WO2016100101A1

WO2016100101A1 - Ruthenium-based metathesis pre-catalyst compounds

Info

Publication number: WO2016100101A1
Application number: PCT/US2015/065142
Authority: WO
Inventors: Michael J. Williams; Jongrock Kong; Cheol CHUNG
Original assignee: Merck Sharp & Dohme Corp.
Priority date: 2014-12-15
Filing date: 2015-12-11
Publication date: 2016-06-23

Abstract

The present disclosure relates to ruthenium pre-catalyst compounds of the structure of Formula I or the structure of Formula II, which are recyclable, highly reactive for olefin metathesis reactions and have a novel activation mechanism.

Description

TITLE OF THE APPLICATION

RUTHENIUM-BASED METATHESIS PRE-CATALYST COMPOUNDS

FIELD OF THE INVENTION

The present disclosure relates to novel ruthenium-based metathesis pre-catalyst compounds incorporating novel ligands, which are recyclable, stable, tunable, highly reactive for olefin metathesis reactions and have a novel activation mechanism. This disclosure also relates to the preparation and use of novel ruthenium-based metathesis pre-catalyst compounds. BACKGROUND OF THE INVENTION

Olefin metathesis reactions, catalyzed by transition metal carbene complexes, are broadly employed in organic synthesis, particularly in drug discovery and development of polymeric materials and industrial syntheses.

Metathesis reactions have been extensively studied, and numerous transition metal complexes have been reported as active metathesis catalysts (often referred to as "pre- catalysts", "catalyst complexes" or "pre-catalyst complexes"), for example, Robert H. Grubbs & Sukbok Chang, Recent Advances in Olefin Metathesis and Its Application in Organic Synthesis, 54 TETRAHEDRON 4413-4450 (1998). The first and second generation ruthenium-based pre- catalysts, discovered by Grubbs et al. {see generally, HANDBOOK OF METATHESIS (Robert H. Grubbs, ed. WILEY-VCH Verlag GmbH & Co. KGaA 2003); Georgios C. Vougioukalakis & Robert H. Grubbs, Ruthenium-Based Heterocyclic Carbene-Coordinated Olefin Metathesis Catalysts, 110 CHEM. REV. 1746-1787 (2010)), have good metathesis activity, but the ruthenium- based pre-catalysts having tricyclohexylphosphine ligand are unstable in air and water.

Ruthenium-based pre-catalyst complexes were developed with new monomeric and dendritic alkoxybenzylidene ligand-based ruthenium pre-catalysts; these pre-catalysts offered higher activity and better stability in comparison to earlier ruthenium-based pre-catalysts without alkoxybenzylidene ligands. Incorporation of substituted alkoxybenzylidene ligands improved the catalytic activity. See Jason S. Kingsbury et al., A Recyclable Ru-Based Metathesis Pre- catalyst, 121 J. AM. CHEM. SOC. 791-799 (1999); Steven B. Garber et al, Efficient and

Recyclable Monomeric and Dendritic Ru-Based Metathesis Pre-catalysts, 122 J. AM. CHEM.

SOC. 8168-8179 (2000). However, a disadvantage of previously reported ruthenium-based pre- catalysts is the substrate-dependence for different kinds of reported ruthenium-based complexes in metathesis reactions with multiple functionally substituted substrates. Thus, there remains a need to develop new metathesis pre-catalyst compounds, particularly highly reactive pre-catalyst compounds that are tunable to the particular reactions to be catalyzed, as an alternative to known catalytic systems. There is also a need for pre-catalyst compounds that have novel mechanisms of activation and that can be recycled and reduce manufacturing costs for pharmaceutical and industrial chemistry.

SUMMARY OF THE INVENTION

The present invention relates to novel phosphine-free ruthenium-based metathesis pre-catalyst compounds of Formula I and novel phosphine-free ruthenium-based metathesis pre- catalyst compounds of Formula II. In particular, the present invention relates to ruthenium-based pre-catalyst compounds that incorporate tunable carbene ligands. In particular, the present invention relates to ruthenium pre-catalyst compounds selected from compounds having the structure of Formula I or the structure of Formula II:

Formula I Formula II.

Embodiments of the invention include phosphine-free ruthenium-based metathesis pre-catalyst compounds of Formula I and of Formula II, comprising tunable, chelating quinoxaline or pyrazine rings, as well as synthesis and isolation of pre-catalyst compounds of Formula I and pre-catalyst compounds of Formula II. Use of pre-catalyst compounds of Formula I and pre-catalyst compounds of Formula II are also disclosed.

Further embodiments include the use of pre-catalyst compounds of Formula I and/or pre-catalyst compounds of Formula II in combination with one or more acid co-pre- catalyst(s). The use of such acid co-pre-catalyst(s) may modify and/or enhance the "latent" nature of the compounds of Formula I and pre-catalyst compounds of Formula II, which may increase the ability to increase the rate of metathesis reactions.

The claimed pre-catalyst compounds of Formula I and pre-catalyst compounds of Formula II are useful in olefin metathesis reactions, particularly ring-closing metathesis (RCM), ring-opening metathesis (ROM), ring-opening metathesis polymerization (ROMP), and cross- metathesis (CM). In particular, the pre-catalyst compounds of Formula I and pre-catalyst compounds of Formula II provide new classes of enhanceable pre-catalyst compounds, which are isolable with ease and allow ease of operation in metathesis reactions that contain hetero atoms and non-hetero atoms.

Embodiments, aspects and features of the present invention are either further described in or will be apparent from the ensuing description, examples, and appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1 provides an ORTEP representation (a perspective view structural model), with thermal ellipsoids set at the 30% probability level, of the ruthenium-based pre-catalyst complex of Example 4 (Alternate Preparation), which was calculated from the geographic coordinates.

Figure 2 provides a graphical representation showing the conversion (%) of Example 20, which was obtained using the ruthenium-based pre-catalyst complex of Example 4 with and without the addition of a co-pre-catalyst, benzene sulfonic acid (BSA), at 30°C.

Figure 3 provides a graphical representation showing the conversion (%) of Example 21, which was obtained using the ruthenium-based pre-catalyst complex of Example 4 with and without the addition of a co-pre-catalyst, benzene sulfonic acid (BSA), at 30°C.

Figure 4 provides a graphical representation showing the conversion (%) of Example 22, which was obtained using the ruthenium-based pre-catalyst complex of Example 2 with and without the addition of a co-pre-catalyst, benzene sulfonic acid (BSA), at 30°C.

DETAILED DESCRIPTION OF THE INVENTION

The present invention includes ruthenium-based pre-catalyst compounds, particularly novel ruthenium-based metathesis pre-catalyst compounds of Formula I and novel ruthenium-based metathesis pre-catalyst compounds of Formula II. These compounds and their analogs are useful as pre-catalyst compounds for metathesis reactions.

In a first embodiment of the invention, the novel phosphine-free ruthenium metathesis pre-catalyst compounds are selected from compounds having the structure of Formula I or the structure of Formula II:

wherein:

L is a neutral electron-donating ligand selected from the group consisting of phosphine ligands and heterocyclic carbene ligands, which are selected from the group consisting of:

wherein:

R⁷, R⁸, and R⁹ are each independently selected from H, Ci-Cg alkyl, C3-C8 cycloalkyl, and C6-C12 aryl;

R¹⁰ and R¹¹ are each independently selected from Ci-Cg alkyl, C₃-C8 cycloalkyl, and C6-C12 aryl, substituted by 0, 1, 2, or 3 substituents R¹⁴, where each R¹⁴ is independently selected from Ci-Cg alkyl;

R¹² and R¹³ are each independently selected from H, Ci-Cg alkyl, Ci-Cg alkoxy, C6-C12 aryl, C6-C12 aryloxy, Ci-Cg alkylcarbonyl, C6-C12 arylcarbonyl, Ci-Cg alkoxycarbonyl, C6-C12 aryloxycarbonyl, C5-C12 heteroaryl, carboxyl, cyano, nitro, amido, amino, Ci-Cs alkylsulfonyl, C6-C12 arylsulfonyl, Ci-Cs alkylsulfinyl, C6-C12 arylsulfinyl, Ci-Cs alkylthio, C6-C12 arylthio, and sulfonamide groups;

X and X¹ are each an independently selected electron-withdrawing anionic ligand and are each independently selected from the group consisting of halogens, carboxylates, and C6-C12 aryloxides;

n is selected from 0, 1, 2, 3, 4, or 5;

T is selected from H, R¹, -OR¹, -SR.¹, -NR , -NR^OR¹, -SO2R¹, -SOR¹,

and -COR¹; each R¹ may be the same or different and is independently selected from Ci-C₈ alkyl and C3-C8 cycloalkyl;

R², R³, R⁴, and R⁵ are each independently selected from H, halogen atoms, -OH, Ci-C₆ alkyl, Ci-C₆ alkoxy, Ci-C₆ haloalkyl, Ci-C₆ haloalkoxy, -CN, -C(0)OH, -C(0)OCH₃, d- C₆ thioalkoxy, -S0₂(Ci-C₆ alkyl), C₃-C₈ cycloalkyl, C₃-C₈ cycloalkoxy, -NR , -NHR¹, phenyl, naphthyl, and heterocycles selected from the group consisting of 5- and 6-membered saturated and unsaturated heterocyclic rings that have 1 or 2 heteroatoms independently selected from the group consisting of N, O, and S, wherein the heterocycles have 0 to 3 substituents independently selected from H, halogen atoms, -OH, C1-C6 alkyl, C 1-C6 alkoxy, C 1-C6 haloalkyl, C1-C6 haloalkoxy, -CN, -C(0)OH, -C(0)OCH₃, C_rC₆ thioalkoxy, -S0₂(Ci-C₆ alkyl), C₃-C₈ cycloalkyl, C₃-C₈ cycloalkoxy, -NR , and -NHR¹; and

R⁶ is selected from H, halogen atoms, Ci-C₈ alkyl, C₃-C₈ cycloalkyl, Ci-C₈ alkoxy, and C₃-C₈ cycloalkoxy;

or R³ and R⁶ optionally are taken together with the atoms to which they are attached to form a 5- to 7-membered ring, containing 0 to 3 heteroatoms independently selected from N, O, and S.

