Ruthenium Catalysis Research Articles

ChemInform Abstract: Ruthenium Catalyzed Diastereo‐ and Enantioselective Coupling of Propargyl Ethers with Alcohols: Siloxy‐Crotylation via Hydride Shift Enabled Conversion of Alkynes to π‐Allyls.

AbstractThis is the first enantioselective carbonyl siloxy‐crotylation using TIPS‐protected propargyl ethers, which upon deprotection and reduction give 1,4‐diols (III), (VI), (VIII), and (X) with high regio‐, diastereo‐ and enantioselectivities in good yields.

The contrasting catalytic efficiency and cancer cell antiproliferative activity of stereoselective organoruthenium transfer hydrogenation catalysts.

The rapidly growing area of catalytic ruthenium chemistry has provided new complexes with potential as organometallic anticancer agents with novel mechanisms of action. Here we report the anticancer activity of four neutral organometallic Ru(II) arene N-tosyl-1,2-diphenylethane-1,2-diamine (TsDPEN) tethered transfer hydrogenation catalysts. The enantiomers (R,R)-[Ru(η(6)-C6H5(CH2)3-TsDPEN-N-Me)Cl] (8) and (S,S)-[Ru(η(6)-C6H5(CH2)3-TsDPEN-N-Me)Cl] (8a) exhibited higher potency than cisplatin against A2780 human ovarian cancer cells. When the N-methyl was replaced by N-H, i.e. to give (R,R)-[Ru(η(6)-Ph(CH2)3-TsDPEN-NH)Cl] (7) and (S,S)-[Ru(η(6)-Ph(CH2)3-TsDPEN-NH)Cl] (7a), respectively, anticancer activity decreased >5-fold. Their antiproliferative activity appears to be linked to their ability to accumulate in cells, and their mechanism of action might involve inhibition of tubulin polymerisation. This appears to be the first report of the potent anticancer activity of tethered Ru(II) arene complexes, and the structure-activity relationship suggests that the N-methyl substituents are important for potency. In the National Cancer Institute 60-cancer-cell-line screen, complexes 8 and 8a exhibited higher activity than cisplatin towards a broad range of cancer cell lines. Intriguingly, in contrast to their potent anticancer properties, complexes 8/8a are poor catalysts for asymmetric transfer hydrogenation, whereas complexes 7/7a are effective asymmetric hydrogenation catalysts.

ChemInform Abstract: Ruthenium and Osmium Complexes Containing 2‐(Aminomethyl)pyridine (Ampy)‐Based Ligands in Catalysis

AbstractReview: 150 refs.

Preparation of 3-Methylthiodecanal, a Flavour Compound

1-Undecen-4-ol was converted into its benzyl ether in 92% yield by reaction with benzyl chloride in the presence of NaH and was then oxidised with a ruthenium catalysis to give the corresponding aldehyde, which was treated directly with ethylene glycol in the presence of pyridinium p-toluenesulfonate to produce 2-(2′-benzyloxynonyl)-1,3-dioxolane in an overall yield of 87%. This intermediate underwent deprotection of the benzyloxy group and mesylation to give 2-(2′-mesyloxynonyl)-1,3-dioxolane in 90% yield, treatment of which with sodium methyl mercaptide followed by cleavage of the 1,3-dioxolane group afforded 3-methylthiodecanal in 81% yield.

Ruthenium Catalyzed Diastereo- and Enantioselective Coupling of Propargyl Ethers with Alcohols: Siloxy-Crotylation via Hydride Shift Enabled Conversion of Alkynes to π-Allyls.

