WO2011059803A2

WO2011059803A2 - Ruthenium-alkylidenes containing acyclic diaminocarbenes for obtaining low e/z ratios in cross metathesis

Info

Publication number: WO2011059803A2
Application number: PCT/US2010/054661
Authority: WO
Inventors: Christopher W. Bielawski; Evelyn Rosen
Original assignee: Board Of Regents, The University Of Texas System
Priority date: 2009-10-29
Filing date: 2010-10-29
Publication date: 2011-05-19
Also published as: WO2011059803A3

Abstract

According to one embodiment, the disclosure provides a ruthenium (Ru)-based olefin metathesis reaction catalyst containing a core including a ruthenium-based alkylidene and at least one acyclic diaminocarbene (ADC) ligand covalently bound to the core. The disclosure also provides a method of catalyzing an olefin metathesis reaction by reacting a first olefin and a second olefin in the presence of a ruthenium (Ru)-based olefin metathesis reaction catalyst comprising a core comprising a ruthenium-based alkylidene and at least one acyclic diaminocarbene (ADC) ligand covalently bound to the core to synthesize a third olefin mixture. Finally, the disclosure further provides methods of preparing ruthenium (Ru)-based catalysts.

Description

RUTHENIUM- ALKYLIDENE S CONTAINING ACYCLIC

DIAMINOCARBENES FOR OBTAINING LOW E/Z RATIOS IN CROSS

METATHESIS

PRIORITY CLAIM

The present application claims priority under 35 U.S.C. § 119(e) to both U.S. Provisional Patent Application 61/256,108 filed October 29, 2010 and U.S.

Provisional Patent Application 61/348,132 filed May 25, 2010, both of which are incorporated by reference herein in their entirety.

STATEMENT OF GOVERNMENT INTEREST

The present invention was made with support under Grant Number CHE- 0645563 awarded by the National Science Foundation. The U.S. government has certain rights in the invention.

TECHNICAL FIELD

The present disclosure relates to ruthenium-based olefin metathesis catalysts and associated methods for their use. More particularly, the present disclosure relates to ruthenium-based olefin metathesis catalysts containing acyclic diaminocarbene ligands and associated method, including methods for their use in obtaining low E:Z ratios in cross metathesis reactions.

BACKGROUND

The olefin metathesis reaction has become an indispensible tool for synthesizing small molecules, such as many pharmaceuticals, as well as

macromolecular materials. Although a variety of catalysts for facilitating this useful transformation are known, those based on late transition metals, particularly ruthenium, often show the highest stabilities toward oxygen, moisture, and a broad range of functional groups. Many of these same catalysts also display high activities and react with a broad range of substrates. Commercially available Ruthenium (Ru)- based catalysts have been found widespread utility in a variety of olefin metathesis reactions. Common commercially available Ru-based catalysts are shown in

FIGURE 1. Current commercially available Ru-based compounds often are not able to react, or can react in only very limited ways with sterically hindered olefins. They also tend to be unable to provide products with high diastereo- or enantioselectivities, which is useful in many synthesis reactions. Ligands attached to the Ru-based catalysts have been used to address some of these problems. Many ligands include N- heterocyclic carbenes (NHCs), which are widely accepted to be stronger electron donors than typical phosphines, allowing them to enhance the activities of Ru-based catalysts upon coordination. In addition to exhibiting favorable electronic properties, the steric properties of NHCs can be modified by varying the nature of their N- substituents. For example, Ru-based catalysts containing symmetric or unsymmetric NHC ligands have been investigated for their abilities to afford cross-metathesis products with different E:Z ratios and have had varying degrees of success.

Improvements in catalyst properties, such as E:Z ratios and catalytic activity, remain desirable.

SUMMARY

According to one embodiment, the disclosure provides a ruthenium (Ru)- based olefin metathesis reaction catalyst containing a core including a ruthenium- based alkylidene and at least one acyclic diaminocarbene (ADC) ligand covalently bound to the core.

According to a second embodiment, the disclosure provides a method of catalyzing an olefin metathesis reaction by reacting a first olefin and a second olefin in the presence of a ruthenium (Ru)-based olefin metathesis reaction catalyst comprising a core comprising a ruthenium-based alkylidene and at least one acyclic diaminocarbene (ADC) ligand covalently bound to the core to synthesize a third olefin mixture.

According to a third embodiment, the disclosure provides a method for preparing a ruthenium (Ru)-based olefin metathesis reaction catalyst including providing a quantity of (SIMes)(pyridine)₂Cl₂Ru=CHPh, providing a quantity of acyclic diaminocarbene (ADC), and reacting the quantity of

(SIMes)(pyridine)₂Cl₂Ru=CHPh with the quantity of acyclic diaminocarbene (ADC) to form a ruthenium (Ru)-based olefin metathesis reaction catalyst comprising at least one ADC ligand.

According to a fourth embodiment, the disclosure provides a method for preparing a Hoveyda-Grubbs-type ruthenium (Ru)-based olefin metathesis reaction catalyst including providing a quantity of (PCy₃)Cl₂Ru=CH(2-isopropoxy)Ph, providing a quantity of acyclic diaminocarbene (ADC), and reacting the quantity of (PCy₃)Cl₂Ru=CH(2-isopropoxy)Ph with the quantity of acyclic diaminocarbene to form the Hoveyda-Grubbs-type catalyst comprising at least one ADC ligand. DRAWINGS

Some specific example embodiments of the disclosure may be understood by referring, in part, to the following description and the accompanying drawings.

FIGURE 1 shows representative examples of commercially available Ru- based catalyst (catalysts 1-3) and representative examples of Ru catalysts containing unsymmetrical NHC ligands (catalysts 4a, 4b, 4c, 5a, and 5b). In the figure,

Cy=cyclohexyl, Mes=2,4,6-trimethylphenyl, and DIPP=2,6-di-isopropylphenyl.

FIGURE 2 shows the structure of two acyclic diaminocarbenes (ADCs) that may be used as ligands for Ru alkylidenes catalysts (structures 6 and 7), according to an embodiment of the present disclosure.

FIGURE 3 shows four representative examples of Ru alkylidene catalysts containing ADC ligands (catalysts 8a, 8b, 9a, and 9b), according to an embodiment of the present disclosure.

FIGURE 4 shows an ORTEP diagram of catalyst 8b showing 50% probability ellipsoids, according to an embodiment of the present disclosure. H atoms and solvent molecules have been removed for clarity.

FIGURE 5 shows ORTEP diagrams of catalysts 9a (left) and 9b (right) showing ellipsoids at 50% probability, according to an embodiment of the present disclosure. H atoms have been removed for clarity.

