Catalyst and synthesis thereof

Abstract

The invention relates to nickel complexes comprising a ketone moiety and one or more stabilising ligands, as well as methods to synthesise such complexes by contacting precursor nickel complexes with a reducing agent and either a glycol or a ketone. The invention further relates to use of the nickel complexes as catalysts, such as cross-coupling catalysts.

Description

[0001] CATALYST AND SYNTHESIS THEREOF FIELD The invention relates to nickel complexes comprising a ketone moiety and one or more stabilising ligands, as well as methods to synthesise such complexes by contacting precursor nickel complexes with a reducing agent and either a glycol or a ketone. The invention further relates to use of the nickel complexes as catalysts, such as cross- coupling catalysts. BACKGROUND Cross-coupling reactions enable the rapid assembly of molecules from two functionalised fragments. The Nobel Prize in Chemistry 2010 was awarded to three pioneers of this technology (Heck, Negishi and Suzuki) and a recent literature survey noted that these reactions are amongst the few modern reactions to be rapidly and widely adopted by the pharmaceutical industry (D. G. Brown and J. Boström, J. Med. Chem., 2015, 59, 4443-4458). Most reactions of this class are catalysed by palladium. This metal is expensive, supply is constrained, prices fluctuate considerably, and the production of palladium is very energy-intensive (ca.4,000 kg CO2equiv. per kg palladium). Attention in the field has turned towards nickel owing ly lower (and more stable) cost, and lower environmental impact (ca.6.5 kg CO2 equiv. per kg nickel). Nickel catalysis has not yet been widely adopted in industry, this relying on the provision of commercially available and robust nickel catalysts, which are currently limited. Current options can be divided into two categories: (i) nickel sources that are combined with a ligand in situ to form an active catalyst, or (ii) nickel sources that include a ligand already attached to the nickel centre. The former is preferred for reaction screening purposes and where flexibility is needed, such as in discovery chemistry applications, where many different reactions are executed. Commercially available nickel sources that may be combined with a ligand in situ to form active catalysts include [Ni(COD)2] (COD = 1,5-cyclooctadiene), [NiCl2(DME)] (DME = 1,2-dimethoxyethane), NiCl2(OH2)4.2H2O, [Ni(stbX)3] (stbX-disubstituted stilbene, where X refers to the substituent at the 4-position and which is typically CF3or t-Bu), and [Ni(COD)(DQ)] (DQ = duroquinone). However, each of these has disadvantages. [Ni(COD)2] is the market-leading source of nickel. It is typically prepared using 155425773-4 hazardous aluminium reducing agents at low (<< 0°C) temperatures, and requires storage under inert atmosphere, in a freezer, protected from light, to avoid decomposition in the solid state. To be useful in catalysis, [NiCl2(DME)] (DME = 1,2-dimethoxyethane) requires reduction to nickel(0) in situ, which can lead to unwanted by-products. Coordination of a ligand to NiCl2(OH2)4.2H2O requires the displacement of water, which is then introduced into the reaction mixture, which may lead to unwanted side-reactions. [Ni(stbX)3] complexes are a recent development and are prepared using pyrophoric aluminium reagents at << 0 °C (see L. Nattmann and J. Cornella, Organometallics, 2020, 39, 3295-3300; and L. Nattmann et al., Nature Catalysis, 2019, 3, 6). Coordination of a ligand to these complexes displaces the stilbene ligand, which remains in solution and can compete with reaction substrates for binding to the nickel complex. The inventors have found that [Ni(COD)(DQ)] is best prepared from [Ni(COD)2]. They have found that [Ni(COD)(DQ)] is resistant to ligand displacement, limiting its use in reactions where forcing conditions are not used. Nickel sources that include a ligand already attached to the nickel centre are more suited to applications in process-scale chemistry, where the preferred ligand has already been identified and where decreasing the number of operations is advantageous for safety reasons. Several classes of complex are known, and include [NiX(Ar)(L)n] (where X is a halo-type ligand, Ar is an aryl, L is a mono- or bidentate phosphine, and n is 2 when L is monodentate and n is 1 when L is bidentate, see E. A. Standley, S. J. Smith, P. Müller and T. F. Jamison, Organometallics, 2014, 33, 2012-2018); [NiCl(allyl)(L)] (where L is a bidentate phosphine or an N-heterocyclic carbene), prepared from [Ni(COD)2] (see S. Ge and J. F. Hartwig, Angew. Chem. Int. Ed., 2012, 51, 12837-12841 and A. R. Martin, D. J. Nelson, S. Meiries, A. M. Z. Slawin and S. P. Nolan, Eur. J. Org. Chem., 2014, 2014, 3127-3131); and [Ni(alkene)2(L)] (where L is an N-heterocyclic carbene), prepared from [Ni(COD)2] (see A. J. Nett, S. Cañellas, Y. Higuchi, M. T. Robo, J. M. Kochkodan, M. T. Haynes, J. W. Kampf and J. Montgomery, ACS Catal., 2018, 8, 6606-6611). These complexes require reduction to nickel(0). The timescale of reactions in which these complexes are reduced is not well-understood, and such reactions generate unwanted by-products that contaminate the desired products. As described above, there are significant disadvantages to using [Ni(COD)2] as a nickel catalyst precursor. Some catalytically active nickel(0) complexes comprising labile ketone ligands and stabilising di-phosphine, mono-phosphine or N-heterocyclic carbene ligands are known in the art. Tsou, Huffman and Kochi, in Inorg. Chem., 1979, 18, 2311-2317, describe the synthesis of a nickel(0) complex comprising benzophenone and triethylphosphine from reaction of [Ni(PEt3)4] and benzophenone. The same disadvantages associated with the 255425773-4 synthesis and storage of [Ni(COD)2] also apply to the synthesis and storage of [Ni(PEt3)4]. Newman-Stonebraker et al., in Science, 374, 301-308 (2021) and in J. Am. Chem. Soc., 2022, 144, 19635-19648, describe the synthesis of nickel(0) complexes comprising 4- fluorobenzaldehyde and one or two monodentate phosphine ligands from reaction of [Ni(COD)2] with the phosphine ligand and 4-fluorobenzaldehyde. The same synthetic procedure is also used by Desnoyer et al. in Chemistry A European Journal, 25, 20, 5259-5268 (2019) to synthesise nickel(0) complexes comprising benzaldehyde, cyclohexanone or cyclohexenone, and di-tert-butylphosphinoethane (dtbpe). Mindiola et al., in Inorg. Chim. Acta, 2003, 345, 299-308, describe the synthesis of a nickel(0) complex comprising benzophenone and dtbpe from reaction of the nickel(I) dimer [Ni(dtbpe)Cl]2 with sodium and benzophenone. The dimer is synthesised from [Ni(dtbpe)Cl2] by reducing with potassium graphite (KC8). Tendera et al., in European Journal of Inorganic Chemistry, 2020, 33, 3194-3207, describe the synthesis of nickel(0) complexes comprising 1,3-Bis(2,4,6-trimethylphenyl)- 1,3-dihydro-2H-imidazol-2-ylidene (IMes) or 1,3-diisopropyl-imidazoline-2-ylidene (ImiPr), and an olefin, ketone or aldehyde. These complexes are made by reacting a [Ni(IMes)2] or [Ni(ImiPr)2] complex, prepared from [Ni(COD)2] and two equivalents of the N-heterocyclic carbene, with the olefin, ketone or aldehyde. As described above, there are significant disadvantages to using [Ni(COD)2] as a nickel catalyst precursor. N. Ishida et al., in Organometallics, 2019, 38, 1413- preparation of [Ni(COD)2] from [Ni(acac)2] (where acac is acetylacetone) by reducing the nickel(II) of [Ni(acac)2] using a mixture of xanthone, isopropanol, acetic acid and COD, and solar or LED light. On irradiation, the xanthone is reductively dimerised to form a highly sterically congested vicinal diol, which breaks apart to form two ketyl radicals. The ketyl radicals reduce the nickel(II) to nickel(0), which becomes bound by COD. The ketyl radicals are oxidised to re-form xanthone. Thus, the ketyl radicals are used as part of a catalytic cycle in which xanthone re-forms and does not bind to the nickel. There is a need in the art for alternative or improved methods to produce a broad range of catalytically active nickel(0) complexes from nickel(II) starting materials, that are prepared using less hazardous agents than, for example, the aluminium reducing agents used to produce [Ni(COD)2], and / or that are more easily stored than, for example, [Ni(COD)2]. The present invention addresses this need. 355425773-4 SUMMARY OF THE INVENTION The invention is based on the inventors having found that ketyl anions or ketyl dianions derived from ketones or glycols may be used to reduce nickel(II) to nickel(0), with the resultant nickel(0) being bound to the ketone or a ketone derived from the glycol. The process has proven to be highly resilient to different ligand types and has been used by the inventors to synthesise a broad range of nickel(0) complexes stabilised by various different ketones and other stabilising ligands. The nickel(II) starting materials used in the process are commercially available and are prepared using less hazardous agents than, for example, the aluminium reducing agents used to produce [Ni(COD)2]. The nickel(II) starting materials are also very easy to handle and to store (they are chemically stable under standard ambient conditions). Viewed from a first aspect, therefore, the present invention provides a method for the formation of a [Ni(L)n(Q)] complex from a [Ni(L)n(X)2] complex, the method comprising contacting the [Ni(L)n(X)2] complex with: (i) (a) a reducing metal or a base; and (b) a glycol comprising tertiary vicinal hydroxy moieties wherein at least one of the carbon atoms bonded to a tertiary vicinal hydroxy moiety is adjacent to a pi system; or (ii) (a) a reducing metal; and (b) a ketone comprising a carbonyl moiety conjugated with a pi system, wherein: Q is the ketone, or a ketone derived from the glycol, complexed to nickel; L is a mono-, di-, or tri-dentate L-type ligand, wherein n is 2 when L is monodentate and n is 1 when L is di- or tri-dentate; and X is a monovalent or divalent monoanionic ligand. The inventors have found that the process of the first aspect allows for the preparationof otherwise elusive species that, to the best of the inventors knowledge, cannot beproduced by any other means. 455425773-4 Accordingly, viewed from a second aspect, the invention provides a [Ni(L)n(Q)] complex wherein: Q is a ketone complexed to nickel, wherein the ketone comprises a carbonyl moiety conjugated with a pi system; L is a mono-, di-, or tri-dentate L-type ligand selected from tri-C1-6alkylphosphine (such as tri-n-butylphosphine), tri-cycloC5-6hydrocarbylphosphine, C1-4alkyl-di-cycloC5- 6hydrocarbylphosphine, -tetraC1-4alkylC2-4alkylenediamine, - pentaC1-4alkylC2-4alkylenetriamine, N,N-containing C12-14heterotricyclic ligand, bis(di- cycloC5-6hydrocarbylphosphino)C2-4alkylene, bis(di-cycloC5- 6hydrocarbylphosphino)xanthene, bis(di-C1-4alkylphosphino)xanthene, bis(di-cycloC5- 6hydrocarbylphosphino)ferrocene, bis(di-C1-4alkylphosphino)ferrocene, bis(di-cycloC5- 6hydrocarbylphosphinophenyl)ether, and bis(di-C1-4alkylphosphinophenyl)ether, each of which is optionally substituted with one or more substituents selected from C1-4alkyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy and morpholino, L is an N,N-containing C10heterobicyclic ligand optionally substituted with one or more substituents selected from C1-4alkyl, halo, C1-4haloalkyl, hydroxy, and C1-4alkoxy, L is a diC1-4alkyl-phosphino-biphenyl or a di-cycloC5-6hydrocarbylphosphino- biphenyl, wherein each biphenyl is optionally substituted with one or more substituents selected from C1-4alkyl, di(C1-4alkyl)amino, and C1-4alkoxy, or L comprises a di-cycloC5-6hydrocarbylphosphino binding moiety linked, optionally by an alkyl linker, to an N-heterocyclic carbene binding moiety; wherein when L is monodentate, n is 2 and when L is bi- or tri-dentate, n is 1; and X is halo. Nickel(0) complexes of the type obtainable by the process of the first aspect have been reported in the art to be active catalysts, for example in carbon-coupling reactions such as Suzuki-Miyaura and C-N coupling reactions (see Newman-Stonebraker, 2022 and 2021, supra). Similarly, the inventors have found the complexes of the second aspect to be active in catalysis, including cross-coupling. Thus, viewed from a third aspect, the invention provides for the use of a complex as defined in the second aspect as a catalyst, such as a cross-coupling catalyst. DETAILED DESCRIPTION OF THE INVENTION As described above, the inventors have found that ketyl anions or ketyl dianions derived from ketones or glycols may be used to reduce nickel(II) to nickel(0), with the resultant 555425773-4 nickel(0) being bound to the ketone or a ketone derived from the glycol. The ketone bonded to the nickel(0) is labile, and so is easily displaced by, for example, a chemical substrate that is to be reacted with another in a nickel-catalysed process. Accordingly, the nickel(0) complexes obtainable by the process of the invention are catalytically active and find use, for example, as carbon coupling catalysts. Advantageously, the nickel(II) starting materials used in the process are commercially available and are prepared using less hazardous agents than, for example, the aluminium reducing agents used to produce [Ni(COD)2]. The nickel(II) starting materials are also very easy to handle and to store (they are chemically stable under standard ambient conditions). 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 . 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. rein 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. 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. ng a number or value, is used to refer to values that lie within ± 5% of the value specified. For example, where L is defined as having a natural bite angle of about 75 ° to about 140 °, bite angles of 71.3° to 147° are included.As the skilled person is aware, t p-orbitals with delocalized electrons in a molecule, which in general lowers the overall energy of the molecule and increases stability. It is conventionally represented as having alternating single and multiple bonds, although lone pairs, radicals or carbenium ions may be part of the system, which may be cyclic, acyclic, linear or mixed. 655425773-4 overlap of one p-orbital with another across an adjacent allows a delocalization of across all the adjacentaligned p- atom, but rather toa group of atoms. a monovalent radical derived from a cyclic hydrocarbon by the removal of a hydrogen atom from the hydrocarbon. A hydrocarbon is any molecule comprising only the elements carbon and hydrogen. Hydrocarbons may be aliphatic, aromatic, unsaturated or saturated. Cyclic hydrocarbons may comprise a single ring or a spiro, fused or bridged ring system having two or more rings. at least two rings share only a single atom. refers to a ring system comprising two or more rings, where at least two rings share two adjacent atoms. 