Concise synthesis of 2,3-disubstituted quinoline derivatives via ruthenium-catalyzed three-component deaminative coupling reaction of anilines, aldehydes and amines.

The Ru-H complex (PCy3)2(CO)RuHCl (1) was found to be a highly effective catalyst for the three-component deaminative coupling reaction of anilines with aldehydes and allylamines to form 2,3-disubstituted quinoline products. The analogous coupling reaction of anilines with aldehydes and cyclic enamines led to the selective formation of the tricyclic quinoline derivatives. The reaction profile study showed that the imine is initially formed from the dehydrative coupling of aniline and aldehyde, and it undergoes the deaminative coupling and annulation reaction with amine substrate to form the quinoline product. The catalytic coupling method provides a step-efficient synthesis of 2,3-disubstituted quinoline derivatives without employing any reactive reagents or forming wasteful byproducts.

Correction: Concise synthesis of 2,3-disubstituted quinoline derivatives via ruthenium-catalyzed three-component deaminative coupling reaction of anilines, aldehydes and amines.

Correction for 'Concise synthesis of 2,3-disubstituted quinoline derivatives via ruthenium-catalyzed three-component deaminative coupling reaction of anilines, aldehydes and amines' by Aldiyar Shakenov et al., Org. Biomol. Chem., 2023, https://doi.org/10.1039/d3ob00348e.

Synthesis of Flavanone and Quinazolinone Derivatives from the Ruthenium-Catalyzed Deaminative Coupling Reaction of 2'-Hydroxyaryl Ketones and 2-Aminobenzamides with Simple Amines.

The cationic Ru-H complex [(C6H6)(PCy3)(CO)RuH]+BF4- (1) with 3,4,5,6-tetrachloro-1,2-benzoquinone (L1) was found to be a highly effective catalyst for the deaminative coupling reaction of 2'-hydroxyaryl ketones with simple amines to form 3-substituted flavanone products. The analogous deaminative coupling reaction of 2-aminobenzamides with branched amines directly formed 3,3-disubstituted quinazolinone products. The catalytic method efficiently installs synthetically useful flavanone and quinazolinone core structures without employing any reactive reagents.

Experimental and Computational Studies on the Ruthenium-Catalyzed Dehydrative C-H Coupling of Phenols with Aldehydes for the Synthesis of 2-Alkylphenol, Benzofuran, and Xanthene Derivatives.

The cationic Ru-H complex [(C6H6)(PCy3)(CO)RuH]+BF4- (1) was found to be an effective catalyst for the dehydrative C-H coupling reaction of phenols and aldehydes to form 2-alkylphenol products. The coupling reaction of phenols with branched aldehydes selectively formed 1,1-disubstituted benzofurans, while the coupling reaction with salicylaldehydes yielded xanthene derivatives. A normal deuterium isotope effect was observed from the coupling reaction of 3-methoxyphenol with benzaldehyde and 2-propanol/2-propanol-d8 (kH/kD = 2.3 ± 0.3). The carbon isotope effect was observed on the benzylic carbon of the alkylation product from the coupling reaction of 3-methoxyphenol with 4-methoxybenzaldehyde (C(3) 1.021(3)) and on both benzylic and ortho-arene carbons from the coupling reaction with 4-trifluorobenzaldehdye (C(2) 1.017(3), C(3) 1.011(2)). The Hammett plot from the coupling reaction of 3-methoxyphenol with para-substituted benzaldehydes p-X-C6H4CHO (X = OMe, Me, H, F, Cl, CF3) displayed a V-shaped linear slope. Catalytically relevant Ru-H complexes were observed by NMR from a stoichiometric reaction mixture of 1, 3-methoxyphenol, benzaldehyde, and 2-propanol in CD2Cl2. The DFT calculations provided a detailed catalysis mechanism featuring an electrophilic aromatic substitution of the aldehyde followed by the hydrogenolysis of the hydroxy group. The calculations also revealed a mechanistic rationale for the strong electronic effect of the benzaldehdye substrates p-X-C6H4CHO (X = OMe, CF3) in controlling the turnover-limiting step. The catalytic C-H coupling method provides an efficient synthetic protocol for 2-alkylphenols, 1,1-disubstituted benzofurans, and xanthene derivatives without employing any reactive reagents or forming wasteful byproducts.

