbon Bond Activation of Aryl Nitriles for Cyano Transfer.

Herein, we report the C-H cyanation of indoles via a palladium-catalyzed directed C-CN activation reaction using aryl nitrile as a cyano source. The employment of the phenoxy-oriented group is the key to the cleavage of the C-CN bond. This protocol features a broad substrate scope, good efficiency, and high regioselectivity. Furthermore, the practical application of this protocol was showcased in the late-stage functionalization and synthesis of indole derivatives, which were derived from drugs and natural products, through the process of cyanation.

Rhodium catalyzed tunable amide homologation through a hook-and-slide strategy.

Preparation of diverse homologs from lead compounds has been a common and important practice in medicinal chemistry. However, homologation of carboxylic acid derivatives, particularly amides, remains challenging. Here we report a hook-and-slide strategy for homologation of tertiary amides with tunable lengths of the inserted carbon chain. Alkylation at the α-position of the amide (hook) is followed by highly selective branched-to-linear isomerization (slide) to effect amide migration to the end of the newly introduced alkyl chain; thus, the choice of alkylation reagent sets the homologation length. The key step involves a carbon-carbon bond activation process by a carbene-coordinated rhodium complex with assistance from a removable directing group. The approach is demonstrated for introduction of chains as long as 16 carbons and is applicable to derivatized carboxylic acids in complex bioactive molecules.

Pd-Catalyzed Activation of Carbon-Carbon Bonds in Hydroxymethylfurfural Derivatives.

Palladium-catalyzed activation of C-C bonds in organic molecules is a powerful tool for the synthesis of value-added compounds. 5-Hydroxymethylfurfural (HMF) derivatives are a promising class of biomass-derived chemicals that have received considerable attention due to their potential applications in the synthesis of biologically active molecules and materials. However, the selective activation of unstrained C-C bonds is a challenging task, mainly due to their relatively high bond dissociation energies. Herein, we report a palladium-catalyzed method for the efficient C-C bond activation of HMF derivatives, enabling their arylation with iodobenzenes. Mechanistic studies, including reaction-profile analysis, competition experiments and head-space IR spectroscopy suggest a decarboxylative mechanism.

Carbon-carbon bond activation by Mg, Al, and Zn complexes.

Examples of carbon-carbon bond activation reactions at Mg, Al, and Zn are described in this review. Several distinct mechanisms for C-C bond activation at these metals have been proposed, with the key C-C bond activation step occurring by (i) α-alkyl elimination, (ii) β-alkyl elimination, (iii) oxidative addition, or (iv) an electrocyclic reaction. Many of the known pathways involve an overall 2-electron redox process. Despite this, the direct oxidative addition of C-C bonds to these metals is relatively rare, instead most reactions occur through initial installation of the metal on a hydrocarbon scaffold (e.g. by a cycloaddition reaction or hydrometallation) followed by an α-alkyl or β-alkyl elimination step. Emerging applications of Mg, Al, and Zn complexes as catalysts for the functionalisation of C-C bonds are also discussed.

Exporting Homogeneous Transition Metal Catalysts to Biological Habitats.

The possibility of performing designed transition‐metal catalyzed reactions in biological and living contexts can open unprecedented opportunities to interrogate and interfere with biology. However, the task is far from obvious, in part because of the presumed incompatibly between organometallic chemistry and complex aqueous environments. Nonetheless, in the past decade there has been a steady progress in this research area, and several transition‐metal (TM)‐catalyzed bioorthogonal and biocompatible reactions have been developed. These reactions encompass a wide range of mechanistic profiles, which are very different from those used by natural metalloenzymes. Herein we present a summary of the latest progress in the field of TM‐catalyzed bioorthogonal reactions, with a special focus on those triggered by activation of multiple carbon‐carbon bonds.

