DFT Study on the Recovery of Hoveyda–Grubbs‐Type Catalyst Precursors in Enyne and Diene Ring‐Closing Metathesis

DFT (B3LYP‐D) calculations have been used to better understand the origin of the recovered Hoveyda–Grubbs derivative catalysts after ring‐closing diene or enyne metathesis reactions. For that, we have considered the activation process of five different Hoveyda–Grubbs precursors in the reaction with models of usual diene and enyne reactants as well as the potential precursor regeneration through the release/return mechanism. The results show that, regardless of the nature of the initial precursor, the activation process needs to overcome relatively high energy barriers, which is in agreement with a relatively slow process. The precursor regeneration process is in all cases exergonic and it presents low energy barriers, particularly when compared to those of the activation process. This indicates that the precursor regeneration should always be feasible, unlike the moderate recoveries sometimes observed experimentally, which suggests that other competitive processes that hinder recovery should take place. Indeed, calculations presented in this work show that the reactions between the more abundant olefinic products and the active carbenes usually require lower energy barriers than those that regenerate the initial precatalyst, which could prevent precursor regeneration. On the other hand, varying the precursor concentration with time obtained from the computed energy barriers shows that, under the reaction conditions, the precursor activation is incomplete, thereby suggesting that the origin of the recovered catalyst probably arises from incomplete precursor activation.     

Catalysts for new tasks: preparation and applications of tunable ruthenium catalysts for olefin metathesis

A continuous survey across structures, made over the past decades, has led to the development of highly active olefin metathesis catalysts for sophisticated synthetic tasks and for polymer technology. In this paper, our efforts toward novel and improved ruthenium complexes with even better performance in olefin metathesis are described. Oxygen ether derivatives 3, pioneered by Hoveyda, exhibit high activity and possess excellent functional group tolerance. We have successfully fine-tuned catalyst 3b to increase its activity and applicability by the introduction of electron-withdrawing groups to diminish the donor properties of the oxygen atom. As a result, the stable and easily accessible nitro-substituted catalyst 6 has found a number of successful applications in various research and industrial laboratories. We were intrigued by the possibility to further fine-tune the Hoveyda-type catalysts by combining two activating effects-steric and electronic-in a single catalyst. This was possible to achieve in so-called scorpio carbenes, which are currently under investigation in our laboratory. These modifications can be used not only to control the catalyst activity, but also to alter its physical-chemical properties, such as solubility in a given medium or an affinity to silica gel. An example of immobilization strategy based on this concept is presented.     

Cp*RuCl-Vinyl Carbenes: Two Faces and the Bifunctional Role in Catalytic Processes

Ruthenium vinyl carbenes derived from Cp/Cp*RuCl-based complexes (Cp=cyclopentadiene, Cp*=1,2,3,4,5-pentamethylcyclopentadiene) have been routinely invoked as key intermediates in tandem reactions involving a carbene/alkyne metathesis (CAM). A priori, these intermediates resemble the Grubbs-type family of catalysts, but they exhibit a completely different reactivity pattern that few, if any, other catalytic system can reproduce so far. The reactivity of these species with α-unsubstituted and α-substituted alkynals showcases the peculiarities of these intermediates. Although Z-vinyl dihydrooxazines are preferentially obtained with the former, Z-vinyl epoxypyrrolidines are obtained with the latter. A combination of spectroscopic and computational data now prove that a η³-coordination mode of the ruthenium vinyl carbene and the presence of a Lewis basic chloride ligand give rise to two markedly different stereoelectronic faces, which are responsible for the unconventional reactivity of these species.     

Mechanistic insights into ring-closing enyne metathesis with the second-generation Grubbs-Hoveyda catalyst: a DFT study

The full catalytic process (precatalyst activation, propagating cycle and active-species interconversion) of the ring-closing enyne metathesis (RCEYM) reaction of 1-allyloxy-2-propyne with the Grubbs-Hoveyda complex as catalyst was studied by B3LYP density functional theory. Both the ene-then-yne and yne-then-ene pathways are considered and, for the productive catalytic cycle, the feasibility of the endo-yne-then-ene route is also explored. Calculations predict that the ene-then-yne and yne-then-ene pathways proceed through equivalent steps, the only major difference being the order in which they take place. In this way, all alkene metathesis processes studied here involve four steps: olefin coordination, cycloaddition, cycloreversion and olefin decoordination. Among them, the two more energetically demanding ones are the olefin coordination and decoordination steps. The reaction of the alkyne fragment consists of two steps: alkyne coordination and alkyne skeletal reorganization, the latter of which has the highest Gibbs energy barrier. Comparison between the ene-then-yne and yne-then-ene pathways shows that there is no clear energetic preference for either of the two processes, and thus both should be operative when unsubstituted enynes are involved. In addition, although the endo orientation is computed to be slightly disfavored, it is not ruled out for 1-allyloxy-2-propyne, and thus calculations seem to indicate that the exo versus endo selectivity is strongly influenced by the presence of substituents in the reagent.     