Synthesis of Quinazoline and Quinazolinone Derivatives via Ligand-Promoted Ruthenium-Catalyzed Dehydrogenative and Deaminative Coupling Reaction of 2-Aminophenyl Ketones and 2-Aminobenzamides with Amines.

The in situ formed ruthenium catalytic system ([Ru]/L) was found to be highly selective for the dehydrogenative coupling reaction of 2-aminophenyl ketones with amines to form quinazoline products. The deaminative coupling reaction of 2-aminobenzamides with amines led to the efficient formation of quinazolinone products. The catalytic coupling method provides an efficient synthesis of quinazoline and quinazolinone derivatives without using any reactive reagents or forming any toxic byproducts.

Experimental and Computational Study of the ( Z)-Selective Formation of Trisubstituted Olefins and Benzo-Fused Oxacycles from the Ruthenium-Catalyzed Dehydrative C-H Coupling of Phenols with Ketones.

The cationic Ru-H complex was found to be an effective catalyst for the dehydrative C-H coupling of phenols with ketones to form the trisubstituted olefin products. The coupling of phenol with linear ketones led to highly stereoselective formation of the ( Z)-olefin products. The dehydrative coupling of phenol with enones and diones efficiently formed the benzopyrene and related oxacyclic derivatives. The reaction of 3,5-dimethoxyphenol with cyclohexanone-2,2,6,6- d4 showed a significant H/D exchange to both vinyl and α-CH2 positions on the olefin product (72-75% D). A significant carbon isotope effect was observed on the ortho-arene carbon of the olefin product. The free energies of intermediate species for the entire catalytic cycle were successfully computed by using the DFT method. The DFT study revealed that the E/ Z stereoselectivity is a result of the energy difference in the insertion step of ortho-metalated phenol to an enol form of the ketone substrate (ΔΔ E = 9.6 kcal/mol). The coupling method provides a direct catalytic C-H olefination method for ketones to form trisubstituted olefins without employing any reactive reagents or forming any wasteful byproducts.

Synthesis of Symmetric and Unsymmetric Secondary Amines from the Ligand-Promoted Ruthenium-Catalyzed Deaminative Coupling Reaction of Primary Amines.

The catalytic system generated in situ from the tetranuclear Ru-H complex with a catechol ligand (1/L1) was found to be effective for the direct deaminative coupling of two primary amines to form secondary amines. The catalyst 1/L1 was highly chemoselective for promoting the coupling of two different primary amines to afford unsymmetric secondary amines. The analogous coupling of aniline with primary amines formed aryl-substituted secondary amines. The treatment of aniline- d7 with 4-methoxybenzylamine led to the coupling product with significant deuterium incorporation on CH2 (18% D). The most pronounced carbon isotope effect was observed on the α-carbon of the product isolated from the coupling reaction of 4-methoxybenzylamine (C(1) = 1.015(2)). A Hammett plot was constructed from measuring the rates of the coupling reaction of 4-methoxyaniline with a series of para-substituted benzylamines 4-X-C6H4CH2NH2 (X = OMe, Me, H, F, CF3) (ρ = -0.79 ± 0.1). A plausible mechanistic scheme has been proposed for the coupling reaction on the basis of these results. The catalytic coupling method provides an operationally simple and chemoselective synthesis of secondary amine products without using any reactive reagents or forming wasteful byproducts.

Catalytic Synthesis of Substituted Indoles and Quinolines from the Dehydrative C-H Coupling of Arylamines with 1,2- and 1,3-Diols.

