Ruthenium Reagents Research Articles

Stereoselective Synthesis of α‐ʟ‐Rhamnopyranosides from ʟ‐Rhamnal Employing Ruthenium‐Catalysis

AbstractAn alternative and highly efficient ʟ‐rhamnosylation highlighting the dual‐catalysis of ruthenium reagent under a stereocontrolled process has been realized. The Ru‐mediated direct glycosylation‐dihydroxylation from ʟ‐rhamnal is amenable to a wide range of acceptors, including sugars, amino acids, natural products, and bioactive scaffolds. The one‐pot protocol tolerating diverse functional groups is attractive due to the valuable synthetic utility in assembling biologically significant α‐ʟ‐rhamnopyranosides in good yields. The mechanistic rationalization for the α‐anomeric selectivity and syn‐diastereoselective dihydroxylation employing Ru‐catalysis has been presented.

18F-labeled radiotracers for invivo imaging of DREADD with positron emission tomography.

Designer Receptors Exclusively Activated by Designer Drugs (DREADD) are a preclinical chemogenetic approach with clinical potential for various disorders. Invivo visualization of DREADDs has been achieved with positron emission tomography (PET) using 11C radiotracers. The objective of this study was to develop DREADD radiotracers labeled with 18F for a longer isotope half-life. A series of non-radioactive fluorinated analogs of clozapine with a wide range of invitro binding affinities for the hM3Dq and hM4Di DREADD receptors has been synthesized for PET. Compound [18F]7b was radiolabeled via a modified 18F-deoxyfluorination protocol with a commercial ruthenium reagent. [18F]7b demonstrated encouraging PET imaging properties in a DREADD hM3Dq transgenic mouse model, whereas the radiotracer uptake in the wild type mouse brain was low. [18F]7b is a promising long-lived alternative to the DREADD radiotracers [11C]clozapine ([11C]CLZ) and [11C]deschloroclozapine ([11C]DCZ).

ChemInform Abstract: Oxidation of Aryl Sulfides to Sulfones with Alumina‐Supported Ruthenium Catalyst in Dimethyl Carbonate—Water Media.

A new procedure for the oxidation of sulfides to sulfones utilizing heterogeneous ruthenium reagent has been developed. A small amount of ruthenium trichloride (RuCl 3 ) supported on alumina and excess sodium metaperiodate (NaIO 4 ) was used to produce the ruthenium oxidizing catalyst in the reaction mixture. Sodium metaperiodate oxidized the pre-catalyst RuCl 3 to RuO 4 and also maintained a constant supply of RuO 4 by oxidizing lower valent ruthenium ions during the course of the reaction. An environmentally friendly solvent mixture of dimethyl carbonate (DMC) and water was employed. A wide variety of aromatic sulfides were oxidized to sulfones in good to excellent yields by utilizing this procedure.

Oxidation of Aryl Sulfides to Sulfones with Alumina-Supported Ruthenium Catalyst in Dimethyl Carbonate–Water Media

A new procedure for the oxidation of sulfides to sulfones utilizing heterogeneous ruthenium reagent has been developed. A small amount of ruthenium trichloride (RuCl 3 ) supported on alumina and excess sodium metaperiodate (NaIO 4 ) was used to produce the ruthenium oxidizing catalyst in the reaction mixture. Sodium metaperiodate oxidized the pre-catalyst RuCl 3 to RuO 4 and also maintained a constant supply of RuO 4 by oxidizing lower valent ruthenium ions during the course of the reaction. An environmentally friendly solvent mixture of dimethyl carbonate (DMC) and water was employed. A wide variety of aromatic sulfides were oxidized to sulfones in good to excellent yields by utilizing this procedure.

ChemInform Abstract: The Glycol Cleavage in Natural Product Synthesis: Reagent Classics and Recent Advances

AbstractReview: [141 refs.