In a first aspect of the first embodiment of the invention, ruthenium-based pre- catalyst compounds selected from compounds having the structure of Formula I are provided. In this aspect of the first embodiment, all other groups are as provided above in the first embodiment.

In a second aspect of the first embodiment of the invention, ruthenium-based pre- catalyst compounds selected from compounds having the structure of Formula II are provided. In this embodiment, all other groups are as provided above in the first embodiment.

In a second embodiment of the invention, L is selected from the group consisting

of

, wherein R¹⁰ and R^{1 1} are each phenyl, substituted by 0, 1, 2, or 3 substituents R¹⁴, where each R¹⁴ is independently selected from C1-C6 alkyl; R¹² and R¹³ are each independently selected from H, Ci-C₈ alkyl, C₃-C₈ cycloalkyl, and C6-C12 aryl, and R¹² and R¹³ may optionally be bonded to form a ring, which may be an alkyl ring or aryl ring. In a first aspect of this second embodiment, wherein L is

wherein R¹⁰ and R¹¹ are each phenyl, substituted by 0, 1, 2, or 3 substituents R¹⁴, where each R is independently selected from Ci-C₆ alkyl; R¹² and R¹³ are each H. In a particular instance of

this first aspect of this second embodiment, wherein

_; wherein R^1U and

R¹¹ are each phenyl, substituted by 0, 1, 2, or 3 substituents R¹⁴, where each R¹⁴ is independently selected from C 1-C6 alkyl; R¹² and R¹³ are each H. In a second aspect of this second

embodiment, R¹⁰ and R¹¹ are the same and are each

; in particular instances of this second aspect of the second embodiment, R¹⁰ and R¹¹ are the same and are each selected

from the group consisting

this embodiment, all other groups are as provided above in the first embodiment.

In a third embodiment of the invention, X and X¹ are each independently selected from the group consisting of halogens. In particular aspects of the third embodiment, X and X¹ are each chloride. In this embodiment, all other groups are as provided in the first and/or second embodiments.

In a fourth embodiment of the invention, n is selected from 0 or 1. In this embodiment, all other groups are as provided in the first, second, and/or third embodiments.

In a fifth embodiment of the invention, T is selected from the group consisting of -OCH₃, -OC₂H₅, -OC(CH₃)₂, -SCH₃, -SC₂H₅, -SC(CH₃)₂, -NH₂, -N(CH₃)₂, -NHCOCH₃, -NHCOCF₃, -S0₂CH₃, -S0₂N(CH₃)₂, and -SOCH₃. In particular aspects of this fifth embodiment, T is selected from the group consisting of -OCH₃, -OC(CH₃)₂, -SCH₃,and -N(CH₃)₂. In this embodiment, all other groups are as provided in the first, second, third, and/or fourth embodiments.

In a sixth embodiment of the invention, R², R³, R⁴, and R⁵ are each independently selected from H, halogen atoms, -OH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, -CN, -C(0)OH, and -C(0)OCH₃. In aspects of this sixth embodiment, R², R³, R⁴, and R⁵ are each independently selected from H, halogen atoms, -CH₃, -CH₂CH₃, -OCH₃, -CF₃, -CF₂CF₃, and -OCF₃. In particular aspects of this embodiment, R², R³, R⁴, and R⁵ are each independently selected from H, -CH₃, -OCH₃, -CF₃, and -OCF₃. In further aspects of this embodiment, R², R³, R⁴, and R⁵ are each H. In this embodiment, all other groups are as provided in the first, second, third, fourth, and/or fifth embodiments.

In a seventh embodiment, of the invention, R⁶ is selected from H, F, CI, Br, -CH₃, -CF₃, -CH₂CH₃, and -OCH₃. In this embodiment, all other groups are as provided in the first, second, third, fourth, fifth, and/or sixth embodiments.

In an eighth embodiment, R³ and R⁶ optionally are taken together with the atoms to which they are attached to form a 5- to 7-membered ring, containing 0 to 3 heteroatoms independently selected from N, O, and S. In aspects of this embodiment, R³ and R⁶ are linked to form -0-CH₂-0- or -(CH₂)₃-. In this embodiment, all other groups are as provided in the first, second, third, fourth, and/or fifth embodiments.

In a nineth embodiment, the ruthenium-based pre-catalyst compound is selected from the group consisting of:

In another embodiment, for the ruthenium-based pre-catalyst compounds selected from compounds having the structure of Formula I and the structure of Formula II, variables L, X^X,X², n, T, R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², R¹³, and R¹⁴ are each selected independently from each other.

In another embodiment of the invention, the compound of the invention is selected from the exemplary species depicted in Examples 1 through 19 shown below.

Other embodiments of the present invention include the following: (a) Methods of preparing a ruthenium-based metathesis pre-catalyst compound of the structure of Formula I or the structure of Formula II.

(b) Methods of using a ruthenium-based metathesis pre-catalyst compound of the structure of Formula I or the structure of Formula II, in an olefin metathesis reaction.

(c) Methods of using a ruthenium-based metathesis pre-catalyst compound of the structure of Formula I or the structure of Formula II, in ring-closing metathesis (RCM) reactions.

(d) Methods of using a ruthenium-based metathesis pre-catalyst compound of the structure of Formula I or the structure of Formula II, in ring-opening metathesis (ROM) reactions.

(e) Methods of using a ruthenium-based metathesis pre-catalyst compound of the structure of Formula I or the structure of Formula II, in cross-metathesis reactions (CM).

(f) Methods of using a ruthenium-based metathesis pre-catalyst compound of the structure of Formula I or the structure of Formula II, in ring-opening metathesis

polymerization (ROMP) reactions. The present invention also includes a compound of the present invention for use in olefin metathesis reactions, particularly ring-closing metathesis (RCM), ring-opening metathesis (ROM), cross-metathesis (CM), and ring-opening metathesis polymerization

(ROMP), optionally in combination with use of an acid co-pre-catalyst.

In the embodiments of the compounds provided above, it is to be understood that each embodiment may be combined with one or more other embodiments, to the extent that such a combination provides a stable compound and is consistent with the description of the embodiments. It is further to be understood that the embodiments of compositions and methods provided as (a) through (f) above are understood to include all embodiments of the compounds, including such embodiments as result from combinations of embodiments.

It is further to be understood that the terms "catalyst" and "pre-catalyst" are often used interchangeably in the art. As used herein, the term "pre-catalyst" refers to a stable compound that may be activated and used to catalyze a chemical reaction, herein specifically, metathesis. Similarly, the term "catalyst", as used herein, refers to the activated species that takes part in and increases the rate of a chemical reaction.

Compounds

The term "alkyl" refers to a monovalent straight or branched chain, saturated aliphatic hydrocarbon radical having a number of carbon atoms in the specified range. Thus, for example, "C_1-6 alkyl" refers to any of the hexyl alkyl and pentyl alkyl isomers as well as n-, iso-, sec- and fert-butyl, n- and iso-propyl, ethyl, and methyl. As another example, "CM alkyl" refers to n-, iso-, sec- and tert-butyl, n- and isopropyl, ethyl, and methyl.

The term "cycloalkyl" refers to any monocyclic ring of an alkane having a number of carbon atoms in the specified range. Thus, for example, "C3-8 cycloalkyl" (or "C3-C8 cycloalkyl") refers to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl.

The term "heterocycle" refers to any monocyclic ring having 5 to 6 ring atoms, in which 1 or 2 ring atoms are heteroatoms that are independently selected from the group consisting of N, O, and S. The heterocycles herein may be saturated or unsaturated. In addition, the heterocycles herein may be substituted as indicated.

The term "halogen" (or "halo") refers to fluorine, chlorine, bromine and iodine (alternatively referred to as fluoro, chloro, bromo, and iodo or F, CI, Br, and I). The term "aryl" as a group or part of a group means an aromatic monocyclic, bicyclic or tricyclic group, containing from 6 to 12 carbon atoms.

The term "heteroaryl" as a group or part of a group means an aromatic monocyclic, bicyclic or tricyclic group, containing from 6 to 12 carbon atoms and having 1, 2, or 3 heteroatoms selected from N, O, and S, attached through a ring carbon or nitrogen. Examples of such groups include pyrrolyl, furanyl, thienyl, pyridyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazolyl, oxadiazolyl, thiadiazolyl, triazinyl, and tetrazolyl.

As us

indicates a resonance structure in the indicated position that provides a stable carbene and is consistent with the description of the embodiments.

As used herein, any alkyl group, cycloalkyl group, aryl group, or heteroaryl group may be substituted, as indicated, by 0, 1, 2, 3, or 4 substituents independently selected from the group as indicated.

As used herein, the term "acid co-catalyst" refers to any Bronsted acid or Lewis acid that can act as an electron pair acceptor and can catalyze an olefin metathesis reaction.

Particular Bronsted acids that may act as co-catalysts include hydrochloric acid, hydrobromic acid, hydroiodic acid, acetic acid, trifluoroacetic acid, benzenesulfonic acid, /?- toluene sulfonic acid, formic acid, and perchloric acid.

Particular Lewis acids that may act as co-catalysts include hydrochloric acid, hydrobromic acid, hydroiodic acid, acetic acid, trifluoroacetic acid, benzenesulfonic acid, /?- toluene sulfonic acid, formic acid, and perchloric acid as well as metal-based Lewis acids.

