Studies on Electronic Effects in O‐, N‐ and S‐Chelated Ruthenium Olefin‐Metathesis Catalysts

A short overview on the structural design of the Hoveyda–Grubbs‐type ruthenium initiators chelated through oxygen, nitrogen or sulfur atoms is presented. Our aim was to compare and contrast O‐, N‐ and S‐chelated ruthenium complexes to better understand the impact of electron‐withdrawing and ‐donating substituents on the geometry and activity of the ruthenium complexes and to gain further insight into the trans–cis isomerisation process of the S‐chelated complexes. To evaluate the different effects of chelating heteroatoms and to probe electronic effects on sulfur‐ and nitrogen‐chelated latent catalysts, we synthesised a series of novel complexes. These catalysts were compared against two well‐known oxygen‐chelated initiators and a sulfoxide‐chelated complex. The structures of the new complexes have been determined by single‐crystal X‐ray diffraction and analysed to search for correlations between the structural features and activity. The replacement of the oxygen‐chelating atom by a sulfur or nitrogen atom resulted in catalysts that were inert at room temperature for typical ring‐closing metathesis (RCM) and cross‐metathesis reactions and showed catalytic activity only at higher temperatures. Furthermore, one nitrogen‐chelated initiator demonstrated thermo‐switchable behaviour in RCM reactions, similar to its sulfur‐chelated counterparts.     

Z‐Selective Cross Metathesis with Ruthenium Catalysts: Synthetic Applications and Mechanistic Implications

Olefin cross metathesis is a particularly powerful transformation that has been exploited extensively for the formation of complex products. Until recently, however, constructing Z‐olefins using this methodology was not possible. With the discovery and development of three families of ruthenium‐based Z‐selective catalysts, the formation of Z‐olefins using metathesis is now not only possible but becoming increasingly prevalent in the literature. In particular, ruthenium complexes containing cyclometalated NHC architectures developed in our group have been shown to catalyze various cross metathesis reactions with high activity and, in most cases, near perfect selectivity for the Z‐isomer. The types of cross metathesis reactions investigated thus far are presented here and explored in depth.     

Ruthenium dihydride complexes as enyne metathesis catalysts

Ruthenium–catalyzed enyne metathesis is a reliable and efficient method for the formation of 1,3-dienes, a common structural motif in synthetic organic chemistry. The development of new transition-metal complexes competent to catalyze enyne metathesis reactions remains an important research area. This report describes the use of ruthenium (IV) dihydride complexes with the general structure RuH₂Cl₂(PR₃)₂ as new catalysts for enyne metathesis. These ruthenium (IV) dihydrides have been largely unexplored as catalysts in metathesis-based transformations. The reactivity of these complexes with 1,6 and 1,7-enynes was investigated. The observed reaction products are consistent with the metathesis activity occurring through a ruthenium vinylidene intermediate.     

ESIMS Studies and Calculations on Alkali‐Metal Adduct Ions of Ruthenium Olefin Metathesis Catalysts and Their Catalytic Activity in Metathesis Reactions