The Glycol Cleavage in Natural Product Synthesis: Reagent Classics and Recent Advances

This review focuses on the application of glycol cleavage reactions in the synthesis and derivatization of complex natural products. Reagent classics as well as recent developments are discussed. 1 Introduction 2 Mechanistic Aspects 3 Reagents and Examples 3.1 Periodate and Hypervalent Iodine 3.1.1 Periodic Acid and Periodates 3.1.2 Periodate on Wet Silica Gel 3.1.3 Phenyliodine Diacetate 3.1.4 Other Iodine Reagents 3.2 Lead Tetraacetate 3.3 Chromium Reagents 3.3.1 Pyridinium Chlorochromate 3.3.2 Other Chromium Reagents 3.4 Ruthenium Reagents 3.4.1 Tetra- n -propylammonium Perruthenate 3.4.2 Other Ruthenium Reagents 3.5 Manganese Reagents 3.5.1 Manganese(III) Acetate 3.5.2 Manganese Dioxide 3.5.3 Other Manganese Reagents 3.6 Miscellaneous 4 Conclusion

ChemInform Abstract: Allylic Oxidations of Olefins to Enones

AbstractReview: 234 refs.

Allylic Oxidations of Olefins to Enones

Allylic oxidations of olefins to enones are C–H functionalizations and are valuable organic transformations that permit the synthesis of value-added products from simple precursors. A variety of stoichiometric and catalytic metal-based methods are available for these conversions. In addition, metal-free and biocatalytic protocols are gaining in importance. This review summarizes the available oxidation methods and compares their regio- and chemoselectivities. 1 Introduction 2 Chromium-Based Oxidation 2.1 Stoichiometric Methods 2.2 Catalytic Methods 2.3 Chromium on Solid Support 3 Regio- and Chemoselectivity of Allylic Oxidations 4 Other Metal-Based Oxidations 4.1 Copper Reagents 4.2 Rhodium Reagents 4.3 Selenium Reagents 4.4 Cobalt Reagents 4.5 Ruthenium Reagents 4.6 Palladium Reagents 4.7 Iron Reagents 4.8 Other Metal Reagents 5 Metal-Free and Biocatalytic Methods 5.1 Metal-Free Methods 5.2 Biocatalytic Methods 6 Conclusion

ChemInform Abstract: Chiral Lewis Acids in Catalytic Asymmetric Reactions

This review examines the recent advances in the use of chiral Lewis acids, usually generated in situ from a Lewis acid and a chiral auxiliary, in the Diels-Alder reaction, the ene reaction, the hydrocyanation of aldehydes, the ring-opening of epoxides and various miscellaneous reactions. Structural studies of the complex formed between carbonyl compounds and Lewis acids are also reported. The Sharpless epoxidation is not covered by this review. 1. Introduction 2. Asymmetric Diels-Alder Reactions 2.1. Chiral Titanium Reagents 2.2. Chiral Aluminum Reagents 2.3. Chiral Boron Reagents 2.4. Chiral Ruthenium Reagents 3. Asymmetric [2+2] Cycloaddition Reactions 4. Asymmetric Ene Reaction 5. Asymmetric Hydrocyanation of Aldehydes 6. Asymmetric Ring Opening of Epoxides 7. Miscellaneous Asymmetric Reactions 8. Structural Studies on the Complexes of Carbonyl Compounds and Lewis Acids

The development of zeolite-entrapped organized molecular assemblies.