Activation of carbon-carbon bonds in d9 (Co, Rh, Ir) and d8 (Ru) metal coordinated bicyclo[3.2.1]octa-2,6-diene via agostic M-H-C and M-H interactions

This contribution reveals the first synthesis, protonation reactions and skeletal rearrangements of a series of [M(η5-C5R5)(η2:η2-bicyclo[3.2.1]octa-2,6-diene or 2,6-bcod)(M=Co, Rh, Ir, R=H, Me)] 1-3 and [Ru(η6-arene)(η2:h2-bicyclo[3.2.1]octa-2,6-diene)(arene= C6Me6, C6Me4H2, C6H3Me3)] 4 complexes. Monoprotonation of these coordinated bicyclo[3.2.1]octa-2,6-diene or 2,6-bcod complexes, 1,3,4 with super acids such as HPF6 (60% aq), HBF4.Et2O or CF3SO3H at low temperature (-80° to -20 °C) forms agostic M-H-C structures for [Rh(µ-H)(η5-C5R5)(η2:h2-2,6-bcod)]+, 5, [Co(µ-H)(h5-C5H5)(h2: h2-2,6-bcod)]+6 and [Ru(µ-H)(η6-arene)(η2:h2-2,6-bcod)]+, 7. Similar reactions of 2a, b with the 5d transition metals gave terminal hydride complexes [Ir(H)(η5-C5Me5)(η2:h2-2,6-bcod)][PF6] 8a, b as isolable salts at room temperature. Initial products of all these monoprotonated cationic salts 5 - 8, undergo isomerization via hydride migration and subsequent cleavage of carbon-carbon bonds to the corresponding η2-vinyl η3-cyclohexenyl cations 9 - 12, independent of the non-coordinating anions. All metal coordinated η2- vinyl, η3-cyclohexenyl cations were isolated and characterized by 1H and 13C NMR spectroscopic methods. The structure of 9b was solved by X-ray crystallographic analysis. Nucleophilic addition of H− to the [Ruthenium(η6-hexamethyl)(η2-vinyl η3-cyclohexenyl)]PF6 cation, 12c resulted in the formation of 5-ethyl-η4-1,3-cyclohexadiene complex, 14c as the isomerized product.

Tetranuclear Dicationic Aurophilic Gold(I) Catalysts in Enyne Cycloisomerization: Cooperativity for a Dramatic Shift in Selectivity.

In comparison to mononuclear gold Lewis acid catalysts, digold complexes and dual-gold catalysis have illustrated a distinct and powerful potential for the activation of carbon-carbon multiple bonds. Herein, this concept is pushed further by designing novel tetranuclear gold(I) dicationic complexes structurally supported by strongly stabilizing constraint diphosphinoferrocenyl ligands and attractive closed-shell Au⋅⋅⋅Au aurophilic interactions. The use of a molecularly-defined tetranuclear dicationic aurophilic gold(I) precatalyst for the selectivity-challenging cycloisomerization of low-substituted 1,6-enynes favors the formation with high selectivity of strained azabicyclo[4.1.0]hept-4-enes - even in the complete absence of activating/orienting substituents on alkyne and olefin reactive functions. This selectivity is not achieved by the reported phosphine- and carbene-stabilized mono- and dinuclear cationic gold(I) complexes, including the ones formed from the same ligands. More importantly this selectivity differs also from nanoparticles and heterogeneous gold catalysts reported to date. DFT studies correlated to experimental mechanistic investigations support an unprecedented "cluster-like" reactivity from polynuclear cooperation at the origin of this peculiar selectivity where the aurophilic interactions preexist, and pre-organize, gold cluster reactive intermediates.

Catalytic Net Oxidative C-C Activation and Silylation of Cyclopropanols with a Traceless Acetal Directing Group.

Redox-neutral carbon-carbon (C-C) bond activation and functionalization strategies of cyclopropanols that give metallo homoenolate have offered merits to construct a range of useful β-functionalized ketones in an inverse-polarity fashion. Discovery and identification of oxidative C-C activation reactions of cyclopropanols that generate metallo enolate-homoenolate would provide an opportunity to afford α,β-difunctionalized ketones. We report catalytic, net oxidative C-C activation, and silylation of cyclopropanols with traceless acetal directing groups under consecutive Ir and Rh catalysis in regio-, stereo-, and chemo-selective fashion. In detail, Ir-catalyzed hydrosilylation of cyclopropyl acetates provides the acetal directing group in quantitative yield. Rh-catalyzed proximal C-C silylation of the resulting cyclopropyl silyl acetal produces the metallo enolate-homoenolate equivalent, dioxasilepine, which uniquely holds an interconnected β-silyl moiety and Z-vinyl acetal. Upon sequential treatment of a silaphile that removes the acetal directing group and electrophile, the seven-membered silicon-containing heterocycle, serving as the ketone α,β-dianion equivalent, delivers α,β-difunctionalized ketones. Scope of the hitherto unexplored reactivity of cyclopropanols toward net oxidative C-C silylation and the versatility of the resulting dioxasilepines were demonstrated. These include late-stage, net oxidative C-C silylation of biologically relevant molecules and facile production of a range of α,β-difunctionalized ketones. Preliminary mechanistic studies suggest that the C-C activation harnessing the electron-rich Wilkinson-type catalyst is likely the turnover-determining step and a Rh-π interaction is the key to the efficient metal insertion to the proximal C-C bond in cyclopropanols.

