Valerian Dragutan

Targeted drugs by olefin metathesis: piperidine-based iminosugars

Examining advances in the class of natural and non-natural piperidine azasugars, important therapeutic agents and potent glycosidase inhibitors, this review looks at syntheses applying olefin metathesis as a highly efficient key step and gateway strategy for discovery of better iminosugar leads for treatment of widespread affections like viral and metabolic diseases. Amply illustrated is how ring-closing metathesis (RCM and RCEYM), promoted by commercial ruthenium alkylidene catalysts, manage to construct the common tetrahydropyridine core while cross-metathesis (CM), starting from this generic scaffold, provides general access to families of novel azasugars. Special consideration is given to high-profile iminosugar drugs of this class (1-deoxynojirimycin and congeners, adenophorine, fagomine, isofagomine and some of their N- and C-substituted analogues) stressing upon newest trends for enhancing biological activity and modulating previously unexploited targets in multispecific therapies.

New catalysts for linear polydicyclopentadiene synthesis

Abstract The ring-opening polymerization of dicyclopentadiene (DCPD) may occur in two ways: in the first way the reaction occurs by opening of the norbornene ring, in the second one both rings, norbornene and cyclopentene are involved. The polymerization of DCPD via opening of norbornene moiety implies the utilization of very selective catalytic systems. In our work, several new catalytic systems for synthesis of linear polydicyclopentadiene, derived from WCl 6 and WOCl 4 and organosilicon compounds have been employed. The microstructure of the linear polydicyclopentadiene (prepared from endo -DCPD) was evaluated from IR, and 13 C -NMR spectroscopy, showing that the polymer has prevailingly “ cis ” double bond configuration. The thermal behavior has been followed by differential scanning calorimetry. The linear polydicyclopentadiene obtained under these conditions has a glass-transition temperature of 53°C.

Metathesis access to monocyclic iminocyclitol-based therapeutic agents

Summary By focusing on recent developments on natural and non-natural azasugars (iminocyclitols), this review bolsters the case for the role of olefin metathesis reactions (RCM, CM) as key transformations in the multistep syntheses of pyrrolidine-, piperidine- and azepane-based iminocyclitols, as important therapeutic agents against a range of common diseases and as tools for studying metabolic disorders. Considerable improvements brought about by introduction of one or more metathesis steps are outlined, with emphasis on the exquisite steric control and atom-economical outcome of the overall process. The comparative performance of several established metathesis catalysts is also highlighted.

Ruthenium Complexes Bearing N-Heterocyclic Carbene (NHC) Ligands

A review of recently published aspects on ruthenium complexes with nucleophilic N-heterocyclic carbene (NHC) ligands is presented here, in continuation of a paper published in the July issue of this Journal, that covered initial work and subsequent main developments in this chemistry. In Part II selected applications of these complexes as pre-catalysts in metathesis reactions are highlighted. Particular attention is paid to metathesis in room temperature ionic liquids as the solvents, asymmetric catalysis, and in situ generated, very active catalytic systems based on NHC-platinum group metals. Most NHC-platinum group metal complexes are useful as highly active and selective pre-catalysts for fundamental chemical transformations.

Rational design and convenient synthesis of a novel family of ruthenium complexes with O,N-bidentate ligands

A two step procedure for the synthesis of a novel family of homogeneous and immobilized Ru-complexes containing Schiff bases as O,N-bidentate ligands is described. The new Ru-complexes have been structurally characterized by IR, Raman,1H-,13C-NMR spectroscopy. The Schiff bases were associated with a diversity of inorganic and organic ligands such as chloride, phosphane, arenes, various carbenes (alkylidene, vinylidene, indenylidene and allenylidene as well as N-heterocyclic carbenes) and cyclodienes. By choosing a selective range of substituents for the Schiff base, useful physical and chemical properties of the prepared Rucomplexes can be induced. This synthetic approach is promising in creating a valuable and diverse selection of Ru-complexes, valuable for future applications.

Editorial of Special Issue Ruthenium Complex: The Expanding Chemistry of the Ruthenium Complexes

Recent trends in Ru complex chemistry are surveyed with emphasis on the development of anticancer drugs and applications in catalysis, polymers, materials science and nanotechnology.