Electrospray ionization mass spectrometry (ESIMS) and subsequent tandem mass spectrometry (MS/MS) analyses were used to study some important metathesis reactions with the first‐generation ruthenium catalyst 1 , focusing on the ruthenium complex intermediates in the catalytic cycle. In situ cationization with alkali cations (Li⁺, Na⁺, K⁺, and Cs⁺) using a microreactor coupled directly to the ESI ion source allowed mass spectrometric detection and characterization of the ruthenium species present in solution and particularly the catalytically active monophosphine–ruthenium intermediates present in equilibrium with the respective bisphosphine–ruthenium species in solution. Moreover, the intrinsic catalytic activity of the cationized monophosphine–ruthenium complex 1 a ?K⁺ was directly demonstrated by gas‐phase reactions with 1‐butene or ethene to give the propylidene Ru species 3 a ?K⁺ and the methylidene Ru species 4 a ?K⁺, respectively. Ring‐closing metathesis (RCM) reactions of 1,6‐heptadiene ( 5 ), 1,7‐octadiene ( 6 ) and 1,8‐nonadiene ( 7 ) were studied in the presence of KCl and the ruthenium alkylidene intermediates 8 , 9 , and 10 , respectively, were detected as cationized monophosphine and bisphosphine ruthenium complexes. Acyclic diene metathesis (ADMET) polymerization of 1,9‐decadiene ( 14 ) and ring‐opening metathesis polymerization (ROMP) of cyclooctene ( 18 ) were studied analogously, and the expected ruthenium alkylidene intermediates were directly intercepted from reaction solution and characterized unambiguously by their isotopic patterns and ESIMS/MS. ADMET polymerization was not observed for 1,5‐hexadiene ( 22 ), but the formation of the intramolecularly stabilized monophosphine ruthenium complex 23 a was seen. The ratio of the signal intensities of the respective with potassium cationized monophosphine and bisphosphine alkylidene Ru species varied from [I _4a ]/[I ₄ ]=0.02 to [I _23a ]/[I ₂₃ ]=10.2 and proved to be a sensitive and quantitative probe for intramolecular π‐complex formation of the monophosphine–ruthenium species and of double bonds in the alkylidene chain. MS/MS spectra revealed the intrinsic metathesis catalytic activity of the potassium adduct ions of the ruthenium alkylidene intermediates 8 a , 9 a , 10 a , 15 a , and 19 a , but not 23 a by elimination of the respective cycloalkene in the second step of RCM. Computations were performed to provide information about the structures of the alkali metal adduct ions of catalyst 1 and the influence of the alkali metal ions on the energy profile in the catalytic cycle of the metathesis reaction.     

Alkyne gem‐Hydrogenation: Formation of Pianostool Ruthenium Carbene Complexes and Analysis of Their Chemical Character

Parahydrogen (p‐H₂) induced polarization (PHIP) NMR spectroscopy showed that [Cp^XRu] complexes with greatly different electronic properties invariably engage propargyl alcohol derivatives into gem‐hydrogenation with formation of pianostool ruthenium carbenes; in so doing, less electron rich Cp^X rings lower the barriers, stabilize the resulting complexes and hence provide opportunities for harnessing genuine carbene reactivity. The chemical character of the resulting ruthenium complexes was studied by DFT‐assisted analysis of the chemical shift tensors determined by solid‐state ¹³C NMR spectroscopy. The combined experimental and computational data draw the portrait of a family of ruthenium carbenes that amalgamate purely electrophilic behavior with characteristics more befitting metathesis‐active Grubbs‐type catalysts.     

The doping effect of fluorinated aromatic solvents on the rate of ruthenium-catalysed olefin metathesis

A study concerning the effect of using a fluorinated aromatic solvent as the medium for olefin metathesis reactions catalysed by ruthenium complexes bearing N-heterocyclic carbene ligands is presented. The use of fluorinated aromatic hydrocarbons (FAH) as solvents for olefin metathesis reactions catalysed by standard commercially available ruthenium pre-catalysts allows substantially higher yields of the desired products to be obtained, especially in the case of demanding polyfunctional molecules, including natural and biologically active compounds. Interactions between the FAH and the second-generation ruthenium catalysts, which apparently improve the efficiency of the olefin metathesis transformation, have been studied by X-ray structure analysis and computations, as well as by carrying out a number of metathesis experiments. The optimisation of reaction conditions by using an FAH can be regarded as a complementary approach for the design of new improved ruthenium catalysts. Fluorinated aromatic solvents are an attractive alternative medium for promoting challenging olefin metathesis reactions.     

Chemodivergent Metathesis of Dienynes Catalyzed by Ruthenium–Indenylidene Complexes: An Experimental and Computational Study

A study on the enyne metathesis reaction leading to the formation cyclic compounds using ruthenium–indenylidene complexes is presented. Several 1,11‐dien‐6‐ynes have been subjected to ruthenium metathesis cyclization by using ruthenium–indenylidene complexes bearing various phosphine and N‐heterocyclic carbene (NHC) ligands. Interestingly, for some substrates chemodivergent metathesis occurs and is a function of the catalyst employed. This led us to investigate the competing “ene‐then‐yne” or “yne‐then‐ene” reaction pathways apparently at play in these systems using both experimental observations and DFT calculations. Experimental and computational studies were found in good agreement and permit to conclude that for phosphine‐containing catalysts, the “ene‐then‐yne” pathway is exclusively adopted. On the other hand, for catalysts bearing NHC ligands, both pathways are possible.     