Examples of Lewis acid co-catalysts include hydrochloric acid, hydrobromic acid, hydroiodic acid, acetic acid, trifluoroacetic acid, benzenesulfonic acid, >-toluene sulfonic acid, formic acid, perchloric acid, trifluoroborane (BF₃), perchlorostannane (SnC ), hydron tetrafluoroborate (HBF4), and zinc chloride (ZnCl2). Examples of metals that may be incorporated in metal-based Lewis Acid co-catalyst include aluminum, boron, silicon, tin, titanium, zirconium, iron, copper, and zinc. Ligands that may be incorporated in metal-based Lewis acid co-catalyst include halogens, and ligands such as substituted and unsubstituted bisoxazoline (BOX) ligands, substituted and unsubstituted 2,2'-diphenylphopino-l- -dinaphthyl) (BINAP) ligands, substituted and unsubstituted (l,l '-binaphthyl-2,2'-diol) (BINOL) ligands, and substituted and unsubstituted tetraary 1-1, 3 -dioxolane-4,5 -dimethyl (TADDOL) ligands. In the compounds having the structure of Formula I and the structure of Formula II, the atoms may exhibit their natural isotopic abundances, or one or more of the atoms may be artificially enriched in a particular isotope having the same atomic number, but an atomic mass or mass number different from the atomic mass or mass number predominantly found in nature. The present invention is meant to include all suitable isotopic variations of the compounds of having the structure of Formula I and the structure of Formula II. For example, different isotopic forms of hydrogen (H) include protium (^ΧΗ) and deuterium (²H). Protium is the predominant hydrogen isotope found in nature. Enriching for deuterium may afford certain therapeutic advantages, such as increasing in vivo half-life or reducing dosage requirements, or may provide a compound useful as a standard for characterization of biological samples. Isotopically- enriched compounds within the structure of Formula I and the structure of Formula II can be prepared without undue experimentation by conventional techniques well known to those skilled in the art or by processes analogous to those described in the Schemes and Examples herein using appropriate isotopically-enriched reagents and/or intermediates.

Isotopically-enriched compounds described herein can be prepared without undue experimentation by conventional techniques well known to those skilled in the art or by processes analogous to those described in the Schemes and Examples provided herein using appropriate isotopically-enriched reagents and/or intermediates. Precursor ruthenium-based metathesis pre-catalvsts

The ruthenium-based metathesis pre-catalyst compounds of the structure of Formula I and of the structure of Formula II may be prepared from precursor ruthenium-based metathesis complexes, which may be commercially available or prepared from ruthenium according to known techniques. Ruthenium-based metathesis complexes that may be used as precursor ruthenium-based metathesis complexes include the ruthenium-based species of olefin metathesis catalysts disclosed in F. Miller et al, 118 J. AM. CHEM. SOC. 9606 (1996); G.

Kingsbury et al , 121 J. AM. CHEM. SOC. 791 (1999); H. Scholl et al, 1 ORG. LETT. 953 (1999); U.S. Patent Application Publication US2002/0107138; K. Furstner et al, 64 J. ORG. CHEM. 8275 (1999). Specific examples of potentially useful precursor ruthenium-based metathesis complexes include

Method of Preparation

The ruthenium-based metathesis pre-catalyst compounds of the structure of Formula I and of the structure of Formula II may be prepared by a method that comprises reacting a precursor ruthenium metal complex with a ligand, wherein a precursor ruthenium metal pre-catalyst, selected from those described above, is reacted with a ligand is selected from the group consisting of com ounds of Formula IA and compounds of Formula IIA:

Formula IA Formula IIA

in which R², R³, R⁴, and R⁵ are each independently selected from H, halogen atoms, -OH, C1-C6 alkyl, Ci-C₆ alkoxy, C C₆ haloalkyl, Ci-C₆ haloalkoxy, -CN, -C(0)OH, -C(0)OCH₃, d-C₆ thioalkoxy, -S0₂(Ci-C₆ alkyl), C₃-C₈ cycloalkyl, C₃-C₈ cycloalkoxy, -NR^¹, -NHR¹, phenyl, naphthyl, and heterocycles selected from the group consisting of 5- and 6-membered saturated and unsaturated heterocyclic rings that have 1 or 2 heteroatoms independently selected from the group consisting of N, O, and S, wherein the heterocycles have 0 to 3 substituents independently selected from H, halogen atoms, -OH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, -CN, -C(0)OH, -C(0)OCH₃, C C₆ thioalkoxy, -S0₂(Ci-C₆ alkyl), C₃-C₈ cycloalkyl, C₃-C₈ cycloalkoxy, -NR^¹, and -NHR¹; and R⁶ is selected from H, halogen atoms, Ci-Cg alkyl, C₃-Cg cycloalkyl, Ci-Cg alkoxy, and C₃-Cg cycloalkoxy; or R³ and R⁶ optionally are taken together with the atoms to which they are attached to form a 5- to 7-membered ring, containing 0 to 3 heteroatoms independently selected from N, O, and S.

Catalytic Methods

The ruthenium-based metathesis pre-catalyst compounds of the structure of Formula I and of the structure of Formula II may catalyze olefin metathesis reactions. The olefin metathesis reaction may be selected form ring-closing metathesis reactions, ring-opening metathesis reactions, cross-metathesis reactions, and ring-opening polymerization reactions. The ruthenium-based pre-catalyst compound of the structure of Formula I or the structure of Formula II may be charged into a vessel, which is then charged with the remaining olefin reactant metathesis reactants. EXAMPLES

The examples provided below are intended to illustrate the invention and its practice. Unless otherwise provided in the claims, the examples are not to be construed as limitations on the scope or spirit of the invention.

ABBREVIATIONS

μί, μΐ Microliter

μιτιοΐ Micromole

^XH NMR Proton nuclear magnetic resonance spectroscopy

A Angstrom, lA = 1 · 10^"10m

aq., aq Aqueous

BSA Benzene sulfonic acid

CDCI₃ Deuterated chloroform

CH2CI2, DCM Dichloromethane, methylene chloride

CD2CI2 Deuterated dichloromethane, dideuteromethylene chloride

DBU l,8-Diazabicyclo[5.4.0]undec-7-ene

DMAc, DMA Dimethylacetamide

equiv., eq. Equivalents, stoichiometric equivalents

EtOAc Ethyl acetate

EtOH Ethyl alcohol, ethanol

Fe(acac)3 Iron (III) acetylacetonate

g Gram

h Hour

H₂ Hydrogen gas, hydrogen gas atmosphere

HC1 Hydrochloric acid

Hex Hexanes

HPLC High-performance liquid chromatography

Hz Hertz

z-PrOH, 2-PrOH Isopropyl alcohol, isopropanol, CH₃CHOHCH₃

J Coupling constant

K Kelvin

LHMDS Lithium hexamethyldisilazide, lithium bis(trimethylsilyl)amide LiCl Lithium chloride

M Molar

MeOH Methyl alcohol, methanol, CH₃OH

mg Milligram

MgS0₄ Magnesium sulfate

MHz Megahertz

min Minute

ml, mL Milliliter

mmol Millimole

mol% Mole percent

MTBE Methyl fert-butyl ether

N₂ Nitrogen gas, nitrogen gas atmosphere

NaHC0₃ Sodium bicarbonate or sodium hydrogen carbonate

NaHMDS Sodium bis(trimethylsilyl)amide

NaOiBu Sodium fc/V-butoxyde

NaSMe Sodium thiomethoxide

NMP N-Methyl-2-pyrrolidone

NMR Nuclear magnetic resonance spectroscopy

Pd(OAc)₂ Palladium (II) acetate

POCI3 Phosphorus(V) oxychloride

psi Pounds per square inch [gauge], 1 Pascal = 0.000145037738007 psi q quartet

Ra-Ni Sponge metal pre-catalyst, also known as Raney nickel®

RT, rt, r.t. Room temperature

THF Tetrahydrofuran

Vol Volumes relative to the limiting reagents

wt% Weight percent Example 1; [1 -bis(2 _^6-trimethylphenyl)-2-imidazolidinylideneldichloro[3-(6-methoxy-3- (methylthio)quinoxalin-2-yl)propylidenelruthenium(II)

Step 1: Ethyl 2-oxohex-5-enoate

To a solution of diethyl oxalate (100g, 684mmol) in THF (500ml) at -65°C was added 3-butenylmagnesium bromide (0.5M in THF, 1382ml, 691ml) slowly to keep reaction temperature below -60°C. The reaction was stirred at -60°C for lh to reach completion monitored by NMR. The reaction was diluted with MTBE (1500ml), quenched with 10 wt% citric acid (1100ml) at -60°C, maintaining temperature below -20°C. The reaction was warmed to RT. The organic layer was separated, washed with 10 wt% citric acid (550ml), followed by water wash (600ml). The organic layer was washed with saturated NaHCC (500ml X 2), followed by brine (500ml), dried over MgSC>4, filtered, concentrated under vacuum to yield an oil.

¾ NMR δ (500 MHz, CDC1₃): 1.36 (q, J=7.2 Hz, 3H), 2.36-2.41 (m, 2H), 2.93-

2.96 (q, J=7.40 Hz, 2H), 4.29-4.34 (q, J=7.15 Hz, 2H), 5.01 (dq, J=1.4, 10.1 Hz, 1H), 5.06 (dq, J= 6.4, 17.3 Hz, 1H), 5.77-5.85 (m, 1H).

Step 2: 4-Methoxybenzene-l, 2-diamine

4-Methoxy-2-nitroaniline (27. Og, 160mmol) was dissolved in EtOH (300ml). The reaction was flushed with N₂, and Raney Ni pre-catalyst (14. Og) was added. The reaction was hydrogenated under 45psi H₂ for lOh, in an extremely exothermic reaction. The resulting mixture was filtered through a layer of CELITE®, rinsed with EtOH (60ml), and the filtrate was concentrated to yield desired product as a solid, which was used in the next step without purification. ¾ NMR δ (500 MHz, CDC1₃): 3.27 (br s, 4H), 6.25 (dd, J=2.5, 8.4Hz, 1H), 6.30 (d, J=2.7 Hz, 1H), 6.62 (d, J=8.4 Hz, 1H).

