Catalysts and synthesis thereof

Abstract

The present invention relates to nickel complexes comprising a ketone moiety and one or more stabilizing ligands, and to a method of synthesizing such complexes by contacting a precursor nickel complex with a reducing agent and a diol or ketone. The present invention further relates to the use of said nickel complexes as catalysts, such as cross-coupling catalysts.

Description

Technical Field

[0001] This invention relates to nickel complexes comprising a ketone moiety and one or more stable ligands, and to a method for synthesizing such complexes by contacting a precursor nickel complex with a reducing agent and a diol or ketone. The invention also relates to the use of said nickel complexes as catalysts, such as cross-coupling catalysts. Background Technology

[0002] Cross-coupling reactions enable the rapid assembly of molecules from two functionalized fragments. The 2010 Nobel Prize in Chemistry was awarded to three pioneers of this technology (Heck, Negishi, and Suzuki), and a recent literature review indicates that these reactions are among the few modern reactions rapidly and widely adopted by the pharmaceutical industry (D. G. Brown and J. Boström). J.Med.Chem. ,2015,59,4443-4458).

[0003] Most of these reactions are catalyzed by palladium. This metal is expensive, its supply is limited, its price fluctuates significantly, and the production of palladium is very energy-intensive. about 4000 kg CO2 equivalent / kg palladium). Attention in this field has shifted to nickel due to its abundance in the Earth's crust, significantly lower cost (and greater stability), and lower environmental impact. about (6.5 kg CO2 equivalent / kg nickel). Nickel catalysis has not yet been widely adopted in industry, which depends on the availability of commercially viable, robust nickel catalysts, which are currently limited.

[0004] The current options can be divided into two categories: (i) nickel sources that combine in situ with ligands to form active catalysts, or (ii) nickel sources containing ligands already attached to nickel centers. The former is preferred for reaction screening purposes and situations requiring flexibility (e.g., in discovery chemistry applications where many different reactions are performed).

[0005] Commercially available nickel sources that can be combined in situ with ligands to form active catalysts include [Ni(COD)2] (COD = 1,5-cyclooctadiene), [NiCl2(DME)] (DME = 1,2-dimethoxyethane), NiCl2(OH2)4.2H2O, [Ni(stb X )3](stb X =4,4'-disubstituted X refers to the substituent at the 4-position, which is usually CF3 or t-Bu) and [Ni(COD)(DQ)] (DQ = duquinone). However, each of them has its drawbacks. [Ni(COD)2] is the market-leading nickel source. It is typically prepared at low (<< 0°C) temperatures using hazardous aluminum reducing agents and needs to be stored in a refrigerated cooler under an inert atmosphere to prevent decomposition in the solid state. For use in catalysis, [NiCl2(DME)] (DME = 1,2-dimethoxyethane) requires in-situ reduction to nickel(O), which can lead to unwanted byproducts. The coordination of the ligand with NiCl2(OH2)4·2H2O requires the displacement of water, which is then introduced into the reaction mixture, potentially leading to unwanted side reactions. [Ni(stb) X [3] The complex is a recent development and is prepared using a self-igniting aluminum reagent at << 0 °C (see L. Nattmann and J. Cornella, Organometallics ,2020,39,3295-3300; and L. Nattmann et al., Nature Catalysis (2019, 3, 6). The coordination of ligands with these complexes will... Ligand substitution occurs, leaving the ligand in solution and competing with the reaction substrate for binding to the nickel complex. The inventors have found that [Ni(COD)(DQ)] is best prepared from [Ni(COD)₂]. They have also found that [Ni(COD)(DQ)] resists ligand substitution, limiting its use in reactions without forced conditions.