The cationic ruthenium-hydride complex catalyzes dehydrative C-H coupling reaction of arylamines with 1,2-diols to form the indole products. The analogous coupling of arylamines with 1,3-diols afforded the substituted quinolines. The catalytic method directly forms these coupling products in a highly regioselective manner without generating any toxic byproducts.

Intermolecular Markovnikov-Selective Hydroacylation of Olefins Catalyzed by a Cationic Ruthenium-Hydride Complex.

The cationic Ru-H complex was found to be an effective catalyst for the intermolecular hydroacylation of aryl-substituted olefins with aldehydes to form branched ketone products. The preliminary kinetic and spectroscopic studies elucidated a ruthenium-acyl complex as the key intermediate species. The catalytic method directly afforded branched ketone products in a highly regioselective manner while tolerating a number of heteroatom functional groups.

Scope and Mechanistic Analysis for Chemoselective Hydrogenolysis of Carbonyl Compounds Catalyzed by a Cationic Ruthenium Hydride Complex with a Tunable Phenol Ligand.

A cationic ruthenium hydride complex, [(C6H6)(PCy3)(CO)RuH](+)BF4(-) (1), with a phenol ligand was found to exhibit high catalytic activity for the hydrogenolysis of carbonyl compounds to yield the corresponding aliphatic products. The catalytic method showed exceptionally high chemoselectivity toward the carbonyl reduction over alkene hydrogenation. Kinetic and spectroscopic studies revealed a strong electronic influence of the phenol ligand on the catalyst activity. The Hammett plot of the hydrogenolysis of 4-methoxyacetophenone displayed two opposite linear slopes for the catalytic system 1/p-X-C6H4OH (ρ = -3.3 for X = OMe, t-Bu, Et, and Me; ρ = +1.5 for X = F, Cl, and CF3). A normal deuterium isotope effect was observed for the hydrogenolysis reaction catalyzed by 1/p-X-C6H4OH with an electron-releasing group (kH/kD = 1.7-2.5; X = OMe, Et), whereas an inverse isotope effect was measured for 1/p-X-C6H4OH with an electron-withdrawing group (kH/kD = 0.6-0.7; X = Cl, CF3). The empirical rate law was determined from the hydrogenolysis of 4-methoxyacetophenone: rate = kobsd[Ru][ketone][H2](-1) for the reaction catalyzed by 1/p-OMe-C6H4OH, and rate = kobsd[Ru][ketone][H2](0) for the reaction catalyzed by 1/p-CF3-C6H4OH. Catalytically relevant dinuclear ruthenium hydride and hydroxo complexes were synthesized, and their structures were established by X-ray crystallography. Two distinct mechanistic pathways are presented for the hydrogenolysis reaction on the basis of these kinetic and spectroscopic data.

Synthesis of 2-Acylphenol and Flavene Derivatives from the Ruthenium-Catalyzed Oxidative C-H Acylation of Phenols with Aldehydes.

The cationic ruthenium hydride complex [(C6H6)(PCy3)(CO)RuH]+BF4- has been found to be an effective catalyst for the oxidative C-H coupling reaction of phenols with aldehydes to give 2-acylphenol compounds. The coupling of phenols with α,ß-unsaturated aldehydes selectively gives the flavene derivatives. The catalytic method mediates direct oxidative C-H coupling of phenol and aldehyde substrates without using any metal oxidants or forming wasteful byproducts.

Chemoselective formation of unsymmetrically substituted ethers from catalytic reductive coupling of aldehydes and ketones with alcohols in aqueous solution.

A well-defined cationic Ru-H complex catalyzes reductive etherification of aldehydes and ketones with alcohols. The catalytic method employs environmentally benign water as the solvent and cheaply available molecular hydrogen as the reducing agent to afford unsymmetrical ethers in a highly chemoselective manner.

Deaminative and decarboxylative catalytic alkylation of amino acids with ketones.