FIGURE 6 A shows a first cross-metathesis reaction scheme (1) for conversion of structure 11 to structure 10 and a second cross-metathesis reaction scheme (2) for conversion of structure 11 to structure 12, according to an embodiment of the present disclosure. FIGURE 6B is a graph which shows the E:Z ratio of structure 12 versus the % conversion of structure 11 to structure 12 using catalysts 3 (hollow circle), 4a (hollow square), 9a (filled square), and 9b (filled circle), according to embodiments of the present disclosure.

While the present disclosure is susceptible to various modifications and alternative forms, specific example embodiments have been shown in the figures and are herein described in more detail. It should be understood, however, that the description of specific example embodiments is not intended to limit the invention to the particular forms disclosed, but on the contrary, this disclosure is to cover all modifications and equivalents as illustrated, in part, by the appended claims.

DETAILED DESCRIPTION

The present disclosure generally relates to ruthenium (Ru)-based olefin metathesis catalysts and associated methods. More particularly, the present disclosure relates to ruthenium-based olefin metathesis catalysts containing acyclic

diaminocarbene (ADC) ligands and associated methods, including methods for their use in obtaining low E:Z ratios in cross metathesis reactions.

In general, the catalysts of this disclosure may contain a core containing at least one Ru atom or ion with one or more ADC ligands attached. The ADC ligand may be attached via a covalent bond. The disclosure also relates to the use of such catalysts to achieve enhanced activity or stereoselectivity in an olefin metathesis reaction. Finally, the disclosure relates to methods of selecting the N-substituents of the ADC ligands and methods of synthesizing the ADC ligands.

Compared to NHC ligands, ADC ligands typically possess wider N-C-N bond angles, are stronger σ-donors, and may be generated in a straightforward manner via deprotonation of readily accessible formamidinium salts. Although a broad range of metal complexes containing ADCs are known, there are relatively few reported examples that are catalytically active.

In addition to their unique electronic and steric properties, ADCs also have an unusual structure. Enabled by free rotation about their C-N bonds, ADCs are capable of adopting multiple, unique conformations if their N-substituents are differentially substituted. For example, the conformations adopted by unsymmetrical N-aryl ADCs as well as their parent formamidinium salts and derivative metal complexes may be controlled by steric tuning of the N- substituents.

According to particular embodiments, the Ru-based catalysts may include catalysts s of the type (ADC)Cl₂Ru=CH(2-isopropoxy)Ph and

(ADC)(SIMes)Cl₂Ru=CHPh (ADC = N,N'-dimesityl-N,N'-dimethylformamidin-2- ylidene or N,N'-bis(2,6-di-isopropylphenyl)-A ,N'-dimethylformamidin-2-ylidene; SIMes = l,3-dimesitylimidazolin-2-ylidene). With such catalysts, depending on their N-substituents and the metal center to which they were coordinated, the ADC ligands adopt different conformations. These Ru-based catalysts may exhibit high catalytic activities in a variety of olefin metathesis reactions at elevated temperatures and may afford cross-metathesis products with significantly lower E:Z ratios than catalysts containing analogous N-heterocyclic carbene ligands.

According to one embodiment, the Ru-based catalyst may contain two ligands. More specifically, if may contain both an ADC ligand, and another ligand, such as an NHC ligand or a phosphine ligand. Alternatively, it may contain two ADC ligands. In either embodiment, the ADC ligand may be symmetric or unsymmetric. In either embodiment, the ADC ligand may be in a pseudo cis conformation of a pseudo trans conformation. Similarly, in embodiments containing an NHC ligand, it may be in a pseudo cis conformation of a pseudo trans conformation. The conformation found in the solid state may differ from that in solution. The conformation in either solid state or solution may be determined, at least in part, by the nature of the substituents. It may also be determined, at least in part, by the other ligand and its substituents. Certain ligands may be able to adopt multiple

conformations.

Also according to particular embodiments, the ligands may be selected to achieve a desirable lability of at least one ADC ligand. For example, the ligands may include two ligands, one of which is an ADC ligand, and the second of which is selected to provide a desired lability of the ACD ligand. In such embodiments, the second ligand may also be a NHC or phosphine ligand.

According to another embodiment, the disclosure provides a method for olefin metathesis using any of the Ru-based catalysts containing at least one ADC ligand disclosed herein. The olefin metathesis reaction in the presence of the catalyst may have a conversion percentage of at least 15%, at least 20%, at least 30%, or at least 35%, at least 60%, at least 80%, at least 90%, or even 100%. The olefin methathesis reaction may be of any type, but in a specific embodiment it may be a ring-closing metathesis (RCM). The reaction may take place at any temperature, but in particular embodiments it may take place at higher temperatures such as 40°C or above, at 60°C or above, or even at 100 °C or above. In other embodiments, the reaction may take place at lower temperatures, such as between 15°C and 30°C. Reaction times may be less than 12 hours, less than 8 hours, or even less than one hour. Reaction time may be shorter for higher temperatures in some reactions with some catalysts. In certain embodiments, the methods of olefin metathesis used herein may yield a mixture of structures in which the E:Z ratio is as 4: 1 2: 1, 1 : 1 , or even 0.5 : 1 or less.

EXAMPLES

The present disclosure may be better understood through reference to the following examples. These examples are included to describe exemplary

embodiments only and should not be interpreted to encompass the entire breadth of the invention.

Example 1: Materials and Methods.

Benzene was distilled from sodium and benzophenone under an atmosphere of nitrogen. Dichloromethane (CH₂CI₂) and toluene were distilled from CaH₂ under an atmosphere of nitrogen. All solvents were degassed by three, consecutive freeze- pump-thaw cycles. Allylbenzene, acrylonitrile, cis-l,4-diacetoxy-2-butene, and n- octane were purchased from Aldrich and degassed using three consecutive freeze- pump-thaw cycles before use. (PCy3)₂Cl₂Ru=CHPh (1) and

(SIMes)(PCy₃)Cl₂Ru=CHPh (2) were generously donated by Materia, Inc. The Hoveyda-Grubbs first-generation catalyst, (PCy₃)Cl₂Ru=CH(2-isopropoxy)Ph, was purchased from Aldrich. (SIMes)(pyridine)₂Cl₂Ru=CHPh, N,N'-bis-(DIPP)-N,N'- dimethylformamidinium iodide (6ΉΙ), N,N'-dimesitylformamidine,

(SIMes)Cl₂Ru=CH(2-isopropoxy)Ph (3), and (l-DIPP-3-methylimidazolin-2- ylidene)Cl₂Ru=CH-(2-isopropoxy)Ph (4a) were synthesized according to literature procedures. All other materials and solvents were of reagent quality and were used as received. Unless otherwise noted, all manipulations were performed under an atmosphere of nitrogen using drybox or Schlenk techniques.

Example 2: Instrumentation.