[0006] Nickel sources containing ligands already attached to the nickel center are more suitable for applications in process-scale chemistry, where preferred ligands have been identified, and reducing the number of operations is advantageous for safety reasons. Several complex classes are known, including [NiX(Ar)(L]). n (Where X is a halogenated ligand, Ar is an aryl group, and L is a monodentate or bidentate phosphine, with n being 2 when L is monodentate and n being 1 when L is bidentate; see E.A. Standley, S.S. Smith, P. Müller, and T.F. Jamison.) Organometallics ,2014,33,2012-2018); [NiCl(allyl)(L)] (where L is bidentate phosphine or N-heterocyclic carbene), prepared from [Ni(COD)2] (see S. Ge and JF Hartwig, 2014,33,2012-2018); Angew.Chem.Int.Ed. ,2012,51,12837-12841 and Armartin, DJ Nelson, S. Meiries, AMZSlawin and SP Nolan, Eur.J.Org.Chem.,2014,2014,3127-3131); and [Ni(olefin)2(L)] (where L is an N-heterocyclic carbene), prepared from [Ni(COD)2] (see AJNett, S. Cañellas, Y. Higuchi, MTRrobo, JMKochkodan, MTRHaynes, JWKampf and J. Montgomery, ... ACS Catal. (2018, 8, 6606-6611). These complexes require reduction to nickel(0). The timescale of the reactions that reduce these complexes is not well understood, and these reactions produce unwanted byproducts that contaminate the desired product. As mentioned above, there are significant drawbacks to using [Ni(COD)2] as a nickel catalyst precursor.

[0007] Several catalytically active nickel(0) complexes containing unstable ketone ligands and stable diphosphine, monophosphine, or N-heterocyclic carbene ligands are known. Tsou, Huffman, and Kochi... Inorg.Chem. The synthesis of nickel(O) complexes comprising benzophenone and triethylphosphine by reaction of [Ni(PEt3)4] and benzophenone is described in 1979, 18, 2311-2317. The same disadvantages associated with the synthesis and storage of [Ni(COD)2] also apply to the synthesis and storage of [Ni(PEt3)4].

[0008] Newman-Stonebraker, etc. Science ,374,301-308(2021) and in J.Am.Chem.Soc., The synthesis of nickel(0) complexes containing 4-fluorobenzaldehyde and one or two monodentate phosphine ligands by reacting [Ni(COD)2] with phosphine ligands and 4-fluorobenzaldehyde is described in 2022, 144, 19635-19648. Desnoyer et al. in Chemistry A European Journal The same synthetic procedure was also used in ,25,20,5259-5268 (2019) to synthesize nickel (0) complexes containing benzaldehyde, cyclohexanone or cyclohexenone and di-tert-butylphosphine ethane (dtbpe).

[0009] Mindiola et al. Inorg.Chim.Acta The synthesis of a nickel (O) complex containing benzophenone and dtbpe is described in 2003, 345, 299-308, by reacting the nickel (I) dimer [Ni(dtbpe)Cl]₂ with sodium and benzophenone. The dimer is synthesized from [Ni(dtbpe)Cl₂] by reduction with potassium graphite (KC8).

[0010] Tendera et al. European Journal of Inorganic Chemistry2020, 33, 3194-3207 describes compounds containing 1,3-bis(2,4,6-trimethylphenyl)-1,3-dihydro-2H-imidazol-2-ylene (IMes) or 1,3-diisopropyl-imidazol-2-ylene (Im i Synthesis of nickel(O) complexes of olefins, ketones, or aldehydes. This is achieved by preparing [Ni(IMes)2] or [Ni(Im] by using [Ni(COD)2] and two equivalents of N-heterocyclic carbene. i These complexes are prepared by reacting [Ni(COD)2] complexes with olefins, ketones, or aldehydes. As mentioned above, using [Ni(COD)2] as a nickel catalyst precursor has significant drawbacks.

[0011] N. Ishida et al. Organometallics The method described in 2019, 38, 1413-1416 is as follows: A mixture of tonone, isopropanol, acetic acid, and COD, along with the reduction of nickel(II) from [Ni(acac)2] by sunlight or LED light, yields a "cleaner" preparation of [Ni(acac)2] (where acac is acetylacetone). Under irradiation, the... Tonone is reductively dimerized to form a highly sterically hindered vicinal diol, which decomposes to form two carbonyl radicals. These carbonyl radicals reduce nickel(II) to nickel(O), which is then bound to COD. The carbonyl radicals are oxidized to reform [the product / organization]. Tonone. Therefore, the carbonyl radical is used as a component therein. It is part of a catalytic cycle in which tonone reforms and does not bind with nickel.