Step 3: 3-(But-3-en-l-yl)-7-methoxyquinoxalin-2-ol

desired undesired To a solution of ethyl 2-oxohex-5-enoate (7.27g, 38.6mmol) in EtOH (65.0ml,

13X) and water (7.50ml, 1.5X) at 50°C was added a solution of 4-methoxybenzene-l, 2-diamine

(5g, 35.1mmol) in EtOH (10.00ml, 2X) through syringe pump over 30min. The reaction turned into a slurry. The reaction mixture was then stirred and heated at 50°C for 3h. The reaction reached completion, at which point the ratio of desired isomer to undesired isomer was 12 to 1 monitored by HPLC. The reaction mixture was cooled to RT. The precipitate was collected by filtration, rinsed with water (15ml) twice, dried under vacuum and N₂ sweep overnight to yield desired product as a solid.

¾ NMR δ (500 MHz, CDC1₃): 2.60 (2H, m), 3.05 (2H, q, J=7.7 Hz), 3.92 (3H, s), 5.02 (1H, dd, J=1.2, 10.3 Hz), 5.14 (1H, dd, J=1.7, 17.1 Hz), 5.95-6.03 (1H, m), 6.74 (1H, d, J=2.8 Hz), 6.93 (1H, d, J=8.9 Hz), 7.73 (1H, d, J=8.8 Hz).

Step 4: 2-(But-3-en-l-yl)-3-chloro-6-methoxyquinoxaline

To 3-(but-3-en-l-yl)-7-methoxyquinoxalin-2-ol (4.63g, 18.50mmol) from step 3 was charged POCI₃ (17.24ml, 185mmol, lO.Oequiv.) to form a thick slurry. The mixture was heated to 100°C and judged complete (lh) after HPLC analysis. The mixture was cooled to RT, and concentrated on a rotary evaporator to remove most of the POCI₃. The resulting residue was quenched into a mixture of saturated NaHCC (200mL), ice (200mL), and EtOAc (300mL) with good agitation. The layers were split, and the organic layer was washed with brine (lOOmL), dried over MgSC , filtered and concentrated to afford the product compound as a solid.

Step 5: 2-(But-3-en-l-yl)-6-methoxy-3-(methylthio)quinoxaline

To a 200-mL round-bottom flask were charged 2-(but-3-en-l-yl)-3-chloro-6- methoxyquinoxaline (3.00g, 12.1mmol, l.Oequiv.) and DMAc (45.0ml). The reaction mixture was cooled to 0°C, and NaSMe (1.860g, 26.5mmol, 2.2equiv.) was charged to the mixture. The reaction mixture was allowed to age at 0°C and judged complete (45min) by HPLC analysis. Water (150mL) was then slowly charged to the reaction mixture, whereupon a white precipitate formed. The resulting slurry was warmed to RT and filtered. The resulting wet cake was washed with water (3 x 50mL), and the cake was dried on the filter with N₂ and vacuum, yielding the desired product as a solid.

Step 6:

To a round-bottom flask was charged 2-(but-3-en-l-yl)-6-methoxy-3- (methylthio)quinoxaline (0.797g, 3.06mmol), and purged with N₂. After toluene (3.00ml) and precursor pre-catalyst complex (l.OOg, 1.361mmol, commercially available as Zhan IB) were charged under a stream of N₂, the system was sealed, and the walls were washed with additional toluene (2mL). The resulting mixture was aged (3h) at 40°C, deemed complete by TiNMR, and hexanes (10.00ml) were charged at 40°C. The resulting slurry was then allowed to cool to RT, filtered through a sintered funnel, washed in 2 portions with 25% toluene in hexane (20.00ml; 2x lOmL), and then washed with 4 portions of hexanes (40.0ml; 4 x lOmL). The resulting wet cake was dried in a vacuum oven to yield the desired product (981mg, 87% yield) as a deep red solid.

Example 2; [1 -bis(2 _^6-trimethylphenyl)-2-imidazolidinylideneldichloro[3-(6-methoxy-3- (diniethylaniiiio)quiiio\aliii-2-yl)i)i oi)\ ideiie|i utheiiiuni(l l)

Step 1: 3-(B -3-en-l-yl)-7-methoxy-N,N-dimethylquinoxalin-2-amine

To a 250-mL round-bottom flask were charged 2-(but-3-en-l-yl)-3-chloro-6- methoxyquinoxaline (3.00g, 12.06mmol) from step 4 of Example 1, DMA (22.5ml), and dimethylamine (7.64ml, 15.28mmol, 1.27equiv. as a 2.0M solution in THF). The reaction mixture was heated to 55°C. The reaction mixture was judged incomplete (5h) and additional dimethylamine (20ml, 40.0mmol, 3.32equiv.) was charged to the mixture. The reaction mixture was heated (lOh) at 55°C and then allowed to stir at RT over the weekend. The reaction mixture was judged complete (>90% conversion by HPLC analysis), and the reaction was quenched with 200mL of water and EtOAc (75mL). The layers were split, and the aqueous layer was extracted again with EtOAc (50mL). The organic layers were combined, washed with water (lOOmL), 10 wt% LiCl (75mL), dried over MgSC^, filtered, and concentrated to yield yellow oil. The resulting crude product was purified via silica gel chromatography (0 to 50 % EtOAc in hexanes over 10 column volumes) to yield the desired product as an oil.

Step 2:

To a round-bottom flask was charged 3-(but-3-en-l-yl)-7-methoxy-N,N- dimethylquinoxalin-2-amine (0.788g, 3.06mmol), and the system was purged with N₂. Toluene (3.00ml) was charged to the system under inert handling; precursor pre-catalyst complex (l .OOg, 1.361mmol, commercially available as Zhan IB) was charged under a stream of N₂; the system was sealed; and toluene (2mL) was utilized to wash down the walls of the flask. The system was aged at 40°C until judged complete by ^XH NMR. Addition hexanes (10.00ml) were changed at 40°C. The resulting mixture was allowed to age for approximately lh at RT, then filtered through a sintered funnel, washed in two portions with 25% toluene in hexanes (20.00ml; 2 x lOmL), and in four portions with hexanes (40.0ml; 4 x lOmL). The resulting wet cake was dried on the filter with vacuum and N₂ purge to yield the desired product (962mg, 94% yield) solid.

Example 3; [1 -bis(2 .6-trimethylphenyl)-2-imidazolidinylideneldichloro[3-(3,6- dimethoxyquinoxalin-2-yl)propylidenelrathenium(lI)

To a 250-mL flask were charged 2-(but-3-en-l-yl)-3-chloro-6- methoxyquinoxaline (3.00g, 12.06mmol), DMAc(45.0ml), and then MeOH (2.79ml, 69.0mmol, 5.7equiv.). The mixture was cooled in an ice/water bath below 5°C, and LiHMDS (13.27ml, 13.27mmol, 1. lequiv.) was charged keeping the internal temperature below 10°C. The reaction mixture was stirred for lOmin and then allowed to warm to RT. When the reaction mixture was judged complete (23h) by HPLC analysis, the system was quenched with water (lOOmL), EtOAc (lOOmL), and 1M HC1 (50mL). The organic layer was washed with water (2 x 50mL), dried over MgS0₄, filtered, and concentrated to yield crude oil. The resulting crude material was purified via silica gel chromatography (120g silica gel column (ISCO, Inc. Lincoln, NE, USA), 0 to 50% EtOAc in hexanes over 10 column volumes) to yield the desired product as an oil, which crystallized to a solid upon standing at -20°C.

Step 2:

To a round-bottom flask was charged 2-(but-3-en-l-yl)-3,6-dimethoxyquinoxaline (0.916g), and then the system was purged with N_2. Toluene (3.00ml) was charged to the system under inert handling; precursor pre-catalyst complex (l .OOg, 1.363mmol, commercially available as Zhan IB) was charged under a stream of N₂, and the system was sealed. Toluene (2.0mL) was utilized to wash the sides of the flask. The system was aged at 40°C (45min) until judged complete by ^XH NMR. Hexanes (15.00ml) were added dropwise at 40°C, and then the mixture was allowed to cool to RT and to age for lh. To the resulting slurry was further added 25% toluene in hexane (20.00ml). The slurry was filtered through a sintered funnel, and the solid was slurry washed with hexanes (40.0ml; 4 x lOmL) to yield the desired product (984mg) as an orange solid. Example 4; [1 -bis(2 .6-trimethylphenyl)-2-imidazolidinylideneldichloro[3-(3-isopropoxy- 6-methoxyquinoxalin-2-yl)propylidenelruthenium(II)

Step 1: 2-( -3-en-l-yl)-3-isopropoxy-6-methoxyquinoxaline

To a 250-mL round-bottom flask were charged 2-(but-3-en-l-yl)-3-chloro-6- methoxyquinoxaline (3.50g, 14.07mmol), 2-PrOH (2.155ml, 28.1mmol), and DMAc (35ml). The system was cooled in an ice/water bath, NaHMDS (8.80ml, 17.59mmol) was charged to the reaction mixture via syringe. The reaction mixture was allowed to stir at RT under N₂ and judged complete (72h) by HPLC analysis. The system was quenched with water (lOOmL), 1M HC1 (50mL), and EtOAc (lOOmL). The resulting biphasic system was split, and the aqueous layer was extracted with EtOAc (lOOmL). The organic layers were combined, washed with water (50mL), washed with 10 wt% brine (50mL), dried over MgSC>4, filtered, and concentrated. The crude blackish oil was purified via silica gel chromatography (loaded with 1 : 1 DCM:hex; 220g silica gel column (ISCO, Inc. Lincoln, NE, USA); eluted with 100% hexanes for 1 column volume; then 0 to 30% EtOAc in hexanes over 10 column volumes) to yield the desired product as an oil. Step 2:

To a round-bottom flask was charged 2-(but-3-en-l-yl)-3-isopropoxy-6- methoxyquinoxaline (0.98g, 3.60mmol). The system was purged with N₂, and degassed toluene (3.00ml) was charged to the system under inert handling. Precursor pre-catalyst complex (1.00g, 1.363mmol, commercially available as Zhan IB) was charged to the system under a stream of N₂, and the system was sealed. The walls of the flask were washed with degassed toluene (2mL). The system was heated and aged at 40°C, where it was judged complete by ^XH NMR and TLC analysis (30min). The mixture was treated with hexanes (10.00ml) dropwise at 40°C was then allowed to cool to RT and age (lh). The slurry was filtered through a sintered funnel, and the solid was slurry washed with 3: 1 hexanes: toluene (20mL; 2 x lOmL portions), and then hexanes (40mL; 4 x lOmL portions) to yield the desired product (985mg, 98% yield) as a light red solid after drying in a vacuum oven at RT. Example 4, Alternate Preparation of [l,3-bis(2,4,6-trimethylphenyl)-2- imidazolidinylideneldichloro[3-(3-isopropoxy-6-methoxyquinoxalin-2- vDpropylidenel ruthenium(II)

Step 1: 2-(But-3-en-l-yl)-3-isopropoxy-6-methoxyquinoxaline

To a 250-mL round-bottom flask were charged 2-(but-3-en-l-yl)-3-chloro-6- methoxyquinoxaline (3.50g, 14.07mmol), 2-PrOH (2.155ml, 28.1mmol), and DMAc (35ml). The system was cooled in an ice/water bath, NaHMDS (8.80ml, 17.59mmol) was charged to the reaction mixture via syringe. The reaction mixture was allowed to stir at RT under N₂ and judged complete (72h) by HPLC analysis. The system was quenched with water (lOOmL), 1M HC1 (50mL), and EtOAc (lOOmL). The resulting biphasic system was split, and the aqueous layer was extracted with EtOAc (lOOmL). The organic layers were combined, washed with water (50mL), washed with 10 wt% brine (50mL), dried over MgS0₄, filtered, and concentrated. The crude oil was purified via silica gel chromatography (loaded with 1 : 1 DCM:hex; 220g silica gel column (ISCO, Inc. Lincoln, NE, USA); eluted with 100% hexanes for 1 column volume; then 0 to 30% EtOAc in hexanes over 10 column volumes) to yield the desired product as an oil. Step 2:

To a round-bottom flask was charged the precursor pre-catalyst complex (106mg, 0.12mmol; commercially available as Materia-C884) and CH2CI2 (0.16mL, 1.5vol). This resulting homogeneous mixture was then degassed via subsurface N₂ gas bubbling. 2-(but-3-en- l-yl)-3-isopropoxy-6-methoxyquinoxaline (49mg, 0.18mmol) was dissolved in CH2CI2 (0.16mL, 1.5vol) in a separate round-bottom flask, where it was likewise degassed via subsurface N₂ gas bubbling. The 2-(but-3-en-l-yl)-3-isopropoxy-6-methoxyquinoxaline solution was transferred to the round-bottom flask containing the pre-catalyst and aged for 30min at RT. The mixture was concentrated under reduced pressure; hexanes (2.1mL, 20vol) were charged; and the resulting slurry was sonicated for lmin to yield a solid after filtration. The wet cake was washed with degassed hexanes twice, and the solid was dried under vacuum with N₂ sweep to yield the desired product (90mg) as a brownish red solid. The desired product was further crystallized to yield X-ray quality crystals.

The structure of the product, the ruthenium complex, C36H44CI2N4O2RU, was determined by single-crystal X-ray crystallography on a crystal isolated from toluene.

Data were collected on a Bruker CCD diffractometer using copper Ka radiation and integrated to a resolution of 0.84A-1, which yielded 5873 unique reflections from 19426 measured reflections. Data was acquired at 100K. The structure was solved using direct methods. The refined model has all non-H atoms refined anisotropically and H atoms at their calculated positions. Full crystallographic details are shown in Table 1 below. An ORTEP representation of the product compound of Example 4 (Altemate Preparation) is shown in Figure 1.

Table 1. Crystallographic Information

Example 5; [1 -bis(2 .6-trimethylphenyl)-2-imidazolidinylideneldichloro[3-(3- isopropoxypyrazin-2-yl)propylidenelruthenium(II)

Step 1: 2-Chloro-3-isopropoxypyrazine

To a 250-mL round-bottom flask were charged 2,3-dichloropyrazine (lO.Og,

67.1mmol), 2-PrOH (20.55ml, 268mmol), and DMA (100ml), and then the system was cooled in an ice bath. NaO^Bu (6.32g, 63.8mmol) was charged to the reaction mixture portionwise. The reaction was allowed to warm and age at RT (64h), where upon it was deemed complete by HPLC analysis. The mixture was quenched with water (lOOmL), 1M HC1 (50mL), and EtOAc (lOOmL), the layers were separated, and the aqueous layer was extracted with EtOAc (lOOmL). The organic layers were combined, washed with water (lOOmL), 10 wt% brine (50mL), dried over MgSC>4, filtered and concentrated. The resulting material was purified via silica gel chromatography (loaded with hexanes) and eluted with EtOAc:hexanes to yield the product compound.

Step 2: 2-(But-3-en-l-yl)-3-isopropoxypyrazine

To a round-bottom flask purged with N2 were charged 2-chloro-3- isopropoxypyrazine (8.75g, 50.7mmol), THF (61.3ml), and Fe(acac (0.895g, 2.53mmol). The mixture was then cooled below -60°C. 3-Butenylmagnesium bromide (223ml, 112mmol, 0.5M) was charged to the mixture dropwise over a period of lh. The reaction was allowed to age in the dry ice/acetone bath and deemed complete (lOmin) by HPLC analysis. The mixture was quenched with 1M HC1 (200mL), while keeping the internal temperature below 30°C. EtOAc (lOOmL) was charged; the layers were split; and the aqueous layer was extracted with EtOAc (lOOmL). The organic layers were combined and washed with water (lOOmL) and 10 wt% brine (50mL). The washed layers were dried over MgS0₄, filtered and concentrated to yield an oil. The crude material was further purified via silica gel chromatography (loaded with hexanes) and eluted with EtOAc:Hex to yield the desired product as an oil. Step 3

To a round-bottom flask was charged 2-(but-3-en-l-yl)-3-isopropoxypyrazine (0.589g, 3.06mmol). The system was purged with N₂, and then toluene (3.00ml) was charged to the system under inert handling. Precursor pre-catalyst complex (l .OOg, 1.361mmol, commercially available as Zhan IB) was charged to the system under a stream of N₂, and the system then sealed. The walls were then washed with toluene (2mL), and the mixture was heated and aged (2h) at 40°C, whereupon it was allowed to cool to RT. Hexane (30.0ml) was charged to the reaction mixture in 3 x lOmL portions. The mixture was then cooled to -40°C and allowed to age (~1.5h), after which the mixture was then allowed to warm to RT where a slurry had formed after aging (30min). The gum on the sides of the wall was sonicated, and the system was allowed to stir at RT for an additional 30min. The mixture was filtered through a sintered funnel at RT, the wet cake was slurry washed with hexane (30.0ml) in 3 x lOmL portions, and the wet cake was dried in a vacuum oven to yield the desired product (722mg, 74% yield) as a tan-yellow solid.

Example 6; [1 -bis(2,4.,6-trimethylphenyl)-2-imidazolidinylideneldichloro[3-(3- isopropoxyquinoxalin-2-yl)propylidenelruthenium(II)

Step 1: 2-Chloro-3-isopropoxyquinoxaline

To a 250-mL round-bottom flask were charged 2,3-dichloroquinoxaline (8.00 g, 40.2 mmol), 2-PrOH (12.31 ml, 161 mmol), and DMA (120 ml), and then the system was cooled in an ice bath. NaO/Bu (3.98 g, 40.2 mmol) was charged to the reaction mixture. The reaction mixture was allowed to warm and age (18 h) at RT. The reaction was quenched with water (100 mL), 1 M HC1 (50 mL), and EtOAc (100 mL). The layers were split, and the organic layer was washed with EtOAc (100 mL). The organic layers were combined and washed with water (100 mL) and 10 wt% brine (50 mL). The washed organic layers were dried over MgSC>4, filtered, and concentrated to yield yellow oil. The crude material was purified via silica gel

chromatography (loaded with hexanes and eluted with 0 to 15% EtOAc in hexanes) to yield the desired product.

Step 2: 2-(But-3-en-l-yl)-3-isopropoxyquinoxaline

To a round-bottom flask were charged 2-chloro-3-isopropoxyquinoxaline (7.30g, 32.8mmol), THF (51.1ml) and Fe(acac (0.579g, 1.639mmol), and the mixture was cooled in a dry ice/acetone bath under N₂. 3-Butenylmagnesium bromide (144ml, 72. lmmol) was charged to the mixture dropwise. The reaction mixture was sampled after lOmin of aging, until judged complete by HPLC. The reaction was quenched with 1M HC1 (200mL) and EtOAc (lOOmL); the reaction mixture was stirred, and then the layers were separated. The aqueous layer was extracted with EtOAc (lOOmL), and the organic layers were combined. The organic layer was washed with water (lOOmL), 10 wt% brine (50mL), dried over MgS0₄, filtered, and

concentrated. The crude oil was purified via silica gel chromatography (loaded with hexanes; eluted with 0 to 20% EtOAc in hexanes) and further purified with a second silica gel column (0 to 30%) EtOAc in CH₂C1₂) to yield the desired product as an oil.