A brief summary is presented of the development of organized molecular assemblies entrapped within the supercages of Y-zeolite. Emphasis is placed on work originating in the author's laboratory, although a discussion of some of the important contributions made by other workers, which inspired and facilitated this work, are included. Following pioneering studies by Lunsford and co-workers, which demonstrated the feasibility of encapsulating the common photosensitizer [Ru(bpy)3]2+ within the Y-zeolite supercage, Dutta and co-workers documented efficient photoinduced electron transfer to viologen acceptors occupying neighboring supercages. We have extended the range of available materials by developing synthetically versatile methods to permit the incorporation of heteroleptic complexes, including constituent ligands which contain peripheral nitrogen donor groups; for example, 2,2'-bipyrazine. In an impressive study employing zeolite-excluded acceptors, Dutta and co-workers showed that the reducing equivalents available from photoinduced electron transfer from the zeolite entrapped sensitizer to intra-zeolite acceptors could be transferred to the extra-zeolite acceptors in aqueous suspensions, although the net charge-separation efficiency was low, presumably because of a persistent relatively efficient back-electron transfer process involving the primary photoproduct; that is, the entrapped sensitizer-acceptor dyad. Exploiting the susceptibility of certain heteroleptic complexes to add reactive ruthenium reagents, methods were developed to construct spatially organized donor-sensitizer-acceptor triads within the supercage framework of Y-zeolite. Such assemblies exhibit dramatically improved net charge-separation efficiencies, presumably as a consequence of inhibiting the wasteful back-electron transfer reaction between the initial sensitizer-acceptor couple.

Comparison between Iron and Ruthenium Reagents Mediating GifIV-Type Oxygenation of Cyclohexane

A ruthenium-based version of Barton's GifIV-type system (Rucat/Zn/O2 in pyridine/acetic acid) for the selective oxygenation of cycloalkanes has been studied in detail for the first time using a range of analytical techniques. The system, based on the use of the triruthenium complex [Ru3O(O2CCH3)6(py)3] in the presence of zinc powder in aerated pyridine/acetic acid (10:1 v/v), affords yields of cyclohexanone (main product) and cyclohexanol from cyclohexane comparable to that of the well-studied iron system based on the use of [Fe3O(O2CCH3)6(py)3]·py but with a lower selectivity for the ketone product. The time taken for the appearance and distribution of the -one/-ol products is different for the two metals and also depends on the efficiency of stirring of the zinc powder. The differing -one/-ol ratios and their times of appearance have been correlated with competing reactions on the intermediate cyclohexylhydroperoxide, most likely generated via oxygen- and carbon-centered radical chemistry. The appearanc...

Polymerization of 2-Ethyl-2-oxazoline Using Di-, Tetra-, and Hexafunctional Ruthenium Tris(bipyridine) Metalloinitiators

Ruthenium reagents with two, four, and six chloromethyl functionalities, [(bpy)nRu{bpy(CH2Cl)2}3-n](PF6)2 (n = 0−2), were employed as multifunctional metalloinitiators for the cationic polymerization of 2-ethyl-2-oxazoline to generate orange, glassy polymers with narrow molecular weight (MW) distributions. MWs were determined by GPC vs PMMA standards and for selected samples by GPC with multiangle laser light scattering (MALLS) detection. In-line diode array UV/vis spectroscopic analysis coupled with GPC MW determination confirms the presence of [Ru(bpy)3]2+ chromophores in the eluting polymers. Polymers are luminescent, and they exhibit thermal properties analogous to the metal-free PEOX counterparts (Tg ∼ 54 °C; onset of thermal decomposition at 365−385 °C). Unlike reactions run with a labile hexafunctional Fe initiator, reactions wherein MWs > 100K and degrees of polymerization (dp) >200 are attainable, Ru-centered polymers reach an upper MW limit of ∼25K regardless of the number of functionalities on the initiator (difunctional, dp = ∼125; tetrafunctional, dp = ∼63; hexafunctional, dp = ∼42 per initiator site). High monomer loadings and concentrations and elevated reaction temperatures were explored to surmount this barrier, and control experiments using different combinations of components found in typical Ru reaction mixtures are also described. Though Mn vs percent conversion plots are roughly linear for the Ru initiators, observed MWs are lower than expected values based on monomer/initiator loading. This may be due to poor correlation of polyoxazolines with linear PMMA standards and/or to competing chain transfer side reactions during the polymerization. Linear first-order kinetics plots were obtained. Comparison of rate constants obtained from the slopes of these plots reveals the trend expected for the targeted structures: hexa > tetra > di.