1H and ¹³C{¹H} NMR spectra were recorded using a Varian 300, 400, 500, or 600 MHz spectrometer. Chemical shifts δ (in ppm) were referenced to

tetramethylsilane using the residual solvent as an internal standard. For 1H NMR: CDC1₃, 7.24 ppm; C₆D₆, 7.15 ppm; toluene-d₈, 2.09 ppm; CD₂C1₂, 5.32 ppm; DMSO- d₆, 2.49 ppm. For ¹³C NMR: CDC1₃, 77.0 ppm; DMSO-d₆, 39.5 ppm. Coupling

31

constants (J) are expressed in hertz (Hz). P NMR spectra were recorded using a Varian 300 MHz spectrometer, with chemical shifts δ (in ppm) referenced to H₃PO₄. To determine the proton-decoupled chemical shift corresponding to the benzylidene

13 1

C nuclei in catalysts 8 and 9, the decoupling frequencies were set to the H chemical shifts of their respective benzylidene signals. High-resolution mass spectra (HRMS) were obtained with a VG analytical ZAB2-E or a Karatos MS9 instrument (ESI or CI) and are reported as mlz (relative intensity). Gas chromatography (GC) was performed on an Agilent 6850 gas chromatograph. Elemental analyses were performed by Midwest Microlabs, LLC (Indianapolis, IN).

Example 3: N,N'-Dimesityl-N,N'-dimethylformamidinium Iodide (?HI). Under an atmosphere of air, a 30 mL pressure vessel equipped with a stir bar was charged with N,N'-dimesitylformamidine (2.79 g, 9.96 mmol), NaHCC>3 (4.20 g, 49.8 mmol), and CH₃CN (20mL). Methyl iodide (4.24 g, 29.9 mmol) was added to the resulting suspension, and the vessel was sealed with a Teflon-lined cap. The reaction mixture was stirred for 12 h at 85 °C. After the mixture was allowed to cool to ambient temperature, it was filtered. The filtrate was concentrated to dryness and then triturated with diethyl ether. The resulting solid was recovered via vacuum filtration and dried under high vacuum to afford the desired product as a pale yellow powder (3.82 g, 88% yield). Crystals of 7ΉΙ were grown as colorless prisms by slow evaporation from ethyl acetate. Mp: 220-222 °C. 1H NMR (300 MHz, DMSO-d₆): δ 8.46 (s, 1H), 7.12 (s, 2H), 7.04 (s, 2H), 3.52 (s, 3H), 2.61 (s, 3H), 2.36 (s, 6H), 2.26 (s, 9H), 2.24 (s, 3H). ¹³C NMR (100 MHz, DMSO-d₆): δ 156.0, 140.7, 139.7, 138.8, 134.3, 134.0, 133.8, 129.4, 129.3, 45.8, 37.4, 20.5, 20.4, 17.4, 17.0. HRMS: calcd for C21H29N2 ([M⁺]) 309.2329; found 309.2325. Anal. Calcd (%) for C21H29N2I: C, 57.80; H, 6.70; N, 6.42. Found: C, 57.77; H, 6.73; N, 6.47.

Example 4: Synthesis of (N,N'-Bis(2,6-di-isopropylphenyl)-N,N'- dimethylformamidin-2-ylidene)(SIMes)Cl2Ru=CHPh (Sturcture 8a).

A 6 mL glass vial equipped with a stir bar was charged with 6ΉΙ (213 mg, 0.409 mmol) and NaN(SiMe₃)₂ (85 mg, 0.464 mmol). Toluene (5 mL) was added to the mixture, and the vial was sealed with a Teflon-lined cap. The solution was stirred for 30 min at ambient temperature and then filtered through a 0.2 μιη PTFE filter into a second clean vial equipped with a stir bar. (SIMes)(pyridine)₂-Cl₂Ru=CHPh (85 mg, 0.117 mmol) was then added, and the vial was sealed with a Teflon-lined cap. The reaction was allowed to stir for 1.5 h at 60 °C. The solvent was then removed under reduced pressure. Hexanes (2 mL) was added to the resulting green solid, which resulted in the formation of a yellow-brown precipitate, which was removed by filtration. The green filtrate was then loaded onto a short column of silica gel. The silica gel was washed with hexanes (20 mL) followed by ethyl acetate (10 mL), and the green band which eluted was collected. The green solution was concentrated under reduced pressure and dried under high vacuum to afford the desired product as a green solid (73.6 mg, 66% yield). 1H NMR (300 MHz, CDC1₃): δ 18.59 (s, 1H), 8.97 (d, 1H, J= 7.8), 7.27-7.22 (m overlapping with solvent, 1H, J= 15.3), 7.09-7.03 (m, 3H), 6.94 (s, 1H), 6.87-6.74 (m, 3H), 6.66-6.61 (m, 2H), 6.36 (t, 1H, J= 7.5), 5.99 (t, 2H, J= 6.0), 5.52 (s, 1H), 4.02-3.92 (m, 2H), 3.79-3.74 (m, 2H), 3.61 (s, 3H), 3.57- 3.50 (m, 3H), 2.88-2.83 (m, 1H), 2.62 (s, 3H), 2.56 (s, 3H), 2.45 (s, 3H), 2.35 (s, 3H), 2.19 (s, 3H), 1.88 (s, 3H), 1.84 (s, 3H), 1.40 (d, 3H, J= 6.6), 1.25 (d, 6H, J= 6.6), 1.18 (d, 3H, J= 6.9), 1.13 (d, 3H, J= 6.3), 1.05 (d, 3H, J= 6.9), 0.81 (d, 3H, J= 6.6), 0.62 (d, 3H, J= 6.6). ¹³C NMR (100 MHz, CDC1₃): δ 296.1, 222.9, 216.6, 149.8, 148.8, 146.5, 146.0, 145.8, 143.8, 143.2, 139.5, 138.3, 137.9, 137.71, 137.66, 137.3, 136.8, 136.1, 132.6, 130.9, 129.4, 128.94, 128.90, 128.5,128.3, 128.2, 126.8, 126.3, 125.6, 123.5, 123.42, 123.39, 40.7, 27.8, 27.7, 27.6, 27.4, 27.2, 26.5, 26.0, 25.6, 25.2, 24.1, 22.5, 22.4, 22.3, 20.95, 20.94, 19.8, 19.1, 18.6, 18.4. HRMS: calcd for

C₅₅H₇₂Cl₂Ru ([M⁺]) 960.4178; found 960.4163. Anal. Calcd (%) for

C, 68.73; H, 7.55; N, 5.83. Found: C, 68.63; H, 7.41; N, 5.94. Example 5: Synthesis of (N,N'-Dimesityl-N,N'-dimethylformamidin-2- ylidene)(SIMes)-Cl₂Ru=CHPh (Catalyst 8b).