Step 3:

To a 25-mL round-bottom flask was charged 2-(but-3-en-l-yl)-3- isopropoxyquinoxaline (0.907g, 3.74mmol). The system was purged with N₂; toluene (3.00ml) was charged; precursor pre-catalyst complex (l .OOg, 1.36mmol, commercially available as Zhan IB) was charged under a stream of N₂; and the system was sealed. Once sealed, another portion of toluene (2mL) was charged to wash the walls of the flask. The system was aged at 40°C (45min) and determined complete by ^XH NMR. Hexanes (15.00ml) were charged dropwise at 40°C, and then the mixture was allowed to cool and age at RT (lh). Additional 25% toluene in hexanes (20.00ml) was charged to the mixture; the resulting slurry was filtered through a sintered funnel; and the solid was slurry washed with hexanes (40.0ml; 4 x lOmL) to yield the desired product (789mg, 82%) as a light brown solid.

Example 7; [1 -bis(2 ,6-trimethylphenyl)-2-imidazolidinylideneldichloro[2-(3-isopropoxy- 6-methoxyquinoxalin-2-yl)ethylidenelruthenium(II)

Step 1: 2-Chlor -3-isopropoxy-6-methoxyquinoxaline

To a 100-mL round-bottom flask were charged 2,3-dichloro-6- methoxyquinoxaline (9g, 39.3mmol), 2-PrOH (3.31mL, 43.2mmol), DMAc(45mL) and DBU (7.62mL, 51.1mL), and then system was warmed to 40°C. The reaction was aged at 40°C for 48h. The mixture was quenched with water (lOmL), 1M HCl (30mL), and EtOAc (50mL). The layers were separated, and the aqueous layer was washed again with EtOAc (50mL). The organic layers were combined, washed with water (50mL), 10 wt% brine (50mL), dried over MgS0₄, filtered and concentrated. The resulting material was purified via silica gel

chromatography (loaded with toluene) and eluted with EtOAc and Hex (EtOAc:Hexane = 1 :5) to yield of the desired product. Step 2: -Allyl-3-isopropoxy-6-methoxyquinoxaline

To a round-bottom flask was charged potassium phosphate tribasic (8.82g,

41.6mmol), 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (0.569g, 1.385mmol) and Pd(OAc)2 (0.155g, 0.693mmol). After the mixture was degassed, THF (35mL) was charged; the mixture was slowly added allylboronic acid pinacol ester (5.20mL, 27.7mmol); and then the system was degassed. The reaction was heated to 60°C and aged overnight. Unsoluble particles were removed by filtration. The particles were washed with MTBE several times. The organic solution was transferred to a separatory funnel. Water (50mL) and EtOAc (50mL) was charged; the layers were split; and the aqueous layer was extracted with EtOAc (50mL). The organic layers were combined, washed with water (50mL), 10 wt% brined (50mL), dried over MgS0₄, filtered and concentrated to yield an oil. The crude material was further purified via silica gel chromatography (loaded with toluene) and eluted with EtOAc:Hex (1 :20) to yield the desired product as an oil.

Step 3

To a vial were charged 2-allyl-3-isopropoxy-6-methoxyquinoxaline (0.88g, 3.41mmol) and toluene (3.5mL). The system was degassed. Precursor pre-catalyst complex (l.OOg, 1.361mmol, commercially available as Zhan IB) was charged under a stream of N₂, and the system was sealed. The mixture was heated and aged (2h) at 40°C. Hexanes (11.7mL) were slowly added over 30min at 40°C. The slurry was slowly cooled to RT and aged (lh) at RT. The mixture was filtered through a sintered funnel at RT; the wet cake was slurry washed with hexanes (30.0ml) in 3 x lOmL portions; and the wet cake was dried in a vacuum oven to yield the desired product (986mg, 96% yield) as a brown solid.

Example 8; [1 -bis(2,4,6-trimethylphenyl)-2-imidazolidinylideneldichloro[3-(6-methoxy- 3-(isopropylthio)quinoxalin-2-yl)propylidenelruthenium(II)

Step 1: 2-(but-3-en-l-yl)-3-(isopropylthio)-6-methoxyquinoxaline

To a 100-mL round-bottom flask were charged 2-(but-3-en-l-yl)-3-chloro-6- methoxyquinoxaline (3.99g, 16.04mmol, l.Oequiv.) and DMF (61.0ml). After aging the reaction mixture over 5min at RT, sodium propane-2-thiolate (7.87g, 80mmol, 5.0equiv.) was charged to the reaction mixture. The reaction mixture was aged at RT over lh. Water (150mL) was then slowly charged to the reaction mixture, whereupon a white precipitate formed. The resulting slurry was filtered. The resulting wet cake was washed with water (3 x 50mL), and the cake was dried on the filter with N₂ and vacuum. The further purification by S1O2 purification (0 - 50% EtOAc to hexane) yielded the desired product (4. lOg).

Step 2:

To a round-bottom flask was charged 2-(but-3-en-l-yl)-3-(isopropylthio)-6- methoxyquinoxaline (0.644g, 2.23mmol), and purged with N₂. After toluene (5.00ml) and (1,3 dimesitylimidazolidin-2-ylidene)(2-isopropoxy-5-nitrobenzylidene)ruthenium chloride (lg, 1.489mmol, commercially available as nitro-Grela catalyst) were charged under a stream of N₂, the system was sealed. The resulting mixture was aged (lh) at 40°C, deemed complete by ^XH NMR, and hexanes (15.00ml) were slowly charged at 40°C over 30min. The resulting slurry was then allowed to cool to RT, filtered through a sintered funnel, washed in 2 portions with 25% toluene in hexane (20.00ml; 2 x lOmL), and then washed with 4 portions of hexanes (40.0ml; 4 x lOmL). The resulting wet cake was dried in a vacuum oven to yield the desired product (900mg) as a solid. Example 9; [1 -bis(2 _^6-trimethylphenyl)-2-imidazolidinylideneldichloro[3-(6-methoxy-3- (isopropylsulfonyl)quinoxalin- -yl)propylidenelnithenium(II)

Step 1: 2-(but-3-en-l-yl)-3-(isopropylsulfonyl)-6-methoxyquinoxaline

To a 250-mL round-bottom flask were charged 2-(but-3-en-l-yl)-3-

(isopropylthio)-6-methoxyquinoxaline (2.76g, 9.57mmol), MeOH (55.2ml) was charged. The resulting mixture was aged over lOmin at RT. Potassium peroxymonosulfate (11.77g,

19.14mmol, commercially known as OXONE®) was added to the reaction. The resulting heterogeneous solution was aged overnight at RT. The reaction was quenched with water (50mL) and EtOAc (75mL). The layers were split, and the aqueous layer was extracted again with EtOAc (50mL). The organic layers were combined, washed with water (50mL), brine (50mL), dried over MgS0₄, filtered, and concentrated to yield yellow oil. The resulting crude product was purified via silica gel chromatography (0 to 50 % EtOAc in hexanes over 20 column volumes) to yield the desired product (2. lOg). Ste

To a round-bottom flask was charged 2-(but-3-en-l -yl)-3-(isopropylsulfonyl)-6- methoxyquinoxaline (1.193g, 3.72mmol), and the system was purged with N₂. Toluene (10.00ml) was charged to the system under inert handling; (l ,3-dimesitylimidazolidin-2- ylidene)(2-isopropoxy-5-nitrobenzylidene)ruthenium(VI) chloride (lg, 1.489mmol, commercially available as nitro-Grela catalyst) was charged under a stream of N₂. The system was sealed and aged at 40°C over lh. Then, hexanes (1 1.70mL) was slowly added to the reaction at 40°C over 30min. The resulting mixture was allowed to age for approximately lh at RT, then filtered through a sintered funnel, washed in two portions with 25% toluene in hexanes (20.00ml; 2 x lOmL), and in four portions with hexanes (40.0ml; 4 x lOmL). The resulting wet cake was dried on the filter with vacuum and N₂ purge to yield the desired product (l .OOg).

Example 10; [l,3-bis(2-methylphenyl)-2-imidazolidinylideneldichloro[3-(3-isopropoxy-6- methoxyquinoxalin-2-yl)propylidenelruthenium(II)

Step

To a round-bottom flask was charged 2-(but-3-en-l-yl)-3-isopropoxyquinoxaline (1.006g, 3.66mmol, prepared according to the procedures of Example 4), and the system was purged with N₂. Toluene (5.00ml) was charged to the system under inert handling; ruthenium precomplex (lg, 1.625mmol, commercially available from Apeiron) was charged under a stream of N₂; the system was sealed. The system was aged at 40°C, when a brownish thick slurry had formed. Additional toluene (2mL) was charged to the system to thin the slurry, and then the reaction was deemed complete via ^XH NMR spectroscopy after lh. The reaction mixture was cooled to RT, then filtered through a sintered funnel, washed with four portions of hexanes (20.00ml; 4 x 5mL), and dried on the filter with vacuum and N2 purge to yield the desired product (901mg).

Example 11; [l,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylideneldichloro[3-(6,7-

Step 1: 3-(but- -en-l-yl)-6, 7-dimethoxyquinoxalin-2-ol

To a solution of ethyl 2-oxohex-5-enoate (7.27g, 38.6mmol) in EtOH (65.0ml,

13X) and water (7.50ml, 1.5X) at 50°C is added a solution of 4,5-dimethoxy-l ,2- benzenediamine (35. lmmol) in EtOH (10.00ml, 2X) through syringe pump over 30min. The reaction mixture is then stirred and heated at 50°C for 3h. Upon reaction completion, the mixture would be cooled to RT. Any precipitate is collected by filtration, rinsed with water, dried under vacuum and N₂ sweep overnight, or the solution is extracted with an organic solvent (such as EtOAc, MTBE, DCM, etc.), dried, concentrated, and purified via silica gel

chromatography to yield desired product.

To 3-(but-3-en-l -yl)-6,7-dimethoxyquinoxalin-2-ol (18.5mmol) is charged POCI₃

(17.24ml, 185mmol, lO.Oequiv.). The mixture is heated to 100°C and judged complete after HPLC analysis. The mixture is cooled to RT, and concentrated on a rotary evaporator to remove most of the POCI₃. The resulting residue is quenched into a mixture of saturated NaHCC (200mL), ice (200mL), and EtOAc (300mL) with good agitation. The layers are split, and the organic layer is washed with brine (lOOmL), dried over MgSC^, filtered and concentrated to afford the product.

