Ruthenium n-heterocyclic carbene complexes as catalysts for olefin metathesis

Abstract

The present invention concerns ligands, ruthenium complexes and salts thereof, as well as methods of preparing the ligands from the salts and of preparing the complexes from the ligands The ligands and complexes have been found to be suitable for use in catalysis, particularly in olefin metathesis. Therefore, uses and methods employing the ligands or complexes in catalysis, such as olefin metathesis, are also described.

Description

[0001] LIGANDS FOR CATALYSIS

[0002] FIELD

[0003] The present invention concerns ligands, ruthenium complexes and salts thereof, as well as methods of preparing the ligands from the salts and of preparing the complexes from the ligands. The ligands and complexes have been found to be suitable for use in catalysis, particularly in olefin metathesis. Therefore, uses and methods employing the ligands or complexes in catalysis, such as olefin metathesis, are also described.

[0004] BACKGROUND

[0005] Olefin metathesis, a reaction that redistributes fragments of olefins by the scission and regeneration of carbon-carbon double bonds, is the most versatile method known for the construction and manipulation of carbon-based frameworks. Moreover, with an unmatched atom economy, a scope that spans across chemistry and chemical biology, and benign reaction conditions, olefin metathesis also holds enormous potential in sustainable chemical manufacturing.

[0006] Ruthenium-catalysed olefin metathesis is a Nobel-Prize-winning technology for the assembly and manipulation of organic molecules, with tremendous potential in pharmaceutical manufacturing, chemical feedstock production, and materials science. Despite its potential, ruthenium-based olefin metathesis is notorious for severe problems arising from catalyst decomposition, which restrict productivity and industrial uptake.

[0007] Specifically, there are two main decomposition modes intrinsic to all olefin metathesis processes: p-hydride elimination and bimolecular coupling. Whereas recently developed catalysts based on neutral cyclic(alkyl)(amino)carbene (CAAC) ligands largely suppress P-hydride elimination, these ligands at the same time increase the susceptibility of the catalyst to bimolecular decomposition, a reaction in which two catalyst molecules react with each other instead of with the olefin substrate. For more information on these processes, see J. Engel et al., “Loss and Reformation of Ruthenium Alkylidene: Connecting Olefin Metathesis, Catalyst Deactivation, Regeneration, and Isomerization”, J. Am. Chem. Soc., 2017, 139, 16609-16619; D. L. Nascimento et al., “Bimolecular Coupling in Olefin Metathesis: Correlating Structure and Decomposition for Leading and Emerging Ruthenium-Carbene Catalysts”, J. Am. Chem. Soc., 2021, 143, 11072-11079; and G. Occhipinti et al., “The Janus face of high trans-effect carbenes in olefin metathesis: gateway to both productivity and decomposition”, Chem. Sci., 2022, 13, 5107-5117. The probability of bimolecular decomposition taking place may be reduced by lowering the concentration of catalyst used for the reaction. However, this has the disadvantage of increasing the time required for the reaction to go to completion.

[0008] N-heterocyclic carbene ligands are described in US 2022 / 0161246 A1 (Paimai New Materials (Chengdu) Co. Ltd.). The ligands are analogues of 1,3-Bis(2,4,6-trimethylphenyl)-1,3-dihydro-2 / 7-imidazol-2-ylidene (also known as IMes), in which the methyl groups at the 2 and 6 positions of the benzene rings are replaced with disubstituted methyl groups and the methyl groups at the 4 positions of the benzene rings are replaced with tertiary amines.

[0009] In EP 3548501 A1 (Univ Warszawski), ruthenium complexes are described which comprise asymmetric NHC ligands. One of the N-substituents is 10-phenyl-9-phenanthrenyl, while the other is benzyl.

[0010] Ruthenium complexes comprising N-heterocyclic carbene ligands based on IMes, in which the methyl group at the 4-position of one of the benzene rings is replaced with an imidazole ionic liquid group (an imidazolium salt ionic liquid group), are described in CN 106925351 A (Tianjin 3& G Chemtech Res. Inst. Co. Ltd). It is reported that the imidazolium salt ionic liquid group may play a role in improving the stability of the catalyst and its catalytic efficiency.

[0011] In CN 11594636 A (Univ. Xihua), ruthenium complexes comprising N-heterocyclic carbene ligands with polyoxyethylene groups at the 4-position of N-aryl groups are described. These groups are reported to improve the water solubility of the complexes.

[0012] T. Fujihara et al., in “Ruthenium-catalyzed ring-closing metathesis accelerated by long-range steric effect”, Chem. Commun., 2011, 47, 9699-9701, describe phosphine-containing ruthenium catalyst precursors which display high catalytic activity at 0°C. H2lMes analogues are employed, in which the methyls at the 4-positions of the benzene rings are replaced with planar2,3,4,5-tetraphenylphenyl (TPPh). It is reported that such long-range sterics facilitate phosphine dissociation and shield the resultant 14-electron catalyst species against decomposition.

[0013] S. Shahane et al., in “Synthesis and Characterisation of Sterically Enlarged Hoveyda-Type Olefin Metathesis Catalysts”, Eur. J. Inorg. Chem., 2013, 54-60, describe ruthenium catalysts designed for separation by nanofiltration. Two such catalysts bear IMes analogues in which the methyls at the 4-positions of the benzene rings are replaced with OCH2-(adamantyl) or O(CH2CH2O)2Me).

[0014] Monomeric ruthenium complexes, such as those used for olefin metathesis, adopt three-dimensional configurations: octahedral for 18-electron complexes, distorted square-pyramidal for 16-electron complexes, and distorted tetrahedral for 14-electron complexes. In contrast, monomeric complexes of other metals, such as copper, palladium and gold, have significantly different configurations. For example, monomeric complexes of copper and gold typically exhibit linear geometries, and those of palladium are typically square planar. These fundamental differences in geometry and electronic structure influence steric and bonding interactions. The greater flexibility of the ruthenium centre makes it more likely that dimeric species will form, thereby adopting arrangements that minimize steric clashes between bulky ligands.

[0015] Given these differences, inhibition of bimolecular decomposition of monomeric ruthenium complexes is generally more challenging than for other metal complexes. It is unpredictable if methods reported to inhibit bimolecular deposition of other metal complexes can also inhibit bimolecular deposition of ruthenium. Generally, the strategies adopted in the field to inhibit bimolecular deposition of monomeric ruthenium catalysts are based on increasing steric bulk near the metal centre. This approach has led to record-high turnover numbers in ethenolysis (see, for example, Gawin R. et al., Angew. Chem. Int. Ed. Engl. 2017, 56, 981-986; and Gawin R. et al., ACS Catal. 2017, 7, 5443-5449). However, the increased bulk near the metal limits effective reactivity in metathesis reactions other than ethenolysis.

[0016] There remains a need for ruthenium complexes suitable for effective catalysis, specifically olefin metathesis, that are stable to degradation, particularly bimolecular coupling, and thus may be used for longer reactions or in reactions that require harsher conditions, and / or may be recovered after reaction for re-use. The present invention provides ruthenium complexes comprising alternative ligands, as well as methods and uses, that address one or more of these needs and the above-noted problems and / or limitations.

[0017] SUMMARY

[0018] The invention is based on the finding that carbene ligands comprising particularly bulky substituents positioned away from (at sites remote from) the carbene binding site of the ligand are able to form stable and effective catalysts, particularly ruthenium catalysts for use, for example, in olefin metathesis. Without being bound by theory, the inventors believe that positioning such substituents at the carbene ligand of a complex comprising a metal centre, and away from the carbene binding site, sterically blocks other complexes from approaching the metal centre of the complex and thus inhibits bimolecular reactions, which would otherwise degrade or deactivate the complex, without inhibiting the desired catalytic reaction.

[0019] The inventors have found that increased catalyst stability, and more effective catalysis, arises when bulky three-dimensional (i.e. non-planar) ZY3 groups (as defined herein) are employed and are positioned at the carbene at the positions defined herein. It was particularly surprising to the inventors that increasing steric bulk at positions away from the metal centre led to increased stability and more effective catalysis. Catalysts comprising the carbene ligands defined herein have been found by the inventors to be stable and to be active catalysts in, for example, olefin metathesis. In particular, the catalysts comprising the carbene ligands defined herein, may be more stable, for example, in olefin metathesis, and more active catalysts, with greater turnover numbers (greater number of moles of substrate converted by the catalyst before degradation or deactivation of the catalyst) and therefore enable greater conversion and yield of substrate obtained relative to analogous catalysts without the bulky groups, under the same reaction conditions.

[0020] Viewed from a first aspect, therefore, the invention provides a ruthenium complex comprising a ligand of formula (I):

[0021] (R4)n^1

[0022] R1-N^X

[0023] R

[0024]

[0025] ” (I),

[0026] wherein:

[0027] R1is a C1-6alkyl, or C6-10aryl;

[0028] wherein the Ce- aryl is optionally substituted with one or more substituents selected from formula (II), Ci-ealkyl, Cs-wcarbocyclyl (e.g. Cs-ecarbocyclyl), C3-wheterocyclyl (e.g. 5- or 6-membered heterocyclyl), halo, and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SOs'), or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumCs-wheterocyclyl), and further wherein the substituent Ci-ealkyl, Cs- carbocyclyl and Cs-wheterocyclyl are each optionally substituted with one or more substituents selected from Cs-wcarbocyclyl (e.g. Cs-ecarbocyclyl), Cs-wheterocyclyl (e.g. 5- or 6-membered heterocyclyl) and formula (II), or wherein two substituent Ci-ealkyl together form a Cs-ecarbocyclyl ring;

[0029] wherein formula (II) is:

[0030] —(X)n2— ZY3(II)

[0031] wherein:

[0032] each X is independently selected from methylene, ethynylene, Ce- arylene (e.g. phenylene), and C3-wheteroarylene (e.g. 5- or 6-membered heteroarylene), wherein the Ce- arylene and C3-wheteroarylene are each optionally substituted with one or more substituents selected from Ci-ealkyl, halo, Ci-ehaloalkyl, and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3‘), or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumC3-ioheterocyclyl);

[0033] n2 is 0, 1 or 2;

[0034] Z is C or Si; and

[0035] each Y is independently selected from C3-wcarbocyclyl (e.g. Cs-ecarbocyclyl), C3. loheterocyclyl (e.g. 5- or 6-membered heterocyclyl), Ci-ealkyl (e.g. Ca-ealkyl or C3-ealkyl, such as C3-6branched alkyl), Ci-ehaloalkyl, C1-4alkenyl, Ci-ehaloalkenyl, Ciwalkynyl, and Ci-ehaloalkynyl, or two Y groups together with Z form a C3- carbocycle or C3. loheterocycle, or three Y groups together with Z form a bridged polycyclic Cs-wcarbocycle or bridged polycyclic C3-ioheterocycle,

[0036] wherein each Y is optionally substituted with one or more substituents selected from Ci-ealkyl, C3-iocarbocyclyl (e.g. Cs-ecarbocyclyl), C3-ioheterocyclyl (e.g. 5- or 6-membered heterocyclyl), halo, Ci-ehaloalkyl, and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3‘) or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumC3-ioheterocyclyl));

[0037] X1is N-R2or C(R3)2, wherein:

[0038] R2is a Ci-ealkyl, or Ce- aryl; wherein the C6-14aryl is optionally substituted with one or more substituents selected from formula (II), Ci-ealkyl, C3-wcarbocyclyl (e.g. Cs-ecarbocyclyl), C3-wheterocyclyl (e.g. 5- or 6-membered heterocyclyl), halo, and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3‘) or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumC3-ioheterocyclyl)), and further wherein the substituent Ci-ealkyl, C3-wcarbocyclyl and C3-wheterocyclyl are each optionally substituted with one or two substituents selected from C3-wcarbocyclyl (e.g. Cs- ecarbocyclyl) and Ca-wheterocyclyl (e.g. 5- or 6-membered heterocyclyl) and formula (II), or wherein two substituent Ci-ealkyl together form a Cs-ecarbocyclyl ring;

[0039] each R3is independently selected from Ci-ealkyl, C1-6alkenyl, halo, cyano, Ci-ealkoxy, C6-10aryloxy, C1-6alkylthiolate, C6-14arylthiolate, amino, Ca-wcarbocyclyl (e.g. Cs-ecarbocyclyl), Ca-wheterocyclyl (e.g. 5- or 6-membered heterocyclyl), Ci-ealkynyl, and a substituent of formula (II), wherein the Ci-ealkyl, C1-6alkenyl, Ci-ealkoxy, C6-10aryloxy, C1-6alkylthiolate, C6-14arylthiolate, Cs-wcarbocyclyl, the Ca-wheterocyclyl, and the Ci-ealkynyl are each optionally substituted with one or more substituents selected from Ci-ealkyl, C3. wcarbocyclyl, Ca-wheterocyclyl, halo, Ci-ealkoxy, C6-10aryloxy, C1-6alkylthiolate, C6-14arylthiolate, amino and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3‘) an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumC3-10heterocyclyl));

[0040] or wherein two R3groups together with the C form a Cs-wcarbocycle or C3-wheterocycle, each optionally substituted with one or more substituents selected from Ci-ealkyl, Cs-wcarbocyclyl, Ca-wheterocyclyl, halo, Ci-ealkoxy, C6-10aryloxy, C1-6alkylthiolate, C6-14arylthiolate, amino, a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3⁻) an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumCs-wheterocyclyl), and a substituent of formula (II);

[0041] each R4is independently selected from C1-6alkyl, halo, C1-6haloalkyl, and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3⁻), or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumC3-10heterocyclyl); and

[0042] the dashed line is an optionally present bond, wherein n is 0 to 2 when the dashed line is a bond and n is 0 to 4 when the dashed line is not a bond;

[0043] with the proviso that at least one of R1, R2or R3is substituted with a substituent of formula (II).

[0044] In a further aspect, there is provided a ligand of formula (I), as described above. The ligands of this aspect are typically formed as a salt comprising the ligand in a protonated form and a counterion. Viewed from another aspect, therefore, there is provided a salt of formula (1):

[0045] < R4)"^,

[0046] R^NVX'

[0047]

[0048] x' (1)

[0049] wherein R1, R4, X1, n and the dashed line are as defined in the first aspect; and X’ is a monoanion.

[0050] As described above, the ligands and the salts are able to form stable and effective catalysts, particularly ruthenium catalysts for use, for example, in olefin metathesis.

[0051] Typically, the ruthenium complex is of formula (i):

[0052] L1

[0053] L4, I.. X2

[0054] ^. Ru^

[0055] X3" I ^L2

[0056]

[0057] L3(i),

[0058] wherein:

[0059] L1is a ligand as defined in the first aspect;

[0060] L2is an ylidene;

[0061] L3is an L-type ligand, optionally wherein L3is a ligand as defined in the first aspect; L4is an optionally present L-type ligand; and

[0062] X2and X3are each independently an X-type ligand,

[0063] wherein L2and L3; L3and X2or X3; or L2and X2or X3are optionally linked.

[0064] Viewed from a second aspect, the invention provides for the use of a ruthenium complex as defined in the first aspect, in catalysis, such as in olefin metathesis. In a further aspect, there is provided a ligand as defined in the first aspect or a salt as defined above, in catalysis, such as in olefin metathesis. For example, a method of catalysis may comprise contacting the ruthenium complex (e.g. the ruthenium catalyst) with one or more substrates and / or reagents, wherein the ruthenium catalyst may be formed through the contacting of a ruthenium catalyst precursor with the ligand or salt.

[0065] The ruthenium complexes of the first aspect are particularly effective as catalysts in olefin metathesis. Thus, viewed from a third aspect, there is provided a method of olefin metathesis comprising contacting a ruthenium complex as defined in the first aspect with two olefins.

[0066] As described above, the ligand of the first aspect is typically formed as a salt. The ligand may be prepared from the salt by deprotonation to form a carbene binding site. In a further aspect, there is provided a method of preparing a ligand as defined in the first aspect from a salt as defined above, the method comprising contacting the salt with a base. As described above, the ruthenium complexes of the first aspect may be prepared from a ruthenium precursor and a ligand of the first aspect. Accordingly, viewed from a fourth aspect, there is provided a method of preparing a ruthenium complex as defined in the first aspect, the method comprising contacting a ligand as defined in the first aspect with a ruthenium precursor such that the ligand binds to the ruthenium.

[0067] Typically, the ruthenium precursor is of formula (pa):

[0068] L5

[0069] L4, I _. X2

[0070] ^. Ru^

[0071] X3" I ^L2

[0072]

[0073] L3(pa),

[0074] wherein:

[0075] L2is an ylidene;

[0076] L3and L5are each an L-type ligand;

[0077] L4is an optionally present L-type ligand; and

[0078] X2and X3are each independently an X-type ligand,

[0079] wherein L2and L3; L3and X2or X3; or L2and X2or X3are optionally linked.

[0080] DESCRIPTION OF THE FIGURES

[0081] Fig. 1: Scatter graph showing the impact of remote steric bulk in the ruthenium complex when used in ring-closing metathesis of diethyl 2,2-bis(2-methylprop-1-en-1-yl)malonate.

[0082] DETAILED DESCRIPTION

[0083] As described above, the invention is based on the finding that carbene ligands of formula (I) comprising particularly bulky ZY3 substituents, defined herein, positioned away from (at sites remote from) the carbene binding site of the ligand are able to form stable and effective catalysts, particularly ruthenium catalysts for use, for example, in olefin metathesis. Catalysts comprising the carbene ligands defined herein have been found by the inventors to be more stable and to be more active catalysts, with greater turnover numbers and therefore greater conversion and yield of substrate obtained relative to analogous catalysts without the bulky groups, under the same reaction conditions.

[0084] Definitions

[0085] In the discussion that follows, reference is made to a number of terms, which have the meanings provided, unless a particular context indicates to the contrary. The nomenclature used herein for defining compounds, in particular the compounds according to the invention, is in general based on the rules of the IUPAC organisation for chemical compounds, specifically the “IIIPAC Compendium of Chemical Terminology (Gold Book)”. For the avoidance of doubt, if a rule of the IUPAC organisation is in conflict with a definition provided herein, the definition herein is to prevail. Furthermore, if a compound structure is in conflict with the name provided for the structure, the structure is to prevail.

[0086] For the avoidance of doubt, the bivalent or zerovalent analogues of univalent species listed below as suitable for particular univalent groups are also suitable for the corresponding bivalent or zerovalent groups. For example, cyclopropyl is listed as a suitable Cs- carbocyclyl group. Cyclopropylene is thus a suitable Cs- carbocyclylene group and cyclopropane is thus a suitable Cs- carbocycle.

[0087] The term “comprising” or variants thereof is to be understood herein to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.

[0088] The term “consisting” or variants thereof is to be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, and the exclusion of any other element, integer or step or group of elements, integers or steps.

[0089] The term “about” herein, when qualifying a number or value, is used to refer to values that lie within ± 5% of the value specified. For example, where contacting is defined as being carried out at temperature of about 20 to about 100 °C, temperatures of 19 to 105 °C are included.

[0090] The term “alkyl” is well known in the art and defines univalent groups derived from alkanes by removal of a hydrogen atom from any carbon atom, wherein the term “alkane” is intended to define acyclic branched or unbranched hydrocarbons having the general formula CnH2n+2, wherein n is an integer >1. Alkyl groups may be Ci-ealkyl groups. In some cases, alkyl groups are Ci-4alkyl groups. Ci-4alkyl refers to any selected from the group consisting of methyl, ethyl, n-propyl, / so-propyl, n-butyl, sec-butyl, / so-butyl and tert-butyl.

[0091] The term “aryl” is well known in the art and defines all univalent groups formed on removing a hydrogen atom from an arene ring carbon. The term “arene” defines monocyclic or polycyclic aromatic hydrocarbons, where “aromatic” defines a cyclically conjugated molecular entity with a stability (due to delocalisation) significantly greater than that of a hypothetical localised structure. The Huckel rule is often used in the art to assess aromatic character; monocyclic planar (or almost planar) systems of trigonally (or sometimes digonally) hybridised atoms that contain (4n+2) TT-electrons (where n is a non-negative integer) will exhibit aromatic character. The rule is generally limited to n = 0 to 5. As used herein, the term "aryl" refers to a mono- or polycyclic aromatic hydrocarbon system having 6 to 14 carbon atoms, in some cases having 6 to 10 carbon atoms. Representative examples of suitable "aryl" groups include, but are not limited to, phenyl, biphenyl, naphthyl, 1 -naphthyl, 2-naphthyl and anthracenyl. As used herein, “substituted aryl” refers to an aryl group as defined herein which comprises one or more substituents on the aromatic ring. When an aryl group is substituted, any hydrogen atom(s) may be replaced with the substituent(s), providing valencies are satisfied. For the avoidance of doubt, Ce- aryl includes phenyl, naphthyl, 1-naphthyl, and 2-naphthyl.

[0092] The term “carbocyclyl”, used interchangeably with the term “cyclic hydrocarbyl” refers to a monovalent radical derived from a carbocycle or cyclic hydrocarbon by the removal of a hydrogen atom from the carbocycle or cyclic hydrocarbon. A hydrocarbon is any molecule comprising only the elements carbon and hydrogen. Hydrocarbons may be aliphatic, aromatic, unsaturated or saturated. Carbocycles or cyclic hydrocarbons may comprise a single ring or a spiro, fused or bridged ring system having two or more rings. Carbocyclyl groups may comprise 3 to 10 carbon atoms. Examples of suitable C3-locarbocyclyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, cycloheptyl, cyclooctyl, bicyclo[1.1.0]butanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.1.1]hexanyl, bicyclo[2.2.1]heptanyl, bicyclo[3.1.1]heptanyl, bicyclo[2.2.2]octanyl, bicyclo[3.2.1]octanyl, cubanyl, naphthyl, decalyl, norbornyl, adamantyl and indanyl. Carbocyclyl groups may comprise 5 or 6 carbon atoms. Examples of suitable Cs-ecarbocyclyl groups include cyclopentyl, cyclohexyl, phenyl, bicyclo[1.1.1]pentanyl and bicyclo[2.1.1]hexanyl. Carbocyclyl groups may be aliphatic and / or saturated. Examples of aliphatic and / or saturated carbocyclyl groups include cyclopentanyl, cyclohexanyl, cycloheptanyl, cyclooctanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.1.1]hexanyl, bicyclo[2.2.2]octanyl and adamantanyl.

[0093] The term “spiro ring system” refers to a ring system comprising two or more rings, where at least two rings share only a single atom.

[0094] The term “fused ring system” refers to a ring system comprising two or more rings, where at least two rings share two adjacent atoms. The term “bridged ring system” refers to a ring system comprising two or more rings, where at least two rings share three or more atoms. Bridged ring systems comprise two bridgeheads, which correspond to the outer of the shared atoms, and a bridge separating the two bridgehead atoms, which corresponds to the remaining shared atoms.

[0095] As used herein, the term “heterocyclyl” refers to a monovalent radical derived from a heterocycle. A heterocycle is a cyclic compound (a compound comprising one or more rings of connected atoms) having ring atoms of at least two different elements (such as carbon and nitrogen). A heterocyclyl may comprise at least 1 heteroatom selected from O, N and S. The heterocyclic ring may be a monocyclic or polycyclic ring, each ring comprising 3 to 10 atoms, in some cases 5 to 6 atoms. The heterocyclyl may be aliphatic or aromatic. One or more of the rings may be aliphatic or aromatic. The heterocyclyl may comprise 3 to 10 carbon atoms.

[0096] Examples of suitable Ca- heterocyclyl groups include azetidinyl, 1,4-Diazacycloheptanyl, azacycloheptanyl (also known as azepanyl), 2-azacycloheptanonyl, 6,7-dihydro-5H-pyrrolo[3,4-b]pyridine, 2,3,4,5-tetrahydro-1,4-benzoxazepine, 2, 3,4,5-tetrahydro-1H-2-benzazepine, pyrrolidinyl, tetrahydrofuranyl (also known as oxolanyl), tetrahydrothiophenyl (also known as thiolanyl), dioxolanyl, dithiolanyl, thiazolidinyl, isothiazolidinyl, oxazolidinyl, isoxazolidinyl, pyrazolidinyl, imidazolidinyl, piperidinyl, piperazinyl, N-alkylpiperazinyl, morpholinyl, dioxanyl, oxepanyl, thiepanyl, hexahydropyrimidinyl, hexahydropyridazinyl, tetrahydropyranyl (also known as oxanyl), tetrahydro-2 / 7-thiopyran (also known as thianyl), dithianyl (including 1,2-dithianyl, 1,3-dithianyl and 1,4-dithianyl), triazinanyl, quinuclidinyl, azaspirooctanyl (such as 2-azabicyclo[2.2.2]octanyl), diazaspiroundecanyl, diazaspiroheptanyl, azaspiroheptanyl (such as 2-azabicyclo[2.2.1]heptanyl), diazaspirodecanyl, octahydropyrrolopyrrolyl, pyrrolizidinyl, pyrrolyl, furanyl, thiophenyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, indolyl, benzofuranyl, benzothiazolyl, benzimidazolyl, indazolyl, benzoxazolyl, and benzisoxazolyl. The heterocyclyl may comprise 5 or 6 carbon atoms. Examples of suitable Cs-eheterocyclyl groups include 1,4-Diazacycloheptanyl, azacycloheptanyl, 2-azacycloheptanonyl, piperidinyl, N-alkylpiperazinyl, oxepanyl, thiepanyl, tetrahydropyranyl, thianyl, diazaspiroheptane, azaspiroheptane, octahydropyrrolopyrrole and pyridinyl. The heterocyclyl may be 5- or 6-membered. Examples of suitable 5- or 6-membered heterocyclyl groups include pyrrolidinyl tetrahydrofuranyl, thiolanyl, dioxolanyl, dithiolanyl, thiazolidinyl, isothiazolidinyl, oxazolidinyl, isoxazolidinyl, pyrazolidinyl, imidazolidinyl, piperidinyl, N-alkylpiperazinyl, piperazinyl, morpholinyl, dioxanyl, hexahydropyrimidinyl, hexahydropyridazinyl, tetrahydropyranyl, thianyl, dithianyl, triazinanyl, pyrrolyl, furanyl, thienyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, pyridinyl, pyrimidinyl, pyridazinyl, and pyrazinyl.

[0097] As used herein, the term “heterocycloalkyl” refers to a monovalent radical derived from a heterocycloalkane. A heterocycloalkane is a cyclic compound (a compound comprising one or more rings of connected atoms) having ring atoms of at least two different elements (such as carbon and nitrogen). A heterocycloalkyl may comprise at least 1 heteroatom selected from O, N and S. The heterocyclic ring may be a monocyclic or polycyclic ring, each ring comprising 3 to 10 atoms. The heterocycloalkyl may be 5-or 6-membered. Examples of suitable Ca- heterocycloalkyl groups include azetidinyl, 1,4-diazacycloheptanyl, azacycloheptanyl, 2-azacycloheptanonyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl (also known as thiolanyl), dioxolanyl, dithiolanyl, thiazolidinyl, isothiazolidinyl, oxazolidinyl, isoxazolidinyl, pyrazolidinyl, imidazolidinyl, piperidinyl, piperazinyl, N-alkylpiperazinyl, morpholinyl, dioxanyl, oxepanyl, thiepanyl, hexahydropyrimidinyl, hexahydropyridazinyl, oxazolidinyl, tetrahydropyranyl, tetrahydro-2 / 7-thiopyran (also known as thianyl), dithianyl (including 1,2-dithianyl, 1,3-dithianyl and 1,4-dithianyl), triazinanyl, quinuclidinyl, azaspirooctanyl (such as 2-azabicyclo[2.2.2]octanyl), diazaspiroundecane, diazaspiroheptane, azaspiroheptane, diazaspirodecane, octahydropyrrolopyrrole and pyrrolizidinyl. The heterocycloalkyl may be 5- or 6-membered. Examples of suitable 5- or 6-membered heterocycloalkyl groups include pyrrolidinyl tetrahydrofuranyl, thiolanyl, dioxolanyl, dithiolanyl, thiazolidinyl, isothiazolidinyl, oxazolidinyl, isoxazolidinyl, pyrazolidinyl, imidazolidinyl, piperidinyl, N-alkylpiperazinyl, piperazinyl, morpholinyl, dioxanyl, oxazolidinyl, hexahydropyrimidinyl, hexahydropyridazinyl, tetrahydropyranyl, thianyl, dithianyl and triazinanyl.

[0098] Halo refers to a halogen radical. Typically, halo refers to any selected from fluoro, bromo, chloro and iodo. In some cases, halo refers to fluoro.

[0099] The term “water-soluble group” refers to a substituent which has a water solubility of 10 mg / L or more, typically 100 mg / L or more, or 1000 mg / L or more. When introduced into the relevant compound, the water-soluble group increases the water solubility of the resultant compound. Examples of suitable water-soluble groups include polyols (such as polyethylene glycol, PEG), carboxylates (COO-), sulfonates (SO3-), and ammonium groups (such as ammonium (NH3+), an ammoniumC1-6alkyl, or cyclic ammonium group, such as ammoniumC3-10heterocyclyl). The term “polyol” is used herein to refer to a compound comprising two or more hydroxy groups. The polyol may be a polyether polyol, such as polyethylene glycol (PEG), polyethylene oxide, polypropylene glycol (PPG), polytetrahydrofuran or polytetramethylene ether glycol (PTMEG).

[0100] The term “ammonium group” is used herein to refer to a compound comprising a positively charged nitrogen atom with a valency of four. The ammonium group may be a primary, secondary, tertiary or quaternary ammonium group. The ammonium group may be represented by NR4+, where each R is independently selected from hydrogen and an organyl group. Where two or more R comprise organyl groups, the two or more R may link together to form a cyclic ammonium group, such as ammoniumCs-loheterocyclyl, e.g. an ammonium group comprising a substituted diazinanyl such as a substituted piperazinyl. By “ammoniumCs-ioheterocyclyl” is meant a heterocyclyl comprising 3 to 10 carbon atoms and at least 1 N atom with a valency of four.

[0101] The term “organyl” is well known in the art and is used herein to refer to a substituent with one or more free valences at a carbon atom.

[0102] The terms “methylene” and “ethylene” refer to a C1alkylene and a C2alkylene, respectively (where an “alkylene” is a bivalent saturated aliphatic radical, derived from an alkane by the removal of two hydrogen atoms).

[0103] The term “arylene” refers to a bivalent radical that is derived from an aromatic hydrocarbon, or arene, by the removal of two hydrogen atoms from two different carbon atoms. An example of a C6-10arylene is a phenylene or a naphthylene. The C6-10arylene may be a phenylene.

[0104] The term “heteroarylene” refers to a bivalent radical that is derived from an arylene by replacement of one or more methine (-C=) and / or vinylene (-CH=CH-) groups by trivalent or divalent heteroatoms, respectively, in such a way as to maintain the continuous TT-electron system characteristic of aromatic systems and a number of out-of-plane TT-electrons corresponding to the Huckel rule (4n+2). Examples of suitable C5-10heteroarylene groups include pyrrolylene, furanylene, thiophenylene, pyrazolylene, imidazolylene, oxazolylene, isoxazolylene, thiazolylene, pyridinylene, pyrimidinylene, pyridazinylene, pyrazinylene, indolylene, benzofuranylene, benzothiazolylene, benzimidazolylene, indazolylene, benzoxazolylene, and benzisoxazolylene. The heteroarylene may be 5- or 6-membered. Examples of suitable 5- or 6-membered heteroarylene groups include pyrrolylene, furanylene, thiophenylene, pyrazolylene, imidazolylene, oxazolylene, isoxazolylene, thiazolylene, pyridinylene, pyrimidinylene, pyridazinylene and pyrazinylene.

[0105] The term “alkenyl” defines univalent groups derived from alkenes by removal of a hydrogen atom from any carbon atom, wherein the term “alkene” is intended to define acyclic branched or unbranched hydrocarbons having one carbon-carbon double bond and the general formula CnH2n, where n is an integer ≥2. C2-C4alkenyl refers to any one selected from the group consisting of ethenyl, prop-1-enyl, prop-2-enyl, 1-methyl-ethenyl, but-1-enyl, but-2-enyl, but-3-enyl, 1-methyl-prop-1-enyl, 1-methyl-prop-2-enyl, 2-methyl-prop-1-enyl, and 2-methyl-prop-2-enyl.