A 6 mL glass vial equipped with a stir bar was charged with 7ΉΙ (158 mg, 0.363 mmol), NaN(SiMe₃)₂ (66.0 mg, 0.363 mmol), and toluene (4 mL) and then sealed with a Teflon-lined cap. The reaction mixture was stirred for 30 min at ambient temperature. A cloudy mixture formed, which was subsequently filtered through a 0.2 μιη PTFE filter into a clean glass vial equipped with a stir bar (in a drybox). (SIMes)- (pyridine)₂Cl₂Ru=CHPh (251 mg, 0.346 mmol) was added, and the vial was sealed with a Teflon- lined cap. The solution was stirred at ambient temperature for 12 h and then concentrated under reduced pressure to afford a green solid. The solid was triturated with pentane and filtered. The recovered solid was then dissolved in ethyl acetate and filtered through a short column of silica gel. Removal of residual solvent under high vacuum afforded the desired product as a light green solid (104.9 mg, 35% yield). Crystals of 8b^'C₅Hi₂ were grown as green plates by slow evaporation from pentane. 1H NMR (300 MHz, CDC1₃): δ 19.16 (s, 1H), 9.50 (br s, 2H), 7.31 (t, 1H, J = 7.3), 7.07 (br s, 2H), 6.90 (s, 2H), 6.85 (s, 1H), 6.43 (s, 1H), 6.30 (s, 1H), 6.18 (s, 1H), 6.07 (s, 1H), 5.87 (s, 1H), 4.06-3.89 (m, 3H), 3.78-3.73 (m, 1H), 3.11 (s, 3H), 2.77 (s, 3H), 2.62 (s, 3H), 2.53 (s, 3H), 2.22 (s, 3H), 2.19 (s, 3H), 2.07 (s, 3H), 2.02 (s, 3H), 1.99 (s, 3H), 1.97 (s, 3H), 1.94 (s, 3H), 1.86 (s, 3H), 1.62 (s, 3H). ¹³C NMR(125 MHz, CDC13): δ 295.8, 227.4, 222.7, 152.0, 144.0, 142.1, 139.2, 139.0, 138.3, 138.0, 137.6, 137.5, 136.8, 136.6, 135.6, 135.1, 135.0, 134.4, 133.9, 133.8, 129.4, 129.3, 129.1, 128.9, 128.2, 128.0, 127.9, 127.8, 127.4, 51.8, 51.6, 47.4, 40.6, 21.1, 21.0, 20.6, 20.4, 19.8, 19.66, 19.63, 19.5, 18.8, 18.65, 18.57, 18.3. HRMS: calcd for C₄₉H₆₀Cl₂N₄Ru([M⁺]) 876.3239; found 876.3237. Anal. Calcd (%) for 485

C₄₉H₆₀Cl₂N₄Ru: C, 67.11; H, 6.90; N, 6.39. Found: C, 66.82; H, 6.83; N, 6.40.

Example 6: Synthesis of (N,N'-Bis(2,6-di-isopropylphenyl)-N,N'~

dimethylformamidin-2-ylidene) Cl₂Ru=CH(2-isopropoxy)Ph ( Catalyst 9a).

A 6 mL glass vial equipped with a stir bar was charged with 6ΉΙ (185 mg, 0.355 mmol), NaN(SiMe )₂ (65.0 mg, 0.355 mmol), and benzene (4 mL) and then sealed with a Teflon-lined cap. The mixture was stirred for 30 min at ambient temperature, after which it was filtered through a 0.2 um PTFE filter into a second clean glass vial containing a stir bar. (PCy₃)Cl₂Ru=CH(2-isopropoxy)Ph (100 mg, 0.166 mmol) was added, and the vial was sealed with a Teflon-lined cap. The resulting purple-red solution was then stirred for 5 h at ambient temperature, after which the color had changed to green-brown. The solution was then concentrated under reduced pressure to afford a dark green solid. The solid was dissolved in a minimal amount of dichloromethane (ca. 2 mL) and then filtered through a short column of silica gel with the aid of additional dichloromethane (ca. 4 mL). The filtrate was then evaporated to a volume of approximately 1 mL, and pentane (5 mL) was added, which caused a green precipitate to form. The green precipitate was collected and dried under vacuum to afford the desired product as a dark green micro- crystalline solid (34 mg, 28% yield). Crystals of catalyst 9a were grown as green prisms by vapor diffusion of pentane into a C6¾ solution of the catalyst. 1H NMR (300 MHz, CDCls): δ 15.94 (s, 1H), 7.58-7.48 (m, 2H), 7.37-7.33 (m, 3H), 7.20 (d, 2H, J= 7.5), 6.95 (d, 1H, J= 7.2), 6.85 (t, 2H, J= 7.5), 5.05-5.01 (m, 1H), 4.97 (s, 3H), 3.98-3.90 (m, 2H), 3.30-3.21 (m, 2H), 2.88 (s, 3H), 1.69 (d, 6H, J= 6.0), 1.36- 1.34 (2 overlapping d, 12H), 1.06 (d, 6H, J= 6.9), 0.94 (d, 6H, J= 6.6). ¹³C NMR (125 MHz, CDCI₃): δ 299.3, 202.1, 152.0, 148.4, 146.6, 146.1, 145.3, 144.9, 129.5, 129.0, 128.7, 124.9, 124.2, 122.9, 122.4, 133.0, 74.5, 46.9, 46.8, 28.0, 27.7, 26.2, 26.1, 23.6, 23.0, 22.4. HRMS: calcd for C₃7H₅₂Cl₂N₂ORu ([M⁺]) 712.2500, found 712.2500. Anal. Calcd (%) for C₃₇H₅₂Cl₂N₂ORu: C, 62.35; H, 7.35; N, 3.93. Found: C, 62.41; H, 7.29; N, 4.03.

Example 7: Synthesis of (N,N'-Dimesityl-N,N'-dimethylformamidin-2- ylidene)Cl₂Ru=CH(2-isopropoxy)Ph (Catalyst 9b).

A 6 mL glass vial equipped with a stir bar was charged with 7ΉΙ (191 mg,

0.438 mmol), NaN(SiMe₃)₂ (80.0 mg, 0.438 mmol), and benzene (4 mL) and then sealed with a Teflon-lined cap. The solution was stirred for 30 min at ambient temperature, after which it was filtered through a 0.2 μιη PTFE filter into a second clean glass vial containing a stir bar. (PCy₃)Cl₂Ru=CH(2-isopropoxy)Ph (105 mg, 0.175 mmol) was added, and the vial was sealed with a Teflon- lined cap. The reaction mixture was stirred at 50 °C for 3 h. The solution was then concentrated under reduced pressure to afford a dark green solid. The resulting solid was purified by column chromatography on silica gel using hexanes/ethyl acetate (5:1 v/v) as the eluent. A dark green band eluted first, which was determined to be an intermediate where PCy₃ had displaced the coordinating isopropoxy moiety. An analogous intermediate has been reported in the synthesis of related NHC-containing Hoveyda- Grubbs-type catalysts. This solution was concentrated, dissolved in 5 mL of CHC1₃, and then stirred for 10 h to induce phosphine dissociation. A second band was eluted from the aforementioned column, which contained the desired product. This solution was concentrated under reduced pressure to afford a green solid. After the first band had finished stirring, it was combined with the second band and the resulting solution was concentrated under reduced pressure. Diethyl ether (5 mL) was then added, which caused a light green solid to precipitate upon standing. After decanting the mother liquor, the residual solids were collected and washed with hexanes (5 mL). The solids were then collected by vacuum filtration and dried under high vacuum to afford the desired product as a light green powder (59 mg, 54% yield). Crystals of catalyst 9b^'1.5(C₆H₆) were grown as green needles by vapor diffusion of pentane into a