It cuts two ways: The cationic [Ru-H] complex catalyzes selective coupling of α- and ß-amino acids with ketones to form α-alkylated ketone products. The reaction involves CC and CN bond cleavage which result in regio- and stereoselective alkylation using amino acids. A broad substrate scope and high functional-group tolerance is demonstrated.

Dehydrative C-H alkylation and alkenylation of phenols with alcohols: expedient synthesis for substituted phenols and benzofurans.

A well-defined cationic Ru-H complex catalyzes the dehydrative C-H alkylation reaction of phenols with alcohols to form ortho-substituted phenol products. Benzofuran derivatives are efficiently synthesized from the dehydrative C-H alkenylation and annulation reaction of phenols with 1,2-diols. The catalytic C-H coupling method employs cheaply available phenols and alcohols, exhibits a broad substrate scope, tolerates carbonyl and amine functional groups, and liberates water as the only byproduct.

Scope and Mechanistic Study of the Coupling Reaction of α, ß-Unsaturated Carbonyl Compounds with Alkenes: Uncovering Electronic Effects on Alkene Insertion vs Oxidative Coupling Pathways.

The cationic ruthenium-hydride complex [(C(6)H(6))(PCy(3))(CO)RuH](+)BF(4) (-) (1) was found to be a highly effective catalyst for the intermolecular conjugate addition of simple alkenes to α,ß-unsaturated carbonyl compounds to give (Z)-selective tetrasubstituted olefin products. The analogous coupling reaction of cinnamides with electron-deficient olefins led to the oxidative coupling of two olefinic C-H bonds in forming (E)-selective diene products. The intramolecular version of the coupling reaction efficiently produced indene and bicyclic fulvene derivatives. The empirical rate law for the coupling reaction of ethyl cinnamate with propene was determined as: rate = k[1](1)[propene](0)[cinnamate](-1). A negligible deuterium kinetic isotope effect (k(H)/k(D) = 1.1±0.1) was measured from both (E)-C(6)H(5)CH=C(CH(3))CONHCH(3) and (E)-C(6)H(5)CD=C(CH(3))CONHCH(3) with styrene. In contrast, a significant normal isotope effect (k(H)/k(D) = 1.7±0.1) was observed from the reaction of (E)-C(6)H(5)CH=C(CH(3))CONHCH(3) with styrene and styrene-d(10). A pronounced carbon isotope effect was measured from the coupling reaction of (E)-C(6)H(5)CH=CHCO(2)Et with propene ((13)C(recovered)/(13)C(virgin) at C(ß) = 1.019(6)), while a negligible carbon isotope effect ((13)C(recovered)/(13)C(virgin) at C(ß) = 0.999(4)) was obtained from the reaction of (E)-C(6)H(5)CH=C(CH(3))CONHCH(3) with styrene. Hammett plots from the correlation of para-substituted p-X-C(6)H(4)CH=CHCO(2)Et (X = OCH(3), CH(3), H, F, Cl, CO(2)Me, CF(3)) with propene and from the treatment of (E)-C(6)H(5)CH=CHCO(2)Et with a series of para-substituted styrenes p-Y-C(6)H(4)CH=CH(2) (Y = OCH(3), CH(3), H, F, Cl, CF(3)) gave the positive slopes for both cases (ρ = +1.1±0.1 and +1.5±0.1, respectively). Eyring analysis of the coupling reaction led to the thermodynamic parameters, Δ H(‡) = 20±2 kcal mol(-1) and S(‡) = -42±5 e.u. Two separate mechanistic pathways for the coupling reaction have been proposed on the basis of these kinetic and spectroscopic studies.

Selective catalytic C-H alkylation of alkenes with alcohols.