Step 3: 2-(but-3-en-l-yl)-3-isopropoxy-6, 7-dimethoxyquinoxaline

To a 250-mL round-bottom flask is charged 2-(but-3-en-l-yl)-3-chloro-6,7- dimethoxyquinoxaline (14.07mmol), 2-PrOH (2.155ml, 28. lmmol), and DMAc (35ml). The system is cooled in an ice/water bath; NaHMDS (8.80ml, 17.59mmol) is charged to the reaction mixture via syringe. The reaction mixture is allowed to stir at RT under N₂ and judged complete by HPLC analysis. The system is quenched with water (lOOmL), 1M HC1 (50mL), and EtOAc (lOOmL). The resulting biphasic system is split, and the aqueous layer is extracted with EtOAc (lOOmL). The organic layers is combined, washed with water (50mL), washed with 10 wt% brine (50mL), dried over MgS04, filtered, and concentrated. The crude oil is purified via silica gel chromatography to yield the desired product as an oil. Step 4:

To a round-bottom flask is charged 2-(but-3-en-l-yl)-3-isopropoxy-6,7- dimethoxyquinoxaline (3.60mmol). The system is purged with N₂, and degassed toluene (3.00ml) is charged to the system under inert handling. Precursor pre-catalyst complex (l.OOg, 1.363mmol, commercially available as Zhan IB) is charged to the system under a stream of N₂, and the system is sealed. The walls of the flask are washed with degassed toluene (2mL). The system is heated and aged at 40°C, where it is judged complete by ^XH NMR and TLC analysis. The mixture is treated with hexanes (10.00ml) dropwise at 40°C, and then allowed to cool to RT and age (lh). The slurry is filtered through a sintered funnel, and the solid is slurry washed with 3: 1 hexanes: toluene (20mL; 2 x lOmL portions), and then hexanes (40mL; 4 x lOmL portions) to yield the desired product.

Examples 12-19

Examples 12 through 19 may be prepared according to the procedures outlined in Example 11 above. In Examples 12 through 19, the catalyst may be the Zhan lb catalyst as used in Example 11 or may be replaced by a similar catalyst such as:

Further in Examples 12 through 19, the 4,5-Dimethoxy-l,2-benzenediamine reagent in Step 1 of Example 11 is replaced as indicated in the Table 2 below. Table 2

Example 20; Rins-Closins Metathesis of Diethyl 2,2-diallylmalonate Using the Ruthenium- based Precatalyst Compound of Example 4

Ring-Closing Metathesis without Br ousted Acid Co-catalyst

In a glovebox, the ruthenium-based pre-catalyst compound of Example 4 (12mg, 0.016mmol) was diluted in a lmL volumetric flask with CD2CI2. To an NMR tube in the glovebox was charged CD2CI2 (0.75mL), and then ruthenium-based pre-catalyst compound solution (50μί, 0.8μηιο1). The tube was sealed and removed from the glovebox. The tube was then placed in the NMR, and the system was equilibrated to 303K. The system was locked; the probe was tuned and then shimmed. The sample was ejected, and diethyl 2,2-diallylmalonate (20μί, 0.083mmol) was charged, and the sample was placed back into the NMR. The reaction conversion was then measured.

Ring-Closing Metathesis with Bronsted Acid Co-catalyst

In a glovebox, the ruthenium-based pre-catalyst compound of Example 4 (12mg, 0.016mmol) was weighed and then diluted to lmL in volumetric flask with CD2CI2 (0.016M).

Benzene sulfonic acid (25mg, 0.16mmol) was charged to a 2mL volumetric flask and then diluted with CD2CI2.

To an NMR tube with a septum was charged 0.70mL of CD2CI2, and the benzene sulfonic acid solution prepared above (50μΕ, 3.95μηιο1, 5mol%). Diethyl 2,2-diallylmalonate (20μί, 83μηιο1) was then finally charged to the NMR tube, and solution was sealed and brought outside of the glove box. The tube was then placed in the NMR, and the system was equilibrated to 303K. The system was locked, the probe was tuned, and the system was shimmed. The sample was then ejected, and the ruthenium-based pre-catalyst compound solution (50μί, 0.8μηιο1) was charged, under inert handling, and placed back into the NMR, where the conversion was measured.

The results in Figure 2 show the conversion (%) obtained using the ruthenium- based pre-catalyst compound of Example 4 with and without the addition of co-catalyst benzene sulfonic acid (BSA) at 30°C.

Example 21; Ring-Closing Metathesis of tert-Butyldiallylcarbamate Using the Ruthenium- based Pre-catalyst Compound of Example 4

Unless otherwise indicated, all manipulations were performed outside of a glovebox, but performed using Schlenk/inert techniques.

Ring-Closing Metathesis without Br ousted Acid Co-catalyst

To a 2-mL volumetric flask with screw-top septum was charged the ruthenium- based pre-catalyst compound of Example 4 (24mg, 0.033mmol), inerted, sealed and diluted with CD₂C1₂ (0.016M). To an NMR tube with septum was charged 0.75mL of CD₂C1₂, and then the ruthenium-based pre-catalyst compound solution (50μΕ, 0.8μηιο1) was then charged to the NMR tube. The NMR tube was then placed in the NMR, and the system was equilibrated to 303K. The sample was locked, tuned, and shimmed. The sample was ejected, tert-butyl

diallylcarbamate (18μΕ, 0.083mmol) was charged, and the mixed sample was placed back into the NMR where conversion was measured.

Ring-Closing Metathesis with Bronsted Acid Co-catalyst

To a 2-mL volumetric flask with screw top septum was charged the ruthenium- based pre-catalyst compound of Example 4 (24mg, 0.033mmol), inerted, sealed and diluted with CD2CI2 (0.0165M). In a glovebox, benzensulfonic acid (13mg) was charged to a lmL volumetric flask with screw top septum and then diluted with CD2CI2. To an NMR tube with septum were charged CD2CI2 (0.7mL), benzensulfonic acid (50μΕ, 5 mol%), and tert-butyl diallylcarbamate (18μί, 0.083mmol). The NMR tube was then placed in the NMR, and the system was equilibrated to 30°C. The sample was locked, tuned, and shimmed. The sample was ejected, and the ruthenium-based pre-catalyst compound solution (50μΕ, 0.8μηιο1) was then charged, and the mixed sample was placed back into the NMR where conversion was measured.

The results in Figure 3 show the conversion (%) obtained using the ruthenium- based pre-catalyst compound of Example 4 with and without the addition of co-catalyst benzene sulfonic acid (BSA) at 30°C. Example 22; Ring-Closing Metathesis of tert-Butyldiallylcarbamate Using the Ruthenium- based Pre-Catalyst Compound of Example 2

Ring-Closing Metathesis without Br ousted Acid Co-catalyst

To a 2-mL volumetric flask with screw-top septum was charged the ruthenium- based pre-catalyst compound of Example 2 (23mg, 0.032mmol), inerted, sealed and diluted with CD₂C1₂ (0.016M). To an NMR tube with septum was charged CD₂C1₂ (0.75mL), and then the ruthenium-based pre-catalyst compound solution (50μί, 0.0008mmol). The NMR tube was then placed in the NMR, and the system was equilibrated to 303K, locked, tuned, and then shimmed. The sample was ejected, tert-butyl diallylcarbamate (18μί, 0.083mmol) was charged, and the mixed sample was placed back into the NMR where conversion was measured.

Ring-Closing Metathesis without Bronsted Acid Co-catalyst

To a 2 mL volumetric flask with screw top septum was charged the ruthenium- based pre-catalyst compound of Example 2 (23mg, 0.032mmol), inerted, sealed and diluted with CD2CI2 (0.016M). In a glovebox, benzensulfonic acid (13mg) was charged to a ImL volumetric flask with screw top septum and then diluted with CD2CI2. To an NMR tube with septum were charged CD2CI2 (0.7mL), benzensulfonic acid (50μΕ, 5mol%), and tert-butyl diallylcarbamate (18μί, 0.083mmol). The NMR tube was then placed in the NMR, and the system was equilibrated to 303K, locked, tuned, and shimmed. The sample was ejected and the ruthenium- based pre-catalyst compound solution (50μΕ, 0.0008mmol) was then charged, and the mixed sample was placed back into the NMR where conversion was measured.

The results in Figure 4 show the conversion (%) obtained using the ruthenium- based pre-catalyst compound of Example 2 with and without the addition of co-catalyst benzene sulfonic acid (BSA) at 30°C.

It will be appreciated that various of the above-discussed and other features and functions, or alternatives thereof, may be desirably combined into many other different systems or applications. Also that various presently unforeseen or unanticipated alternatives, modifications, variations or improvements therein may be subsequently made by those skilled in the art which are also intended to be encompassed by the following claims.

