complex

Abstract

The invention relates to organometallic compounds useful as pre-catalysts or catalysts in cross-coupling reactions. The invention provides a solid form composition comprising a nickel complex of formula (I) and a stabilising agent, which is an aryl or heteroaryl compound.

Description

[0001] P102548W001

[0002] 1

[0003] COMPLEX

[0004] Field

[0005] The present invention relates to a stabilised transition metal complex. More specifically, the present invention relates to nickel complexes which are stabilised against decomposition, e.g. from exposure to air and / or moisture.

[0006] Background

[0007] Transition metal catalyst complexes, which are organometallic in nature, find extensive application as catalysts and pre-catalysts in coupling reactions, including photochemical reactions such as photosensitised reactions.

[0008] Catalysts for coupling reactions traditionally comprise a platinum group metal and may be palladium (Pd) or platinum (Pt) centred. However, complexes that are Ni centred have in recent years become attractive in terms of cost and versatility, however. One such popular complex is bis(cyclooctadiene)nickel(0) (Ni(COD)2). This complex is regrettably highly air unstable and must be stored and used in airless environments, and / or be freshly prepared before each use.

[0009] Another Ni centred complex, which is regarded as advantageous compared to (Ni(COD)2) -at least because of its reported stability when used in an atmospheric environment (i.e. in air) - is (TMEDA)Ni(R)X. (TMEDA)Ni(R)X comprises a Ni(ll) centre that is coordinated to the diamine ligand TMEDA (N,N,N’,N’-tetramethylethylenediamine), an aryl or heteroaryl ligand (R), and a leaving group (X) which may typically be a halide.

[0010] In one embodiment of the abovementioned catalyst, the aryl ligand (R) is preferably o-tolyl and the halide leaving group (X) is preferably chloride, such that a preferred form of the complex is (TMEDA)Ni(o-tolyl)CI.

[0011] Although exhibiting air stability in use, (TMEDA)Ni(o-tolyl)CI is subject to chemical degradation and / or decomposition under ambient conditions in air, particularly when stored for extended periods of time. P102548W001

[0012] 2

[0013] More specifically, losses of active (TMEDA)Ni(o-tolyl)CI material over a period of one month, under atmospheric conditions, may be as high as 50 mol% or more.

[0014] This degradation cannot be obviated by taking steps to reduce or avoid exposure of the complex to air. Although storing the material at a lower temperature and under less humid conditions may improve the retention of active material, such an approach is not practical outside of a laboratory environment, e.g. in a production environment.

[0015] It would be advantageous to improve the stability of solid forms of transition metal catalyst complexes, particularly to allow for storage thereof in air for prolonged periods of time, and to do so in a manner that can be practically implemented outside of laboratory environments, e.g. in a production environment.

[0016] Summary

[0017] In a first aspect of the present invention there is provided a solid form composition comprising a nickel complex and a stabilising agent, wherein the nickel complex is a complex of Formula(l):

[0018] (L)nNi(R)X

[0019] (I)

[0020] wherein

[0021] L is a monodentate coordinating ligand, or a bidentate coordinating ligand;

[0022] R is aryl or heteroaryl;

[0023] X is a leaving group; and

[0024] n is 1 or 2,

[0025] the stabilising agent is a liquid aryl or heteroaryl compound, and the solid form composition comprises from 15 mol% to 50 mol% of the stabilising agent based on a combined molar amount of the nickel complex and the stabilising agent.

[0026] It has surprisingly been found that solid form compositions of the invention exhibit improved stability in air. Without being bound by any sort of theory, it is believed that the stabilising agent of the solid form composition functions to not only protect the nickel composition from P102548W001

[0027] 3

[0028] degradation by direct exposure to air, but further retards other decomposition mechanisms such as pathways which include degradation from reductive elimination of R and X ligands from the nickel complex.

[0029] In a second aspect of the invention there is provided a process for carrying out a coupling reaction using the solid form composition of the first aspect of the invention as a catalyst or pre-catalyst.

[0030] Definitions

[0031] The point of attachment of a moiety or substituent is represented by For example, -OH is attached through the oxygen atom.

[0032] “Alkyl” refers to a straight-chain or branched saturated hydrocarbon group. The alkyl group may be unsubstituted. Alternatively, the alkyl group may be substituted. Unless otherwise specified, the alkyl group may be attached at any suitable carbon atom and, if substituted, may be substituted at any suitable atom. Typical alkyl groups include but are not limited to methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl and the like.