Alkenes and alcohols are among the most abundant and commonly used organic feedstock in industrial processes. We report a selective catalytic alkylation reaction of alkenes with alcohols that forms a carbon-carbon bond between vinyl carbon-hydrogen (C-H) and carbon-hydroxy centers with the concomitant loss of water. The cationic ruthenium complex [(C(6)H(6))(PCy(3))(CO)RuH](+)BF(4)(-) (Cy, cyclohexyl) catalyzes the alkylation in solution within 2 to 8 hours at temperatures ranging from 75° to 110°C and tolerates a broad range of substrate functionality, including amines and carbonyls. Preliminary mechanistic studies are inconsistent with Friedel-Crafts-type electrophilic activation of the alcohols, suggesting instead a vinyl C-H activation pathway with opposite electronic polarization.

Recent advances in the synthetic and mechanistic aspects of the ruthenium-catalyzed carbon-heteroatom bond forming reactions of alkenes and alkynes.

The group's recent advances in catalytic carbon-to-heteroatom bond forming reactions of alkenes and alkynes are described. For the C-O bond formation reaction, a well-defined bifunctional ruthenium-amido catalyst has been successfully employed for the conjugate addition of alcohols to acrylic compounds. The ruthenium-hydride complex (PCy(3))(2)(CO)RuHCl was found to be a highly effective catalyst for the regioselective alkyne-to-carboxylic acid coupling reaction in yielding synthetically useful enol ester products. Cationic ruthenium-hydride catalyst generated in-situ from (PCy(3))(2)(CO)RuHCl/HBF(4)·OEt(2) was successfully utilized for both the hydroamination and related C-N bond forming reactions of alkenes. For the C-Si bond formation reaction, regio- and stereoselective dehydrosilylation of alkenes and hydrosilylation of alkynes have been developed by using a well-defined ruthenium-hydride catalyst. Scope and mechanistic aspects of these carbon-to-heteroatom bond-forming reactions are discussed.

Chain- and Regioselective Ethylene and Styrene Dimerization Reactions Catalyzed by a Well-Defined Cationic Ruthenium-Hydride Complex: New Insights on the Styrene Dimerization Mechanism.

The cationic ruthenium-hydride complex [(eta(6)-C(6)H(6))(PCy(3))(CO)RuH](+)BF(4) (-) was found to be a highly regioselective catalyst for the ethylene dimerization reaction to give 2-butene products (TOF = 1910 h(-1), >95% selectivity for 2-butenes). The dimerization of styrene exclusively produced the head-to-tail dimer (E)-PhCH(CH(3))CH=CHPh at an initial turnover rate of 2300 h(-1). A rapid and extensive H/D exchange between the vinyl hydrogens of styrene-d(8) and 4-methoxystyrene was observed within 10 min without forming the dimer products at room temperature. The inverse deuterium isotope effect of k(H)/k(D) = 0.77+/-0.10 was measured from the first order plots on the dimerization reaction of styrene and styrene-d(8) in chlorobenzene at 70 degrees C. The pronounced carbon isotope effect on both vinyl carbons of styrene as measured by using Singleton's method ((13)C(recovered)/(13)C(virgin) at C(1) = 1.096 and C(2) = 1.042) indicates that the C-C bond formation is the rate-limiting step for the dimerization reaction. The Eyring plot of the dimerization of styrene in the temperature range of 50-90 degrees C led to DeltaH(double dagger) = 3.3(6) kcal/mol and DeltaS(double dagger) = -35.5(7) e.u. An electrophilic addition mechanism has been proposed for the dimerization of styrene.

Intermolecular Dehydrative Coupling Reaction of Arylketones with Cyclic Alkenes Catalyzed by a Well-Defined Cationic Ruthenium-Hydride Complex: A Novel Ketone Olefination Method via Vinyl C-H Bond Activation.

The cationic ruthenium-hydride complex [(eta(6)-C(6)H(6))(PCy(3))(CO)RuH](+)BF(4) (-) was found to be a highly effective catalyst for the intermolecular olefination reaction of arylketones with cycloalkenes. The preliminary mechanistic analysis revealed that electrophilic ruthenium-vinyl complex is the key species for mediating both vinyl C-H bond activation and the dehydrative olefination steps of the coupling reaction.