In situ Generated Ruthenium Catalyst Systems Bearing Diverse N‐Heterocyclic Carbene Precursors for Atom‐Economic Amide Synthesis from Alcohols and Amines

The transition‐metal‐catalyzed direct synthesis of amides from alcohols and amines is herein demonstrated as a highly environmentally benign and atom‐economic process. Among various catalyst systems, in situ generated N‐heterocyclic carbene (NHC)‐based ruthenium (Ru) halide catalyst systems have been proven to be active for this transformation. However, these existing catalyst systems usually require an additional ligand to achieve satisfactory results. In this work, through extensive screening of a diverse variety of NHC precursors, we discovered an active in situ catalyst system for efficient amide synthesis without any additional ligand. Notably, this catalyst system was found to be insensitive to the electronic effects of the substrates, and various electron‐deficient substrates, which were not highly reactive with our previous catalyst systems, could be employed to afford the corresponding amides efficiently. Furthermore, mechanistic investigations were performed to provide a rationale for the high activity of the optimized catalyst system. NMR‐scale reactions indicated that the rapid formation of a Ru hydride intermediate (signal at δ=?7.8 ppm in the ¹H NMR spectrum) after the addition of the alcohol substrate should be pivotal in establishing the high catalyst activity. Besides, HRMS analysis provided possible structures of the in situ generated catalyst system.     

An [(NHC)(NHCEWG)RuCl2(CHPh)] Complex for the Efficient Formation of Sterically Hindered Olefins by Ring‐Closing Metathesis

NHC with EWGs for RCM : Ruthenium complexes with two N‐heterocyclic carbenes (NHCs), one of them substituted with electron‐withdrawing groups (EWGs), are highly efficient (pre)catalysts for the synthesis of tetrasubstituted olefins and trisubstituted olefins by ring‐closing metathesis reactions (RCM, see scheme).

     

Factors relevant for the ruthenium-benzylidene-catalyzed cyclopolymerization of 1,6-heptadyines

Fourteen metathesis initiators that had been designed for use in the living polymerization of diethyl dipropargylmalonate (DEDPM), including the Hoveyda catalyst [RuCl(2)(IMesH(2))([double bond]CH-2-(2-PrO)[bond]C(6)H(4))] (1 a), as well as [Ru(CF(3)COO)(2)(IMesH(2))([double bond]CH-2-(2-PrO)[bond]C(6)H(4))] (1 b), [Ru(CF(3)CF(2)COO)(2)(IMesH(2))([double bond]CH-2-(2-PrO)[bond]C(6)H(4))] (1 c), [Ru(CF(3)CF(2)CF(2)COO)(2)(IMesH(2))([double bond]CH-2-(2-PrO)[bond]C(6)H(4))] (1 d), [RuCl(2)(IMesH(2))([double bond]CH-2,4,5-(MeO)(3)[bond]C(6)H(2))] (2 a), [Ru(CF(3)COO)(2)(IMesH(2))([double bond]CH-2,4,5-(MeO)(3)[bond]C(6)H(2))] (2 b), [Ru(CF(3)CF(2)COO)(2)(IMesH(2))([double bond]CH-2,4,5-(MeO)(3)[bond]C(6)H(2))] (2 c), [Ru(CF(3)CF(2)CF(2)COO)(2)(IMesH(2))([double bond]CH-2,4,5-(MeO)(3)[bond]C(6)H(2))] (2 d), [RuCl(2)(IMes)([double bond]CH-2-(2-PrO)[bond]C(6)H(4))] (3 a), [Ru(CF(3)COO)(2)(IMes)([double bond]CH-2-(2-PrO)[bond]C(6)H(4))] (3 b), [RuCl(2)(IMesH(2))([double bond]CH-2-(2-PrO)-5-NO(2)[bond]C(6)H(3))] (4 a), [Ru(CF(3)COO)(2)(IMesH(2))([double bond]CH-2-(2-PrO)-5-NO(2)[bond]C(6)H(3))] (4 b), [Ru(CF(3)CF(2)COO)(2)(IMesH(2))([double bond]CH-2-(2-PrO)-5-NO(2)[bond]C(6)H(3))] (4 c), and [Ru(CF(3)CF(2)CF(2)COO)(2)(IMesH(2))([double bond]CH-2-(2-PrO)-5-NO(2)[bond]C(6)H(3))] (4 d) (IMes=1,3-dimesitylimidazol-2-ylidene; IMesH(2)=1,3-dimesityl-4,5-dihydroimidazol-2-ylidene) were prepared. Living polymerization systems could be generated with DEDPM by careful tuning of the electronic nature and steric placement of the ligands. Although 1 a, 2 a, 3 a, 3 b, and 4 a were inactive in the cyclopolymerization of DEDPM, and initiators 1 b-d did not allow any control over molecular weight, initiators 2 b-d and 4 b-d offered access to class VI living polymerization systems. In particular, compounds 2 b and 4 d were superior. The livingness of the systems was demonstrated by linear plots of M(n) versus the number of equivalents of monomer added (N). For initiators 2 b-d and 4 b-d, values for k(p)/k(i) were in the range of 3-7, while 1 b, 1 c, and 1 d showed a k(p)/k(i) ratio of >1000, 80, and 40, respectively. The use of non-degassed solvents did not affect these measurements and underlined the high stability of these initiators. The effective conjugation length (N(eff)) was calculated from the UV/Vis absorption maximum (lambda(max)). The final ruthenium content in the polymers was determined to be 3 ppm.     

