A Diverse View of Science to Catalyse Change.

Valuing diversity leads to scientific excellence, the progress of science and most importantly, it is simply the right thing to do. We can value diversity not only in words, but also in actions.

Electronic effects in mixed N-heterocyclic carbene/phosphite indenylidene ruthenium metathesis catalysts.

Five new complexes [RuCl2(SIMes)(Ind)(O-pXC5H4)] bearing different para-substituted triphenylphosphites (X = H, OCH3, CF3, Cl, SF5 and CN) were synthesised and used to study the effect of the electronic properties of the phosphite on olefin metathesis activity. Investigations of the physical properties of the new ligands and complexes were performed using physicochemical and DFT calculations. The catalytic activity of the complexes was benchmarked in challenging ring closing metathesis transformations featuring the formation of tetra-substituted double bonds. Complex [RuCl2(SIMes)(Ind)P(O-pCF3C5H4)3] (3c) exhibited a particularly high catalytic activity, superior to state-of-the-art catalysts, and was further tested on a wide range of substrates.

Key processes in ruthenium-catalysed olefin metathesis.

While the fundamental series of [2+2]cycloadditions and retro[2+2]cycloadditions that make up the pathways of ruthenium-catalysed metathesis reactions is well-established, the exploration of mechanistic aspects of alkene metathesis continues. In this Feature Article, modern mechanistic studies of the alkene metathesis reaction, catalysed by well-defined ruthenium complexes, are discussed. Broadly, these concern the processes of pre-catalyst initiation, propagation and decomposition, which all have a considerable impact on the overall efficiency of metathesis reactions.

Synthesis and structure of large difluoromethylene containing alicycles by ring closing metathesis (RCM).

Cyclotetra- and cyclohexa-decane ring systems were prepared with CF2 groups spaced 1,4- and 1,6- for tetradecanes together with 1,5- and 1,6- for hexadecanes. These alicyclic systems were assembled by ring closing metathesis reactions of long terminal diolefins. Ring cyclisation by RCM was promoted by the introduction of the dithiane motif, using a sulfur compatible metathesis catalyst. This gave rise to macrocyclic E-cycloalkanes, which were hydrogenated also using a sulfur compatible catalyst. Finally the dithianes emerged as appropriate precursor motifs for the introduction of difluoromethylene groups. X-Ray structures revealed that the resultant rings have the CF2 groups located only at corner positions and that these groups dictated the overall macrocyclic ring conformations.

Synthesis and broad spectrum antiviral evaluation of bis(POM) prodrugs of novel acyclic nucleosides.

A series of seventeen hitherto unknown ANP analogs bearing the (E)-but-2-enyl aliphatic side chain and modified heterocyclic base such as cytosine and 5-fluorocytosine, 2-pyrazinecarboxamide, 1,2,4-triazole-3-carboxamide or 4-substituted-1,2,3-triazoles were prepared in a straight approach through an olefin acyclic cross metathesis as key synthetic step. All novel compounds were evaluated for their antiviral activities against a large number of DNA and RNA viruses including herpes simplex virus type 1 and 2, varicella zoster virus, feline herpes virus, human cytomegalovirus, hepatitis C virus (HCV), HIV-1 and HIV-2. Among these molecules, only compound 31 showed activity against human cytomegalovirus in HEL cell cultures with at EC50 of ∼10 µM. Compounds 8a, 13, 14, and 24 demonstrated pronounced anti-HCV activity without significant cytotoxicity at 100 µM.

Accelerating influence of the gem-difluoromethylene group in a ring-closing olefin metathesis reaction. A Thorpe-Ingold effect?

The gem-difluoromethylene (CF2) group significantly accelerates ring-closing metathesis of 1,8-nonadienes relative to the methylene (CH2) group demonstrating similar rate accelerations to that observed for the classic Thorpe-Ingold substituents, diester malonates and ketals.

The activation mechanism of Ru-indenylidene complexes in olefin metathesis.