[0106] The term “alkynyl” defines univalent groups derived from alkynes by removal of a hydrogen atom from any carbon atom, wherein the term “alkyne” is intended to define acyclic branched or unbranched hydrocarbons having one carbon-carbon triple bond and the general formula CnH2n-2, where n is an integer ≥2. C2-C4alkynyl refers to any one selected from the group consisting of ethynyl, prop-1-ynyl, prop-2-ynyl, but-1-ynyl, but-2-ynyl, but-3-ynyl, and 1-methyl-prop-2-ynyl.

[0107] The term “ethynylene” refers to a C2alkynylene (where an “alkynylene” is a bivalent radical derived from an alkyne by the removal of two hydrogen atoms).

[0108] For the avoidance of doubt, where a group, such as an alkyl, alkenyl or alkynyl, is prefixed with the term “halo”, one or more hydrogen atoms of that group is replaced with a halo.

[0109] The term “amino” refers to primary (-NH2), secondary (-NRH) or tertiary (-NR2) amino groups, where R is, or each R is independently, a hydrocarbyl group, such as a C1-6alkyl or C6-10aryl. Often, where the amino is a secondary or tertiary amino, it is a C1-C6alkylamino or diC1-C6alkylamino.

[0110] The term “ylidene” refers to divalent groups formed from a saturated carbon atom by removal of two hydrogen atoms from the same carbon atom, the free valencies of which are part of a double bond. The ylidene may be represented by =CR2, where each R is independently selected from hydrogen and an organyl group. Where two or more R comprise organyl groups, the two or more R may link together to form a cyclic ylidene. “Alkylidene” refers to a divalent, aliphatic radical that is formed by removing two hydrogen atoms from the same carbon atom of an alkane, which alkane may be substituted with substituents other than alkyl. “Cyclic hydrocarbylidene” refers to a divalent radical that is formed by removing two hydrogen atoms from the same carbon atom of a cyclic hydrocarbon, which cyclic hydrocarbon is aliphatic and may be saturated or unsaturated. For the avoidance of doubt, the cyclic hydrocarbylidene may be aromatic, for example it may be indenylidene. The term “heterocyclylidene” refers to a divalent radical that is formed by removing two hydrogen atoms from the same carbon atom of a heterocycle, which may be aromatic or aliphatic. For the avoidance of doubt, the cyclic hydrocarbylidene and the heterocyclylidene may each be substituted.

[0111] Ligands may be described using the covalent bond classification (CBC) method. This method provides notation for the donor atoms of a ligand. Under the neutral / covalent counting method, a donor atom that donates two electrons to a metal atom is an L-type; a donor atom that donates one electron to a metal atom is an X-type; and a donor atom that donates zero electrons to a metal atom is a Z-type. Monodentate ligands may be described as any one of L-, X-, or Z-type. An example of an L-type ligand is acetonitrile. An example of an X-type ligand is halide. Bidentate ligands may be described as any one of LL-, XL-, LZ-, XX-, XZ-, or ZZ-type. An LL-type ligand comprises two donor atoms that each donate two electrons to a metal atom. An example of an LL-type ligand is naphthyridine. An XL-type ligand comprises two donor atoms, wherein the X-type atom donates one electron to the metal atom and the L-type atom donates two electrons to the donor atom. An example of an XL-type ligand is acetate.

[0112] The term “thiolate” refers to monovalent groups derived from thiols by the removal of the hydrogen atom bonded to the sulfur atom of the thiol. “Arylthiolates” are therefore arylthiol groups absent the hydrogen atom of the thiol. The term “alkylsulfanyl” refers to monovalent groups derived from an alkylthiol by the removal of a hydrogen atom bonded to the sulfur atom of the thiol.

[0113] The term “sulfinyl” refers to a bivalent S(O) moiety, which is typically part of a monovalent moiety RS(O), where R is an organyl. Similarly, “alkylsulfinyl” refers to monovalent RS(O) groups where R is an alkyl, “benzylsulfinyl” refers to monovalent RS(O) groups where R is a benzyl.

[0114] The term “sulfonyl” refers to a bivalent S(O)2 moiety, which is typically part of a monovalent moiety RS(O)2, where R is an organyl. For example, (dimethylamino)sulfonyl is of formula Me2NS(O)2. The term “phosphine” refers to PH3 and compounds derived from this by substituting one, two or three hydrogen atoms with organyls. Where a compound is described as comprising a phosphine binding moiety, the compound comprises a phosphine (optionally in addition to other chemical groups).

[0115] The term “carbene” refers to compounds comprising a carbon atom covalently bonded to two univalent groups of any kind or a divalent group, and which bears two nonbonding electrons, which may be spin-paired (singlet state) or spin-non-paired (triplet state). A carbene may be an N-heterocyclic carbene, which refers to compounds comprising carbene moieties wherein the carbon of the carbene moiety is part of an N-heterocycle and is directly bonded to two nitrogen atoms. Alternatively, the carbene may be a cyclic alkyl amino carbene (CAAC), which refers to compounds comprising carbene moieties wherein the carbon of the carbene moiety is part of an N-heterocycle and is directly bonded to one nitrogen atom and one carbon atom.

[0116] The term “alkoxy” defines univalent groups derived from alcohols by removal of a hydrogen atom from an OH group, wherein the term “alcohol” is intended to define groups derived from alkanes by the replacement of a hydrogen atom with a hydroxy group. Often, alkoxy groups are C1-6alkoxy groups or C1-4alkoxy groups. Similarly, the term “aryloxy” defines univalent groups derived from arylols by removal of a hydrogen atom from an OH group, wherein the term “arylol” is intended to define groups derived from arenes by the replacement of a hydrogen atom with a hydroxy group. An example of an arylol is phenol.

[0117] Whilst the terms “alkene” and “olefin” are often used interchangeably in the art, they are defined differently herein. Whilst an alkene is defined as a hydrocarbon having one carbon-carbon double bond, an olefin is defined herein as any compound comprising one or more aliphatic carbon-carbon double bonds. For example, the olefin may be represented by R2C=CR2, wherein each R is independently selected from an organyl and hydrogen. Where the olefin contains at least two organyl groups, at least two of the organyl groups may be linked so as to form a cyclic olefin. The one or more aliphatic carbo-carbon double bonds may or may not be part of the cycle. As described above, the term “olefin metathesis” is used to refer to the redistribution of fragments of olefins by the scission and regeneration of carbon-carbon double bonds. This is exemplified in Scheme 1, below. R01R03R01R03[scheme image] R02R04R02R04Scheme 1: Example of redistribution of the fragments of olefins on olefin metathesis.

[0118] For the avoidance of doubt, a wavy line in a chemical structure bisects the bond linking the moiety shown to the rest of the compound.

[0119] The term “solvate” is used herein to refer to a complex comprising a solute, such as a compound or salt of the compound, and a solvent. If the solvent is water, the solvate may be termed a hydrate, for example a mono-hydrate, di-hydrate, tri-hydrate etc., depending on the number of water molecules present per molecule of substrate.

[0120] The term “isotope” is used herein to define a variant of a particular chemical element, in which the nucleus necessarily has the same atomic number but has a different mass number owing to it possessing a different number of neutrons.

[0121] The term “stereoisomer” is used herein to refer to isomers that possess identical molecular formulae and sequence of bonded atoms, but which differ in the arrangement of their atoms in space.

[0122] The term “enantiomer” defines one of a pair of molecular entities that are mirror images of each other and non-superimposable, i.e. cannot be brought into coincidence by translation and rigid rotation transformations. Enantiomers are chiral molecules, i.e. are distinguishable from their mirror image.

[0123] The term “racemic” is used herein to pertain to a racemate. A racemate defines a substantially equimolar mixture of a pair of enantiomers.

[0124] The term “diastereoisomers”(also known as diastereomers) defines stereoisomers that are not related as mirror images.

[0125] Ligands

[0126] As described above, in a first aspect, there is provided a ruthenium complex comprising a ligand of formula (I):(R4)n^1

[0127] R1-N^X

[0128] R

[0129]

[0130] ” (I),

[0131] wherein R1, R4, n, X1and the dashed line are as described herein.

[0132] X1may be N-R2(in which case the ligand of formula (I) is an N-heterocyclic carbene (NHC)) or X1may be C(R3)2(in which case the ligand of formula (I) is a cyclic alkyl amino carbene (CAAC)).

[0133] In some embodiments, the ligand is an NHC. Where the ligand is an NHC, one of R1and R2is C1-6alkyl, and the other is C6-10aryl or each of R1and R2is independently a C6-10aryl; wherein the C6-10aryl (phenyl or naphthyl) is optionally substituted with one or more substituents selected from formula (II), C1-6alkyl, C3-10carbocyclyl, C3-10heterocyclyl, halo, and a water-soluble group, and further wherein the substituent C1-6alkyl, C3-10carbocyclyl and C3-10heterocyclyl are each optionally substituted with one or more (e.g. one or two) substituents selected from C3-10carbocyclyl, C3-10heterocyclyl and formula (II), or wherein two substituent C1-6alkyls together form a C5-6carbocyclyl ring. In some embodiments, the substituent C3-10carbocyclyl and C3-10heterocyclyl are unsubstituted. In some embodiments, the substituent C1-6alkyl is optionally substituted with one or more (e.g. one or two) substituents selected from C3-10carbocyclyl, C3-10heterocyclyl, or two substituent C1-6alkyls together form a C5-6carbocyclyl ring.

[0134] For the avoidance of doubt, where the ligand is an NHC, at least one of R1and R2is a C6-10aryl substituted with at least a substituent of formula (II).

[0135] In some embodiments, one of R1and R2is C1-6alkyl, and the other is C6-10aryl or each of R1and R2is independently a C6-10aryl; wherein the C6-10aryl (phenyl or naphthyl) is optionally substituted with one or more substituents selected from formula (II), C1-6alkyl, C5-6carbocyclyl, 5- or 6-membered heterocyclyl, halo, and a water-soluble group, and further wherein the substituent C1-6alkyl, C5-6carbocyclyl and 5- or 6-membered heterocyclyl are each optionally substituted with one or more (e.g. one or two) substituents selected from C5-6carbocyclyl and 5- or 6-membered heterocyclyl, or wherein two substituent C1-6alkyls together form a C5-6carbocyclyl ring.

[0136] In some embodiments, each of R1and R2is independently an optionally substituted C6-10aryl (phenyl or naphthyl, typically phenyl). The C6-10aryl of R1and / or R2may be optionally substituted with one or more substituents selected from formula (II) and C1-6alkyl, wherein the substituent C1-6alkyl is optionally substituted with one or more substituents selected from C3-10carbocyclyl (such as C5-6carbocyclyl) and C3-10heterocyclyl (such as 5- or 6-membered heterocyclyl), or wherein two substituent C1-6alkyls together form a C5-6carbocyclyl ring. The substituent C1-6alkyl may be optionally substituted with one or more (e.g. one or two) substituents independently selected from C3-10carbocyclyl, such as C5-6carbocyclyl, e.g. phenyl or naphthyl. In particular embodiments, the C1-6alkyl may be a C1-3alkyl, such as methyl, optionally substituted with one or two phenyl.

[0137] In some embodiments, R1is a substituted phenyl. In some embodiments, R2is an optionally substituted phenyl.

[0138] In some embodiments, when X1is N-R2and R1is phenyl, the phenyl is substituted at the ortho-position with substituents other than iso-propyl and CHPh2. In some embodiments, when X1is N-R2and R1is phenyl, the phenyl is substituted at the ortho-position with one or more substituents selected from formula (II), methyl, ethyl, n-propyl, C4-6alkyl, C3-10carbocyclyl, C3-10heterocyclyl, halo, and a water-soluble group, and further wherein the substituent ethyl, n-propyl, C4-6alkyl, C3-10carbocyclyl and C3-10heterocyclyl are each optionally substituted with one or more substituents selected from C3-10carbocyclyl, C3-10heterocyclyl and formula (II), the substituent methyl is optionally substituted with one or more substituents selected from C3-10heterocyclyl and formula (II), or wherein two substituent C1-6alkyl together form a C5-6carbocyclyl ring.

[0139] In some embodiments, the ligand is a CAAC. Where the ligand is a CAAC, X1is C(R3)2, where each R3is independently selected from C1-6alkyl, C1-6alkenyl, halo, cyano, C1-6alkoxy, C6-10aryloxy, C1-6alkylthiolate, C6-10arylthiolate, amino, C3-10carbocyclyl (e.g. C5-6carbocyclyl), C3-10heterocyclyl (e.g. 5- or 6-membered heterocyclyl), C1-6alkynyl, and a substituent of formula (II), wherein the C1-6alkyl, C1-6alkenyl, C1-6alkoxy, C6-10aryloxy, C1-6alkylthiolate, C6-10arylthiolate, C3-10carbocyclyl, the C3-10heterocyclyl, and the C1-6alkynyl are each optionally substituted with one or more substituents selected from C1-6alkyl, C3-10carbocyclyl, C3-10heterocyclyl, halo, C1-6alkoxy, C6-10aryloxy, C1-6alkylthiolate, C6-10arylthiolate, amino and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3-) an ammonium group (e.g. ammonium (NH3+), an ammoniumC1-6alkyl, or cyclic ammonium group, such as ammoniumC3-10heterocyclyl)); or wherein two R3groups together with the C form a C3-10carbocyclyl or C3-10heterocyclyl, each optionally substituted with one or more substituents selected from C1-6alkyl, C3-10carbocyclyl, C3-10heterocyclyl, halo, C1-6alkoxy, C6-10aryloxy, C1-6alkylthiolate, C6-10arylthiolate, amino, a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3-) an ammonium group (e.g. ammonium (NH3+), an ammoniumC1-6alkyl, or cyclic ammonium group, such as ammoniumC3-10heterocyclyl), and a substituent of formula (II). As described herein, an amino group refers to primary (-NH2), secondary (-NRH) or tertiary (-NR2) amino groups, where R is, or each R is independently, a hydrocarbyl group, such as a Ci-ealkyl or C6-14aryl. In some embodiments of the above, each amino may be optionally substituted with one or two substituents selected from Ci-ealkyl and Ce- aryl.

[0140] R1of CAAC ligands may be as defined above in relation to NHC ligands, for example, R1may be C1-6alkyl, or C6-10aryl, wherein the C6-10aryl (phenyl or naphthyl) is optionally substituted with one or more substituents selected from formula (II), C1-6alkyl, C5-6carbocyclyl, 5- or 6-membered heterocyclyl, halo, and a water-soluble group, and further wherein the substituent C1-6alkyl, C5-6carbocyclyl and 5- or 6-membered heterocyclyl are each optionally substituted with one or more (e.g. one or two) substituents selected from C5-6carbocyclyl and 5- or 6-membered heterocyclyl, or wherein two substituent C1-6alkyls together form a C5-6carbocyclyl ring.

[0141] In some embodiments, and typically for the CAAC ligands, R1is an optionally substituted C6-10aryl (phenyl or naphthyl, typically phenyl). The C6-10aryl may be optionally substituted with one or more substituents selected from formula (II) and C1-6alkyl, wherein the substituent C1-6alkyl is optionally substituted with one or more (e.g. one or two) substituents selected from C3-10carbocyclyl (such as C5-6carbocyclyl) and C3-10heterocyclyl (such as 5- or 6-membered heterocyclyl), or wherein two substituent C1-6alkyls together form a C5-6carbocyclyl ring. The substituent C1-6alkyl may be optionally substituted with one or more (e.g. one or two) substituents independently selected from C3-10carbocyclyl, such as C5-6carbocyclyl (e.g. phenyl), or naphthyl. In particular embodiments, the C1-6alkyl may be a C1-3alkyl, such as methyl, optionally substituted with one or two phenyl.

[0142] In some embodiments, each R3of the CAAC ligand is independently selected from C1-6alkyl, C1-6alkenyl, C5-6carbocyclyl, 5- or 6-membered heterocyclyl, C1-6alkynyl, and a substituent of formula (II), wherein the C1-6alkyl, C1-6alkenyl, C5-6carbocyclyl, 5- or 6-membered heterocyclyl, and the C1-6alkynyl are each optionally substituted with one or more substituents selected from C1-6alkyl, C5-6carbocyclyl, 5- or 6-membered heterocyclyl, and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3‘) an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniurnC3-ioheterocyclyl)); or wherein two R3groups together with the C form a Cs-iacarbocyclyl or C3-ioheterocyclyl, each optionally substituted with one or more substituents selected from Ci-ealkyl, Cs-ecarbocyclyl, 5- or 6-membered heterocyclyl, a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3‘) an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumCa-wheterocyclyl), and a substituent of formula (II).

[0143] In particular embodiments, each R3is independently selected from Ci-ealkyl, Cs-ecarbocyclyl, 5- or 6-membered heterocyclyl, Ci-ealkynyl, and a substituent of formula (II), wherein the Ci-ealkyl, Cs-ecarbocyclyl, 5- or 6-membered heterocyclyl, and the Ci-ealkynyl are each optionally substituted with one or more substituents selected from Ci-ealkyl, Cs-ecarbocyclyl, 5- or 6-membered heterocyclyl, and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3‘), an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumCa-wheterocyclyl)); or wherein two R3groups together with the C form a Cs-iacarbocyclyl optionally substituted with one or more substituents selected from Ci-ealkyl, Cs-ecarbocyclyl, 5- or 6-membered heterocyclyl, a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3‘) an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumC3-ioheterocyclyl), and a substituent of formula (II).

[0144] In more particular embodiments, one R3is selected from Ci-ealkyl, Ci-ealkynyl, and a substituent of formula (II), wherein the Ci-ealkyl, and the Ci-ealkynyl are each optionally substituted, as described above. In some embodiments, the other R3is selected from C3-iocarbocyclyl (e.g. Cs-ecarbocyclyl), C3-ioheterocyclyl (e.g. 5- or 6-membered heterocyclyl), each of which may be optionally substituted, as described above.

[0145] In specific embodiments, one R3is optionally substituted Ci-ealkyl and the other is optionally substituted C3-iocarbocyclyl (e.g. optionally substituted Cs-ecarbocyclyl). In more specific embodiments, one R3is Ci-ealkyl and the other is optionally substituted C3. locarbocyclyl (e.g. optionally substituted Cs-ecarbocyclyl). In some embodiments, the optional substituents of the C3-iocarbocyclyl or Cs-ecarbocyclyl are selected from Ci-ealkyl and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3‘) an ammonium group (e.g. ammonium (NH3+), an ammoniumCi- ealkyl, or cyclic ammonium group, such as ammoniumC3-ioheterocyclyl), e.g. C1-6alkyl. In some embodiments, the C3-iocarbocyclyl or Cs-ecarbocyclyl is unsubstituted.

[0146] Two R3groups may, together with the C form a Cs-iscarbocycle or C3-ioheterocycle (such as a Cs-iscarbocycle), each optionally substituted with one or more substituents selected from Ci-ealkyl, C3-iocarbocyclyl, C3-ioheterocyclyl, a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3‘) an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumCs-wheterocyclyl), and a substituent of formula (II). For the avoidance of doubt, the C of X1(of formula (I)) is counted as one of the carbon atoms of the C3. iscarbocycle.

[0147] In some embodiments, the optionally substituted C3-iscarbocycle or C3-ioheterocycle (such as C3-iscarbocycle) is polycyclic, i.e. it comprises two or more interconnected rings of atoms. In some embodiments, the C3-ioheterocycle comprises one or more heteroatoms selected from nitrogen and sulfur, optionally in just one of the rings of the polycycle. The optionally substituted C3-iscarbocycle or C3-ioheterocycle (such as C3. iscarbocycle) typically comprises two or more fused rings of atoms. Typically, just one carbon-carbon bond is shared between the pairs of rings in the optionally substituted polycyclic C3-iscarbocycle or C3-ioheterocycle. In some embodiments, at least one of the rings of the optionally substituted polycyclic C3-iscarbocycle or C3-ioheterocycle is aromatic. In some embodiments, the optionally substituted polycyclic C3-iscarbocycle or C3-ioheterocycle is an optionally substituted C9-i3carbocycle or C8-i2heterocycle, optionally comprising one 5-membered ring and up to two 5- or 6-membered rings. In particular embodiments, the optionally substituted C3-iscarbocycle or C3-ioheterocycle is selected from fluorene, indane, indoline, indene, 1,4,5,6-tetrahydrocyclopenta[b]pyrrole and 1,4,5,6-tetrahydrocyclopenta[b]thiophene, each of which is optionally substituted. In particular embodiments, the optionally substituted C3-iscarbocycle or C3-ioheterocycle is a C3-iscarbocycle selected from fluorene, indane, indene and indoline.

[0148] In alternative embodiments, the optionally substituted C3-iscarbocycle orC3-ioheterocycle (such as C3-iscarbocycle) is monocyclic, for example the optionally substituted C3. iscarbocycle or C3-ioheterocycle (such as C3-iscarbocycle) may be a 5- or 6-membered carbocycle or heterocycle, each of which is optionally substituted. In specific embodiments, the optionally substituted C3-iscarbocycle or C3-ioheterocycle is a C3. iscarbocycle, such as cyclopentadiene. In some embodiments, the substituents of the optionally substituted Cs-iscarbocycle or Ca- heterocycle are selected from Ci-ealkyl, Cs-ecarbocyclyl, 5- or 6-membered heterocyclyl, halo, Ci-ealkoxy, C6-10aryloxy, C1-6alkylthiolate, C6-14arylthiolate, amino, a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3‘) an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumC3-wheterocyclyl), and a substituent of formula (II). In some embodiments, the substituents of the optionally substituted C3. iscarbocycle or C3-ioheterocycle are selected from Ci-ealkyl, Cs-ecarbocyclyl, 5- or 6-membered heterocyclyl, a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3‘) an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumC3. loheterocyclyl), and a substituent of formula (II). In more specific embodiments, the substituents of the optionally substituted C3-iscarbocycle or C3-ioheterocycle are selected from Ci-ealkyl and phenyl.

[0149] In some embodiments, each R3is independently selected from Ci-ealkyl, phenyl, Ci-ealkynyl, and a substituent of formula (II), wherein the Ci-ealkyl, phenyl and the Ci-ealkynyl are each optionally substituted with one or more substituents selected from Ci-ealkyl, and phenyl, or wherein two R3groups together with the C form a C8-i4carbocycle, optionally substituted with one or more substituents selected from Ci-ealkyl, phenyl and a substituent of formula (II).

[0150] In some embodiments, the ligand is of formula (III) or (IV):

[0151]

[0152] wherein each R5, R6and R7is independently selected from H or one of the optional substituents listed in respect of the optionally substituted Ce- aryl of R1and / or R2, above, and R3, R4and n are as described herein. For the avoidance of doubt, in formula (III) at least one of R5, R6and R7is a substituent of formula (II); in formula (IV) at least one of R3, R5, R6and R7is a substituent of formula (II) (in some cases, at least one of R5, R6and R7is a substituent of formula (II)).

[0153] In some embodiments, each R5is independently selected from hydrogen, Ci-ealkyl, Ce- aryl (e.g. phenyl), Cs-ecycloalkyl, 5- or 6-membered heteroaryl, 5- or 6-membered heterocycloalkyl, halo, a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3‘) or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumC3. loheterocyclyl)), and a substituent of formula (II), wherein the Ci-ealkyl, Cs-ecycloalkyl, Ce- aryl (e.g. phenyl) and the 5- or 6-membered heteroaryl are each optionally substituted with one or more substituents selected from phenyl and 5- or 6-membered heteroaryl. In some embodiments, where R5is a substituent of formula (II), n2 of the substituent of formula (II) is 1 or 2.

[0154] Each R5may be independently selected from hydrogen, Ci-ealkyl, halo, a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3-) or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumC3-ioheterocyclyl)), and a substituent of formula (II), wherein the Ci-ealkyl, is optionally substituted with one or more substituents selected from phenyl and 5- or 6-membered heteroaryl and optionally wherein n2 of the substituent of formula (II) is 1 or 2.

[0155] In some embodiments, each R5is independently selected from hydrogen and Ci-ealkyl, wherein the Ci-ealkyl, is optionally substituted with one or more phenyl substituents. For example, each R5may be Ci-3alkyl optionally substituted with one or more phenyl substituents. In some embodiments, each R5may be Ci-3alkyl.

[0156] In some embodiments, each R6is independently selected from hydrogen, Ci-ealkyl, Ce- aryl (e.g. phenyl), 5- or 6-membered heteroaryl, a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), (NH3+) sulfonate (SO3‘) or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumC3-ioheterocyclyl)), and a substituent of formula (II), wherein the Ci-ealkyl, Ce- aryl (e.g. phenyl) and the 5- or 6-membered heteroaryl are each optionally substituted with one or more substituents selected from phenyl and 5- or 6-membered heteroaryl. In some embodiments, where R6is a substituent of formula (II), n2 of the substituent of formula (II) is 1 or 2.

[0157] Each R6may be independently selected from hydrogen, Ci-ealkyl, halo, a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3‘) or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumC3-ioheterocyclyl)), and a substituent of formula (II), optionally wherein n2 of the substituent of formula (II) is 1 or 2. In some embodiments, each R6is independently selected from hydrogen and a substituent of formula (II), optionally wherein n2 of the substituent of formula (II) is 1 or 2.

[0158] In some embodiments, at least one of R5and at least one of R6together form a Cs-ecarbocyclic ring, such as a cyclopentene, cyclopentadiene, cyclohexene, cyclohexadiene or a benzene ring. For the avoidance of doubt, the Cs-ecarbocyclic ring is fused with the benzene ring to which the at least one of R5and the at least one of R6are bonded, thus the double bond of the cyclopentene and cyclohexene is shared with the benzene ring to which the at least one of R5and the at least one of R6are bonded.

[0159] In some embodiments, each R7is independently selected from hydrogen, Ci-ealkyl, Ce- aryl (e.g. phenyl), Cs-ecycloalkyl, 5- or 6-membered heteroaryl, 5- or 6-membered heterocycloalkyl, a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3‘) or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumC3-ioheterocyclyl)), and a substituent of formula (II).

[0160] Each R7may be independently selected from hydrogen, Ci-ealkyl, halo, a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3-) or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumC3-ioheterocyclyl)), and a substituent of formula (II), wherein n2 of the substituent of formula (II) is 0, 1 or 2.

[0161] In some embodiments, each R7is independently selected from hydrogen, Ci-ealkyl and a substituent of formula (II), wherein n2 of the substituent of formula (II) is 0, 1 or 2.

[0162] Typically, one or more substituents of formula (II) are positioned at either R5, R6or R7. For example, in some embodiments, 1 or 2 of R5may be of formula (II), and R6and R7may not be of formula (II). In some embodiments, 1 to 4 of R6(formula (III)) or 1 or 2 of R6(formula (IV)) may be of formula (II), and R5and R7may not be of formula (II). In some embodiments, 1 or 2 of R7(formula (III)) or R7(formula (IV)) may be of formula (II), and R5and R6may not be of formula (II).

[0163] In some embodiments, each R7is selected from a substituent of formula (II). In such embodiments, R5and R6may not be of formula (II). For example, each R5may be independently selected from hydrogen, Ci-ealkyl, C6-14aryl (e.g. phenyl), Cs-ecycloalkyl, and 5- or 6-membered heteroaryl; wherein the Ci-ealkyl, Cs-ecycloalkyl, Ce- aryl (e.g. phenyl) and the 5- or 6-membered heteroaryl are optionally substituted with one or more substituents selected from phenyl and 5- or 6-membered heteroaryl. The Ci-ealkyl may be a methyl group substituted with one or two substituents each selected from phenyl and 5- or 6-membered heteroaryl. Each R5may be independently selected from hydrogen, and Ci-ealkyl, which is optionally substituted with one or more phenyl substituents. Each R5may be independently selected from hydrogen and a methyl group substituted with one or two phenyl substituents. In such embodiments, each R6may be hydrogen.

[0164] In some embodiments, each R5is independently selected from a substituent of formula (II) wherein n2 is 1 or 2. In such embodiments, R6and R7may not be of formula (II). For example, each R6may be hydrogen. In such embodiments, each R7may be independently selected from hydrogen, Ci-ealkyl, Ce- aryl, Cs-ecycloalkyl, and 5- or 6-membered heteroaryl, such as hydrogen or C1-6alkyl.

[0165] In some embodiments, each R6is independently selected from a substituent of formula (II), wherein n2 is 1 or 2. In such embodiments, R5and R7may not be of formula (II). For example, each R5may be independently selected from hydrogen, Ci-ealkyl, C6-14aryl (e.g. phenyl), Cs-ecycloalkyl, and 5- or 6-membered heteroaryl; wherein the Ci-ealkyl, Cs-ecycloalkyl, C6-14aryl (e.g. phenyl) and the 5- or 6-membered heteroaryl are optionally substituted with one or more substituents selected from phenyl and 5- or 6-membered heteroaryl. The Ci-ealkyl may be a methyl group substituted with one or two substituents each selected from phenyl and 5- or 6-membered heteroaryl. Each R5may be independently selected from hydrogen, and Ci-ealkyl, which is optionally substituted with one or more phenyl substituents. Each R5may be independently selected from hydrogen and a methyl group substituted with one or two phenyl substituents. In such embodiments, each R7may be independently selected from hydrogen, Ci-ealkyl, C6-14aryl, Cs-ecycloalkyl, and 5- or 6-membered heteroaryl, such as hydrogen or C1-6alkyl.

[0166] Typically, each R5is the same, each R6is the same, and / or each R7is the same. In some embodiments, each R5is the same, each R6is the same, and each R7is the same. In such embodiments, the ligand of formula (III) may be considered as symmetrical.

[0167] As defined above, each R4is independently selected from Ci-ealkyl, halo, Ciwhaloalkyl, and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3‘), or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-6alkyl, or cyclic ammonium group, such as ammoniumC3-wheterocyclyl). In some embodiments, each R4is independently selected from Ci-ealkyl and Ci-ehaloalkyl. In more specific embodiments, each R4is independently selected from Ci-ealkyl, such as methyl.

[0168] As described above, the dashed line is an optionally present bond, wherein n is 0 to 2 when the dashed line is a bond and n is 0 to 4 when the dashed line is not a bond. Typically, the dashed line is not a bond and n is 0 to 4, such as 0 to 2. In some embodiments, n is 0 or 2. In some embodiments, where n is 2, the two R4are each bonded to the same carbon atom of the ligand of formula (I).

[0169] In some embodiments, n2 is 1 or 2. Typically, however, n2 is 0 or 1. For example, where the substituent of formula (II) is positioned at R5or R6, n2 may be 1, and when the substituent of formula (II) is positioned at R7, n2 may be 0 or 1.

[0170] As described above, formula (II) is:

[0171] —(X)n2— ZY3(II)

[0172] wherein n2 is as defined herein.

[0173] Each X is independently selected from methylene, ethynylene, C6-14arylene (e.g. phenylene or naphthylene), and C3-wheteroarylene (e.g. 5- or 6-membered heteroarylene, typically 6-membered heteroarylene), wherein the Ce- arylene and C3. wheteroarylene are each optionally substituted with one or more substituents selected from Ciwalkyl, halo, Ci-ehaloalkyl, and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO'), sulfonate (SO3‘), or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumC3-wheterocyclyl).

[0174] In some embodiments, where n2 is 2, and one X is ethynylene, the other is independently selected from methylene, C6-14arylene (e.g. phenylene or naphthylene), and C3. wheteroarylene (e.g. 5- or 6-membered heteroarylene, typically 6-membered heteroarylene), wherein the C6-14arylene and C3-wheteroarylene are optionally substituted, as described above. In some embodiments, where n2 is 2, and one X is methylene, the other is independently selected from ethynylene, C6-14arylene (e.g. phenylene or naphthylene), and C3-wheteroarylene (e.g. 5- or 6-membered heteroarylene), wherein the C6-14arylene and Cs-wheteroarylene are optionally substituted, as described above.

