CpRu Complex Research Articles

Evaluation of the Antiproliferative Properties of CpRu Complexes Containing N-Methylated Triazaphosphaadamantane Derivatives.

Piano-stool-{CpRu} complexes containing 1,3,5-triaza-7-phosphaadamantane (PTA), N-methyl-1,3,5-triaza-7-phosphaadamantane (mPTA), and 3,7-dimethyl-1,3,7-triaza-5-phosphabyciclo[3.3.1]nonane (dmoPTA) were evaluated as drugs against breast cancer. The evaluated compounds include two new examples of this family, the complexes [RuCp(DMSO-κS)(HdmoPTA)(PPh3)](CF3SO3)2 (8) and [RuCp(PPh3)2-µ-dmoPTA-1κP-2κ2N,N'-PdCl2](CF3SO3) (11), which have been synthesized and characterized by NMR, IR, and single-crystal X-ray diffraction. The cytotoxic activity of compounds was evaluated against MDA-MB-231 breast cancer cells, and the three most active complexes were further tested against the hormone-dependent MCF-7 breast cancer cell line. Their cell death mechanism and ruthenium uptake were also evaluated, as well as their binding ability to human serum albumin.

Mechanism of the Asymmetric Dehydrative Allylative Cyclization of Alcohols to Cyclic Ethers Catalyzed by a CpRu Complex of the Chiral Picolinic Acid-Type Ligand, Cl-Naph-PyCOOH: Is a π-Allyl Intermediate Present?

Abstract [Ru(II)Cp((R)-Cl-Naph-PyCOOH)]PF6 ((R)-1) catalyzes the dehydrative cyclization of (E)-hept-2-ene-1,7-diol (2) to 2-vinyltetrahydro-2H-pyran (3) with a 97:3 S/R enantiomer ratio. Complex (R)-1 is in equilibrium between two diastereomers (R,RRu)-1 (AR) and (R,SRu)-1 (AS). A difference of turn over efficiency between the AS and AR cycles is thought to be the origin of the high enantioselectivity. The AS gives a major enantiomeric product (S)-3, according to the results of detailed mechanistic investigation via i) X-ray crystallographic analysis of related complexes, ii) NMR experiments using allylic alcohol 2, OH-lacking 2-mimic 4, d-labeled (S)-4-1d, enantiomerically enriched hept-6-ene-1,5-diol (6) as branched isomer of 2, and OH-lacking 6-mimic 5, iii) substrate structure/reactivity and selectivity relationships, iv) deuterium-labeling experiment, v) kinetics via calorimetric analysis, and vi) ligand structure/reactivity and selectivity relationships. AS captures 2 via hydrogen and halogen bonds. Oxidative addition in an H2Oin mode leads to a macrocyclic σ-allyl intermediate. Here, an efficient nC(7)OH/π*C(3)=C(2) trans-annular (TA) interaction facilitates an SN2′ nucleophilic addition of OH in an OHTA manner to furnish (S)-3. Contrary to the AS, AR cannot capture 2 using the halogen bond and slowly operates to give (R)-3. A conventional π-allyl-complex-involved mechanism is ruled out by a contradiction in the result of ii) and iii).

CpRuII-chiral bisamidine complex catalyzed asymmetric Carroll-type decarboxylative allylation of β-keto allyl esters

Carroll-rearrangement-type intramolecular decarboxylative allylation of β-keto allyl esters with a cationic CpRu complex bearing a chiral bisamidine-type bidentate ligand is reported. The catalytic system allows the efficient transformation of the mono substituted, 3-arylallyl esters of β-keto acids to the corresponding γ,δ-enones. Notably, the catalytic turnover is more than an order higher than that of the previously reported examples. The developed reaction system displays improved regioselectivity and enantioselectivity and a broad substrate scope. Mechanistic studies using NMR experiments, substrate-structure/reactivity relationship studies, and crossover experiment reveal a possible reaction pathway involving the enolate of the β-keto acid.

CpRu Complexes Containing Water Soluble Phosphane PTA and Natural Purines Adenine, Guanine and Theophylline: Synthesis, Characterization, and Antiproliferative Properties

Complexes [RuCp(Adeninate‐κN9)(PTA)2] (1), [RuCp(Guaninate‐κN9)(PTA)2] (2), [RuCp(Theophyllinate‐κN7)(PTA)2] (3), [RuCp(Adeninate‐κN9)(PPh3)(PTA)] (4), [RuCp(Guaninate‐κN9)(PPh3)(PTA)] (5) and [RuCp(Theophyllinate‐κN7)(PPh3)(PTA)] (6) were synthesized and characterized by NMR spectroscopy, elemental analysis and FT‐IR (PTA = 1,3,5‐triaza‐7‐phosphaadamantane). Crystal structures of 1·H2O·3EtOH, 3·CH3COCH3 and 4·H2O were also determined by single‐crystal X‐ray diffraction. The antiproliferative activities of the complexes against cisplatin‐sensitive T2 and cisplatin‐resistant SKOV3 cell lines have also been evaluated. Theoretical studies were preformed to elucidate how the adeninate ligand is coordinated to the metal.