Cyclometalated Compounds. XI.1 Single and Double Cyclometalations of Poly(pyrazolylmethyl)benzenes

Six ligands containing 1,3-bis(pyrazol-1-ylmethyl)benzene subunits are shown to readily undergo cyclometalation reactions. 1,3-Bis(pyrazol-1-ylmethyl)-4,6-dimethylbenzene (1) is cyclopalladated to form the complex PdCl[C6HMe2(CH2pz)2-N,C,N] (3), containing two fused-ring six-membered metallocycles, for which the X-ray crystal structure of the DMSO solvate is described. The tetramethyl-substituted derivative C6H2Me2(CH2Me2pz)2 (2) and the 1,3,5-tris(pyrazol-1-ylmethyl)benzenes C6HMe2(CH2pz)3 (7) and C6HMe2(CH2Me2pz)3 (8) behave similarly. Reaction of 1 with a (terpyridine)ruthenium reagent ultimately produces the cycloruthenated derivative (tpy)Ru[C6HMe2(CH2pz)2-N,C,N]+ (6), the hexafluorophosphate salt of which is also crystallographically characterized. This reaction proceeds by way of a novel intermediate dication (tpy)Ru[C6H2Me2(CH2pz)2-N,N]2+ (5) that is shown, by detailed NMR studies, to contain an aryl C−H···Ru interaction. The 1,2,4,5-tetrakis(pyrazol-1-ylmethyl)benzenes C6H2(CH2pz)4 (12) and C6H2(...

Synthesis of Stegobiol and Its Oxidation to Stegobinone, the Components of the Female-Produced Sex Pheromone of the Drugstore Beetle

Crystalline (–)-stegobinone [(2S,3R,1′R)]-2,3-dihydro-2,3,5-trimethyl-6-(1′-methyl-2′-oxobutyl)-4H-pyran-4-one (1)], the major component of the female-produced sex pheromone of the drugstore beetle (Stegobium paniceum L.), was synthesized by oxidation of crystalline and the minor component (–)-stegobiol [(2S,3R,1′S,2′S)-2,3-dihydro-2,3,5-trimethyl-6-(2′-hydroxy-1′-methylbutyl)-4H-pyran-4-one (2)] under the appropriate conditions using Jones's chromic acid, Dess-Martin's periodinane or Ley's ruthenium reagent. The latter (2) was synthesized by employing lipase and the Sharpless epoxidation for the introduction of the proper chiral centers. The streostructure of 1 was comfirmed by X-ray analysis.

Carborane Complexes of Ruthenium: Reactions of [Ru(THF)(CO)2(η5-7,8-R2-7,8-C2B9H9)] (R = H or Me) with Alkylidyne Complexes of Molybdenum and Tungsten