[0012] There is a need in the art for alternative or improved methods to prepare a wide range of catalytically active nickel (0) complexes from nickel (II) starting materials prepared using reagents that are less hazardous than, for example, aluminum reducing agents used to prepare [Ni(COD)2], and / or easier to store than, for example, [Ni(COD)2]. This invention addresses this need. Summary of the Invention

[0013] Overview of the Invention

[0014] This invention is based on the inventors' discovery that ketyl anions or ketyl dianions derived from ketones or diols can be used to reduce nickel(II) to nickel(O), wherein the resulting nickel(O) is bonded to the ketone or ketone derived from the diol. This method has proven highly resilient to different ligand types and has been used by the inventors to synthesize a wide range of nickel(O) complexes stabilized by a variety of different ketones and other stable ligands. The nickel(II) starting materials used in this method are commercially available and prepared using reagents that are less hazardous than, for example, aluminum reducing agents used to prepare [Ni(COD)2]. The nickel(II) starting materials are also very easy to handle and store (they are chemically stable under standard environmental conditions).

[0015] Therefore, from a first aspect, the present invention provides a method for using [Ni(L)] n [X)2] complex formation [Ni(L)] n A method for producing a [Ni(L)] complex, the method comprising: […]. n [X]2] complexes come into contact with the following substances:

[0016] (i) (a) Reducing metals or bases; and

[0017] (b) A diol containing a tertiary or ortho-hydroxyl structural moiety, wherein at least one of the carbon atoms bonded to the tertiary or ortho-hydroxyl structural moiety is adjacent to the π system.

[0018] or

[0019] (ii) (a) reducing metals; and

[0020] (b) Ketones containing a carbonyl moiety conjugated with the π system;

[0021] in:

[0022] Q is the ketone complexed with nickel or a ketone derived from the diol;

[0023] L is a monodentate, bidentate, or tridentate L-type ligand, wherein when L is monodentate, n is 2, and when L is bidentate or tridentate, n is 1; and

[0024] X is a monovalent or divalent monoanion ligand.

[0025] The inventors have discovered that the method of the first aspect allows for the preparation of species that are difficult to obtain by other methods and, to the best of the inventors' knowledge, cannot be produced by any other means.

[0026] Therefore, from a second perspective, the present invention provides [Ni(L)] n [Q] complex, wherein:

[0027] Q is a ketone complexed with nickel, wherein the ketone contains a carbonyl structural moiety conjugated with the π system;

[0028] L is a monodentate, bidentate, or tridentate L-type ligand selected from tri-C 1-6 Alkylphosphine (e.g., tri-n-butylphosphine), tri-cyclic C 5-6 Hydrophosphine, C 1-4 alkyl-di-cycloC 5-6 Hydroxyphosphine, N,N,N',N'-tetrachlorophosphine 1-4 Alkyl C 2-4 alkylene diamine, N,N,N',N'',N''-pentacarbonyl 1-4 Alkyl C 2-4 alkyltriamines, C containing N,N 12-14 Heterocyclic tricyclic ligands, bis(di-cyclic C) 5-6 (Hydrocarbon phosphine)C 2-4 Alkylene, bis(di-cycloC) 5-6 (Hydrocarbon-phosphine-) Tons, double (di-C) 1-4 Alkylphosphine Tons, double (two-ring C) 5-6 (Hydrophosphino)ferrocene, bis(di-C) 1-4 Alkylphosphinyl)ferrocene, bis(di-cycloC) 5-6 (Hydrophosphinophenyl) ether and bis(di-C) 1-4 Alkylphosphine phenyl ethers, each of which is optionally composed of one or more compounds selected from C 1-4 Alkyl, Halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Substitution of alkoxy and morpholino groups,

[0029] L is a C that includes N, N 10 Heterocyclic bicyclic ligands, optionally using one or more selected from C 1-4 Alkyl, Halogenated, C 1-4 Halogenated alkyl, hydroxyl and C 1-4 Substitution of alkoxy groups,

[0030] L is two C 1-4 Alkyl-phosphino-biphenyl or di-cyclic C 5-6 Hydroxylphosphine-biphenyl, wherein each biphenyl is optionally made of one or more compounds selected from C 1-4 Alkyl, di(C) 1-4 alkyl)amino and C 1-4 Substitution of alkoxy groups, or

[0031] L contains bicyclic C 5-6 The alkylphosphine-bonded structural portion is optionally linked to the N-heterocyclic carbene-bonded structural portion via an alkyl linker;

[0032] Where n is 2 when L is monodentate, and n is 1 when L is bidentate or tridentate; and X is a halogenated group.

