Search

In this study, we present the successful application of new and known stable 16‐electron ruthenium(II) pincer complexes POCOP, based on the naphthoresorcinate backbone, [Ru(X)(POCOP)(CO)] (X = H, Cl, Br, I, OCOCF3), in the catalytic alkylation of ketones and the coupling between amines and primary alcohols under mild conditions. These protocols demonstrated tolerance to a wide range of alcohols, ketones, and anilines, with reactions proceeding in high conversions and selectivity towards the hydrogenated ketones and the imines. The use of an excess of alcohol as the proton source facilitated the formation of the hydrogenated products. These results mark a significant advancement in the development of catalytic reactions with ruthenium POCOP pincer derivatives. [ABSTRACT FROM AUTHOR]

A diaminocyclopentadienone ruthenium complex has proven to be a highly effective catalyst for the alkylation of indoles or ketones with poorly reactive alcohols. The catalyst is readily available, air and moisture stable and exhibits wide functional group tolerance. The environmentally benign procedure follows a borrowing hydrogen mechanism and requires no excess of either component. Various indoles and ketones are selectively monoalkylated in high yield. [ABSTRACT FROM AUTHOR]

Sulfondiimines are diaza‐analogues of sulfones with a chiral sulfur center. Compared to sulfones and sulfoximines, their synthesis and transformations have so far been studied to a lesser extent. Here, we report the enantioselective synthesis of 1,2‐benzothiazine 1‐imines, i.e. cyclic sulfondiimine derivatives from sulfondiimines and sulfoxonium ylides via C−H alkylation/cyclization reactions. The combination of [Ru(p‐cymene)Cl2]2 and a newly developed chiral spiro carboxylic acid is key to achieving high enantioselectivity. [ABSTRACT FROM AUTHOR]

Enantioselective C−H activation has surfaced as a transformative toolbox for the efficient assembly of chiral molecules. However, despite of major advances in rhodium and palladium catalysis, ruthenium(II)‐catalyzed enantioselective C−H activation has thus far largely proven elusive. In contrast, we herein report on a ruthenium(II)‐catalyzed highly regio‐, diastereo‐ and enantioselective C−H alkylation. The key to success was represented by the identification of novel C2‐symmetric chiral imidazolidine carboxylic acids (CICAs), which are easily accessible in a one‐pot fashion, as highly effective chiral ligands. This ruthenium/CICA system enabled the efficient installation of central and axial chirality, and featured excellent branched to linear ratios with generally >20 : 1 dr and up to 98 : 2 er. Mechanistic studies by experiment and computation were carried out to understand the catalyst mode of action. [ABSTRACT FROM AUTHOR]

The catalyst generated in situ from RuH2(CO)(PPh3)3, (S)-SEGPHOS, and a chiral phosphoric acid promotes asymmetric hydrohydroxyalkylation of butadiene and affords enantioenriched α-methyl homoallylic alcohols. The observed diastereo- and enantioselectivities are determined by both the chiral phosphine and chiral phosphate ligands. Density functional theory calculations (M06/SDD-6-311G(d,p)-IEFPCM(acetone)//B3LYP/SDD-6-31G(d)) predict that the product distribution is controlled by the kinetics of carbon-carbon bond formation, and this process occurs via a closed-chair Zimmerman-Traxler-type transition structure (TS). Chiral-phosphate-dependent stereoselectivity arising from this TS is enabled through a hydrogen bond between the phosphoryl oxygen and the aldehyde formyl proton present in TADDOL-derived catalysts. This interaction is absent in the corresponding BINOL-derived systems, and the opposite diastereo- and enantioselectivity is observed. Additional factors influencing the stereochemical control are determined.

Herein, we report a simple, efficient, and sustainable method for the synthesis of α‐alkylated ketones and quinolines using a hydrogen‐borrowing strategy, which has emerged as a greener alternative in organic transformation reactions. Synthesis of a range of α‐alkylated ketones and quinoline derivatives was achieved by using the water‐soluble [Ru(8‐AQ)Cl(p‐cym.)]+Cl− [Ru]‐1 (AQ=aminoquinoline) catalyst with water as the reaction medium. By adopting this strategy, we have synthesized α‐alkylated ketones and quinolines using ketones or secondary alcohols as starting materials and the primary alcohol as a green and naturally abundant alkylating agent. [ABSTRACT FROM AUTHOR]