[0175] Typically, each X is independently selected from methylene, ethynylene, phenylene and 6-membered heteroarylene, wherein the phenylene and 6-membered heteroarylene are optionally substituted, as described above. In some embodiments, the phenylene and 6-membered heteroarylene are linked to the rest of the ligand at positions that are para to one another, for example the phenylene is phenyl-1, 4-ene.

[0176] In some embodiments, the Ce- arylene and Cs-wheteroarylene are each optionally substituted with one or more substituents selected from Ciwalkyl, and Ci-ehaloalkyl. In some embodiments, the C6-14arylene and Cs-wheteroarylene are unsubstituted.

[0177] In particular embodiments, each X is independently selected from ethynylene, and phenylene, wherein the phenylene is optionally substituted, as described above. In some embodiments, each X is independently selected from ethynylene and unsubstituted phenylene. In some embodiments, (X)n2 is selected from formulae (Ila) and (lib):

[0178]

[0179] where either one end may bond to ZY3.

[0180] As described above, each Z is independently selected from C or Si. In some embodiments, each Z is C.

[0181] As described above, each Y is independently selected from Cs-wcarbocyclyl (e.g. C5-ecarbocyclyl), Ca-wheterocyclyl (e.g. 5- or 6-membered heterocyclyl), Ciwalkyl, Ci-ehaloalkyl, C1-4alkenyl, Ciwhaloalkenyl, Ciwalkynyl, and Ciwhaloalkynyl, or two Y groups together with Z form a Cs-wcarbocycle or Ca-wheterocycle, or three Y groups together with Z form a bridged polycyclic Cs-wcarbocycle or bridged polycyclic Ca-wheterocycle, wherein each substituent is optionally substituted with one or more substituents selected from Ciwalkyl, Cs-wcarbocyclyl (e.g. Cs-ecarbocyclyl), Ca-wheterocyclyl (e.g. 5- or 6-membered heterocyclyl), halo, Ci-ehaloalkyl, and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3‘) or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumC3-10heterocyclyl)). In some embodiments, just the C3-wcarbocyclyl, Ca-wheterocyclyl, Ciwalkyl, the Cs-wcarbocycle, Ca-wheterocycle, the bridged polycyclic Cs-wcarbocycle and the bridged polycyclic Ca-wheterocycle are optionally substituted, each with one or more substituents selected from Ci-ealkyl, C3-locarbocyclyl (e.g. Cs-ecarbocyclyl), Ca-wheterocyclyl (e.g. 5- or 6-membered heterocyclyl), halo, Ci-ehaloalkyl, and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3⁻) or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumCs-ioheterocyclyl)).

[0182] For the avoidance of doubt, the C of Z is counted as one of the carbon atoms of the C3-locarbocycle and the bridged polycyclic Cs-wcarbocycle.

[0183] In some embodiments, where two Y groups together with Z form an optionally substituted Cs- carbocycle or Ca-wheterocycle, the optionally substituted Cs-wcarbocycle and C3-loheterocycle are each aliphatic, for example are each saturated. Examples of suitable Cs- carbocycle include cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclooctane, bicyclo[1.1.0]butane, bicyclo[1.1.1]pentane, bicyclo[2.1.1]hexane, bicyclo[2.2.1]heptane, bicyclo[3.1.1]heptane, bicyclo[2.2.2]octane, bicyclo[3.2.1]octane, cubane and adamantane, each of which are optionally substituted as described above. In some embodiments, the Cs-wcarbocycle is an aliphatic and / or saturated Cs-wcarbocycle, such as any one selected from cyclopentane, cyclohexane, cycloheptane, cyclooctane, bicyclo[1.1.1]pentane, bicyclo[2.1.1]hexane, bicyclo[2.2.2]octane and adamantane, each of which are optionally substituted as described above. Examples of suitable Ca-wheterocycle include pyrrolidine, oxolane, thiolane, piperidine, oxane, thiane, dithiane, azepane, oxepane, tetrahydropyran, thiepane, hexahydropyrimidine or hexahydropyridazine, a triazinane, quinuclidine, 2-azabicyclo[2.2.2]octane, 2-azabicyclo[2.2.1]heptane, each of which are optionally substituted as described above. In some embodiments, Ca-wheterocycle is an aliphatic and / or saturated Ca-wheterocycle, which is optionally substituted.

[0184] For the avoidance of doubt, where two Y groups together with Z form an optionally substituted Cs-wcarbocycle or Ca-wheterocycle, the other Y is as described above or herein, e.g. it may be independently selected from Cs-wcarbocyclyl (e.g. Cs-ecarbocyclyl), Ca- heterocyclyl (e.g. 5- or 6-membered heterocyclyl), Ci-ealkyl, Ci-ehaloalkyl, C1-ealkenyl, Ci-ehaloalkenyl, Ciwalkynyl, and Ci-ehaloalkynyl, each optionally substituted with one or more substituents selected from Ci-ealkyl, Cs-wcarbocyclyl (e.g. C5-ecarbocyclyl), Ca-wheterocyclyl (e.g. 5- or 6-membered heterocyclyl), halo, Ci-ehaloalkyl, and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3‘) or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-6alkyl, or cyclic ammonium group, such as ammoniumC3-ioheterocyclyl)).

[0185] In some embodiments, where three Y groups together with Z form an optionally substituted bridged polycyclic Cs- carbocycle or bridged polycyclic C3- heterocycle, the optionally substituted bridged polycyclic Cs- carbocycle and bridged polycyclic C3. loheterocycle are each aliphatic, for example are each saturated. Examples of suitable bridged polycyclic Cs- carbocycle include bicyclo[1.1.1]pentane, bicyclo[2.1.1]hexane, bicyclo[2.2.1]heptane, bicyclo[3.1.1]heptane, bicyclo[3.2.1]octane, bicyclo[2.2.2]octane, cubane and adamantane, each of which are optionally substituted as described above. Examples of suitable bridged polycyclic C3- heterocycle include quinuclidine, 2-azabicyclo[2.2.2]octane, and 2-azabicyclo[2.2.1]heptane, each of which are optionally substituted as described above.

[0186] In some embodiments, each Y is independently selected from C3- carbocyclyl (e.g. Cs-ecarbocyclyl), C3- heterocyclyl (e.g. 5- or 6-membered heterocyclyl), Ci-ealkyl, Ci-ehaloalkyl, C1-6alkenyl, Ci-ehaloalkenyl, Ci-ealkynyl, and Ci-ehaloalkynyl, each optionally substituted with one or more substituents selected from Ci-ealkyl, C3- carbocyclyl (e.g. Cs-ecarbocyclyl), C3- heterocyclyl (e.g. 5- or 6-membered heterocyclyl), halo, Ci-ehaloalkyl, and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO'), sulfonate (SO3‘) or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-6alkyl, or cyclic ammonium group, such as ammoniumC3-ioheterocyclyl)). In some embodiments, just the C3-iocarbocyclyl, C3-ioheterocyclyl, Ci-ealkyl, the C3. locarbocycle, C3-ioheterocycle, the bridged polycyclic Cs- carbocycle and the bridged polycyclic C3-ioheterocycle are optionally substituted, each with one or more substituents selected from Ci-ealkyl, C3-iocarbocyclyl (e.g. Cs-ecarbocyclyl), C3-ioheterocyclyl (e.g. 5-or 6-membered heterocyclyl), halo, Ci-ehaloalkyl, and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO'), sulfonate (SO3‘) or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumC3-ioheterocyclyl)).

[0187] In some embodiments, each Y is independently selected from C3- carbocyclyl (e.g. Cs-ecarbocyclyl), C3- heterocyclyl (e.g. 5- or 6-membered heterocyclyl), and Ci-ealkyl, each optionally substituted as described above. In some embodiments, where each Y is an unsubstituted Ci-ealkyl, it independently selected from a C2-6alkyl, such as C3-ealkyl, e.g. a branched C3-6alkyl. In some embodiments, where one or more Y is an unsubstituted Ci-ealkyl, the Ci-ealkyl is a C2-ealkyl, such as C3-ealkyl, e.g. a branched C3-6alkyl. In some embodiments, each Y is independently selected from Cs-ecarbocyclyl (e.g. phenyl, cyclohexyl or cyclopentyl), 5- or 6-membered heterocyclyl (e.g. pyridyl, piperidinyl or pyrrolidinyl), and Ci-ealkyl, each of which is optionally substituted as described above. In some embodiments, the Ci-ealkyl is unsubstituted.

[0188] In some embodiments, the optional substituents of the Y groups are independently selected from Ci-ealkyl, Cs-ecarbocyclyl, 5- or 6-membered heterocyclyl, halo, Ci-ehaloalkyl, and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3‘) or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumCa-wheterocyclyl)).

[0189] In some embodiments, the optional substituents of the Y groups are independently selected from Ci-ealkyl, Cs-ecarbocyclyl (e.g. phenyl, cyclohexyl or cyclopentyl), and 5- or 6-membered heterocyclyl (e.g. pyridyl, piperidinyl or pyrrolidinyl). In more particular embodiments, the optional substituents of the Y groups are independently selected from Ci-ealkyl and Cs-ecarbocyclyl, such as Ci-4alkyl, and phenyl.

[0190] In specific embodiments, each Y is independently selected from Cs-ecarbocyclyl and Ci-ealkyl, wherein the Cs-ecarbocyclyl is optionally substituted with one or more selected from Ci-ealkyl, such as Ci-4alkyl, and phenyl. In more specific embodiments, each Y is independently selected from phenyl and Ci-ealkyl, wherein the phenyl is optionally substituted with one or more selected from Ci-ealkyl, such as Ci-4alkyl, and phenyl. In yet more specific embodiments, each Y is phenyl, each independently optionally substituted with one or more selected from Ci-ealkyl, such as Ci-4alkyl (e.g. methyl or tert-butyl), and phenyl.

[0191] As defined above, the water-soluble group is a substituent which has a water solubility of 10 mg / L or more, typically 100 mg / L or more, or 1000 mg / L or more. When introduced into the relevant compound, the water-soluble group increases the water solubility of the resultant compound. Examples of suitable water-soluble groups include polyols, carboxylates (COO-), sulfonates (SO3-), and ammonium groups.

[0192] The polyol may be any one or more selected from PEG, polyethylene oxide, PPG, polytetrahydrofuran and PTMEG. In some embodiments, the polyol is PEG or PPG, typically PEG. The ammonium group may be a primary, secondary, tertiary or quaternary ammonium group. In some embodiments, the ammonium group is represented by N R4+, where each R is independently selected from hydrogen and an organyl group. Where two or more R comprise organyl groups, the two or more R may link together to form a cyclic ammonium group, such as ammoniumC3-10heterocyclyl, e.g. an ammonium group comprising a substituted diazinanyl such as a substituted piperazinyl. In some embodiments, the ammonium group is one or more selected from N-(Ci-6alkyl)nammonium (including NH3+, N(Ci-ealkyl)3+, NH(Ci-ealkyl)2+, NH2(Ci-ealkyl)+), N-(Ci-6alkyl)nammoniumCi-6alkyl (including -Ci-6alkylNH3+, -Ci-6alkylN(Ci-6alkyl)3+, -Ci-6alkylNH(Ci-6alkyl)2+, and -Ci-6alkylNH2(Ci-6alkyl)+), and cyclic ammonium groups and cyclic ammonium Ci-ealkyl groups, such as ammoniumCs-wheterocyclyl or ammoniumC3-10heterocyclylC1-6alkyl groups. In some embodiments, the cyclic ammonium groups and the cyclic ammonium Ci-ealkyl groups are of formulae W1 or W2:

[0193]

[0194] wherein Lwis optionally present and is a Ci-ealkylene;

[0195] Xwis CH or N;

[0196] Awis a C3-10heterocycle, such as a 5- or 6-membered heterocycle;

[0197] each R1wis independently selected from Ci-ealkyl, Ci-ehaloalkyl, halo, hydroxy and Ci-ealkoxy;

[0198] nw is 0 to 4; and

[0199] each R2wis independently selected from H and C1-6alkyl.

[0200] In some embodiments, Awis a 5- or 6-membered heterocycle, such as a 6-membered heterocycle. In some embodiments, Awis saturated.

[0201] In some embodiments, the cyclic ammonium groups and the cyclic ammonium Ci-ealkyl groups are of formulae W1 a or W2a:

[0202]

[0203] wherein Lw, Xw, R1w, nw, and R2ware as defined above and nw1 is 1 or 2. In some embodiments, nw is 0. In particular embodiments, Xwis N. Typically, nw1 is 1. In some embodiments, Lwis present and is methylene.

[0204] In some embodiments, each water-soluble group is independently selected from PEG, carboxylate, sulfonate and an ammonium group.

[0205] For the avoidance of doubt, where the ligand comprises a charged water-soluble group, it may be zwitterionic or be a charged ligand. Where the ligand is charged, it is typically stabilised by one or more counterions. The skilled person is able to identify suitable counterions without burden.

[0206] In particular embodiments, the ligand is any one of formulae (V) to (XIV):

[0207] R10R10

[0208] (VIII)

[0209]

[0210]

[0211] (XIV)

[0212] wherein:

[0213] each R8is independently a Ci-ealkyl optionally substituted with one or more phenyl, or is H,

[0214] R9is phenyl optionally substituted with one or more substituents selected from Ci-ealkyl, and phenyl;

[0215] each R10is independently a Ci-ealkyl;

[0216] each R11is independently selected from a Ci-ealkyl and phenyl;

[0217] each R12is independently selected from H, a Ci-ealkyl and phenyl;

[0218] n3 is 0 to 3; and

[0219] each ZY3is as defined herein, for example each Z may be C and each Y may be independently selected from C5-6carbocyclyl and C1-6alkyl, wherein the C5-6carbocyclyl is optionally substituted with one or more selected from C1-6alkyl, such as C1-4alkyl, and phenyl.

[0220] In more particular embodiments, the ligand is selected from:

[0221]

[0222] 

[0223]

[0224]

[0225] 5 In some embodiments, the ligand is not of any of the following structures:

[0226]

[0227] wherein each A1is Ph, each A1is para-tolyl, or each A1is para-terf-butylphenyl. In a further aspect, there is provided a ligand of formula (I), as described above. In particular embodiments of this aspect, when X1is N-R2and R1is phenyl, the phenyl is substituted at the ortho-position with substituents other than iso-propyl and CHPh2. In some embodiments, when X1is N-R2and R1is phenyl, the phenyl is substituted at the ortho-position with one or more substituents selected from formula (II), methyl, ethyl, n- propyl, C^alkyl, Cs- carbocyclyl, Ca- heterocyclyl, halo, and a water-soluble group, and further wherein the substituent ethyl, n-propyl, C^alkyl, Cs- carbocyclyl and C3- loheterocyclyl are each optionally substituted with one or more substituents selected from Cs- carbocyclyl, Cs- heterocyclyl and formula (II), the substituent methyl is optionally substituted with one or more substituents selected from Cs- heterocyclyl and formula (II), or wherein two substituent Ci-ealkyl together form a Cs-ecarbocyclyl ring. In some embodiments, the dashed line is not a bond. In some embodiments, the ligand is a CAAC ligand. In some embodiments, n2 is 1 or 2. In some embodiments, the ligand is not of any of the following structures:

[0228]

[0229] Ph Ph wherein each A1is Ph, each A1is para-tolyl, or each A1is para-terf-butylphenyl.

[0230] Salts

[0231] As described above, the ligands of the first aspect are typically formed as a salt and may be considered as comprising a protonated ligand (i.e. protonated ligand of the first aspect) and a counterion. In a further aspect of the invention, there is provided a salt of formula (1):

[0232] < R4)"^,

[0233] R^NVX'

[0234]

[0235] x' (1)

[0236] wherein R1, R4, X1, n and the dashed line are as defined in the first aspect; and

[0237] X’-is a monoanion. For the avoidance of doubt, each of the embodiments described in relation to the ligand of the first aspect may be applied mutatis mutandis to the salt. For example, the salt may be of formula (1III) or (1IV):

[0238]

[0239] (11V), wherein R3, R4, R5, R6, R7and n are as defined in the first aspect; and X’-is a monoanion.

[0240] The skilled person is able to ascertain which monoanions are suitable as part of the salts without burden. Typically, X’-is monovalent. In some embodiments, X’-is selected from a hydrogencarbonate, tetraphenylborate, perchlorate, p-toluenesulfonate, triflate, halide (such as chloride or bromide), tetrafluoroborate and hexafluorophosphate. In particular embodiments, X’-is selected from a halide (such as chloride) and a tetrafluoroborate.

[0241] Ruthenium catalysts

[0242] As described above, the ligands of the first aspect and the salts described above are able to form stable and effective catalysts, particularly ruthenium catalysts.

[0243] Typically, the ruthenium complex of the first aspect is of formula (i):

[0244] L1

[0245] L4, I.. X2

[0246] ^. Ru^

[0247] X3" I ^L2

[0248]

[0249] L3(i),

[0250] wherein:

[0251] L1is a ligand as defined in the first aspect;

[0252] L2is an ylidene;

[0253] L3is an L-type ligand, optionally wherein L3is a ligand as defined in the first aspect; L4is an optionally present L-type ligand; and

[0254] X2and X3are each independently an X-type ligand,

[0255] wherein L2and L3; L3and X2or X3; or L2and X2or X3are optionally linked.

[0256] Ruthenium catalysts for olefin metathesis, such as Grubb’s catalysts, are well known in the art, and the skilled person is able to ascertain which L2, L3, L4, X2and X3groups are suitable for use as part of the ruthenium complexes of the first aspect without burden. Ruthenium catalysts suitable for olefin metathesis include those sold by Apeiron (see in particular https: / / apeiron-synthesis.com / offer / catalysts); Umicore (see in particular https: / / pmc.umicore.com / en / products / grubbs-catalysts-portfolio); and STREM (see in particular https: / / ascensusspecialties.my.salesforce.eom / sfc / p / #2E000000pAb6 / a / VN000001fw13 / Zu7K8Hhi5LpeQ7cl1ZYeKO9bt2QMx3IPYfXCxQAoFDc). For the avoidance of doubt, the ligand defined in the first aspect may replace any N-heterocyclic carbene or cyclic alkyl amino carbene present in these complexes. The ylidene, L-type and X-type ligands included in these complexes are suitable for use in the ruthenium complexes described herein.

[0257] As described above, ligands may be described using the covalent bond classification (CBC) method. Under the neutral / covalent counting method, a donor atom that donates one electron to a metal atom is an X-type ligand.

[0258] In some embodiments, X2and X3are each independently selected from halo (such as chloro, bromo or iodo), isothiocyanato (NCS), isocyanato (NCO), phenoxy, arylthiolate, Ci-ealkoxy and C1-6alkylthiolate, wherein the phenoxy, arylthiolate, Ci-ealkoxy and C1-6alkylthiolate are each optionally substituted, for example with one or more substituents selected from halo (such as fluoro, chloro or bromo), Ci-ealkyl, Ci-ehaloalkyl and C6-i4aryl (i.e. phenyl, naphthyl or anthryl), wherein the C6-i4aryl is optionally substituted with one or more substituents selected from halo (such as fluoro, chloro or bromo), Chalky I, Ci-ehaloalkyl and phenyl. For example, X2and X3may each be independently selected from halo (such as chloro, bromo or iodo), isothiocyanato (NCS), isocyanato (NCO), phenoxy, arylthiolate, and C1-6alkylthiolate, wherein the phenoxy, arylthiolate, and C1-6alkylthiolate are each optionally substituted with one or more substituents selected from halo (e.g. fluoro, chloro or bromo), Ci-ealkyl, C1-6haloalkyl and C6-14aryl, wherein the C6-i4aryl is optionally substituted with one or more substituents selected from halo (e.g. fluoro, chloro or bromo), Ci-ealkyl, Ci-ehaloalkyl and phenyl.

[0259] In some embodiments, X2and X3are each independently selected from halo (such as chloro, bromo or iodo), isothiocyanato (NCS), isocyanato (NCO), phenoxy, arylthiolate, and C1-6alkylthiolate, wherein the phenoxy is optionally substituted with one or more halo substituents (such as one or more selected from fluoro, chloro and bromo) and the arylthiolate, and C1-6alkylthiolate are each optionally substituted with one or more substituents selected from halo (e.g. fluoro, chloro or bromo), Ci-ealkyl, C1-6haloalkyl and C6-14aryl, wherein the C6-i4aryl is optionally substituted with one or more substituents selected from halo (e.g. fluoro, chloro or bromo), Ci-ealkyl, Ci-ehaloalkyl and phenyl. In particular embodiments, the arylthiolate is optionally substituted with one or more substituents selected from halo (e.g. fluoro, chloro or bromo), phenyl, anthryl, Ci-ealkyl and Ci-ehaloalkyl, wherein the phenyl and anthryl are each optionally substituted with one or more substituents selected from Ci-ealkyl, Ci-ehaloalkyl and phenyl. In particular embodiments, the C1-6alkylthiolate is optionally substituted with one or more substituents selected from halo (e.g. fluoro, chloro or bromo), Ci-ealkyl and Ci-ehaloalkyl, such as halo and Ci-ehaloalkyl.

[0260] In more particular embodiments, the optionally substituted arylthiolate is selected from 2,3,4,5,6-pentafluorobenzenethiolate, 2,4,6-triphenylbenzenethiolate, 2,4,6-tris(3,5-dimethylphenyl)benzenethiolate, 2,4,6-tris(3,5-diphenylphenyl)benzenethiolate, 2,4,6-tris(3,5-ditertbutylphenyl)benzenethiolate, 2,6-diphenyl(4-anthryl)benzenethiolate, 2,6-diphenyl(4-(2,4-ditrifluoromethylphenyl)benzenethiolate, 2,6-diphenyl(4-(2,4,6-trimethylphenyl)benzenethiolate, 2,6-diphenyl(4-(2,4-dimethylphenyl)benzenethiolate, 2,6-dichlorobenzenethiolate, 2-chloro-6-methylbenzenethiolate, 2-methylbenzene-thiolate, 2,6-dimethylbenzenethiolate and 2-trifluoromethylbenzenethiolate. In more particular embodiments, the optionally substituted C1-6alkylthiolate is 1, 1,1, 3,3,3-hexafluoro-2-(trifluoromethyl)-2-propanethiolate.

[0261] In some embodiments, at least one of X2and X3is an optionally substituted arylthiolate or an optionally substituted Ci -eal ky Ithiolate. It is known in the art that such ligands, when part of a ruthenium catalyst, may improve Z-selectivity of olefin metathesis (see, for example, Occhipinti et al., “Simple and Highly Z-Selective Ruthenium-Based Olefin Metathesis Catalyst”, J. Am. Chem. Soc., 2013, 135, 9, 3331-3334). In particular embodiments, one of X2and X3is an optionally substituted arylthiolate or an optionally substituted C1-6alkylthiolate, and the other of X2and X3is a halo, such as chloro.

[0262] In particular embodiments, X2and X3are each halo, such as chloro, bromo or iodo, typically chloro.

[0263] As described above, under the neutral / covalent counting method, a donor atom that donates two electrons to a metal atom is an L-type ligand.

[0264] In some embodiments, L1and L3are each CAAC ligands, for example, are each CAAC ligands defined in the first aspect. In some embodiments, L3and L4(when present) are each selected from a phosphine, an N-heterocycle, such as pyridine, and an ether. In some embodiments, L4is either absent or is an N-heterocycle, such as pyridine. In particular embodiments, L4is absent.

[0265] In some embodiments, L3is selected from a phosphine (such as a monodentate phosphine ligand), an N-heterocycle, such as pyridine, an ether, an amino, an imine and a phosphite (such as a monodentate phosphite, e.g. triisopropylphosphite). Typically, where L3is an ether or an amino, the ether or amino is part of the ylidene of L2, i.e. L2and L3are linked. Where L3is an imine, it may link to X2or X3, particularly where the X2or the X3is an optionally substituted phenoxy.

[0266] In some embodiments, the phosphine is of formula P(Rp)3, wherein each Rpis selected from phenyl, cyclohexyl, cyclopentyl and Ci-ealkyl, wherein the phenyl, cyclohexyl, and cyclopentyl are each optionally substituted with one or more substituents selected from Ci-ealkyl, halo, Ci-ehaloalkyl and phenyl and the C1-6alkyl is optionally substituted with one or more halo. In some embodiments, each Rpis the same. In particular embodiments, the phosphine is selected from optionally substituted tricyclohexylphosphine and triphenylphosphine. In more particular embodiments, the phosphine is unsubstituted tricyclohexylphosphine. Thus, L3may be selected from a cyclohexylphosphine, pyridine, an ether that is part of the ylidene of L2, an amino that is part of the ylidene of L2, an imine that is linked with X2or X3and a phosphite, such as triisopropylphosphite.

[0267] Where L3and X2or X3are linked, they may form a chelating ligand that is a [2-[[phenyl)imino]methyl]-phenolyl], optionally substituted, e.g. with one or more selected from Ci-ealkyl, nitro and phenyl, such as Ci-ealkyl (e.g. methyl) and / or nitro. In particular embodiments, where L3and X2or X3are linked, they form a 2-[[(4-methylphenyl)imino]methyl]-phenolyl or a 2-[[(2-methylphenyl)imino]methyl]-4-nitro-phenolyl.

[0268] L2is an ylidene. The ylidene may be represented by =CRL2, where each RLis independently selected from hydrogen and an organyl group. Two or more RLmay link together to form a cyclic ylidene. In some embodiments, the ylidene of L2is selected from an alkylidene, cyclic hydrocarbylidene and a heterocyclylidene, each of which is optionally substituted. For the avoidance of doubt, the optionally substituted cyclic hydrocarbylidene may be aromatic, for example it may be optionally substituted indenylidene. In some embodiments, the cyclic hydrocarbylidene and heterocyclylidene are each optionally substituted with one or more substituents selected from halo, C1-6alkyl, C1-6alkoxy, phenoxy, C1-6alkylsulfanyl, C1-6haloalkylsulfanyl, C1-6alkylsulfinyl, benzylsulfinyl, phenyl, nitro, (dimethylamino)sulfonyl, isobutoxycarbonylamido and trifluoroacetamido, and wherein the phenyl is optionally substituted with one or more substituents selected from halo, C1-6alkyl, and C1-6alkoxy. In some embodiments, the optionally substituted cyclic hydrocarbylidene is optionally substituted indenylidene, for example, indenylidene optionally substituted with one or more substituents selected from halo, C1-6alkyl, C1-6alkoxy, phenoxy, C1-6alkylsulfanyl, C1-6haloalkylsulfanyl, C1-6alkylsulfinyl, benzylsulfinyl, phenyl, nitro, (dimethylamino)sulfonyl, isobutoxycarbonylamido and trifluoroacetamido, wherein the phenyl is optionally substituted with one or more substituents selected from halo, C1-6alkyl, and C1-6alkoxy.

[0269] In some embodiments, the alkylidene is optionally substituted with one or more substituents selected from cyclic hydrocarbyl (such as cyclic Cs-ehydrocarbyl), heterocyclyl (such as 5- or 6-membered heterocyclyl), C1-4alkenyl, phenoxy, arylthiolate, and C1-6alkylthiolate, wherein each hydrocarbyl and heterocyclyl is optionally substituted with one or more substituents selected from Ci-ealkyl, Ci-ealkoxy, C6-10aryloxy, phenyl, nitro, and (dimethylamino)sulfonyl, wherein the phenyl substituent is optionally substituted with one or more substituents selected from halo, C1-6alkyl, and C1-6alkoxy, and wherein the phenoxy is optionally substituted with one or more halo substituents (such as one or more selected from fluoro, chloro and bromo) and the arylthiolate, and C1-6alkylthiolate are each optionally substituted with one or more substituents selected from halo (e.g. fluoro, chloro or bromo), Ci-ealkyl, Ci-ehaloalkyl and C6-14aryl, wherein the C6-14aryl is optionally substituted with one or more substituents selected from halo (e.g. fluoro, chloro or bromo), C1-6alkyl, C1-6haloalkyl and phenyl. In particular embodiments, the alkylidene is substituted with an optionally substituted cyclic hydrocarbyl (such as a cyclic Cs-ehydrocarbyl, e.g. phenyl), an optionally substituted 5-membered heteroaryl (such as thiophenyl), Ci-4alkenyl (such as isobutenyl) and an optionally substituted arylthiolate (such as phenylthiolate). In more particular embodiments, the alkylidene is substituted with an optionally substituted phenyl or thiophenyl, such as a phenyl or thiophenyl optionally substituted with one or more substituents selected from Ci-ealkyl, Ci-ealkoxy, C6-10aryloxy, phenyl, nitro, and (dimethylamino)sulfonyl, and wherein the substituent phenyl is optionally substituted with one or more substituents selected from halo, C1-6alkyl, and C1-6alkoxy, or the alkylidene is substituted with a Ci-4alkenyl (such as isobutenyl) or an optionally substituted arylthiolate (such as phenylthiolate). In some embodiments, the ylidene of L2is selected from benzylidene and indenylidene, each optionally substituted as described above. In some embodiments, the ylidene is selected from benzylidene and indenylidene, each optionally substituted with one or more substituents selected from Ci-ealkyl, Ci-ealkoxy, phenoxy, phenyl, nitro, (dimethylamino)sulfonyl, isobutoxycarbonylamido and trifluoroacetamido, and wherein the substituent phenyl is optionally substituted with one or more substituents selected from C1-6alkyl, and C1-6alkoxy. In particular embodiments, the ylidene is selected from benzylidene and indenylidene, each optionally substituted with one or more substituents selected from C1-6alkyl, C1-6alkoxy, and phenyl optionally substituted with one or more substituents selected from C1-6alkyl, and C1-6alkoxy.

[0270] In particular embodiments, where L2and L3are not linked, the ylidene of L2may be selected from benzylidene and indenylidene, each optionally substituted with a phenyl and / or a C1-6alkyl. In such embodiments, L3is typically selected from a phosphine and an N-heterocycle, such as pyridine. In such embodiments, where L4is present, it is typically an N-heterocycle, such as pyridine.

[0271] Where L2and L3are linked, they may form a chelating ligand:

[0272] (i) that is an ortho-C1-6alkoxyarylmethylene or an ortho-C1-6alkoxyheteroarylmethylene, each optionally substituted as described above, e.g. with C1-6alkyl or phenyl; or

[0273] (ii) comprising a C1-6alkylidene substituted with a C5-6heteroaryl, wherein the C5-6heteroaryl is optionally substituted as described above, e.g. with one or more C1-6alkyl or phenyl, optionally wherein the chelating ligand is 3-(2- pyridyl)propylidene.

[0274] In some embodiments of (ii), the C1-6alkylidene is substituted with a C5-6heteroaryl group at the 2- or 3-position (i.e. at the carbon atom next to or a carbon atom away from the ylidene carbon). In some embodiments, the C5-6heteroaryl comprises a heteroatom, typically a nitrogen atom, (at position 1) and is connected to the alkylidene at position 2.

[0275] In some embodiments, where L2and L3are linked, they may form a chelating ligand that is an ortho-di(C1-6alkylphenyl)aminoarylmethylene or an ortho-di(C1-6alkylphenyl)amino heteroarylmethylene, each optionally substituted as described above, e.g. with C1-6alkyl or phenyl. Where L2and X2or X3are linked, they may form a chelating ligand that is a 2-oxo-arylmethylene or 2-oxoheteroarylmethylene, each optionally substituted, e.g. with nitro or C1-6alkyl. For example, where L2and X2or X3are linked, they may form a (2-oxo-5-nitrobenzylidene).

[0276] In some embodiments, where L2and L3are linked, they form a chelating ligand of formula (ia) or (ib):

[0277]

[0278] wherein:

[0279] L1, L4, X2and X3are as defined above and herein;

[0280] ring B is an arene, such as benzene;

[0281] R1ais Ci-ealkyl, optionally substituted with one or more selected from phenyl and -C(O)N(C1-6alkyl)(OC1-6alkyl);

[0282] each RBis independently selected from Ci-ealkyl, phenyl, nitro, (dimethylamino)sulfonyl, isobutoxycarbonylamido and trifluoroacetamido;

[0283] each nB is independently selected from 0 to 3;

[0284] ring C is a heteroarene, such as a 5- or 6-membered heteroarene (e.g. pyridine);

[0285] XBis selected from N, S and O (e.g. N); and

[0286] nB1 is 1 or 2.