[0033] Nickel (0) complexes of the type obtainable by the method of the first aspect have been reported in the art as active catalysts, for example in carbon coupling reactions such as Suzuki-Miyaura and CN coupling reactions (see Newman-Stonebraker, 2022 and 2021, above). Similarly, the inventors have found that the complexes of the second aspect are active in catalysis involving cross-coupling.

[0034] Therefore, from a third aspect, the present invention provides the use of complexes as defined in the second aspect as catalysts such as cross-coupled catalysts.

[0035] Detailed Description of the Invention

[0036] As described above, the inventors have discovered that carbonyl free anions or carbonyl free dianions derived from ketones or diols can be used to reduce nickel(II) to nickel(O), wherein the resulting nickel(O) is bonded to the ketone or ketone derived from the diol. The ketone bonded to nickel(O) is unstable and therefore readily displaced by a chemical substrate, for example, to be used in nickel-catalyzed methods. Thus, the nickel(O) complexes obtained by the method of the present invention are catalytically active and can be used, for example, as carbon coupling catalysts. Advantageously, the nickel(II) starting materials used in this method are commercially available and prepared using reagents that are less hazardous than, for example, aluminum reducing agents used to prepare [Ni(COD)2]. The nickel(II) starting materials are also very easy to handle and store (they are chemically stable under standard environmental conditions).

[0037] In the following discussion, numerous terms will be used, and unless the specific context otherwise requires, these terms shall have the meanings provided herein. The nomenclature used herein to define compounds (especially those according to the invention) is generally based on the rules of the IUPAC organization for chemical compounds, specifically the "IUPAC Compendium of Chemical Terminology (Gold Book)". For the avoidance of doubt, if the IUPAC rules conflict with the definitions provided herein, the definitions herein shall prevail. Furthermore, if a compound structure conflicts with a name provided for that structure, the structure shall prevail.

[0038] The term “comprising” or variations thereof is understood to mean including the elements, integers or steps stated therein, or groups of elements, integers or steps, but does not exclude any other elements, integers or steps, or groups of elements, integers or steps.

[0039] The term “consisting” or variations thereof is understood to mean including the elements, integers or steps of the statement, or groups of elements, integers or steps, and excluding any other elements, integers or steps, or groups of elements, integers or steps.

[0040] The term "about" in this document, when modifying a number or value, refers to a value falling within ±5% of the specified value. For example, when L is defined as having a natural bite angle of about 75° to about 140°, it includes bite angles from 71.3° to 147°.

[0041] As those skilled in the art will know, the term "pi system" refers to a system in a molecule with connected p orbitals containing delocalized electrons, which generally lowers the total energy of the molecule and increases its stability. It is typically represented as having alternating single and multiple bonds, although lone pairs of electrons, free radicals, or carbocations may be part of the system, which can be cyclic, acyclic, linear, or mixed.

[0042] The term "conjugated" refers to the overlap of one p orbital with another across an adjacent σ bond. This allows π electrons to delocalize across all adjacent and aligned p orbitals. These π electrons do not belong to a single bond or a single atom, but rather to a group of atoms.

[0043] The term "cyclic hydrocarbon group" refers to a monovalent group derived from a cyclic hydrocarbon by removing a hydrogen atom from the hydrocarbon. A hydrocarbon is any molecule containing only the elements carbon and hydrogen. Hydrocarbons can be aliphatic, aromatic, unsaturated, or saturated. Cyclic hydrocarbons can include monocyclic or spirocyclic, fused, or bridged ring systems with two or more rings.

[0044] The term "spirocyclic system" refers to a cyclic system containing two or more rings, where at least two rings share a single atom.

[0045] The term "fused ring system" refers to a ring system containing two or more rings, wherein at least two rings share two adjacent atoms.

[0046] The term "bridged ring system" refers to a ring system containing two or more rings, wherein at least two rings share three or more atoms. A bridged ring system comprises two bridgeheads (corresponding to the exterior of the shared atoms) and a bridge separating the two bridgehead atoms (corresponding to the remaining shared atoms).