CH₂C1₂ solution of the catalyst. 1H NMR (300 MHz, CDC1₃): δ 15.92 (s, 1H), 7.52 (t, 1H, J= 8.7), 7.04 (s, 2H), 7.00-6.97 (m, 1H), 6.93 (s, 2H), 6.89-6.86 (m, 2H), 5.06 (h, 1H, J= 6.0), 4.80 (s, 3H), 2.82 (s, 3H), 2.54 (s, 6H), 2.46 (s, 3H), 2.30 (s, 3H), 2.26 (s, 6H), 1.67 (d, 6H, J= 6.00). ¹³C NMR (125 MHz, CDC1₃): δ 302.8, 201.2, 151.7, 148.4, 145.4, 144.9, 138.0, 137.5, 136.7, 135.6, 129.9, 129.8, 129.0, 123.3, 122.6, 113.0, 74.4, 44.6, 42.7, 22.2, 21.1, 21.0, 18.7, 18.3. HRMS: calcd for

C₃iH₄₀Cl₂N₂ORu ([M⁺]) 628.1561, found 628.1559. Anal. Calcd for

C₃iH₄₀Cl₂N₂ORu: C, 59.23; H, 6.41; N, 4.46. Found: C, 58.91; H, 6.29; N, 4.60. Example 8: Synthesis and Analysis of Two ADC Ligands Employed in Ru-

Based Catalysts.

Metal-based catalysts containing NHC ligands with bulky N-aryl substituents often result in catalystes with superior stabilities due to protection provided by steric shielding about the metal center. FIGURE 2 illustrates the structures of two ADCs, structures 6 and 7, that were tested as ligands in Ru-based catalysts. The

conformations shown for the ACDs in this figure are consistent with their solid state structures. Structure 6 features an ADC with an N-DIPP (2,6-di-isopropylphenyl) substituent and structure 7 features an ADC with an N-Mes (2,4,6-trimethylphenyl) substituent.

The respective conjugate acids of these ADCs, formamidinium iodides 6ΉΙ and 7ΉΙ, were also synthesized by independently treating acetonitrile solutions of N,N'-bis(2,6-di-isopropylphenyl)formamidine or N,N'-dimesitylformamidine with excess iodomethane in 69% and 88% yields, respectively. It was previously determined that 6ΉΙ adopts a pseudo trans conformation in solution as well as in the solid state; 7ΉΙ follow suit. Two inequivalent signals attributed to the N-methyl groups can be observed in the 1H NMR spectrum of 7ΉΙ at δ = 3.50 and 2.64 ppm (OMSO-de), chemical shifts that were nearly identical to those exhibited by 6ΉΙ (δ = 3.59 and 2.69 ppm in the same solvent). Additionally, two distinct singlets were observed for the N-aryl protons of the mesityl groups at δ = 7.14 and 7.07 ppm. The solid state structure of 7ΉΙ was consistent with the solution state assessment, and the key bond lengths and angles exhibited by this catalyst were similar to those observed in the solid state structure of 6ΉΙ.

Once the 6HI and 7HI formaminidinum iodides were obtained, Ru alkylidenes that contained the respective ADCs as ligands were synthesized. Using one method, (ADC)(PCy3)Cl₂Ru=CHPh-type catalystes were obtained by treating independent benzene solutions of 6ΉΙ or 7ΉΙ with NaN(SiMe₃)₂ (to generate their respective ADCs in situ) followed by the addition of (PCy₃)₂Cl₂Ru=CHPh. Once reacted, free PCy₃ were observed in the NMR spectra of the crude product mixtures along with new diagnostic signals that were tentatively assigned to (6)(PCy₃)Cl₂Ru=CHPh (1H: 19.20 and ³¹P: 31.90 ppm, CDC1₃) and (7)(PCy₃)Cl₂Ru=CHPh (1H: 18.91 and ³¹P: 32.26 ppm, CDC1₃), respectively.

Example 9: Synthesis and Analysis of Mixed ADC/NHC Ligand Catalysts.

Without limiting the disclosure to any particular theory, instability of the aforementioned (ADC)(PCy₃)Cl₂Ru=CHPh-type catalysts may be related to the lability of the phosphine ligand trans to the ADC. Accordingly, mixed NHC-ADC Ru catalysts may be prepared because analogous bis-(NHC)-type Ru complexes are known to be relatively stable.

The addition of (SIMes)(pyridine)₂Cl₂Ru=CHPh (SIMes = 1,3- dimesitylimidazolin-2-ylidene) to a solution of the ADC (generated in situ via deprotonation of 6ΉΙ or 7ΉΙ with NaN(SiMe3)₂) affords the desired catalysts 8a and 8b, in 35% and 66% isolated yields, respectively, after purification by column chromatography. FIGURE 3 illustrates the structures of catalysts 8a and 8b. The conformations shown are consistent with the structures observed in solution. For catalyst 8b the conformations shown is also consistent with their solid state structure.

The characteristic benzylidene signals in these catalysts were observed at δ = 18.59 and 19.16 ppm (CDC1₃) in their respective 1H NMR spectra. To elucidate the solution structures adopted by catalysts 8a and 8b in their ground states, a series of NOESY experiments were performed in CDCI3. Irradiation of the benzylidene proton at δ = 18.60 ppm (CDCI3) in catalyst 8a lead to an enhancement of signals that was attributed to both N-DIPP and N-Mes substituents present in this catalyst. This result suggests that the benzylidene moiety was oriented between these two aromatic systems. Irradiation of the N-methyl signal at δ = 3.62 ppm in catalyst 8a lead to enhancement of two singlets at 6.87 and 6.82 ppm, which were assigned to the N- mesityl's aryl protons. Collectively, these spectroscopic results are consistent with the ADC ligand in catalyst 8a adopting a pseudo trans conformation, which was similar to the structure of its respective free ADC and 6ΉΙ.