[0033] “Aryl” refers to an aromatic carbocyclic group. The aryl group may have a single ring or multiple condensed rings. The aryl group may be unsubstituted. Alternatively, the aryl group may be substituted. Unless otherwise specified, the aryl group may be attached at any suitable carbon atom and, if substituted, may be substituted at any suitable atom. Examples of aryl groups include, but are not limited to, phenyl, naphthyl, anthracenyl and the like.

[0034] “Complex” is used in this specification to describe molecules in which multiple ligands are coordinated to a central metal atom. In the context of the invention, the metal atom is that of a transition metal. The ligands may be coordinated to the metal atom by covalent bonds and / or by electron donation coordination, or by intermediate bonds.

[0035] “Coordinating ligand” refers to chemical species that possess one or more donor atoms and that are capable of forming coordinate bonds with a metal centre, to serve a stabilising function with respect to the metal centre. Such ligands would, in the context of the invention, typically not participate in a reaction, such as a coupling reaction, in which the complex is used. These ligands can be either monodentate, binding through a single donor atom, or P102548W001

[0036] 4

[0037] polydentate, binding through multiple donor atoms, e.g. bidentate in which case the binding occurs through two donor atoms.

[0038] “Coupling” refers to a chemical reaction in which two molecules or parts of a molecule join together (Oxford Dictionary of Chemistry, Sixth Edition, 2008).

[0039] “Halo”, “halide”, or “hal” refers to F, Cl, Br and I atoms or ions.

[0040] “Heteroalkyl” refers to a straight-chain or branched saturated hydrocarbon group wherein one or more carbon atoms are independently replaced with one or more heteroatoms (e.g. nitrogen, oxygen, phosphorus and / or sulfur atoms). The heteroalkyl group may be unsubstituted. Alternatively, the heteroalkyl group may be substituted. Unless otherwise specified, the heteroalkyl group may be attached at any suitable atom and, if substituted, may be substituted at any suitable atom. Examples of heteroalkyl groups include but are not limited to ethers, thioethers, primary amines, secondary amines, tertiary amines and the like.

[0041] “Heteroaryl” refers to an aromatic carbocyclic group wherein one or more carbon atoms are independently replaced with one or more heteroatoms (e.g. nitrogen, oxygen, phosphorus and / or sulfur atoms). The heteroaryl group may be unsubstituted. Alternatively, the heteroaryl group may be substituted. Unless otherwise specified, the heteroaryl group may be attached at any suitable atom and, if substituted, may be substituted at any suitable atom. Examples of heteroaryl groups include but are not limited to thienyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, thiadiazolyl, thiophenyl, oxadiazolyl, pyridinyl, pyrimidyl, benzoxazolyl, benzthiazolyl, benzimidazolyl, indolyl, quinolinyl and the like.

[0042] “Heterocycloalkyl” refers to a saturated cyclic hydrocarbon group wherein one or more carbon atoms are independently replaced with one or more heteroatoms (e.g. nitrogen, oxygen, phosphorus and / or sulfur atoms). The heterocycloalkyl group may be unsubstituted. Alternatively, the heterocycloalkyl group may be substituted. Unless otherwise specified, the heterocycloalkyl group may be attached at any suitable atom and, if substituted, may be substituted at any suitable atom. Examples of heterocycloalkyl groups include but are not limited to epoxide, morpholinyl, piperadinyl, piperazinyl, thirranyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, thiazolidinyl, thiomorpholinyl and the like. P102548W001

[0043] 5

[0044] “Leaving group” is used in this specification to refer to an atom or group that detaches from a complex during a reaction, such as a coupling reaction. Without limitation, typical leaving groups include halides, sulfonates, and sulfonate esters. This does not exclude other functionally equivalent leaving groups.

[0045] Unless the context clearly indicates otherwise, the use of the term “stable”, including variations thereof such as “stabilised”, “stabilising” and the like, should in this specification be understood as meaning having, or causing, improved resistance to chemical degradation and / or decomposition over time, most prominently in air, e.g. under atmospheric conditions which would include the presence of moisture. Stability is preferably expressed in terms of the retention of “active” material of the nickel complex, i.e. material that remains fit for purpose (e.g. the nickel complex has an unaltered chemical composition / structure). In the context of the invention such purpose would be as a catalyst or pre-catalyst for use in coupling, including photosensitised, reactions. Such improved resistance would preferably be observed as retention of the nickel complex of the solid form composition of the invention, compared to the same nickel complex that did not comprise the stabilising agent according to the invention, when both materials are exposed to the same conditions for the same amount of time.