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. om 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 4 to 10 atoms, in some cases 5 to 8 atoms. The heterocyclyl may be aliphatic or aromatic. One or more of the rings may be aliphatic or aromatic. 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. A 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. 755425773-4arenes, 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 -electron system characteristic of aromatic systems and a number ofout-of- -electrons corresponding to the Hückel rule. The Hückel rule is often usedin the art to assess aromatic character; monocyclic planar (or almost planar) systems of -electrons (where n is a non-negative integer) will exhibit aromatic character. Heteroaromatic rings may be 5- or 6-membered. Examples of 5- or 6-membered aromatic rings include pyridine, thiophene, pyrrole, furan, imidazole, oxazole, thiazole, pyrazole, isoxazole and isothiazole. Heteroaryl groups are univalent groups derived from heteroaromatic rings by removal of a hydrogen atom from any carbon atom. alkanes by removal of a hydrogen atom from any carbon at is intended to define acyclic branched or unbranched hydrocarbons having the general formula CnH2n+2 1-6alkyl groups. In some cases, alkyl groups are C1-4alkyl groups. C1-4alkyl refers to any selected from the group consisting of methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl and tert-butyl. hydrogen atom from any carbon a acyclic branched or unbranched hydrocarbons having the general formula CnH2n, -propylenyl, iso-propylenyl, n-butylenyl, sec-butylenyl, iso-butylenyl and tert-butylenyl. When an alkenyl group is substituted, any hydrogen atom(s) may be replaced with the substituent(s), pro monovalent groups derived from dialkenes by removal of a hydrogen atom from any is intended to define acyclic branched or unbranched hydrocarbons having the general formula CnH2n-2, wherein n is an integer from trialkenes by removal is intended to 855425773-4 define acyclic branched or unbranched hydrocarbons having the general formula CnH2n- 4 ovalent groups derived from alkynes by removal of a acyclic branched or unbranched hydrocarbons having the general formula CnH2n-2, alkynyl groups include ethynyl, n-propylynyl, iso-propylynyl, n-butylynyl, sec-butylynyl, iso-butylynyl and tert-butylynyl. When an alkynyl group is substituted, any hydrogen atom(s) may be replaced with the substituent(s), providing valencies are satisfied. groups derived from dialkynes by removal of a hydrogen atom from any carbon atom, is intended to define acyclic branched or unbranched hydrocarbons having the general formula CnH2n-6 is intended to define acyclic branched or unbranched hydrocarbons having the general formula CnH2n-10, wherein n is 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. fines univalent groups derived from alkyl groups by replacement of one or more hydrogen atoms from one or more carbon atoms with a halo group. Haloalkyl groups may comprise one or more different types of halo. For example, one or more independently selected from fluoro, chloro, bromo and iodo. In some cases, the haloalkyl is a fluoroalkyl. 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. PH3and compounds derived from it by substituting one, two or three hydrogen atoms with hydrocarbyl groups, i.e. groups made of just carbon and hydrogen atoms. Where a compound is described as comprising a phosphine binding moiety, the compound comprises a phosphine (optionally in addition to other chemical groups). 955425773-4 The term 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 at least one nitrogen atom. derived from ammonia by replacing one, two or three hydrogen atoms with hydrocarbyl groups. The nitrogen atom of primary amines is bonded to two hydrogen atoms and one carbon atom, that of secondary amines is bonded to one hydrogen atom and two carbon atoms, and that of tertiary amines is bonded to three carbon atoms. Where a compound is described as comprising an amine-binding moiety, the compound comprises an amine (optionally in addition to other chemical groups). having the structure RN=CR2, where each R is independently selected from H and hydrocarbyl. Where a compound is described as comprising an imine binding moiety, the compound comprises an imine (optionally in addition to other chemical groups). The term pseudo-halide is well known in the art and refers to univalent anions that are weak Lewis bases and are not ions from group 17 of the periodic table. Examples of pseudo-halides include triflate, cyanide, cyaphide, isocyanide, hydroxide, hydrosulfide, hydroselenide, hydrotelluride, cyanate, isocyanate, fulminate, thiocyanate, isothiocyanate, selenocyanate, tellurocyanate, azide, and nitroxide. Particularly useful pseudo-halides include triflate, cyanide, cyaphide, isocyanide, hydroxide, hydrosulfide, cyanate, isocyanate, fulminate, thiocyanate, isothiocyanate, azide, and nitroxide. denticity. A monodentate ligand binds through via a single atom (e.g. by a single pair of electrons donating from a single atom). A bidentate ligand binds through two different atoms and a tridentate ligand binds through three different atoms. between each of the binding moieties of a bidentate ligand or two of the three binding moieties of a tridentate ligand to a metal ion. It is obtained using molecular 1055425773-4 mechanics calculations and is determined only by ligand backbone restrictions and not by metal valence angles. used to measure the size of a monodentate ligand and is defined herein as the apex angle of a cone with its origin at the metal centre with spreading edges along the van der Waals spheres of the outermost atoms of the ligand. reported by Jover and Cirera in Dalton Trans., 2019, 48, 15036 for a [Ni(CO)3(L)] coordination environment. A base may be used in the method of the present invention. 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 (KOtBu), for example, the conjugate acid is tert-butanol (HOtBu); where the base used is sodium phenoxide (KOPh), 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. 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. 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. riant 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. 1155425773-4 As described above, the invention provides a method for the formation of a [Ni(L)n(Q)] complex from a [Ni(L)n(X)2] complex, the method comprising contacting the [Ni(L)n(X)2] complex with: (i) (a) a reducing metal or a base; and (c) a glycol comprising tertiary vicinal hydroxy moieties wherein at least one of the carbon atoms bonded to a tertiary vicinal hydroxy moiety is adjacent to a pi system; or (ii) (a) a reducing metal; and (c) a ketone comprising a carbonyl moiety conjugated with a pi system, wherein: Q is the ketone, or a ketone derived from the glycol, complexed to nickel; L is a mono-, di-, or tri-dentate L-type ligand, wherein n is 2 when L is monodentate and n is 1 when L is di- or tri-dentate; and X is a monovalent or divalent monoanionic ligand. It will be understood that contacting may be achieved in a variety of ways. Typically, where a ketone is used, the reducing metal and the ketone are contacted, and the [Ni(L)n(X)2] is added to the resultant mixture. Often, the ketone is first added to a solvent and stirred or agitated to form a solution or suspension to which the reducing metal is added. Typically, the reducing metal is added slowly, for example over 1 to 30 minutes or 5 to 20 minutes. The [Ni(L)n(X)2] is then added to the resultant solution or suspension. The solution or suspension comprising the ketone and the reducing metal may be blue or purple. A blue solution or suspension typically indicates the presence of a ketyl anion and a purple solution or suspension typically indicates the presence of a ketyl dianion. Where a glycol is used, the [Ni(L)n(X)2] and glycol are typically contacted, and the base or reducing metal is added to the resultant mixture. Often, the glycol and [Ni(L)n(X)2] are first added to a solvent and stirred or agitated to form a solution or suspension to which the base or reducing metal is added. The base may be, and often is, added to the solution or suspension as a solution. The glycol, [Ni(L)n(X)2] and solvent may be combined in any order. For example, the glycol may first be added to the solvent to form a solution or suspension to which [Ni(L)n(X)2] is added. Alternatively, the [Ni(L)n(X)2] may 1255425773-4 first be added to the solvent to form a solution or suspension to which glycol is added. As another alternative, the glycol and [Ni(L)n(X)2] may be added to the solvent at the same time or may be mixed together before being added to the solvent. As yet another alternative, the glycol and [Ni(L)n(X)2] may be mixed together and the solvent added to the resultant mixture, or the solvent may be added to one of the glycol and [Ni(L)n(X)2] and the other added to the resultant solution or suspension. Ketyl anions are often the major ketyl species formed when around 1 or fewer equivalents of reducing metal are used relative to ketone or around 2 or fewer equivalents of reducing metal are used relative to glycol. Ketyl dianions are often the major ketyl species formed when around 2 or more equivalents of reducing metal are used relative to ketone or around 4 or more equivalents of reducing metal are used relative to glycol. Ketyl anions are often the major reducing ketyl species formed when a base is used, particularly when around 2 or fewer equivalents of base are used relative to glycol. For the avoidance of doubt, the contacting of the [Ni(L)n(X)2] complex with (i) is such that the reducing metal or base reacts with the glycol to produce a reducing agent capable of reducing nickel (II) to nickel (0), and the contacting of the [Ni(L)n(X)2] complex with (ii) is such that the reducing metal reacts with the ketone to produce a reducing agent capable of reducing nickel (II) to nickel (0). As described above, Q is the ketone, or a ketone derived from the glycol, complexed to nickel. The glycol from which the ketone may be derived comprises tertiary vicinal hydroxy moieties wherein at least one of the carbon atoms bonded to a tertiary vicinal hydroxy moiety is adjacent to a pi system. For the avoidance of doubt, by the at least one of the carbon atoms bonded to a tertiary vicinal hydroxy moiety being adjacent to a pi system is meant that the relevant carbon atom is one bond away from a pi system, i.e. the carbon atom is bonded to an atom that is part of a pi system. Without being bound by theory, reduction of the glycol is understood to lead to cleavage of the bond between the two carbon atoms bonded to the tertiary vicinal hydroxy moieties to form ketyl radical anions or dianions. Since at least one of the carbon atoms bonded to a tertiary vicinal hydroxy moiety is adjacent to a pi system, the radical and / or negative charge of the ketyl radical anion or dianion comprising that carbon atom is able to delocalise across the pi system. The ketyl radical anion or dianion is able to reduce the nickel of the [Ni(L)n(X)2] complex, and form a ketone (Q) in the process, which is able to bind to the reduced 1355425773-4 nickel. Q, i.e. the ketone or a ketone derived from the glycol, comprises a carbonyl moiety conjugated with a pi system. Q may be of formula (I): wherein: R1and R2are each independently selected from cyclic C5-C18hydrocarbyl (such as C6-C18hydrocarbyl), C1-C17heterocyclyl, C1-6alkyl, C2-6alkenyl, C4-6dialkenyl, C6trialkenyl, C2-6alkynyl, C4-6dialkynyl, and C6trialkynyl, each of which is optionally substituted with one or more substituents selected from cyclic C3-C18hydrocarbyl (such as C6-C18hydrocarbyl), cyclic C1-C17heterocarbyl, C1-4alkyl, C2-6alkenyl, halo, C1- 4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino, wherein the optional cyclic C3- C18hydrocarbyl (such as C6-C18hydrocarbyl) and cyclic C1-C17heterocarbyl substituents are optionally substituted with C1-4alkyl, C2-6alkenyl, halo, C1-4haloalkyl, hydroxy, C1- 4alkoxy, and di(C1-4alkyl)amino; and wherein at least one of R1and R2comprises a pi system with which the carbonyl moiety is conjugated. For example, where R1is a moiety without a pi system with which the carbonyl moiety can be conjugated (e.g. where R1is a C1-6alkyl), R2is a moiety with a pi system with which the carbonyl moiety can be conjugated (e.g. R2may be an aryl or heteroaryl, or R2may be phenyl or an ethynyl). Typically, at least one of R1and R2is an aryl or a heteroaryl (e.g. an aryl). In particular embodiments, when R1and / or R2is optionally substituted with halo, the halo is not alpha to the ketone moiety of formula (I). In particular embodiments, R1and R2are not substituted with halo. For example, R1and and R2may be each independently selected from cyclic C5-C18hydrocarbyl (such as C6-C18hydrocarbyl), C1-C17heterocyclyl, C1-6alkyl, C2-6alkenyl, C4-6dialkenyl, C6trialkenyl, C2-6alkynyl, C4-6dialkynyl, and C6trialkynyl, each of which is optionally substituted with one or more substituents selected from cyclic C3-C18hydrocarbyl (such as C6-C18hydrocarbyl), cyclic C1- C17heterocarbyl, C1-4alkyl, C2-6alkenyl, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1- 4alkyl)amino, wherein the optional cyclic C3-C18hydrocarbyl (such as C6-C18hydrocarbyl) and cyclic C1-C17heterocarbyl substituents are optionally substituted with C1-4alkyl, C2- 6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino; and wherein at least one of R1and R2comprises a pi system with which the carbonyl moiety is conjugated. 