[0047] As used herein, the term "heterocyclic group" refers to a monovalent group derived from a heterocycle. A heterocycle is a cyclic compound (a compound containing one or more linked atoms) having ring atoms of at least two different elements (e.g., carbon and nitrogen). A heterocyclic group may contain at least one heteroatom, selected from O, N, and S. The ring of the heterocycle may be a monocyclic or polycyclic ring, each ring containing 4 to 10 atoms, and in some cases 5 to 8 atoms. The heterocyclic group may be aliphatic or aromatic. One or more of the rings may be aliphatic or aromatic.

[0048] As used herein, the term "aryl" refers to a monocyclic or polycyclic aromatic hydrocarbon system having 6 to 14 carbon atoms, and in some cases 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 anthraceneyl. As used herein, "substituted aryl" refers to an aryl group as defined herein that contains one or more substituents on an aromatic ring. When an aryl group is substituted, any hydrogen atom(s) may be substituted by one or more substituents, provided that the valence state is satisfied.

[0049] The term "heteroaromatic ring" refers to a compound derived from an aromatic ring or aromatic hydrocarbon by replacing one or more methine (-C=) and / or 1,2-vinylidene (-CH=CH-) groups with trivalent or divalent heteroatoms to maintain a continuous π-electron system characteristic of aromatic systems and the number of out-of-plane π electrons conforming to Hückel's rule. Hückel's rule is commonly used in the art to evaluate aromatic properties; a monocyclic planar (or nearly planar) system containing (4n+2) trigonal (or sometimes bigonal) hybrid atoms (where n is a non-negative integer) will exhibit aromatic properties. Heteroaromatic rings can be 5- or 6-membered. Examples of 5- or 6-membered aromatic rings include pyridine, thiophene, pyrrole, furan, imidazole, etc. azole, thiazole, pyrazole, isoazole Zolpidem and isothiazine.

[0050] A heteroaryl group is a monovalent group derived from a heteroaryl ring by removing a hydrogen atom from any carbon atom.

[0051] The term "alkyl" is well known in the art and is defined as a monovalent group derived from an alkane by removing a hydrogen atom from any carbon atom, wherein the term "alkane" is intended to define a group having the general formula C n H 2n+2 Acyclic branched or unbranched hydrocarbons, where n is an integer ≥1. The alkyl group can be C16-264. 1-6 Alkyl group. In some cases, the alkyl group is C. 1-4 Alkyl group. C 1-4Alkyl refers to any one selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, and tert-butyl.

[0052] The term "alkene" is defined as a monovalent group derived from an alkene by removing a hydrogen atom from any carbon atom, wherein the term "alkene" is intended to define an alkene having the general formula C n H 2n Acyclic branched or unbranched hydrocarbons, where n is an integer ≥2. Examples of alkenyl groups include vinyl, n-propenyl, isopropenyl, n-butenyl, sec-butenyl, isobutenyl, and tert-butenyl. When an alkenyl group is substituted, any hydrogen atom(s) may be substituted by one or more substituents, provided that the valence state is satisfied. The term "dienyl" defines a monovalent group derived from a diene by removing a hydrogen atom from any carbon atom, wherein the term "diene" is intended to define a group having the general formula C n H 2n-2 Acyclic branched or unbranched hydrocarbons, where n is an integer ≥ 4. The term "trienyl" is defined as a monovalent group derived from a triene by removing a hydrogen atom from any carbon atom, wherein the term "triene" is intended to define a group having the general formula C n H 2n-4 Acyclic branched or unbranched hydrocarbons, where n is an integer ≥ 6.