[0046] “Substituted” refers to a group in which one or more hydrogen atoms are each independently replaced with substituents (e.g. 1, 2, 3, 4, 5 or more) which may be the same or different. Examples of substituents include but are not limited to -halo, -C(halo)3, -R9, =0, =S, -O-R9, -S-R9, -NR9Rh, -CN, -NO2, -C(O)-R9, -COOR9, -C(S)-R9, -C(S)OR9, -S(O)2OH, -S(O)2-R9, -S(O)2NR9Rh, -O-S(O)-R9and -CONR9Rh, such as -halo, -C(halo)3(e.g. -CF3), -R9, -O-R9, -NR9Rh, -CN, or-NO2. R9and Rhare independently selected from the groups consisting of H, alkyl, aryl, heteroalkyl, heteroaryl, or R9and Rhmay be linked to form a heterocycloalkyl group. R9and Rhmay be unsubstituted or further substituted as defined herein.

[0047] Detailed Description

[0048] Each aspect or embodiment of the present invention as defined below may be combined with any other aspect(s) unless clearly indicated to the contrary. In particular, any feature(s) indicated as being preferred or advantageous may be combined with any other feature(s) indicated as being preferred or advantageous. Lower and / or upper limits of any ranges P102548W001

[0049] 6

[0050] disclosed herein are envisaged to be combinable with one another to provide new ranges, whether explicitly stated or not.

[0051] The invention relates to solid form compositions comprising nickel complexes, particularly those complexes that are useful as catalysts and precursors in coupling reactions, including photosensitised reactions.

[0052] Functionally, in the context of coupling and photosensitised reactions, the nickel complexes to which the present invention relates are typically referred to in the art as catalyst precursors, pre-catalysts, catalysts, catalyst compounds, transition metal compounds, transition metal catalysts, and transition metal complex catalysts. These terms may be used interchangeably.

[0053] In the first aspect, the present invention provides a solid form composition comprising a nickel complex of Formula (I):

[0054] (L)nNi(R)X

[0055] (I)

[0056] wherein

[0057] L is a monodentate coordinating ligand, or a bidentate coordinating ligand;

[0058] R is aryl or heteroaryl;

[0059] X is a leaving group; and

[0060] n is 1 or 2.

[0061] The nickel complex of formula (I) may be an air-unstable nickel complex, i.e. a nickel complex that is subject to chemical decomposition and / or degradation in air, e.g. under atmospheric conditions. Such instability may, for example, be of an extent that results in a loss of active nickel complex of more than 30 mol%, or more than 40 mol%, e.g. up to 50 mol%, or more, over a period of 1 month or more.

[0062] The nickel complex of formula (I) is preferably one that is functionally suitable as a catalyst or pre-catalyst in coupling reactions, including photosensitised reactions.

[0063] In the complex of formula (I), the nickel atom may be present in an oxidation state of +2. The nickel complex of formula (I) may therefore be a nickel(ll) complex of formula (I). In such a P102548W001

[0064] 7

[0065] +2 oxidation state, Ni typically exhibits a coordination number of 4 or 6, however, complexes with a coordination number of 3 are known (e.g. where L is a highly electron donating ligands such as a carbene). In the complex of formula (I), Ni preferably has a coordination number of 4.

[0066] Without limiting the abovementioned meaning of the term “stable”, it is understood that typical chemical degradation and / or decomposition to which nickel complexes are prone, most prominently in air, include the formation of Ni hydroxide (Ni(OH)2), Ni halides (e.g. NiCh), Ni(l) species, and / or Ni(0) species.

[0067] In the nickel complex of formula (I), the coordinating ligand, L, is a monodentate ligand or a bidentate ligand. The coordinating ligand, L, in the nickel complex of formula (I) may be a monodentate ligand and n may have a value of 1 or 2. Preferably, the coordinating ligand, L, in the nickel complex of Formula (I) may be a monodentate ligand and n may have a value of 2. Alternatively, the coordinating ligand, L, in the nickel complex of formula (I) may be a bidentate ligand and n may have a value of 1.