New latent metathesis catalysts equipped with exchangeable boronic ester groups on the NHC

Abstract

Latent metathesis catalysts equipped with boronate esters of diols as exchangeable end-groups on their NHC ligands and an S-chelated ruthenium-benzylidene core were synthesized. The stable S-chelated ruthenium complexes underwent hydrolysis under mild acidic conditions, allowing easy exchange of terminal units by several 1,2- and 1,3-diols, without degrading the central ruthenium benzylidene. Using this strategy, we also prepared metathesis catalysts equipped with diallyl substrates at the termini that showed concentration dependency on RCM reactions. Notably, the larger dendritic catalysts were more efficient at the more dilute condition.     

Synthesis and Evaluation of Ruthenium 2‐Alkyl‐6‐mercaptophenolate Catalysts for Olefin Metathesis

A series of ruthenium carbene catalysts containing 2‐sulfidophenolate bidentate ligand with an ortho‐substituent next to the oxygen atom were synthesized. The molecular structure of ruthenium carbene complex containing 2‐isopropyl‐6‐sulfidophenolate ligand was confirmed through single crystal X‐ray diffraction. An oxygen atom can be found in the opposite position of the N‐heterocyclic carbene (NHC) based on the steric hindrance and strong trans‐effects of the NHC ligand. The ruthenium carbene catalyst can catalyze ring‐opening metathesis polymerization (ROMP) reaction of norbornene with high activity and Z‐selectivity and cross metathesis (CM) reactions of terminal alkenes with (Z)‐but‐2‐ene‐1,4‐diol to give Z‐olefin products (Z/E ratios, 70:30–89:11) in low yields (13%–38%). When AlCl₃ was added into the CM reactions, yields (51%–88%) were considerably improved and process becomes highly selective for E‐olefin products (E/Z ratios, 79:21–96:4). Similar to other ruthenium carbene catalysts, these new complexes can tolerate different functional groups.     

Mechanistic Studies of Hoveyda–Grubbs Metathesis Catalysts Bearing S‐, Br‐, I‐, and N‐coordinating Naphthalene Ligands

Derivatives of the Hoveyda–Grubbs complex bearing S‐, Br‐, I‐, and N‐coordinating naphthalene ligands were synthesized and characterized with NMR and X‐ray studies. Depending on the arrangement of the coordinating sites on the naphthalene core, the isomeric catalysts differ in activity in model metathesis reactions. In particular, complexes with the Ru?CH bond adjacent to the second aromatic ring of the ligand suffer from difficulties experienced on their preparation and initiation. The behavior most probably derives from steric hindrance around the double bond and repulsive intraligand interactions, which result in abnormal chemical shifts of benzylidene protons observed with ¹H NMR. Furthermore EXSY studies revealed that the halogen‐chelated ruthenium complexes display an equilibrium, in which major cis‐Cl₂ structures are accompanied with small amounts of isomeric forms. In general, contents of the minor forms, measured at 80 °C, correlate with the observed activity trends of the catalysts, although some exceptions complicate the mechanistic picture. We assume that for the family of halogen‐chelated metathesis catalysts the initiation mechanism starts with the cis‐Cl₂?trans‐Cl₂ isomerization, although further steps may become rate‐limiting for selected systems.     

Latent ruthenium carbene complexes with six-membered N- and S-chelate rings

New ruthenium carbene complexes with chelating N- and S-benzylidene ligands were synthesized by the reactions of second- and third-generation Grubbs catalysts with ortho-vinylbenzyl-substituted amines or sulfides. These complexes were shown to exhibit catalytic activity in ring-opening metathesis polymerization and ring-closing metathesis.     