Herein, we disclose a ruthenium‐catalyzed regioselective β‐C(sp3)−H bond functionalization on the piperazine core using aldehydes as alkylating agents. The present transformation appears to go through the dehydrogenation of the piperazine to propagate to enamine in situ, followed by nucleophilic addition to the aldehyde and hydrogenation to result in the regioselective β‐C(sp3)−H alkylation. A variety of aromatic, heteroaromatic, aliphatic aldehydes were employed for the C‐3 alkylation of N‐alkyl‐N′‐p‐nitrophenyl substituted piperazines. [ABSTRACT FROM AUTHOR]

Ruthenium(II)biscarboxylate complexes enabled the selective alkylation of C−H and C−C bonds at the ortho‐ or meta‐position. ortho‐C−H Alkylations were achieved with 4‐, 5‐ as well as 6‐membered halocycloalkanes. Furthermore, the judicious choice of the directing group allowed for a full control of ortho‐/meta‐selectivities. Detailed mechanistic studies by experiment and computation were performed and provided strong support for an oxidative addition/reductive elimination process for ortho‐alkylations, while a homolytic C−X cleavage was operative for the meta‐selective transformations. [ABSTRACT FROM AUTHOR]

An efficient ruthenium‐catalyzed divergent alkylation and olefination of methyl 1,3,5‐triazines with alcohols have been developed. The selectivity can be rationally tuned by the judicious choice of ruthenium catalyst, wherein Ru(PPh3)3Cl2 delivers alkylated 1,3,5‐triazines and RuCl3 gives olefinated 1,3,5‐triazines in up to 98 % yield. Following this simple, facile, and high atom economical protocol, a broad range of products was prepared in moderate to good yields and tolerated heterocyclic or benzylic alcohols containing functionalities. The overall transformation operates through dehydrogenation of primary alcohols under the reaction conditions to provide the corresponding aldehydes, which further undergo condensation with methyl 1,3,5‐triazines. [ABSTRACT FROM AUTHOR]

Herein, we presented Ru‐SNS complex that serves as a useful catalyst for C‐3 alkylation of 1H‐indoles with various aliphatic primary and secondary alcohols including cyclic alcohols as well as benzylic alcohols. The selective synthesis of bisindolylmethane derivatives is also achieved from the same set of indole and alcohol just by altering the reaction parameters. Furthermore, the sustainable synthesis of C‐3 alkylated indoles directly from 2‐(2‐nitrophenyl)ethan‐1‐ol and alcohols catalysed by a Ru‐complex via "borrowing hydrogen" strategy is reported. This protocol provides an atom‐economical sustainable route to access structurally important compounds like arundine, vibrindole A and tryptamine based derivatives. [ABSTRACT FROM AUTHOR]

We report herein an unprecedented highly efficient Guerbet‐type reaction at room temperature (catalytic TON up to >6000). This β‐alkylation of secondary methyl carbinols with primary alcohols has significant advantage of delivering higher‐order secondary alcohols in an economical, redox‐neutral fashion. In addition, the first enantioselective Guerbet reaction has also been achieved using a commercially available chiral ruthenium complex to deliver secondary alcohols with moderate yield and up to 92 % ee. In both reactions, the use of a traceless ketone promoter proved to be beneficial for the catalytic efficiency. [ABSTRACT FROM AUTHOR]

The first example of an asymmetric Guerbet reaction has been developed. Using commercially available, classic Noyori RuII‐diamine‐diphosphine catalysts, well‐known in asymmetric hydrogenation, racemic secondary alcohols are shown to couple with primary alcohols in the presence of a base, affording new chiral alcohols with enantiomeric ratios of up to 99:1. Requiring no reducing agents, the protocol provides an easy, alternative route for the synthesis of chiral alcohols. Mechanistic studies reveal that the reaction proceeds via a Ru‐catalyzed asymmetric hydrogen autotransfer process in concert with a base‐promoted allylic alcohol isomerization. [ABSTRACT FROM AUTHOR]

Herein, we report a ruthenium‐catalyzed redox‐neutral α‐alkylation of unsaturated alcohols based on a synergistic relay process involving olefin isomerization (chain walking) and umpolung hydrazone addition, which takes advantage of the interaction between the two rather inefficient individual reaction steps to enable an efficient overall process. This transformation shows the compatibility of hydrazone‐type "carbanions" and active protons in a one‐pot reaction, and at the same time achieves the first Grignard‐type nucleophilic addition using olefinic alcohols as latent carbonyl groups, providing a higher yield of the corresponding secondary alcohol than the classical hydrazone addition to aldehydes does. A broad scope of unsaturated alcohols and hydrazones, including some complex structures, can be successfully employed in this reaction, which shows the versatility of this approach and its suitability as an alternative, efficient means for the generation of secondary and tertiary alcohols. [ABSTRACT FROM AUTHOR]