Metal-free alkylation of quinoxalinones with aryl alkyl ketones.

The first metal-free method for alkylation of quinoxalinones using cheap and stable aryl alkyl ketones as nucleophilic alkylation reagents is reported. This strategy greatly broadens the application channels of aryl alkyl ketones through carbon-carbon bond activation. In addition, the protocol has the advantages of simple operation, broad substrate scope, and good functional group tolerance.

Asymmetric dearomatization catalysed by chiral Brønsted acids via activation of ynamides.

Chiral Brønsted acid-catalysed asymmetric synthesis has received tremendous interest over the past decades, and numerous efficient synthetic methods have been developed based on this approach. However, the use of chiral Brønsted acids in these reactions is mostly limited to the activation of imine and carbonyl moieties, and the direct activation of carbon-carbon triple bonds has so far not been invoked. Here we show that chiral Brønsted acids enable the catalytic asymmetric dearomatization reactions of naphthol-, phenol- and pyrrole-ynamides by the direct activation of alkynes. This method leads to the practical and atom-economic construction of various valuable spirocyclic enones and 2H-pyrroles that bear a chiral quaternary carbon stereocentre in generally good-to-excellent yields with excellent chemo-, regio- and enantioselectivities. The activation mode of chiral Brønsted acid catalysis revealed in this study is expected to be of broad utility in catalytic asymmetric reactions that involve ynamides and the related heteroatom-substituted alkynes.

Metal-Catalyzed Carbon-Carbon Bond Cleavage of Unstrained Alcohols.

The functionalization of molecules by cleaving inert carbon-carbon single bonds is regarded as a great synthetic challenge due to their inherent stability. In recent years, significant progress has been made in the activation of small rings relying on the release of strain energy. By contrast, the number of catalytic methodologies for the activation of unstrained carbon-carbon single bonds is still limited. This review focuses on the recent developments in transition-metal-catalyzed cleavage of C-C bonds in unstrained alcohols via β-carbon elimination. Emphasis is placed on the mechanistic aspects of the discussed transformations and their applications to the deconstruction and reorganization of molecules.

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.

Remote Nickel-Catalyzed Cross-Coupling Arylation via Proton-Coupled Electron Transfer-Enabled C-C Bond Cleavage.

Cross-coupling reactions for carbon-carbon and carbon-heteroatom bond formation are of great importance in modern chemical synthesis. In addition to classical cross-couplings involving preformed or preactivated coupling partners, more recently breakthroughs have been made in the selective, direct coupling of abundant aliphatic carbon-hydrogen bonds using hydrogen atom transfer reactions in which the bond-dissociation energy is the thermodynamic driving force. The more challenging carbon-carbon bond activation is still rather underdeveloped due to the bond inertness. Herein, we report a mild and general strategy for the activation of a diverse set of readily available cyclic alcohols for the remote and site-specific arylation of ketones via the combination of photoredox-mediated multisite concerted proton-electron transfer (MS-PCET) and nickel catalysis. The current cross-coupling proceeds with the generation of an alkoxy radical utilizing bond-dissociation free energy (BDFE) as the thermodynamic driving force. Subsequently, the resulting remote carbon-centered radicals formed by C-C cleavage merge with the nickel catalytic cycle to create the challenging C(sp3)-C(sp2) bonds.