[0053] The term "alkynyl" is defined as a monovalent group derived from an alkyne by removing a hydrogen atom from any carbon atom, wherein the term "alkynyl" is intended to define a hydrocarbon having the general formula C n H 2n-2 Acyclic branched or unbranched hydrocarbons, where n is an integer ≥2. Examples of alkynyl groups include ethynyl, n-propynyl, isopropynyl, n-butynyl, sec-butynyl, isobutynyl, and tert-butynyl. When an alkynyl group is substituted, any hydrogen atom (one or more) can be substituted by one or more substituents, provided that the valence state is satisfied. The term "diynyl" defines a monovalent group derived from a diynylene by removing a hydrogen atom from any carbon atom, wherein the term "diynylene" is intended to define a hydrocarbon having the general formula C n H 2n-6 Acyclic branched or unbranched hydrocarbons, where n is an integer ≥ 4. The term "triyneyl" defines a monovalent group derived from a triyne by removing a hydrogen atom from any carbon atom, wherein the term "triyne" is intended to define a hydrocarbon having the general formula C n H 2n-10 Acyclic branched or unbranched hydrocarbons, where n is an integer ≥ 6.

[0054] A halo group is a halogenated group. Typically, a halo group is selected from fluorinated, brominated, chloroinated, and iodinated groups. In some cases, a halo group refers to a fluorinated group.

[0055] The term "haloalkyl" is also well-known and is defined as a monovalent group derived from an alkyl group by replacing one or more hydrogen atoms on one or more carbon atoms with a halogroup. A haloalkyl group may contain one or more different types of halogroups. For example, one or more are independently selected from fluorinated, chlorinated, brominated, and iodinated groups. In some cases, the haloalkyl is a fluoroalkyl.

[0056] The term "alkoxy" defines a monovalent group derived from an alcohol by removing a hydrogen atom from the OH group, while the term "alcohol" is intended to define a group derived from an alkane by replacing a hydrogen atom with a hydroxyl group. Typically, the alkoxy group is C60. 1-6 alkoxy group or C 1-4 Alkoxy group.

[0057] The term "phosphine" refers to PH3 and compounds derived therefrom by replacing one, two, or three hydrogen atoms with a hydrocarbon group (i.e., a group consisting only of carbon and hydrogen atoms). When a compound is described as containing a phosphine-bonded structural moiety, the compound contains phosphine (optionally, in addition to other chemical groups).

[0058] The term "carbene" refers to a compound containing a carbon atom that is covalently bonded to two monovalent groups or one divalent group of any kind and has two unbonded electrons, which can be spin-paired (singlet state) or spin-unpaired (tritt state). A carbene can be an N-heterocyclic carbene, which refers to a compound containing a carbene moiety in which the carbon atom of the carbene moiety is part of an N-heterocycle and directly bonded to at least one nitrogen atom.

[0059] The term "amine" refers to a compound derived from ammonia by replacing one, two, or three hydrogen atoms with a hydrocarbon group. Primary amines have their nitrogen atom bonded to two hydrogen atoms and one carbon atom, secondary amines have their nitrogen atom bonded to one hydrogen atom and two carbon atoms, and tertiary amines have their nitrogen atom bonded to three carbon atoms. When a compound is described as containing an amine-bonded structural moiety, the compound contains an amine (optionally, in addition to other chemical groups).

[0060] The term "imine" refers to a compound having the structure RN=CR2, where each R is independently selected from H and a hydrocarbon group. When a compound is described as containing an imine-bonded structural moiety, the compound contains an imine (optionally in addition to other chemical groups).

[0061] The term pseudo-halide is well known in the art and refers to a monovalent anion that is a weak Lewis base and not from Group 17 of the periodic table. Examples of pseudo-halides include trifluoromethanesulfonate, cyanide, cyanophosphate, isocyanide, hydroxide, hydrogen sulfide, hydrogen selenide, hydrogen telluride, cyanate, isocyanate, fulminate, thiocyanate, isothiocyanate, selenocyanate, tellurate, azide, and nitroxide. Particularly useful pseudo-halides include trifluoromethanesulfonate, cyanide, cyanynylene, isocyanide, hydroxide, hydrogen sulfide, cyanate, isocyanate, fulminate, thiocyanate, isothiocyanate, azide, and nitroxide.

[0062] The number of atoms that a ligand bonds to a metal ion is called the ligand's denticity. Monodentate ligands are bonded by a single atom (e.g., by a single pair of electrons provided by a single atom). Bamperdentate ligands are debonded by two different atoms, and tripentate ligands are bonded by three different atoms.

[0063] The term "natural bite angle" is defined herein as the preferred angle at which each of the bonded structural portions of a bidentate ligand or two of the three bonded structural portions of a tripentate ligand chelates with a metal ion. It is obtained using molecular mechanics calculations and is determined solely by the ligand skeleton, not by the metal valence bond angle.

