Ruthenium Catalysis Research Articles

Ruthenium Catalyzed Formation of Fused Pyridine Derivatives or Substituted Indoles from Hydrazine‐Derived Enamines and Propargyl Alcohols

New ruthenium‐catalyzed transformations of secondary propargyl alcohols with hydrazine‐derived enamines are presented, affording fused pyridines or substituted indoles depending on the hydrazine derivative used. The cascade reactions are catalyzed by an air‐ and moisture‐stable bifunctional ruthenium complex and proceed via redox‐isomerization of the propargyl alcohol, subsequent Michael addition and cyclocondensation. In case of phenylhydrazine a Fischer‐indole synthesis also takes place, prior to the final release of the products. The produced heterocyclic motifs are important scaffolds in medicinal and agricultural chemistry.

Ruthenium-Catalyzed Interrupted Transfer Hydrogenation: An Approach for Reductive Functionalization of Quinolinium and Napthyridinium Salts.

Until now, a myriad of effective approaches have emerged for the functionalization of N-heteroaryl C-H bonds. In contrast, dearomatization and construction of fused heterocycles from activated heteroarenes is still a subject to explore. In this work, we present a refined approach for both dearomatization of N-heteroarenes and the synthesis of fused heterocycles from activated heteroarenes ruthenium catalysis using paraformaldehyde along with additive and base. Notably, quinolinium salts with a hydrogen at the C-4 position yield a methoxymethyl-substituted fused cyclic product through the Thorpe Ingold effect. An innovative aspect of this research is the dual functionality of paraformaldehyde as both a hydride donor and electrophile, utilizing readily available feedstock chemicals. A broad range of electron withdrawing and donating substituents was tolerable under standardized reaction conditions.

Ruthenium Catalyzed Additive‐Free N‐Formylation of Amines with CO2 and H2: Exploring Carbon Neutral Hydrogen Cycle

Ruthenium Catalyzed Additive‐Free N‐Formylation of Amines with CO2 and H2: Exploring Carbon Neutral Hydrogen Cycle

Enantioselective N-H Bond Insertion Reaction of Anilines Enabled by Ruthenium and Chiral Phosphoric Acid Cooperative Catalysis.

The enantioselective carbene insertion into N-H bonds of anilines has been realized by cooperative catalysis of ruthenium complexes and chiral phosphoric acids, providing the expected α-aryl glycines in moderate to good yields with high enantioselectivity. Typically, by slightly modifying the reaction conditions, this approach allows the N-H bond insertion reaction to be effective for both α-aryl and α-alkyl diazoacetates for the first time with high enantioselectivity (up to 96% and 95% ee, respectively).

High-Performance Ammonia Gas Sensor Based on a Catalytic Ruthenium- Gated Field-Effect Transistor

High-Performance Ammonia Gas Sensor Based on a Catalytic Ruthenium- Gated Field-Effect Transistor

1,5-disubstituted 1,2,3-triazolylated carbohydrates and nucleosides

In general, 1,5-disubstituted 1,2,3-triazolyl moiety is much less common in the synthesis and applications in comparison to its regioisomeric counterpart. Moreover, the synthesis of 1,5-disubstituted 1,2,3-triazoles are not so straightforward as is the case for copper catalyzed strategy of 1,4-disubstituted 1,2,3-triazoles. The preparation of 1,5-triazolylated carbohydrates and nucleosides are even more complex because of the difficulties in accessing the appropriate starting materials as well as the compatibility of reaction conditions with the various protecting groups. 1,5-Disubstitution regioisomeric triazoles of carbohydrates and nucleosides were traditionally obtained as minor products through straightforward heating of the mixture of azides and terminal alkynes. However, the separation of isomers was tedious or in some cases futile. On the other hand, regioselective synthesis using ruthenium catalysis triggered serious concern of residual metal content in therapeutically important ingredients. Therefore, serious efforts are being made by several groups to develop non-toxic metal based or completely metal-free synthesis of 1,5-disubstituted 1,2,3-triazoles. This article strives to summarize the pre-Click era as well as the post-2001 reports on the synthesis and potential applications of 1,5-disubstituted 1,2,3-triazoles in biological systems.