Olefin metathesis is a powerful tool for the formation of carbon-carbon double bonds. Several families of well-defined ruthenium (Ru) catalysts have been developed during the past 20 years; however, the reaction mechanism for all such complexes was assumed to be the same. In the present study, the initiation mechanism of Ru-indenylidene complexes was examined and compared with that of benzylidene counterparts. It was discovered that not all indenylidene complexes followed the same mechanism, highlighting the importance of steric and electronic properties of so-called spectator ligands, and that there is no single mechanism for the Ru-based olefin metathesis reaction. The experimental findings are supported quantitatively by DFT calculations.

How does the addition of steric hindrance to a typical N-heterocyclic carbene ligand affect catalytic activity in olefin metathesis?

Density functional theory (DFT) calculations were used to predict and rationalize the effect of the modification of the structure of the prototype 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) N-heterocyclic carbene (NHC) ligand. The modification consists in the substitution of the methyl groups of ortho isopropyl substituent with phenyl groups, and here we plan to describe how such significant changes affect the metal environment and therefore the related catalytic behaviour. Bearing in mind that there is a significant structural difference between both ligands in different olefin metathesis reactions, here by means of DFT we characterize where the NHC ligand plays a more active role and where it is a simple spectator, or at least its modification does not significantly change its catalytic role/performance.

Simple synthetic routes to ruthenium-indenylidene olefin metathesis catalysts.

An efficient synthetic protocol involving reactions between the free carbene and [RuCl(2)(PPh(3))(2)(Ind)] followed by addition of pyridine leads to the isolation of olefin metathesis active [RuCl(2)(L)(Py)(Ind)] (L = SIMes and SIPr) complexes. This novel approach circumvents the use of costly tricyclohexylphosphine.

Olefin metathesis featuring ruthenium indenylidene complexes with a sterically demanding NHC ligand.

The synthesis and characterization of two new ruthenium indenylidene complexes [RuCl(2)(SIPr)(Py)(Ind)] 6 and [RuCl(2)(SIPr)(3-BrPy)(Ind)] 7 featuring the sterically demanding N-heterocyclic carbene 1,3-bis(2,6-di isopropylphenyl)-4,5-dihydroimidazol-2-ylidene (SIPr) are reported. Remarkable activity was observed with these complexes in ring closing, enyne, and cross metathesis of olefins at low catalyst loadings. The performance of SIPr-bearing complexes 6 and 7 as well as [RuCl(2)(SIPr)(PCy(3))(Ind)] 5 in ring opening metathesis polymerization is also disclosed. This work highlights the enormous influence of the neutral "spectator" ligands on catalyst activity and stability.

Halide exchanged Hoveyda-type complexes in olefin metathesis.

The aims of this contribution are to present a straightforward synthesis of 2(nd) generation Hoveyda-type olefin metathesis catalysts bearing bromo and iodo ligands, and to disclose the subtle influence of the different anionic co-ligands on the catalytic performance of the complexes in ring opening metathesis polymerisation, ring closing metathesis, enyne cycloisomerisation and cross metathesis reactions.

Backbone tuning in indenylidene-ruthenium complexes bearing an unsaturated N-heterocyclic carbene.

The steric and electronic influence of backbone substitution in IMes-based (IMes = 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene) N-heterocyclic carbenes (NHC) was probed by synthesizing the [RhCl(CO)2(NHC)] series of complexes to quantify experimentally the Tolman electronic parameter (electronic) and the percent buried volume (%V(bur), steric) parameters. The corresponding ruthenium-indenylidene complexes were also synthesized and tested in benchmark metathesis transformations to establish possible correlations between reactivity and NHC electronic and steric parameters.

The influence of phosphane ligands on the versatility of ruthenium-indenylidene complexes in metathesis.

The aim of the present study is to develop readily available and stable pre-catalysts that could be easily prepared on large scale from simple starting materials. Based on the hypothesis that substitution of classical PCy(3) with phosphanes of varying electron-donating properties could be a straightforward manner to improve catalytic activity, a methodical study dealing with the effect of phosphane fine-tuning in ruthenium-indenylidene catalysts was performed. Challenged to establish how the electronic properties of para-substituted phosphane ligands translate into catalyst activity, the versatile behaviour of these new ruthenium-indenylidene complexes was investigated for a number of metathesis reactions.