Different spectroscopic results were obtained with catalyst 8b. When the benzylidene signal (found at δ = 19.16 ppm; CDCI₃) was irradiated, a positive enhancement to a signal found at δ = 2.22 ppm may be observed, suggesting the presence of a juxtaposed N-methyl group. This interaction was be confirmed after irradiating that same group (δ = 2.22 ppm), which, in addition to enhancing the signal attributed to the benzylidene moiety, also enhances the signals found at δ= 2.00 and 1.62 ppm. These latter chemical shifts were assigned to the 2,6-dimethyl groups on the N-mesityl substituent connected to same nitrogen atom as the N-methyl group under interrogation. Irradiation of the signal at δ = 3.10 ppm, which was attributed to the other N-methyl substituent, lead to enhancement of the aromatic N-mesityl protons found at δ = 6.90 ppm as well as two singlets at 2.08 and 1.86 ppm. This interaction was attributed to a NOE contact with a mesityl group on the SIMes fragment.

Collectively, these results are consistent with the ADC ligand in catalyst 8b adopting a pseudo cis conformation where both N-methyl substituents were orientated toward the Ru center. This geometry differs from its respective free ADC and formamidinium salt, and indicates that structure 7 may undergo C-N bond rotation either prior to or after metalation.

Upon in situ deprotonation of 7ΉΙ using NaHMDS, structure 7 adopts a pseudo trans conformation in solution, as determined by NMR spectroscopy. The ADC ligand found coordinated to the Ru center in catalyst 8b adopts a different ground state conformation than its respective formidinium precursor, both in solution and in the solid state. To determine if this catalyst is capable of displaying multiple conformations, a solution of 8b in toluene-^ was examined by variable temperature 1H NMR spectroscopy. No changes were observed, even at 100°C. Furthermore, the lack of Overhauser effects between the benzylidene protons in catalysts 8 and 9 and the N-methyl groups pointing toward the Ru centers in these catalysts suggest that rotation about the Ru-ADC bond is slow.

Additional support for the unique conformation adopted by the ADC ligand in catalyst 8b was obtained using X-ray crystallography. X-ray quality crystals were obtained by vapor diffusion of hexanes into a benzene solution saturated with this catalyst. Unfortunately, all efforts to obtain X-ray quality crystals of catalyst 8a were unsuccessful. The ORTEP diagram shown in FIGURE 4reveals that the ADC ligand in catalyst 8b adopts a pseudo cis conformation in the solid state, a result that is consistent with the aforementioned assessment of its solution state structure.

Selected bond lengths (A° ) and angles (deg) of catalyst 8b are: Ru-Cl,

2.112(3); Ru-C2, 2.132(3); Ru-C5, 1.840(3); Nl-Cl, 1.356(3); N2-C1, 1.356(4); N3- C2, 1.360(4); N4-C2, 1.343(3); Nl-Cl -Ru, 110.6(2); N2-Cl-Ru, 130.6(2); N3-C2-Ru, 125.4(2); N4-C2-Ru, 128.3(2); Cl-Ru-C5, 104.0(1); C2-Ru-C5, 95.7(1); Cl-Ru-C2, 160.1(1); Cll-Ru-C12, 170.76; N1-C1-N2, 118.7(3); N3-C2-N4, 106.3(2).

The crystal data shows that the distance between the adjoining arenes of the

N-mesityl substituents in the ADC (3.58 A) was in accord with a favorable π-π interaction, which, without limiting the disclosure to a particular theory, may facilitate formation of the unusual conformation observed. The angle between the planes of these arenes was calculated to be 19.4°. Regardless, the ADC ligand possesses a relatively wide N-C-N angle (118.7(3)°), which, without limiting the disclosure to a particular theory, may impose more steric constraint on the Ru center than may be otherwise expected and may explain why the observed CN_HC-RU-CA_DC bond angle (CI- Ru-C2: 160.1(1)°) in catalyst 8b is significantly more acute than the analogous angles observed in other reported bis(NHC) Ru complexes (162.0(2)-171.2(1)°). This angle is similar to that observed for (l-methyl-3-(2,6-di- isopropylphenyl)imidazolinylidene)₂Cl₂Ru=CHPh (162.0(2)°). The other structural metrics of catalyst 8b are relatively similar to those found in reported bis(NHC) Ru catalysts. For example, the Ru-Cbenzyiidene bond distance (Ru-C5, 1.840(3) A) was comparable to the analogous bond distances reported for related bis(NHC) Ru catalysts (1.818(4)- 1.835(2) A). Likewise, the RU-C_NHC bond distance (Ru-C2, 2.132(3) A) in catalyst 8b was only slightly longer than analogous distances observed in a range of other bis(NHC) Ru catalysts(2.115(3)-2.122(3) A).

It was additionally determined whether the ADC or the NHC ligand in catalysts 8a and 8b were more likely to dissociate. It has been previously reported that the addition of excess PCy₃ to bis(NHC)₂Cl₂Ru=CHPh-type catalysts can be used to determine ligand lability. Heating a mixture of either catalyst 8a or 8b (20 mg in 0.8 mL of CeD₆) in the presence of a 10-fold molar excess of PCy₃ at 100°C (sealed tube) resulted in a dramatic color change from olive green to tan-red and in the formation of (SIMes)(PCy₃)Cl₂Ru=CHPh (2). 1H and ³¹P NMR analysis of the crude reaction mixture showed the formation of new signals at δ = 19.60 and 30.54 ppm and δ = 19.62 and 30.54 ppm for the reaction involving catalysts 8a and 8b, respectively. These signals are nearly identical to those observed in C₆D6 solutions of 2 (δ = 19.63 and 30.53 ppm). While the exchange reaction between catalyst 8a and PCy₃ may was within 2 hours, the analogous reaction with catalyst 8b may took nearly 8 hours. Without limiting the disclosure to a particular theory, the rate difference may be related to the increased steric hinderance associated with structure 6 as compared to structure 7, facilitating dissociation of the former. Regardless, these results suggest that the relatively bulky ADC ligands in catalysts 8a and 8b disassociate from their respective metal centers in preference to SIMes. As such, the catalytically active species generated from these catalysts are effectively the same as those generated from the commercially available catalysts 2 or 3 (FIGURE 1). Example 10: Synthesis and Analysis of Labile ADC Ligand Catalysts.

Synthesis of ADC-containing derivatives with more labile ligands may also be desirable. In particular, synthesizing Hoveyda-Grubbs-type catalysts, which contain a weakly bound aryl ether trans to either an NHC or phosphine, may be desirable. (ADC)(PCy₃)Cl₂Ru=CH(2-isopropoxy)Ph-type catalysts, 9a and 9b, may be synthesized via treatment of (PCy₃)-C12Ru=CH(2-isopropoxy)Ph with structures 6 or 7 (generated in situ from their respective formamidinium salts), respectively. Figure 3 illustrates the structures of catalysts 9a and 9b. The conformations shown are consistent with the structures observed in solution. The conformations shown are also consistent with the solid state structures of these catalysts.