1455425773-4 In particular embodiments, R1and R2are not or do not comprise unsaturated aliphatic groups. For example, R1and R2may each be independently selected from cyclic C5- C18hydrocarbyl (such as C6-C18hydrocarbyl), C1-C17heterocyclyl, C1-6alkyl, each of which is optionally substituted with one or more substituents selected from cyclic C3- C18hydrocarbyl (such as C6-C18hydrocarbyl), cyclic C1-C17heterocarbyl, C1-4alkyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino, wherein the optional cyclic C3- C18hydrocarbyl (such as C6-C18hydrocarbyl) and cyclic C1-C17heterocarbyl substituents are optionally substituted with C1-4alkyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino; and wherein at least one of R1and R2comprises a pi system with which the carbonyl moiety is conjugated. The R1and R2groups may be connected to the carbonyl moiety of figure (I) at any position, provided that it has the correct valency and is chemically suitable. For example, where R1and / or R2is an optionally substituted C1-C17heterocyclyl, it may be connected to the carbonyl moiety through a carbon atom or a heteroatom. In particular embodiments, the cyclic C5-C18hydrocarbyl of formula (I) is a cyclic C6- C14hydrocarbyl. In some embodiments, the cyclic hydrocarbyl is aromatic, e.g. any one selected from phenyl, naphthyl and fluorenyl. Alternatively, the cyclic C5-C18hydrocarbyl of formula (I) may be aliphatic, e.g. a C5-C18cycloalkyl such as any one selected from cyclopentyl, cyclohexyl and cycloheptyl. In particular embodiments, the C1-C17heterocyclyl of formula (I) comprises 1 to 3 heteroatoms independently selected from N, S and O, such as N and S. In particular embodiments, the C1-C17heterocyclyl comprises 1 or 2 heteroatoms. Typically, the ring(s) of the C1-C17heterocyclyl is / are 5- or 6-membered. Typically, the C1- C17heterocyclyl is a C1-C9heterocyclyl, which may be mono- or bi-cyclic. In particular embodiments, the C1-C17heterocyclyl is selected from pyridyl, piperidinyl, pyrrolidinyl, thiazolyl, imidazolyl, indolyl and tetrazolyl, e.g. pyridyl. In some embodiments, R1and R2are each independently selected from phenyl, naphthyl, pyridyl, anthracenyl, phenthracenyl, C5-6cycloalkyl, C1-6alkyl, C2-6alkenyl, C4- 6dialkenyl, C6trialkenyl, C2-6alkynyl, C4-6dialkynyl, and C6trialkynyl, each of which is optionally substituted with one or more substituents selected from phenyl, C1-4alkyl, C2- 6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino, wherein the optional phenyl substituent is optionally substituted with C1-4alkyl, C2-6alkenyl, halo, C1- 4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino; and wherein at least one of R1and R2comprises a pi system with which the carbonyl moiety is conjugated. 1555425773-4 In some embodiments, R1and R2are each independently selected from phenyl, C1-6alkyl, C2-6alkenyl, C4-6dialkenyl, C6trialkenyl, C2-6alkynyl, C4-6dialkynyl, and C6trialkynyl, each of which is optionally substituted with one or more substituents selected from phenyl, C1-4alkyl, C2-6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino, wherein the optional phenyl substituent is optionally substituted with C1-4alkyl, C2- 6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino; and wherein at least one of R1and R2comprises a pi system with which the carbonyl moiety is conjugated. Typically, R1and R2are each independently selected from phenyl, naphthyl, pyridyl, C5- 6cycloalkyl, C1-6alkyl (such as C1-4alkyl), C2-6alkenyl (such as C2-4alkenyl), and C2-6alkynyl (such as C2-4alkynyl), each of which is optionally substituted with one or more substituents selected from phenyl, C1-4alkyl, C2-6alkenyl (such as C2-4alkenyl), halo, C1- 4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino, wherein the optional phenyl substituent is optionally substituted with C1-4alkyl, C2-6alkenyl (such as C2-4alkenyl), halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino; and wherein at least one of R1and R2comprises a pi system with which the carbonyl moiety is conjugated. Typically, R1and R2are each independently selected from phenyl, C1-6alkyl (such as C1-4alkyl), C2-6alkenyl (such as C2-4alkenyl), and C2-6alkynyl (such as C2-4alkynyl), each of which is optionally substituted with one or more substituents selected from phenyl, C1-4alkyl, C2-6alkenyl (such as C2-4alkenyl), halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino, wherein the optional phenyl substituent is optionally substituted with C1-4alkyl, C2-6alkenyl (such as C2-4alkenyl), halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino; and wherein at least one of R1and R2comprises a pi system with which the carbonyl moiety is conjugated. In some embodiments, R1and R2are each independently selected from phenyl, naphthyl, pyridyl, C5-6cycloalkyl, and C1-6alkyl (such as C1-4alkyl), each of which is optionally substituted with one or more substituents selected from phenyl, C1-4alkyl, C1- 4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino, wherein the optional phenyl substituent is optionally substituted with C1-4alkyl, halo, C1-4haloalkyl, hydroxy, C1- 4alkoxy, and di(C1-4alkyl)amino; and wherein at least one of R1and R2comprises a pi system with which the carbonyl moiety is conjugated. In specific embodiments, R1and R2are independently selected from phenyl, naphthyl, pyridyl, cyclopentyl, cyclohexyl and C1-4alkyl, each of which is optionally substituted as 1655425773-4 described above. In particular embodiments, at least one of R1and R2is optionally substituted phenyl, pyridyl or naphthyl, e.g. optionally substituted phenyl or pyridyl. In specific embodiments, R1and R2are independently selected from optionally substituted phenyl and optionally substituted ethenylphenyl. In some embodiments, R1and R2are optionally substituted with one or more substituents selected from phenyl, C1-4alkyl, C2-6alkenyl (such as C2-4alkenyl), halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-6alkyl)amino. In more specific embodiments, R1and R2are optionally substituted with one or more substituents selected from phenyl, C1-4alkyl, C1-4haloalkyl, C1-4alkoxy, and di(C1-6alkyl)amino. In specific embodiments, R1and R2are optionally substituted with one or more substituents selected from C1-4alkyl, C2-6alkenyl (such as C2-4alkenyl), halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-6alkyl)amino. In more specific embodiments, R1and R2are optionally substituted with one or more substituents selected from C1-4alkyl, C1- 4haloalkyl, C1-4alkoxy, and di(C1-6alkyl)amino. In more specific embodiments, R1and R2are independently selected from optionally substituted phenyl, optionally substituted pyridyl, C1-4alkyl, optionally substituted cyclopentyl and optionally substituted cyclohexyl. In some embodiments, at least one of R1and R2is optionally substituted phenyl (e.g. unsubstituted phenyl) and the other is independently selected from optionally substituted phenyl, optionally substituted pyridyl, C1-4alkyl, optionally substituted cyclopentyl and optionally substituted cyclohexyl. For example, Q may be benzophenone, 4-benzoylbiphenyl, phenyl(4-tolyl)methanone, 2-benzoylpyridine -acetonaphthone, isobutyrophenone, cyclopentyl phenyl ketone orcyclohexyl phenyl ketone. In yet more specific embodiments, R1and R2are each optionally substituted phenyl, e.g. are each unsubstituted phenyl. For the avoidance of doubt, where Q is of formula (I), the glycol from which Q is derived : 1755425773-4 wherein R1and R2are as defined for formula (I), above. Alternatively, Q may be of formula (II): wherein A is a cyclic C6-C18hydrocarbyl or a C3-C17heterocyclyl, each being optionally substituted with one or more substituents selected from cyclic C3-C18hydrocarbyl (e.g. C6-C18hydrocarbyl), cyclic C1-C17heterocarbyl, C1-4alkyl, C2-6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino wherein the optional cyclic C3-C18hydrocarbyl (e.g. C6-C18hydrocarbyl) and cyclic C1-C17heterocarbyl substituents are optionally substituted with C1-4alkyl, C2-6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1- 4alkyl)amino; and wherein A comprises a pi system with which the carbonyl moiety of formula (II) is conjugated. For the avoidance of doubt, and as depicted in formula (II), ring A comprises a ketone moiety. For example, where ring A is defined as being a cyclic C6-C18hydrocarbyl, for example, fluorene, Q is a cyclic C6-C18hydrocarbyl comprising a ketone moiety, for example, fluorenone. In particular embodiments, when A is optionally substituted with halo, the halo is not alpha to the ketone moiety of formula (II). In particular embodiments, A is not substituted with halo. For example, A may be a cyclic C6-C18hydrocarbyl or a C3-C17heterocyclyl, each optionally substituted with one or more substituents selected from cyclic C3- C18hydrocarbyl, cyclic C1-C17heterocarbyl, C1-4alkyl, C2-6alkenyl, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino wherein the optional cyclic C6-C18hydrocarbyl and cyclic C1-C17heterocarbyl substituents are optionally substituted with C1-4alkyl, C2-6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino; and wherein A comprises a pi system with which the carbonyl moiety of formula (II) is conjugated. In particular embodiments, A is not or does not comprise an unsaturated aliphatic group. For example, A may be a cyclic C6-C18hydrocarbyl or a C3-C17heterocyclyl, each optionally substituted with one or more substituents selected from cyclic C3- C18hydrocarbyl (e.g. C6-C18hydrocarbyl), cyclic C1-C17heterocarbyl, C1-4alkyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino wherein the optional cyclic C3- C18hydrocarbyl (e.g. C6-C18hydrocarbyl) and cyclic C1-C17heterocarbyl substituents are optionally substituted with C1-4alkyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-1855425773-4 4alkyl)amino; and wherein A comprises a pi system with which the carbonyl moiety of formula (II) is conjugated. In particular embodiments, A is an optionally substituted cyclic C6-C18hydrocarbyl, such as a cyclic C6-C14hydrocarbyl, or an optionally substituted C5-C17heterocyclyl, such as a cyclic C5-C13heterocyclyl, each comprising a pi system with which the carbonyl moiety of formula (II) is conjugated. In some embodiments, the cyclic hydrocarbyl or cyclic heterocyclyl is aromatic. The cyclic hydrocarbyl or cyclic heterocyclyl may be polycyclic and may comprise fused rings. In some embodiments, the cyclic hydrocarbyl or cyclic heterocyclyl is bi- or tri-cyclic. Typically, the cyclic hydrocarbyl or cyclic heterocyclyl is tri-cyclic, such as a tricyclic moiety comprising three rings fused together, e.g. optionally substituted fluorene or xanthone. In particular embodiments, A is an optionally substituted cyclic C6-C18hydrocarbyl, such as a cyclic C6-C14hydrocarbyl, comprising a pi system with which the carbonyl moiety of formula (II) is conjugated. In some embodiments, the cyclic hydrocarbyl is aromatic. The cyclic hydrocarbyl may be polycyclic and may comprise fused rings. In some embodiments, the cyclic hydrocarbyl is bi- or tri-cyclic. Typically, the cyclic hydrocarbyl is tri-cyclic, such as a tricyclic moiety comprising three rings fused together, e.g. optionally substituted fluorene. In particular embodiments, Q is optionally substituted fluorenone. A may be optionally substituted with one or more substituents selected from phenyl, C1- 4alkyl, C2-6alkenyl (such as C2-4alkenyl), halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino wherein the optional phenyl substituents are optionally substituted with C1-4alkyl, C2-6alkenyl (such as C2-4alkenyl), halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino. In some embodiments, A is optionally substituted with one or more substituents selected from phenyl, C1-4alkyl, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1- 4alkyl)amino wherein the optional phenyl substituents are optionally substituted with C1- 4alkyl, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino. In some embodiments, A is optionally substituted with one or more substituents selected from phenyl, C1-4alkyl, C1-4haloalkyl, C1-4alkoxy, and di(C1-4alkyl)amino wherein the optional phenyl substituents are optionally substituted with C1-4alkyl, C1-4haloalkyl, C1-4alkoxy, and di(C1-4alkyl)amino. In specific embodiments, Q is of formula (IIa) or (IIb): 1955425773-4 , wherein: each ring B is independently selected from benzene, naphthalene and C3- C17heteroarene, each optionally substituted with one or more substituents selected from cyclic C3-C18hydrocarbyl, cyclic C1-C17heterocarbyl, C1-4alkyl, C2-6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino wherein the optional cyclic C3- C18hydrocarbyl and cyclic C1-C17heterocarbyl substituents are optionally substituted with C1-4alkyl, C2-6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino; each ring C is optionally present and, when present, is independently selected from a cyclic C5-C11hydrocarbon or a C3-C10heterocycle, each optionally substituted with one or more substituents selected from cyclic C3-C18hydrocarbyl, cyclic C1- C17heterocarbyl, C1-4alkyl, C2-6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino wherein the optional cyclic C6-C18hydrocarbyl and cyclic C1-C17heterocarbyl substituents are optionally substituted with C1-4alkyl, C2-6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino; Rfis selected from cyclic C3-C18hydrocarbyl, cyclic C1-C17heterocarbyl, C1-4alkyl, C2-6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino wherein the optional cyclic C6-C18hydrocarbyl and cyclic C1-C17heterocarbyl substituents are optionally substituted with C1-4alkyl, C2-6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino; and nf2 is 0 and nf1 is 0; nf2 is 1 and nf1 is 0 to 2; or nf2 is 2 and nf1 is 0 to 4. In particular embodiments, when ring C is present and is optionally substituted with halo, the halo is not alpha to the ketone moiety of formula (I). In particular embodiments, ring C is an optionally substituted arene or an optionally substituted heteroarene, such as benzene, naphthene or a C3-C9heteroarene, each optionally substituted with one or more substituents selected from cyclic C3-C18hydrocarbyl, cyclic C1-C17heterocarbyl, C1-4alkyl, C2-6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino wherein the optional cyclic C6-C18hydrocarbyl and cyclic C1-C17heterocarbyl substituents are optionally substituted with C1-4alkyl, C2-6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, 2055425773-4 and di(C1-4alkyl)amino. In some embodiments, ring C is optionally substituted with one or more substituents selected from phenyl, C1-6cycloalkyl, C1-4alkyl, halo, C1-4haloalkyl, C1-4alkoxy, and di(C1-4alkyl)amino wherein the phenyl and C1-6cycloalkyl are optionally substituted with C1-4alkyl, halo, C1-4haloalkyl, C1-4alkoxy, and di(C1-4alkyl)amino. In some embodiments, ring C is present and rings B and C are each selected from benzene and naphthalene, such as benzene, each of which is optionally substituted as described above. In some embodiments, ring C is present and rings B and C are each selected from benzene and naphthalene, each of which is optionally substituted with one or more substituents selected from phenyl, C1-6cycloalkyl, C1-4alkyl, halo, C1-4haloalkyl, C1- 4alkoxy, and di(C1-4alkyl)amino wherein the phenyl and C1-6cycloalkyl are optionally substituted with C1-4alkyl, halo, C1-4haloalkyl, C1-4alkoxy, and di(C1-4alkyl)amino. In particular embodiments, B and C are each optionally substituted benzene. In some embodiments, Rfis selected from phenyl, C1-6cycloalkyl, C1-4alkyl, halo, C1- 4haloalkyl, C1-4alkoxy, and di(C1-4alkyl)amino wherein the phenyl and C1-6cycloalkyl are each optionally substituted with C1-4alkyl, halo, C1-4haloalkyl, C1-4alkoxy, and di(C1- 4alkyl)amino. In particular embodiments, Rfis selected from C1-6cycloalkyl, C1-4alkyl, halo, C1-4haloalkyl, C1-4alkoxy, and di(C1-4alkyl)amino. In some embodiments, nf2 is 0 and nf1 is 0 or nf2 is 1 and nf1 is 0 to 2. In particular embodiments, nf1 is 0. In more particular embodiments, nf2 is 0. For the avoidance of doubt, where Q is of formula (II) or of formula (IIa) or (IIb), the glycol , : 2155425773-4