[0287] In some embodiments, XBis N. In some embodiments, nB1 is 2. In some embodiments, ring C is pyridine. In some embodiments, nB of formula (ib) is 0.

[0288] In particular embodiments, ring B is benzene. For example, the ruthenium complex may be of formula (ii):

[0289]

[0290] wherein: R1ais a Ci-ealkyl, optionally substituted with one or more selected from phenyl and -C(O)N(C1-6alkyl)(OC1-6alkyl);

[0291] R2ais selected from hydrogen, C1-6alkyl, and phenyl; and

[0292] R3ais selected from hydrogen, C1-6alkyl, nitro, (dimethylamino)sulfonyl, isobutoxycarbonylamido and trifluoroacetamido.

[0293] In specific embodiments, R2aand R3aare each hydrogen.

[0294] In yet more specific embodiments, the ruthenium complex is selected from formula (iii), (iv), (v), (vi), (vii) and (viii):

[0295]

[0296] Uses and methods

[0297] As described above, the second aspect provides for the use of a ruthenium complex as defined in the first aspect, in catalysis, such as in olefin metathesis. In a further aspect, there is provided use of a ligand as defined in the first aspect or a salt as defined above, in catalysis, such as in olefin metathesis.

[0298] The catalysis may comprise contacting a ruthenium catalyst as defined in the first aspect with one or more substrates and / or reagents, wherein the ruthenium catalyst may be formed through the contacting of a ruthenium catalyst precursor with a ligand as defined in the first aspect or salt as defined above.

[0299] Viewed from a third aspect, there is provided a method of olefin metathesis comprising contacting a ruthenium complex as defined in the first aspect with two olefins. The olefins may be as defined herein, i.e. any compound comprising one or more aliphatic carboncarbon double bonds. In some embodiments, each of the two olefins comprise at least one aliphatic double bond in which the two carbon atoms of the double bond are secondary, primary or tertiary carbon atoms, i.e. the two carbon atoms of the double bond are each bonded 2, 1 or 3 carbon atoms. The two olefins need not be, but typically are different to each other. Typically, at least one of the carbon atoms of the double bond of at least one of the two olefins is a primary carbon atom, i.e. at least one of the olefins is of formula H2C=CR°2, wherein each R° is independently selected from H or an organyl. In some embodiments, the two olefins are linked together, e.g. one R° of one olefin is linked with an R° of the other olefin, to form one compound with two or more aliphatic carbon-carbon double bonds. The resultant di-olefin may undergo ring-closing metathesis when contacted with the ruthenium complex.

[0300] The contacting of the third aspect may be by any suitable means such that the two olefins react with the ruthenium complex and undergo olefin metathesis. Typically, the complex and olefins are contacted in an unreactive solvent, such as any one or a combination selected from an alkane, benzene, chloroalkane, alkyl acetate, dialkyl carbonate, cyclopentyl alkyl ether, dialkyl ether, tetra hydrofuran, tetrahydropyran, alcohol, water, supercritical carbon dioxide, polyethylene glycol, and alkyl lactate, wherein the benzene is optionally substituted with one or more Ci-ealkyl, Ci-ealkoxy and halo, and the tetra hydrofuran is optionally substituted with one or more C1-6alkyl. The solvent may be any one or a combination selected from an C5-10alkane, benzene, chloroCi-ealkane, Ci-ealkyl acetate, diCi-ealkyl carbonate, cyclopentyl Ci-ealkyl ether, diCi-ealkyl ether, tetra hydrofuran, tetrahydropyran, Ci-ealcohol, water, supercritical carbon dioxide, polyethylene glycol, and Ci-ealkyl lactate, wherein the benzene is optionally substituted with one or more Ci-ealkyl, Ci-ealkoxy and halo, and the tetra hydrofuran is optionally substituted with one or more C1-6alkyl. In particular embodiments, the solvent is any one or a combination selected from heptane, hexane, pentane, toluene, benzene, xylene, p-cymene, dichloromethane, dichloroethane, methyl acetate, ethyl acetate, dimethyl carbonate, cyclopentyl methyl ether, THF, methyltetrahydrofuran (2-MeTHF), ethanol, isopropanol, water, fluorobenzene, perfluorotoluene, perfluorobenzene supercritical carbon dioxide (scCO2), poly(ethylene glycol), ethyl lactate, methyl tert-butyl ether, 4-methyltetrahydropyran and anisole. In yet more particular embodiments, the solvent is any one or a combination selected from heptane, hexane, pentane, toluene, and benzene.

[0301] In alternative embodiments, the complex and olefins are contacted without solvent (e.g. in neat olefin). The contacting may be carried out at room temperature, or at lowered (e.g. at or less than 0 °C) or elevated temperatures, i.e. temperatures lower or higher than room temperature (e.g. below or above about 25 °C). In some embodiments, the contacting is carried out at temperatures of about 20 to about 100 °C. The skilled person is able to identify temperatures suitable for olefin metathesis without burden. The specific temperature used for a particular reaction may depend on the solvent, the type of olefins used and the identity of the complex.

[0302] One or more of the olefins used may be a gas, e.g. ethylene (also known as ethene). Where a gaseous olefin is used, it may be contacted with the ruthenium complex and other olefin at pressures greater than atmospheric pressure (i.e. at pressures greater than about 1 atm, i.e. greater than about 101.325 kPa). For example, gaseous olefins may be contacted at pressures of about 101.325 kPa to about 800 kPa, or about 101.325 kPa to about 700 kPa. Alternatively, gaseous olefins may be bubbled through the reaction mixture without pressurising the mixture.

[0303] The contacting of the third aspect may be for any suitable amount of time. The skilled person is able to analyse reaction progress using standard techniques routinely used in the art, such as thin layer chromatography (TLC), gas chromatography, gas chromatography mass spectrometry (GC-MS), liquid chromatography mass spectrometry (LC-MS), or nuclear magnetic resonance spectroscopy (NMR spectroscopy), such as1H or13C NMR spectroscopy. Suitable reaction times for olefin metathesis may be identified by the skilled person by applying such techniques, without burden. In some embodiments, the contacting is for about 24 hours.

[0304] Whilst the contacting of the third aspect is usually carried out under an inert atmosphere, e.g. under nitrogen or argon, the inventors have found that the high activity of the ruthenium complexes of the first aspect is such that the complexes are able to carry out metathesis reactions in the presence of air and / or using unpurified materials, such as unpurified olefins and / or unpurified solvents. The reactions may be, e.g. are, effective at room temperature, thus there is no need to heat the reaction mixture. Typically, however, the reactions are heated.

[0305] Viewed from a further aspect, there is provided a method of preparing a ligand as defined in the first aspect from the salt as defined above, the method comprising contacting the salt with a base. Without being bound by theory, the base deprotonates the salt to form a carbene binding site. The base may be defined by the pKa of its conjugate acid. For the avoidance of doubt, these pKa values relate to determinations conducted in water, at 25°C, for the reaction BH+⇌ H++ B, wherein BH+denotes the conjugate acid of the base concerned, as described in the CRC Handbook of Chemistry and Physics, 91stedition, 2010, Dissociation Constants of Organic Acids and Bases, and Dissociation Constants of Inorganic Acids and Bases, and the references cited therein. Accordingly, where the base used is potassium tert-butoxide (KO‘Bu), for example, the conjugate acid is tert-butanol (HO‘Bu); where the base used is sodium phenoxide (NaOPh), for example, the conjugate acid is phenol (HOPh). For further avoidance of doubt, the pKa of water at 25°C is defined herein, as is generally recognised in the art, as being 14.0. Accordingly, for example, the pKa of the conjugate acid of both sodium hydroxide and potassium hydroxide (i.e. water) is 14.0.

[0306] In some embodiments, the pKa of the conjugate acid of the base is greater than or equal to about 10, such as greater than or equal to about 15 or 17. Suitable bases include salts (e.g. lithium, sodium or potassium salts) comprising N(SiMe3)2, hydrides or Ci-ealkoxides (such as O‘Bu). In some embodiments, the base is selected from Li[N(SiMe3)2] (LiHMDS), KH, KO‘Bu and K[N(SiMe3)2] (KHMDS). In particular embodiments, the base is LiHMDS or KHMDS. In some embodiments, the pKa of the conjugate acid of the base is greater than or equal to about 20. In such embodiments, the base may be a salt (e.g. lithium, sodium or potassium salt) comprising N(SiMe3)2or hydrides, such as a base selected from Li[N(SiMe3)2] (LiHMDS), KH, and K[N(SiMe3)2] (KHMDS). In some embodiments, the base is Li[N(SiMe3)2],

[0307] The contacting of the salt with the base may be by any suitable means such that the salt reacts with the base to form the carbene ligand. Typically, the salt and base are contacted in an unreactive solvent, such as any one or a combination selected from an ether (such as tetra hydrofuran), benzene and an alkane, wherein the benzene is optionally substituted with Ci-ealkyl (e.g. toluene). In particular embodiments, the solvent is any one or a combination selected from tetrahydrofuran (THF), benzene and toluene, such as THF and benzene.

[0308] The contacting of the salt with the base may be carried out at room temperature (e.g. about 25 °C). The contacting may be for any suitable amount of time. Again, the skilled person is able to analyse reaction progress using standard techniques routinely used in the art. Suitable reaction times for carbene formation may be identified by the skilled person by applying such techniques, without burden. In some embodiments, the contacting is for about 1 to about 30 minutes, e.g. about 10 minutes. The formation of the carbene from the salt may be observable by colour change or solubilisation of the salt.

[0309] The fourth aspect provides a method of preparing a ruthenium complex as defined in the first aspect, the method comprising contacting a ligand as defined in the first aspect with a ruthenium precursor such that the ligand binds to the ruthenium.

[0310] Typically, the ruthenium precursor is of formula (pa):

[0311] L5

[0312] L4, I _. X2

[0313] ^. Ru^

[0314] X3" I ^L2

[0315]

[0316] L3(pa),

[0317] wherein:

[0318] L2is an ylidene;

[0319] L3and L5are each an L-type ligand;

[0320] L4is an optionally present L-type ligand; and

[0321] X2and X3are each independently an X-type ligand,

[0322] wherein L2and L3are optionally linked.

[0323] L2, L3, L4, X2and X3are as defined above and herein. In some embodiments, L5is as defined for L3, above. Without being bound by theory, on contacting the ruthenium precursor with the ligand as defined in the first aspect, L5is displaced by the ligand, thereby forming the ruthenium complex defined in the first aspect.

[0324] In some embodiments, L5is not a carbene. In some embodiments, each of L3and L5are not carbene ligands. For example, one or both of L3and L5may be selected from a phosphine (such as a monodentate phosphine ligand, e.g. tricyclohexylphosphine), and an N-heterocycle, such as pyridine.

[0325] In some embodiments, at least one of L3and L5is a phosphine. In some embodiments, L3and L5are each a phosphine or one of L3and L5is a phosphine and the other is an N-heterocycle, such as pyridine.

[0326] In specific embodiments, the ruthenium precursor is selected from any one of formulae (pb) to (pd):

[0327]

[0328] The contacting of the fourth aspect may be by any suitable means such that the ligand reacts with the ruthenium precursor and displaces L5to form the ruthenium complex as defined in the first aspect. Typically, the ligand and ruthenium precursor are contacted in an unreactive solvent, such as any one or a combination selected from an ether (e.g. tetrahydrofuran), benzene and alkane, wherein the benzene is optionally substituted with Ci-ealkyl (e.g. toluene). In particular embodiments, the solvent is any one or a combination selected from tetra hydrofuran (THF), benzene and toluene, such as THF and benzene.

[0329] The contacting of the fourth aspect may be carried out at room temperature (e.g. about 25 °C). The contacting of the fourth aspect may be for any suitable amount of time. Again, the skilled person is able to analyse reaction progress using standard techniques routinely used in the art. Suitable reaction times for ruthenium complex formation may be identified by the skilled person by applying such techniques, without burden. In some embodiments, the contacting is for about 1 minute to about 4 hours, e.g. about 10 minutes to about 2 hours. The formation of the ruthenium complex may be observable by colour change.

[0330] For the avoidance of doubt, each of the embodiments described in relation to the ligand of the first aspect, the salt described above, and the ruthenium complex of the first aspect may be applied mutatis mutandis to the uses and methods disclosed herein. For example, the ligand may be of formula (III) or (IV); Z may be C; and / or each Y may be independently selected from Cs-ecarbocyclyl and Ci-ealkyl, wherein the Cs-ecarbocyclyl is optionally substituted with one or more selected from Ci-ealkyl, such as Ci-4alkyl, and phenyl; X’-may be selected from a hydrogencarbonate, tetraphenylborate, perchlorate, p-toluenesulfonate, triflate, halide (such as chloride or bromide), tetrafluoroborate and hexafluorophosphate; and the ruthenium complex may be of formula (i), (ia), (ib) or (ii).

[0331] Where the ruthenium complex as defined in the first aspect is of formula (i), wherein L3and X2or X3; or L2and X2or X3are linked, the chelating ylidene is typically introduced after the contacting of the ligand as defined in the first aspect with the ruthenium precursor. This may be carried out, for example, by contacting the intermediate ruthenium complex with the desired chelating ylidene in the presence of an excess of phosphine.

[0332] Solvates, isotopes and isomers

[0333] For the avoidance of doubt, the compounds depicted in the structures disclosed herein are not to be limited to the bond angles and bond lengths depicted schematically herein. For example, the ruthenium complexes of the invention may range in shape from about square pyramidal or trigonal bipyramidal to about octahedral, depending on the specific identity of the ligands.

[0334] Also included are solvates and isotopically-labelled compounds of the invention. Isotopically-labelled compounds are identical to those recited herein, but for the fact that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number predominantly found in nature. Examples of isotopes that can be incorporated into compounds of the invention include isotopes of hydrogen, carbon, nitrogen, oxygen, sulfur, fluorine and chlorine, such as2H (i.e. deuterium),3H,13C,14C,15N,18O,17O,35S,18F, and36CI, respectively.

[0335] A protium atom (H) is a hydrogen atom with zero neutrons. A deuterium atom (D or2H) is a hydrogen atom with one neutron. Naturally occurring hydrogen contains about 0.02 molar per cent deuterium and 99.98% protium. Physical chemical properties between protium and deuterium are small but measurable. Deuterium is slightly less lipophilic than protium, has a smaller molar volume and carbon-deuterium bonds are shorter than carbon-protium bonds. Deuterium keeps the 3D surface, shape and steric flexibility of a molecule unaltered compared to H. A ratio of deuterium:protium in a compound greater than 1:99 is considered to be greater than that found naturally in hydrogen. In particular embodiments, where a moiety is specified as being “H”, the ratio of deuterium:protium at this position is greater than the natural isotopic abundance of deuterium, i.e. the percentage of deuterium found at his position of the compounds of the invention is greater than its natural isotopic abundance in hydrogen, which is about 0.02 mol%.

[0336] The compounds of the invention also include all amorphous and crystalline forms.

[0337] The ligands, salts and complexes of the invention may exist in different stereoisomeric forms. All stereoisomeric forms and mixtures thereof, including enantiomers and racemic mixtures, are included within the scope of the invention. Such stereoisomeric forms include enantiomers and diastereoisomers. Individual stereoisomers of compounds of the invention, i.e., associated with less than 5 %, preferably less than 2 % and in particular less than 1 % of the other stereoisomer, are included. Mixtures of stereoisomers in any proportion, for example a racemic mixture comprising substantially equal amounts of two enantiomers are also included within the invention.

[0338] Each and every patent and non-patent reference referred to herein is hereby incorporated by reference in its entirety, as if the entire contents of each reference were set forth herein in their entirety.

[0339] EXAMPLES

[0340] The invention may be further understood with reference to the clauses and examples that follow.

[0341] Clauses

[0342] 1. A ligand of formula (I):

[0343] (R4)n^1

[0344] R1-N^X

[0345] R

[0346]

[0347] ” (I),

[0348] wherein:

[0349] R1is a C1-6alkyl, or C6-10aryl;

[0350] wherein the Ce- aryl is optionally substituted with one or more substituents selected from formula (II), Ci-ealkyl, C3-wcarbocyclyl (e.g. Cs-ecarbocyclyl), C3-wheterocyclyl (e.g. 5- or 6-membered heterocyclyl), halo, and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3‘), or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumC3-10heterocyclyl)), and further wherein the substituent Ci-ealkyl, C3. wcarbocyclyl and C3-wheterocyclyl are each optionally substituted with one or more substituents selected from C3-iocarbocyclyl (e.g. Cs-ecarbocyclyl), C3- heterocyclyl (e.g.

[0351] 5- or 6-membered heterocyclyl) and formula (II), or wherein two substituent Ci-ealkyl together form a Cs-ecarbocyclyl ring;

[0352] wherein formula (II) is:

[0353] —(X)n2— ZY3(II)

[0354] wherein:

[0355] each X is independently selected from methylene, ethynylene, Ce- arylene (e.g. phenylene), and C3-wheteroarylene (e.g. 5- or 6-membered heteroarylene), wherein the Ce- arylene and C3-wheteroarylene are each optionally substituted with one or more substituents selected from Ci-ealkyl, halo, Ci-ehaloalkyl, and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3‘), or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumC3-ioheterocyclyl);

[0356] n2 is 0, 1 or 2;

[0357] Z is C or Si; and

[0358] each Y is independently selected from C3-wcarbocyclyl (e.g. Cs-ecarbocyclyl), C3. loheterocyclyl (e.g. 5- or 6-membered heterocyclyl), Ci-ealkyl, Ci-ehaloalkyl, C1-4alkenyl, Ci-ehaloalkenyl, Ciwalkynyl, and Ci-ehaloalkynyl, or two Y groups together with Z form a C3- carbocycle or C3-ioheterocycle, or three Y groups together with Z form a bridged polycyclic Cs- carbocycle or bridged polycyclic C3-ioheterocycle,

[0359] wherein each Y is optionally substituted with one or more substituents selected from Ci-ealkyl, C3-iocarbocyclyl (e.g. Cs-ecarbocyclyl), C3-ioheterocyclyl (e.g. 5- or 6-membered heterocyclyl), halo, Ci-ehaloalkyl, and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3‘) or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumC3-ioheterocyclyl));

[0360] X1is N-R2or C(R3)2, wherein:

[0361] R2is a Ci-ealkyl, or Ce- aryl; wherein the C6-14aryl is optionally substituted with one or more substituents selected from formula (II), Ci-ealkyl, C3-wcarbocyclyl (e.g. Cs-ecarbocyclyl), C3-wheterocyclyl (e.g. 5- or 6-membered heterocyclyl), halo, and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3‘) or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumC3-ioheterocyclyl)), and further wherein the substituent Ci-ealkyl, C3-wcarbocyclyl and C3-wheterocyclyl are each optionally substituted with one or two substituents selected from C3-wcarbocyclyl (e.g. Cs- ecarbocyclyl) and Ca-wheterocyclyl (e.g. 5- or 6-membered heterocyclyl) and formula (II), or wherein two substituent Ci-ealkyl together form a Cs-ecarbocyclyl ring;

[0362] each R3is independently selected from Ci-ealkyl, C1-6alkenyl, halo, cyano, Ci-ealkoxy, C6-10aryloxy, C1-6alkylthiolate, C6-14arylthiolate, amino, Cs-wcarbocyclyl (e.g. Cs-ecarbocyclyl), Ca-wheterocyclyl (e.g. 5- or 6-membered heterocyclyl), Ci-ealkynyl, and a substituent of formula (II), wherein the Ci-ealkyl, C1-6alkenyl, Ci-ealkoxy, C6-10aryloxy, C1-6alkylthiolate, Ce- arylthiolate, Cs-wcarbocyclyl, the Ca-wheterocyclyl, and the Ci-ealkynyl are each optionally substituted with one or more substituents selected from Ci-ealkyl, C3- carbocyclyl, Ca-wheterocyclyl, halo, Ci-ealkoxy, C6-10aryloxy, C1-6alkylthiolate, C6-14arylthiolate, amino, and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3‘) an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumC3-10heterocyclyl));

[0363] or wherein two R3groups together with the C form a Cs-wcarbocycle or a C3-wheterocycle, each optionally substituted with one or more substituents selected from Ci-ealkyl, Cs-wcarbocyclyl, Ca-wheterocyclyl, halo, Ci-ealkoxy, C6-10aryloxy, C1-6alkylthiolate, C6-14arylthiolate, amino, a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3⁻) an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumCs-wheterocyclyl), and a substituent of formula (II);

[0364] each R4is independently selected from C1-6alkyl, halo, C1-6haloalkyl, and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3-), or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumC3-10heterocyclyl); and

[0365] the dashed line is an optionally present bond, wherein n is 0 to 2 when the dashed line is a bond and n is 0 to 4 when the dashed line is not a bond;

[0366] with the proviso that at least one of R1, R2or R3is substituted with a substituent of formula (II).

[0367] 2. The ligand of clause 1, wherein R1is a substituted phenyl.

[0368] 3. The ligand of clause 1 or clause 2, wherein R2is an optionally substituted phenyl.

[0369] 4. The ligand of any one of clauses 1 to 3, which is of formula (III) or (IV):

[0370]

[0371] wherein:

[0372] each R5is independently selected from hydrogen, Ci-ealkyl, C6-14aryl (e.g. phenyl), Cs-ecycloalkyl, 5- or 6-membered heteroaryl, 5- or 6-membered heterocycloalkyl, halo, a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3‘) or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumC3-wheterocyclyl)), and a substituent of formula (II), wherein the Ci-ealkyl, Cs-ecycloalkyl, Ce- aryl (e.g. phenyl) and the 5- or 6-membered heteroaryl are optionally substituted with one or more substituents selected from phenyl and 5- or 6-membered heteroaryl;

[0373] each R6is independently selected from hydrogen, Ci-ealkyl, C6-14aryl (e.g. phenyl), 5- or 6-membered heteroaryl, a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), (NH3+) sulfonate (SO3‘) or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumC3-wheterocyclyl)), and a substituent of formula (II), wherein the Ci-ealkyl, C6-14aryl (e.g. phenyl) and the 5- or 6-membered heteroaryl are optionally substituted with one or more substituents selected from phenyl and 5- or 6-membered heteroaryl or wherein at least one of R5and at least one of R6together form a Cs-ecarbocyclic ring; each R7is independently selected from hydrogen, Ci-ealkyl, C6-14aryl (e.g. phenyl), Cs-ecycloalkyl, 5- or 6-membered heteroaryl, 5- or 6-membered heterocycloalkyl, a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3‘) or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumC3-wheterocyclyl)), and a substituent of formula (II); and

[0374] at least one of R5, R6and R7is a substituent of formula (II).

[0375] 5. The ligand of clause 4, wherein:

[0376] (i) each R6is hydrogen; or

[0377] (ii) each R6is independently selected from a substituent of formula (II), wherein n2 is 1 or 2.

[0378] 6. The ligand of clause 4 or clause 5, wherein: (i) each R5is independently selected from hydrogen, Ci-ealkyl, C6-14aryl (e.g. phenyl), Cs-ecycloalkyl, and 5- or 6-membered heteroaryl, wherein the Ci- ealkyl, Cs-ecycloalkyl, Ce- aryl (e.g. phenyl) and the 5- or 6-membered heteroaryl are optionally substituted with one or more substituents selected from phenyl and 5- or 6-membered heteroaryl; optionally wherein the Ci-ealkyl is a methyl group substituted with one or two substituents each selected from phenyl and 5- or 6-memberedheteroaryl;

[0379] each R6is hydrogen; and

[0380] each R7is selected from a substituent of formula (II);

[0381] (ii) each R5is independently selected from a substituent of formula (II) wherein n2 is 1 or 2;

[0382] each R6is hydrogen; and

[0383] each R7is independently selected from hydrogen, Ci-ealkyl, C6-14aryl, Cs-ecycloalkyl, and 5- or 6-membered heteroaryl; or

[0384] (iii) each R5is independently selected from hydrogen, Ci-ealkyl, C6-14aryl (e.g.

[0385] phenyl), Cs-ecycloalkyl, and 5- or 6-membered heteroaryl; optionally wherein the Ci-ealkyl is a methyl group substituted with one or two substituents each selected from phenyl and 5- or 6-membered heteroaryl;

[0386] each R6is independently selected from a substituent of formula (II), wherein n2 is 1 or 2; and

[0387] each R7is independently selected from hydrogen, Ci-ealkyl, C6-14aryl, Cs-ecycloalkyl, and 5- or 6-membered heteroaryl.

[0388] 7. The ligand of any one of clauses 4 to 6, wherein each R5is the same, each R6is the same, and / or each R7is the same.

[0389] 8. The ligand of any one preceding clause, wherein each R4is independently selected from C1-6alkyl.

[0390] 9. The ligand of any one preceding clause, wherein the dashed line is not a bond and n is 0 to 4, such as 0 to 2.

[0391] 10. The ligand of any one preceding clause, wherein each R3is independently selected from Ci-ealkyl, phenyl, Ciwalkynyl, and a substituent of formula (II), wherein the Ci-ealkyl, phenyl and the Ciwalkynyl are each optionally substituted with one or more substituents selected from Ci-ealkyl, and phenyl, or wherein two R3groups together with the C form a C8-i4carbocyclyl, optionally substituted with one or more substituents selected from Ci-ealkyl, phenyl and a substituent of formula (II).

[0392] 11. The ligand of any one preceding clause, wherein n2 is 0 or 1 and X is phenylene or ethynylene.

[0393] 12. The ligand of any one preceding clause, wherein each Y is independently selected from phenyl, 5- or 6-membered heteroaryl, Cs-ecycloalkyl, and Ci-ealkyl, wherein the phenyl, 5- or 6-membered heteroaryl, and Cs-ecycloalkyl are optionally substituted with one or more substituents selected from Ci-ealkyl, phenyl, and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3⁻) or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumCs-ioheterocyclyl)).

[0394] 13. The ligand of any one preceding clause, wherein Z is C.

[0395] 14. The ligand of any one preceding clause, wherein each Y is phenyl, optionally substituted with one or more substituents selected from Ci-ealkyl (e.g. tert-butyl), and phenyl.

[0396] 15. The ligand of any one preceding clause, which is any one of formulae (V) to (IX):

[0397]

[0398]

[0399] (Rlq)n3 (IX)

[0400] wherein:

[0401] each R8is independently a Ci-ealkyl optionally substituted with one or more phenyl, or is H,

[0402] R9is phenyl optionally substituted with one or more substituents selected from Ci-ealkyl, and phenyl;

[0403] each R10is independently a Ci-ealkyl;

[0404] each R11is independently selected from a Ci-ealkyl and phenyl;

[0405] each R12is independently selected from H, a Ci-ealkyl and phenyl; and

[0406] n3 is 0 to 3.

[0407] 16. The ligand of any one preceding clause, which is selected from:

[0408]

[0409]

[0410] 17. A salt of formula (1):

[0411] (R4)"^,R.-NV*’

[0412]

[0413] x' (1) wherein R1, R4, X1, n and the dashed line are as defined in any one preceding clause; and

[0414] is a monoanion.

[0415] 18. The salt of clause 17, wherein X’ is selected from a hydrogencarbonate, tetraphenylborate, perchlorate, p-toluenesulfonate, triflate, halo, tetrafluoroborate and hexafluorophosphate.

[0416] 19. A ruthenium complex comprising a ligand as defined in any one of clauses 1 to 16. 20. The ruthenium complex of clause 19, which is of formula (i):

[0417] L1

[0418] L4, I.. X2

[0419] X3" I ^L2

[0420]

[0421] L3(i),

[0422] wherein:

[0423] L1is the ligand as defined in any one of clauses 1 to 16;

[0424] L2is an ylidene;

[0425] L3is an L-type ligand, optionally wherein L3is the ligand as defined in any one of clauses 1 to 16;

[0426] L4is an optionally present L-type ligand; and

[0427] X2and X3are each independently an X-type ligand,

[0428] wherein L2and L3; L3and X2or X3; or L2and X2or X3are optionally linked.

[0429] 21. The ruthenium complex of clause 20, wherein X2and X3are each independently selected from halo, isothiocyanato (NCS), isocyanato (NCO), phenoxy optionally substituted with one or more halo substituents, and optionally substituted arylthiolate such as 2,3,4,5,6-pentafluorobenzenethiolate, 2,4,6-triphenylbenzenethiolate, 2,4,6-tris(3,5-dimethylphenyl)benzenethiolate, 2,4,6-tris(3,5-diphenylphenyl)benzenethiolate, 2.4.6-tris(3,5-ditertbutylphenyl)benzenethiolate, 2,6-diphenyl(4-anthryl)benzenethiolate, 2.6-diphenyl(4-(2,4-ditrifluoromethylphenyl)benzenethiolate, 2,6-diphenyl(4-(2,4,6-trimethylphenyl)benzenethiolate, 2,6-diphenyl(4-(2,4-dimethylphenyl)benzenethiolate, 2,6-dichlorobenzenethiolate, 2-chloro-6-methylbenzenethiolate, 2-methylbenzene-thiolate, 2,6-dimethylbenzenethiolate, 2-trifluoromethylbenzenethiolate or 1, 1,1, 3,3,3-hexafluoro-2-(trifluoromethyl)-2-propanethiolate.

[0430] 22. The ruthenium complex of clause 20 or clause 21, wherein L3and L4are each selected from a phosphine, an N-heterocycle, such as pyridine, an ether, an amino, an imine and a phosphite.

[0431] 23. The ruthenium complex of any one of clauses 20 to 22, wherein the ylidene is selected from an alkylidene, cyclic hydrocarbylidene and a heterocyclylidene, wherein: the alkylidene is optionally substituted with one or more substituents selected from cyclic hydrocarbyl, heterocyclyl, C1-6alkenyl, phenoxy, arylthiolate, and C1-6alkylthiolate, wherein each cyclic hydrocarbyl and heterocyclyl is optionally substituted with one or more substituents selected from Ci-ealkyl, Ci-ealkoxy, C6-10aryloxy, phenyl, nitro, and (dimethylamino)sulfonyl, wherein the phenyl substituent is optionally substituted with one or more substituents selected from halo, C1-6alkyl, and C1-6alkoxy, the phenoxy substituent is optionally substituted with one or more halo substituents and the arylthiolate, and C1-6alkylthiolate substituents are each optionally substituted with one or more substituents selected from halo (e.g. fluoro, chloro or bromo), Ci-ealkyl, C1-6haloalkyl and C6-14aryl, wherein the C6-i4aryl is optionally substituted with one or more substituents selected from halo (e.g. fluoro, chloro or bromo), Ci-ealkyl, Ci-ehaloalkyl and phenyl; and

[0432] the cyclic hydrocarbylidene and heterocyclylidene are each optionally substituted with one or more substituents selected from halo, C1-6alkyl, C1-6alkoxy, phenoxy, C1-6alkylsulfanyl, C1-6haloalkylsulfanyl, C1-6alkylsulfinyl, benzylsulfinyl, phenyl, nitro, and (dimethylamino)sulfonyl, and wherein the phenyl is optionally substituted with one or more substituents selected from halo, C1-6alkyl, and C1-6alkoxy.

[0433] 24. The ruthenium complex of clause 23, wherein the ylidene is selected from benzylidene and indenylidene optionally substituted with a phenyl and / or a C1-6alkyl.

[0434] 25. The ruthenium complex of any one of clauses 20 to 22, wherein:

[0435] (i) L2and L3are linked to form an optionally substituted ortho-C1-6alkoxyarylmethylene or an optionally substituted ortho-C1-6alkoxyheteroarylmethylene; or

[0436] (iii) L2and L3together comprise a chelating ligand comprising a C1-6alkylidene substituted with a C5-6heteroaryl, wherein the C5-6heteroaryl is optionally substituted with one or more C1-6alkyl, optionally wherein the chelating ligand is 3-(2-pyridyl)propylidene.