As observed with catalysts 8a and 8b, catalysts 9a and 9b are stable toward column chromatography, which facilitate their isolation. On the basis of a series of NOESY measurements, the ADCs in these catalysts were determined to adopt pseudo trans conformations in which one N-aryl ring was juxtaposed with the benzylidene moieties. This assessment was confirmed by analyzing single crystals of the aforementioned catalysts using X-ray diffraction. FIGURE 5 illustrates the ORTEP diagrams of catalysts 9a and 9b.

For catalysts 9a, key bond lengths (A° ) and angles (deg) are: Ru-Cl, 2.015(2); Ru-C2, 1.834(2); Ru-O, 2.333(2); Nl-Cl, 1.359(3); N1-C2, 1.350(3); Nl- Cl-Ru, 110.4; N2-Cl-Ru, 130.2(2); Cl-Ru-C2, 106.56(9); Cl-Ru-O, 175.75(7); Cll- Ru-C12, 155.70(2); N1-C1-N2, 119.4(2). For catalyst 9b, Key bond lengths (A° ) and angles (deg) are: Ru-Cl, 2.012(2); Ru-C2, 1.838(1); Ru-O, 2.307(1); Nl-Cl, 1.355(2); N1-C2, 1.481(3); Nl-Cl -Ru, 110.2(1); N2-Cl-Ru, 130.1(1); Cl-Ru-C2, 107.361(7); Cl-Ru-O, 174.47(6); Cll-Ru-C12, 158.97(2); Nl-Cl -N2, 119.6(2).

Compared to NHC analogues of catalyst 4, N-C-N bond angles observed in the solid state structures of catalysts 9a and 9b are significantly more obtuse

(119.4(2)-119.6(2)° versus 107.2(5)-107.6(3)°). Without limiting the disclosure to a particular theory, these relatively large angles may impose additional steric constraints on the ligated metal centers and may explain why the 1H NMR signals attributed to the benzylidene moieties of these catalysts (δ = 15.94 and 15.92 ppm, respectively; CDC1₃) are upfield compared to those observed in 4 (δ = 16.13-16.22 ppm). The distances between the benzylidene proton and the centroid of the juxtaposed arenes are significantly shorter for catalysts 9a and 9b (2.321 and 2.365 A, respectively) than for catalyst 3 (3: 2.489 A, 4a: 2.567 A, 4b: 2.595 A). In addition, the Ru-0 bond lengths in catalysts 9a and 9b were longer than analogous distances found in the crystal structures of catalyst 4 (2.307(l)-2.333(2) A versus 2.269(3)- 2.281(4) A), which, without limiting the disclosure to a particular theory, may reflect the relatively strong electron donicities of the ADCs as compared to NHCs.

Example 11: Catalytic Activity ofRu-Based Olefin Metathesis Catalysts Containing an ADC Ligand.

After the synthesis and characterization of catalysts 8a, 8b, 9a, and 9b, a preliminary investigation of their catalytic activities was conducted. Under standardized conditions, these catalysts showed relatively low catalytic activities in various ring-closing metathesis (RCM) reactions, compared to commercially available Ru-based catalyst represented by catalysts 1 and 2, at ambient temperature. Although the highest activity in the RCM of diethyl diallyl malonate (DDM) was observed when catalyst 9b was used (23% conversion after 1 h), this catalyst was less active then the commercially available Ru-based catalyst represented by catalyst 2 (~ 100% conversion within 30 min) (conditions: [DDM]o = 0.1 M, 1.0 mol % catalyst, CD₂CI₂, 269 30 °C). Without limiting the disclosure to a particular theory, in accord with results observed in Ru-based catalysts containing exceptionally bulky NHC ligands (e.g., l-(l-adamantyl)-3-mesityl-4,5-dihydroimidazol-2-ylidene), the relatively slow kinetics displayed by catalysts 8a, 8b, 9a, and 9b may be due to the increased steric bulk of the ADCs interfering with olefin coordination or the catalysts' mechanism.

However, significantly enhanced catalytic activities were observed at elevated temperatures. For example, at 40°C, conversions of DDM to its cyclic product were determined to be 89%, 62%, 100%, and 100%, for catalysts 8a, 8b, 9a, and 9b, respectively, after 12 hours (conditions: [DDM]0 = 0.1 M, 5.0 mol % catalyst, CD2C12). Diethyl bis(2-methylallyl)malonate, a sterically encumbered olefin, was quantitatively converted to its respective cyclic products in less than 1 hour when the reactions were performed at 100 °C using catalysts 9a and 9b (conditions: [substrate]o = 0.1 M, 5.0 mol % catalyst, toluene- g). Under otherwise identical conditions, the analogous RCM reaction involving catalysts 8a or 8b required up to 12 hours to reach similar conversion percentages.

Catalysts 9a and 9b were studied in two representative cross-metathesis (CM) reactions to allow comparison of their inherent E.Z selectivities to those exhibited by the analogous commercially available NHC catalysts represented by catalysts 4a and

4b. FIGURE 6 A illustrates reaction scheme 1 and reaction scheme 2 that govern those reactions. Under the conditions summarized in reaction scheme 1, catalysts 9a and 9b afforded a 30% and 32% yield of structure 10 with E.Z ratios = 1.2: 1 and 0.6: 1, respectively, after 3 hours. For comparison, commercially available catalysts 4a and 4b, which contain NHCs analogous to the ADCs in catalysts 9a and 9b, were reported to afford the same product with higher E.Z ratios {E.Z = 2.8 : 1 and 1.8: 1, respectively) at similar conversions (<33%) and under similar conditions.

Analogous results were obtained when Ru-based catalysts were used for the cross-metathesis reaction shown in reaction scheme 2 (FIGURE 6A) to convert structure 11 with 1 ,4-diacetoxy-2-butene to afford structure 12. Results are shown in

FIGURE 6B. The reaction using catalyst 9a was performed at 60°C; all other reactions were performed at 23°C. Ratios and conversions were determined by gas chromatography.

As shown in FIGURE 6B, catalyst 9a afforded structure 12 in a nearly 1 : 1 ratio of its E and Z isomers at conversion percentages that exceeded 75%. For comparison, the commercially available catalyst represented by catalyst 4a also afforded structure 12, but with an E.Z ratio = 2.5:1 at similar conversion percentages. Although catalyst 9b yielded a product comparable to that obtained with the commercially available catalyst represented by catalyst 3, the E:Z ratio of structure 12 obtained at 80% conversion (ca. 4: 1) was lower than that reported for commercially available catalyst represented by catalyst 4b {E.Z = 6: 1) under otherwise identical conditions.