[0064] The "Tolman's cone angle" is used to measure the size of monodentate ligands and is defined in this paper as the apex angle of a cone with an extended edge, centered at the metal center and extending along the outermost atoms of the ligand. The Tolman's cone angle mentioned in this paper is based on the measurements of Jover and Cirera. Dalton Trans. The Tolman cone angles obtained by the methods reported in 2019, 48, 15036 for the coordination environment of [Ni(CO)3(L)] were obtained.

[0065] A base can be used in the method of the present invention. This base can be defined by the pKa of its conjugate acid. For the avoidance of doubt, these pKa values ​​relate to the reaction BH carried out in water at 25°C. + H + The determination of B+, where BH + Indicate the conjugate acid of the base under consideration, such as in CRC Handbook of Chemistry and Physics,91st edition, 2010, *Dissociation Constants of Organic Acids and Bases*, and *Dissociation Constants of Inorganic Acids and Bases*, as described in the cited literature. Therefore, when the base used is, for example, potassium tert-butoxide (KO... t When Bu), the conjugate acid is tert-butanol (HO). t Bu); when the base used is, for example, sodium phenolate (KOPh), the conjugate acid is phenol (HOPh). To further avoid doubt, the pKa of water at 25°C is defined herein as 14.0, as is generally accepted in the art. Thus, for example, the pKa of the conjugate acid of sodium hydroxide and potassium hydroxide (i.e., water) is 14.0.

[0066] To avoid any doubt, the wavy lines in the chemical structure bisect the bonds that connect the structural portion shown to the rest of the compound.

[0067] The term "solvate" is used herein to refer to a complex containing a solute (e.g., a compound or a salt of that compound) and a solvent. If the solvent is water, the sovate may be referred to as a hydrate, such as a monohydrate, dihydrate, trihydrate, etc., depending on the number of water molecules present in each substrate molecule.

[0068] The term "isotope" is used in this document to define variants of a particular chemical element in which the atomic nuclei necessarily have the same atomic number, but have different mass numbers due to different numbers of neutrons.

[0069] As described above, the present invention provides a method for using [Ni(L)] n [X)2] complex formation [Ni(L)] n A method for producing a [Ni(L)] complex, the method comprising: […]. n [X]2] complexes come into contact with the following substances:

[0070] (i) (a) Reducing metals or bases; and

[0071] (c) A diol containing a tertiary or ortho-hydroxyl structural moiety, wherein at least one of the carbon atoms bonded to the tertiary or ortho-hydroxyl structural moiety is adjacent to the π system.

[0072] or

[0073] (ii) (a) reducing metals; and

[0074] (c) Ketones containing a carbonyl structural moiety conjugated with the π system;

[0075] in:

[0076] Q is the ketone complexed with nickel or a ketone derived from the diol;

[0077] L is a monodentate, bidentate, or tridentate L-type ligand, wherein when L is monodentate, n is 2, and when L is bidentate or tridentate, n is 1; and

[0078] X is a monovalent or divalent monoanion ligand.

[0079] It should be understood that contact can be achieved in various ways. Typically, when using a ketone, the reducing metal and the ketone are brought into contact, and the [Ni(L)] is... n [X)2] is added to the resulting mixture. Typically, the ketone is first added to a solvent and stirred or agitated to form a solution or suspension, into which a reducing metal is added. Typically, the reducing metal is added slowly, for example over 1 to 30 minutes or 5 to 20 minutes. Then the [Ni(L)] is added... n [X]2] is added to the resulting solution or suspension. The solution or suspension containing the ketone and the reducing metal can be blue or purple. A blue solution or suspension generally indicates the presence of a carbonyl free anion, and a purple solution or suspension generally indicates the presence of a carbonyl free dianion.