The first enantioselective carbonyl crotylations through direct use of alkynes as chiral allylmetal equivalents are described. Chiral ruthenium(II) complexes modified by Josiphos (SL-J009-1) catalyze the C-C coupling of TIPS-protected propargyl ether 1a with primary alcohols 2a-2o to form products of carbonyl siloxy-crotylation 3a-3o, which upon silyl deprotection-reduction deliver 1,4-diols 5a-5o with excellent control of regio-, anti-diastereo-, and enantioselectivity. Structurally related propargyl ethers 1b and 1c bearing ethyl- and phenyl-substituents engage in diastereo- and enantioselective coupling, as illustrated in the formation of adducts 5p and 5q, respectively. Selective mono-tosylation of diols 5a, 5c, 5e, 5f, 5k, and 5m is accompanied by spontaneous cyclization to deliver the trans-2,3-disubstituted furans 6a, 6c, 6e, 6f, 6k, and 6m, respectively. Primary alcohols 2a, 2l, and 2p were converted to the siloxy-crotylation products 3a, 3l, and 3p, which upon silyl deprotection-lactol oxidation were transformed to the trans-4,5-disubstituted γ-butyrolactones 7a, 7l, and 7p. The formation of 7p represents a total synthesis of (+)-trans-whisky lactone. Unlike closely related ruthenium catalyzed alkyne-alcohol C-C couplings, deuterium labeling studies provide clear evidence of a novel 1,2-hydride shift mechanism that converts metal-bound alkynes to π-allyls in the absence of intervening allenes.

ChemInform Abstract: Alkyne Hydroacylation: Switching Regioselectivity by Tandem Ruthenium Catalysis.

Abstractβ,γ‐Unsaturated carbonyl compounds are synthesized through the coupling of internal alkynes with aldehydes using tandem Ru‐catalysis.

Development of New Photocatalysts for Solar-to-Fuel Conversion

Photocatalytic water splitting and CO2 fixation under visible light have attracted attention as potential means of solar-to-fuel energy conversion. Our group has studied such photocatalytic systems based on non-oxide type semiconductors such as oxynitrides and nitrides. As a representative example of our materials, zirconia-modified TaON exhibits the functionality as a hydrogen evolution photocatalyst in a Z-scheme water splitting system, in combination with a WO3-based oxygen evolution photocatalyst in the presence of an iodate/iodide redox couple. The apparent quantum efficiency of this system is ~6.3% at 420 nm, which is the highest record among photocatalytic water splitting systems reported so far. For visible-light-driven CO2 fixation, we have recently developed a composite material consisting of a polymeric carbon nitride semiconductor and a catalytic ruthenium(II) complex, which photocatalyzes CO2 reduction to formic acid under visible light. Importantly, isotope-labeling experiments showed that the products obtained during the reaction originate from not the decomposition of carbon nitride itself but CO2 used as the reactant. Optimizing the structure of the ruthenium complex led to an improvement in the performance, giving a high turnover number (>1000 for 20 hours), an apparent quantum yield of 5.7% (at 400 nm) and selectivity (>80%). These numbers are greatest among photocatalytic CO2 reduction systems reported so far. In this presentation, the details of such photosystems we have developed will be introduced.

ChemInform Abstract: Dehydrative C—H/N—OH Functionalizations in H2O by Ruthenium(II) Catalysis: Subtle Effect of Carboxylate Ligands and Mechanistic Insight.

A ruthenium(II) complex derived from the electron-deficient aromatic carboxylic acid 3-(F3C)C6H4CO2H proved to be a highly efficient catalyst for dehydrative alkyne annulation by NH-free hydroxamic acids in water. The C–H/N–OH functionalization occurred with excellent positional selectivity as well as ample substrate scope, setting the stage for effective intermolecular alkenylations of hydroxamic acids. Detailed mechanistic studies were suggestive of a kinetically relevant C–H metalation by carboxylate assistance along with subsequent migratory alkyne insertion, reductive elimination, and intramolecular oxidative addition.

A Stereoselective Access to Cyclic cis‐1,2‐Amino Alcohols from trans‐1,2‐Azido Alcohol Precursors

AbstractA unique one‐pot synthesis of cyclic cis‐1,2‐amino alcohols from trans‐1,2‐azido alcohol precursors was developed. The key step is highlighted by the stereoselective reduction of the cyclic α‐alkoxy imines, which could be prepared from the corresponding azides by ruthenium catalysis under photolytic conditions. Remarkably, this unprecedented reaction pathway offers a stereodivergent access to structurally diverse cyclic 1,2‐amino alcohols.magnified image

ChemInform Abstract: Early Steps of Homogeneous Catalysis in Rennes: Carbon Dioxide Incorporation, Alkyne Activation and Ruthenium Catalysis

AbstractReview: 109 refs.