The ring-opening metathesis polymerization of 1,5-cyclooctadiene (COD) over time using catalyst 4a and catalyst 9a as catalysts was monitored by quantitative

1 13

H and C NMR spectroscopy (conditions: C₆D6 as solvent, 75°C (sealed tube),

[COD]o=0.50 M, [catalyst]₀=0.016 M). At low monomer conversions (<35%), both catalysts afforded predominantly cis polybutadiene (E:Z=1.0:4.8 for catalyst 9a at 32% monomer conversion and 1.0:3.2 for catalyst 4a at 34% were observed).

However, at conversions approaching 50%, catalyst 9a afforded polymer with a higher cis content (E:Z=1.0:4.0 at 49% monomer conversion) than catalyst 4a (E:Z=1.0:2.8 at 48%).

Although the origin of the selectivities observed in the reactions described above might have been due to the increased sterics of the ADC-containing catalysts as compared to their NHC analogues, it might also be have been related to a reduced ability of the ADC catalysts to facilitate olefin isomerization and other secondary metatheses. To investigate, a cross-metathesis reaction involving allyl benzene (structure 1 1) and 1 ,4-diacetoxy-2-butene was performed as described in reaction scheme 2 (FIGURE 6A), using catalyst 9a. When the conversion of structure 1 1 to structure 12 reached 95% (E:Z of product = 1.5 : 1), the reaction mixture was split into two fractions. One fraction was left untreated and a the second fraction was treated with additional catalyst ([Ru]_finai =5.0 mol %). After heating both fractions to 60 °C for an additional 12 hours, they were analyzed. The E:Z of structure 12 found in both samples increased to 3.0: 1 and 7.0: 1 , respectively. Hence, although catalyst 9a facilitates secondary metathesis reactions, these processes appear to be relatively slow and were likely not occurring to a significant extent over the course of the

aforementioned cross-metathesis reactions. Accordingly, the observed selectivities of the ADC-ligand-containing catalysts are likely due to increased sterics of the ADC- containing catalysts as compared to their NHC analogues.

Therefore, the present invention is well adapted to attain the ends and advantages mentioned as well as those that are inherent therein. The particular embodiments disclosed above are illustrative only, as the present invention may be modified and practiced in different but equivalent manners apparent to those skilled in the art having the benefit of the teachings herein. Furthermore, no limitations are intended to the details of construction or design herein shown, other than as described in the claims below. It is therefore evident that the particular illustrative embodiments disclosed above may be altered or modified and all such variations are considered within the scope and spirit of the present invention. While compositions and methods are described in terms of "comprising," "containing," or "including" various components or steps, the compositions and methods can also "consist essentially of or "consist of the various components and steps. All numbers and ranges disclosed above may vary by some amount. Whenever a numerical range with a lower limit and an upper limit is disclosed, any number and any included range falling within the range is specifically disclosed. In particular, every range of values (of the form, "from about a to about b," or, equivalently, "from approximately a to b," or, equivalently, "from approximately a-b") disclosed herein is to be understood to set forth every number and range encompassed within the broader range of values. Also, the terms in the claims have their plain, ordinary meaning unless otherwise explicitly and clearly defined by the patentee. Moreover, the indefinite articles "a" or "an," as used in the claims, are defined herein to mean one or more than one of the element that it introduces. If there is any conflict in the usages of a word or term in this specification and one or more patent or other documents that may be incorporated herein by reference, the definitions that are consistent with this specification should be adopted.

Claims

CLAIMS What is claimed is:

1. A ruthenium (Ru)-based olefin metathesis reaction catalyst comprising:

a core comprising a ruthenium-based alkylidene; and

at least one acyclic diaminocarbene (ADC) ligand covalently bound to the core.

2. The catalyst according to Claim 1, wherein at least one ligand comprises an ADC ligand and at least a second ligand comprises an N-heterocyclic carbine ligand.

3. The catalyst according to Claim 1, wherein at least one ligand comprises an ADC ligand and at least a second ligand comprises a phosphine ligand.

4. The catalyst according to Claim 1, wherein at least one ADC ligand comprises a symmetric ADC ligand.

5. The catalyst according to Claim 1, wherein at least one ADC comprises an asymmetric ADC ligand.

6. The catalyst according to Claim 1, wherein at least one ADC ligand is in a pseudo cis conformation.

7. The catalyst according to Claim 1, wherein at least one ADC ligand is in a pseudo trans confirmation.

8. The catalyst according to Claim 1, wherein at least one ADC ligand comprises at least one 2,6-di-isopropylphenyl (DIPP) substituent.

9. The catalyst according to Claim 1, wherein at least one ADC ligand comprises at least one 2,4,6-trimethylphenyl (Mes) substituent.

10. The catalyst according to Claim 1, wherein at the catalyst has a structure of:

11. The catalyst according to Claim 1 , wherein at the catalyst has a

structure of:

12. The catalyst according to Claim 1, wherein at the catalyst has a structure of:

13. The catalyst according to Claim 1, wherein at the catalyst has a

l

structure of:

14. A method of catalyzing an olefin metathesis reaction comprising reacting a first olefin and a second olefin in the presence of a ruthenium (Ru)-based olefin metathesis reaction catalyst comprising a core comprising a ruthenium-based alkylidene and at least one acyclic diammocarbene (ADC) ligand covalently bound to the core to synthesize a third olefin mixture.

15. The method according to Claim 14, wherein the third olefin mixture has an E:Z ratio of 2: 1 or less.

16. The method according to Claim 14, wherein the reacting step is carried out for less than one hour.

17. The method according to Claim 14, wherein the conversion percentage of the first and second olefins to the third olefin mixture is at least 30%.

18. A method of preparing an olefin mixture with a low E:Z ratio comprising reacting a first olefin and a second olefin in the presence of a ruthenium (Ru)-based olefin metathesis reaction catalyst comprising a core comprising a ruthenium-based alkylidene and at least one acyclic diaminocarbene (ADC) ligand covalently bound to the core to synthesize an olefin mixture having a E:Z ratio of 2: 1 or less.

19. A method for preparing a ruthenium (Ru)-based olefin metathesis reaction catalyst comprising:

providing a quantity of (SIMes)(pyridine)₂Cl₂Ru=CHPh;

providing a quantity of acyclic diaminocarbene (ADC); and

reacting the quantity of (SIMes)(pyridine)₂Cl₂Ru=CHPh with the quantity of acyclic diaminocarbene (ADC) to form a ruthenium (Ru)-based olefin metathesis reaction catalyst comprising at least one ADC ligand.

20. A method for preparing a Hoveyda-Grubbs-type ruthenium (Ru)-based olefin metathesis reaction catalyst comprising:

providing a quantity of (PCy₃)Cl₂Ru=CH(2-isopropoxy)Ph;

providing a quantity of acyclic diaminocarbene (ADC); and

reacting the quantity of (PCy₃)Cl₂Ru=CH(2-isopropoxy)Ph with the quantity of acyclic diaminocarbene to form the Hoveyda-Grubbs-type catalyst comprising at least one ADC ligand.