A simple and environmentally benign procedure for the synthesis of secondary amines in water has been developed. Combining Ru3(CO)12, tetraphenylcyclopentadienone and a small quantity of TGPS-750-M surfactant, primary and secondary alcohols were alkylated at N employing equimolar amounts of aromatic amines in water. The reaction occurs under microwave (MW) dielectric heating with high conversion and high yield. When required, the use of biomass-derived 2-MeTHF or GVL as a co-solvent is possible. Under the influence of MWs, a Ru nanoparticle–nanomicelle combination was formed acting as an effective and recyclable catalyst. This protocol was also employed for "in water" cyclisation to synthesise biologically relevant pyrrolobenzodiazepines (PBDs). [ABSTRACT FROM AUTHOR]

We report the use of ruthenium–NNN‐pincer complexes of the type (R2NNN)RuCl2(PPh3) (R = tBu, iPr, Cy and Ph) for the catalytic N‐alkylation of primary amines under solvent‐free conditions. For the first time, the base that is required to promote these reactions is generated in situ from the alcohol by the use of sodium. The resulting sodium alkoxide regenerates the alcohol substrate while acting as the water scavenger thus mitigating the need of an additional base. Among the catalysts screened, (tBu2NNN)RuCl2(PPh3) (0.02 mol‐%) gives very high turnovers and good yields at 140 °C. The (tBu2NNN)RuCl2(PPh3) catalyzed N‐alkylation tolerates a variety of amine and alcohol substrates. While excellent turnover (29000) was obtained for the (tBu2NNN)RuCl2(PPh3) (0.002 mol‐%) catalyzed alkylation of aniline with cyclohexyl methanol, the turnovers obtained in the corresponding catalytic methylation of p‐anisidine was also very high (12000). The (tBu2NNN)RuCl2(PPh3) catalyzed reactions have also been accomplished under open‐vessel conditions resulting in a net dehydrogenative coupling reaction. This protocol has been used to transform benzene‐1,2‐diamines to benzimidazoles with high productivity (12000 turnovers). DFT studies indicate that while β‐hydride elimination is rate‐determining (RDTS: 24.31 kcal/mol) for the alcohol dehydrogenation segment which is endothermic, insertion of the imine is rate‐determining (RDTS: 11.26 kcal/mol) for its hydrogenation that is exothermic. [ABSTRACT FROM AUTHOR]

A ruthenium‐catalyzed protocol to access conjugate addition or decarboxylative conjugate addition of aromatic acids with maleimides has been developed. The reaction shows interesting chemoselectivity with different substituted benzoic acids. The reaction pathway of C−H alkylation is controlled by the intrinsic property of aromatic acids but not reaction conditions. Under almost the same reaction conditions, carboxyl can act as either a classical directing group or a traceless directing group, thereby generating two kinds of products, i. e. 2‐alkyl substituted benzoic acids and alkyl substituted benzenes. These two reactions proceeded under mild and redox‐neutral conditions in neat water under the atmosphere of air, and could be easily scaled up to grams. The decarboxylative conjugate addition, where carboxyl acts as a traceless directing group, can be realized without the addition of any ligand, silver or copper salt. [ABSTRACT FROM AUTHOR]

• [3 + 2] Cycloaddition of a ruthenium azido complex with two acetylacetylenes. • Synthesis and characterization of two novel ruthenium triazolates. • Regiospecific alkylation of a ruthenium triazolato complex. • The first example of N-coordinated triazolato complex using 3-butyn-2-one. • The X-ray structures of four new compounds were determined. The [3 + 2] cycloaddition of two acetylacetylenes with ruthenium azido complex [Ru]−N 3 (1 , [Ru] = (η 5-C 5 H 5)(dppe)Ru, dppe = Ph 2 PCH 2 CH 2 PPh 2) is reported. The metal-bound heterocyclic complexes produced are triazolato complexes [Ru]N 3 C 2 H(COCH 3) (2) and [Ru]N 3 C 2 (Ph)(COCH 3) (3) from 3-butyn-2-one and 4-phenyl-3-butyn-2-one, respectively. Both of the structures of 2 and 3 are clearly established as N(2)-bound. Alkylation of 2 with organic halides affords a series of N(1)-bound N(3)-alkyl-4-acetyl triazolato complexes {[Ru]N 3 (CH 2 R)C 2 H(COCH 3)}[X] (4a , R = H, X = I; 4b , R = C 6 F 5 , X = Br; 4c , R = Ph, X = Br; 4d , R = 2,6-F 2 -C 6 H 3 , X = Br; 4e , R = 4-CN-C 6 H 4 , X = Br). Treatment of 4a with CH 3 I in refluxing CHCl 3 afforded [Ru]-I (5). The structures of complexes 2 , 3 , 4a and 5 have been determined by single-crystal X-ray diffraction analysis. [ABSTRACT FROM AUTHOR]