Ruthenium Complexes Containing Bidentate Schiff Base Ligands as Precursors of Homogeneous and Immobilized Catalysts

The paper presents recent work conducted in our group on the synthesis of a novel class of homogeneous and immobilized Ru- complexes containing Schiff bases as O,N-bidentate ligands benefiting from a versatile, quite general and thoroughly exemplified two- step procedure. The new Ru-complexes with improved stability incorporate a variety of Schiff bases, associated with traditional inorganic and organic ligands such as chloride, phosphanes, arenes, cyclodienes, NHC etc., and different carbenes (alkylidene, vinylidene, allenylidene and indenylidene). By a proper choice of the Schiff base, useful physical and chemical properties of the derived Ru- complexes could be induced resulting in tunable catalytic activity for metathesis and related processes. A pertinent example is the latency of selected Schiff base Ru catalysts which by becoming active only under specific conditions (heat or acid activation) are ideal for industrial applications, e.g. reaction injection molding processes. The synthetic approaches that are critically discussed in this artcile have led to a diversity of Ru-complexes of which several members have risen to the rank of commercial catalysts.

New aspects of the mechanism of the ring-opening polymerization of cyclo-olefins

Abstract The polymerization activity of the cyclopentene/WCl6 system initiated by water has been correlated with the occurrence of paramagnetic species involving the lower oxidation states of tungsten as detected by ESR spectroscopy. The W(III) species formed by the cyclo-olefin-controlled reduction of WCl6 were shown to be the precursors of the active species in polymerization reactions initiated by water in the absence of the alkylaluminium compound as a carbene source. The same W(III) species are assumed to be the precursor of the active species in the cyclopentene polymerization initiated by the WCl6/i-Bu3Al system. Attempts to polymerize cyclohexene in the presence of WCl6/i-Bu3Al failed; however, ESR signals assigned to W(V) and W(III) species were recorded. Independent studies carried out by mass spectrometry for the products resulting from the interaction between cyclopentene or cyclohexene and WCl6 demonstrated the existence of well-defined cyclic hydrocarbons along with 3-chlorocyclopentene and 3-chlorocyclohexene, respectively. The formation of these compounds may be explained via a cationic mechanism. The mechanisms of the initiation and propagation steps in polymerizations generated by carbene species from cyclo-olefin and WCl6 in the absence of alkylaluminium compounds are discussed. The role of the cyclo-olefin for reducing the tungsten compounds and producing the metallacarbene species is outlined. The sharp influence of strongly complexing additives on the reaction kinetics, catalyst activity and on the evolution of molecular weight with time in the polymerization of cyclopentene is presented.

ESR investigation of the interaction between WCl6-based catalysts and cyclo-olefins

Abstract Tungsten hexachloride, after 20 min contact with cyclopentene at room temperature, exhibited an ESR signal with a g-factor of 1.918 ± 0.004, aw = 70 G, ΔH

ROMP Synthesis of Iron-Containing Organometallic Polymers

25 G, assigned to a W(V) species. The intensity of this signal increased with time and showed a maximum after 200 min. After 72 h interaction, a second signal with a g-factor of 1.680 ± 0.04, ΔH = 110 ± 10 G, assigned to a W(III) species was detected. In a control experiment, the same W(III) signal was recorded for a reduced tungsten compound (in aqueous medium) whose oxidation state was determined by cerium sulphate titration. The above W(V) signal also resulted from the interaction of WCI6 with cyclohexene, cyclo-octene and cyclododecene. The variation with time of the intensity of this signal was characteristic for each cyclo-olefin. Higher reduction rates were observed for cyclopentene and cyclo-octene. Three distinct ESR signals were recorded during the polymerization of cyclopentene in the presence of the WCl6/epichlorohydrin/i-Bu3Al system. The first signal (g= 1.955 ± 0.005, ΔH =65 G) was assigned to a W(V) species, the second (g = 1.720 ± 0.03, ΔH = 45 G) to a W(III) species and the third (g = 2.018 ± 0.002, ΔH = 30 G) to a hydrocarbon radical species. The intensity of the W(III) species was related to the polymerization activity while that of the hydrocarbon radical species was related to catalyst deactivation. The ESR spectrum obtained during the interaction of cyclohexene with the WCl6/epichlorohydrin/i-Bu3Al system exhibited three characteristic signals (g1 = 2.008 ± 0.001, ΔH1 = 12 G;g2 = 1.830 ± O.02, ΔH2 = 60-100 G; g3 = 1.740 ± 0.02, ΔH3 = 40 G) assigned to the W(V) and W(III) species.