[0002] wherein rings A, B, C, Rf, nf1 and nf2 are as defined for formula (II) or formula (IIa), above. In specific embodiments, Q is fluorenone, xanthone or dibenzosuberone, e.g. fluorenone, each optionally substituted with one or more substituents selected from phenyl, C1-6alkyl, C2-6alkenyl, C4-6dialkenyl, C6trialkenyl, C2-6alkynyl, C4-6dialkynyl, and C6trialkynyl, each of which is optionally substituted with one or more substituents selected from phenyl, C1-4alkyl, C2-6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino wherein the optional phenyl substituent is optionally substituted with C1-4alkyl, C2-6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy and di(C1-4alkyl)amino. In some embodiments, Q is fluorenone, xanthone or dibenzosuberone, e.g. fluorenone, each optionally substituted with one or more substituents selected from phenyl and C1- 6alkyl, wherein the phenyl is optionally substituted with one or more substituents selected from C1-4alkyl, halo, C1-4haloalkyl, C1-4alkoxy, and di(C1-4alkyl)amino. In some embodiments, the optional substituents of the fluorenone, xanthone or dibenzosuberone are selected from phenyl and C1-6alkyl, wherein the phenyl is optionally substituted with one or more substituents selected from C1-4alkyl, halo and C1-4haloalkyl. In specific embodiments, Q is 9-fluorenone, 9H-xanthen-9-one, 10,10-dimethyl-9-10- dihydroanthracen-9-one or 10,11-dihydro-5H-dibenzo[a,d][7]annulen-5-one. 2255425773-4 In particular embodiments, Q is of formula (I) or (II) and the [Ni(L)n(Q)] complex is of formula (IIIa) or (IIIb): wherein: R1, R2and A are as defined for formula (I) and (II), above. In some embodiments, the [Ni(L)n(Q)] complex is of formula (IIIc) or (IIId): wherein: ring B, ring C, Rf, nf2 and nf1 are as defined above for formula (IIa) or (IIb). In particular embodiments, Q is of formula (I) and the [Ni(L)n(Q)] complex is of formula (IIIa). In some embodiments, R1and R2are independently selected from phenyl, naphthyl, pyridyl, anthracenyl, phenanthracenyl, C5-6cycloalkyl, C1-6alkyl, C2-6alkenyl, C4-6dialkenyl, C6trialkenyl, C2-6alkynyl, C4-6dialkynyl, and C6trialkynyl, each of which is optionally substituted with one or more substituents selected from phenyl, C1-4alkyl, C2-6alkenyl (such as C2-4alkenyl), halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino wherein the optional phenyl substituent is optionally substituted with C1-4alkyl, C2-6alkenyl (such as C2-4alkenyl), halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino; and wherein at least one of R1and R2comprises a pi system with which the carbonyl moiety is conjugated. In some embodiments, R1and R2are each independently selected from phenyl, napththyl, pyridyl, anthracenyl, phenanthracenyl, C5-6cycloalkyl and C1-6alkyl, each of which is optionally substituted. In more particular embodiments, R1and R2are each optionally substituted phenyl. 2355425773-4 In some embodiments, ring C is present and rings B and C are each selected from benzene and naphthalene, such as benzene, each of which is optionally substituted. In some embodiments, Rfis selected from C1-4alkyl, halo and C1-4haloalkyl. As described above, L of [Ni(L)n(Q)] and [Ni(L)n(X)2] is a mono-, di-, or tri-dentate L-type ligand, wherein n is 2 when L is monodentate and n is 1 when L is di- or tri-dentate. An L-type ligand is a neutral ligand capable of donating one or more pairs of electrons to the nickel, regardless of the electron counting method being used, to form one or more dative bonds with the nickel. The pairs of electrons are typically from a lone pair of electrons. L may bind to the nickel through any suitable atom capable of donating two electrons to nickel to form a dative bond. Typically, L binds to the nickel through phosphorus, nitrogen, carbon and / or oxygen atoms, for example L binds to the nickel through phosphorus, nitrogen and / or carbon atoms. In some embodiments, L is monodentate and binds to the nickel through a phosphorus atom or a carbon atom. L may be a phosphine, carbene (such as a N-heterocyclic carbene), amine, imine or optionally substituted N-heterocycle, such as an optionally substituted N-heteroaryl (e.g. pyridine). In specific embodiments, L is a phosphine or a carbene. Alternatively, L may be bidentate and chelate to the nickel through two binding atoms independently selected from phosphorus, nitrogen, carbon and oxygen. L may comprise two binding moieties independently selected from phosphine, amine, imine, pyridine, and carbene (such as N-heterocyclic carbene) moieties. Typically, the two binding atoms or the two bonding moieties are the same. For example, L may be bidentate and comprise two phosphine- two amine- or two pyridine-binding moieties. In alternative embodiments, L is tridentate, and chelates to the nickel through nitrogen, phosphorus and / or carbon atoms. Tridentate L-type ligands are capable of donating three pairs of electrons to nickel, through three different binding atoms. However, where L is tridentate, it typically chelates to the nickel through just two of the three pairs of electrons available, i.e. one of the binding atoms is typically not bonded to the nickel. When L is tridentate, it typically comprises three binding moieties independently selected 2455425773-4 from phosphine, amine, imine, pyridine, and carbene (such as N-heterocyclic carbene) moieties. L may be or comprise a phosphine. Phosphine ligands suitable for use as L includethose described in Tamao, Journal of Organometallic Chemistry, 653, 1 2, 2002, 23-26;Newman-Stonebraker et al., J. Am. Chem. Soc.2022, 144, 42, 19635 19648; Bodé,Organometallics 2021, 40, 16, 2915 2922; Li et al., Chapter 4 - AsymmetricPhosphorous Based Ligands in Earth- 2023, 141-186; and Wen et al., Chem. Soc. Rev., 2021, 50, 3211-3237. Ferrocenylphosphine ligands such as those described by Bandaru et al., in Coordination Chemistry Reviews, 491, 2023, 215250, are popularly used in cross-coupling reactions and are also suitable for use as L. Particularly useful bidentate phosphine ligands aredescribed by Clevenger et al., in Chem. Rev. 2020, 120, 13, 6124 6196 and particularlyuseful polydentate phosphine ligands are described by Pascariu et al., in Journal of Organometallic Chemistry, 694, 25, 2009, 3982-4000. The bidentate and tri-dentate ligands described in these papers are also suitable for use as L. L may be or comprise a carbene, such as an N-heterocyclic carbene. A review of nickel N-heterocyclic carbene complexes and their use in homogeneous catalysis is provided by Prakasham and Ghosh, in Inorganica Chimica Acta, 431, 2015, 61-100; Henrion etal., in ACS Catal.2015, 5, 2, 1283 1302; and Ritleng et al., in ACS Catal. 2016, 6, 2,890 906. The N-heterocyclic carbene ligands described in these reviews are suitablefor use as L. L may comprise an N-donor moiety such as an amine, imine or optionally substituted N- heterocycle. A review of coordination compounds with dicarboxylic acids and N-donor ligands is provided by Loubalová and Kopel, in Molecules, 2023, 28(3), 1445. Other N-donor ligands are described by Tellis et al., in Acc. Chem. Res. 2016, 49, 7, 1429 1439;Huang, Journal of Chemical Research.2022;46(1); and Tasker et al., Nature 509, 299 309 (2014). L may be one or more of the mono-dentate and any one of the bi- or tri- dentate ligands described in these papers. As described above, the natural bite angle is the preferred angle of chelation between each of the binding moieties of a bidentate ligand or two of the three binding moieties of a tridentate ligand, to a metal ion. It is obtained using molecular mechanics calculations and is determined only by ligand backbone restrictions and not by metal valence angles 2555425773-4 (see, for example, the bite angles reported by Mansell in Dalton Trans., 2017, 46, 15157 and calculated by the method described in van Leeuwen, in Homogeneous Catalysis: Understanding the Art, Springer, Netherlands, 2004). The bite angle of a ligand in a complex is known to have an effect on the catalytic activity of the complex. The inventors have found that, where L is bidentate or tridentate, the method of the invention proceeds unexpectedly more effectively when L has a natural bite angle of at least about 75 °, such as about 75 ° to about 140 °. According to some embodiments, L is not diphenylphosphinomethane (dppm). Dppm is reported to have a natural bite angle of about 72 °, and so is excluded by the bite angle ranges described above. In some embodiments, L has a natural bite angle of about 80 ° to about 140 °. In particular embodiments, when the method comprises contacting the [Ni(L)n(X)2] complex with a reducing metal and a ketone, L has a natural bite angle of about 90 ° to about 140 °, such as about 95 ° to about 140 °. According to some embodiments, L is not diphenylphosphinoethane (dppe). Dppe is reported to have a natural bite angle of about 85 °, and so is excluded by the bite angle ranges of about 90 ° to about 140 °, and about 95 ° to about 140 °. According to some embodiments, L is not diphenylphosphinopropane (dppp). This is reported to have a bite angle of about 91 ° and is excluded by the ranges just described. In yet more particular embodiments, when the method comprises contacting the [Ni(L)n(X)2] complex with a reducing metal and a ketone or glycol, L has a natural bite angle of at least about 90 ° to about 140 °, such as about 95 ° to about 140 °.As described above, t he size of amonodentate ligand. The inventors have found that, where L is monodentate, the method of the invention proceeds unexpectedly more effectively when L cone angle of at least about 125 °, such as about 130 ° to about 190 ° or about 180 °. According to some embodiments, L is not trimethylphospine. Trimethylphosphine is not in the range of at least about 125 °, such as about 130 ° to about 190 ° or about 180 °. In particular embodiments, when the method comprises contacting the [Ni(L)n(X)2] complex with a reducing metal and a ketone, L has a of about 160 ° to about 190 °, such as about 160 ° to about 180 °. In a yet more particular embodiment, 2655425773-4 when the method comprises contacting the [Ni(L)n(X)2] complex with a reducing metal and a ketone, L is bidentate or tridentate. In some embodiments, when the method comprises contacting the [Ni(L)n(X)2] complex with a reducing metal and a ketone or glycol, L has a of about 160 ° to about 190 °, such as about 160 ° to about 180 °. In a yet more particular embodiment, when the method comprises contacting the [Ni(L)n(X)2] complex with a reducing metal and a ketone, L is bidentate or tridentate. In particular embodiments, L is not dppm, dppe, dppp or trimethylphosphine. In particular embodiments, L is selected from a tri-cycloC5-6hydrocarbylphosphine, C1- 4alkyl-di-cycloC5-6hydrocarbylphosphine, tetraC1-4alkylC2-4alkylenediamine, pentaC1- 4alkylC2-4alkylenetriamine, N,N-containing C10heterobicyclic ligand, N,N-containing C12- 14heterotricyclic ligand, bis(di-cycloC5-6hydrocarbylphosphino)C2-4alkylene, bis(di- cycloC5-6hydrocarbylphosphino)xanthene, bis(di-C1-4alkylphosphino)xanthene, bis(di- cycloC5-6hydrocarbylphosphino)ferrocene, bis(di-C1-4alkylphosphino)ferrocene, bis(di- cycloC5-6hydrocarbylphosphinophenyl)ether, and bis(di-C1-4alkylphosphinophenyl)ether, each of which is optionally substituted with one or more substituents selected from C1- 4alkyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy and morpholino. In some embodiments, L is unsubstituted, i.e. not substituted with one or more substituents selected from C1-4alkyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy and morpholino. In more particular embodiments, L is selected from triphenylphosphine, bis(diphenylphosphino)propane, bis(diphenylphosphino)butane, bis(diphenylphosphino)ethane, bis(diphenylphosphino)ferrocene, bis(diphenylphosphino)xanthene, -tetramethylethylenediamine, - pentamethyldiethylenetriamine, bipyridine, di-tert-butyl-bipyridine, bis(dicyclohexyphosphino)ethane, bis(di-iso-propyl-phosphino)ferrocene, bis(di-tert- butyl-phosphino)ferrocene, diadamantylmorpholinophenylphosphine, methyldiphenylphosphine, and tricyclohexylphosphine. In some embodiments, L is a diC1-4alkyl-phosphino-biphenyl or a di-cycloC5-6hydrocarbylphosphino-biphenyl, wherein each biphenyl is optionally substituted with one or more substituents selected from C1-4alkyl, di(C1-4alkyl)amino, and C1-4alkoxy. In 2755425773-4 some embodiments, L is a 2-diC1-4alkyl-phosphino-biphenyl or a 2-di-cycloC5- 6hydrocarbylphosphino-biphenyl, wherein each biphenyl is optionally substituted as described above. In some embodiments, L is a 2-di-tert-butyl-phosphino-biphenyl or a 2-di-cyclohexylphosphino-biphenyl, wherein each biphenyl is optionally substituted as described above. In some embodiments, each optional substituent is a di(C1- 4alkyl)amino, such as a dimethylamino. In some embodiments, L is 2-Dicyclohexylphosphino- -(N,N-dimethylamino)biphenyl (also known as DavePhos).In some embodiments, L is bidentate and comprises a phosphine and a carbene binding moiety. Typically, in such embodiments, the carbene moiety is an N-heterocyclic carbene moiety. For example, L may comprise a di-cycloC5-6hydrocarbylphosphino binding moiety linked, e.g. by an alkyl linker, to an N-heterocyclic carbene binding moiety. In some embodiments, L is a 1-di-cycloC5-6hydrocarbylphosphinoC1-4alkyl-3- phenylimidazol-2-ylide, wherein the cycloC5-6hydrocarbyl and the phenyl are each optionally substituted with one or more substituents selected from C1-4alkyl, di(C1- 4alkyl)amino, and C1-4alkoxy. In particular embodiments, L is 1-(2- diphenylphosphinoethyl)-3-(2,4,6-trimethylphenyl)imidazol-2-ylide. As described above, X of [Ni(L)n(X)2] is a monoanionic ligand which can be monovalent (e.g. halide or pseudo-halide) or divalent (e.g. acetate or acetylacetonate). In some embodiments, X is selected from halide, triflate, acetate, trifluoroacetate, acetylacetonate, nitrate and sulfonate. In some embodiments, X is any one selected from chloride, bromide, iodide, acetate and nitrate. In some embodiments, X is any one selected from chloride, bromide, iodide and nitrate. In particular embodiments, X is chloride, bromide or iodide, for example X is chloride. Where L is bidentate and binds to the nickel through two nitrogen atoms, X may be any one selected from chloride, bromide, iodide and acetate. Where L is bidentate and binds to the nickel through two phosphorus atoms, X may be chloride, bromide or iodide. Where each L is monodentate and binds to the nickel through a phosphorus atom, X may be any one selected from chloride, bromide, iodide, nitrate and sulfate. The [Ni(L)n(X)2] complex may be contacted with a reducing metal and a glycol or ketone. The reducing metal may be any metal suitable to reduce the glycol or ketone to a ketyl 2855425773-4 anion or ketyl dianion. Typically, the reducing metal comprises a Group I metal, i.e. lithium, sodium, potassium, rubidium, caesium or francium. In some embodiments, reducing metal comprises lithium, sodium, potassium or rubidium, such as lithium, sodium or potassium. The reducing metal may be provided as an oil or salt dispersion, or as part of an intercalation compound, such as a graphite intercalation compound. In particular embodiments, the reducing metal is provided as a metal or as part of an intercalation compound, such as a graphite intercalation compound. In particular embodiments, the method comprises contacting the [Ni(L)n(X)2] complex with a glycol or ketone, and any one selected from sodium metal, lithium metal, potassium metal, caesium metal, rubidium metal and graphite intercalation compounds comprising potassium or lithium. Alternatively, and preferably, the [Ni(L)n(X)2] complex may be contacted with a base and a glycol. The inventors have found that bases, many of which are easier to handle and store than reducing metals, may be used to synthesise a [Ni(L)n(Q)] complex from a [Ni(L)n(X)2] complex and a glycol, and are unexpectedly effective and resilient to variation in Q, L and X. The base may be any base suitable to reduce the glycol to a ketyl anion.In some embodiments, the base has a conjugate acid with a pKa of 9.5 or 15. For