Visible‐light‐induced ruthenium catalysis has enabled remote C−H alkylations with excellent levels of position control under exceedingly mild conditions at room temperature. The metallaphotocatalysis occurred under exogenous‐photosensitizer‐free conditions and features an ample substrate scope. The robust nature of the photo‐induced mild meta‐C−H functionalization is reflected by the broad functional group tolerance, and the reaction can be carried out in an operationally simple manner, setting the stage for challenging secondary and tertiary meta‐C−H alkylations by ruthenaphotoredox catalysis. [ABSTRACT FROM AUTHOR]

Under oxidative conditions the complexes M(bpy)2Cl2, M = Ru or Os, react with 1,2‐dipivaloylhydrazine H2L = tBuC(O)‐NH‐NH‐C(O)‐tBu to yield the paramagnetic compounds [M(L)(bpy)2](PF6) {1(PF6), M = Ru and 2(PF6), M = Os}. Crystal structures of 1(ClO4) and 2(PF6) reveal an NNCO chelate coordination of L with d(NN) ≈ 1.39 Å. EPR spectroscopy suggests a metal/ligand mixed situation for the unpaired electron, with 29 % (Ru, 1+) or 46 % (Os, 2+) metal spin contribution according to DFT calculations. Both complex cations exhibit reversible one‐electron oxidation and reduction (Kc ≈ 1019 for 1+ and 1012 for 2+) which could also be monitored by IR (νCO) and UV/Vis‐NIR spectroelectrochemistry. These data confirm a metal/ligand orbital mixing MII(L·–) ↔ MIII(L2–), with the osmium analogue favoring the latter alternative. Reaction of Ru(bpy)2Cl2 under non‐oxidizing conditions yields the intermediate (1H)(PF6) which could be oxidatively deprotonated to 1+ or methylated to (1Me)(PF6), both identified by 1H and 13C NMR. While oxidation of (1H)+ proceeds irreversibly due to proton loss, the reversible spectroelectrochemical oxidation of (1Me)+ suggests a metal‐based process RuII(LMe–) → RuIII(LMe–). The results reveal that not only dinuclear complexes of 1,2‐diacylhydrazido ligands but also mononuclear analogues are distinguished by remarkably variable metal/ligand mixed contributions to the frontier orbitals. [ABSTRACT FROM AUTHOR]

A series of unsymmetrical 1,3‐disubstituted benzimidazolium chlorides were synthesized as N‐heterocyclic carbene (NHC) precursors. These compounds were used for synthesis of the new ruthenium(II) complexes of the type [RuCl2(arene)(NHC)], (arene = η6‐p‐cymene). The structures of all compounds were characterized by 1H NMR, 13C NMR and FT‐IR spectroscopy techniques. The catalytic activity of the ruthenium complexes has been evaluated with respect to the mono‐N‐alkylation reactions of aromatic amines with various alcohol derivatives under solvent‐free conditions at 120 °C using the borrowing hydrogen strategy. [ABSTRACT FROM AUTHOR]

Density functional theory calculations have been performed to quantitatively characterize ruthenium‐catalyzed meta‐selective C–H functionalizations of 2‐phenylpyridine. The reaction with tert‐butyl bromide was used as a model, and the proposed catalytic cycle is comprised of three successive steps: C–H activation, alkylation of the ruthenacycle, and demetalation, and separation of the product, among which C–H activation is the rate‐determining step having a free‐energy barrier of 29.2 kcal mol–1. Alkylation of the ruthenacycle is predicted to be the selectivity‐determining step. The plausible reaction mechanism of the alkylation of the ruthenacycle depends on the nature of alkylating reagents, because use of simple alkyl halides would favor the electrophilic aromatic substitution mechanism over the radical mechanism, while the radical mechanism might become more competitive if a tertiary α‐bromo ester serves as an alkylating source. To address the regioselectivity issue, the kinetic parameters for the formation of different regioisomeric products have been calculated, which are consistent with the experimental findings and can provide additional insights. The meta‐selective C–H alkylation of 2‐phenylpyridine catalyzed by ruthenium was studied by using DFT calculations. The competition between electrophilic and radical mechanisms is determined by the nature of the alkylating reagents. The regioselectivity issue was addressed in detail. [ABSTRACT FROM AUTHOR]