Deconstructive Functionalization of Ketones via an LMCT-Promoted C–C Cleavage

In this issue of Chem, Zuo and coworkers report an exciting new strategy for the deconstructive functionalization of ketones. Through merging Lewis-acid-catalyzed nucleophilic 1,2-addition and ligand-to-metal charge transfer (LMCT)-promoted C–C cleavage, common strained and unstrained ketones are transformed into synthetically valuable scaffolds with high efficiency under mild conditions.

Chiral N-heterocyclic Carbene Gold Complexes: Synthesis and Applications in Catalysis

N-Heterocyclic carbenes have found many applications in modern metal catalysis, due to the formation of stable metal complexes, and organocatalysis. Among a myriad of N-heterocyclic carbene metal complexes, gold complexes have gained a lot of attention due to their unique propensity for the activation of carbon-carbon multiple bonds, allowing many useful transformations of alkynes, allenes, and alkenes, inaccessible by other metal complexes. The present review summarizes synthetic efforts towards the preparation of chiral N-heterocyclic gold(I) complexes exhibiting C2 and C1 symmetry, as well as their applications in enantioselective catalysis. Finally, the emerging area of rare gold(III) complexes and their preliminary usage in asymmetric catalysis is also presented.

Agro waste derived nanosilica supported Pd(ll) complex: A protocol for copper free Sonogashira reaction in water

A palladium (II) complex immobilized onto nanosilica(Pd-imine@nanoSiO2) has been developed and evaluated as a highly efficient, retrievable catalyst for carbon-carbon triple bond activation reactions between aryl halides and terminal alkynes. Nanosilica has been derived from rice husk by simple and eco-compatible methodology. The catalyst has been extensively characterized by techniques such as FT-IR, UV–vis, powder XRD, XPS, SEM-EDX, thermogravimetric analysis, BET surface area measurement. The catalyst can be reused for five consecutive runs without compromising much with the activity. Easy preparation, its long shelf life, air-stability, wide substrate scope, ‘in water’ reactions, easy separability and good recyclability make it an ideal system for Sonogashira cross-coupling reaction. Moreover, various alkyne substrates were efficiently cross-coupled with a broad range of aryl iodides and aryl bromides to afford diaryl alkynes, providing improved yields with low catalyst loading in water. This protocol is also suitable for aliphatic alkynes.

Cleavage of carbon-carbon bonds by radical reactions.

In recent years, radical C-C bond cleavage reactions have been increasingly understood and used to perform transformations that complement traditional ionic processes. However, to date radical C-C bond cleavage/functionalization reactions have not been the subject of a dedicated review. Herein we summarize the most recent and significant developments in the radical activation and functionalization of carbon-carbon bonds, with an emphasis on both synthetic outcomes and reaction mechanisms, and highlight how these radical C-C bond cleavage reactions enable challenging transformations.

SCREENING OF THE CATALYTIC ACTIVITY OF Pd0 AND Pd2+- SUPPORTED ON CHITOSAN BEADS AND CRYOGELS

Here, we report the results of screening of the catalytic activity of Pd-containing chitosan beads and cryogels in the cross-coupling reaction, hydrogenation of alkenes, nitro-, and carbonyl compounds and the hydrodechlorination of chlorophenols. Pd0-containing chitosan beads and cryogels show moderate catalytic activity in the reduction of alkenes and nitroaromatics. The conversion of nitroaromatics decreases for substrates with electron-withdrawing substituents, while the conversion of alkenes increases with the activation of carbon-carbon double bonds. For several substrates, a significant difference in kinetics and conversion degrees was observed for Pd nanoparticles supported on chitosan beads and cryogels. It was found that conversion in the hydrodechlorination reaction depends on substrate structure, being higher for substrates containing substituents with a positive mesomeric effect. Pd2+-chitosan catalysts showed high catalytic activity in cross-coupling (Heck reaction) offering the following advantages over known catalytic systems: lower reaction temperature, the selective functionalisation of C-I bonds, and the possibility to perform reactions with iodobenzene without base addition.

Ketone C–C Bond Activation Meets the Suzuki-Miyaura Cross-coupling

In a recent issue of the Journal of the American Chemical Society, Dong and coworkers report that ketones can participate as electrophiles in the Suzuki-Miyaura cross-coupling reaction under Rh(I) catalysis. They show that activation of C–C bonds of unstrained ketones is a versatile process that can engage in cross-coupling reaction with aryl boronates.