[0437] 26. The ruthenium complex of clause 25, which is of formula (ii):

[0438] L1

[0439] L4„. I

[0440] *

[0441] R1a]|

[0442]

[0443] R2aR-wherein:

[0444] R1ais a Ci-ealkyl, optionally substituted with one or more selected from phenyl and -C(O)N(C1-6alkyl)(OC1-6alkyl);

[0445] R2ais selected from hydrogen, C1-6alkyl, and phenyl; and

[0446] R3ais selected from hydrogen, C1-6alkyl, nitro, (dimethylamino)sulfonyl, isobutoxycarbonylamido and trifluoroacetamido. 27. The ruthenium complex of any one of clauses 20 to 26, wherein L4is:

[0447] (i) absent; or

[0448] (ii) an N-heteroaryl such as pyridine.

[0449] 28. The ruthenium complex of any one of clauses 20 to 27, which is selected from formula (iii), (iv), (v) and (vi):

[0450]

[0451] 29. Use of a ligand as defined in any one of clauses 1 to 16, a salt as defined in clause 17 or clause 18, or a ruthenium complex as defined in any one of clauses 19 to 28, in catalysis.

[0452] 30. The use of clause 29, wherein the catalysis is olefin metathesis.

[0453] 31. A method of olefin metathesis comprising contacting a ruthenium complex as defined in any one of clauses 19 to 28 with two olefins.

[0454] 32. A method of preparing a ligand as defined in any one of clauses 1 to 16 from the salt as defined in clause 17 or clause 18, the method comprising contacting the salt with a base.

[0455] 33. The method of clause 32, wherein the pKa of the conjugate acid of the base is greater than or equal to about 10, such as greater than or equal to about 15.

[0456] 34. A method of preparing a ruthenium complex as defined in any one of clauses 19 to 28, the method comprising contacting a ligand as defined in any one of clauses 1 to 16 with a ruthenium precursor such that the ligand binds to the ruthenium. 35. The method of clause 34, wherein the ruthenium precursor is of formula (pa): L5

[0457] L4, I _. X2

[0458] ^Ru’^

[0459] X3" I ^L2

[0460]

[0461] L3(pa),

[0462] wherein:

[0463] L2is an ylidene;

[0464] L3and L5are each an L-type ligand;

[0465] L4is an optionally present L-type ligand; and

[0466] X2and X3are each independently an X-type ligand,

[0467] wherein L2and L3are optionally linked.

[0468] Experimental

[0469] General Procedures

[0470] Ligand syntheses was carried out in air unless otherwise noted. Catalyst synthesis was carried out under N2 in HPLC-grade solvents, dried and degassed using a Glass Contour solvent purification system, then stored under N2 over 4 A molecular sieves for at least 16 h prior to use. NMR solvents (CDCI3, C6D6; Cambridge Isotopes) and styrene were freeze-pump-thaw degassed (5x) and stored as above. Styrene was degassed by five consecutive freeze / pump / thaw cycles, and then stored at -35 °C under N2 in the glovebox freezer. Dimethyl terephthalate (DMT, 99.9%; Sigma Aldrich) and ethylene (99.9%; Messer) were used as received. All other reagents were purchased at the highest commercial quality and used without purification. Literature protocols were used to synthesize ruthenium complexes HI, Hll, Gill, and 1-O-TPPh, structures shown in Scheme 2, below (see Kingsbury et al., “Recyclable Ru-Based Metathesis Catalyst”. J. Am. Chem. Soc. 1999, 121, 791-799; Nascimento et al., “Resin-Assisted Routes to Second-Generation Catalysts for Olefin Metathesis”. Catal. Sci. Technol. 2018, 1535-1544; Sanford et al., “Mechanism and Activity of Ruthenium Olefin Metathesis Catalysts”. J. Am. Chem. Soc. 2001, 123, 6543-6554; Trnka et al., “Ruthenium alkylidene complexes coordinated with tricyclohexylphosphine and heterocyclic N-donor ligands”. Arkivoc, 2002, 2002, 28-41; Marx et al., “Cyclic Alkyl Amino Carbene (CAAC) Ruthenium Complexes as Remarkably Active Catalysts for Ethenolysis”. Angew. Chem., Int. Ed.

[0471] 2015, 54, 1919-1923; Angew. Chem. 2015, 127, 1939-194); and Fujihara et al., “Ruthenium-catalyzed ring-closing metathesis accelerated by long-range steric effect”. Chem. Commun., 2011,47, 9699-9701. Synthesis of new catalysts is described below.

[0472]

[0473]

[0474] Scheme 2: (a) established ruthenium catalysts, (b) new ruthenium catalysts used in this work.

[0475] NMR spectra were recorded on Avance 300, II-300, III-500, II-600, or NEO-600 spectrometers at 25 ±0.5 °C. Chemical shifts are reported in ppm and referenced as follows:1H NMR spectra to the residual proton of the deuterated solvent (CDCh, 7.26 ppm; CD2CI2, 5.32 ppm; C6D6, 7.16 ppm);13C{1H} NMR spectra to the carbon of the deuterated solvent (CDCI3, 77.16 ppm; CD2CI2, 53.84 ppm; C6D6, 128.06 ppm). Air-sensitive NMR experiments were carried out using either screw-capped NMR tubes equipped with PTFE septa (Rotoflo), or J. Young valved NMR tubes. Controlled mixing of solutions in NMR tubes was achieved by attaching the tubes to a rotary motor with electrical tape. HRMS ESI mass spectra were recorded by means of an orthogonal electron spray ionization ion source (ESI) interfaced to a 6546 LC / Q-TOF mass spectrometer from Agilent. The ions were transported into the orthogonal accelerating time-of-flight (TOF) single-stage reflectron mass analyzer by a high-frequency and high- voltage quadrupole ion guide. Detection was achieved with a dual microchannel plate detector.

[0476] Synthesis of p-trityl anilines

[0477] Ph

[0478] Ph

[0479] , N

[0480]

[0481] 2,6-Dimethyl-4-tritylaniline (3a). In a 100 mL round-bottom flask, 2,6-dimethylaniline (3.40 g, 27.94 mmol) was mixed in glacial acetic acid (30 mL) and HCI 35% (4 mL). Triphenylmethanol (4.85 g, 18.63 mmol) was added in a single portion, and the resulting mixture was refluxed for 5 h. The reaction mixture was cooled to RT, transferred to a 250 mL round-bottom flask, and diluted with EtOAc (100 mL). The pH was adjusted to pH 7-8 by adding dropwise a solution of 12 M KOH. The resulting biphasic mixture was separated, and the organic layer was evaporated to obtain a brown crystalline residue. The residue was resuspended in EtOH (50 mL) and cooled to 0 °C. The product was filtered, rinsed with EtOH (2 x 20 mL) and dried under high vacuum to obtain 2,6-dimethyl-4-tritylaniline (6.60 g, 97%) as a white crystalline powder.

[0482] Ph

[0483] Ph

[0484] , N

[0485]

[0486] 3b

[0487] 2,6-Diethyl-4-tritylaniline (3b). As for 3a, using 2,6-diethylaniline. The product 2,6-diethyl-4-tritylaniline was obtained as a white crystalline powder (7.05 g, 97%).

[0488]

[0489] 3c

[0490] 2.6-Diisopropyl-4-tritylaniline (3c). As for 3a, using 2,6-diisopropylaniline. The product 2.6-diisopropylaniline-4-tritylaniline (7.71 g, 99%) was obtained as a white crystalline powder.

[0491]

[0492] 2,4-Dimethyl-2-phenylpent-4-enal (4). In a 250 mL round-bottom flask equipped with a magnetic stir bar, potassium carbonate (10.3 g, 74.53 mmol) and tetrabutylammonium iodide (688 mg, 1.86 mmol) were mixed in water (30 mL) and toluene (25 mL). A solution of 2-phenylpropanaldehyde (5.0 g, 37.26 mmol) and 3-chloro-2-methylpropene (4.39 g, 48.44 mmol) in toluene (25 mL) was added dropwise at 70 °C in 1 h. The resulting biphasic mixture was stirred at 70 °C for 18 h. The reaction mixture was cooled to RT. The product was extracted with toluene (2 x 20 mL), and the combined organic layers were washed with water (2 x 20 mL), dried with Na2SO4, and evaporated to obtain a yellow transparent liquid with some salt crystals. The residue was resuspended in hexanes (30 mL) and filtered, rinsing with hexanes (2 x 30 mL). The filtrate was evaporated to obtain 2,4-dimethyl-2-phenylpent-4-enal 4 (6.50 g, 93%) as a light-yellow transparent liquid.

[0493] Synthesis of CAAC Salts

[0494] Ph

[0495] Ph'

[0496]

[0497] 4 Ph

[0498] 6a

[0499] 1-(2,6-Dimethyl-4-tritylphenyl)-2,2,4-trimethyl-4-phenyl-3,4-dihydro-2H-pyrrol-1-ium tetrafluoroborate (6a). In a 100 mL round-bottom flask, tritylaniline 3a (1.16, 3.19 mmol), aldehyde 4 (721 mg, 3.83 mmol), p-toluensulfonic acid (27.48 mg, 0.16 mmol) and MgSCL (5.0 g) were mixed in toluene (15 mL). The resulting mixture was refluxed for 24 h until complete consumption of the tritylaniline 3a. The mixture was filtered, rinsed with toluene (2 x 10 mL) and the filtrate concentrated to ca. 10 mL. The resulting solution was transferred to a pressure vessel, and ethereal 2M HCI (4.8 mL, 9.55 mmol) was added in a single portion. The sealed tube was heated at 75 °C for 24 h. The reaction mixture was evaporated, the residue was redissolved in CH2CI2 (30 mL) and a solution of sodium tetrafluoroborate (693.2 mg, 6.31 mmol) in water (20 mL) was added. The biphasic mixture was stirred for 1 h, after which the organic layer was separated and evaporated to obtain an oily residue. The product was precipitated by adding Et20 (30 mL), crushing the powder, filtering, rinsing with Et2O (2 x 30 mL) and dried under high vacuum to obtain the product 6a (1.74 g, 64%) as a beige powder.

[0500] 1H NMR (600 MHz, CDCI3) δ 9.49 (s, 1H, NCH), 7.44 (dd,4JH-H = 8.5, 1.5 Hz, 2H, Ph o-CH), 7.41 (dd,4JH-H = 8.7, 6.8 Hz, 2H, Ph m-CH), 7.33 - 7.29 (m, 1H, Ph p-CH), 7.27 -7.22 (m, 6H, Tr m-CH), 7.20- 7.16 (m, 3H, Trp-CH), 7.16- 7.13 (m, 6H, Tro-CH), 7.10 (d,4JH-H = 2.2 Hz, 1H, NAr m-CH), 7.01 (d,4JH-H = 2.2 Hz, 1H, NAr m-CH), 3.08 (d,2JH-H = 13.9 Hz, 1H, Heterocycle CH2), 2.66 (d,2JH-H = 13.9 Hz, 1H, Heterocycle CH2), 2.24 (s, 3H, NAr CH3), 1.97 (s, 3H, NAr CH3), 1.96 (s, 3H, CPhCH3), 1.62 (s, 3H, CN(CH3)2), 1.42 (s, 3H, CN(CH3)2).

[0501] 13C NMR (150 MHz, CDCI3) 5 190.4, 150.3, 145.8, 140.5, 133.5, 132.9, 132.8, 132.2, 131.2, 130.8, 130.2, 128.8, 128.0, 126.5, 125.8, 83.9, 64.9, 55.6, 49.0, 29.2, 27.9, 27.8, 19.8, 19.7.

[0502] ESI-MS (MeOH): Calculated for C40H40N ([M-BF4]), m / z 534.3161 Found: m / z 534.3487

[0503]

[0504] 6b

[0505] 1-(2,6-Diethyl-4-tritylphenyl)-2,2,4-trimethyl-4-phenyl-3,4-dihydro-2H-pyrrol-1-ium tetrafluoroborate (6b). As for 6a, but using 2,6-diethyl-4-tritylaniline (3b), to obtain 6b (2.08 g, 68%) as a beige powder.

[0506] 1H NMR (600 MHz, CDCI3) δ 9.59 (s, 1H, NCH), 7.47 (dd,4JHH = 8.3, 1.4 Hz, 2H, Ph o-CH), 7.44 (dd,4JH-H = 8.7, 6.8 Hz, 2H, Ph m-CH), 7.37 - 7.33 (m, 1 H, Ph p-CH ), 7.28 (t,3JH-H = 7.7 Hz, 6H, Tr m-CH), 7.23 - 7.17 (m, 11 H, Tr o and m-CH, NAr m-CH), 7.11 (d,4JH-H = 2.2 Hz, 1H, NAr m-CH), 3.13 (d,2JH-H = 13.9 Hz, 1H, Heterocycle CH2), 2.67 (d,2JH-H = 13.9 Hz, 1H, Heterocycle CH2), 2.53 (dq,3JH-H= 14.9, 7.4 Hz, 1H, NAr-CH2CH3), 2.46 (dq,3JH-H = 15.0, 7.5 Hz, 1H, NAr-CH2CH3), 2.23 (dq,3JH-H = 15.0, 7.6 Hz, 1H, NAr-CH2CH3), 2.12 (dq,3JH-H = 14.8, 7.4 Hz, 1H, NAr-CH2CH3), 1.98 (s, 3H, PhCCH3), 1.57 (s, 3H, NC(CH3)2), 1.35 (s, 3H, NC(CH3)2), 1.13 (t,3JH-H = 7.4 Hz, 3H, NAr-CH2CH3), 0.96 (t,3JH-H = 7.5 Hz, 3H, NAr-CH2CH3).

[0507] 13C NMR (150 MHz, CDCI3) 5 190.2, 150.6, 145.9, 140.7, 139.0, 138.3, 131.2, 131.0, 130.8, 130.2, 128.8, 128.7, 127.9, 126.5, 125.8, 83.4, 65.2, 55.7, 48.8, 29.3, 27.6, 27.2, 25.2, 25.0, 15.6, 14.8.

[0508] ESI-MS (MeOH): Calculated for C42H44N ([M-BF4]), m / z 534.3474 Found: m / z 534.3474

[0509]

[0510] 1-(2,6-diisopropyl-4-tritylphenyl)-2,2,4-trimethyl-4-phenyl-3,4-dihydro-2H-pyrrol-1-ium tetrafluoroborate (6c). As for 6a, but using 2,6-diisopropyl-4-tritylaniline (3c; 2.0 g, 4.77 mmol), to obtain 6c (1.96 g, 66%) as a beige powder.

[0511] 1H NMR (600 MHz, CDCI3) δ 9.60 (s, 1H, NCH), 7.48 (dd,4JH-H = 8.4, 1.3 Hz, 2H, Ph o-CH), 7.44 (dd,4JH-H = 8.7, 7.0 Hz, 2H, Ph m-CH), 7.36 - 7.33 (m, 1H, Ph p-CH), 7.30 -7.26 (m, 6H, Tr m-CH), 7.23 - 7.20 (m, 3H, Tr p-CH), 7.20 (d,3JH-H = 2.3 Hz, 1 H, NAr m-CH), 7.18 - 7.15 (m, 6H, Tr o-CH), 7.13 (d,3JH-H = 2.1 Hz, 1H, NAr m-CH), 3.19 (d,2JH-H = 14.0 Hz, 1H, Heterocycle CH2), 2.71 (d,2JH-H = 14.0 Hz, 1H, Heterocycle CH2), 2.64 (hept,3JH-H = 6.8 Hz, 1H, (CH3)2CH), 2.28 (hept,3JH-H = 6.8 Hz, 1H, (CH3)2CH), 1.96 (s, 3H, PhCCH3), 1.60 (s, 3H, NC(CH3)2), 1.35 (s, 3H, NC(CH3)2), 1.15 (d,3JH-H = 6.7 Hz, 3H, CH(CH3)2), 1.09 (d,3JH-H = 6.7 Hz, 3H, CH(CH3)2), 0.95 (d,3JH-H = 2.6 Hz, 3H, CH(CH3)2), 0.94 (d,3JH-H = 2.6 Hz, 3H, CH(CH3)2).

[0512] 13C NMR (150 MHz, CDCI3) 5 190.4, 151.2, 145.9, 143.7, 143.1, 140.7, 131.1, 130.2, 128.85, 128.82, 128.7, 127.9, 126.8, 126.6, 125.8, 83.3, 65.4, 55.7, 51.1, 48.6, 30.2, 29.4, 29.1, 27.7, 25.9, 25.8, 22.4, 22.3.

[0513] ESI-MS (MeOH): Calculated for C44H48N ([M-BF4]), m / z 590.3763 Found: m / z 590.3787

[0514] Synthesis of bis-imines

[0515]

[0516] 8a

[0517] N1, N2-Bis(2,6-dimethyl-4-tritylphenyl)ethane-1,2-diimine (8a). In a 100 mL roundbottom flask, glyoxal solution 40% w / w (713 μL, 6.20 mmol), 2,6-dimethyl-4-tritylaniline (3a; 4.51 g, 12.41 mmol) and 5 drops of formic acid were mixed in isopropanol (50 mL). The resulting mixture was refluxed for 18 h to obtain a yellow suspension. The solids were filtered while hot through a glass frit, rinsing with MeOH (3 x 20 mL). The product was dried under high vacuum to obtain N 1, N2-bis(2,6-dimethyl-4-tritylphenyl)ethane-1,2-diimine (8a; 3.72 g, 80%) as a dark yellow powder.

[0518]

[0519] N1, N2-Bis(2,6-diethyl-4-tritylphenyl)ethane-1,2-diimine (8b). As for 8a, but using 2,6-diethyl-4-tritylaniline (3b), to obtain 8b (3.90 g, 83%) as a pale yellow powder.

[0520]

[0521] 8c

[0522] N1, N2-bis(2,6-diisopropyl-4-tritylphenyl)ethane-1,2-diimine (8c). As for 8a, but using 2,6-diisopropyl-4-tritylaniline (3c), to obtain 8c (4.08 g, 88%) as a pale yellow powder.

[0523] Synthesis of Diamine Dihydrochlorides

[0524]

[0525] N1, N2-Bis(2,6-dimethyl-4-tritylphenyl)ethane-1,2-diamine dihydrochloride (9a). In a 250 mL round-bottom flask, glacial acetic acid (7.5 mL, 111.02 mmol) was added dropwise at 0 °C to a suspension of sodium borohydride (1.4 g, 37.01 mmol) in CH2CI2 (70 mL). The reaction mixture was stirred at 0 °C for 10 minutes and then warmed to RT. N1, N2-bis(2,6-dimethyl-4-tritylphenyl)ethane-1,2-diimine (8a; 3.25 g, 4.34 mmol) was added in a single portion and the resulting mixture was stirred for 1 h. The reaction was quenched by adding dropwise saturated ammonium chloride solution (30 mL). The resulting biphasic mixture was stirred until hydrogen evolution ceased. The biphasic mixture was separated, the organic layer was washed with water (2 x 25 mL) and evaporated to obtain a brown crystalline residue. The residue was redissolved in THF (20 mL) and the HCI 0.5 M was added dropwise until pH 1-2, a beige powder precipitated upon the addition of HCI. The solids were filtered, rinsed with water (2 x 20 mL) and Et20 (2 x 30 mL) and dried on a hot plate overnight to obtain N1, N2-bis(2,6-dimethyl-4-tritylphenyl)ethane-1,2-diamine dihydrochloride (9a; 3.27 g, 80%) as a white powder.

[0526]

[0527] N1, N2-Bis(2,6-diethyl-4-tritylphenyl)ethane-1,2-diamine dihydrochloride (9b). As for 9a, but using N1, N2-bis(2,6-diethyl-4-tritylphenyl)ethane-1,2-diimine (8b; 3.9 g, 4.84 mmol) to obtain a yellow crystalline residue. Workup as above afforded 9b (3.25 g, 76%)

[0528]

[0529] N1, N2-bis(2,6-diisopropyl-4-tritylphenyl)ethane-1,2-diamine dihydrochloride (9c).

[0530] As for 9a, but using N1, N2-bis(2,6-diisopropyl-4-tritylphenyl)ethane-1,2-diimine (8c; 4.08 g, 4.74 mmol) to obtain a yellow crystalline residue. Workup as above afforded 9c (3.67 g, 83%) as a white powder.

[0531] Synthesis of p-trityl NHC salts.

[0532]

[0533] 10a

[0534] 1,3-Bis(2,6-dimethyl-4-tritylphenyl)-4,5-dihydro-1 H-imidazol-3-ium chloride (10a).

[0535] In a 25 mL round-bottom flask, N1, N2-bis(2,6-dimethyl-4-tritylphenyl)ethane-1,2-diamine dihydrochloride (9a; 1.0 g, 1.21 mmol), triethyl orthoformate (12.0 mL, 72.64 mmol) and 4 drops of aqueous 2 M HCI were mixed. The reaction was heated at 110 °C for 18 h, with the flask open to allow evaporation of the released EtOH. The reaction mixture was cooled to RT, and diluted with Et20 (20 mL). The solids were filtered, rinsed with Et20 (2 x 20 mL) and dried under high vacuum to obtain 10a (727 mg, 75%) as a white powder.

[0536] 1H NMR (600 MHz, CDCI3) δ 8.58 (s, 1H, NCH), 7.28 - 7.24 (m, 12H, Tr, m-CH), 7.22 -7.17 (m, 18H, Tr o and p-CH), 7.05 (s, 4H, NAr m-CH), 4.77 (s, 4H, Heterocycle CH2), 2.34 (s, 12H, NAr CH₃).

[0537] 13C NMR (151 MHz, CDCI3) 6 158.6, 149.9, 146.1, 134.4, 132.3, 131.1, 130.6, 127.9, 126.4, 65.0, 52.6, 18.7.

[0538] ESI-MS (MeOH): Calculated for C57H51N2 ([M-CI]), m / z 763.4052 Found: m / z 763.4052

[0539]

[0540] 1,3-Bis(2,6-diethyl-4-tritylphenyl)-4,5-dihydro-1H-imidazol-3-ium chloride (10b). As for 10a, but using N1, N2-bis(2,6-diethyl-4-tritylphenyl)ethane-1,2-diamine dihydrochloride (9b; 1.0 g, 1.13 mmol), to obtain 10b (790 mg, 81%) as a white powder.

[0541] 1H NMR (600 MHz, CDCI3) δ 8.07 (s, 1H, NCH), 7.35 -7.29 (m, 12H, Tr m-CH), 7.26 - 7.21 (m, 18H, Tr o and p-CH), 7.15 (s, 4H, NAr m-CH), 4.93 (s, 4H, Heterocycle CH₂), 2.73-2.60 (m, J= 7.4 Hz, 8H, NArCH₂CH₃), 1.17 (t, J= 7.5 Hz, 12H, NArCH2C / 73).13C NMR (151 MHz, CDCI3) 5 157.8, 150.4, 146.1, 140.2, 131.1, 130.6, 128.9, 127.9, 126.4, 65.2, 54.5, 24.5, 15.6.

[0542] ESI-MS (MeOH): Calculated for C61H59N2 ([M-CI]), m / z 819.4678 Found: m / z 819.4678

[0543] QCI

[0544] Ph3C'' \^< J<y^CPh3

[0545]

[0546] 10c

[0547] 1,3-Bis(2,6-diisopropyl-4-tritylphenyl)-4,5-dihydro-1H-imidazol-3-ium (10c). As for 10a, but using N1, N2-bis(2,6-diisopropyl-4-tritylphenyl)ethane-1,2-diamine dihydrochloride (9c; 1.0 g, 1.07 mmol), to obtain 1,3-bis(2,6-diisopropyl-4-tritylphenyl)-4,5-dihydro-1H-imidazol-3-ium (10c; 750 mg, 77%) as a white powder.

[0548] 1H NMR (600 MHz, CDCI3) δ 7.71 (s, 1H, NCHN), 7.30 - 7.23 (m, 12H, Tr m-CH), 7.23 - 7.19 (m, 6H, Tr p-CH), 7.18 - 7.15 (m, 12H, Tr o-CH), 7.12 (s, 4H, NAr m-CH), 4.92 (s, 4H, Heterocycle CH2), 2.93 (hept, J= 6.8 Hz, 4H, NAr-CH(CH3)2), 1.18 (d, J= 6.8 Hz, 12H, NAr-CH(CH3)2), 1.03 (d, J= 6.8 Hz, 12H, NAr-CH(CH3)2).

[0549] 13C NMR (151 MHz, CDCI3) 6 157.4, 150.8, 146.1, 144.9, 131.0, 128.2, 127.9, 126.8, 126.5, 65.4, 56.0, 29.3, 25.3, 23.7.

[0550] ESI-MS (MeOH): Calculated for C65H67N2 ([M-CI]), m / z 875.5304 Found: m / z 875.5304

[0551] Synthesis and Characterization of Trityl Carbenes and Catalysts

[0552]

[0553] 1,3-bis(2,6-dimethyl-4-tritylphenyl)-4,5-dihydro-1 H-imidazol-3-ium-2-ide (TrMes). A suspension of 10a (150 mg, 0.187 mmol) and Li[N(SiMe3)2] (33 mg, 0.197 mmol, 1.05 equiv) in 5 mL THF was stirred for 10 min, over which time it formed a pale-yellow solution. The solution was evaporated to dryness and redissolved in minimal benzene, filtering through Celite, oncentrated, and treated with cold hexanes to precipitate the white product. Yield after filtering and drying under vacuum: 300 mg (83%).

[0554] 1H NMR (C6D6, 500 MHz): d 7.45 (d,3JH-H = 8 Hz, 12H, CPh3o-CH), 7.29 (s, 4H, N-Ar m-C / 7), 7.07 (t,3JH-H = 8 Hz, 12H, CPh3m-CH), 7.00 (t,3JH-H = 8 Hz, 6H, CPh3p-CH), 3.14 (s, 4H, NCH2), 2.16 (s, 12H, N-Ar o-CH3).

[0555] 13C{1H} NMR (C6D6, 125 MHz): 147.5, 140.1, 135.7, 131.7(2), 128.3, 128.1,126.2, 65.4, 50.5, 18.6.

[0556]

[0557] Representative Synthesis of Hoveyda-Class p-Trityl Catalysts. A suspension ofTrMes salt 10a (292 mg, 0.366 mmol, 1.1 equiv vs Ru) and Li[N(SiMe3)2] (64 mg, 0.383 mmol, 1.15 equiv) in 5 mL THF was stirred for 10 min. The suspension dissolved to form a pale-yellow solution within 5 min. It was added to a stirred solution of HI (200 mg, 0.332 mmol) in 3 mL THF to form a brown solution. Over 30 min, the colour turned a dark green. Complete conversion of HI was confirmed by31P NMR analysis, after which free PCy3was removed by adding Merrifield-iodide resin (308 mg, 0.929 mmol, 2.8 equiv) and stirring for 30 min. The solution was then filtered over Celite and evaporated to dryness to yield a green residue, which was extracted with C₆H₆, filtered (Celite), concentrated and reprecipitated with cold hexanes. The green precipitate was filtered off and dried by vacuum to afford 300 mg HTrMes (83% yield).

[0558] 1H NMR (C6D6, 600 MHz): d 16.8 (s, 1H, [Ru]=CH), 7.60 (d,3JH-H = 7 Hz, 12H, CPh3o-C / 7), 7.44 (s, 4H, NAr o-CH), 7.33 (dd,3JH-H = 7,4JH-H = 2 Hz, Ru=CHAr C / 7), 7.20 (dd,3JH-H = 8,3JH-H = 8, 1H, Ru=CHAr C / 7), 7.16 (C6D5H overlap, 12H, NAr m-CH), 7.04 (tt,3JH-H = 7,4JH-H = 2, 6H, CPh3p-CH), 6.74 (td,3JH-H = 7,4JH-H = 2 Hz, Ru=CHAr C / 7), 6.45 (d,3JH-H = 7, 1H, Ru=CHAr C / 7), 4.63 (sept,3JH-H = 6 Hz, 1H, OCH(CH3)2), 3.21 (s, 4H, heterocycle CH2), 2.43 (br s, 12H, NAr CH3), 1.55 (d,3JH-H = 6 Hz, 6H, OCH(CH3)2). Key NMR values are summarized in Table 1.

[0559] 13C{1H} NMR (150 MHz, C6D6) 5289.8, 212.1, 152.9, 148.1, 147.5, 145.9, 138.6, 132.2, 132.0, 131.8, 129.2, 128.4, 126.5, 123.0, 122.5, 113.4, 75.2, 65.7, 51.5, 22.1, 20.1.1H NMR (CDCI3, 600 MHz): d 17.0 (s, 1H, [Ru]=CH), 7.55 (t,3JH-H = 8, 1H, Ru=CHAr C / 7), 7.36 (br s, 12H, CPh3C / 7), 7.32-7.30 (m, 12H, CPh3C / 7), 7.25-7.23 (m, 6H, CPh3C / 7), 7.14 (br s, 6H, NAr m-C / 7), 6.98 (d,3JH-H = 8, 1H, Ru=CHAr C / 7), 6.89 (t,3JH-H = 8, 1H, Ru=CHAr C / 7), 5.02 (sept,3JH-H = 6 Hz, 1H, OCH(CH3)2), 4.14 (s, 4H, heterocycle CH2), 2.44 (br s, 12H, NAr CH3), 1.47 (d,3JH-H = 6 Hz, 6H, OCH(CH3)2).

[0560] 13C{1H} NMR (150 MHz, CDCI3) 5295.0, 211.0, 152.5, 147.5, 146.9, 145.2, 131.8, 131.3, 129.8, 127.7, 126.1, 123.5, 122.5, 113.1, 77.4, 77.2, 76.9, 75.0, 65.0, 51.8, 21.8, 20.8, 19.0.

[0561] 1H NMR (CD2CI2,600 MHZ): 5 16.94 (s, 1H, [Ru]=CH), 7.64-7.58 (m, 1H, Ru=CHAr C / 7), 7.48-7.34 (br d,3JH-H = 7,2 Hz, 12 H, CPh3C / 7), 7.30 (t,3JH-H = 7.7 Hz, 12H, CPh3C / 7), 7.23 (t,3JH-H = 7.2 Hz, 6H, CPh3C / 7), 7.18 (br s, 4H, NAr m-CH), 6.98-6.90 (m, 3H, Ru=CHArC / 7), 5.01 (sept,3JH-H = 6.1 HZ, 1H, OCH(CH3)2), 4.12 (S, 4H, heterocycle CH2), 2.41 (br s, 12H, N-Ar CH3), 1.44 (d,3JH-H = 6.1 Hz, 6H, OCH(CH3)2).

[0562] 13C{1H} NMR (150.89 MHz, CD2CI2): 5 293.26 ([Ru]=CH), 210.62 (NHC carbene), 152.51, 147.36, 145.27, 131.60, 129.90, 128.05, 126.07, 122.84, 113.37, 75.53, 65.33, 21.95. HRMS (ESI+): calculated for C67H62ClN2ORu [M - Cl]+: m / z = 1047.3594, found: m / z = 1047.3598.

[0563]

[0564] HTrC4Ph. As above, but using the HBF4salt 6c. Yield: 273 mg (69%).1H NMR (CDCI3, 600 MHz): d 16.8 (s, 1H), 8.23 (d, 2H), 7.54 (t, 2H), 7.47 (t, 1H), 7.41-7.34 (m, 10H), 7.32 (t, 6H), 7.25 (m, 4H), 4.92 (sept, 1H), 3.12 (d, 1H), 3.03-2.93 (m, 4H), 2.33 (d, 1H) 2.32 (s, 4H), 1.52 (m, 6H), 1.40 (s, 3H), 1.35 (d, 3H), 1.16 (d, 3H), 1.08 (d, 3H), 0.64 (d, 3H), 0.32 (d, 3H).

[0565] 13C{1H} NMR (150 MHz, CDCI3) 5298.6, 264.2, 152.8, 147.8, 146.9, 146.8, 146.6, 143.0, 142.2, 133.8, 130.9, 130.8, 129.4, 129.1, 128.8, 128.6, 128.4, 127.7, 127.5, 126.1, 124.1, 121.7, 113.3, 77.5, 74.6, 65.1, 62.9, 48.0, 32.9, 28.9, 28.7, 28.1, 27.4, 26.7, 25.8, 23.9, 23.8, 22.7.