The complex [Ru(THF)(CO)2(η5-7,8-C2B9H11)] (1a, THF = tetrahydrofuran) reacts with the alkylidyne reagents [M(⋮CC6H4Me-4)(CO)2(η5-C5H5)] (M = Mo or W) to give the compounds [MRu(μ-CC6H4Me-4)(CO)4(η5-7,8-C2B9H11)(η5-C5H5)] (M = W (2a), Mo (2b)), which readily isomerize to the species [MRu(CO)4{σ,η5-9-CH(C6H4Me-4)-7,8-C2B9H10}(η5-C5H5)] (M = W (3a), Mo (3b)). The structure of 3b was established by X-ray diffraction. The Mo(CO)2(η5-C5H5) fragment is attached to the closo-RuC2B9 framework by a Mo−Ru bond and a three-center two-electron B−H⇀Mo linkage involving a boron atom in an α site in the CCBBB ring ligating the ruthenium. The CH(C6H4Me-4) moiety bridges between the Ru(CO)2 group and the B atom located in the other α site in the CCBBB ring. The oxo complex [WRuO{μ-σ,η5-9-CH(C6H4Me-4)-7,8-C2B9H10}(CO)2(η5-C5H5)] (4a) is a side product in the formation of 3a, and it also was characterized by X-ray diffraction. Treatment of the species 3 with PMe3 affords the zwitterionic compounds [MRu(CO)4{η5-9-CH(PMe3)(C6H4Me-4)-7,8-C2B9H10}(η5-C5H5)] (M = W (5a), Mo (5b)). A single-crystal X-ray diffraction study of 5a revealed that the (OC)2W−Ru(CO)2 unit is bridged by the nido-9-CH(PMe3)(C6H4Me-4)-7,8-C2B9H10 group. The open C2B3 face is pentacoordinated to the Ru atom, and there is an exopolyhedral B−H⇀W bond involving a Bα atom in the CCBBB ring. The other Bα site carries the CH(PMe3)(C6H4Me-4) substituent. Reactions between the ruthenium reagent [Ru(THF)(CO)2(η5-7,8-Me2-7,8-C2B9H9)] (1b) and [W(⋮CC6H4Me-4)(CO)2(η5-C5H5)] gave [WRuO{μ-σ,η5-7,8-Me2-10-CH(C6H4Me-4)-7,8-C2B9H8}(CO)2(η5-C5H5)] (4b), [WRu(μ-H){μ-η5,η‘5-7,8-Me2-9-C5H4-10-CH2(C6H4Me-4)-7,8-C2B9H7}(CO)5] (6a), and [WRu{μ-σ,η5-2,7-Me2-8-CH2(C6H4Me-4)-9-C(H)O-2,7-C2B9H6}(CO)4(η5-C5H5)] (7a) that were separated by column chromatography. The corresponding reaction between 1b and [W(⋮CC6H4Me-2)(CO)2(η5-C5H5)] afforded [WRuO{μ-σ,η5-7,8-Me2-n-CH(C6H4Me-2)-7,8-C2B9H8}(CO)2(η5-C5H5)] (n = 9 (4c), 10 (4d)) and [WRu{μ-σ,η5-2,7-Me2-8-CH2(C6H4Me-2)-9-C(H)O-2,7-C2B9H6}(CO)4(η5-C5H5)] (7b). Treatment of 1b with [Mo(⋮CC6H4Me-n)(CO)2(η5-C5H5)] (n = 4 or 2) yielded [MoRu(μ-H){μ-η5,η‘5-7,8-Me2-9-C5H4-10-CH2(C6H4Me-n)-7,8-C2B9H7}(CO)5] (n = 4 (6b), 2 (6c)). The structures of 4b, 6b, and 7b were established by X-ray diffraction. In 6b, the (OC)3Mo(μ-H)Ru(CO)2 unit is bridged by a 7,8-Me2-9-C5H4-10-CH2(C6H4Me-4)-7,8-C2B9H7 moiety, a structure resulting from a linking of C5H5 and nido-C2B9 groups. The C5 ring is η5-coordinated to the molybdenum, while the open CCBBB face of the carborane cage is similarly attached to the ruthenium. In complex 7b, a nido-2,7-Me2-8-CH2(C6H4Me-2)-9-C(H)O-2,7-C2B9H6 cage system bridges the Ru−W bond with an η5-CB4 ring coordinated to the Ru atom and with the cage joined to the W atom by a B−W bond. In addition, the C(H)O group forms a second bridge linking the cage to the tungsten, with the latter coordinated by the formyl O atom.

Measurement of the Atomic Weight of Ruthenium by Negative Thermal Ionization Mass Spectrometry

Methods for ruthenium isotope measurement by both positive and negative ion thermal ionization mass spectrometry (PTI-MS and NTI-MS, respectively) are studied in this work. We found that Ru isotopes 100 and 104 are subjected to isobaric interferences from the silica gel used to improve sensitivity in PTI-MS. Measurement of ruthenium isotopes by NTI-MS is discussed here. The method is proved to be sensitive and free from the isobaric interferences. With precise isotope ratios of several ruthenium reagents measured by NTI-MS, we calculated the atomic weight of ruthenium to be 101.064 98 ± 0.000 16 (2σ), which is much more accurate than the data of 101.07 ± 0.02 currently suggested by IUPAC.