[0068] Preferably, the coordinating ligand, L, may be a diamine, a diimine, a phosphine, a bis(phosphine), a N-heterocyclic carbene (NHC), a pyridine, ora bipyridine.

[0069] Specific diamine ligands that are particularly preferred include substituted ethylenediamines including mono-, di-, tri-, or tetra- substituted ethylenediamines, substituted with substituents such as methyl, ethyl, or isopropyl.

[0070] Suitable diamines preferably include, for example, N,N,N’,N’-tetramethylethylenediamine (TMEDA), N,N,N’,N’-tetraethylethylenediamine (TEEDA), N,N,N’,N’-tetraphenylethylenediamine (TPhEDA), N,N,N',N'-Tetramethyl-1,3-propylenediamine (TMPDA), N,N,N',N'-Tetraethyl-1,3-propylenediamine (TEPDA), and N,N,N',N'-Tetraphenyl-1,3-propylenediamine (TPhPDA). Most preferably, the coordinating ligand, L, is N,N,N’,N’-tetramethylethylenediamine (TMEDA).

[0071] Specific diimines preferably include, for example, N,N'-1,2-Ethanediylidenebis[2-isopropanamine]. P102548W001

[0072] 8

[0073] Specific phosphine ligands that are particularly preferred include tricyclohexylphosphine (PCys), triphenylphosphine (PPhs), tri-terf-butylphoshine (P‘Bu3), triadamantylphosphine (PAds), n-butyl-dicylcohexylphosphine (PnBuCy2), and n-butyl-di-terf-butylphosphine (PnBu‘Bu2).

[0074] Specific bis(phosphine) ligands that are particularly preferred include 1,2-bis(diphenylphosphino)ethane (DPPE), 1,2-bis(diphenylphosphino)propane (DPPP), and 1,2-bis(di-terf-butylphosphino)ethane.

[0075] Specific N-heterocyclic carbene ligands that are particularly preferred include imidazolidines, 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (IPr), 1 ,3-Bis(2,6-Di-3-pentylphenyl)imidazol-2-ylidene (I Pent), 1,3-Bis-(2,4,6-Tribenzhydrylphenyl)-1H-imidazol-3-ylidene (IPr*), (1S,2S,2"S,5R,5"R,7'S)-2,2"-Diisopropyl-5,5"-dimethyl-2'H,8'H-dispiro[cyclohexane-1,3'-imidazo[4,3-b:5,1-b']bis(oxazole)-7',T'-cyclohexan]-4'-ylidene or an isomer thereof (IBiox).

[0076] Specific pyridine and bipyridine ligands that are particularly preferred include 4,4’-Di-tert-butyl-2,2-dipyrine (Dtbbpy), 1,10-phenanthroline, 3,4,7,8-Tetramethyl-1,10-phenanthroline (Me4Phen), 4,4’-dimethyl-2,2’-bipyridine, 2,2’-bipyridine, 2,9-Dimethyl-4,7-diphenyl-1,10-phenanthroline (bathocuproine).

[0077] In the nickel complex of formula (I), the leaving group, X, may be an anionic ligand selected from a halide ligand, a sulfonate ligand, a sulfonate ester, or a weakly-coordinating anionic ligand.

[0078] Where X may be a halide ligand, X may be chloride (Cl’), bromide (Br), or iodide (I’), preferably chloride (Cl’). Where X may be a sulfonate, suitable sulfonates may include alkyl sulfonates and aryl sulfonates. Where X may be a sulfonate, X may preferably be trifyl, tosyl, mesyl, or nonafyl. Where X may be a weakly-coordinating anionic ligand, X may be selected from ’BF4, ’PFe, ’SbFe, and CIO4. Where X may be a sulfonate ester, X may be selected from alkyl and aryl sulfonate esters, preferably triflate, tosylate, mesylate, or nonaflate.

[0079] It may be preferred thatX is a halide ligand, most preferably chloride (Cl’). P102548W001

[0080] 9

[0081] In the nickel complex of formula (I), R is aryl or heteroaryl. R may be aryl or heteroaryl as defined hereinabove.