[0566]

[0567] HTrC3Ph. As above, but using the HBF4salt 6a. Yield: 210 mg (74%).1H NMR (CDCI3, 600 MHz): d 17.7 (s, 1H), 16.73 (s, 0.6H), 8.16 (d, 1H), 7.72 (d, 2H), 7.55-7.48 (m, 3H), 7.37-7.32 (m, 6H), 7.30-7.17 (m, 30H), 7.14 (s, 1.2H), 7.02 (s, 1.2H), 6.92 (d, 1H), 6.88 (t, 1H), 6.82 (d, 0.6H), 6.78 (t, 0.6H), 6.51 (d, 0.6H), 5.05 (sept, 1H), 4.93 (sept, 0.6H), 3.08 (d, 0.6H), 2.54 (s, 4H), 2.40 (d, 1.2H), 2.37 (s, 4H), 2.30 (s, 2H), 2.27 (s, 2H), 2.16 (s, 2H), 1.95 (s, 3H), 1.58 (s, 3H), 1.46-1.44 (m, 9H), 1.41 (d, 3H), 1.34 (s, 3H), 1.31 (d, 3H), 1.24 (s, 6H), 1.17 (s, 3H), 0.95 (d, 1H), 0.87-0.81 (m, 9H).

[0568] Synthesis of Grubbs-Class Trityl NHC Catalysts

[0569]

[0570] CPh3

[0571] RuCI2(NHC)(PCy3)(=CHPh) (NHC =TrMes); GTrMes. A suspension ofTrMes salt 10a (107 mg, 0.134 mmol, 1.1 equiv vs Ru) and Li[N(SiMe3)2] (24 mg, 0.140 mmol, 1.05 equiv) in 2 mL toluene was stirred for 10 min. The resulting pale-yellow carbene solution was added to a stirring solution of Gl (100 mg, 0.121 mmol) in 3 mL toluene. A colour change from purple to red occurred over 10 min. Stirring was continued for 2 h, after which the reaction was concentrated to ca. 2 mL, filtered (Celite), concentrated, and treated with cold hexanes to precipitate the product. The dark pink solid was isolated by filtration. Yield: 120 mg (76%). Key NMR values: Table 1.

[0572]

[0573] RuCI2(NHC)(py)2(=CHPh) (NHC =TrMes); GpyTrMes. To a solution of the PCy3-stabilized complex GTrMes (110 mg, 0.083 mmol) in 2 mL toluene was added pyridine (0.130 mL, 131 mg, 1.66 mmol, 20 equiv vs Ru). The solution was stirred for 15 min, after which cold hexanes (ca. 15 mL) was added to precipitate the product as a bright green solid suspended in an orange solution. The bright green solid was isolated by filtration. Yield after washing with hexanes and drying under vacuum: 70 mg (80%). Key NMR values: Table 1.

[0574] Synthesis of Grubbs-Class Trityl CAAC Catalysts

[0575]

[0576] RuCI2(CAAC)(py)2(=CHPh) (CAAC =TrC3Ph); GpyTrC3Ph. In a representative procedure, a suspension ofTrC3Phsalt 6a (60 mg, 0.096 mmol, 1.0 equiv vs Ru) and Li[N(SiMe3)2] (15 mg, 0.090 mmol, 1.05 equiv) in 2 mL toluene was stirred for 10 min. The solution becomes transparent with a pale-yellow colour within 5 min of stirring. The carbene solution was then added over 2 min to a stirring 3 mL toluene solution of GIpy(60 mg, 0.096 mmol). During the addition, a colour change from deep green to brown occurs. After 15 min stirring the solution was concentrated to ca. 2 mL, filtered (Celite), concentrated, and treated with cold hexanes. The bright green product was isolated by filtration. Yield: 33 mg (39%). Key NMR values: Table 1. Table 1. Key NMR data for p-Trityl Carbene Catalysts.

[0577] product solvent1H alkylidene13C31P PCys alkylidene

[0578] HTrMes CDCh 17.00 294.9

[0579] HTrMes C6D617.22 289.6

[0580] HTrC4PhCDCh 16.81 298.5

[0581] HTrC3PhCDCh 17.72, 16.73 295.7

[0582] GTrMes CDCh 19.39 N. D.a18.8

[0583] GTrMes C6D619.92 N. D.a21.1

[0584] GpyTrMes CDCh 19.37 315.2

[0585] GpyTrC3PhCDCh 18.85 324.2

[0586] aNot determined.

[0587] Scheme3. Imidazolinium Chlorides 10d, 10e, and 10f were or are prepared as outlined below. See further below for full procedure and characterization data for

[0588] 10f and related intermediates.

[0589] iPrOH reflux, 18h 2d Ar = Ar12e Ar = Ar23e Ar = Ar28e Ar = Ar22f Ar = Ar33f Ar = Ar38f Ar = Ar3

[0590] 1. NaBH4, AcOH, CH2CI2, RT, 1h 2. HCI

[0591] 10d Ar= Ar110e Ar = Ar2

[0592]

[0593] 10f Ar = Ar32,6-Bimethyl-4-(tri([1,1 '-biphenyl]-4-yl)methyl)aniline (3d) was prepared as for 3a but using tri ([ 1, 1 '-biphenyl]-4-yl)methanol 2d. The product 2, 6-d i methy l-4-(tri ( [ 1, 1 '-biphenyl]-4-yl)methyl)aniline (10.06 g, 91%) was obtained as a white crystalline powder.1H NMR (400 MHz, CDCI3) 67.66 (d, J = 7.2 Hz, 6H), 7.56 (d, J = 8.5 Hz, 6H), 7.49 - 7.40 (m, 13H), 7.35 (t, J= 7.4 Hz, 3H), 6.93 (s, 2H), 3.59 (s, 2H), 2.16 (s, 6H).

[0594] 2.6-Bimethyl-4-(tris(4-(tert-butyl)phenyl)methyl)aniline (3e) was prepared as for 3a but using tris(4-(tert-butyl)phenyl)methanol 2e. The product (6.62 g, 66%) was obtained as a white crystalline powder.1H NMR (300 MHz, CDCI3) 67.22 (d, J= 8.5 Hz, 6H), 7.10 (d, J= 8.3 Hz, 6H), 6.76 (s, 2H), 2.11 (s, 6H), 1.31 (s, 28H).

[0595] 2.6-Bimethyl-4-(tris(3,5-dimethylphenyl)methyl)aniline (3f) was prepared as for 3a but using tris(3,5-dimethylphenyl)methanol 2f.

[0596] N1, N2-Bis(2,6-dimethyl-4-(tri([1, T-biphenyl]-4-yl)methyl)phenyl)ethane-1,2-diimine (8d) was prepared as for 8a but using 2,6-Bimethyl-4-(tri([1,1'-biphenyl]-4-yl)methyl)aniline (3d) to obtain the product (4.08 g, 89%) as a pale-yellow powder. N1, N2-Bis(2,6-dimethyl-4-(tris(4-(tert-butyl)phenyl)methyl)phenyl)ethane-1,2-diimine (8e) was prepared as for 8a but using 2,6-Bimethyl-4-(tris(4-(tert-butyl)phenyl)methyl)aniline (3e) to obtain the product (4.08 g, 91%) as a pale-yellow powder.

[0597] N1, N2-Bis(2,6-dimethyl-4-(tris(3,5-dimethylphenyl)methyl)phenyl)ethane-1,2-diimine (8f) was prepared as for 8a but using 2,6-dimethyl-4-(tris(3,5-dimethylphenyl)methyl)aniline (3f).

[0598] N1, N2-Bis(2,6-dimethyl-4-(tri([1, T-biphenyl]-4-yl)methyl)phenyl)ethane-1,2-diamine dihydrochloride (9d) is prepared as for 9a, but using N1, N2-bis(2,6-dimethyl-4-(tri ([ 1, 1 '-biphenyl]-4-yl)methyl)phenyl)ethane-1,2-diimine (8d).

[0599] N1, N2-Bis(2,6-dimethyl-4-(tris(4-(tert-butyl)phenyl)methyl)phenyl)ethane-1,2-diamine dihydrochloride (9e) is prepared as for 9a, but using N1, N2-bis(2,6-dimethyl-4-(tris(4-(tert-butyl)phenyl)methyl)phenyl)ethane-1,2-diimine (8e).

[0600] N1, N2-Bis(2,6-dimethyl-4-(tris(3,5-dimethylphenyl)methyl)phenyl)ethane-1,2-diamine dihydrochloride (9f) was prepared as for 9a, but using N1, N2-bis(2,6-dimethyl-4-(tris(3,5-dimethylphenyl)methyl)phenyl)ethane-1,2-diimine (8f).

[0601] 1.3-Bis(2,6-dimethyl-4-(tri([1,1 '-biphenyl]-4-yl)methyl)phenyl)-4,5-dihydro-1 H-imidazol-3-ium chloride (10d) is prepared as for 10a, but using N1, N2-bis(2,6-dimethyl-4-(tri ([ 1, 1 '-biphenyl]-4-yl)methyl)phenyl)ethane-1,2-diamine dihydrochloride (9d).

[0602] 1.3-Bis(2,6-dimethyl-4-(tris(4-(tert-butyl)phenyl)methyl)phenyl)-4,5-dihydro-1H-imidazol-3-ium (10e) is prepared as for 10a, but using N1, N2-bis(2,6-dimethyl-4-(tris(4-(tert-butyl)phenyl)methyl)phenyl)ethane-1,2-diamine dihydrochloride (9e).

[0603] 1.3-Bis(2,6-dimethyl-4-(tris(3,5-dimethylphenyl)methyl)phenyl)-4,5-dihydro-1H-imidazol-3-ium (10f) was prepared as for 10a, but using N1, N2-bis(2,6-dimethyl-4-(tris(3,5-dimethylphenyl)methyl)phenyl)ethane-1,2-diamine dihydrochloride (9f) Scheme 4. Imidazolinium Chloride 10h is prepared as outlined below, see below for full procedure and characterisation data for 3h, 8h and related 10h’.

[0604]

[0605] 2,6-Dibenzhydryl-4-tritylaniline (3h) is prepared as for 2,4,6-tribenzhydrylaniline,1but using 4-tritylaniline (3g) and 2 equiv. of diphenylmethanol.

[0606] N1, N2-Bis(2,6-dibenzhydryl-4-tritylphenyl)ethane-1,2-diimine (8h) is prepared as for 8a but using 2,6-di benzhydryl-4-tritylaniline (3h).

[0607] N1, N2-Bis(2,6-dibenzhydryl-4-tritylphenyl)ethane-1,2-diamine dihydrochloride (9h) is prepared as for 9a, but using N1, N2-bis(2,6-dibenzhydryl-4-tritylphenyl)ethane- 1.2-diimine (8h).

[0608] 1.3-Bis(2,6-dibenzhydryl-4-tritylphenyl)-4,5-dihydro-1 H-imidazol-3-ium chloride (10h) is prepared as for 10a, but using N1, N2-bis(2,6-dibenzhydryl-4-tritylphenyl)ethane-1,2-diamine dihydrochloride (9h).

[0609] Scheme 5. Imidazolinium Chloride 10i is prepared as outlined below.

[0610] RC2= (triphenylsilyl)ethynyl

[0611]

[0612] 10i 9i ((4-Bromo-3,5-dimethylphenyl)ethynyl)triphenylsilane (3i) is prepared as for [(pentafluorophenyl)ethynyl]triphenylsilane,2but using 2-bromo-5-iodo-1,3- dimethylbenzene (2i) instead of bromopentafluorobenzene.

[0613] N1, N2-Bis(2,6-dimethyl-4-((triphenylsilyl)ethynyl)phenyl)ethane-1,2-diamine (8i) is prepared as for N1, N2-bis(3,5-dimethyl-3',4',5'-triphenyl-[1, T:2',1"-terphenyl]-4- yl)ethane-1,2-diamine,3but using ((4-bromo-3,5-dimethylphenyl)ethynyl)triphenylsilane (3i) instead of 4-bromo-3,5-dimethyl-3', 4', 5'-triphenyl-1,1':2',1 "-terphenyl.

[0614] N1, N2-Bis(2,6-dimethyl-4-((triphenylsilyl)ethynyl)phenyl)ethane-1,2-diamine dihydrochloride (9i) is prepared as described for 9a: to a solution of diamine (8i) in THF, HCI 0.5 M is added dropwise until pH 1-2. The solid is filtered, rinsed with water and Et20, and dried on a hot plate overnight to deliver the title compound N1, N2-bis(2,6- dimethyl-4-((triphenylsilyl)ethynyl)phenyl)ethane-1,2-diamine dihydrochloride (9i).

[0615] 1,3-Bis(2,6-dimethyl-4-((triphenylsilyl)ethynyl)phenyl)-4,5-dihydro-1H-imidazol-3- ium chloride (10i) is prepared as for 10a, but using N1, N2-bis(2,6-dimethyl-4- ((triphenylsilyl)ethynyl)phenyl)ethane-1,2-diamine dihydrochloride (9i).

[0616] Scheme 6. Imidazolinium Chloride 101 is prepared as outlined below.

[0617] HCI

[0618]

[0619] ((5-Bromo-2,4,6-trimethyl-1,3-phenylene)bis(prop-2-yne-3,1,1,1- tetrayl))hexabenzene (3I) is prepared as for 1,4-bis(3,3,3-triphenylpropynyl)benzene,4but using 1-bromo-3,5-diiodo-2,4,6-trimethylbenzene (2I) and 2 equiv. of 3,3,3- triphenylpropyne. 1-bromo-3,5-diiodo-2,4,6-trimethylbenzene5(2I) and 3,3,3- triphenylpropyne6are prepared according to known literature procedures.

[0620] N1, N2-Bis(2,4,6-trimethyl-3,5-bis(3,3,3-triphenylprop-1-yn-1-yl)phenyl)ethane-1,2- diamine (8I) is prepared as for N1, N2-bis(3,5-dimethyl-3',4',5'-triphenyl-[1,1':2',1"- terphenyl]-4-yl)ethane-1,2-diamine,3but using ((5-bromo-2,4,6-trimethyl-1,3-phenylene)bis(prop-2-yne-3,1,1,1-tetrayl))hexabenzene (3I) instead of 4-bromo-3,5-dimethyl-3', 4', 5'-triphenyl-1,1':2',1 "-terphenyl.

[0621] N1, N2-Bis(2,4,6-trimethyl-3,5-bis(3,3,3-triphenylprop-1-yn-1-yl)phenyl)ethane-1,2-diamine dihydrochloride (9I) is prepared as described for 9a: to a solution of diamine (8I) in THF, HCI 0.5 M is added dropwise until pH 1-2. The solid is filtered, rinsed with water and Et20, and dried on a hot plate overnight to deliver the title compound N1, N2-bis(2,4,6-trimethyl-3,5-bis(3,3,3-triphenylprop-1-yn-1-yl)phenyl)ethane-1,2-diamine dihydrochloride (9I).

[0622] 1,3-Bis(2,4,6-trimethyl-3,5-bis(3,3,3-triphenylprop-1 -yn-1 -yl)phenyl)-4,5-dihydro- 1 H-imidazol-3-ium chloride (101) is prepared as for 10a, but using N1, N2-bis(2,4,6-trimethyl-3,5-bis(3,3,3-triphenylprop-1-yn-1-yl)phenyl)ethane-1,2-diamine dihydrochloride (9I).

[0623] Scheme 7. CAAC Salt 6m is prepared as outlined below.

[0624] 1 rui® @ p— CF3SO3H, p[q^_p _ / , f-AmOK benzene, 25°C, 4h THF / toluene, 0-5°C, overnight 2. H2SO4(5M), 55 °C, THF / toluene, overnight

[0625] K2CO3, PTSA = p-toluensulfonic acid Bu4N+I-,

[0626] H2O, toluene 70°C 18h

[0627] 2. HCI, 75 °C, toluene, 24h

[0628]

[0629] 3. NaBF4_ water / DCM RT, 1h 3,3-Diphenyl-2,3-dihydro-1H-indene-1-carbaldehyde (3m) is prepared as for 2,3-dihydro-1H-indene-1-carbaldehyde7but using 3,3-diphenyl-2,3-dihydro-1H-inden-1-one (2m). 2m is prepared from 1,3-indandione (1m) according to literature procedure.8

[0630] 1 -(2-Methylallyl)-3,3-diphenyl-2,3-dihydro-1 H-indene-1 -carbaldehyde (4m) is prepared as for 2,4-dimethyl-2-phenylpent-4-enal (4) but using 3,3-diphenyl-2,3-dihydro-1 H-indene-1 -carbaldehyde (3m).

[0631] 1,-(2,6-Dimethyl-4-tritylphenyl)-4,,4,-dimethyl-3,3-diphenyl-2,3,4,,5'-tetrahydrospiro[indene-1,3'-pyrrol]-1'-ium tetrafluoroborate (6m) is prepared as for 1-(2,6-dimethyl-4-tritylphenyl)-2,2,4-trimethyl-4-phenyl-3,4-dihydro-2H-pyrrol-1-ium tetrafluoroborate (6a), but using 1-(2-methylallyl)-3,3-diphenyl-2,3-dihydro-1H-indene-1-carbaldehyde (4m).

[0632] Scheme 8. CAAC Salt 6n is prepared as outlined below.

[0633]

[0634] 2.7-Diphenyl-9H-fluorene (2n) is prepared from 2,7-dibromo-9H-fluorene (1n) according to literature procedure.9

[0635] 2.7-Diphenyl-9H-fluorene-9-carbaldehyde (3n) is prepared as for 9H-fluorene-9-carbaldehyde10but using 2,7-diphenyl-9H-fluorene (2n).

[0636] 9-(2-Methylallyl)-2,7-diphenyl-9H-fluorene-9-carbaldehyde (4n) is prepared as for 2,4-dimethyl-2-phenylpent-4-enal (4) but using 2,7-diphenyl-9H-fluorene-9-carbaldehyde (3n).

[0637] 1 '-(2,6-Dimethyl-4-tritylphenyl)-4',4'-dimethyl-2,7-diphenyl-4',5'-dihydrospiro[fluorene-9,3'-pyrrol]-1'-ium tetrafluoroborate (6n) is prepared as for 1-(2,6-dimethyl-4-tritylphenyl)-2,2,4-trimethyl-4-phenyl-3,4-dihydro-2H-pyrrol-1-ium tetrafluoroborate (6a), but using 9-(2-methylallyl)-2,7-diphenyl-9H-fluorene-9-carbaldehyde (4n).

[0638] Scheme 9. CAAC Salt 6o was prepared as outlined below.

[0639] OH

[0640] AcOH, HCI, reflux 5h

[0641]

[0642] 2. HCI, 75 °C, toluene, 24h 6o 3. NaBF4water / DCM RT, 1h

[0643] PTSA = p-toluensulfonic acid 2-(Tert-butyl)-4-tritylaniline (3o) was prepared as for 2,6-dimethyl-4-tritylaniline (3a) but using 2-(tert-butyl)aniline (2o). The product (5.50 g, 75%) was obtained as a white crystalline powder.

[0644] 1-(2-(Tert-butyl)-4-tritylphenyl)-3,3,4-trimethyl-4-phenyl-3,4-dihydro-2H-pyrrol-1- ium tetrafluoroborate (60) was prepared as for 1-(2,6-dimethyl-4-tritylphenyl)-2,2,4-trimethyl-4-phenyl-3,4-dihydro-2H-pyrrol-1-ium tetrafluoroborate (6a), but using 2-(tert- butyl)-4-tritylaniline (3o, 2.0 g, 5.10 mmol), to obtain 60 as a mixture of atropisomers 60:40 (1.85 g, 56%) as a beige powder.1H NMR (600 MHz, CDCl3) δ 9.89 (s, 1H), 9.43 (s, 1H), 7.60 (d, J = 2.1 Hz, 1H), 7.53 - 7.41 (m, 8H), 7.30 (m, 16H), 7.26 - 7.16 (m, 20H), 6.74 (d, J = 8.5 Hz, 1H), 3.19 (d, J = 13.8 Hz, 1H), 3.08 (d, J = 13.4 Hz, 1H), 2.77 (d, J = 13.4 Hz, 1H), 2.57 (d, J = 13.8 Hz, 1H), 2.02 (s, 2H), 1.88 (d, J = 4.2 Hz, 6H), 1.55 (d, J = 4.6 Hz, 6H), 1.37 (s, 3H), 1.31 (s, 9H), 1.28 (s, 2H), 0.97 (s, 6H).

[0645] 13C NMR (150 MHz, CDCl3) δ 189.3, 187.7, 150.5, 150.3, 145.7, 145.6, 143.8, 143.0, 140.7, 139.9, 136.0, 135.4, 131.1, 131.0, 130.1, 129.8, 129.4, 129.2, 128.9, 128.9, 128.5, 128.3, 127.8, 127.8, 127.4, 126.8, 126.5, 126.4, 125.6, 125.6, 125.4, 82.1, 81.4, 64.9, 55.2, 55.1, 48.9, 47.0, 38.0, 37.4, 33.3, 30.8, 30.3, 29.9, 28.3, 28.1, 27.1, 26.0.

[0646] HTrC5Ph

[0647] Bu

[0648] N

[0649] oCI

[0650]

[0651] HTrC5Phwas synthesised as for HTrC3Phusing the HBF4 salt of 60. Yield: 120 mg (82%).

[0652] 1H NMR (600 MHz, C6D6) δ 18.28 (s, 1H), 9.02 (dd, J= 8.4, 1.2 Hz, 2H), 7.85 (d, J= 7.9 Hz, 2H), 7.82 (t, J= 1.7 Hz, 1H), 7.66 (dt, J= 8.4, 1.7 Hz, 1H), 7.54 (dt, J= 8.5, 1.3 Hz, 7H), 7.26 (t, J = 7.5 Hz, 2H), 7.21 (d, J= 7.3 Hz, 5H), 7.11 - 7.06 (m, 4H), 6.92 (dt, J = 7.7, 1.6 Hz, 1 H), 6.53 (t, J = 7.4 Hz, 1 H), 6.47 (d, J = 8.3 Hz, 1 H), 4.66 (h, J = 6.1 Hz, 1H), 2.19 (m, 4H), 2.02 (dd, J= 12.5, 1.5 Hz, 1H), 1.53 (d, J= 6.2 Hz, 6H), 1.51 (s, 9H), 1.37 (s, 3H), 1.03 (s, 2H).13C NMR (150 MHz, C6D6) δ 274.70, 153.83, 151.02, 147.50, 147.09, 146.82, 143.78, 137.07, 136.73, 132.74, 131.48, 130.23, 128.30, 126.82, 126.36, 126.22, 123.19, 121.73, 112.93, 74.43, 73.71, 65.29, 63.98, 55.00, 37.33, 33.42, 32.56, 28.91, 26.78, 22.08, 21.78. Scheme 10. CAAC Salt 6p is prepared as outlined below. See further below for full procedure and characterization data for 6p and related intermediates.

[0653] 1. PTSA, MgSO4, toluene,

[0654] reflux, 24 h

[0655]

[0656] 2. HCI, 75 °C, toluene, 24h

[0657] 3. NaBF4water / DCM RT, 1h

[0658] PTSA = p-toluensulfonic acid

[0659] 1-(2,6-Dibenzhydryl-4-tritylphenyl)-3,3,4-trimethyl-4-phenyl-3,4-dihydro-2H-pyrrol-1-ium tetrafluoroborate (6p) is prepared as for 1-(2,6-dimethyl-4-tritylphenyl)-2,2,4-trimethyl-4-phenyl-3,4-dihydro-2H-pyrrol-1-ium tetrafluoroborate (6a), but using 2,6-dibenzhydryl-4-tritylaniline (3h). The synthesis of 3h is described in Scheme 4.

[0660] Scheme11. CAAC Salt 6q is prepared as outlined below.

[0661]

[0662] 3. NaBF4water / DCM RT, 1h

[0663] PTSA = p-toluensulfonic acid

[0664] 1'-(2,6-Dibenzhydryl-4-tritylphenyl)-4',4'-dimethyl-2,3,4',5'-tetrahydrospiro[indene-1,3'-pyrrol]-1'-ium tetrafluoroborate (6q) is prepared as for 1-(2,6-dimethyl-4-tritylphenyl)-2,2,4-trimethyl-4-phenyl-3,4-dihydro-2H-pyrrol-1-ium tetrafluoroborate (6a), but using 2,6-dibenzhydryl-4-tritylaniline (3h) and 1-(2-methylallyl)-2,3-dihydro-1H-indene-1-carbaldehyde (4q). 4q is according to literature procedure.7The synthesis of 3h is described in Scheme 4.

[0665] References

[0666] (1) Dai, S.; Li, S. Effect of Aryl Orientation on Olefin Polymerization in Iminopyridyl Catalytic System. Polymer 2020, 200, 122607. https: / / doi. Org / 10.1016 / j.polymer.2020.122607. (2) Linnemannstöns, M.; Neumann, B.; Stammler, H.-G.; Mitzel, N. W. Synthesis and Structural Diversity of Triaryl(Phenylethyl)Silanes. Synthesis 2020, 52, 1025-1034. https: / / doi. Org / 10.1055 / S-0039- 1690785.

[0667] (3) Fujihara, T.; Tomike, Y.; Ohtake, T.; Terao, J.; Tsuji, Y. Ruthenium-Catalyzed Ring-Closing Metathesis Accelerated by Long-Range Steric Effect. Chem. Commun.

[0668] 2011, 47, 9699-9701. https: / / doi.org / 10.1039 / C1CC13304G.

[0669] (4) Dominguez, Z.; Dang, H.; Strouse, M. J.; Garcia-Garibay, M. A. Molecular “Compasses” and “Gyroscopes”. I. Expedient Synthesis and Solid State Dynamics of an Open Rotor with a Bis(Triarylmethyl) Frame. J. Am. Chem. Soc. 2002, 124, 2398-2399. https: / / doi.org / 10.1021 / ja0119447.

[0670] (5) Kajigaeshi, S.; Kakinami, T.; Moriwaki, M.; Tanaka, T.; Fujisaki, S.; Okamoto, T. Halogenation Using Quaternary Ammonium Polyhalides. XIV. Aromatic Bromination and Iodination of Arenes by Use of Benzyltrimethylammonium Polyhalides-Zinc Chloride System. Bull. Chem. Soc. Jpn. 1989, 62, 439-443. https: / / doi.org / 10.1246 / bcsj.62.439. (6) Dominguez, Z.; Dang, H.; Strouse, M. J.; Garcia-Garibay, M. A. Molecular “Compasses” and “Gyroscopes.” III. Dynamics of a Phenylene Rotor and Clathrated Benzene in a Slipping-Gear Crystal Lattice. J. Am. Chem. Soc. 2002, 124, 7719-7727. h ttps: / / do i. org / 10.1021 / ja025753v.

[0671] (7) Gawin, R.; Tracz, A.; Krajczy, P.; Kozakiewicz-Piekarz, A.; Martínez, J. P.; Trzaskowski, B. Inhibition of the Decomposition Pathways of Ruthenium Olefin Metathesis Catalysts: Development of Highly Efficient Catalysts for Ethenolysis. J. Am. Chem. Soc. 2023, 145, 25010-25021. https: / / doi.org / 10.1021 / jacs.3c10635.

[0672] (8) Koltunov, K. Yu. Superacidic and HUSY-Zeolite Activation of 1,3-lndandione: Reactions with Benzene and Cyclohexane. Tetrahedron Lett. 2007, 48, 5631-5634. https: / / doi. Org / 10.1016 / j.tetlet.2007.06.023.

[0673] (9) Nakazono, K.; Yamashita, C.; Ogawa, T.; Iguchi, H.; Takata, T. Synthesis and Properties of Pendant Fluorene Moiety-Tethered Aliphatic Polycarbonates. Polym. J.

[0674] 2015, 47, 355-361. https: / / doi. Org / 10.1038 / pj.2015.7.

[0675] (10) Erdélyi, Á.; Farkas, V.; Turczel, G.; Nagyházi, M.; Bényei, A.; Recta, M. L. L.; Nagy, T.; Kéki, S.; Osterthun, O.; Klankermayer, J.; Tuba, R. Synthesis and Application of Robust Spiro [Fluorene-9] CAAC Ruthenium Alkylidene Complexes for the “One-Pot” Conversion of Allyl Acetate to Butane-1,4-Diol. Chem. - Eur. J. 2024, 30, e202401918. https: / / doi.org / 10.1002 / chem.202401918.

[0676] Assessing Impact of Remote Bulk on Catalyst Decomposition.

[0677] Representative procedure: A solution of RuCl2(NHC)(py)2(=CHPh), Gill (10 mg, 0.013 mmol) and DMT (ca. 1 mg; internal standard) was dissolved in 0.6 mL CDCl3and transferred to a screw-cap NMR tube. The sample was analyzed (1H NMR) within 10 min of dissolution to determine the initial ratio of GIII: DMT. A solution of HCI (6 pL of a 2.0 M solution in Et2O, 1 equiv) was then added via gas-tight syringe. The puncture was sealed with Parafilm, and stirring was conducted at RT (ca. 25 °C) by attaching the NMR tube to a rotary mixer. The sample was analyzed periodically to assess decomposition of Gill and formation of stilbene (Table 2).

[0678] Over 10% of Gill had decomposed at 2 h, at which point the trityl analogue was completely unaffected (0% of GpyTrMes had decomposed at 2 hr). The latter complex remained 84% intact at 24 h.

[0679] Table 2. Bimolecular decomposition of labile, pyridine-stabilized precatalysts.a

[0680] 1 equiv HCI

[0681] CDCI3Ph

[0682] - ► 0.5 |l + decomposed Ru

[0683] 25 °C, 24 h ^ph

[0684]

[0685] internal standard, IS c

[0686] Gill: L = H2IMes

[0687] GpyTrMes: L =TrMes

[0688] entry catalyst time (h) % catalyst % stilbene (5) 1 Gill 2 87 5

[0689] 2 Gill 24 6 64

[0690] 3 GpyTrMes 2 100 0

[0691] 4 GpyTrMes 24 84 15

[0692] aA standard relaxation time of 30 s was used for quantitation.

[0693] Assessing Impact of Remote Bulk on Catalysis.

[0694] Representative procedure for Ethenolysis of Methyl Oleate (MO). In the glovebox, a solution of DMT (ca. 10 mg, 0.05 mmol, 0.02 equiv) in 100 mL toluene was added to (1 mL, 0.874 g, 2.95 mmol) to form a clear, colourless solution. The solution was then transferred to a glass-lined pressure reactor equipped with a stirring bar, warmed to 30 °C, and stirred for 5 min to ensure total dissolution of the internal standard. An aliquot was removed for1H NMR analysis to establish the initial ratio of MO: DMT, while allowing the reaction to cool to RT. Catalyst HTrC3Ph(2.5 pL of a stock solution of 10.0 mg in 1.0 mL C₆H₆; 0.0295 pmol, 0.001 mol%) was then added. The reactor was assembled, transferred from the glovebox, and connected to ethylene (99.9% purity). The gas line was purged 5x, the reactor was pressurized to 100 psi, sealed, and stirring was commenced. After 2 h, the reactor was vented and metathesis was quenched by addition of KTp (10 equiv vs. starting Ru) and stirred for 1 min. A 0.1 mL aliquot was removed for NMR analysis. The sample was diluted with ca. 0.5 mL CDCh and the conversion of MO and yields of 1 / 2 were assessed by1H NMR analysis, from integration of their olefinic signals (MO: 5.33 ppm; 1 / 2: 5.78 ppm) vs DMT internal standard (8.01 ppm). Catalytic results are summarized in Table 3. Notable is the drop in TONs for Hll as catalyst concentrations increase, in contrast with HTrMes. The apparent increase in TON for the latter is presumably an artifact arising from the difficulty in accurately measuring yields at the lowest level (3%). These data suggest that the trityl catalyst resists bimolecular coupling, which leads to bimolecular degradation.

[0695] Table 3. Probing the impact of remote steric bulk on productivity in cross-metathesis of methyl oleate (MO) with ethylene (ethenolysis)

[0696]

[0697] entry catalyst mol % CM yield (%) TON

[0698] 1 Hll 0.001 1 1,000 2 Hll 0.010 2 200

[0699] 3 Hll 0.015 4 250

[0700] 4 HTrMes 0.001 3 3,000 5 HTrMes 0.010 19 1,900 6 HTrMes 0.015 56 3,700 7 HTrC3Ph0.001 2.5 2,500 8 HTrC3Ph0.010 46 4,600aReproducibility ±2% in replicate runs.

