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A variety of structurally intricate polycycles have been assembled through ruthenium-catalysed ring-rearrangement metathesis of norbornene derivatives. The various substrates required for this work were prepared using Diels?Alder reactions and Grignard additions as key steps. Enyne ring-rearrangement metathesis of a norbornene system containing a propargyl moiety produced a 1,3-diene; this was then treated with an appropriate dienophile to deliver the corresponding cycloaddition product.

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Reference:
Highly efficient and robust molecular ruthenium catalysts for water oxidation,
Catalysts | Special Issue : Ruthenium Catalysts – MDPI

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To access high-quality small-molecule libraries to screen lead candidates for neglected diseases exemplified by human African trypanosomiasis, we sought to develop a synthetic process that would produce collections of cyclic scaffolds relevant to an assortment of natural products exhibiting desirable biological activities. By extracting the common structural features among several sesquiterpenes, including artemisinin, anthecularin, and transtaganolides, we designed six types of scaffolds with systematic structural variations consisting of three types of stereochemical relationships on the sp3 ring-junctions and two distinct arrays of tricyclic frameworks. A modular and stereodivergent assembly of dienynes exploiting a versatile manifold produced a series of cyclization precursors. Divergent cyclizations of the dienynes employing tandem ring-closing metathesis reactions overrode variant reactivities of the cyclization precursors, leading to the six canonical sets of the tricyclic scaffolds incorporating a diene group. Screenings of trypanosomal activities of the canonical sets, as well as regio- and stereoisomers of the tricyclic dienes, allowed generation of several antitrypanosomal agents defining the three-dimensional shape of the pharmacophore. The candidate tricyclic dienes were selected by primary screenings and further subjected to installation of a peroxide bridge, which generated artemisinin analogues that exhibited potent in vitro anti-trypanosomal activities comparable or even superior to those of artemisinin and the approved drugs, suramin and eflornithine.

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Reference:
Highly efficient and robust molecular ruthenium catalysts for water oxidation,
Catalysts | Special Issue : Ruthenium Catalysts – MDPI

Extended knowledge of (1,3-Bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene)dichloro(phenylmethylene)(tricyclohexylphosphine)ruthenium

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The thermal reaction of ester-tethered 1,3,8-triynes provides novel benzannulation products with concomitant incorporation of a nucleophile. Evidence suggests that this reaction proceeds via an allene-enyne intermediate generated by an Alder-ene reaction in the first step. Depending on the substituent of the alkyne moiety on the allene-enyne intermediate, the subsequent transformation can take one of two different paths, each leading to discrete aromatization products. The benzannulation of a silane-substituted 1,3,8-triynes provides arene products with a nucleophile incorporated onto the newly formed benzene core, whereas an aryl substituent leads to nucleophile trapping at the benzylic carbon atom connected to the aryl substituent. The formation of these two different products results from the involvement of two regioisomeric allene-enyne intermediates.

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Reference:
Highly efficient and robust molecular ruthenium catalysts for water oxidation,
Catalysts | Special Issue : Ruthenium Catalysts – MDPI

Extracurricular laboratory:new discovery of (1,3-Bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene)dichloro(phenylmethylene)(tricyclohexylphosphine)ruthenium

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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. Setting a trap: 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.

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Reference:
Highly efficient and robust molecular ruthenium catalysts for water oxidation,
Catalysts | Special Issue : Ruthenium Catalysts – MDPI

The important role of (1,3-Bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene)dichloro(phenylmethylene)(tricyclohexylphosphine)ruthenium

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(Chemical Equation Presented) H-bonding interactions have been exploitedextensively in the design of catalysts for stereoselective synthesis bu t have rarely been utilized in the development of metal-catalyzed processes. Studies described herein demonstrate that intramolecular H-bonding interactions can significantly increase the rate and levels of stereochemical control in Ru-catalyzed olefin metathesis reactions. The utility of H-bonding in catalytic olefin metathesis is elucidated through development of exceptionally facile and highly diastereoselective ring-opening/cross-metathesis (DROCM) reactions, involving achiral Ru catalysts and enantiomerically enriched allylic alcohols. Transformations proceed to completion readily (>98percent conversion, up to 87percent yield), often within minutes, in the presence of ?2 mol percent of an achiral catalyst to afford synthetically versatile products of high stereochemical purity (up to >98:2 dr and 11:1 E:Z).