[0082] In the nickel complex of formula (I), R may preferably be a mono- or polycyclic aryl or heteroaryl group, which may be substituted or unsubstituted. R may preferably be selected from substituted or unsubstituted phenyl, naphthyl, benzyl, and tolyl. Substituents, if present, preferably include one or more of alkyl, alkoxy, halo, nitro, cyano, and aryl.

[0083] It may be preferred that R is a sterically hindered aryl or heteroaryl group.

[0084] It may be particularly preferred that R is tolyl, most preferably o-tolyl.

[0085] In preferred solid form compositions of the invention, the nickel complex of formula (I) may be (TMEDA)Ni(R)CI, wherein R is preferably 2-toluene (o-tolyl). For the avoidance of doubt, in such a nickel complex of formula (I), L is the bidentate coordinating ligand TMEDA, R is o-tolyl, X is Cl; and n is 1.

[0086] The solid form composition of the invention comprises a stabilising agent that is a liquid aryl or heteroaryl compound.

[0087] Since the composition of the invention is in a solid form, it will be appreciated that the stabilising agent would preferably not be a solvent for the nickel complex.

[0088] When the stabilising agent is a solvent for the nickel complex, however, the quantity of the stabilising agent would preferably be selected such that it would not dissolve the nickel complex to an appreciable extent.

[0089] As discussed below, the amount of the stabilising agent may be selected such that the nickel complex is not formed into a paste, slurry, suspension, or solution by the stabilising agent. Instead, it is preferred that the amount of the stabilising agent may be selected such that the nickel complex is surface treated, e.g. wetted, with the stabilising agent.

[0090] The solid form composition of the invention comprises from 15 mol% to 50 mol% of the stabilising agent, based on a combined molar amount of the nickel complex and the stabilising agent. Preferably, the solid form composition of the invention may comprise from P102548W001

[0091] 10

[0092] 18 mol% to 45 mol%, e.g. 18 mol%, more preferably from 20 mol% to 40 mol%, more preferably from 20 mol% to 30 mol% (e.g. 22 mol%, 25 mol%, or 28 mol%) of the stabilising agent, based on a combined molar amount of the nickel complex and the stabilising agent.

[0093] It has surprisingly been found that when the solid form composition of the invention comprises less than 15 mol% of the stabilising agent then the stabilising ability of the stabilising agent is vastly diminished.

[0094] The solid form composition may comprise the stabilising agent in an amount sufficient to retain at least 30 mol%, preferably at least 40 mol%, more preferably at least 50 mol%, more preferably at least 60 mol%, more preferably at least 70 mol% of the nickel complex in a stable form at the end of a retention period.

[0095] As used here, “retention period” refers to a period of time in which the stability of the nickel complex retains a certain amount of the nickel complex in a stable form. In other words, the quantity of the nickel complex that is retained in a stable form by the presence of the stabilising agent is preferably that as measured at the end of the retention period.

[0096] The retention period may preferably be at least 1 month, more preferably at least 2 months, more preferably at least 3 months.

[0097] Retention of the solid form of the complex in a stable form can be determined by any suitable analytical method, compared to a pre-treated active form of the complex. Preferably, such a method may be a spectroscopic method. One suitable method is nuclear magnetic resonance (NMR) spectroscopy, more specifically quantitative NMR (qNMR). Proton NMR (qHNMR) is particularly suitable.

[0098] It may be preferred that the liquid aryl or heteroaryl compound is a parent compound of R in Formula (I), i.e. the R group is a derivative of the liquid aryl or heteroaryl compound. For example, where R is o-tolyl, the liquid aryl or heteroaryl compound is preferably toluene or a derivate thereof (e.g. a chloro-toluene, e.g. 2-chlorotolune).

[0099] The stabilising agent may be a substituted or unsubstituted liquid aryl or heteroaryl compound. The stabilising agent may be one or more selected from a substituted or unsubstituted toluene, benzene, mesitylene, methoxybenzene, ethylbenzene, cymene, or P102548W001

[0100] 11

[0101] xylene. The stabilising agent may preferably be a substituted or unsubstituted toluene (e.g. toluene, or 2-chlorotoluene). Where the stabilising agent may be a substituted liquid aryl or heteroaryl compound, it may preferably be substituted with a halide atom, preferably substituted with a chloride, bromide, or iodide atom.