[0701] Representative Procedure for Cross-Metathesis (CM) of Styrene with Methyl Acrylate (MA). Styrene (46 iL, 42 mg, 0.4 mmol), MA (145 iL, 76 mg, 1.60 mmol, 4 equiv) and DMT (10 mg, 0.051 mmol, 0.5 equiv) were diluted to 2 mL with C7H8(final concentration 200 mM styrene), and the initial ratio of styrene: DMT was assessed as above. The reaction was stirred at 70 °C for 10 min, after which HTrMes (250 μL of a 10 mg / mL C₆H₆ solution, 0.004 mmol, 1 mol%) was added. The reaction was quenched after 24 h with KTp and analyzed as above (1H NMR, CDCh: styrene (d, 5.87 ppm); product (d, 7.62 ppm); DMT (8.01 ppm)). The results are summarized in Table 4. Notable are the significantly higher yields for HTrMes, again consistent with greater resistance to bimolecular coupling (and thus bimolecular degradation). The absence of an increase in yields for Hll even on increasing loadings five-fold (from 0.01 to 0.05 mol%) is more unexpected. The styrene conversion increases in these reactions, however, may indicate that the acrylate contributes to a further, as-yet unidentified decomposition pathway. The trityl catalyst is likewise affected, but to a lesser extent: that is, Hll undergoes both acrylate-induced decomposition and bimolecular degradation.

[0702] Table 4. Probing the impact of remote steric bulk on productivity in styrene-acrylate CM.

[0703] o

[0704] 70 °C, 24 h − C2H2(CO2Me)2

[0705]

[0706] entry catalyst mol % conv. styrene (%) yield (%) TON 1 Hll 0.01 52 45 4500 2 Hll 0.025 58 44 1760 3 Hll 0.05 78 46 920 4 Hll 0.1 98 57 570 5 HTrMes 0.01 76 64 6400 6 HTrMes 0.025 88 73 2920 7 HTrMes 0.05 95 80 1600 8 HTrMes 0.1 100 100 1000aReproducibility ±2% in replicate runs.

[0707] Representative Procedure for CM of Substituted Stilbene with Methyl Acrylate. As for styrene, using solid, substituted stilbene (30 mg, 0.11 mmol), MA (40 pL, 38 mg, 0.44 mmol, 3 equiv) and DMT (10 mg, 0.051 mmol, 0.5 equiv) in 1.5 mL EtOAc (final stilbene concentration 75 mM), with HTrMes (12 pL of a 10 mg / mL C₆H₆ solution, 0.011 pmol, 0.1 mol%). Analysis: stilbene o-CH (7.01-6.98 ppm (m, 4H)) or product (7.57 ppm (d, 1H)) vs DMT (8.01 ppm). The catalytic results are summarized in Table 5. HTrMes is nearly twice as productive as Hll.

[0708] Table 5. Probing the impact of remote steric bulk on productivity in stilbene-acrylate CM.

[0709]

[0710] entry catalyst mol% equiv MA % conversion % yield3

[0711] 1 Hll 0.1 4 76 55

[0712] 2 HTrMes 0.1 2 95 68

[0713] 3 HTrMes 0.1 6 100 88

[0714] 4 HTrMes 0.1 4 100 92

[0715] aStyrene accounts for the mass balance in all cases.

[0716] Representative Procedure for Ring-Closing Metathesis of diethyl 2,2-bis(2-methylprop-1 -en-1 -yl)malonate (11 ).

[0717] EtO2C CO2Et

[0718] Cat (1% mol)

[0719] C6D6(0.1 M),

[0720]

[0721] 60°C, NMR tube 12

[0722] In a glovebox, stock solutions of HTrMes and Hll were obtained by dissolving HTrMes (1.2 mg, 1.15 pmol) and hexamethylbenzene (internal standard, 1.7 mg, 10.5 pmol) in 850 mg C6D6, and Hll (1.1 mg, 1.83 pmol) and hexamethylbenzene (internal standard, 1.7 mg, 10.5 pmol) in 660 mg C6D6, respectively. Then, 443 mg of the HTrMes stock solution, containing 0.65 mg of catalyst (0.6 pmol, 1 equiv), 16.2 mg of diethyl 2,2-bis(2-methylprop-1-en-1-yl)malonate (60 pmol, 100 equiv), and additional 189 mg C6D6 to achieve an overall volume of 0.6 mL, which corresponds to a concentration of alkene substrate equal to 0.1 M, were transferred to a NMR tube. Similarly, 218 mg of the Hll stock solution containing 0.38 mg of catalyst (0.6 pmol, 1 equiv), 16.2 mg of diethyl 2,2-bis(2-methylprop-1-en-1-yl)malonate (60 pmol, 100 equiv), and 414 mg of C6De, to achieve the same volume (0.6 mL ) and substrate concentration (0.1 M), were transferred to a second NMR tube. The tubes were sealed and a quantitative1H NMR spectrum (d1 = 60 s) was immediately recorded to determine the relative integrations for catalyst, the alkene substrate, and internal standard. The NMR tubes were then immersed in a preheated oil bath at 60 °C. Quantitative1H NMR spectra (d1 = 60 s) were periodically recorded to determine RCM yields and the percentage of remaining catalyst. The data, summarized in Fig. 1, show a higher productivity and greater resistance to decomposition for HTrMes than Hll. Representative Procedure for Self-Metathesis of Non-Purified Allylbenzene in Air. _ _ Cat. (200 ppm)ph

[0723]

[0724] - X / ^Xr^ph + = (non-purified) air, 25°C, 1h

[0725] In a glovebox, stock solutions of the catalysts were obtained by dissolving HTrMes (2.8 mg, 2.55 μmol) in 1 mL of toluene, HII (3.2 mg, 5.10 μmol) in 2 mL of toluene, and 1-O-TPPh (3.5 mg, 2.55 μmol) in 1 mL of toluene, respectively. Then, 100 μL of the catalyst stock solution, corresponding to 0.255 μmol of catalyst were transferred to a 1 mL vial. The solvent was removed by reduced pressure, and hexamethylbenzene (internal standard, 22.8 mg, 0.14 mmol) was transferred to the vial. The vial was exported in a fume hood outside the glovebox and exposed to air in a lying position for ten minutes, to replace argon with air. Then, 169 μL (3.19 mmol, 5000 equiv.) of allylbenzene, nonpurified and stored in air, was added to the vial. The vial was closed with a plastic cap, equipped with a rubber septum, and to prevent overpressure inside the vessel, the rubber septum was pierced with a syringe needle. The mixture was vortexed (800 rpm) at 25 °C for 1 hour. An aliquot was withdrawn from the mixture, quenched with KTp, and analysed by quantitative1H NMR (d1 = 60 s, CDCh). Yields, selectivity, and turnovers (TON) were determined from integration of the olefinic signals vs internal standard (2.23 ppm), see Table 6. Prolonging the reaction time to 4 or 24 hours did not improve the yield, suggesting catalyst decomposition. The data, summarized in Table 6, show a higher productivity and greater resistance to decomposition for HTrMes than both 1-O-TPPh and Hll. The better performance of HTrMes vs 1-O-TPPh suggests that the steric protection imparted by the three-dimensional trityl group is superior to that of the planar 2,3,4,5-tetraphenylphenyl (TPPh), although the latter group contains a higher number of carbon atoms (i.e. trityl (19) vs TPPh (30)). This result supports our claim that three-dimensional bulky substituents provide more stable and effective catalysts than those planar.

[0726] Table 6. Probing the impact of remote steric bulk on productivity in self-metathesis of non-purified allylbenzene in air.

[0727] entry catalyst yield TON

[0728] (%) 30

[0729] 1 Hll 2 100

[0730] 2 HTrMes 11 550

[0731] 3 1-O-TPPh 6 300 Representative Procedure for CM of Estragole with Methyl Acrylate (MA).

[0732] Estragole (63 pL, 59 mg, 0.4 mmol), MA (145 pL, 138 mg, 1.6 mmol, 4 equiv), and decane (78 pL, 57 mg, 0.4 mmol, 1 equiv) were diluted to 2 mL with CyHs (final concentration 200 mM estragole and decane). A 50 mL aliquot was taken and diluted to 1 mL with CH2CI2 to measure the initial estragole-decane ratio by GC-FID analysis. Hll (25 pL of a 10 mg / mL (15.6 mM) C₆H₆ solution, 0.0004 mmol, 0.1 mol%) was added, and the reaction mixture was stirred at 70 °C for 4 hours, after which a 50 pL aliquot was taken and quenched with 10 mg / mL KTp solution. The aliquot was diluted to 1 mL with CH2CI2 and the resulting sample analyzed by GC-FID. The results are summarized in Table 7. In some cases, the percentage conversion and yield of A are not equal. The balance of material is presumed to be due to isomerization to form B.

[0733] Table 7: Probing the impact of remote steric bulk on productivity in estragole-acrylate CM

[0734] cross metathesis Ru (0.1 mol%)

[0735]

[0736] C7H8, decane (IS)

[0737]

[0738] 70 °C, 4 hr isomerisation + cross metathesis

[0739]

[0740] entry catalyst mol % conv. estragole (%) A yield (%) TON 1 Hll 0.1 94 75 750 2 HTrMes 0.1 95 93 930 3 HTrIMes 0.1 93 93 930 4 HtBu'TrIMes 0.1 95 94 940

[0741] Synthesis and activity of further ligands and ruthenium complexes

[0742] General Procedures

[0743] Ligand syntheses were performed in air unless otherwise noted. Catalyst syntheses were carried out under argon using HPLC-grade solvents, which were dried and degassed with a Glass Contour solvent purification system, then stored under argon over 4 A molecular sieves for at least 16 h before use. Anhydrous C6D6 (>99.6 atom % D) was purchased from Sigma-Aldrich, stored in the glove box, and used as received. CDCh (99.8 atom % D) was dried over CaH2 and distilled prior to use. Diethyl diallylmalonate (DDM) was degassed by five consecutive freeze-pump-thaw cycles. The compound was then transferred to an argon-filled glove box and stored over activated Selexsorb® CD for 4 h at room temperature. Afterwards, it was filtered through a short column of activated basic alumina, placed in the glove box freezer (-35 °C), and used within one week. Tris(3,5-dimethylphenyl)methanol was purchased from Chemieliva and used as received. All other reagents were obtained at the highest commercial quality and used without further purification. Indi (structure shown in Scheme 12) was purchased from Merck, stored in the glove box, and used as received. Ruthenium complexes Glpy and HII-NCO (structures shown in Scheme 12) were synthesized following literature protocols: Trnka et al., (supra); Kumar et al., Chem. Asian J., 2009, 4, 1275-1283 (“Isocyanate- and Isothiocyanate-Derived Rulv-Based Alkylidenes: Synthesis, Structure, and Activity”).

[0744] Scheme 12: (a) established ruthenium catalysts, (b) new ruthenium catalysts used in this work, (c) new CAAC salt synthesized in this work.

[0745]

[0746]

[0747] 2,6-Dibenzhydryl-4-tritylaniline (3h). A mixture of 4-tritylaniline (6.48 g, 19.3 mmol) and diphenylmethanol (7.20 g, 38.6 mmol) was heated to 120 °C in a 100 mL roundbottom flask. A solution of anhydrous zinc chloride (0.88 g) and 2.7 mL of HCI (36% w / w) was then added. The temperature was further increased to 160 °C, and the reaction mixture was maintained at this temperature for 30 minutes before being cooled to room temperature. After cooling to room temperature, the mixture was dissolved in 400 mL dichloromethane, followed by washing with sodium bicarbonate solution until the pH was adjusted to 7-8. The dichloromethane solution was dried over anhydrous magnesium sulfate, filtered, and concentrated using a rotary evaporator to a volume of approximately 50 mL. This concentrated solution was transferred to a 500 mL graduated cylinder), and hexane (200 mL) was carefully added to form two separate layers. The cylinder was sealed with aluminum foil and parafilm and left to stand at room temperature for 20 days. The grown crystals were isolated, washed thoroughly with methanol and then hexane to give 2,6-Dibenzhydryl-4-tritylaniline (3h; 7.2 g, 56%).1H NMR (600 MHz, CDCI3) 57.19 - 7.10 (m, 12H, Ar-H), 7.07 - 7.02 (m, 9H, Ar-H), 6.95 - 6.88 (m, 14H, Ar-H), 6.41 (s, 2H, Ar-H), 5.38 (s, 2H, CHPh2), 3.35 (s, 2H, NH2). HRMS (ESI+): calculated for C5iH42N [M + H]+: m / z = 668.3316, found m / z = 668.3312.

[0748]

[0749] N1, N2-Bis(2,6-dibenzhydryl-4-tritylphenyl)ethane-1,2-diimine (8h). In a 100 mL round-bottom flask, glyoxal solution (40% w / w, 206 pL, 1.80 mmol), 2,6-dibenzhydryl-4-tritylaniline (3h; 2.0 g, 2.99 mmol), and two drops of formic acid were mixed in isopropanol (30 mL). The mixture was refluxed for 36 h, resulting in a yellow suspension. The solvent was removed under reduced pressure, and the residue was dissolved in boiling dichloromethane (250 mL) with vigorous stirring. The solution was concentrated by evaporation under magnetic stirring on a hot plate to approximately 50 mL and then stored in a freezer at -20 °C for three days. The resulting solid was isolated by filtration, rinsed with dichloromethane, and dried under high vacuum to afford N1, N2-bis(2,6-dimethyl-4-tritylphenyl)ethane-1,2-diimine (8h; 1.51 g, 74%) as a yellow powder.1H NMR (600.07) MHz, CDCI3, 298 K): 5 7.14 (s, 2H), 7.10-7.05 (m, 42H), 6.98-6.94 (m, 12H), 6.78-6-74 (m, 20H), 5.15 (s, 4H).

[0750]

[0751] 1,3-bis(2,6-dibenzhydryl-4-tritylphenyl)-1H-imidazol-3-ium chloride (10h’). A 10 mL pressure tube equipped with a magnetic stir bar was charged with N1, N2-bis(2,6-dimethyl-4-tritylphenyl)ethane-1,2-diimine (8h; 200 mg, 147 pmol), paraformaldehyde (4.4 mg, 1 equiv relative to 8h), trimethylsilyl chloride (56 pL, 442 pmol), and dichloromethane (5 mL). The tube was sealed and stirred in a preheated oil bath at 60 °C for 6 h. The mixture was cooled to room temperature and filtered through a Macherey-Nagel Chromabond PTS separation column. The pale ochre solution was concentrated under a stream of nitrogen until a thick yellow-ochre liquid remained. The residue was suspended in diethyl ether (10 mL), and the resulting white solid was isolated by filtration, rinsed three times with diethyl ether, and dried overnight under high vacuum at 80 °C to afford 1,3-bis(2,6-dibenzhydryl-4-tritylphenyl)-1H-imidazol-3-ium chloride (10h’; 147 mg, 71%) as a white powder.1H NMR (600.07) MHz, CDCI3, 298 K): 5 13.42 (s, 1H), 7.20-6.90 (m, 66H), 6.44 (br d, J = 7.6, 8H), 5.44 (br s, 2H), 5.35 (br s, 4H).

[0752]

[0753] Ru-10h’. In an argon-filled glove box, carbene salt 10h’ (50 mg, 0.036 mmol) and K[N(SiMe3)2] (7.4 mg, 0.037 mmol) were suspended in a mixture of toluene (2 mL) and THF (1 mL) and stirred for 10 min at room temperature. The suspension dissolved within 5 min to form a pale-yellow solution, which was filtered through glass-fiber filter paper and dried under vacuum. To this residue, containing the free carbene of 10h’, was added a solution of (PCy3)(py)2(CI)2Ru=CHPh (Glpy) in THF (2 mL), and the mixture was stirred at 45 °C for 5 h. The solvent was removed under vacuum, and the residue was dissolved in diethyl ether (ca. 2 mL). The solution was filtered through glass-fiber filter paper and placed overnight in the glove box freezer at -35 °C. During this time, a green microcrystalline precipitate formed. The supernatant was removed, and the green solid was washed thoroughly with hexane and then diethyl ether, and dried under vacuum to give 33.6 mg (73% yield) of Ru-10h’ (with a purity of about 95%, as determined by1H NMR). For further purification, the solid was dissolved in a minimum amount of dichloromethane (ca. 0.5 mL), and diethyl ether (ca. 3 mL) was added slowly. The mixture was placed overnight in the glove box freezer at -35 °C. The resulting bright green crystals were isolated, washed thoroughly with diethyl ether, and dried under vacuum to afford pure Ru-10h’ (13 mg, 28%).1H NMR (600.07) MHz, C6D6, 298 K): 5 = 20.39 (s, 1H), 8.76 (dt, J = 4.9, 1.5 Hz, 2H), 8.18 (dd, J = 8.2, 1.0 Hz, 2H), 7.46-7.26 (br m, 22H), 7.23 (t, J = 7.4, 1H), 7.06-6.76 (br m, 46H), 6.74 (tt, 7.6, 1.5 Hz, 1H), 6.70-6.54 (br m, 10H), 6.45-6.35 (m, 4H), 5.13, (s, 1H), 4.79 (s, 1H).

[0754]

[0755] 2,6-Bimethyl-4-(tris(3,5-dimethylphenyl)methyl)aniline (3f). In a 250 ml round-bottom flask, 2,6-dimethylaniline (1.10 g, 9.08 mmol) was mixed in glacial acetic acid (80 mL) and HCI 36% (1.35 mL). Tris(3,5-dimethylphenyl)methanol (2.00 g, 6.05 mmol) was added in a single portion, and the resulting mixture was refluxed for 3 h. The reaction mixture was cooled to room temperature, and the pH was adjusted to 7-8 by dropwise addition of 12 M KOH solution. The mixture was transferred to a separatory funnel and extracted three times with dichloromethane (3 x 40 mL). The dichloromethane solution was dried using magnesium sulphate and filtered. The solvent was evaporated under reduced pressure to obtain an off-white residue. The residue was resuspended in isopropanol (50 mL). The solid was isolated by vacuum filtration, washed twice with cold isopropanol (2 x 20 mL), then dried under high vacuum to obtain 2,6-dimethyl -4-(tris(3,5-dimethylphenyl)methyl)aniline) (3f; 2.43 g, 93%) as a white powder.1H NMR (CDCh, 600.07 MHz): 56.89 (s, 6H), 6.81 (s, 2H), 6.77 (s, 3H), 3.49 (s, 2H), 2.21 (s, 18H), 52.08 (s, 6H).13C{1H} NMR (C6D6, 150.89 MHz): 148.6, 141.2, 137.1, 136.7, 131.9, 130.0, 127.8, 120.5, 64.9, 21.7, 18.0. HRMS (ESI+): calculated for C33H38N [M + H]+: m / z = 448.2999, found m / z = 448.3001.

[0756] 8f

[0757]

[0758] N1, N2-Bis(2,6-dimethyl-4-(tris(3,5-dimethylphenyl)methyl)phenyl)ethane-1,2- diimine (8f).

[0759] Acetonitrile (60 mL), 3f (1.01 g, 2.26 mmol), and 5 drops of formic acid were added to a 100 mL round-bottom flask. The mixture was stirred and heated to 40 °C. Glyoxal solution (40% w / w, 130 pL, 1.13 mmol) was then added in a single portion, and the reaction was maintained at 40 °C for 24 h. After cooling to room temperature, the yellow precipitate was collected by vacuum filtration on a frit, washed with cold acetonitrile, and dried under high vacuum to afford N1, N2-bis(2,6-dimethyl-4-(tris(3,5- dimethylphenyl)methyl)phenyl)ethane-1,2-diimine (8f; 0.72 g, 70%) as a yellow powder.

[0760] 1H NMR (C6D6, 600.07 MHz): 57.70 (s, 2H), 7.45 (s, 4H), 7.41 (s, 12H), 6.72 (s, 6H), 2.11 (s, 36H), 1.98 (s, 12H). HRMS (ESI+): calculated for C68H73N2 [M + H]+: m / z = 917.5768, found m / z = 917.5760.

[0761] 2HCI

[0762] 9f

[0763]

[0764] N1, N2-Bis(2,6-dimethyl-4-(tris(3,5-dimethylphenyl)methyl)phenyl)ethane-1,2- diamine dihydrochloride (9f).

[0765] Into a 20 mL pressure tube with a magnetic stir bar, dichloromethane (10 mL) and N1, N2- Bis(2,6-dimethyl-4-(tris(3,5-dimethylphenyl)methyl)phenyl)ethane-1,2-diimine (8f, 0.60 g, 0.65 mmol) were added. The mixture was stirred until partial dissolution occurred, then anhydrous sodium triacetoxyborohydride (0.920 g, 4.34 mmol) was added. The tube was sealed and heated at 60 °C for 2 h. After cooling to room temperature, the mixture was transferred to a 100 mL round-bottom flask, and additional dichloromethane was added until complete dissolution. Water (30 mL) was added, and the mixture was vigorously stirred. The layers were allowed to separate, and the aqueous phase was removed. The aqueous washing was repeated once. The organic layer was washed with brine (10 mL), dried over magnesium sulfate, and filtered through a Macherey-Nagel Chromabond PTS separation column to obtain a clear solution. Dichloromethane was evaporated under a nitrogen stream, and the residue was dried under high vacuum to yield N1, N2-bis(2,6- dimethyl-4-(tris(3,5-dimethylphenyl)methyl)phenyl)ethane-1,2-diamine (0.57 g, 96%).1H NMR (C6D6, 600.07 MHz): 57.39 (br s, 12H), 7.37 (br s, 4H), 6.70 (br s, 6H), 3.06 (br, 2H), 2.78 (s, 4H), 2.09 (s, 36H), 2.06 (s, 12H).

[0766] To the dried product, tetra hydrofuran (ca. 10 mL) was added dropwise while gently heating until the solids were almost fully dissolved. After cooling to room temperature, aqueous HCI (36% w / w) was added dropwise under vigorous stirring, resulting in the formation of a white precipitate. Water was then added until no further solid formation was observed. The solid was isolated by vacuum filtration, rinsed with water (2 x 5 mL) and diethyl ether (2 x 5 mL), and dried on a hot plate overnight to afford N1, N2-Bis(2,6- dimethyl-4-(tris(3,5-dimethylphenyl)methyl)phenyl)ethane-1,2-diamine dihydrochloride (9f; 0.52 g, 85%) as a white powder.

[0767]

[0768] 1,3-Bis(2,6-dimethyl-4-(tris(3,5-dimethylphenyl)methyl)phenyl)-4,5-dihydro-1H- imidazol-3-ium (10f). Inside an argon-filled glove box, a 5 mL microwave vial with a magnetic stir bar was charged with N1, N2-Bis(2,6-dimethyl-4-(tris(3,5- dimethylphenyl)methyl)phenyl)ethane-1,2-diamine dihydrochloride (9f, 0.20 g, 0.20 mmol) and anhydrous triethyl orthoformate (1.79 g, 2.0 mL, 12.1 mmol). The vial was sealed, removed from the glove box, and heated at 145 °C for 10 min at high absorption power in a microwave reactor (Biotage I nitiator+). The vial was then returned to the glove box. The solid was isolated by vacuum filtration on a frit, washed sequentially with triethyl orthoformate and anhydrous diethyl ether, and dried under high vacuum at 80 °C inside the glove box to afford 1,3-Bis(2,6-dimethyl-4-(tris(3,5-dimethylphenyl)methyl)phenyl)- 4,5-dihydro-1H-imidazol-3-ium (10f, 0.14 g, 71%).1H NMR (CDCI3, 600.07 MHz): 57.90 (s, 1H), 7.10 (s, 4H), 6.82 (s, 12H), 6.81 (s, 6H), 4.91 (s, 4H), 2.34 (s, 12H), 2.23 (s,

[0769]

[0770] Ru-10f. In an argon-filled glove box, carbene salt 10f (112 mg, 0.12 mmol) and K[N(SiMe3)2] (25.1 mg, 0.13 mmol) were suspended in 5 mL of THF and stirred for 10 min at room temperature. The suspension dissolved within 5 min to form a pale-yellow solution, which was then filtered through glass-fiber filter paper. To this solution, containing the free carbene of 10f, was added 56 mg of Hoveyda first generation catalyst HI at once, and the mixture was stirred overnight at room temperature. During this time, a green precipitate formed. The precipitate was isolated by vacuum filtration on a frit, washed thoroughly with anhydrous diethyl ether, and dried under high vacuum to afford Ru-10f (96 mg, 83%).

[0771] A portion of the compound (49 mg) was further purified by dissolving it in a minimum amount of dichloromethane (ca. 2 mL), followed by slow addition of diethyl ether. The mixture was placed overnight in the glove box freezer at -35 °C. The resulting microcrystalline solid was isolated by decantation, washed thoroughly with diethyl ether, and dried under vacuum to give 19 mg of highly pure Ru-10f.1H NMR (600.07) MHz, C6D6, 298 K): 517.33 (s, 1H, [Ru]=CH), 7.64 (s, 4H), 7.50 (s, 12H), 7.45 (dd,3JH-H = 7.5,4JH-H = 1.6 Hz, 1H), 7.26-7.22 (m, 1H), 6.83 (brt,3JH-H = 7.5 Hz,4JH-H = 1 H), 6.74 (s, 6H), 6.50 (d,3JH-H = 8.4 Hz, 2H), 4.70 (sept,3JH-H = 6.1 Hz, 1H, OCH(CH3)2), 3.10 (s, 4H), 2.46 (s, 12H), 2.14 (s, 36H), 1.64 (d,3JH-H = 6.1 Hz, 6H, OCH(CH3)2).

[0772]

[0773] CPh3

[0774] lndTrMes. In an argon-filled glove box, free carbene 1,3-bis(2,6-dimethyl-4-tritylphenyl)-4,5-dihydro-1H-imidazol-3-ium-2-ide (TrMes, 50 mg, 65.5 pmol) was added to a solution of (3-phenyl-1H-inden-1-ylidene)bis(tricyclohexylphosphine)ruthenium(ll)dichloride (Indi, 43.2 mg, 46.8 pmol) in THF (2 mL). The mixture was stirred at 40 °C for 1 h. The solvent was removed under vacuum, and the residue was extracted with diethyl ether. The solution was filtered through glass-fiber filter paper and stored in the glove box freezer at -35 °C for three days, during which dark-red crystals formed. The supernatant was decanted, and the crystals were washed with diethyl ether and dried under vacuum to afford lndTrMes (20.6 mg, 31%) as a red-orange powder.1H NMR (C6D6, 850.10 MHz): 5 9.31 (dd, J = 7.4, 1.2 Hz, 1H) 8.06 (s, 1H), 7.99-7.95 (m, 2H), 7.55 (d, J = 7.8 Hz, 6H), 7.39-7.29 (m, 6H), 7.26 (d, J = 7.8 Hz, 6H), 7.23 (t, J = 7.8 Hz, 2H), 7.20 (t, J = 7.8 Hz, 6H), 7.06 (distorted t, J = 7.3 Hz, 3H), 7.02 (br s, 1 H), 6.91 (distorted t, J = 7.3 Hz, 3H), 6.88 (distorted t, J = 7.5 Hz, 6H), 6.78 (br s, 1H), 3.14-3.06 (m, 2H), 2.74-2.57 (m, 8H), 2.41-2.30 (m, 6H), 2.16 (s, 3H), 1.93-1.80 (m, 6H), 1.68-1.44 (m, 15H), 1.15-1.01 (m, 9H).13C{1H} NMR (C6D6, 213.76 MHz): 5 293.5, 216.4, 216.1, 147.7, 147.4, 146.5, 145.8, 141.5, 141.2, 139.3, 139.1, 138.8, 138.3, 138.1, 137.6, 136.9, 136.64, 136.59, 133.9, 132.4, 132.1, 131.8, 131.7, 131.2, 130.7, 130.4, 130.0, 129.0, 128.9, 128.8, 128.72, 128.65, 128.5, 128.4, 128.3, 127.82, 127.75, 127.16, 127.05, 126.9, 126.8, 126.5, 125.7, 125.6, 125.5, 125.4, 125.3, 117.3, 65.7, 65.6, 52.2, 34.6, 34.5, 29.68, 29.65, 28.04, 27.98, 26.8, 21.0, 20.9, 20.6, 20.5, 20.4, 19.58, 19.52.

[0775]

[0776] HTrMes-NC0. In an argon-filled glove box, a solution of catalyst HTrMes (54 mg, 49.9 pmol) in dichloromethane (1 mL) was mixed with a suspension of AgOCN (14.9 mg, 99.7 pmol) in DMF (dimethylformamide, 0.2 mL), and stirred at room temperature for 6 h. The mixture was filtered through a pad of Celite, which was washed with dichloromethane (1 mL). The solvent was removed under vacuum, and the residue was redissolved in a minimum amount of dichloromethane (ca. 0.5 mL) and eluted through a short silica gel column using a mixture of diethyl ether and dichloromethane (1:4). The eluted solution was dried under vacuum. The residue was dissolved in a minimum amount of dichloromethane (ca. 1 mL), and diethyl ether (ca. 3 mL) was added slowly. The mixture was placed overnight in the glove box freezer at -35 °C. The resulting microcrystalline green solid was isolated by decantation, washed thoroughly with diethyl ether, and dried under vacuum to afford HTrMes-NCO (40 mg, 73%).1H NMR (C6D6, 600 MHz): 5 17.04 (s, 1H, [Ru]=C / 7), 7.58 (dd,3JH-H = 8.6,4JH-H = 1.2, m, 12H, CPh3o-CH), 7.46 (s, 4H, NAr o-C / 7), 7.22-713 (C6D5H overlap, 14H), 7.06 (tt,3JH-H = 7.4,4JH-H = 1.2, 6H, CPh3p-CH), 6.75 (td,3JH-H = 7.5,4JH-H = 0.7 Hz, 1H, Ru=CHAr C / 7), 6.34 (d,3JH-H = 8.4, 1H, Ru=CHAr C / 7), 4.38 (sept,3JH-H = 6.2 Hz, 1H, OCH(CH3)2), 3.05 (s, 4H, heterocycle CH2), 2.27 (br s, 12H, NAr C / 73), 1.28 (d,3JH-H = 6.2 Hz, 6H, OCH(CH3)2).

[0777]

[0778] 1-(2,6-Dibenzhydryl-4-tritylphenyl)-3,3,4-trimethyl-4-phenyl-3,4-dihydro-2H-pyrrol- 1-ium tetrafluoroborate (6p). In a 25 mL round-bottom flask, 2,6-dibenzhydryl-4-tritylaniline (3h; 1 g, 1.50 mmol), aldehyde 4 (406 mg, 2.16 mmol), p-toluenesulfonic acid (12.9 mg, 0.03 mmol), and MgSC>4 (2.35 g, 19.52 mmol) were mixed in toluene (7 mL). The mixture was refluxed for 24 h until complete consumption of 2,6-dibenzhydryl-4-tritylaniline (3h). The mixture was filtered, and the solids were rinsed with toluene (2 x 5 mL). The combined filtrate was dried under high vacuum to afford 0.99 g of a sticky amber-colored solid. In an argon-filled glove box, the residue was redissolved in anhydrous dioxane (4.65 mL) and transferred to a 5 mL Schlenk flask equipped with a magnetic stir bar. The Schlenk flask was then transferred to a fume hood equipped with a Schlenk line, and 4 M HCI in dioxane (890 pL) was added. The flask was sealed, and the mixture was heated at 90 °C for 18 h. The reaction mixture was evaporated, and the residue was redissolved in CH2CI2 (11 mL). A solution of sodium tetrafluoroborate (259 mg, 2.36 mmol) in water (7.4 mL) was added, and the biphasic mixture was stirred for 1 h. The organic layer was separated and evaporated to obtain a solid residue. The residue was triturated with diethyl ether (15 mL), isolated by vacuum filtration on a frit, washed with diethyl ether (2 x 15 mL), and dried overnight under high vacuum at 80 °C to afford product 3p (273 mg, 20%) as a beige powder.1H NMR (C6D6, 600 MHz): 57.52 (s, 1H), 7.28 (d, J = 2.2, 1H), 7.22 (d, J = 2.2, 1H), 7.13-7.10 (m, 6H), 7.10-6.99 (m, 8H), 6.99-6.82 (m, 20H), 6.72 (d, J = 7.8 Hz, 2H), 6.68 (d, J = 7.8 Hz, 2H), 6.20 (dd, J = 7.8, 1.8 Hz, 2H), 5.77 (s, 1H), 5.15 (s, 1H), 3.19 (d, J = 14.4 Hz, 1H), 3.09 (d, J = 14.4 Hz, 1H), 2.00 (s, 3H), 1.61 (s, 3H), 1.48 (s, 3H). HRMS (ESI+): calculated for Ce^N [M + H]+: m / z = 838.4414, found m / z = 838.4407.