ChemInform Abstract: Direct Allylation of Aromatic and α,β‐Unsaturated Carboxamides under Ruthenium Catalysis.

AbstractOther amide directing groups such as diethyl, methyl, dimethyl, or morpholinyl amido groups deliver the corresponding products with lower yields and lower regioselectivity than the pyrrolidinyl group.

C-H functionalization of phenols using combined ruthenium and photoredox catalysis: in situ generation of the oxidant.

A combination of ruthenium and photoredox catalysis allowed the ortho olefination of phenols. Using visible light, the direct C-H functionalization of o-(2-pyridyl)phenols occurred, and diverse phenol ethers were obtained in good yields. The regeneration of the ruthenium catalyst was accomplished by a photoredox-catalyzed oxidative process.

Alkyne hydroacylation: switching regioselectivity by tandem ruthenium catalysis.

By using tandem Ru-catalysis, internal alkynes can be coupled with aldehydes for the synthesis of β,γ-unsaturated ketones. The catalyst promotes alkyne transformations with high regioselectivity, with examples that include the differentiation of a methyl vs ethyl substituent on the alkyne. Mechanistic studies suggest that the regioselectivity results from a selective allene formation that is governed by allylic strain.

ChemInform Abstract: Ruthenium Catalyzed Regioselective Coupling of Terminal Alkynes, Amine and Carbon Dioxide Leading to anti‐Markovnikov Adducts.

AbstractThe reaction proceeds with excellent regioselectivity providing predominantly Z‐isomers of anti‐Markovnikov adducts.

ChemInform Abstract: Isoquinoline Skeleton Synthesis via Chelation‐Assisted C—H Activation

AbstractReview: [27 refs.

Cyclic (alkyl)(amino)carbenes (CAACs): stable carbenes on the rise.

CONSPECTUS: Carbenes are compounds that feature a divalent carbon atom with only six electrons in its valence shell. In the singlet state, they possess a lone pair of electrons and a vacant orbital and therefore exhibit Lewis acidic and Lewis basic properties, which explains their very high reactivity. Following the preparation by our group in 1988 of the first representative, a variety of stable carbenes are now available, the most popular being the cyclic diaminocarbenes. In this Account, we discuss another class of stable cyclic carbenes, namely, cyclic (alkyl)(amino)carbenes (CAACs), in which one of the electronegative and π-donor amino substituents of diaminocarbenes is replaced by a σ-donating but not π-donating alkyl group. As a consequence, CAACs are more nucleophilic (σ-donating) but also more electrophilic (π-accepting) than diaminocarbenes. Additionally, the presence of a quaternary carbon in the position α to the carbene center provides steric environments that differentiate CAACs dramatically from all other ligands. We show that the peculiar electronic and steric properties of CAACs allow for the stabilization of unusual diamagnetic and paramagnetic main group element species. As examples, we describe the preparation of room temperature stable phosphorus derivatives in which the heteroatom is in the zero oxidation state, nucleophilic boron compounds, and phosphorus-, antimony-, boron-, silicon-, and even carbon-centered neutral and cationic radicals. CAACs are also excellent ligands for transition metal complexes. The most recent application is their use for the stabilization of paramagnetic complexes, in which the metal is often in a formal zero oxidation state. Indeed, bis(CAAC)M complexes in which the metal is gold, copper, cobalt, iron, nickel, manganese, and zinc have been isolated. Depending on the metal, the majority of spin density can reside either on the metal or on the carbene carbons and the nitrogen atoms of the CAAC ligand. In contrast to diaminocarbenes, the higher basicity of CAACs makes them poor leaving groups, and thus they cannot be used for classical organocatalysis. However, because of their superior electrophilicity and smaller singlet-triplet gap, CAACs can activate small molecules at room temperature, such as CO, H2, and P4, as well as enthalpically strong bonds, such as B-H, Si-H, N-H, and P-H. Lastly, excellent results have been obtained in palladium, ruthenium, and gold catalysis. CAAC-metal complexes are extremely thermally robust, which allows for their utilization in harsh conditions. This property has been used to perform a variety of gold-catalyzed reactions in the presence of basic amines, including ammonia and hydrazine, which usually deactivate catalysts.