[0102] Accordingly, the stabilising agent may preferably be a liquid aryl halide or liquid heteroaryl halide, i.e. a liquid aryl or heteroaryl compound with one or more halogen substituents. The liquid aryl or heteroaryl halide may be mono- or polycyclic aromatic, substituted or unsubstituted. The liquid aryl or heteroaryl halide may be a chloro-, bromo-, or iodosubstituted aryl compounds, preferably a chloro- substituted aryl or heteroaryl compound. Suitable aryl groups for the liquid aryl halide preferably include phenyl, tolyl, and naphthyl. For example, the liquid aryl or heteroaryl halide may be selected from 2-chlorotoluene and 1 -chloronaphthalene, preferably, 2-chlorotoluene.

[0103] The stabilising agent may preferably be a compound of formula RX, where R and X are both as defined in, and present in, the nickel complex of formula (I). In other words, it may be preferred that the stabilising agent may be a compound of formula RX, where R and X are both the same as R and X in the nickel complex of formula (I).

[0104] The solid form composition of the invention may be prepared by treatment (e.g. contacting) of the nickel complex with the stabilising agent. This may for example include adding or applying the stabilising agent to or mixing the stabilising agent with the nickel complex.

[0105] The treatment of the nickel complex with the stabilising agent may preferably be a surface treatment, i.e. such that the stabilising agent is applied to the surface of (or surfaces of) the nickel complex (e.g. by spraying of the stabilising agent, such as by nebulising and spraying the stabilising agent).

[0106] The amount of the stabilising agent is preferably selected such that treatment of the nickel complex results in the stabilising agent being applied to the surface of particles or crystals of the nickel complex, e.g. such that a coating or layer of the stabilising agent forms on the surface of the nickel complex. It may be preferred that the stabilising agent encapsulates the nickel complex, e.g. particles or crystals of the nickel complex. It may be preferred that the stabilising agent encapsulates the nickel complex and protects the nickel complex (e.g. P102548W001

[0107] 12

[0108] particles or crystals of the nickel complex) from exposure to air (e.g. from oxygen and / or moisture in air).

[0109] Most preferably, treatment of the nickel complex with the stabilising agent, and selection of the amount of the stabilising agent, are such that the nickel complex is wetted by the stabilising agent.

[0110] The solid form composition is preferably a particulate form. For example, in one embodiment of the invention, the solid form composition is preferably a powder. It is therefore preferred that the solid form composition may have a free-flowing particulate character.

[0111] When the solid form composition is a particulate form, the amount of the stabilising agent is preferably selected such that the solid form composition retains a free-flowing particulate character after treatment with the stabilising agent. As mentioned above, it is undesired for the solid form composition to be formed, for example, into a paste, slurry, suspension, or solution through treatment thereof with the stabilising agent.

[0112] In preferred solid form compositions of the invention, the nickel complex of formula (I) may be (TMEDA)Ni(R)CI, wherein R is preferably 2-toluene (o-tolyl), and the stabilising agent may be toluene or 2-chlorotoluene.

[0113] In a second aspect, the present invention provides a process for carrying out a coupling reaction using the solid form composition of the first aspect of the invention as a catalyst or pre-catalyst.

[0114] The process of the second aspect may comprise the step of contacting the solid form composition of the invention with one or more organic reagents. The process of the second aspect may comprise the step of coupling the one or more organic reagents to form a coupled product.

[0115] The invention is now exemplified with reference to a non-limiting example, in which the invention was applied to stabilise (TMEDA)Ni(o-tolyl)CI in particulate form using different stabilising agents under the same and different conditions. P102548W001

[0116] 13

[0117] It will be appreciated that (TMEDA)Ni(o-tolyl)CI is a complex of Formula 1 wherein L is TMEDA and n is 1 , R is o-tolyl, and X is Cl'.

[0118] Sample preparation

[0119] A bulk quantity of (TMEDA)Ni(o-tolyl)CI material was prepared in a manner that is conventionally known in the art and was recovered in a particulate form. The material was then dried by evaporation under a stream of dry nitrogen.

[0120] Samples of the material were taken and compared to a reference standard for the complex by means of qHNMR. A minimum purity of 98% was required for testing.

[0121] Upon achieving the required minimum purity, samples of the material were weighed and then respectively doped (i.e. treated) with stabilising agents according to the invention. Mass ratios of catalyst material : stabilising agent of 80:20, 70:30, and 95:5 were used.