Imines are observed frequently in ruthenium‐catalyzed N‐alkylation of amines with alcohols. Herein, nitrogen–phosphine functionalized carbene ligands were developed and used in ruthenium‐catalyzed N‐alkylation to explore the mechanism of imine formation. The results showed that strongly electron‐donating ligands were beneficial for imine formation and alcohol dehydrogenation to generate acid. In addition, with an increase of electron density of nitrogen atom in substituted amines, the yield of imines in N‐alkylation was improved. At the same time, with electron‐rich imines as substrates, the transfer hydrogenation of imines became difficult. It is suggested that strongly electron‐donating ligands and substrates caused an increase of electron density on the ruthenium center, which resulted in the elimination of hydrogen atoms in active species [LRuH2] as hydrogen gas rather than transfer onto the imine coordinated with the ruthenium center. [ABSTRACT FROM AUTHOR]

Abstract: meta‐Selective C−H alkylations of bioactive purine derivatives were accomplished by versatile ruthenium catalysis. Thus, the arene‐ligand‐free complex [Ru(OAc)2(PPh3)2] enabled remote C−H functionalizations with ample scope and excellent levels of chemo‐ and positional selectivities. Detailed experimental and computational mechanistic studies provided strong support for a facile C−H activation within a ruthenium(II/III) manifold. [ABSTRACT FROM AUTHOR]

This paper includes the synthesis of 2-(1,3-dioxane-2-yl)ethyl substituted benzimidazole substituted N -heterocyclic carbenes precursors and their ruthenium complexes. Synthesized compounds were characterized by elemental analysis and NMR spectroscopy. All complexes have been tested in the alkylation of pyrrolidine and morpholine with alcohols, showing an excellent activity in this reaction. [ABSTRACT FROM AUTHOR]

Computational studies on decarboxylative C−H alkenylations provided key insights into the solvent-robust nature of C−H activation/decarboxylation domino reactions. These properties were exploited for ruthenium(II)-catalyzed C−H alkylations by a decarboxylative process with ample scope under copper-free and silver-free reaction conditions. [ABSTRACT FROM AUTHOR]

A Ru(II) NHC complex (loading down to 0.001 mol%) catalyzed cross coupling of a broad range of aromatic, aliphatic and heterocyclic alcohols is reported. This protocol also functioned efficiently under solvent-free conditions. Remarkably, this catalytic system disclosed so far the highest TON of 288000 for the cross coupling of alcohols. Notably, this methodology was successfully applied for the one-pot synthesis of a range of flavan derivatives. A detailed DFT studies and kinetic experiments were performed to understand the reaction mechanism as well as the high reactivity of this catalytic system. [ABSTRACT FROM AUTHOR]

The para-selective C−H alkylation of aniline derivatives furnished with a pyrimidine auxiliary is herein reported. This reaction is proposed to take place via an N−H-activated cyclometalate formed in situ. Experimental and DFT mechanistic studies elucidate a dual role of the ruthenium catalyst. Here the ruthenium catalyst can undergo cyclometalation by N−H metalation (as opposed to C−H metalation in meta-selective processes) and form a redox active ruthenium species, to enable site-selective radical addition at the para position. [ABSTRACT FROM AUTHOR]

The acetate complex Ru(OAc)2(D iPPF) ( 2) obtained from Ru(OAc)2(PPh3)2 ( 1) and 1,1′-bis(diisopropylphosphino)ferrocene (D iPPF) reacts cleanly with formaldehyde affording Ru(OAc)2(CO)(D iPPF) ( 3) in high yield. The monocarbonyl complex 3 (0.4-2 mol %) efficiently catalyzes the N-alkylation of primary and secondary alkyl and aromatic amines using primary alcohols ROH (R=Et, nPr, nBu, PhCH2) under mild reaction conditions (30-100 °C) with an alcohol/amine molar ratio of 10-100. Formation of the monohydride RuH(OAc)(CO)(D iPPF) ( 4) has been observed by reaction of 3 with iPrOH in the presence of NEt3 at RT through an equilibrium reaction. [ABSTRACT FROM AUTHOR]