Latent ruthenium olefin metathesis catalysts featuring a phosphine or an N-heterocyclic carbene ligand

The synthesis and characterization of latent 18-electron ruthenium benzylidene complexes (PCy₃)((^κN,O)-picolinate)₂RuCHPh (5) and (H₂IMes)((^κN,O)-picolinate)₂RuCHPh (6) are described. Both complexes appear as two isomers. The ratio between the isomers is dependent on l-type ligand. The complexes are inactive in ring-closing metathesis and ring-opening metathesis polymerization reactions even at elevated temperatures in the absence of stimuli. Upon addition of HCl, complexes 5 and 6 become highly active in olefin metathesis reactions. The advantage of the latent catalysts is demonstrated in the ring-opening metathesis polymerization of dicyclopentadiene, where the latency of 6 assures adequate mixing of catalyst and monomer before initiation. Trapping experiments suggests that the acid converts the 18-electron complexes into their corresponding highly olefin metathesis active 14-electron benzylidenes.     

Unprecedented Selectivity of Ruthenium Iodide Benzylidenes in Olefin Metathesis Reactions

The development of selective olefin metathesis catalysts is crucial to achieving new synthetic pathways. Herein, we show that cis‐diiodo/sulfur‐chelated ruthenium benzylidenes do not react with strained cycloalkenes and internal olefins, but can effectively catalyze metathesis reactions of terminal dienes. Surprisingly, internal olefins may partake in olefin metathesis reactions once the ruthenium methylidene intermediate has been generated. This unexpected behavior allows the facile formation of strained cis‐cyclooctene by the RCM reaction of 1,9‐undecadiene. Moreover, cis‐1,4‐polybutadiene may be transformed into small cyclic molecules, including its smallest precursor, 1,5‐cyclooctadiene, by the use of this novel sequence. Norbornenes, including the reactive dicyclopentadiene (DCPD), remain unscathed even in the presence of terminal olefin substrates as they are too bulky to approach the diiodo ruthenium methylidene. The experimental results are accompanied by thorough DFT calculations.     

Ruthenium‐based metathesis initiators: Development and use in ring‐opening metathesis polymerization

For many years, olefin metathesis has been a central topic of industrial and academic research because of its great synthetic utility. The employed initiators cover a wide range of compounds, from simple transition‐metal salts to highly sophisticated and well‐defined alkylidene complexes. Currently, ruthenium‐based catalysts are at the center of attention because of their remarkable tolerance toward oxygen, moisture, and numerous functionalities. This article focuses on recent developments in the field of ring‐opening metathesis polymerization using ruthenium‐based catalysts. ruthenium‐based initiators and their applications to the preparation of advanced polymeric materials are briefly reviewed. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 2895–2916, 2002     

以N-杂环卡宾为配体的金属络合物催化有机合成的反应

综述了近几年来以N-杂环卡宾为配体的金属络合物催化有机合成的反应。     

Synthesis and Catalytic Study of Ruthenium Carbene Catalyst Containing a Zn‐Porphyrin Ligand

A ruthenium carbene complex containing a Zn‐porphyrin ligand has been developed. The complex was characterized by ¹H NMR, IR, HRMS and elemental analysis. The catalytic activity of the ruthenium carbene complex for olefin metathesis reactions was also investigated. The complex exhibited excellent performance for both ring‐closing and cross metathesis reactions at 35°C.     

Systematic Analysis of the Intramolecular Competition Associated with the Ring Closing Metathesis of Ene‐Diene Systems of Differing Chain Length with a Pair of Ruthenium Catalysts

The (alkylidene) ruthenium complexes 1 and 2b were examined as catalysts for the ring‐closing metathesis of the homologous series of ene‐dienes 16 to ascertain the extent to which a divergence in product distribution would be observed. In each case, the levels of cyclic alkene and conjugated diene were determined (see Table 1). Double bond geometric assignments were made on the basis of vinyl proton ¹H‐NMR chemical shifts and coupling constants. MM3 Calculations were undertaken to gauge the levels of steric strain in end products of varying ring size. The global ensemble of facts, including key control experiments, demonstrate the striking differences between 1 and 2b . Finally, the steric energies are seen not to correlate with the product distributions, most probably due to the distinctive reactivity patterns of the metathesis reagents.     