the avoidance of doubt, this includes bases comprising tert-butoxide, phenoxide, bis(trimethylsilyl)amide, various Grignard reagents such as C1-4alkylmagnesium halide and C5-6hydrocarbylmagnesium halide, various organolithium, organopotassium and organosodium reagents such as C1-4alkyllithium, C1-4alkylpotassium, C1-4alkylsodium, lithium di(C1-4alkyl)amide, potassium di(C1-4alkyl)amide, sodium di(C1-4alkyl)amide, lithium tetraC1-4alkylC5-6hydrocarbyl, potassium tetraC1-4alkylC5-6hydrocarbyl and sodium tetraC1-4alkylC5-6hydrocarbyl. Reviews of Grignard reagents are provided by Seyferth inOrganometallics 2006, 25, 1, 2 24; Seyferth in Organometallics 2009, 28, 1, 2 33;Weiss, Angew. Chem. Int. Ed. Engl., 1993, 32: 1501-1523; and Samineni, ChemistrySelect 2022, 7, e202102853. In some embodiments, the base is selected from potassium tert-butoxide, lithium tert- butoxide, sodium tert-butoxide, sodium phenoxide, potassium bis(trimethylsilyl)amide, lithium bis(trimethylsilyl)amide, sodium bis(trimethylsilyl)amide, C1-4alkylmagnesium chloride, C5-6hydrocarbylmagnesium chloride, C1-4alkyllithium, C1-4alkylpotassium, C1-4alkylsodium, lithium di(C1-4alkyl)amide, potassium di(C1-4alkyl)amide, sodium di(C1-2955425773-4 4alkyl)amide, lithium tetraC1-4alkylC5-6hydrocarbyl, potassium tetraC1-4alkylC5- 6hydrocarbyl, sodium tetraC1-4alkylC5-6hydrocarbyl. In more particular embodiments, the base is selected from potassium tert-butoxide, lithium tert-butoxide, sodium phenoxide, potassium phenoxide, potassium bis(trimethylsilyl)amide, methylmagnesium chloride, and phenylmagnesium chloride. The inventors have found that the method is more effective when the contacting is in an aprotic solvent, i.e. solvents without moieties capable of proton donation. Typically, the solvent is anhydrous, i.e. the solvent comprises less than about 2 wt% water, for example less than about 1 wt%, about 0.5 wt% or about 0.1 wt% water.The solvent may 10 8. Inparticular embodiments, the solvent is selected from one or more of THF, toluene, diethyl ether, dimethoxyethane, hexane, 2-methyltetrahydrofuran, methyl tert-butyl ether, and cyclopentyl methyl ether. Typically, the solvent is selected from one or more of THF, toluene, diethyl ether, dimethoxyethane, hexane. Often, just one type of solvent, rather than a mixture of solvents, is used. Typically, the base, reducing metal, ketone and glycol are in molar excess relative to the [Ni(L)n(X)2] complex, by which is meant that more than 1 equivalent of each is used relative to the [Ni(L)n(X)2] complex. Where the [Ni(L)n(X)2] complex is contacted with a base and a glycol, a small excess of glycol is typically used relative to the [Ni(L)n(X)2] complex. In some embodiments, about 1 to about 1.5, such as about 1 to about 1.2 or about 1 to about 1.1, such as about 1.05, equivalents of glycol are used relative to the [Ni(L)n(X)2] complex. At least 2 equivalents of base are typically used relative to the [Ni(L)n(X)2] complex. Without being bound by theory, at least 2 molecules of base are required to reduce one nickel(II) complex to nickel(0) via ketyl anion species. In some embodiments, about 2 to about 3, for example about 2 to about 2.5 molar equivalents of base are used relative to the [Ni(L)n(X)2] complex. Where the [Ni(L)n(X)2] complex is contacted with a reducing metal and a glycol or ketone, two different reaction pathways are possible. As described above, ketyl anions are often the major ketyl species formed when around 1 or fewer equivalents of reducing metal are used relative to ketone or around 2 or fewer equivalents of reducing metal are used relative to glycol. Ketyl dianions are often the major ketyl species formed when around 3055425773-4 2 or more equivalents of reducing metal are used relative to ketone or around 4 or more equivalents of reducing metal are used relative to glycol. One process may be favoured over the other, for example one may be better suited to the synthesis of a nickel complex over the other. Since ketyl dianions are better reducing agents, the ketyl dianion pathway may be preferred where the [Ni(L)n(X)2] complex is more difficult to reduce. Alternatively, the ketyl radical process may be preferred where more sensitive starting materials are used. About 2 to about 5 molar equivalents of reducing metal, for example about 2 to about 4 molar equivalents of reducing metal, may be used relative to the [Ni(L)n(X)2] complex. Where a ketone is used, greater than about 2 molar equivalents of the ketone are typically used relative to the [Ni(L)n(X)2] complex, such as about 2.05 to about 8 molarequivalents of the ketone. Where a glycol is used, abou ofthe glycol, for example molar equivalents of the glycol, are typically used relative to the Ni(L)n(X)2] complex, such as about 1.05 molar equivalents of the glycol. To favour a ketyl anion pathway, when a reducing metal is used with a glycol, a small e equivalents, is typically used relative to the [Ni(L)n(X)2] complex. equivalents of reducing metal are used relative to the glycol. In some embodiments, about 1.2 to about 1.8, such as about 1.6 equivalents of reducing metal are used relative to the glycol. To favour a ketyl anion pathway, when a reducing metal is used with a ketone, [Ni(L)n(X)2] complex to the ketone. In some embodiments, about 0.5 to about 1, such as about 0.8 equivalents of reducing metal are used relative to the ketone. To favour a ketyl dianion pathway, when a reducing metal is used with a glycol, less than 1 equivalent of glycol is typically used, such as about 0.5 to about 0.9 equivalents, relative to the [Ni(L)n(X)2] complex are used relative to the glycol, such as about 3 to about 5 equivalents (e.g. about 4 equivalents). When a reducing metal is used with a ketone, to favour a ketyl dianion pathway, a small excess of ketone is typically used, such as about 1.2 to about 1.8 equivalents, relative to the [Ni(L)n(X)2] complex. Typically, about 1.5 to about 2.5 3155425773-4 equivalents of reducing metal are used relative to the ketone, such as about 2 equivalents. The method of the invention may be carried out at any convenient temperature, provided the ketyl anion or dianion species is able to form. The skilled person is able to assess which temperature is suitable without undue burden. In some embodiments, the contacting is at a temperature of about 240 K to about 305 K. Advantageously, the inventors have found that the reaction proceeds at ambient temperature. Accordingly, the contacting may be carried out at a temperature of about 240 K to about 298 K, such as about 285 K to about 298 K. The contacting may be carried out for as long as is required for a suitable quantity of product to be produced, for example the time it takes for the reaction to go to completion, i.e. for complete conversion of [Ni(L)n(Q)] from [Ni(L)n(X)2]. The skilled person is well aware of techniques in the art that can be used to monitor the reaction as it proceeds and to assess when a suitable quantity of product has been made, or when the reaction has gone to completion. The skilled person is also aware of methods that can be used to quicken the reaction rate, and so reduce the time required for the reaction to go to completion. Examples include increasing temperature, increasing pressure and using microwave heating. In some embodiments, the contacting is over a duration of about 3 to 12 hours. As described above, the second aspect provides a [Ni(L)n(Q)] complex wherein: Q is a ketone complexed to nickel, wherein the ketone comprises a carbonyl moiety conjugated with a pi system; L is a mono-, di-, or tri-dentate L-type ligand selected from tri-C1-6alkylphosphine (such as tri-n-butylphosphine), tri-cycloC5-6hydrocarbylphosphine, C1-4alkyl-di-cycloC5-6hydrocarbylphosphine, -tetraC1-4alkylC2-4alkylenediamine, N,N -pentaC1-4alkylC2-4alkylenetriamine, N,N-containing C12-14heterotricyclic ligand, bis(di- cycloC5-6hydrocarbylphosphino)C2-4alkylene, bis(di-cycloC5-6hydrocarbylphosphino)xanthene, bis(di-C1-4alkylphosphino)xanthene, bis(di-cycloC5-6hydrocarbylphosphino)ferrocene, bis(di-C1-4alkylphosphino)ferrocene, bis(di-cycloC5-6hydrocarbylphosphinophenyl)ether, and bis(di-C1-4alkylphosphinophenyl)ether, each of which is optionally substituted with one or more substituents selected from C1-4alkyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy and morpholino, L is an N,N-containing C10heterobicyclic ligand optionally substituted with one or more substituents selected from C1-4alkyl, halo, C1-4haloalkyl, hydroxy, and C1-4alkoxy, 3255425773-4 L is a diC1-4alkyl-phosphino-biphenyl or a di-cycloC5-6hydrocarbylphosphino- biphenyl, wherein each biphenyl is optionally substituted with one or more substituents selected from C1-4alkyl, di(C1-4alkyl)amino, and C1-4alkoxy, or L comprises a di-cycloC5-6hydrocarbylphosphino binding moiety linked, optionally by an alkyl linker, to an N-heterocyclic carbene binding moiety; and wherein when L is monodentate, n is 2 and when L is bi- or tri-dentate, n is 1. In some embodiments, L is a mono-, di-, or tri-dentate L-type ligand selected from tri- cycloC5-6hydrocarbylphosphine, C1-4alkyl-di-cycloC5-6hydrocarbylphosphine, - tetraC1-4alkylC2-4alkylenediamine, -pentaC1-4alkylC2-4alkylenetriamine, N,N-containing C12-14heterotricyclic ligand, bis(di-cycloC5-6hydrocarbylphosphino)C2- 4alkylene, bis(di-cycloC5-6hydrocarbylphosphino)xanthene, bis(di-C1- 4alkylphosphino)xanthene, bis(di-cycloC5-6hydrocarbylphosphino)ferrocene, bis(di-C1- 4alkylphosphino)ferrocene, bis(di-cycloC5-6hydrocarbylphosphinophenyl)ether, and bis(di-C1-4alkylphosphinophenyl)ether, each of which is optionally substituted with one or more substituents selected from C1-4alkyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy and morpholino, or L is an N,N-containing C10heterobicyclic ligand optionally substituted with one or more substituents selected from C1-3alkyl, halo, C1-4haloalkyl, hydroxy, and C1-4alkoxy. For the avoidance of doubt, each of the embodiments described in relation to Q and L of the first aspect may be applied mutatis mutandis to the second aspect. For example, Q may be of formula (I) or of formula (II), or more specifically may be an optionally substituted fluorenone or an optionally substituted benzophenone. L may be any one selected from triphenylphosphine, bis(diphenylphosphino)propane, bis(diphenylphosphino)butane, bis(diphenylphosphino)ethane, bis(diphenylphosphino)ferrocene, bis(diphenylphosphino)xanthene, - tetramethylethylenediamine, -pentamethyldiethylenetriamine, bipyridine, bis(dicyclohexyphosphino)ethane, bis(di-iso-propyl-phosphino)ferrocene, bis(di-tert- butyl-phosphino)ferrocene, diadamantylmorpholinophenylphosphine, methyldiphenylphosphine, and tricyclohexylphosphine. For example, Q may be of formula (I) or (II) and, when R1, R2and / or A is optionally substituted with halo, the halo is not alpha to the ketone moiety of formula (I) or formula (II). 3355425773-4 In some embodiments, when L is -bipyridine, Q is not benzophenone. In some embodiments, when L is tri-cycloC5-6hydrocarbylphosphine or an N,N-containing C10heterobicyclic ligand optionally substituted with one or more substituents selected from C1-4alkyl, halo, C1-4haloalkyl, hydroxy, and C1-4alkoxy, Q is not benzophenone. In particular embodiments, R1and R2are each independently selected from phenyl, naphthyl, pyridyl, C5-6cycloalkyl, and C1-6alkyl (such as C1-4alkyl), each of which is optionally substituted with one or more substituents selected from phenyl, C1-4alkyl, C1- 4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino, wherein the optional phenyl substituent is optionally substituted with C1-4alkyl, halo, C1-4haloalkyl, hydroxy, C1- 4alkoxy, and di(C1-4alkyl)amino; and wherein at least one of R1and R2comprises a pi system with which the carbonyl moiety is conjugated. Alternatively, Q may be of formula (IIa) or (IIb). In some embodiments, L is a mono-, di-, or tri-dentate L-type ligand selected from tri-C1- 6alkylphosphine (such as tri-n-butylphosphine), -tetraC1-4alkylC2- 4alkylenediamine (such as -tetramethylethylenediamine (TMEDA) or - tetraethylethylenediamine (TEEDA)), -pentaC1-4alkylC2-4alkylenetriamine (such as -pentamethyldiethylenetriamine (PMDTA)), bis(di-cycloC5- 6hydrocarbylphosphino)C3-4alkylene (such as 1,3-bis(diphenylphosphino)propane (DPPP) or 1,4-bis(diphenylphosphino)butane (DPPB)), bis(di-cycloC5- 6hydrocarbylphosphino)xanthene (such as 4,5-bis(diphenylphosphino)-9,9- dimethylxanthene (XantPhos)), bis(di-cycloC5-6hydrocarbylphosphino)ferrocene (such -bis(diphenylphosphino)ferrocene (DPPF)), each of which is optionally substituted with one or more substituents selected from C1-4alkyl, halo, C1-4haloalkyl, hydroxy, C1- 4alkoxy and morpholino, L is an N,N-containing C10heterobicyclic ligand substituted with one or more substituents selected from C1-4alkyl, halo, C1-4haloalkyl, hydroxy, and C1-4alkoxy (e.g. L -di-tert-butyl- -dipyridyl (dt -dimethoxy- -bipyridine(dMeOBIPY)), L is a diC1-4alkyl-phosphino-biphenyl or a di-cycloC5-6hydrocarbylphosphino- biphenyl, wherein each biphenyl is optionally substituted with one or more substituents selected from C1-4alkyl, di(C1-4alkyl)amino, and C1-4alkoxy (e.g. L is 2-dicyclohexylphosphino- -(N,N-dimethylamino)biphenyl), or3455425773-4 L comprises a di-cycloC5-6hydrocarbylphosphino binding moiety linked, optionally by an alkyl linker (e.g. a C1-4alkyl linker), to an N-heterocyclic carbene binding moiety (e.g. L is 1-(2-diphenylphosphinoethyl)-3-(2,4,6-trimethylphenyl)imidazol-2-ylide). In particular embodiments, L is a mono-, di-, or tri-dentate L-type ligand selected from tri-C1-6alkylphosphine (such as tri-n-butylphosphine), -tetraC1-4alkylC2- 4alkylenediamine (such as -tetramethylethylenediamine (TMEDA) or - tetraethylethylenediamine (TEEDA)), -pentaC1-4alkylC2-4alkylenetriamine (such as -pentamethyldiethylenetriamine (PMDTA)), bis(di-cycloC5- 6hydrocarbylphosphino)C3-4alkylene (such as 1,3-bis(diphenylphosphino)propane (DPPP) or 1,4-bis(diphenylphosphino)butane (DPPB)), bis(di-cycloC5- 6hydrocarbylphosphino)xanthene (such as 4,5-bis(diphenylphosphino)-9,9- dimethylxanthene (XantPhos)), bis(di-cycloC5-6hydrocarbylphosphino)ferrocene (such -bis(diphenylphosphino)ferrocene (DPPF)), each of which is optionally substituted with one or more substituents selected from C1-4alkyl, halo, C1-4haloalkyl, hydroxy, C1- 4alkoxy and morpholino, or L is an N,N-containing C10heterobicyclic ligand substituted with one or more substituents selected from C1-4alkyl, halo, C1-4haloalkyl, hydroxy, and C1-4alkoxy (e.g. Lis -di-tert-butyl- -dipyridyl (dt -dimethoxy- -bipyridine(dMeOBIPY)). In some embodiments, L is a mono-, di-, or tri-dentate L-type ligand selected from tri-C1- 6alkylphosphine (such as tri-n-butylphosphine), -tetraC1-4alkylC2- 4alkylenediamine (such as -tetramethylethylenediamine (TMEDA) or - tetraethylethylenediamine (TEEDA)), -pentaC1-4alkylC2-4alkylenetriamine (such as -pentamethyldiethylenetriamine (PMDTA)), bis(di-cycloC5- 6hydrocarbylphosphino)C3-4alkylene (such as 1,3-bis(diphenylphosphino)propane (DPPP) or 1,4-bis(diphenylphosphino)butane (DPPB)), bis(di-cycloC5- 6hydrocarbylphosphino)xanthene (such as 4,5-bis(diphenylphosphino)-9,9- dimethylxanthene (XantPhos)), bis(di-cycloC5-6hydrocarbylphosphino)ferrocene (such -bis(diphenylphosphino)ferrocene (DPPF)), or L is an N,N-containing C10heterobicyclic ligand substituted with one or more substituents selected from C1-4alkyl, halo, C1-4haloalkyl, hydroxy, and C1-4alkoxy,optionally C1-4alkyl and C1-4alkoxy -di-tert-butyl- -dipyridyl (dtBuBIPY) or-dimethoxy- -bipyridine (dMeOBIPY)).3555425773-4 In more particular embodiments, L is selected from tri-n-butylphosphine, - tetramethylethylenediamine (TMEDA), -tetraethylethylenediamine (TEEDA), -pentamethyldiethylenetriamine (PMDTA), 1,3- bis(diphenylphosphino)propane (DPPP), 1,4-bis(diphenylphosphino)butane (DPPB), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (XantPhos), -bis(diphenylphosphino)ferrocene (DPPF), -di-tert-butyl- -dipyridyl (dtBuBIPY) and-dimethoxy- -bipyridine (dMeOBIPY).In particular embodiments, the [Ni(L)n(Q)] complex is any one selected from the following structures: 3655425773-4