Partial synthesis of 6β-sesquiterpenolides from 6α-sesquiterpenolides

Chemical means were used to achieve the epimerization at C-6 of 6α-eudesmanolides, with several functionalizations, to 7β-eudesmanolides. The process consists of the LiAlH 4 reduction of a 6α-lactone, selective acetylation of the hydroxymethylene group at C-12, oxidation and reduction at C-6 to epimerize this carbon, deacetylation at C-12 and final formation of a 6β-lactone with RuH 2(Ph 3P) 4. The whole process yields nearly 40% of the 6β-lactone, oxidation with the ruthenium reagent (58 and 53%) being the limiting step.

Effect of pH on the reaction of tris(2,2′-bipyridyl)ruthenium(III) with amino-acids: Implications for their detection

A new technique for the detection of amino-acids is described, which is based on their chemiluminescence reaction with tris(2,2′-bipyridyl)ruthenium(III). The pH-dependence of this reaction has been investigated and found to be the key experimental parameter in application of this reaction as a detection technique. The chemiluminescence emission obtained is maximal at pH values higher than the N-terminal amino group p K a of the amino-acid. The background reaction between the ruthenium reagent and hydroxide ion does not occur with the same efficiency as the amino-acid reaction and the optimum signal to noise ratio is obtained at pH 10. A limit of detection of 30 picomole was found for valine and the response was shown to be linear over two orders of magnitude.

Chiral Lewis Acids in Catalytic Asymmetric Reactions

This review examines the recent advances in the use of chiral Lewis acids, usually generated in situ from a Lewis acid and a chiral auxiliary, in the Diels-Alder reaction, the ene reaction, the hydrocyanation of aldehydes, the ring-opening of epoxides and various miscellaneous reactions. Structural studies of the complex formed between carbonyl compounds and Lewis acids are also reported. The Sharpless epoxidation is not covered by this review. 1. Introduction 2. Asymmetric Diels-Alder Reactions 2.1. Chiral Titanium Reagents 2.2. Chiral Aluminum Reagents 2.3. Chiral Boron Reagents 2.4. Chiral Ruthenium Reagents 3. Asymmetric [2+2] Cycloaddition Reactions 4. Asymmetric Ene Reaction 5. Asymmetric Hydrocyanation of Aldehydes 6. Asymmetric Ring Opening of Epoxides 7. Miscellaneous Asymmetric Reactions 8. Structural Studies on the Complexes of Carbonyl Compounds and Lewis Acids

The pentaammineruthenium(III)histidine complex in ribonuclease A: Application to the assignment of histidine proton resonances

The assignment of two histidine proton resonances in the proton NMR spectrum of ribonuclease A has been made by forming a paramagnetic complex between pentaammineruthenium(III) and the N-3 nitrogen of a single histidine residue. Reaction of chloropentaammineruthenium(III)dichloride with ribonuclease A in 0.1 m Tris-HCl, pH 7.0, 25°C yields a variety of products in which various histidine residues have been labeled. Cation-exchange chromatography affords the isolation of a specific derivative, labeled at a single histidine residue, that retains 66% of the activity toward the hydrolysis of 2′,3′-cyclic CMP. The site of labeling was determined by peptide mapping to be histidine 105. The binding of ruthenium results in the disappearance of both a histidine C-2 and a C-4 proton resonance from the downfield region of the proton NMR spectrum, as expected from model compound studies. The assignment of these two resonances to histidine 105 is in agreement with a previous assignment ( J. L. Markley, 1975, Biochemistry, 14, 3546–3554), thereby demonstrating the potential utility of this ruthenium reagent in the assignment of histidine resonances in the proton NMR spectra of other proteins.