The Key Role of the Nonchelating Conformation of the Benzylidene Ligand on the Formation and Initiation of Hoveyda–Grubbs Metathesis Catalysts

Experimental studies of Hoveyda–Grubbs metathesis catalysts reveal important consequences of substitution at the 6‐position of the chelating benzylidene ligand. The structural modification varies conformational preferences of the ligand that affects its exchange due to the interaction of the coordinating site with the ruthenium center. As a consequence, when typical S‐chelated systems are formed as kinetic trans‐Cl₂ products, for 6‐substituted benzylidenes the preference is altered toward direct formation of thermodynamic cis‐Cl₂ isomers. Activity data and reactions with tricyclohexylphosphine (PCy₃) support also a similar scenario for O‐chelated complexes, which display fast trans‐Cl₂?cis‐Cl₂ equilibrium observed by NMR EXSY studies. The presented conformational model reveals that catalysts, which cannot adopt the optimal nonchelating conformation of benzylidene ligand, initiate through a high‐energy associative mechanism.     

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.     

Highly Active Multidentate Ligand‐Based Alkyne Metathesis Catalysts

Alkyne metathesis catalysts composed of molybdenum(VI) propylidyne and multidentate tris(2‐hydroxylbenzyl)methane ligands have been developed, which exhibit excellent stability (remains active in solution for months at room temperature), high activity, and broad functional‐group tolerance. The homodimerization and cyclooligomerization of monopropynyl or dipropynyl substrates, including challenging heterocycle substrates (e.g., pyridine), proceed efficiently at 40–55 °C in a closed system. The ligand structure and catalytic activity relationship has been investigated, which shows that the ortho groups of the multidentate phenol ligands are critical to the stability and activity of such a catalyst system.     

Batchwise and Continuous Organophilic Nanofiltration of Grubbs‐Type Olefin Metathesis Catalysts

Retained : An N‐heterocyclic carbene with eight cyclohexyl groups (see figure) provides increased electron density for a highly active olefin metathesis catalyst as well as sufficient steric bulk to allow the efficient separation of such a complex from the organic products in the solvent‐resistant nanofiltration.

     

Alkyne Metathesis with Silica‐Supported and Molecular Catalysts at Parts‐per‐Million Loadings

Improvement of the activity, stability, and chemoselectivity of alkyne‐metathesis catalysts is necessary before this promising methodology can become a routine method to construct C≡C triple bonds. Herein, we show that grafting of the known molecular catalyst [MesC≡Mo(OtBu_F6)₃] ( 1 , Mes=2,4,6‐trimethylphenyl, OtBu_F6=hexafluoro‐tert‐butoxy) onto partially dehydroxylated silica gave a well‐defined silica‐supported active alkyne‐metathesis catalyst [(≡SiO)Mo(≡CMes)(OtBu_F6)₂] ( 1 /SiO_2‐700). Both 1 and 1 /SiO_2‐700 showed very high activity, selectivity, and stability in the self‐metathesis of a variety of carefully purified alkynes, even at parts‐per‐million catalyst loadings. Remarkably, the lower turnover frequencies observed for 1 /SiO_2‐700 by comparison to 1 do not prevent the achievement of high turnover numbers. We attribute the lower reactivity of 1 /SiO_2‐700 to the rigidity of the surface Mo species owing to the strong interaction of the metal site with the silica surface.     

Ring‐Closing Metathesis Reactions: Interpretation of Conversion–Time Data

Conversion–time data were recorded for various ring‐closing metathesis (RCM) reactions that lead to five‐ or six‐membered cyclic olefins by using different precatalysts of the Hoveyda type. Slowly activated precatalysts were found to produce more RCM product than rapidly activated complexes, but this comes at the price of slower product formation. A kinetic model for the analysis of the conversion–time data was derived, which is based on the conversion of the precatalyst (Pcat) into the active species (Acat), with the rate constant k_act, followed by two parallel reactions: 1) the catalytic reaction, which utilizes Acat to convert reactants into products, with the rate k_cat, and 2) the conversion of Acat into the inactive species (Dcat), with the rate k_dec. The calculations employ two experimental parameters: the concentration of the substrate (c(S)) at a given time and the rate of substrate conversion (?dc(S)/dt). This provides a direct measure of the concentration of Acat and enables the calculation of the pseudo‐first‐order rate constants k_act, k_cat, and k_dec and of k_S (for the RCM conversion of the respective substrate by Acat). Most of the RCM reactions studied with different precatalysts are characterized by fast k_cat rates and by the k_dec value being greater than the k_act value, which leads to quasistationarity for Acat. The active species formed during the activation step was shown to be the same, regardless of the nature of different Pcats. The decomposition of Acat occurs along two parallel pathways, a unimolecular (or pseudo‐first‐order) reaction and a bimolecular reaction involving two ruthenium complexes. Electron‐deficient precatalysts display higher rates of catalyst deactivation than their electron‐rich relatives. Slowly initiating Pcats act as a reservoir, by generating small stationary concentrations of Acat. Based on this, it can be understood why the use of different precatalysts results in different substrate conversions in olefin metathesis reactions.     