Intramolecular Tsuji-Trost-type Allylation of Carboxylic Acids: Asymmetric Synthesis of Highly π-Allyl Donative Lactones.

Tsuji-Trost-type asymmetric allylation of carboxylic acids has been realized by using a cationic CpRu complex with an axially chiral picolinic acid-type ligand (Cl-Naph-PyCOOH: naph = naphthyl, py = pyridine). The carboxylic acid and allylic alcohol intramolecularly condense by the liberation of water without stoichiometric activation of either nucleophile or electrophile part, thereby attaining high atom- and step-economy, and low E factor. This success can be ascribed to the higher reactivity of allylic alcohols as compared with the allyl ester products in soft Ru/hard Brønstead acid combined catalysis, which can function under slightly acidic conditions unlike the traditional Pd-catalyzed system. Detailed analysis of the stereochemical outcome of the reaction using an enantiomerically enriched D-labeled substrate provides an intriguing view of enantioselection.

Original reactivity of α-diazo-β- ketoesters catalyzed by CpRu complexes.

Using α-diazo-β-ketoesters as reagents and combinations of CpRu fragments and diimine ligands as catalysts, a series of original transformations have been obtained that can be rationalized by the formation of metal carbenes and metal-bound ylide intermediates. Interesting 1,3-dioxole, enol-acetal and 1,4-dioxene motifs are obtained directly when the reactive mixture is reacted in presence of aldehydes or ketones, THF and epoxides.

ChemInform Abstract: Enol Acetal Synthesis Through Carbenoid C—H Insertion into Tetrahydrofuran Catalyzed by CpRu Complexes.

AbstractThe investigations indicate that C—O bond forming is kinetically preferred over C—C bond forming using the CpRu‐catalyst combination.

Enol Acetal Synthesis through Carbenoid CH Insertion into Tetrahydrofuran Catalyzed by CpRu Complexes

Enol Acetal Synthesis through Carbenoid CH Insertion into Tetrahydrofuran Catalyzed by CpRu Complexes

Enol Acetal Synthesis through Carbenoid CH Insertion into Tetrahydrofuran Catalyzed by CpRu Complexes

Intermolecular C—O instead of —CC bond formation is achieved with [CpRu(CH3CN)3][PF6] and diimine ligands as catalysts of the decomposition of α-diazo-β-ketoesters in THF leading to original products of 1,3 CH insertion.

ChemInform Abstract: Enantioselective Synthesis of Pyrrolidine‐, Piperidine‐, and Azepane‐Type N‐Heterocycles with α‐Alkenyl Substitution: The CpRu‐Catalyzed Dehydrative Intramolecular N‐Allylation Approach.

A cationic CpRu complex of chiral picolinic acid derivatives [(R)- or (S)-Cl-Naph-PyCOOCH2CH═CH2] catalyzes asymmetric intramolecular dehydrative N-allylation of N-substituted ω-amino- and -aminocarbonyl allylic alcohols with a substrate/catalyst ratio of up to 2000 to give α-alkenyl pyrrolidine-, piperidine-, and azepane-type N-heterocycles with an enantiomer ratio of up to >99:1. The wide range of applicable N-substitutions, including Boc, Cbz, Ac, Bz, acryloyl, crotonoyl, formyl, and Ts, significantly facilitates further manipulation toward natural product synthesis.

Enantioselective Synthesis of Pyrrolidine-, Piperidine-, and Azepane-Type N-Heterocycles with α-Alkenyl Substitution: The CpRu-Catalyzed Dehydrative Intramolecular N-Allylation Approach

A cationic CpRu complex of chiral picolinic acid derivatives [(R)- or (S)-Cl-Naph-PyCOOCH(2)CH═CH(2)] catalyzes asymmetric intramolecular dehydrative N-allylation of N-substituted ω-amino- and -aminocarbonyl allylic alcohols with a substrate/catalyst ratio of up to 2000 to give α-alkenyl pyrrolidine-, piperidine-, and azepane-type N-heterocycles with an enantiomer ratio of up to >99:1. The wide range of applicable N-substitutions, including Boc, Cbz, Ac, Bz, acryloyl, crotonoyl, formyl, and Ts, significantly facilitates further manipulation toward natural product synthesis.

Catalytic nucleophilic activation of acetonitrile via a cooperative catalysis of cationic Ru complex, DBU, and NaPF 6

The development of an efficient catalytic system for the direct addition of acetonitrile under mild amine basic conditions is described. A cooperative catalysis of CpRu complex, DBU, and NaPF 6 enables chemoselective and catalytic generation of nucleophiles from barely acidic acetonitrile, which is integrated into the addition to aldehydes, imines, and activated ketones. Mechanistic investigations revealed that the three catalyst components work together to achieve high catalytic efficiency.