Early Steps of Homogeneous Catalysis in Rennes: Carbon Dioxide Incorporation, Alkyne Activation and Ruthenium Catalysis

This review reports the first discoveries in homogeneous catalysis in Rennes. Ruthenium(II) catalysts are shown to promote the activation of terminal alkynes and the synthesis of vinylcarbamates on addition of CO2 and amines. The ruthenium–vinylidene are the key catalytic species. Applications to the addition of carboxylic acids to alkynes have opened the access to various enolesters and dienylesters via controlled catalyzed Markovnikov or anti-Markonikov additions. The catalytic synthesis of α-methylene cyclic carbonates and oxazolidinones from propargylic alcohols and CO2 is presented and shown to lead to allene derivatives via palladium catalysis. Cp*RuX(COD) catalyst promote the head to tail oxidative couplings of alkene with alkyne, and the synthesis of functional dienes via 1,4 addition of H-nucleophiles to the biscarbene-ruthenium intermediate arising from head to head couplings of alkynes, whereas Cp*RuL2 + catalysts favour activation of alkynes via vinylidene intermediate. This historical review presents the first steps in homogeneous catalysis in Rennes starting in 1985 with ruthenium(II) catalysts promoting the activation of terminal alkynes via ruthenium–vinylidene or oxidative couplings for the synthesis of CO2 derivatives: vinylcarbamates, carbonates or oxazolidinones, enolesters and functional dienes.

Asymmetric reduction of ketones by biocatalysis using clementine mandarin (Citrus reticulata) fruit grown in Annaba or by ruthenium catalysis for access to both enantiomers.

Biocatalytic reduction of prochiral ketones using freshly ripened clementine mandarin (Citrus reticulata) in aqueous medium is reported. High enantioselectivities were observed, especially for the bioreduction of indanone , tetralone , and thiochromanone with respectively 95%, 99%, and 86% enantiomeric excess (ee). Enantioselective bio- and metal-catalyzed reactions were compared. Chiral ruthenium catalysts afforded good asymmetric inductions (>75% ee) in most cases, enantiomeric excesses depending on the nature of substrate and ligand. N-aminoindanol prolinamide was revealed as the best ligand for most ketones. Interestingly, for several substrates both enantiomers could be obtained using either Citrus reticulata or ruthenium complex.

ChemInform Abstract: Vinyl Dihydropyrans and Dihydrooxazines: Cyclizations of Catalytic Ruthenium Carbenes Derived from Alkynals and Alkynones.

A novel synthesis of 2-vinyldihydropyrans and dihydro-1,4-oxazines (morpholine derivatives) from alkynals and alkynones has been developed. The cyclizations require a mild generation of catalytic ruthenium carbenes from terminal alkynes and (trimethylsilyl)diazomethane followed by trapping with carbonyl nucleophiles. Mechanistic aspects of the new cyclizations are discussed.

Dehydrative C-H/N-OH functionalizations in H2O by ruthenium(II) catalysis: subtle effect of carboxylate ligands and mechanistic insight.

A ruthenium(II) complex derived from the electron-deficient aromatic carboxylic acid 3-(F3C)C6H4CO2H proved to be a highly efficient catalyst for dehydrative alkyne annulation by NH-free hydroxamic acids in water. The C-H/N-OH functionalization occurred with excellent positional selectivity as well as ample substrate scope, setting the stage for effective intermolecular alkenylations of hydroxamic acids. Detailed mechanistic studies were suggestive of a kinetically relevant C-H metalation by carboxylate assistance along with subsequent migratory alkyne insertion, reductive elimination, and intramolecular oxidative addition.