Tandem enyne metathesis-Diels-Alder reaction for construction of natural product frameworks

Enynes connected through aromatic rings are used as substrates for metathesis reactions. The reactivity of three ruthenium carbene complexes is compared. The resulting 1,3-dienes are suitable precursors of polycyclic structures via a Diels-Alder process. Some domino RCM-Diels-Alder reactions are performed, suggesting a possible beneficial effect of the ruthenium catalyst in the cycloaddition process. Other examples require Lewis acid cocatalyst. When applied to aromatic ynamines or enamines, a new synthesis of vinylindoles is achieved. Monitorization of several metathesis reactions with NMR shows the different behavior for ruthenium catalysts. New carbenic species are detected in some reactions with an important dependence on the solvent used.     

Oxygen‐chelated indenylidene ruthenium catalysts for olefin metathesis

Olefin metathesis is a transition metal‐mediated transformation that rearranges the carbon atoms of the carbon–carbon double bond of olefins. This reaction has become one of the most important and powerful reactions. Therefore development of new, well‐defined, highly active and selective catalysts is very desirable and a valuable goal. This mini‐review mainly introduces the development of ruthenium catalysts in olefin metathesis highlighting oxygen‐chelated indenylidene ruthenium catalysts. Applying an alkoxyl group on the indenylidene ligand fragment can generate the Ru ? O chelating bond. Additionally, various modifications of the ligand as well as the catalytic activity for ring‐closing metathesis reaction and selectivity of cross metathesis reaction are overviewed. Finally, the perspectives on the development of new catalysts are summarized. Copyright © 2015 John Wiley & Sons, Ltd.     

[(NHC)(NHCewg)RuCl2(CHPh)] Complexes with Modified NHCewg Ligands for Efficient Ring‐Closing Metathesis Leading to Tetrasubstituted Olefins

Imidazolium salts (NHC_ewg ? HCl) with electronically variable substituents in the 4,5‐position (H,H or Cl,Cl or H,NO₂ or CN,CN) and sterically variable substituents in the 1,3‐position (Me,Me or Et,Et or iPr,iPr or Me,iPr) were synthesized and converted into the respective [AgI(NHC)_ewg] complexes. The reactions of [(NHC)RuCl₂(CHPh)(py)₂] with the [AgI(NHC_ewg)] complexes provide the respective [(NHC)(NHC_ewg)RuCl₂(CHPh)] complexes in excellent yields. The catalytic activity of such complexes in ring‐closing metathesis (RCM) reactions leading to tetrasubstituted olefins was studied. To obtain quantitative substrate conversion, catalyst loadings of 0.2–0.5 mol % at 80 °C in toluene are sufficient. The complex with the best catalytic activity in such RCM reactions and the fastest initiation rate has an NHC_ewg group with 1,3‐Me,iPr and 4,5‐Cl,Cl substituents and can be synthesized in 95 % isolated yield from the ruthenium precursor. To learn which one of the two NHC ligands acts as the leaving group in olefin metathesis reactions two complexes, [(FL‐NHC)(NHC_ewg)RuCl₂(CHPh)] and [(FL‐NHC_ewg)(NHC)RuCl₂(CHPh)], with a dansyl fluorophore (FL)‐tagged electron‐rich NHC ligand (FL‐NHC) and an electron‐deficient NHC ligand (FL‐NHC_ewg) were prepared. The fluorescence of the dansyl fluorophore is quenched as long as it is in close vicinity to ruthenium, but increases strongly upon dissociation of the respective fluorophore‐tagged ligand. In this manner, it was shown for ring‐opening metathesis ploymerization (ROMP) reactions at room temperature that the NHC_ewg ligand normally acts as the leaving group, whereas the other NHC ligand remains ligated to ruthenium.