Tuning Photoredox Catalysis of Ruthenium with Palladium: Synthesis of Heterobimetallic Ru-Pd Complexes That Enable Efficient Photochemical Reduction of CO2.

New Ru-Pd heterobimetallic complexes were synthesized and structurally characterized utilizing 6,6″-bis(phosphino)-2,2':6',2″-terpyridine as a scaffold for the metal-metal bond. The dicationic Ru-Pd complex was found to exhibit high catalytic activity as a photocatalyst for photochemical reduction of CO2 to CO under visible light irradiation. This study established a new design of transition metal catalysts that tune photoredox catalysis with metalloligands.

An air- and moisture-stable ruthenium precatalyst for diverse reactivity

Versatile, efficient and robust (pre)catalysts are pivotal in accelerating the discovery and optimization of chemical reactions, shaping diverse synthetic fields such as cross-coupling, C–H functionalization and polymer chemistry. Yet, their scarcity in certain domains has hindered the advancement and adoption of new applications. Here we present a highly reactive air- and moisture-stable ruthenium precatalyst [(tBuCN)5Ru(H2O)](BF4)2, featuring a key exchangeable water ligand. This versatile precatalyst drives an array of transformations, including late-stage C(sp2)–H arylation, primary/secondary alkylation, methylation, hydrogen/deuterium exchange, C(sp3)–H oxidation, alkene isomerization and oxidative cleavage, consistently outperforming conventionally used ruthenium (pre)catalysts. The generality and applicability of this precatalyst is exemplified through the potential for rapid screening and optimization of photocatalytic reactions with a suite of in situ generated ruthenium photocatalysts containing hitherto unknown complexes, and through the rapid discovery of reactivities previously unreported for ruthenium. The diverse applicability observed is suggestive of a generic platform for reaction simplification and accelerated synthetic discovery that will enable broader applicability and accessibility to state-of-the-art ruthenium catalysis.

Free Amine-Directed Redox Neutral Ruthenium(II) Catalysis toward Regioselective Synthesis of Heterobiaryls.

A regioselective coupling of ortho-heteroaryl anilines and 7-oxabenzonorbornadienes has been developed by leveraging free amine-directed redox-neutral Ru(II) catalysis. This protocol facilitates formal C-2 arylation of the indole moiety under mild conditions to offer valuable heterobiaryls in high yields. The reaction displays a broad substrate generality and scalability and retains efficacy in the presence of diverse pharmacophore scaffolds. Moreover, products bearing a free amine group were successfully employed in Mg(NTf2)2-catalyzed double Michael addition cascade, which led to the synthesis of intricate indole- and pyrrole-fused azaheterocycles.

Ruthenium‐Catalysed Asymmetric Intramolecular Isomerization/Esterification Reaction: Direct Synthesis of Chiral Dihydrocoumarins

Comprehensive SummaryAn asymmetric isomerization/intramolecular coupling reaction of allylic alcohols to synthesize chiral dihydrocoumarins was successfully accomplished through ruthenium catalysis. This method demonstrates a wide substrate applicability, excellent tolerance for various functional groups, and good enantioselectivities (up to 90% ee). It provides a convenient pathway to produce a diverse range of structurally distinct chiral dihydrocoumarins in good efficiency.