Claims

WHAT IS CLAIMED IS :

1. A ruthenium-based pre-catalyst compound selected from compounds of the structure of Formula I or of the structure of Formula II:

wherein:

wherein:

R¹⁰ and R¹¹ are each independently selected from Ci-Cg alkyl, C3-C8 cycloalkyl, and C6-C12 aryl, substituted by 0, 1, 2, or 3 substituents R¹⁴, where each R¹⁴ is independently selected from Ci-Cs alkyl;

R¹² and R¹³ are each independently selected from H, Ci-Cg alkyl, Ci-Cg alkoxy, C6-C12 aryl, C6-C12 aryloxy, Ci-Cg alkylcarbonyl, C6-C12 arylcarbonyl, Ci-Cg

alkoxycarbonyl, C6-C12 aryloxycarbonyl, C5-C12 heteroaryl, carboxyl, cyano, nitro, amido, amino, Ci-Cg alkylsulfonyl, C6-C12 arylsulfonyl, Ci-Cg alkylsulfinyl, C6-C12 arylsulfinyl, Ci-Cg alkylthio, C6-C12 arylthio, and sulfonamide groups; X and X¹ are each independently electron-withdrawing anionic ligands and are each independently selected from the group consisting of halogens, carboxylates, and C6-C12 aryloxides;

n is selected from 0, 1, 2, 3, 4, or 5;

T is selected from H, R¹, -OR¹, -SR¹, -NR , -NR^OR¹, -SO2R¹, -SOR¹,

each R¹ may be the same or different and is independently selected from Ci-C₈ alkyl and C3-C8 cycloalkyl;

R², R³, R⁴, and R⁵ are each independently selected from H, halogen atoms, -OH, Ci-C₆ alkyl, Ci-C₆ alkoxy, Ci-C₆ haloalkyl, Ci-C₆ haloalkoxy, -CN, -C(0)OH, -C(0)OCH₃, Ci-C₆ thioalkoxy, -S0₂(Ci-C₆ alkyl), C₃-C₈ cycloalkyl, C₃-C₈ cycloalkoxy, -NR , -NHR¹, phenyl, naphthyl, and heterocycles selected from the group consisting of 5- and 6-membered saturated and unsaturated heterocyclic rings that have 1 or 2 heteroatoms independently selected from the group consisting of N, O, and S, wherein the heterocycles have 0 to 3 substituents independently selected from H, halogen atoms, -OH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, Ci-C₆ haloalkoxy, -CN, -C(0)OH, -C(0)OCH₃, d-C₆ thioalkoxy, -S0₂(Ci-C₆ alkyl), C₃-C₈ cycloalkyl, C₃-C₈ cycloalkoxy, -NR^¹, and -NHR¹; and

2. The ruthenium-based pre-catalyst compound according to claim 1, wherein the compound has the structure of Formula I.

3. The ruthenium-based pre-catalyst compound according to claim 1, wherein the compound has the structure of Formula II.

4. The ruthenium-based pre-catalyst compound according to any claims 1-3, wherein L is selected from the group consisting of:

wherein:

R¹⁰ and R¹¹ are each phenyl, substituted by 0, 1, 2, or 3 substituents R , where each R¹⁴ is independently selected from C1-C6 alkyl;

R¹² and R¹³ are each independently selected from H, Ci-Cg alkyl, C3-C8 cycloalkyl, and C6-C12 aryl, and R¹² and R¹³ may optionally be bonded to form a ring, which may be an alkyl ring or aryl ring.

5. The ruthenium-based pre-catalyst compound according to claim 4, wherein L is

>10 ^K

R

Α ΚΛ

wherein:

R¹⁰ and R¹¹ are each phenyl, substituted by 0, 1, 2, or 3 substituents R , where each R is independently selected from C1-C6 alkyl; and

R¹² and R¹³ are each H.

6. The ruthenium-based pre-catalyst compound according to claim 5, wherein R¹⁰ and R¹¹ are the same and are each selected from the group consisting of

7. The ruthenium-based pre-catalyst compound according to any one of claims 1-6, wherein X and X¹ are each independently selected from the group consisting of halogens.

8. The ruthenium-based pre-catalyst compound according to claim 7, wherein X and X¹ are each chloride.

9. The ruthenium-based pre-catalyst compound according to any one of claims 1-8, wherein n is selected from 0 or 1.

10. The ruthenium-based pre-catalyst compound according to any one of claims 1-9, wherein T is selected from the group consisting of -OCH₃, -OC2H5, -OC(CH₃)2, -SCH3, -SC₂H₅, -SC(CH₃)₂, -NH₂, -N(CH₃)₂, -NHCOCH3, -NHCOCF3, -S0₂CH₃, -S0₂N(CH₃)₂,

11. The ruthenium-based pre-catalyst compound according to claim 10, wherein T is selected from the group consisting of -OCH₃, -OC(CH₃)₂, -SCH₃, and -N(CH₃)₂.

12. The ruthenium-based pre-catalyst compound according to any one of claims 1-11, wherein R 2 , R 3 , R 4 , and R 5 are each selected from the group consisting of R 2 , R 3 , R⁴, and R⁵ are each independently selected from H, halogen atoms, -OH, Ci-Cealkyl,

Ci-C₆alkoxy, Ci-C₆haloalkyl, Ci-Cehaloalkoxy, -CN, -C(0)OH, and -C(0)OCH₃, and R⁶ is selected from H, C1-C6 alkyl, and Ci-Cg alkoxy.

13. The ruthenium-based pre-catalyst compound according to claim 12, wherein R², R³, R⁴, and R⁵ are each independently selected from H, -CH₃, -OCH3, -CF₃, and -OCF₃, and R⁶ is selected from H and -OCH₃.

14. The ruthenium-based pre-catalyst compound according to any one of claims 1-13, wherein R³ and R⁶ are linked to form -0-CH₂-0- or -(CH₂)₃-.

15. A ruthenium-based pre-catalyst compound selected from the group consisting of:

16. A method of preparing a ruthenium-based pre-catalyst compound of the structure of Formula I or the structure of Formula II:

Formula I Formula II

wherein: L is a neutral electron-donating ligand selected from the group consisting phosphine ligands and heterocyclic carbene ligands, which are selected from the group consisting of:

wherein:

R¹⁰ and R¹¹ are each independently selected from Ci-Cs alkyl, C3-C8 cycloalkyl, and C6-C12 aryl, substituted by 0, 1, 2, or 3 substituents R¹⁴, where each R¹⁴ is independently selected from Ci-Cg alkyl;

R¹² and R¹³ are each independently selected from H, Ci-Cg alkyl, Ci-Cg alkoxy, C6-C12 aryl, C6-C12 aryloxy, Ci-Cg alkylcarbonyl, C6-C12 arylcarbonyl, Ci-Cg alkoxycarbonyl, C6-C12 aryloxycarbonyl, C5-C12 heteroaryl, carboxyl, cyano, nitro, amido, amino, Ci-Cg alkylsulfonyl, C6-C12 arylsulfonyl, Ci-Cg alkylsulfinyl, C6-C12 arylsulfinyl, Ci-Cg alkylthio, C6-C12 arylthio, and sulfonamide groups;

X and X¹ are each independently electron-withdrawing anionic ligands and are each independently selected from the group consisting of halogens, carboxylates, and C6-C12 aryloxides;

n is selected from 0, 1, 2, 3, 4, or 5;

T is selected from H, R¹, -OR¹, -SR.¹, -NR , -NR^OR¹, -SO2R¹, -SOR¹,

each R¹ may be the same or different and is independently selected from Ci-Cg alkyl and C3-C8 cycloalkyl;

R², R³, R⁴, and R⁵ are each independently selected from H, halogen atoms, -OH, Ci-C₆ alkyl, Ci-C₆ alkoxy, Ci-C₆ haloalkyl, Ci-C₆ haloalkoxy, -CN, -C(0)OH, -C(0)OCH₃, d- C₆ thioalkoxy, -S0₂(Ci-C₆ alkyl), C₃-C₈ cycloalkyl, C₃-C₈ cycloalkoxy, -NR , -NHR¹, phenyl, naphthyl, and heterocycles selected from the group consisting of 5- and 6-membered saturated and unsaturated heterocyclic rings that have 1 or 2 heteroatoms independently selected from the group consisting of N, O, and S, wherein the heterocycles have 0 to 3 substituents independently selected from H, halogen atoms, -OH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, -CN, -C(0)OH, -C(0)OCH₃, C C₆ thioalkoxy, -S0₂(Ci-C₆ alkyl), C₃-C₈ cycloalkyl, C₃-C₈ cycloalkoxy, -NR , and -NHR¹; and

R⁶ is selected from H, halogen atoms, Ci-Cg alkyl, C3-C8 cycloalkyl, Ci-Cg alkoxy, and C3-C8 cycloalkoxy;

or R³ and R⁶ optionally are taken together with the atoms to which they are attached to form a 5- to 7-membered ring, containing 0 to 3 heteroatoms independently selected from N, O, and S;

said method comprising:

reacting a precursor ruthenium metal complex with a ligand, wherein said precursor ruthenium metal pre-catalyst is selected from the

and

said ligand is selected from the group consisting of compounds of Formula IA and compounds of Formula IIA:

Formula IIA.

17. A method of catalyzing an olefin metathesis reaction comprising

(a) providing to a vessel a ruthenium-based pre-catalyst compound of the structure of Formula I or the structure of Formula II:

Formula II

wherein: L is a neutral electron donating ligand selected from the group consisting of a phosphine ligands and heterocyclic carbene ligands, which are selected from the group consisting of:

wherein:

n is selected from 0, 1, 2, 3, 4, or 5;

T is selected from H, R¹, -OR¹, -SR.¹, -NR , -NR^OR¹, -SO2R¹, -SOR¹,

or R³ and R⁶ optionally are taken together with the atoms to which they are attached to form a 5- to 7-membered ring, containing 0 to 3 heteroatoms independently selected from N, O, and S; and

(b) charging said vessel with olefin metathesis reactants;

wherein said olefin metathesis reaction is selected form ring-closing metathesis reactions, ring-opening metathesis reactions, cross-metathesis reactions, and ring-opening polymerization reactions.

18. The method according to claim 17, wherein said method comprising further providing an acid co-pre-catalyst selected from Bronsted acids and Lewis acids, in combination with said ruthenium-based pre-catalyst compound having the structure of Formula I or the structure of Formula II.

19. The method according to claim 18, wherein said acid co-pre-catalyst is selected from the group consisting of hydrochloric acid, hydrobromic acid, hydroiodic acid, acetic acid, trifiuoroacetic acid, benzenesulfonic acid, >-toluene sulfonic acid, formic acid, perchloric acid, trifluoroborane, perchlorostannane, hydron tetrafiuoroborate, and zinc chloride.