DFT Mechanistic Study on Diene Metathesis Catalyzed by Ru‐Based Grubbs–Hoveyda‐Type Carbenes: The Key Role of π‐Electron Density Delocalization in the Hoveyda Ligand

The catalytic activity and catalyst recovery of two heterogenized ruthenium‐based precatalysts ( H and NO₂(4) ) in diene ring‐closing metathesis have been studied by means of density functional calculations at the B3LYP level of theory. For comparison and rationalization of the key factors that lead to higher activities and higher catalyst recoveries, four other Grubbs–Hoveyda complexes have also been investigated. The full catalytic cycle (catalyst formation, propagation, and precatalyst regeneration) has been considered. DFT calculations suggest that either for the homogeneous and heterogenized systems the activity of the catalysts mainly depends on the ability of the precursor to generate the propagating carbene. This ability does not correlate with the traditionally identified key factor, the Ru???O interaction strength. In contrast, precatalysts with lower alkoxy‐dissociation energy barriers and lower stabilities compared with the propagating carbene also present larger C1? C2 bond length (i.e., lower π character of the C? C bond that exists between the metal–carbene (Ru?C) and the phenyl ring of the Hoveyda ligand). Catalyst recovery, regardless of whether a release–return mechanism occurs or not, is also mainly determined by the π delocalization. Therefore, future Grubbs–Hoveyda‐type catalyst development should be based on fine‐tuning the π‐electron density of the phenyl moiety, with the subsequent effect on the metalloaromaticity of the ruthenafurane ring, rather than considering the modification of the Ru???O interaction.     

In Silico Olefin Metathesis with Ru‐Based Catalysts Containing N‐Heterocyclic Carbenes Bearing C60 Fullerenes

Density functional theory calculations have been used to explore the potential of Ru‐based complexes with 1,3‐bis(2,4,6‐trimethylphenyl)imidazolin‐2‐ylidene (SIMes) ligand backbone ( A ) being modified in silico by the insertion of a C₆₀ molecule ( B and C ), as olefin metathesis catalysts. To this end, we investigated the olefin metathesis reaction catalyzed by complexes A , B , and C using ethylene as the substrate, focusing mainly on the thermodynamic stability of all possible reaction intermediates. Our results suggest that complex B bearing an electron‐withdrawing N‐heterocyclic carbene improves the performance of unannulated complex A . The efficiency of complex B is only surpassed by complex A when the backbone of the N‐heterocyclic carbene of complex A is substituted by two amino groups. The particular performance of complexes B and C has to be attributed to electronic factors, that is, the electronic‐donating capacity of modified SIMes ligand rather than steric effects, because the latter are predicted to be almost identical for complexes B and C when compared to those of A . Overall, this study indicates that such Ru‐based complexes B and C might have the potential to be effective olefin metathesis catalysts.     

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.     

A Main‐Chain de Vries Smectic Liquid Crystal Polymer Prepared by Hoveyda–Grubbs Catalyst Initiated Acyclic Diene Metathesis Polymerization

A main‐chain liquid crystalline polymer has been obtained by applying a Hoveyda–Grubbs 2nd generation catalyst in acyclic diene metathesis polymerization (ADMET) of a monomer containing on one end a terminal dimethylvinylsilyl group and at the other end a terminal C C double bond. This material showed an interesting Iso‐de Vries SmA* – SmC* – Glass phase transition with a very small layer shrinkage on progressing from the SmA* phase into the SmC* phase. Will this material present a helical structure along the fiber axis in the SmC* temperature range? Several physical characterization methods including XRD, optical observation, and microtome technique have been used to investigate the internal structural organization in this liquid crystalline fiber.

     

Cross‐Metathesis/Isomerization/Allylboration Sequence for a Diastereoselective Synthesis of Anti‐Homoallylic Alcohols from Allylbenzene Derivatives and Aldehydes

We describe a highly diastereoselective approach to anti‐homoallylic alcohols from allylbenzene derivatives and aldehydes. The strategy is based on a cross‐metathesis/isomerization/allylboration sequence catalyzed successively by ruthenium and iridium. This methodology provides another way to access this class of compounds, which leads to the preparation of hitherto‐unknown homoallylic alcohols without the requirement to control the stereochemistry of the 1‐alkenyl boronate intermediates. Our study towards an enantioselective version of this sequential reaction is also reported.     

Chiral Amino Acids‐Derived Catalysts and Ligands

Transforming amino acids into novel catalysts and ligands is a remarkable subset of new catalyst development in order to imitate enzymatic efficiencies. Their ability to perform a variety of asymmetric catalytic reactions is complimented by their ready availability, rich transformations, stability and easy procedure. Herein, we focused on describing our endeavor of developing new catalysts and ligands from primary and secondary amino acids. It includes C₂‐symmetric N,N'‐dioxides, guanidine‐amides, bispidine‐based diamines, and other organic salts. The account covered a brief introduction about their discovery, representative applications and related mechanisms.