[0003] 3755425773-4 In yet more particular embodiments, the [Ni(L)n(Q)] complex is any one selected from the following structures: 3855425773-4 5 39 55425773-4 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 compounds of the invention may range in shape from tetrahedral to square planar, depending on the specific identity of the L and Q ligands. 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, and36Cl, respectively. 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 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%. The compounds of the invention also include all amorphous and crystalline forms. As described above, the inventors have found that the complexes of the second aspect are active in catalysis, including cross-coupling reactions, and the third aspect provides for the use of a complex as defined in the second aspect as a catalyst, such as a cross- coupling catalyst. For examples of nickel-catalysed cross-coupling reactions seeHenrion et al., ACS Catal.2015, 5, 2, 1283 1302; Ritleng et al., ACS Catal. 2016, 6, 2,890 906; Tasker. Nature 509, 299 309, 2014; Clevenger et al., Chem. Rev.2020, 120,13, 6124 6196; and Weix, Acc. Chem. Res.2015, 48, 6, 1767 1775.4055425773-4 For the avoidance of doubt, each of the embodiments described in relation to Q and L of the first and second aspects may be applied mutatis mutandis to the third aspect. For example, the complex may be selected from formulae IVa to IVk. 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. The invention may be further understood with reference to the clauses that follow. Clause 1. A method for the formation of a [Ni(L)n(Q)] complex from a [Ni(L)n(X)2] complex, the method comprising contacting the [Ni(L)n(X)2] complex with: (iii) (a) a reducing metal or a base; and (d) a glycol comprising tertiary vicinal hydroxy moieties wherein at least one of the hydroxy moieties is conjugated with a pi system; or (iv) (a) a reducing metal; and (d) a ketone comprising a carbonyl moiety conjugated with a pi system, wherein: Q is the ketone, or a ketone derived from the glycol, complexed to nickel; L is a mono-, di-, or tri-dentate L-type ligand, wherein when n is 2 when L is monodentate and n is 1 when L is di- or tri-dentate; and X is a monovalent or divalent monoanionic ligand. Clause 2. The method of clause 1, wherein: (i) Q is of formula (I): wherein: 4155425773-4 R1and R2are each independently selected from cyclic C6-C18hydrocarbyl, C1- C17heterocyclyl, C1-6alkyl, C2-6alkenyl, C4-6dialkenyl, C6trialkenyl, C2-6alkynyl, C4-6dialkynyl, and C6trialkynyl, each of which is optionally substituted with one or more substituents selected from cyclic C6-C18hydrocarbyl, cyclic C3-C17heterocarbyl, C1-4alkyl, C2-6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino wherein the optional cyclic C6-C18hydrocarbyl and cyclic C3-C17heterocarbyl substituents are optionally substituted with C1-4alkyl, C2-6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino; or (ii) Q is of formula (II): wherein A is a cyclic C6-C18hydrocarbyl or a C3-C17heterocyclyl, each being optionally substituted with one or more substituents selected from cyclic C6-C18hydrocarbyl, cyclic C1-C17heterocarbyl, C1-4alkyl, C2-6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino wherein the optional cyclic C6-C18hydrocarbyl and cyclic C1- C17heterocarbyl substituents are optionally substituted with C1-4alkyl, C2-6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino; and wherein A comprises a pi system with which the carbonyl moiety of formula (II) is conjugated. Clause 3. The method of clause 1, wherein the [Ni(L)n(Q)] complex is of formula (II): wherein: R1and R2are independently selected from phenyl, C1-6alkyl, C2-6alkenyl, C4- 6dialkenyl, C6trialkenyl, C2-6alkynyl, C4-6dialkynyl, and C6trialkynyl, each of which is optionally substituted with one or more substituents selected from phenyl, C1-4alkyl, C2-6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino, wherein the optional phenyl substituent is optionally substituted with C1-4alkyl, C2-6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino. 4255425773-4 Clause 4. The method of clause 2 or clause 3, wherein R1and R2are each optionally substituted phenyl. Clause 5. The method of clause 4, wherein R1and R2are optionally substituted with one or more substituents selected from C1-4alkyl, C2-6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino. Clause 6. The method of clause 3, wherein R1and R2are phenyl. Clause 7. The method of any one preceding clause, wherein L binds to the nickel through phosphorus, nitrogen, oxygen and / or carbon atoms, for example L binds to the nickel through phosphorus, nitrogen and / or oxygen atoms. Clause 8. The method of any one of clauses 1 to 6, wherein: L is monodentate and binds to the nickel through a phosphorus atom or a carbon atom; L is bidentate and chelates to the nickel through phosphorus, nitrogen, carbon and / or oxygen atoms; or L is tridentate, and chelates to the nickel through nitrogen, phosphorus and / or carbon atoms. Clause 9. The method of clause 8, wherein: L is monodentate and is selected from a phosphine ligand and a carbene ligand; L is bidentate and comprises two binding moieties independently selected from phosphine, amine , imine, pyridine, and carbene; or L is tridentate and comprises three binding moieties independently selected from phosphine, amine, imine, pyridine, and carbene. Clause 10. The method of any one preceding clause, wherein L is bidentate or tridentate and has a natural bite angle of at least 75 °, such as 75 ° to 140 °. Clause 11. The method of any one of clauses 1 to 9, wherein L is monodentate and Clause 12. The method of any one preceding clause, wherein L is selected from a tri- cycloC5-6hydrocarbylphosphine, C1-4alkyl-di-cycloC5-6hydrocarbylphosphine, tetraC1-4alkylC2-4alkylenediamine, pentaC1-4alkylC2-4alkylenetriamine, N,N-containing C10heterobicyclic, N,N-containing C12-14heterotricyclic ligand, bis(di-cycloC5-4355425773-4 6hydrocarbylphosphino)C2-4alkylene, bis(di-cycloC5-6hydrocarbylphosphino)xanthene, bis(di-C1-4alkylphosphino)xanthene, bis(di-cycloC5-6hydrocarbylphosphino)ferrocene, bis(di-C1-4alkylphosphino)ferrocene, bis(di-cycloC5-6hydrocarbylphosphinophenyl)ether, and bis(di-C1-4alkylphosphinophenyl)ether, each of which is optionally substituted with one or more substituents selected from C1-4alkyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy and morpholino. Clause 13. The method of clause 12, wherein L is selected from triphenylphosphine, bis(diphenylphosphino)propane, bis(diphenylphosphino)butane, bis(diphenylphosphino)ethane, bis(diphenylphosphino)ferrocene, bis(diphenylphosphino)xanthene, tetramethylethylenediamine, pentamethyldiethylenetriamine, bipyridine, di-tert-butyl-bipyridine, bis(dicyclohexyphosphino)ethane, bis(di-iso-propyl-phosphino)ferrocene, bis(di-tert- butyl-phosphino)ferrocene, diadamantylmorpholinophenylphosphine, methyldiphenylphosphine, and tricyclohexylphosphine. Clause 14. The method of any one preceding clause, wherein X is chloride, bromide or iodide, such as chloride. Clause 15. The method of any one preceding clause, wherein the reducing metal comprises a group I metal. Clause 16. The method of clause 14, wherein the method comprises contacting with any one selected from sodium metal, lithium metal, potassium metal, caesium metal, rubidium metal and graphite intercalation compounds comprising potassium or lithium. Clause 17. The method of any one preceding clause, wherein the base has aconjugate acid with a pKa oClause 18. The method of any one preceding clause, wherein the base is selected from potassium tert-butoxide, lithium tert-butoxide, sodium tert-butoxide, sodium phenoxide, potassium bis(trimethylsilyl)amide, lithium bis(trimethylsilyl)amide, sodium bis(trimethylsilyl)amide, C1-4alkylmagnesium chloride, C5-6hydrocarbylmagnesium chloride, C1-4alkyllithium, C1-4alkylpotassium, C1-4alkylsodium, lithium di(C1-4alkyl)amide, potassium di(C1-4alkyl)amide, sodium di(C1-4alkyl)amide, lithium tetraC1-4alkylC5-6hydrocarbyl, potassium tetraC1-4alkylC5-6hydrocarbyl, sodium tetraC1-4alkylC5-6hydrocarbyl. 4455425773-4 Clause 19. The method of any one preceding clause, wherein the contacting is in an aprotic solvent. Clause 20. The method of clause 19, wherein the aprotic solvent is selected from THF, toluene, diethyl ether, dimethoxyethane, hexane, 2-methyltetrahydrofuran, methyl tert-butyl ether, and cyclopentyl methyl ether. Clause 21. The method of any one preceding clause, wherein the base, reducing metal, ketone and glycol are in molar excess relative to the [Ni(L)n(X)2] complex. Clause 22. The method of any one preceding clause, wherein about 2 to about 3 molar equivalents of base are used relative to the [Ni(L)n(X)2] complex. Clause 23. The method of any one preceding clause, wherein about 2 to about 5 molar equivalents of reducing metal are used relative to the [Ni(L)n(X)2] complex. Clause 24. The method of any one preceding clause, wherein greater than about 2 molar equivalents of the ketone are used relative to the [Ni(L)n(X)2] complex, such as about 2.05 to about 8 molar equivalents of the ketone. Clause 25. The method of any one preceding clause 1.5 molar equivalents of the glycol are used relative to the Ni(L)n(X)2] complex, such as about 1.05 molar equivalents of the glycol. Clause 26. The method of any one preceding clause, wherein: (i) the glycol and the reducing metal or base; or (ii) the ketone and the reducing metal, are contacted prior to contacting with the [Ni(L)n(X)2] complex. Clause 27. The method of any one preceding clause, wherein the [Ni(L)n(X)2] complex is contacted with the glycol. 4555425773-4 Clause 28. A [Ni(L)n(Q)] complex wherein: Q is a ketone complexed to nickel; L is a mono-, di-, or tri-dentate L-type ligand selected from tri-cycloC5-6hydrocarbylphosphine, C1-4alkyl-di-cycloC5-6hydrocarbylphosphine, tetraC1-4alkylC2- 4alkylenediamine, pentaC1-4alkylC2-4alkylenetriamine, N,N-containing C12- 14heterotricyclic ligand, bis(di-cycloC5-6hydrocarbylphosphino)C2-4alkylene, bis(di- cycloC5-6hydrocarbylphosphino)xanthene, bis(di-C1-4alkylphosphino)xanthene, bis(di- cycloC5-6hydrocarbylphosphino)ferrocene, bis(di-C1-4alkylphosphino)ferrocene, bis(di- cycloC5-6hydrocarbylphosphinophenyl)ether, and bis(di-C1-4alkylphosphinophenyl)ether, each of which is optionally substituted with one or more substituents selected from C1- 4alkyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy and morpholino, or L is an N,N-containing C10heterobicyclic ligand optionally substituted with one or more substituents selected from C1-3alkyl, halo, C1-4haloalkyl, hydroxy, and C1-4alkoxy; and wherein when L is monodentate, n is 2 and when L is bi- or tri-dentate, n is 1. Clause 29. The complex of clause 28, wherein Q is as defined in any one of clauses 2 to 6. Clause 30. Use of a complex as defined in clause 28 or clause 29 as a catalyst, such as a cross-coupling catalyst. EXAMPLES The invention may be further understood with reference to the examples that follow. General considerations The following experimental work was air and moisture sensitive, so degassed anhydrous solvents were used. Reactions were conducted in a glovebox or using Schlenk line techniques with relevant equipment. NMR codes beginning with B and D were run on different spectrometers. The variance between the two spectrometers is typically1H ~0.5-1 ppm adjustment and31P ~1-5 ppm. Synthesis Typical procedure (Radical anion pathway) 1) ketone + reducing metal 4655425773-4 To a reaction vessel containing a magnetic stirrer bar, ketone (such as benzophenone, 3 equivalents relative to [(L)nNiX2]) was added along with solvent (such as anhydrous tetrahydrofuran (THF)), after which reducing metal (such as sodium, 2.4 equivalents relative to [(L)nNiX2]) was slowly added to generate a Blue Radical anion species. Once this had stirred at room temperature for at least 10 minutes, [(L)nNiX2] was added to the vessel, which was left to stir at room temperature for 3-12 hr (until the end point of the reaction had been confirmed). The resultant reaction mixture was then filtered before isolation of the filtrate containing [(L)nNi(Q)]. 2) glycol + reducing metal To a reaction vessel containing a magnetic stirrer bar, glycol (such as pinacol, 1.05 equivalents relative to [(L)nNiX2]), [(L)nNiX2]) was added along with solvent (such as anhydrous THF). After this, the reaction vessel was allowed to stir at the relevant temperature for > 10 minutes to suspend and dissolve relevant materials. To the resultant reaction mixture, reducing metal (2.4 equivalents relative to [(L)nNiX2]) was added, and the reaction was left stirring for 3-12 hr (until the end point of the reaction had been confirmed). [(L)nNi(Q)] complexes were then isolated from the resultant reaction mixture. 3) glycol + base To a reaction vessel containing a magnetic stirrer bar, glycol (e.g. pinacol, 1.05 equivalents relative to [(L)nNiX2]), and [(L)nNiX2]) was added along with solvent (e.g. anhydrous THF). After this, the reaction vessel was allowed to stir at the relevant 4755425773-4 temperature for >10 minutes to suspend and dissolve relevant materials. Then, a solution of base (e.g. metal alkoxide base, 2.2 equivalents relative to [(L)nNiX2]) was added, and the reaction was left stirring for 3-12 hr (until the end point of the reaction had been confirmed). [(L)nNi(Q)] complexes were then isolated from the resultant reaction mixture. Typical procedure (dianion pathway): 4) ketone + reducing metal To a reaction vessel containing a magnetic stirrer bar, ketone (such as benzophenone, 1.5 equivalents relative to [(L)nNiCl2]) was added along with solvent (such as anhydrous THF), after which reducing metal (such as sodium, 3 equivalents relative to [(L)nNiCl2]) was slowly added to generate a Purple Dianion species. Once this had stirred at room temperature for at least 10 minutes, [(L)nNiCl2] was added to the vessel, which was left to stir at room temperature for 3-12 hr (until the end point of the reaction had been confirmed). The resultant reaction mixture was then filtered before isolation of the filtrate containing [(L)nNi(Q)]. 5) glycol + reducing metal To a reaction vessel containing a magnetic stirrer bar, glycol (such as pinacol, 0.55 equivalents relative to [(L)nNiCl2]), [(L)nNiCl2]) was added along with solvent (such as anhydrous THF). After this, the reaction vessel was allowed to stir at the relevant temperature for > 10 minutes to suspend and dissolve relevant materials. To the resultant reaction mixture, reducing metal (3 equivalents relative to [(L)nNiCl2]) was added, and the reaction was left stirring for 3-12 hr (until the end point of the reaction had been confirmed). [(L)nNi(Q)] complexes were then isolated from the resultant reaction mixture. 4855425773-4 Results Initial results obtained using method 1) above with benzophenone (BP) and sodium metal in THF and various L ligands. The results are shown in Table 1. Various nickel(0) ketone complexes were successfully synthesised and characterised. Table 1 – Initial results using benzophenone (BP) and sodium metal in method 1) Starting complex Filtrate details Characterised products [(PPh3)2NiCl2] Red [(PPh3)2Ni(BP)] [(DPPB)NiCl2] Red [(DPPB)Ni(BP)] [(DPPF)NiCl2] Red [(DPPF)Ni(BP)] [(XantPhos)NiCl2] Red [(XantPhos)Ni(BP)] [(BIPY)NiCl2] Green [(BIPY)Ni(BP)] [(dtBuBIPY)NiCl2] Green [(dtBuBIPY)Ni(BP)] The same method, but with a ratio of reducing metal:ketone (in this case sodium metal:benzophenone) of 2.4:6 was used to synthesise additional complexes, with the results shown in Table 2. Table 2 - Results using benzophenone (BP) and sodium metal in a ratio of 2.4:6 in method 1) Starting complex Characterised Products [(DCyPE)NiCl2] [(DCyPE)Ni(BP)] [(DiPrPF)NiCl2] [(DiPrPF)Ni(BP)] [(DtBuPF)NiCl2] [(DtBuPF)Ni(BP)] [(MorDalPhos)NiCl2] [(MorDalPhos)Ni(BP)] Reaction method 1) was then employed with L of [(L)nNiCl2] being different bisdiphenylphosphinoalkane ligands. The results are shown in Table 3. Table 3 – Results using method 1) with benzophenone (BP) and sodium metal in a ratio of 2.4:5, LT = low temperature approx -30 °C, SA = slower addition, i.e. adding the nickelcomplex in 4 to 5 equal portions over 15 to 20 minutes, ON = overnight, and S’A = slowaddition of Ni(II) to the radical solution, i.e. adding the nickel complex in 8 to 10 equal portions over 30 to 40 minutes. 