Valorization of Lignocellulosic Molecules through Homogeneous Ru‐Catalyzed C−C and C−N Bond Forming Reactions

AbstractA sustainable upgrading of renewable bulk materials, obtained by decomposition of biomass lignocellulose, could facilitate their use in the industrial production of chemicals. Homogeneous ruthenium catalysis plays a fundamental role in this area. The review deals with the upgradation of lignocellulosic molecules through the formation of new C−C and C−N bonds. Selected examples of catalytic bond forming reactions reported until mid of 2023, include: (a) dehydrogenative based couplings of alcohols, (b) reductive amination of carbonyl compounds, (c) direct C−H functionalization of (hetero)aromatic compounds. These approaches fulfill the requirements of sustainability: application occurs without any previous substrate activation, thus reducing the production of waste. New chemicals containing the intrinsic molecular structure of lignocellulose substrates, showed a broad range of applications: green fuels, hydrogen carriers, monomers of polymers, intermediates of fine chemicals and pharmaceuticals. The results discussed in the review could inspire the reader to improve the valorization process, in terms of bio‐substrate scope as well as product complexity, through more strategic applications of the catalytic methods.

Vinylene Carbonate as Latent Formylmethyl Surrogate: The Expediency of Ruthenium(II) Catalysis in Accessing Arylacetaldehydes, Arylacetates and Acetals

AbstractArylacetaldehydes and its corresponding esters are fundamental structural motifs widespread in natural products and pharmaceuticals. Herein, we developed a ruthenium(II)‐catalyzed direct formylmethylation and sequential dehydrogenative esterification of phthalazinones by adopting vinylene carbonate as a C2 synthon (formylmethyl equivalent). The reaction is compatible with a repertoire of substrates bearing both electron‐donating and electron‐withdrawing substituents. Strikingly, the products obtained are governed by the additive used. A number of control experiments are conducted to elucidate the reaction mechanism. Furthermore, an important highlight is confirmation of possible intermediates by mass spectrometry.

Electrochemical Ruthenium‐Catalysed Directed C−H Functionalization of Arenes with Boron Reagents

AbstractOrtho‐directed electrochemical C−H functionalization of aromatics with boron‐based coupling partners has been achieved under ruthenium catalysis through an oxidatively induced reductive elimination mechanism. Our method provides a single set of conditions delivering C−H arylation, alkenylation and methylation, yielding ortho‐functionalized products with good functional group tolerance, including examples of late‐stage functionalization in synthetically useful yields. By harnessing electricity as a ‘green’ oxidant, this method circumvents the need for stoichiometric quantities of chemical oxidants, enhancing our sustainability metrics.

Benzoxazole or Benzothiazole as an Innate Directing Group for Palladium- and Ruthenium-Catalyzed Complementary C–H Arylation: Functionalization of Biorelevant Heterocyclic Scaffolds

AbstractThe benzoxazole and benzothiazole moieties were used as innate directing groups for Pd(II)- and Ru(II)-catalyzed C–H arylation of the biorelevant heterocycles 2-arylbenzoxazole and 2-arylbenzothiazole with diverse iodoarenes; palladium and ruthenium catalysis could be used complementarily. The use of σ-donor ligands, such as N,N-dimethylacetamide in the Pd(II) catalytic cycle, and σ-donor/π-acceptor ligands, such as PPh3 in the Ru(II) catalytic cycle, enhanced the arylation rate significantly and was governed by the C–H acidity of the C2-aryl ring of the 2-arylbenzoxazole or 2-arylbenzothiazole. These approaches have a broad substrate scope with respect to coupling partners, to accommodate electron-neutral, electron-rich, as well as electron-deficient iodoarenes; the C2-aryl unit of the 2-arylbenzoxazole or 2-arylbenzothiazole exhibited a high degree of site selectivity at the ortho C–H position, affording only monoarylated derivatives in decent yields; the reactions are functional-group-tolerant and applicable to gram-scale production.

Oxoamination of Terminal Alkenes under Visible-Light-Induced Ruthenium Catalysis

Oxoamination of Terminal Alkenes under Visible-Light-Induced Ruthenium Catalysis

Experimental and Computational Studies on RuII -Catalyzed C7-Allylation of Indolines with Allyl Bromide.