[0779]

[0780] 1,3-bis(2,6-dimethyl-4-(tris(4-(tert-butyl)phenyl)methyl)phenyl)-1H-imidazol-3-ium chloride (10e’).

[0781] As for 10h’, but using N1, N2-bis(2,6-diisopropyl-4-tritylphenyl)ethane-1,2-diimine (8e, 1.0g, 0.92 mmol) to obtain the product (10e’, 730 mg, 70%).

[0782]

[0783] Ru-10e’ (HtBu-TrIMes).

[0784] As for Ru-10h’ above, but using 10e’ (246 mg, 0.22 mmol) and HI (100 mg, 0.17mmol) to obtain the product (198 mg, 83%) as a beige powder.

[0785] 1H NMR (600 MHz, C6D6) 6 17.56 (s, 1H), 7.86 (d, J = 7.5 Hz, 2H), 7.73 (d, J = 8.1 Hz, 32H), 7.63 (s, 10H), 7.33 (d, J = 8.1 Hz, 28H), 7.29 (d, J = 8.6 Hz, 5H), 7.03 (t, J = 7.4 Hz, 2H), 6.55 (d, J = 8.2 Hz, 2H), 5.88 (s, 2H), 4.77 (p, J = 6.3 Hz, 1H), 2.26 (s, 27H), 1.77 (d, J = 6.0 Hz, 16H), 1.24 (s, 138H).

[0786]

[0787] 10a'

[0788] 1,3-bis(2,6-dimethyl-4-tritylphenyl)-1 H-imidazol-3-ium chloride (10a’).

[0789] In a 50 mL high- pressure round-bottom flask, N1, N2-bis(2,6-dimethyl-4-tritylphenyl)ethane-1,2-diimine (8a; 1.0 g, 1.34 mmol), paraformaldehyde (42 mg, 1.34 mmol), and trimethylsilyl chloride (0.22 g, 2.0 mmol) were mixed in CH2CI2 (15 mL). The sealed tube was stirred at 65 °C for 24 h. The reaction mixture was evaporated to 5 mL final volume, and cold hexanes was added dropwise while stirring to induce precipitation. The product was filtered and washed with cold hexanes (2x 10 mL) and dried under high vacuum to obtain 1,3-bis(2,6-dimethyl-4-tritylphenyl)-1 / 7-imidazol-3-ium chloride (10a’, 0.7 g, 65%) as a dark yellow powder.1H NMR (600 MHz, MeOD) 59.51 (t, J = 1.6 Hz, 1H, NC / ), 8.11 (d, J = 1.5 Hz, 2H, Heterocycle C / 7), 7.41 - 6.97 (m, 34H, Tr and N-Ar m-C / 7), 2.11 (s, 12H, NAr CH3).13C NMR (150 MHz, MeOD) 5 150.42, 146.06, 138.60, 133.77, 131.59, 131.29, 130.69, 127.49, 126.08, 125.08, 64.88, 16.43. ESI-MS (MeOH): Calculated for C57H49N2 ([M-CI]), m / z 761.3896 Found: m / z 761.3924.

[0790]

[0791] TrIMes

[0792] 1,3-bis(2,6-dimethyl-4-tritylphenyl)-1H-imidazol-3-ium-2-ide (TrIMes)

[0793] As forTrMes, but using 10a’ (200 mg, 0.250 mmol) to obtain the product (170 mg, 89%).

[0794] 1H NMR (600 MHz, C6D6) 5 7.52 - 7.41 (m, 12H), 7.32 (s, 4H), 7.12 - 7.06 (m, 12H), 7.03 - 6.97 (m, 6H), 6.28 (s, 2H), 2.03 (s, 12H).

[0795] 13C NMR (151 MHz, C6D6) 5 218.81, 147.10, 146.50, 139.28, 134.59, 131.33, 131.09, 128.26, 125.97, 120.02, 65.14, 18.11.

[0796]

[0797] HTrIMes

[0798] As above, but usingTrIMes (240 mg, 0.32 mmol) and HI (158 mg, 0.26 mmol) to obtain HTrIMes (180 mg, 63%) as a light brown powder.

[0799] 1H NMR (600 MHz, C6D6) 5 17.43 (s, 1H), 7.65 (d, J = 7.8 Hz, 12H), 7.50 (s, 5H), 7.25 (t, J= 7.9 Hz, 1H), 7.10- 7.05 (m, 8H), 6.81 (t, J= 7.4 Hz, 6H), 6.51 (d, J= 8.2 Hz, 1H), 4.68 (qd, J= 7.0, 3.3 Hz, 1H), 2.29 (s, 12H), 1.64 (d, J= 6.3 Hz, 6H).

[0800] 13C NMR (151 MHz, C6D6) 5 285.30, 176.17, 152.68, 148.46, 147.06, 145.70, 137.42, 136.83, 131.39, 131.36, 126.13, 124.19, 122.27, 122.11, 113.05, 74.93, 65.29, 52.99, 22.72, 21.72, 19.31, 14.02. Catalytic Experiments

[0801] (b)

[0802]

[0803] Scheme 13: (a) new ruthenium catalysts and (b) established ruthenium catalysts used in catalytic experiments.

[0804] Preparation of Stock Solutions of the Catalysts. Inside an argon-filled glove box, 6 pmol of each Ru complex shown in Scheme 13 was transferred to a 4 mL vial equipped with a screw cap, and 4 mL of dichloromethane was added to achieve an initial concentration of 1.5 mM. Then, 40 pL of each solution was transferred to a second 4 mL vial and diluted with 3960 pL of dichloromethane to a final volume of 4 mL, and sealed with a screw cap, resulting in a catalyst concentration of 15 pM. All stock solutions were stored in the glove box freezer at -35 °C and used within one week. Purification of Diethyl Diallylmalonate (DDM). Diethyl diallylmalonate (DDM) was transferred to a Schlenk flask and degassed by five consecutive freeze-pump-thaw cycles. The flask was brought into the glove box, and the compound was purified by storing it over activated Selexsorb® CD for 4 h at room temperature. This was followed by filtration through a short column (approximately 5 cm) of activated basic alumina, packed in a short pipette equipped with a glass-fiber filter. The purified substrate was stored in the glove box freezer (-35 °C) and used within one week.

[0805] Preparation of Diethyl Diallylmalonate (DDM) Stock Solution in Benzene-ds (0.1 M). Inside an argon-filled glove box, 145 pL of purified DDM (144 mg, 0.6 mmol) was diluted with 5855 pL of anhydrous C6D6to obtain a final volume of 6000 pL (6 mL) and a concentration of 0.1 M in DDM.

[0806] Representative Procedure for Ring-Closing Metathesis of diethyl diallylmalonate (DDM).

[0807] EtO2C CO2EtEt02c CO2Et

[0808] [Ru] (10 ppm) X >

[0809] / / ) - *- \ / +—

[0810]

[0811] / C6D6(0.1 M), 70°C

[0812] DDM 13

[0813] In an argon-filled glove box, 40 pL of each catalyst stock solution (15 pM, corresponding to 0.6 nmol of catalyst) was transferred to individual open 4 mL vials arranged in a 4x6 microtiter plate. The vials were left open until the solvent completely evaporated. The vials were then sealed, and the microtiter plate, together with the stock solution of DDM in benzene-D6(0.1 M, described above), was transferred to a nitrogen-filled LC glove box (<1 ppm O2 and <10 ppm H2O) equipped with an Unchained Labs Junior robot. To each vial containing the catalyst, 0.6 mL of the DDM stock solution was added. The vials were sealed, and the plate was placed on a preheated vortexing station (70 °C) and vortexed at 600 rpm. Vortexing was stopped after 24h, and the plate was removed from the heated station and cooled to room temperature. A 200 pL aliquot of each reaction mixture was transferred to separate 4 mL vials containing an excess of potassium tris(1 -pyrazolyl)borohydride (KTp, >10 equiv relative to Ru) to quench the metathesis reaction. The quenched mixtures were placed in a fume hood, filtered through a nylon syringe filter (pore size 0.45 pm), diluted with an additional 450 pL of C6D6, and transferred into NMR tubes. Quantitative1H NMR spectra (di = 60 s) were recorded. RCM yields were determined by comparing the integrals of the allylic methylene peaks of DDM (2.89 ppm, tt, J = 7.40, 1.10 Hz, 4H) and the RCM product (3.18 ppm, s, 4H). The data is summarized in Table 8. Ru-10f is nearly twice as productive as Hll. Increasing steric bulk leads to higher catalyst productivity, following the trend: Ru-10f > HTrMes > Hll.

[0814] Table 8. Probing the impact of remote steric bulk on productivity in ring-closing metathesis of diethyl diallylmalonate (DDM).

[0815] Entry Catalyst Yield (%) TON

[0816] 1 HTrMes-NCO 12 12000

[0817] 2 Ru-10h’ 13 13000

[0818] 3 lndTrMes 14 14000

[0819] 4 Ru-10f 38 38000

[0820] 5 HTrMes 33 33000

[0821] 6 Hll 21 21000

[0822] 7 HII-NCO 10 10000

[0823] 8 Gill 5 5000

[0824]

Claims

CLAIMS:

1. A ruthenium complex comprising a ligand of formula (I):(R4)n^1RRI-N^”X(I),wherein:R1is a C1-6alkyl, or C6-10aryl;wherein the C6-10aryl is optionally substituted with one or more substituents selected from formula (II), C1-6alkyl, C3-10carbocyclyl (e.g. C5-6carbocyclyl), C3-10heterocyclyl (e.g. 5- or 6-membered heterocyclyl), halo, and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3⁻), or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumC3-10heterocyclyl)), and further wherein the substituent Ci-ealkyl, Cs- carbocyclyl and Ca-wheterocyclyl are each optionally substituted with one or more substituents selected from Cs-wcarbocyclyl (e.g. Cs-ecarbocyclyl), Ca-wheterocyclyl (e.g. 5- or 6-membered heterocyclyl) and formula (II), or wherein two substituent Ci-ealkyl together form a Cs-ecarbocyclyl ring;wherein formula (II) is:—(X)n2— ZY3(II)wherein:each X is independently selected from methylene, ethynylene, Ce- arylene (e.g. phenylene), and Cs-wheteroarylene (e.g. 5- or 6-membered heteroarylene), wherein the C6-14arylene and Cs-wheteroarylene are each optionally substituted with one or more substituents selected from Ci-ealkyl, halo, Ci-ehaloalkyl, and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3⁻), or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumC3-10heterocyclyl);n2 is 0, 1 or 2;Z is C or Si; andeach Y is independently selected from Cs-wcarbocyclyl (e.g. Cs-ecarbocyclyl), C3-wheterocyclyl (e.g. 5- or 6-membered heterocyclyl), Ci-ealkyl, Ci-ehaloalkyl, C1-4alkenyl, Ciwhaloalkenyl, Ciwalkynyl, and Ci-ehaloalkynyl, or two Y groups together with Z form a C3-10 carbocycle or Ca-wheterocycle, or three Y groups together with Z form a bridged polycyclic Cs-wcarbocycle or bridged polycyclic Ca-wheterocycle,wherein each Y is optionally substituted with one or more substituents selected from Ci-ealkyl, C3-wcarbocyclyl (e.g. Cs-ecarbocyclyl), C3-wheterocyclyl (e.g. 5- or 6-membered heterocyclyl), halo, Ci-ehaloalkyl, and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3‘) or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumC3-wheterocyclyl));X1is N-R2or C(R3)2, wherein:R2is a Ci-ealkyl, or C6-14aryl; wherein the C6-14aryl is optionally substituted with one or more substituents selected from formula (II), Ci-ealkyl, C3-wcarbocyclyl (e.g. Cs-ecarbocyclyl), C3-wheterocyclyl (e.g. 5- or 6-membered heterocyclyl), halo, and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3‘) or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumC3-wheterocyclyl)), and further wherein the substituent Ci-ealkyl, C3-wcarbocyclyl and C3-wheterocyclyl are each optionally substituted with one or two substituents selected from C3-wcarbocyclyl (e.g. Cs-ecarbocyclyl) and C3-wheterocyclyl (e.g. 5- or 6-membered heterocyclyl) and formula (II), or wherein two substituent Ci-eal kyl together form a Cs-ecarbocyclyl ring;each R3is independently selected from Ci-ealkyl, C1-6alkenyl, halo, cyano, Ci-ealkoxy, C6-10aryloxy, C1-6alkylthiolate, C6-14arylthiolate, amino, C3-wcarbocyclyl (e.g. Cs-ecarbocyclyl), C3-wheterocyclyl (e.g. 5- or 6-membered heterocyclyl), Ci-ealkynyl, and a substituent of formula (II), wherein the Ci-ealkyl, C1-6alkenyl, Ci-ealkoxy, C6-10aryloxy, C1-6alkylthiolate, C6-14arylthiolate, C3-wcarbocyclyl, the C3-wheterocyclyl, and the Ci-ealkynyl are each optionally substituted with one or more substituents selected from Ci-ealkyl, C3. wcarbocyclyl, Ca-wheterocyclyl, halo, Ci-ealkoxy, C6-10aryloxy, C1-6alkylthiolate, C6-14arylthiolate, amino, and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3‘) an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumCa-wheterocyclyl));or wherein two R3groups together with the C form a C3-iscarbocycle or a C3. wheterocycle, each optionally substituted with one or more substituents selected from Ci-ealkyl, C3-wcarbocyclyl, C3-wheterocyclyl, halo, Ci-ealkoxy, C6-10aryloxy, C1-6alkylthiolate, C6-14arylthiolate, amino, a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3‘) an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumC3-wheterocyclyl), and a substituent of formula (II);each R4is independently selected from C1-6alkyl, halo, C1-6haloalkyl, and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-),sulfonate (SO3⁻), or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumCa-wheterocyclyl); andthe dashed line is an optionally present bond, wherein n is 0 to 2 when the dashed line is a bond and n is 0 to 4 when the dashed line is not a bond;with the proviso that at least one of R1, R2or R3is substituted with a substituent of formula (II).

2. The ruthenium complex of claim 1, wherein R1is a substituted phenyl.

3. The ruthenium complex of claim 1 or claim 2, wherein R2is an optionally substituted phenyl.

4. The ruthenium complex of any one of claims 1 to 3, which is of formula (III) or (IV):wherein:each R5is independently selected from hydrogen, Ci-ealkyl, C6-14aryl (e.g. phenyl), Cs-ecycloalkyl, 5- or 6-membered heteroaryl, 5- or 6-membered heterocycloalkyl, halo, a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SOs-) or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumCa-wheterocyclyl)), and a substituent of formula (II), wherein the Ci-ealkyl, Cs-ecycloalkyl, Ce- aryl (e.g. phenyl) and the 5- or 6-membered heteroaryl are optionally substituted with one or more substituents selected from phenyl and 5- or 6-membered heteroaryl;each R6is independently selected from hydrogen, Ci-ealkyl, Ce- aryl (e.g. phenyl), 5- or 6-membered heteroaryl, a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), (NH3+) sulfonate (SO3⁻) or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumC3-10heterocyclyl)), and a substituent of formula (II), wherein the Ci-ealkyl, C6-14aryl (e.g. phenyl) and the 5- or 6-membered heteroaryl are optionally substituted with one or more substituents selected from phenyl and 5- or 6-membered heteroaryl or wherein at least one of R5and at least one of R6together form a Cs-ecarbocyclic ring;each R7is independently selected from hydrogen, Ci-ealkyl, C6-14aryl (e.g. phenyl), Cs-ecycloalkyl, 5- or 6-membered heteroaryl, 5- or 6-membered heterocycloalkyl, a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SOs-) or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-6alkyl, or cyclic ammonium group, such as ammoniumC3-10heterocyclyl)), and a substituent of formula (II); andat least one of R5, R6and R7is a substituent of formula (II).

5. The ruthenium complex of claim 4, wherein:(i) each R6is hydrogen; or(ii) each R6is independently selected from a substituent of formula (II), wherein n2 is 1 or 2.

6. The ruthenium complex of claim 4 or claim 5, wherein:(i) each R5is independently selected from hydrogen, Ci-ealkyl, Ce- aryl (e.g.phenyl), Cs-ecycloalkyl, and 5- or 6-membered heteroaryl, wherein the Ci- ealkyl, Cs-ecycloalkyl, Ce- aryl (e.g. phenyl) and the 5- or 6-membered heteroaryl are optionally substituted with one or more substituents selected from phenyl and 5- or 6-membered heteroaryl; optionally wherein the Ci-ealkyl is a methyl group substituted with one or two substituents each selected from phenyl and 5- or 6-memberedheteroaryl;each R6is hydrogen; andeach R7is selected from a substituent of formula (II);(ii) each R5is independently selected from a substituent of formula (II) wherein n2 is 1 or 2;each R6is hydrogen; andeach R7is independently selected from hydrogen, Ci-ealkyl, C6-14aryl, Cs- ecycloalkyl, and 5- or 6-membered heteroaryl; or(iii) each R5is independently selected from hydrogen, Ci-ealkyl, C6-14aryl (e.g.phenyl), Cs-ecycloalkyl, and 5- or 6-membered heteroaryl; optionally wherein the Ci-ealkyl is a methyl group substituted with one or two substituents each selected from phenyl and 5- or 6-membered heteroaryl;each R6is independently selected from a substituent of formula (II), wherein n2 is 1 or 2; andeach R7is independently selected from hydrogen, C1-6alkyl, C6-10aryl, C5-6cycloalkyl, and 5- or 6-membered heteroaryl.

7. The ruthenium complex of any one of claims 4 to 6, wherein each R5is the same, each R6is the same, and / or each R7is the same.

8. The ruthenium complex of any one preceding claim, wherein each R4is independently selected from C1-6alkyl.

9. The ruthenium complex of any one preceding claim, wherein the dashed line is not a bond and n is 0 to 4, such as 0 to 2.

10. The ruthenium complex of any one preceding claim, wherein each R3is independently selected from Ci-ealkyl, phenyl, Ci-ealkynyl, and a substituent of formula (II), wherein the Ci-ealkyl, phenyl and the Ci-ealkynyl are each optionally substituted with one or more substituents selected from Ci-ealkyl, and phenyl, or wherein two R3groups together with the C form a C8-i4carbocyclyl, optionally substituted with one or more substituents selected from Ci-ealkyl, phenyl and a substituent of formula (II).

11. The ruthenium complex of any one preceding claim, wherein n2 is 0 or 1 and X is phenylene or ethynylene.

12. The ruthenium complex of any one preceding claim, wherein each Y is independently selected from phenyl, 5- or 6-membered heteroaryl, Cs-ecycloalkyl, and Ci-ealkyl, wherein the phenyl, 5- or 6-membered heteroaryl, and Cs-ecycloalkyl are optionally substituted with one or more substituents selected from Ci-ealkyl, phenyl, and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SOs-) or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-6alkyl, or cyclic ammonium group, such as ammoniumCs-ioheterocyclyl)).

13. The ruthenium complex of any one preceding claim, wherein Z is C.

14. The ruthenium complex of any one preceding claim, wherein each Y is phenyl, optionally substituted with one or more substituents selected from Ci-ealkyl (e.g. tertbutyl), and phenyl.

15. The ruthenium complex of any one preceding claim, wherein the ligand is any one of formulae (V’) to (IX’):wherein:each R8is independently a Ci-ealkyl optionally substituted with one or more phenyl, or is H,R9is phenyl optionally substituted with one or more substituents selected from Ci-ealkyl, and phenyl;each R10is independently a Ci-ealkyl;each R11is independently selected from a Ci-ealkyl and phenyl;each R12is independently selected from H, a Ci-ealkyl and phenyl; andn3 is 0 to 3.

16. The ruthenium complex of any one preceding claim, wherein the ligand is selected from:11317. The ruthenium complex of any one preceding claim, which is of formula (i):L1L4, I.. X2X3" I ^L2L3(i),wherein:L1is a ligand as defined in any one of claims 1 to 16;L2is an ylidene;L3is an L-type ligand, optionally wherein L3is the ligand as defined in any one of claims 1 to 16;L4is an optionally present L-type ligand; andX2and X3are each independently an X-type ligand,wherein L2and L3; L3and X2or X3; or L2and X2or X3are optionally linked.

18. The ruthenium complex of claim 17, wherein X2and X3are each independently selected from halo, isothiocyanato (NCS), isocyanato (NCO), phenoxy optionally substituted with one or more halo substituents, and optionally substituted arylthiolate such as 2,3,4,5,6-pentafluorobenzenethiolate, 2,4,6-triphenylbenzenethiolate, 2,4,6-tris(3,5-dimethylphenyl)benzenethiolate, 2,4,6-tris(3,5-diphenylphenyl)benzenethiolate, 2.4.6-tris(3,5-ditertbutylphenyl)benzenethiolate, 2,6-diphenyl(4-anthryl)benzenethiolate, 2.6-diphenyl(4-(2,4-ditrifluoromethylphenyl)benzenethiolate, 2,6-diphenyl(4-(2,4,6-trimethylphenyl)benzenethiolate, 2,6-diphenyl(4-(2,4-dimethylphenyl)benzenethiolate, 2,6-dichlorobenzenethiolate, 2-chloro-6-methylbenzenethiolate, 2-methylbenzene-thiolate, 2,6-dimethylbenzenethiolate, 2-trifluoromethylbenzenethiolate or 1, 1,1, 3,3,3-hexafluoro-2-(trifluoromethyl)-2-propanethiolate.

19. The ruthenium complex of claim 17 or claim 18, wherein L3and L4are each selected from a phosphine, an N-heterocycle, such as pyridine, an ether, an amino, an imine and a phosphite.

20. The ruthenium complex of any one of claims 17 to 19, wherein the ylidene is selected from an alkylidene, cyclic hydrocarbylidene and a heterocyclylidene, wherein:the alkylidene is optionally substituted with one or more substituents selected from cyclic hydrocarbyl, heterocyclyl, C1-6alkenyl, phenoxy, arylthiolate, and C1-6alkylthiolate, wherein each cyclic hydrocarbyl and heterocyclyl is optionally substituted with one or more substituents selected from Ci-ealkyl, Ci-ealkoxy, C6-10aryloxy, phenyl, nitro, and (dimethylamino)sulfonyl, wherein the phenyl substituent is optionally substituted with one or more substituents selected from halo, C1-6alkyl, and C1-6alkoxy, the phenoxy substituent is optionally substituted with one or more halo substituents and the arylthiolate, and C1-6alkylthiolate substituents are each optionally substituted with one or more substituents selected from halo (e.g. fluoro, chloro or bromo), Ci-ealkyl, Ci-ehaloalkyl and C6-i4aryl, wherein the C6-i4aryl is optionally substituted with one or more substituents selected from halo (e.g. fluoro, chloro or bromo), Ci-ealkyl, Ci-ehaloalkyl and phenyl; andthe cyclic hydrocarbylidene and heterocyclylidene are each optionally substituted with one or more substituents selected from halo, C1-6alkyl, C1-6alkoxy, phenoxy, C1-6alkylsulfanyl, C1-6haloalkylsulfanyl, C1-6alkylsulfinyl, benzylsulfinyl, phenyl, nitro, and (dimethylamino)sulfonyl, and wherein the phenyl is optionally substituted with one or more substituents selected from halo, C1-6alkyl, and C1-6alkoxy.

21. The ruthenium complex of claim 20, wherein the ylidene is selected from benzylidene and indenylidene optionally substituted with a phenyl and / or a C1-6alkyl.

22. The ruthenium complex of any one of claims 17 to 19, wherein:(i) L2and L3are linked to form an optionally substituted ortho-C1-6alkoxyarylmethylene or an optionally substituted ortho-C1-6alkoxyheteroarylmethylene; or(iii) L2and L3together comprise a chelating ligand comprising a C1-6alkylidene substituted with a C5-6heteroaryl, wherein the C5-6heteroaryl is optionally substituted with one or more C1-6alkyl, optionally wherein the chelating ligand is 3-(2-pyridyl)propylidene.

23. The ruthenium complex of claim 22, which is of formula (ii):wherein:R1ais a Ci-ealkyl, optionally substituted with one or more selected from phenyl and -C(O)N(C1-6alkyl)(OC1-6alkyl);R2ais selected from hydrogen, C1-6alkyl, and phenyl; andR3ais selected from hydrogen, C1-6alkyl, nitro, (dimethylamino)sulfonyl, isobutoxycarbonylamido and trifluoroacetamido.

24. The ruthenium complex of any one of claims 17 to 23, wherein L4is:(i) absent; or(ii) an N-heteroaryl such as pyridine.

25. The ruthenium complex of any one of claims 17 to 24, which is selected from formula (iii), (iv), (v), (vi), (vii) and (viii):

26. Use of a ruthenium complex as defined in any one of claims 1 to 25, in catalysis.

27. The use of claim 26, wherein the catalysis is olefin metathesis.

28. A method of olefin metathesis comprising contacting a ruthenium complex as defined in any one of claims 1 to 25 with two olefins.

29. A method of preparing a ruthenium complex as defined in any one of claims 1 to 25, the method comprising contacting a ligand as defined in any one of claims 1 to 16 with a ruthenium precursor such that the ligand binds to the ruthenium, optionally wherein:the ligand is prepared by contacting a salt of formula (1) with a base:R^NVX'x' (1)wherein R1, R4, X1, n and the dashed line are as defined in any one of claims 1 to 16; andX’ is a monoanion, optionally selected from a hydrogencarbonate, tetraphenylborate, perchlorate, p-toluenesulfonate, triflate, halo, tetrafluoroborate and hexafluorophosphate,optionally wherein the pKa of the conjugate acid of the base is greater than or equal to about 10, such as greater than or equal to about 15.

30. The method of claim 29, wherein the ruthenium precursor is of formula (pa):L5L4, I _. X2^Ru’^X3" I ^L2L3(pa),wherein:L2is an ylidene;L3and L5are each an L-type ligand;L4is an optionally present L-type ligand; andX2and X3are each independently an X-type ligand,wherein L2and L3are optionally linked.

31. A ligand of formula (I):(R4)n^1R1-N^XR” (I),wherein:R1is a C1-6alkyl, or C6-10aryl;wherein the Ce- aryl is optionally substituted with one or more substituents selected from formula (II), Ci-ealkyl, Cs-wcarbocyclyl (e.g. Cs-ecarbocyclyl), Ca-wheterocyclyl (e.g. 5- or 6-membered heterocyclyl), halo, and a water-soluble group (e.g. a polyol (such aspolyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3‘), or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumCs-ioheterocyclyl)), and further wherein the substituent Ci-ealkyl, C3. locarbocyclyl and C3-ioheterocyclyl are each optionally substituted with one or more substituents selected from C3-iocarbocyclyl (e.g. Cs-ecarbocyclyl), C3-ioheterocyclyl (e.g.5- or 6-membered heterocyclyl) and formula (II), or wherein two substituent Ci-ealkyl together form a Cs-ecarbocyclyl ring;wherein formula (II) is:—(X)n2— ZY3(II)wherein:each X is independently selected from methylene, ethynylene, Ce- arylene (e.g. phenylene), and C3-wheteroarylene (e.g. 5- or 6-membered heteroarylene), wherein the Ce- arylene and C3-wheteroarylene are each optionally substituted with one or more substituents selected from Ci-ealkyl, halo, Ci-ehaloalkyl, and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3‘), or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumC3-ioheterocyclyl);n2 is 0, 1 or 2;Z is C or Si; andeach Y is independently selected from C3- carbocyclyl (e.g. Cs-ecarbocyclyl), C3. loheterocyclyl (e.g. 5- or 6-membered heterocyclyl), Ci-ealkyl, Ci-ehaloalkyl, C1-4alkenyl, Ci-ehaloalkenyl, Ciwalkynyl, and Ci-ehaloalkynyl, or two Y groups together with Z form a C3-io carbocycle or C3-wheterocycle, or three Y groups together with Z form a bridged polycyclic Cs- carbocycle or bridged polycyclic C3-wheterocycle,wherein each Y is optionally substituted with one or more substituents selected from Ci-ealkyl, C3- carbocyclyl (e.g. Cs-ecarbocyclyl), C3-wheterocyclyl (e.g. 5- or 6-membered heterocyclyl), halo, Ci-ehaloalkyl, and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3‘) or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumC3-ioheterocyclyl));X1is N-R2or C(R3)2, wherein:R2is a Ci-ealkyl, or Ce- aryl; wherein the C6-14aryl is optionally substituted with one or more substituents selected from formula (II), Ci-ealkyl, C3-wcarbocyclyl (e.g. Cs-ecarbocyclyl), C3-wheterocyclyl (e.g. 5- or 6-membered heterocyclyl), halo, and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3‘) or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl,or cyclic ammonium group, such as ammoniumC3-10heterocyclyl)), and further wherein the substituent Ci-ealkyl, Cs-wcarbocyclyl and Ca-wheterocyclyl are each optionally substituted with one or two substituents selected from Cs-wcarbocyclyl (e.g. Cs-ecarbocyclyl) and Ca-wheterocyclyl (e.g. 5- or 6-membered heterocyclyl) and formula (II), or wherein two substituent Ci-ealkyl together form a Cs-ecarbocyclyl ring;each R3is independently selected from Ci-ealkyl, C1-6alkenyl, halo, cyano, Ci-ealkoxy, C6-10aryloxy, C1-6alkylthiolate, C6-14arylthiolate, amino, Cs-wcarbocyclyl (e.g. Cs-ecarbocyclyl), Ca-wheterocyclyl (e.g. 5- or 6-membered heterocyclyl), Ci-ealkynyl, and a substituent of formula (II), wherein the Ci-ealkyl, C1-6alkenyl, Ci-ealkoxy, C6-10aryloxy, C1-6alkylthiolate, Ce- arylthiolate, Cs-wcarbocyclyl, the Ca-wheterocyclyl, and the Ci-ealkynyl are each optionally substituted with one or more substituents selected from Ci-ealkyl, C3- carbocyclyl, Ca-wheterocyclyl, halo, Ci-ealkoxy, C6-10aryloxy, C1-6alkylthiolate, C6-14arylthiolate, amino, and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3‘) an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumC3-10heterocyclyl));or wherein two R3groups together with the C form a Cs-wcarbocycle or a C3-wheterocycle, each optionally substituted with one or more substituents selected from Ci-ealkyl, Cs-wcarbocyclyl, Ca-wheterocyclyl, halo, Ci-ealkoxy, C6-10aryloxy, C1-6alkylthiolate, C6-14arylthiolate, amino, a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3⁻) an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumCs-wheterocyclyl), and a substituent of formula (II);each R4is independently selected from C1-6alkyl, halo, C1-6haloalkyl, and a water-soluble group (e.g. a polyol (such as polyethylene glycol, PEG), carboxylate (COO-), sulfonate (SO3-), or an ammonium group (e.g. ammonium (NH3+), an ammoniumCi-ealkyl, or cyclic ammonium group, such as ammoniumC3-10heterocyclyl); andthe dashed line is an optionally present bond, wherein n is 0 to 2 when the dashed line is a bond and n is 0 to 4 when the dashed line is not a bond;with the proviso that at least one of R1, R2or R3is substituted with a substituent of formula (II);and wherein the ligand is not any of the following structures:Ph Phwherein each A1is Ph, each A1is para-tolyl, or each A1is para-terf-butylphenyl.

32. A salt of formula (1):< R4)"^,x(1)wherein R1, R4, X1, n and the dashed line are as defined in claim 31; andX’ is a monoanion

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