Bis(Cyclic Alkyl Amino Carbene) Ruthenium Complexes: A Versatile,Highly Efficient Tool for Olefin Metathesis

The state‐of‐the‐art in olefin metathesis is application of N‐heterocyclic carbene (NHC)‐containing ruthenium alkylidenes for the formation of internal C=C bonds and of cyclic alkyl amino carbene (CAAC)‐containing ruthenium benzylidenes in the production of terminal olefins. A straightforward synthesis of bis(CAAC)Ru indenylidene complexes, which are highly effective in the formation of both terminal and internal C=C bonds at loadings as low as 1 ppm, is now reported.     

Ruthenium Olefin Metathesis Catalysts Featuring N-Heterocyclic Carbene Ligands Tagged with Isonicotinic and 4-(Dimethylamino)benzoic Acid Rests: Evaluation of a Modular Synthetic Strategy

A modular and flexible strategy towards the synthesis of N-heterocyclic carbene (NHC) ligands bearing Brønsted base tags has been proposed and then adopted in the preparation of two tagged NHC ligands bearing rests of isonicotinic and 4-(dimethylamino)benzoic acids. Such tagged NHC ligands represent an attractive starting point for the synthesis of olefin metathesis ruthenium catalysts tagged in non-dissociating ligands. The influence of the Brønsted basic tags on the activity of such obtained olefin metathesis catalysts has been studied.     

[(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.     

Insights into the Decomposition of Olefin Metathesis Precatalysts

The decomposition of a series of benzylidene, methylidene, and 3‐phenylindenylidene complexes has been probed in alcohol solution in the presence of base. Tricyclohexylphosphane‐containing precatalysts are shown to yield [RuCl(H)(H₂)(PCy₃)₂] in isopropyl alcohol solutions, while 3‐phenylindenylidene complexes lead to η⁵‐(3‐phenyl)indenyl products. The potential‐energy surfaces for the formation of the latter species have been probed using density functional theory studies.     

Racemization of secondary alcohols catalyzed by cyclopentadienylruthenium complexes: evidence for an alkoxide pathway by fast beta-hydride elimination-readdition

The racemization of sec-alcohols catalyzed by pentaphenylcyclopentadienyl-ruthenium complex 3a has been investigated. The mechanism involves ruthenium-alkoxide intermediates: reaction of tert-butoxide ruthenium complex 4 with a series of sec-alcohols with different electronic properties gave ruthenium complexes bearing a secondary alkoxide as a ligand. The characterization of these alkoxide complexes by NMR spectroscopy together with a study of the reaction using in situ IR spectroscopy is consistent with a mechanism in which the alkoxide substitution step and the beta-hydride elimination step occur without CO dissociation. The alkoxide substitution reaction is proposed to begin with hydrogen bonding of the incoming alcohol to the active ruthenium-alkoxide intermediate. Subsequent alkoxide exchange can occur via two pathways: i) an associative pathway involving a eta3-CpRu intermediate; or ii) a dissociative pathway within the solvent cage. Racemization at room temperature of a 1:1 mixture of (S)-1-phenylethanol and (S)-1-phenyl-[D4]-ethanol gave only rac-1-phenylethanol, and rac-1-phenyl-[D4]-ethanol, providing strong support for a mechanism in which the substrate stays coordinated to the metal center throughout the racemization, and does not leave the coordination sphere. Furthermore, racemization of a sec-alcohol bearing a ketone moiety within the same molecule does not result in any reduction of the original ketone, which rules out a mechanism where the intermediate ketone is trapped within the solvent cage. These results are consistent with a mechanism where eta3-Ph(5)C(5)-ruthenium intermediates are involved. Competitive racemization on nondeuterated and alpha-deuterated alpha-phenylethanols was used to determine the kinetic isotope effect kH/kD for the ruthenium-catalyzed racemization. The kinetic isotope effect kH/kD for p- X-C(6)H(4)CH(OH)CH(3) was 1.08, 1.27 and 1.45 for X=OMe, H, and CF3, respectively.