[0122] Stabilising agents that were used were toluene as aromatic solvent, and 2-chlorotoluene and 1-chloronapthalene as liquid aryl halides.

[0123] Doping was performed by adding the liquid stabilising agents to the respective samples of material and then gently stirring the resulting mixture of material and stabilising agent. The amount of stabilising agent that was used was selected to avoid forming a paste, slurry, suspension, or solution of the material in the stabilising agent, and to keep the material, once treated, in a free-flowing particulate form.

[0124] The material that was doped was fresh in each case.

[0125] As a result of the treatment with the stabilising agent, the material, which was originally bright red-orange, turned dark red-orange.

[0126] Stability Studies

[0127] Each sample of doped material was placed in an open vial, which was then loaded into a humidity-controlled environment in which it was retained at an evaluation temperature for 1-month and 3-month evaluation periods respectively. P102548W001

[0128] 14

[0129] An evaluation temperature of 21 °C was selected and the samples were exposed to air, at various humidities.

[0130] For evaluation, the material that remained in each of the vials after the respective evaluation periods had elapsed was washed with pentanes. The material was then collected and dried.

[0131] A sample of the washed and dried material was then weighed and analysed by HNMR with an elongated D1 setting.

[0132] From the results of the HNMR analysis, a relationship of the tolyl group and the reference standard was observed. This relationship was translated to a quantification of purity which corresponded to the quantity of the solid form of the complex that survived (i.e. was retained) over the evaluation period in an active state.

[0133] An evaluation was also performed on material that was not treated with any stabilising agent.

[0134] Results

[0135] The results of the evaluations are set out in Tables 1 and 2, below.

[0136] Table 1 : Purity of particulate complex after 1 month

[0137]

[0138] Table 2: Purity of particulate complex after 1 or 3 months

[0139]

[0140] P102548W001

[0141] 15

[0142]

[0143] Discussion

[0144] Each of 2-chlorotlouene and toluene imparted improved stability on the material over the 1-month time frame. It was found that this could viably be extended to 3 months, over which period there was also significantly improved stability compared to untreated material.

[0145] Using 1-chloronapthalene as the stabilising agent also showed an improvement in stability, including over 3 months.

[0146] It was found that an amount of the stabilising agent above 18 mol%, based on the combined molar amount of the stabilising agent and the particulate complex, was particularly effective in achieving long term stability, whereas lower amounts provided no improvement in stability compared to material that was not doped with any stabilising agent.

[0147] While not wishing to be bound by theory, the applicant believes that the stabilization agent of the invention acts as a layer on top of the material and protects it from air and moisture decomposition, e.g. to form Ni(OH)2, a Ni(l) species, Ni(0), or NiCh.

[0148] Toluene is believed to be particularly advantageous in that it is a byproduct of the degradation process of (TMEDA)Ni(o-tolyl)CI and is therefore understood to help prevent such degradation.

[0149] 2-chlorotoluene is believed to work in a similar way, except that, in addition, it may replace any reductive elimination or ligand exchange that occurs in (TMEDA)Ni(o-tolyl)CI by addition of the same ligand(s) via an oxidative addition process.

Claims

P102548W00116Claims1. A solid form composition comprising a nickel complex and a stabilising agent, wherein the nickel complex is a complex of Formula(l):(L)nNi(R)X(I)whereinL is a monodentate coordinating ligand, or a bidentate coordinating ligand; R is aryl or heteroaryl;X is a leaving group; andn is 1 or 2,the stabilising agent is a liquid aryl or heteroaryl compound, and the solid form composition comprises from 15 mol% to 50 mol% of the stabilising agent based on a combined molar amount of the nickel complex and the stabilising agent.

2. A solid form composition according to claim 1, wherein the coordinating ligand, L, is a monodentate ligand and n has a value of 1 or 2, and / or the coordinating ligand, L, is a bidentate ligand and n has a value of 1.

3. A solid form composition according to any one of the preceding claims, wherein the coordinating ligand, L, is a diamine, a phosphine, a bis(phosphine), a diimine, a N- heterocyclic carbene (NHC), a pyridine, or a bipyridine, preferably a diamine.

4. A solid form composition according to any one of the preceding claims, wherein the coordinating ligand, L, is a diamine which is a substituted ethylenediamine, or a mono- , di-, tri-, or tetra- substituted ethylenediamines.