The selective C7-allylation of indolines with allyl bromide under ruthenium catalysis has been revealed here. Under established reaction conditions, C7-allylation of various indolines, including drug compounds, was accomplished with good selectivity and yields. Based on combined experimental and density functional theory (DFT) studies, the olefin insertion route was energetically favorable among four possible pathways. Experimental and DFT studies further revealed that the C-H activation is a reversible rate-limiting step.

Direct Access to meta‐Alkylated N‐Arylazolium Salts via Ruthenium Catalyzed Electronically Controlled Site Selective Functionalization: Scope and Mechanistic Aspect

AbstractEffective access to azolium salts with varying stereoelectronic properties has always fascinated the organometallic chemists. Herein, we described a Ru(II)‐catalyzed one‐step access to diverse meta‐alkylated N‐aryl (benz)imidazolium salts (>40 examples) via σ‐bond activation strategy starting from the readily available azolium salts using alkyl bromide. Notably, the present method is compatible with a wide range of azolium salts and secondary/tertiary alkyl bromides, including the biologically relevant motifs. Various control experiments along with the DFT calculation established the reaction pathway of orthometalated Ru(II)‐NHC complex (6) formation followed by the generation of a Ru(III)‐intermediate, which controls the observed meta‐selectivity, via single electron transfer. Crucially, detailed insight of the reaction mechanism helped to comprehend why some substrates are challenging for this methodology.

Half-Sandwich Ruthenium Complexes with Hydrazone Ligands: Preparation, Structure, and Catalytic Activity in Cyanosilylether Synthesis under an Air Atmosphere.

A new class of N,O-coordinate half-sandwich ruthenium complexes supported by hydrazone ligands with a general formula of [Ru(η6-p-cymene)Cl(L)] have been obtained in moderate to excellent yields conveniently. These air- and moisture-stable ruthenium complexes exhibited excellent catalytic activity in cyanosilylether synthesis under mild reaction conditions. Under the catalysis of ruthenium, various cyanosilylethers with different substituents were obtained through a one-pot reaction of trimethylsilyl cyanide with carbonyl substrates, with good to excellent yields. Excellent catalytic efficiency, a wide substrate range, and mild reaction conditions made this type of ruthenium catalyst have potential for industrial application. All of the half-sandwich ruthenium complexes have been well described by infrared, nuclear magnetic resonance, and EA analysis. Molecular structures of ruthenium complexes 1 and 4 were confirmed by single-crystal X-ray analysis.

Ruthenium-Catalyzed Ligand-Enabled Regiodivergent Difluoroallylation of Aryl C–H Bonds

The gem-difluoroallyl group is a sought-after structural motif commonly found in pharmaceutical compounds. Despite its appeal, achieving a controlled synthesis of both α,α- and γ,γ-difluoroallylated compounds has proven to be a challenging task. This study presents a new approach to difluoroallylation, which utilizes a regiodivergent C-H bond reaction catalyzed by ruthenium catalysis. This method enables the meta and ortho C-H α,α- and ortho C-H γ,γ-difluoroallylation of arenes using 3-bromo-3,3-difluoropropenes.

Ru(II)-Catalyzed Synthesis of Fused Imidazo[1,2-a]pyridine-chromenones and Methylene-Tethered Bis-imidazo[1,2-a]pyridines and Regioselective O-Acetoxylation of Imidazo[1,2-a]pyridines

Herein, we disclose an unprecedented protocol via ruthenium-catalyzed annulation for the synthesis of 6H-chromeno[4',3':4,5]imidazo[1,2-a]pyridin-6-one, and functionalized 2-(3-formylimidazo[1,2-a]pyridin-2-yl)phenyl acetate has been revealed by intramolecular chelation-assisted C-H activation. Additionally, a one-pot approach for creating bis(2-phenylimidazo[1,2-a]pyridin-3-yl)methane (BIP) has been realized through ruthenium catalysis with the use of formic acid. This method was used in gram-scale synthesis of BIP and step-economical late-stage functionalization of a marketed drug, zolimidine, in good yield.