4955425773-4 Starting complex Conditions Product(s) (DPPP)NiCl2 LT in THF [(DPPP)2Ni]:[(DPPP)Ni(BP)] 1:5 (DPPB)NiCl2LT in THF [(DPPB)2Ni]:[(DPPB)Ni(BP)] 1:244 (DPPE)NiCl2SA in THF [(DPPE)2Ni]:[(DPPE)Ni(BP)] 1:3 (DPPP)NiCl2 SA in THF [(DPPP)2Ni]:[(DPPP)Ni(BP)] 1:5 (DPPB)NiCl2 SA in THF [(DPPB)Ni(BP)] only (DPPE)NiCl2 SA ON in THF [(DPPE)2Ni]:[(DPPE)Ni(BP)] 1:6 (DPPP)NiCl2 SA ON in THF [(DPPP)2Ni]:[(DPPP)Ni(BP)] 2:19 (DPPB)NiCl2 SA ON in THF [(DPPP)2Ni]:[(DPPB)Ni(BP)] 1:27 (DPPE)NiCl2 [(DPPE)2Ni]:[(DPPE)Ni(BP)] 1:1 (DPPP)NiCl2[(DPPP)2Ni]:[(DPPP)Ni(BP)] 1:6 (DPPB)NiCl2 [(DPPB)Ni(BP)] only Synthetic route 3) This work involved the use of a suitable base (e.g. pKa > 15) with benzopinacol (BPL) and allowed for the formation of yet more nickel(0) ketone complexes. The results are shown in Table 4. Table 4 – Results using method 3), reactions run at various scales (1 mmol or less with the exception of [(dtBuBIPY)NiCl2] and [(PPh3)2NiCl2] which were run at 10 mmol and 30 mmol respectively) Starting complex Method (Base:BPL) Characterised products [(PMePh2)2NiCl2] 2.2 : 1.05 @240K Product detected, to be characterised [(PPh3)2NiCl2] 2.2 : 1.05 @254K Product detected, to be characterised [(PCy3)2NiCl2] 2.2 : 1.05 @240K Product detected, to be characterised [(DPPE)NiCl2] 2.2 : 1.05 @240K [(DPPE)Ni(BP)] [(DPPP)NiCl2] 2.2 : 1.05 @240K [(DPPP)Ni(BP)] [(dtBuBIPY)NiCl2] 2.2 : 1.05 @254K [(dtBuBIPY)Ni(BP)] 5055425773-4 Different reducing metals and benzophenone, method 1) The formation of the desired product was assessed when different reducing metals were used (Li metal (2.4 eq. = 8.4 mg), K metal (2.4 eq. = 47 mg), KC8(2.4 eq. =163 mg)) with benzophenone (550 mg) and [(PPh3)2NiCl2] (383 mg). Reducing metal was added to a solution containing necessary equivalence of benzophenone which was stirred at room temperature before the addition of the starting complex. The results are shown in Table 5. Table 5 – Results when using method 1) with various reducing metals. Reactions were carried out using a 0.5 mmol scale in THF. Product generation was analysed by31P NMR of the reaction mixture for target complex [(PPh3)2Ni(BP)]. Variable(s) Complex used Product generated Li metal [(PPh3)2NiCl2] Yes K metal [(PPh3)2NiCl2] Yes KC8 [(PPh3)2NiCl2] Yes Different reducing metals and benzopinacol, method 2) The formation of the desired product was assessed when different reducing metals were used. The metals used were: Li metal (2 eq. = 2.8 mg, 4 eq. = 5.6 mg), Na metal (2 eq. = 9.2 mg, 4 eq. = 18.4 mg), K metal (2 eq. = 15.6 mg, 4 eq. =31.2 mg), KC8 (2 eq. = 54 mg, 4 eq. = 108 mg), with benzopinacol (74 mg) and [(PPh3)2NiCl2] (153 mg). The reducing metal was added to a THF solution containing [(PPh3)2NiCl2] and benzopinacol 5155425773-4 at room temperature with magnetic stirring within an Argon filled glovebox. The results are shown in Table 6. Table 6 - Results when using method 2) with various reducing metals. Reactions were carried out using a 0.2 mmol scale in THF. Product generation was analysed by31P NMR of the reaction mixture for target complex [(PPh3)2Ni(BP)]. Variable (eq. used) Metal eq. (quench) Product generated Li Metal 4 (no quench) Yes Li Metal 4 (MeOH quench) Yes Na Metal 4 (no quench) Yes Na Metal 4 (MeOH quench) Yes K Metal 4 (MeOH quench) Yes KC84 (MeOH quench) Yes Different strong bases and benzopinacol, method 3) The formation of the desired product was assessed when different strong bases were used with benzopinacol (74 mg) and [(PPh3)2NiCl2] (153 mg). The base was added to a THF solution containing [(PPh3)2NiCl2] and benzopinacol at room temperature with magnetic stirring within an Argon filled glovebox. The results are shown in Table 7. Table 7 - Results when using method 3) with various reducing metals. Reactions were carried out using a 0.2 mmol scale in THF. Product generation was analysed by31P NMR of the reaction mixture for target complex [(PPh3)2Ni(BP)]. Variable Base:benzopinacol ratio Product generated LiOtBu 2.2:1.05 Yes NaOPh 2.2:1.05 Yes KOtBu 2.2:1.05 Yes KHMDS 2.2:1.05 Yes MeMgCl 2.2:1.05 Yes PhMgCl 2.2:1.05 Yes 5255425773-4 Product Characterisation The following materials were isolated from various reactions utilising methods 1) to 3). N-Ligated complexes Isolated (34% yield) from a reaction using 3 equivalents of Na metal and 1.5 equivalents of benzophenone at 3 mmol.1H NMR (400 MHz, C6D6): 8.36 (d (J = 8.2 Hz), 4H, Ar-H), 7.35-7.22 (m, 6H, Ar-H), 2.24 (s, 6.5H, CH2 & CH3), 1.77 (s, 6.5H / 8H, CH2 & CH3). Crystal structure obtained and confirmed identity of product. Isolated (~25% yield) from a reaction using 4 equivalents of Na metal and 2 equivalents of benzophenone at 1 mmol.1H NMR (400 MHz, C6D6): 8.51 (s(br), 2H, Ar-H), 8.22(s(br), 2H, Ar-H), 7.28 (m, 6H, Ar- H), 2.50 (m, 2H, CH2), 2.38-2.32 (m(br), 6H, CH2 ), 2.19 (s, 4H, CH2), 2.12 (s, 6H, CH3), 2.06 (s(br) 9H, CH3). Crystal structure obtained and confirmed identity of product. Isolated (10% yield) from a reaction using 2.4 equivalents of Na metal and 3 equivalents of benzophenone at 0.5 mmol. Crystal structure obtained and confirmed identity of product. 5355425773-4 Isolated (67% yield) from a reaction using 2.4 equivalents of Na metal and 3 equivalents of benzophenone at 1 mmol.1H NMR (400 MHz, C6D6): 9.27 (d (J = 5.65Hz), 1H, Ar-H), 8.95 (d ( J = 5.85 Hz), 1H, Ar-H, 8.58 (d (J = 7.42Hz), 4H, Ar-H), 7.29 (m, 4H, Ar-H), 7.21 (m, 2H, Ar-H), 6.71 (dd (J = 5.70 Hz, J = 1.44 Hz), 1H, Ar-H), 6.38 (dd ( J = 5.90 Hz, 1.47 Hz), 1H, Ar-H), 0.92 (s, 9H, tBu-CH3), 0.88 (s, 9H, tBu-CH3)1H NMR (400 MHz, DOCD3): 8.86-8.84 (d (J = 5.6 Hz), 1H, Ar-H), 8.50-8.48 (d (J = 5.79 Hz), 1H, Ar-H), 8.25 (s, 1H, Ar-H), 8.11 (s, 1H, Ar-H), 7.85-7.82 (m, 4H, Ar-H), 7.65 (dd ( 5.80 Hz, 1.40 Hz), 1H, Ar-H), 7.34 (dd (5.90 Hz, 1.58 Hz), 1H, Ar-H), 7.21-7.19 (m, 6H, Ar-H),1.46(s, 9H, tBu-CH3) 1.38(s, 9H, tBu-CH3) P-Ligated complexes [(DPPE)Ni(BP)] 1H NMR: 8.05 (4H, Ar-H), 7.92 (4H, Ar-H), 7.10-6.89 (22H, Ar-H), 1.82-1.72 (2H, CH2), 1.36-1.26 (2H, CH2),31P NMR (162 MHz, C6D6): 46.6-46.1 42.2-41.7 (dd (718 Hz, 80.1 Hz)2P)Crystal structure obtained and confirmed identity of product. [(DPPP)Ni(BP)] 1H NMR: 8.02-7.96 (m, 8H, Ar-H), 7.10-7.05 (m, 10H, Ar-H), 7.02- 6.92 (quintet (34.8 Hz), 8H, Ar-H), 6.88-6.84 (m, 4H, Ar-H), 1.97 (s, 2H, CH2), 1.78 (s, 2H, CH2), 1.31 (t (J = 20.9 Hz), 2H, CH2)31P NMR (162 MHz, C6D6): 24.8-24.5 11.6-11.3 (dd (2150 Hz, 44.1 Hz), 2P)Crystal structure obtained and confirmed identity of product. 5455425773-4 [(DPPB)Ni(BP)] 1H NMR: (400 MHz, C6D6): 8.07-8.03 (t (J = 8.45Hz), 4H, Ar-H), 7.86-7.84 (d (J = 7.40 Hz), 4H, Ar-H), 7.18-7.15 (m, 6H, Ar-H), 7.09-7.03 (m, 6H, Ar-H), 7.00-6.96 (m, 6H, Ar- H), 6.91-6.87 (m, 4H, Ar-H), 1.83-1.77 (m, 4H, CH2), 1.43-1.39 (m, 4H, CH2)31P NMR (162 MHz, C6D6): 33.1-32.8 18.9-18.5 (dd (J = 2310 Hz, J = 55 Hz, 2P)Crystal structure obtained and confirmed identity of product. [(PPh3)2Ni(BP)] 1H NMR: (400 MHz, C6D6): 7.86-7.84 (br s, 4H, Ar-H), 7.71-7.65 (br s, 6H, Ar-H), 7.46 (br s, 1H, Ar-H), 7.09 (br s, 11H, Ar-H), 6.97 (s, 8H, Ar-H), 6.88 (br s, 4H, Ar-H), 6.77 (br s, 6H, Ar-H)31P NMR (162 MHz, C6D6): 36.7-36.4 31.1-30.8 (dd (J = 904 Hz, J = 51.5 Hz), 2P)Crystal structure obtained and confirmed identity of product. [(DPPF)Ni(BP)] Isolated (90-95% yield) from a reaction using 2.4 equivalents of Na metal and 3 equivalents of benzophenone at 5 mmol.1H NMR (400 MHz, C6D6): 8.29 (t (J = 8.74 Hz), 4H, Ar-H), 7.79 (d (J = 7 Hz), 4H, Ar- H), 7.38 (t (J = 8.86 Hz), 4H, Ar-H), 7.20-7.10 (m, 8H, Ar-H), 7.04-6.97 (m, 4H, Ar-H), 6.90 (t(J = 7.15 Hz), 4H, Ar-H), 4.20 (s, 2H, Fc-H), 3.90 (s, 2H, Fc-H), 3.82 (s, 2H, Fc- H), 3.75 (s, 2H, Fc-H)31P NMR (162 MHz, C6D6): 30.4-30.2 23.1-22.9 (dd (J = 1182 Hz, J = 36.85 Hz), 2P)Crystal structure obtained and confirmed identity of product. 5555425773-4 [(XantPhos)Ni(BP)] Isolated (90-95% yield) from a reaction using 2.4 equivalents of Na metal and 3 equivalents of benzophenone at 0.8 mmol.1H NMR:1H NMR (400 MHz, C6D6): 7.88-7.82 (m, 8H, Ar-H), 7.11-7.09 (m, 2H, Ar-H), 7.07-7.02 (m, 6H, Ar-H), 6.99-6.95 (m, 6H, Ar-H), 6.92 (m, 2H, Ar-H), 6.77-6.70 (m, 9H, Ar-H), 6.66-6.62 (m, 2H, Ar-H), 6.52-6.48 (t (J = 7.7 Hz), 1H, Ar-H), 1.29 (s, 6H, CH3)31P NMR(162 MHz, C6D6): 21.8-21.4 19.6-19.2(dd (J = 354 Hz, J= 54.2 Hz), 2P)Products detected and characterised in-situ For some reactions,31P NMR was used to detect the formation of products in situ. :65.1-64.7 57.0-56.6 (dd (J = 1374 Hz, J = 65.5 Hz), 2P) 31P NMR (162 MHz, C6D6): 38.9-38.7 36.7-36.5 (dd (J = 388 Hz, J = 31.4 Hz), 2P)5655425773-4 Cross-coupling reactions of (hetero)aryl halides with arylmagnesium halide reagents catalysed by the nickel complexes General All reactions were prepared under anhydrous oxygen-free conditions using an inert atmosphere glovebox with argon as the working gas; typical oxygen and water levels were below 1 ppm. Anhydrous tetrahydrofuran was obtained from a solvent purification system (<10 ppm water according to Karl-Fischer titrations). Arylmagnesium bromide reagents were prepared from the corresponding aryl bromide and elemental magnesium, and their concentration was established by titration versus iodine in THF solution. Reaction Set-up Stock solutions of a known concentration were prepared for [Ni(Ph2CO)(PPh3)2] and the aryl halide by dissolving a known mass or volume of the corresponding material in anhydrous THF. Vials (4 mL) were charged with anhydrous THF at a volume selected such that the final reaction volume was 1 mL. This was followed by appropriate volumes of: the aryl halide stock solution, to achieve a final concentration in the range of 0.15 0.3 mol / L; the catalyst stock solution, to achieve a final concentration in the range of 0.003 0.03 mol / L; and the arylmagnesium halide stock solution, to achieve a final concentration in the range of 0.15 0.3 mol / L. The vials were capped with a septum-fitted screw-cap, removed from the glovebox, and heated with planetary mixing in a machined 24-place aluminium block attached to a Thermomixer C set to 30 °C for 18 h. Each reaction was then quenched by the addition of ethanol; an aliquot of known volume was diluted in ethyl acetate with a known quantity of dodecane and this solution was analysed by gas chromatography flame ionization detection (GC-FID). Each reaction was performed in duplicate. Analysis An Agilent 7890A gas chromatography (GC) system with a HP-530 m x 0.320 mm x 0.25 µm column was used for all analyses. Authentic samples of each product were prepared by independent synthesis, and their identity and purity were confirmed by1H and13C{1H} NMR analysis and by GC-FID analysis, respectively. 5755425773-4 The authentic standards were used to calibrate the GC-FID versus a dodecane standard. Reaction outcomes were determined by integrating the peaks corresponding to dodecane (for which concentration is known) and the analyte of interest and applying a response factor determined from the calibration process in order to obtain the concentration of analyte. This information, together with the known initial concentration of aryl halide, allows the yield of the reaction to be calculated. Reaction Outcomes 2-Bromotoluene Phenylmagnesium [Ni(Ph2CO)(PPh3)2] Product Yield (%) (mol / L) bromide (mol / L) (mean, two (mol / L) replicates) 0.15 0.15 0.003 58(2) 0.30 0.30 0.006 59(1) 0.15 0.15 0.0075 65(1) 0.30 0.30 0.015 64(3) 0.15 0.15 0.015 73(2) 0.30 0.30 0.03 75(2) 0.15 0.275 0.003 75(2) 2-Bromopyridine Phenylmagnesium [Ni(Ph2CO)(PPh3)2] Product Yield (%) (mol / L) bromide (mol / L) (mean, two (mol / L) replicates) 0.15 0.15 0.003 59(3) 0.30 0.30 0.006 64(1) 0.15 0.15 0.0075 60(1) 0.30 0.30 0.015 65(3) 0.15 0.15 0.015 59(1) 0.30 0.30 0.03 66(2) 0.15 0.275 0.003 65(2) 5855425773-4 [Ni(Ph2CO)(PPh3)2] has thus been shown to be an effective catalyst for representative cross-coupling reactions involving either an aryl halide or a heteroaryl halide with an arylmagnesium halide, with high yields obtained in both reactions. Additional Exemplification Note All J values have been averaged to the nearest integer value Reduction reactions using different X anionic ligands For the reduction of various Ni(II) species two different procedures were used and were as described below. 1. Radical anion pathway with ketone and reducing metal: 40% Na / oil dispersion (70 mg) was added to a 14 mL vial containing Benzophenone (270 mg) in 8 mL anhydrous tetrahydrofuran (THF) with magnetic stirring. 0.5 mmol of [(PPh3)2Ni(X)2] X = Br (372 mg), I (419 mg), or NO3(354 mg) was then added to the mixture with stirring. Colour changes were noted and an aliquot (~0.3 mL) was taken and mixed with 0.3 mL deuterated solvent C6D6before NMR analysis was carried out. 2. Radical anion pathway with glycol and base: 0.5 mmol of [(PPh3)2Ni(X)2] X = Br (372 mg), I (419 mg), or NO3 (354 mg) was added to a 14 mL vial containing Benzopinacol (275 mg) in 7 mL anhydrous tetrahydrofuran (THF) with magnetic stirring. Sodium tert- butoxide (0.8 mL ~2M) was then added to the mixture with stirring. Colour changes were noted and an aliquot (~0.3 mL) was taken and mixed with 0.3 mL deuterated solvent C6D6 before NMR analysis was carried out. The reduction of [(PPh3)2NiBr2] by procedure 1 and 2 generated [(PPh3)2Ni(BP)]: 1. (E81835):31P{1H} NMR (C6D6); dd 36.28-36.04, 30.82-30.58 (J = 50 Hz) 2. (E81839)31P{1H} NMR (C6D6); dd 36.28-36.04, 30.82-30.58 (J = 50 Hz) The reduction of [(PPh3)2NiI2] by procedure 2 generated [(PPh3)2Ni(BP)] 2. (E81840)31P{1H} NMR (C6D6); dd 36.28-36.04, 30.82-30.57 (J = 50 Hz) The reduction of [(PPh3)2Ni(NO3)2] by procedure 1 and 2 generated [(PPh3)2Ni(BP)] 1. (E81835)31P{1H} NMR (C6D6); dd 36.22-35.97, 30.78-30.58 (J = 50 Hz) 2. (E81839)31P{1H} NMR (C6D6); dd 36.25-36.00, 30.79-30.55 (J = 50 Hz) The reduction of [(TMEDA)Ni(OAc)2] by procedure 1 generated [(TMEDA)Ni(BP)], detected via1H NMR analysis. 5955425773-4 Reduction reactions using different L ligandsThe reduction of [(DavePhos)NiCl2], where DavePhos is 2-Dicyclohexylphosphino- -(N,N-dimethylamino)biphenyl, was carried out by mixing sodium metal (60 mg) and Benzophenone (365 mg) in a 14 mL vial containing 8 mL tetrahydrofuran (THF). After complete dissolution of sodium metal and formation of the corresponding radical anions, [(DavePhos)NiCl2] (523 mg) was added in one portion, with stirring. Colour changes were noted and an aliquot (~0.3 mL) was taken and mixed with 0.3 mL deuterated solvent C6D6 before NMR analysis was carried out. [(DavePhos)Ni(BP)] (E82093) was formed.31P{1H} NMR (C6D6); s, 35.38. The reduction of [(C-P)NiCl2] was successful and the product was confirmed by comparison with NMR spectra corresponding to the same product, generated by substitution of the C-P ligand onto [(PPh3)2Ni(BP)]. Substitution comprised mixing the C-P BArF salt, KOtBu and [(PPh3)2Ni(BP)] in deuterated solvents. Free C-P ligand was generated in this reaction and displaced the triphenylphosphine ligands from the Ni(0) complex. C-P is 1-(2-diphenylphosphinoethyl)-3-(2,4,6-trimethylphenyl)imidazol-2-ylide, as below: .The reduction pr - [(C-P)NiCl2] was generated inanhydrous THF (2 mL) by reacting [(Lut)2NiCl2] (68 mg), [(C-P)(HBArF24)] (245 mg) and sodium tert-butoxide (0.3 mL ~2M), with magnetic stirring. This was a first reaction mixture. In a separate reaction vessel, sodium metal (18 mg) was reacted with benzophenone (110 mg) in 2 mL of anhydrous tetrahydrofuran (THF), with magnetic stirring. This was a second reaction mixture. The first reaction mixture was taken up with a syringe and needle and added to the second reaction mixture. [(C-P)Ni(BP)] Reduction (E82091)31P{1H} NMR (C6D6); s, 29.89 [(C-P)Ni(BP)] Substitution (D394192)31P{1H} NMR (C6D6); s, 30.17 6055425773-4 General reduction procedure for screening Q ligands Ketones were screened for reaction with sodium metal to generate radical anion species before reaction with [(PPh3)2NiCl2]. 2 mmol of each ketone was reacted with sodium, either 40% Na / oil (138 mg) or Na metal (60 mg), and the mixture was magnetically stirred in 8 mL tetrahydrofuran (THF). After colour changes and complete dissolution of sodium metal was observed (the sodium metal having reacted to form the corresponding radical anions), the mixture was reacted with [(PPh3)2NiCl2] (654 mg) (unless specified otherwise). Colour changes were noted and an aliquot (~0.3 mL) was taken and mixed with 0.3 mL deuterated solvent C6D6 before NMR analysis was carried out. Screening different ketones to generate [(L)nNi(ketone)] 4-Benzoylbiphenyl: successful reduction of [(PPh3)2NiCl2], affording [(PPh3)2Ni(4- Benzoylbiphenyl)] (E81985).31P{1H} NMR (C6D6); dd 36.03-35.79, 31.15-30.91 (J = 49 Hz). Phenyl(4-tolyl)methanone: successful reduction of [(PPh3)2NiCl2], affording [(PPh3)2Ni(Phenyl(4-tolyl)methanone)] (E81986).31P{1H} NMR (C6D6); dd 36.19-35.93, 30.72-30.46 (J = 53 Hz). 2-Benzoylpyridine: successful reduction of [(DPPF)NiCl2], affording [(DPPF)Ni(2- Benzoylpyridine)] (E82066).31P{1H} NMR (C6D6); two singlets 30.74, 24.84 (1:1 integrals). -Acetonaphthone: successful reduction of [(PPh3)2NiCl2], affording [(PPh3)2Ni( -Acetonaphthone)] (E82003)31P{1H} NMR (C6D6); two broad singlets 30.13, 26.96. Isobutyrophenone: successful reduction of [(PPh3)2NiCl2], affording [(PPh3)2Ni(Isobutyrophenone)] (E82067).31P{1H} NMR (C6D6); dd 38.32-38.11, 28.27- 28.06 (J = 42 Hz). Cyclopentyl phenyl ketone: successful reduction of [(PPh3)2NiCl2], affording [(PPh3)2Ni(Cyclopentyl phenyl ketone)] (E82068).31P{1H} NMR (C6D6); dd 38.46-38.24, 28.18-27.93 (J = 45 Hz). Cyclohexyl phenyl ketone: successful reduction of [(PPh3)2NiCl2], affording [(PPh3)2Ni(Cyclohexyl phenyl ketone)] (E82069).31P{1H} NMR (C6D6); dd 37.88-37.65, 27.74-27.49 (J = 51 Hz). 6155425773-4 9-Fluorenone: successful reduction of [(PPh3)2NiCl2], affording [(PPh3)2Ni(9- Fluorenone)] (E81909).31P{1H} NMR (C6D6); dd 40.04-39.84, 33.43-33.23 (J = 42 Hz). 9H-Xanthen-9-one: successful reduction of [(PPh3)2NiCl2], affording [(PPh3)2Ni(9H- Xanthen-9-one)] (E82004).31P{1H} NMR (C6D6); two broad singlets 35.92, 31.64. 10,10-dimethyl-9-10-dihydroanthracen-9-one: successful reduction of [(PPh3)2NiCl2], affording [(PPh3)2Ni(10,10-dimethyl-9-10-dihydroanthracen-9-one)] (E82006).31P{1H} NMR (C6D6); dd 36.39-36.13, 33.49-33.27 (J = 49 Hz). 10,11-Dihydro-5H-dibenzo[a,d][7]annulen-5-one: successful reduction of [(PPh3)2NiCl2], affording [(PPh3)2Ni(10,11-Dihydro-5H-dibenzo[a,d][7]annulen-5-one)] (E82007).31P{1H} NMR (C6D6); dd 37.07-36.82, 33.51-33.27 (J = 50 Hz). 6255425773-4