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Reference:
Highly efficient and robust molecular ruthenium catalysts for water oxidation,
Catalysts | Special Issue : Ruthenium Catalysts – MDPI

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The synthesis and characterization of Ni(II) and Pd(II) alpha-diimine olefin polymerization catalysts bearing a fluorinated cyclophane-based ligand were performed. Fluorine was placed in such a manner as to interact with the metal center from the axial direction. The catalysts were active in the polymerization of ethylene, showing substantial differences in both catalytic behavior and polymer size and structure as compared to their nonfluorinated analogues. Both catalysts afforded polymer of comparatively low branching density and high molecular weight. The Ni(II) catalysts, from precursor [Ni(acetylacetonato)(F-Cyc)]+ salts (F-Cyc = fluorinated cyclophane), exhibited enhanced thermal stability by remaining active after 70 min with little loss in polymerization activity at 105C. The Pd(II) catalysts from salts of [Pd(F-CyC)Me(NCR)]+ (NCR = nitrile) afforded polymer of molecular weights far higher than the nonfluorinated analogue. Additionally, polymerization activity was directly related to ethylene feed pressure for the Pd(II) system, and NMR analysis could not detect the presence of bound olefin, indicating that the polymerization proceeded via different kinetics involving an olefln-free 14- complex as the catalyst resting state. Furthermore, NMR 1H-19F coupling data provide clear evidence that the fluorine atoms were indeed interacting with the metal axial site. The unusual properties of these new complexes are thus attributed to stabilization of the highly reactive 14 e- intermediate by donation of the fluorine lone pair to the metal center.

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Reference:
Highly efficient and robust molecular ruthenium catalysts for water oxidation,
Catalysts | Special Issue : Ruthenium Catalysts – MDPI

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The first total synthesis of the title diterpene was accomplished starting from the Wieland?Miescher ketone. A diastereoselective sulfa-Michael addition enabled the generation of the delicate beta,gamma-unsaturated ketone moiety, while the tetracyclic kempane skeleton was readily constructed through domino metathesis.

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Reference:
Highly efficient and robust molecular ruthenium catalysts for water oxidation,
Catalysts | Special Issue : Ruthenium Catalysts – MDPI

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The 1,4-diphospha-2-azol-5-ylidene is a homologue to the Ender’s type carbene. It is a possible candidate for a ligand in the metathesis reaction of olefins. Based on density functional calculations the differences between the electronic structures of both systems are evaluated. The NHC (N-heterocyclic carbene) possesses a larger singlet-triplet energy separation than the PHC (P-heterocyclic carbene) analogue. Thus the latter exerts a larger Lewis acidity than the former. In comparison with, the donor-ability (sigma-basicity) in both systems is similar. As a consequence for the PHC carbene a Ru-fragment as a ligand for catalysis is stronger bound. This causes in the olefin metathesis a lower dissociation energy (compared to the NHC analogue) with respect to the formation of the catalyst active 14el species. As a consequence, the olefin will be weaker bound as well. This can be overcome by attaching sterically demanding substituents such as mesityl or super-mesityl to the phosphorus atoms. They induce mutual steric hindrance with concomitant increase of the S-T separation of the free carbene. Thus the Lewis acidity of the carbene is reduced. On this basis for the PHC’s with larger S-T energy separations the dissociation energy of the phosphine fragment is raised and the adding olefin fragment will be stronger bound to the transition metal. While these effects describe the electronic situation in the reactive species, steric effects at the ligand carbene mediate the stabilities of the individual intermediates in the metathesis reaction by exertion of inter- and intra-ligand repulsion.

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Reference:
Highly efficient and robust molecular ruthenium catalysts for water oxidation,
Catalysts | Special Issue : Ruthenium Catalysts – MDPI

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The formation of the macrocyclic core of crassin acetate from an acyclic precursor could be effected by ring-closing alkyne metathesis reactions while ring-closing olefin metathesis reactions failed. Installment of necessary stereochemistry was achieved by Sharpless asymmetric epoxidations on allylic alcohols obtained from geranyl acetate or farnesyl acetate. The macrocyclic core of crassin acetate could thus be made from geranyl or farnesyl acetate in 12 steps with a total yield of 6.7% and 11.0%, respectively.

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Reference:
Highly efficient and robust molecular ruthenium catalysts for water oxidation,
Catalysts | Special Issue : Ruthenium Catalysts – MDPI

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A second generation Hoveyda-Grubbs ruthenium carbene complex bearing an ionic liquid tag was prepared and shown to be a highly reactive catalyst for the ring-closing metathesis of di-, tri- and tetrasubstituted diene and enyne substrates in minimally ionic solvent systems ([Bmim]PF6/CH 2Cl2, 1:9-1:1 v/v). Both the catalyst and the ionic liquid can be conveniently recycled and repeatedly reused (up to 17 cycles) with only a very slight loss of activity. The ionic liquid tag is crucial to the high level of recyclability of the catalyst since the original second generation Grubbs and Hoveyda-Grubbs catalysts rapidly lose their activity when recycled in the ionic liquid layer.

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Reference:
Highly efficient and robust molecular ruthenium catalysts for water oxidation,
Catalysts | Special Issue : Ruthenium Catalysts – MDPI