5. A solid form composition according to claim 1, wherein the coordinating ligand, L, is N,N,N’,N’-tetramethylethylenediamine (TMEDA).

6. A solid form composition according to any one of claims 1 to 3, wherein the coordinating ligand, L, is selected from tricyclohexylphosphine (PCys), triphenylphosphine (PPhs), tri-terf-butylphoshine (P‘Bu3), triadamantylphosphineP102548W00117(PAds), n-butyl-dicylcohexylphosphine (PnBuCy2), and n-butyl-di-terf-butylphosphine (PnBu‘Bu2).

7. A solid form composition according to any one of claims 1 to 3, wherein the coordinating ligand, L, is selected from 1,2-bis(diphenylphosphino)ethane (DPPE), 1,2-bis(diphenylphosphino)propane (DPPP), and 1 ,2-bis(di-terf- butylphosphino)ethane.

8. A solid form composition according to any one of claims 1 to 3, wherein the coordinating ligand, L, is N,N'-1,2-Ethanediylidenebis[2-isopropanamine],9. A solid form composition according to any one of claims 1 to 3 or claim 6, wherein the coordinating ligand, L, is selected from imidazolidines, 1,3-bis(2,6- diisopropylphenyl)imidazol-2-ylidene (IPr), 1,3-Bis(2,6-Di-3-pentylphenyl)imidazol-2- ylidene (I Pent), 1,3-Bis-(2,4,6-Tribenzhydrylphenyl)-1H-imidazol-3-ylidene (IPr*), (1S,2S,2"S,5R,5"R,7'S)-2,2"-Diisopropyl-5,5"-dimethyl-2'H,8'H-dispiro[cyclohexane- 1,3'-imidazo[4,3-b:5,1-b']bis(oxazole)-7',T'-cyclohexan]-4'-ylidene or an isomer thereof (I Biox).

10. A solid form composition according to any one of the preceding claims, wherein the leaving group, X, is an anionic ligand selected from a halide ligand, a sulfonate ligand, a sulfonate ester, or a weakly-coordinating anionic ligand.

11. A solid form composition according to any one of the preceding claims, wherein R is a mono- or polycyclic aryl or heteroaryl group which is substituted or unsubstituted.

12. A solid form composition according to any one of the preceding claims, wherein R is tolyl, preferably o-tolyl.

13. A solid form composition according to claim 1 , wherein the nickel complex of formula (I) is (TMEDA)Ni(o-tolyl)CI, where TMEDA is N,N,N’,N’-tetramethylethylenediamine.

14. A solid form composition according to any one of the preceding claims, wherein the solid form composition comprises from 18 mol% to 45 mol%, from 20 mol% to 40 mol%, or from 20 mol% to 30 mol% of the stabilising agent, based on a combined molar amount of the nickel complex and the stabilising agent.P102548W0011815. A solid form composition according to any one of the preceding claims, wherein the solid form composition comprises the stabilising agent in an amount sufficient to retain at least 30 mol%, preferably at least 40 mol%, more preferably at least 50 mol%, more preferably at least 60 mol%, more preferably at least 70 mol% of the nickel complex in a stable form at the end of a retention period.

16. A solid form composition according to claim 15, wherein the retention period if at least 1 month, at least 2 months, or at least 3 months.

17. A solid form composition according to any one of the preceding claims, wherein the stabilising agent is a liquid aryl halide or a liquid heteroaryl halide.

18. A solid form composition according to claim 17, wherein the liquid aryl halide or the liquid heteroaryl halide is a mono- or polycyclic aromatic, which is substituted or unsubstituted.

19. A solid form composition according to any one of the preceding claims, wherein the stabilising agent is a compound of formula RX, where R and X are both the same as R and X in the nickel complex of formula (I) of any one of claims 1 to 18.

20. A solid form composition according to any one of the preceding claims, wherein the stabilising agent encapsulates the nickel complex.

21. A solid form composition according to any one of the preceding claims, wherein the stabilising agent wets the nickel complex.

22. A solid form composition according to any one of the preceding claims, wherein the solid form composition is a powder and / or the solid form composition has a free- flowing particulate character.

23. A process for carrying out a coupling reaction using the solid form composition any one of claims 1 to 22 as a catalyst or pre-catalyst.

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