Claims

CLAIMS:

1. A method for the formation of a [Ni(L)n(Q)] complex from a [Ni(L)n(X)2] complex, the method comprising contacting the [Ni(L)n(X)2] complex with: (v) (a) a reducing metal or a base; and (e) a glycol comprising tertiary vicinal hydroxy moieties wherein at least one of the carbon atoms bonded to a tertiary vicinal hydroxy moiety is adjacent to a pi system; or (vi) (a) a reducing metal; and (e) a ketone comprising a carbonyl moiety conjugated with a pi system, wherein: Q is the ketone, or a ketone derived from the glycol, complexed to nickel; L is a mono-, di-, or tri-dentate L-type ligand, wherein when n is 2 when L is monodentate and n is 1 when L is di- or tri-dentate; and X is a monovalent or divalent monoanionic ligand.

2. The method of claim 1, wherein: (iii) Q is of formula (I):wherein: R1and R2are each independently selected from cyclic C5-C18hydrocarbyl, C1- C17heterocyclyl, C1-6alkyl, C2-6alkenyl, C4-6dialkenyl, C6trialkenyl, C2-6alkynyl, C4-6dialkynyl, and C6trialkynyl, each of which is optionally substituted with one or more substituents selected from cyclic C3-C18hydrocarbyl, cyclic C3-C17heterocarbyl, C1-4alkyl, C2-6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino wherein the optional cyclic C3-C18hydrocarbyl and cyclic C3-C17heterocarbyl substituents are optionally substituted with C1-4alkyl, C2-6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino; 6355425773-4or (iv) Q is of formula (II):wherein A is a cyclic C6-C18hydrocarbyl or a C3-C17heterocyclyl, each being optionally substituted with one or more substituents selected from cyclic C3- C18hydrocarbyl, cyclic C1-C17heterocarbyl, C1-4alkyl, C2-6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino wherein the optional cyclic C3-C18hydrocarbyl and cyclic C1-C17heterocarbyl substituents are optionally substituted with C1-4alkyl, C2- 6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino; and wherein A comprises a pi system with which the carbonyl moiety of formula (II) is conjugated 3. The method of claim 1, wherein the [Ni(L)n(Q)] complex is of formula (IIIa), (IIIc) or (IIId):wherein: R1andare independently selected from phenyl, napththyl, pyridyl, anthracenyl, phenanthracenyl, C5-6cycloalkyl, C1-6alkyl, C2-6alkenyl, C4-6dialkenyl, C6trialkenyl, C2-6alkynyl, C4-6dialkynyl, and C6trialkynyl, each of which is optionally substituted with one or more substituents selected from phenyl, C1-4alkyl, C2-6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino, wherein the optional phenyl substituent is optionally substituted with C1-4alkyl, C2-6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino; 6455425773-4each ring B is independently selected from benzene, naphthalene and C3- C17heteroarene, each optionally substituted with one or more substituents selected from cyclic C3-C18hydrocarbyl, cyclic C1-C17heterocarbyl, C1-4alkyl, C2-6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino wherein the optional cyclic C3- C18hydrocarbyl and cyclic C1-C17heterocarbyl substituents are optionally substituted with C1-4alkyl, C2-6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino; each ring C is optionally present and, when present, is independently selected from a cyclic C5-C11hydrocarbon or a C3-C10heterocycle, each optionally substituted with one or more substituents selected from cyclic C3-C18hydrocarbyl, cyclic C1- C17heterocarbyl, C1-4alkyl, C2-6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1- 4alkyl)amino wherein the optional cyclic C3-C18hydrocarbyl and cyclic C1-C17heterocarbyl substituents are optionally substituted with C1-4alkyl, C2-6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino; Rfis selected from cyclic C3-C18hydrocarbyl, cyclic C1-C17heterocarbyl, C1-4alkyl, C2-6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino wherein the optional cyclic C3-C18hydrocarbyl and cyclic C1-C17heterocarbyl substituents are optionally substituted with C1-4alkyl, C2-6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino; and nf2 is 0 and nf1 is 0; nf2 is 1 and nf1 is 0 to 2; or nf2 is 2 and nf1 is 0 to 4.

4. The method of claim 2 or claim 3, wherein: (i) R1and R2are each independently selected from phenyl, napththyl, pyridyl, anthracenyl, phenanthracenyl, C5-6cycloalkyl and C1-6alkyl, each of which is optionally substituted; and / or (ii) ring C is present and rings B and C are each selected from benzene and naphthalene, such as benzene, each of which is optionally substituted; and Rfis selected from C1-4alkyl, halo and C1-4haloalkyl.

5. The method of any one of claims 2 to 4, wherein R1and R2are optionally substituted with one or more substituents selected from C1-4alkyl, C2-6alkenyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy, and di(C1-4alkyl)amino.

6. The method of any one of claims 2 to 4, wherein one of R1and R2is phenyl or pyridyl and the other is selected from phenyl, naphthyl, pyridyl, cyclopentyl, cyclohexyl and C1-4alkyl, each of which is optionally substituted; and B and C are each benzene. 6555425773-47. The method of any one preceding claim, wherein L binds to the nickel through phosphorus, nitrogen, oxygen and / or carbon atoms, for example L binds to the nickel through phosphorus, nitrogen and / or oxygen atoms.

8. The method of any one of claims 1 to 6, wherein: L is monodentate and binds to the nickel through a phosphorus atom or a carbon atom; L is bidentate and chelates to the nickel through phosphorus, nitrogen, carbon and / or oxygen atoms; or L is tridentate, and chelates to the nickel through nitrogen, phosphorus and / or carbon atoms.

9. The method of claim 8, wherein: L is monodentate and is selected from a phosphine ligand and a carbene ligand; L is bidentate and comprises two binding moieties independently selected from phosphine, amine , imine, pyridine, and carbene; or L is tridentate and comprises three binding moieties independently selected from phosphine, amine, imine, pyridine, and carbene.

10. The method of any one preceding claim, wherein L is bidentate or tridentate and has a natural bite angle of at least 75 °, such as 75 ° to 140 °.

11. The method of any one of claims 1 to 9, wherein L is monodentate and has a least 120 °, such as 120 ° to 190 °.

12. The method of any one preceding claim, wherein L is selected from a tri-C1- 6alkylphosphine, tri-cycloC5-6hydrocarbylphosphine, C1-4alkyl-di-cycloC5- 6hydrocarbylphosphine, -tetraC1-4alkylC2-4alkylenediamine, - pentaC1-4alkylC2-4alkylenetriiamine, N,N-containing C10heterobicyclic ligand, N,N- containing C12-14heterotricyclic ligand, bis(di-cycloC5-6hydrocarbylphosphino)C2-4alkylene, bis(di-cycloC5-6hydrocarbylphosphino)xanthene, bis(di-C1-4alkylphosphino)xanthene, bis(di-cycloC5-6hydrocarbylphosphino)ferrocene, bis(di-C1-4alkylphosphino)ferrocene, bis(di-cycloC5-6hydrocarbylphosphinophenyl)ether, and bis(di-C1-4alkylphosphinophenyl)ether, each of which is optionally substituted with one or more substituents selected from C1-4alkyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy and morpholino; 6655425773-4L is a diC1-4alkyl-phosphino-biphenyl or a di-cycloC5-6hydrocarbylphosphino- biphenyl, wherein each biphenyl is optionally substituted with one or more substituents selected from C1-4alkyl, di(C1-4alkyl)amino, and C1-4alkoxy; L is a diC1-4alkyl-phosphino-biphenyl or a di-cycloC5-6hydrocarbylphosphino- biphenyl, wherein each biphenyl is optionally substituted with one or more substituents selected from C1-4alkyl, di(C1-4alkyl)amino, and C1-4alkoxy; or L comprises a di-cycloC5-6hydrocarbylphosphino binding moiety linked, optionally by an alkyl linker, to an N-heterocyclic carbene binding moiety.

13. The method of claim 12, wherein L is selected from triphenylphosphine, bis(diphenylphosphino)propane, bis(diphenylphosphino)butane, bis(diphenylphosphino)ethane, bis(diphenylphosphino)ferrocene, bis(diphenylphosphino)xanthene, tetramethylethylenediamine, pentamethyldiethylenetriamine, bipyridine, di-tert-butyl-bipyridine, bis(dicyclohexyphosphino)ethane, bis(di-iso-propyl-phosphino)ferrocene, bis(di-tert- butyl-phosphino)ferrocene, diadamantylmorpholinophenylphosphine,methyldiphenylphosphine, tricyclohexylphosphine, dicyclohexylphosphino- -(N,N-dimethylamino)biphenyl and 1-(2-diphenylphosphinoethyl)-3-(2,4,6- trimethylphenyl)imidazol-2-ylide.

14. The method of any one preceding claim, wherein X is selected from halide, acetate and nitrate, optionally wherein X is chloride, bromide or iodide, such as chloride.

15. The method of any one preceding claim, wherein the reducing metal comprises a group I metal.

16. The method of claim 14, wherein the method comprises contacting with any one selected from sodium metal, lithium metal, potassium metal, caesium metal, rubidium metal and graphite intercalation compounds comprising potassium or lithium.

17. The method of any one preceding claim, wherein the base has a conjugate acid with a pKa of 9.5 or 15.

18. The method of any one preceding claim, wherein the base is selected from potassium tert-butoxide, lithium tert-butoxide, sodium tert-butoxide, sodium phenoxide, potassium bis(trimethylsilyl)amide, lithium bis(trimethylsilyl)amide, sodium bis(trimethylsilyl)amide, C1-4alkylmagnesium chloride, C5-6hydrocarbylmagnesium 6755425773-4chloride, C1-4alkyllithium, C1-4alkylpotassium, C1-4alkylsodium, lithium di(C1-4alkyl)amide, potassium di(C1-4alkyl)amide, sodium di(C1-4alkyl)amide, lithium tetraC1-4alkylC5-6hydrocarbyl, potassium tetraC1-4alkylC5-6hydrocarbyl, sodium tetraC1-4alkylC5-6hydrocarbyl.

19. The method of any one preceding claim, wherein the contacting is in an aprotic solvent, optionally wherein the aprotic solvent is selected from THF, toluene, diethyl ether, dimethoxyethane, hexane, 2-methyltetrahydrofuran, methyl tert-butyl ether, and cyclopentyl methyl ether.

20. The method of any one preceding claim, wherein the base, reducing metal, ketone and glycol are in molar excess relative to the [Ni(L)n(X)2] complex, optionally wherein: (i) about 2 to about 3 molar equivalents of base are used relative to the [Ni(L)n(X)2] complex; or (ii) about 2 to about 5 molar equivalents of reducing metal are used relative to the [Ni(L)n(X)2] complex.

21. The method of any one preceding claim, wherein: (i) greater than about 2 molar equivalents of the ketone are used relative to the [Ni(L)n(X)2] complex, such as about 2.05 to about 8 molar equivalents of the ketone; or (ii) about 1.01 to about 1.5 molar equivalents of the glycol are used relative to the Ni(L)n(X)2] complex, such as about 1.05 molar equivalents of the glycol.

22. The method of any one preceding claim, wherein: (iii) the glycol and the reducing metal or base; or (iv) the ketone and the reducing metal, are contacted prior to contacting with the [Ni(L)n(X)2] complex.

23. The method of any one preceding claim, wherein the [Ni(L)n(X)2] complex is contacted with the glycol. 6855425773-424. A [Ni(L)n(Q)] complex wherein: Q is a ketone complexed to nickel, wherein the ketone comprises a carbonyl moiety conjugated with a pi system; L is a mono-, di-, or tri-dentate L-type ligand selected from tri-C1-6alkylphosphine (such as tri-n-butylphosphine), tri-cycloC5-6hydrocarbylphosphine, C1-4alkyl-di-cycloC5- 6hydrocarbylphosphine, -tetraC1-4alkylC2-4alkylenediamine, - pentaC1-4alkylC2-4alkylenetriamine, N,N-containing C12-14heterotricyclic ligand, bis(di- cycloC5-6hydrocarbylphosphino)C2-4alkylene, bis(di-cycloC5- 6hydrocarbylphosphino)xanthene, bis(di-C1-4alkylphosphino)xanthene, bis(di-cycloC5- 6hydrocarbylphosphino)ferrocene, bis(di-C1-4alkylphosphino)ferrocene, bis(di-cycloC5- 6hydrocarbylphosphinophenyl)ether, and bis(di-C1-4alkylphosphinophenyl)ether, each of which is optionally substituted with one or more substituents selected from C1-4alkyl, halo, C1-4haloalkyl, hydroxy, C1-4alkoxy and morpholino, L is an N,N-containing C10heterobicyclic ligand optionally substituted with one or more substituents selected from C1-4alkyl, halo, C1-4haloalkyl, hydroxy, and C1-4alkoxy, L is a diC1-4alkyl-phosphino-biphenyl or a di-cycloC5-6hydrocarbylphosphino- biphenyl, wherein each biphenyl is optionally substituted with one or more substituents selected from C1-4alkyl, di(C1-4alkyl)amino, and C1-4alkoxy, or L comprises a di-cycloC5-6hydrocarbylphosphino binding moiety linked, optionally by an alkyl linker, to an N-heterocyclic carbene binding moiety; andwherein when L is monodentate, n is 2 and when L is bi- or tri-dentate, n is 1, optionally wherein Q is as defined in any one of claims 2 to 6.

25. Use of a complex as defined in claim 24 as a catalyst, such as a cross-coupling catalyst. 6955425773-4

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