[0080] When using diols, the [Ni(L)] is typically... n [Ni(L)2] is contacted with a diol, and the alkali or reducing metal is added to the resulting mixture. Typically, the diol and [Ni(L)2] are first reacted... n [X)2] is added to a solvent and stirred or agitated to form a solution or suspension, to which the alkali or reducing metal is added. The alkali can and typically is added to the solution or suspension in solution form. The diol, [Ni(L)] n [(X)2] and the solvent can be combined in any order. For example, the diol can be added to the solvent first to form a solution or suspension, and [Ni(L)] can be added to the solution or suspension. n (X)2]. Alternatively, [Ni(L) can be added first. n [X)2] is added to the solvent to form a solution or suspension, and a diol is added to the solution or suspension. Alternatively, the diol and [Ni(L)] can be added... n [X)2] can be added to the solvent simultaneously, or the diol and [Ni(L)] can be added to the solvent before being added to the solvent. n [X)2] can be mixed together. Alternatively, the diol and [Ni(L)] can be mixed together. n (X)2] are mixed together and the solvent is added to the resulting mixture, or the solvent can be added to the diol and [Ni(L)].n One of (X)2] is added to the resulting solution or suspension and the other is added to the solution or suspension.

[0081] Carbonyl free anions are typically the major carbonyl free species formed when about 1 or less equivalent of reducing metal is used relative to ketones or about 2 or less equivalent of reducing metal is used relative to glycols. Carbonyl dianions are typically the major carbonyl free species formed when about 2 or more equivalents of reducing metal is used relative to ketones or about 4 or more equivalents of reducing metal is used relative to glycols. Carbonyl free anions are typically the major reduced carbonyl free species formed when a base is used, particularly when about 2 or less equivalents of base is used relative to glycols.

[0082] To avoid any doubt, the [Ni(L)] n The contact between the [X)2] complex and (i) causes the reducing metal or alkali to react with the diol to produce a reducing agent capable of reducing nickel (II) to nickel (O), and the [Ni(L)] complex reacts with the diol to produce a reducing agent capable of reducing nickel (II) to nickel (O). n The contact between the (X)2] complex and (ii) causes the reducing metal to react with the ketone to produce a reducing agent capable of reducing nickel (II) to nickel (O).

[0083] As described above, Q is the ketone complexed with nickel, or a ketone derived from the diol. The diol from which the ketone can be derived comprises a tertiary-ortho-hydroxyl moiety, wherein at least one of the carbon atoms bonded to the tertiary-ortho-hydroxyl moiety is adjacent to the π system. For the avoidance of doubt, the statement "at least one of the carbon atoms bonded to the tertiary-ortho-hydroxyl moiety is adjacent to the π system" means that the relevant carbon atom is separated from the π system by one bond, i.e., the carbon atom is bonded to an atom that is part of the π system. Not limited by theory, the reduction of the diol is understood to result in the cleavage of the bond between the two carbon atoms bonded to the tertiary-ortho-hydroxyl moiety to form a carbonyl radical anion or dianion. Since at least one of the carbon atoms bonded to the tertiary-ortho-hydroxyl moiety is adjacent to the π system, the radical and / or negative charge of the carbonyl radical anion or dianion containing that carbon atom can be delocalized across the π system. The carbonyl radical anion or dianion can reduce [Ni(L)]. n [X]2] nickel complex, and in the process forming a ketone (Q), which is capable of bonding with reduced nickel. Q, i.e., the ketone or a ketone derived from the diol, contains a carbonyl structural moiety conjugated with the π system.

[0084] Q can have the following formula (I):

[0085]

[0086] in:

[0087] R 1 and R2 Each is independently selected from cyclic C5-C 18 Hydrocarbon groups (such as C6-C) 18 hydrocarbon group), C1-C 17 Heterocyclic group, C 1-6 Alkyl, C 2-6 alkenyl, C 4-6 Dienyl, C6 trienyl, C 2-6 alkynyl group, C 4-6 Diynyl and C6 triynyl, each of which is optionally composed of one or more compounds selected from cyclic C3-C6 groups. 18 Hydrocarbon groups (such as C6-C) 18 Hydrocarbon group), cyclic C1-C 17 heterohydrocarbon group, C 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Substitution of alkyl)amino groups, wherein the optional cyclic C3-C 18 Hydrocarbon groups (such as C6-C) 18 (hydrocarbon group) and cyclic C1-C 17 The heteroalkyl substituent is optionally C 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Alkyl)amino substitution; and wherein R 1 and R 2 At least one of them contains a π system conjugated with the carbonyl structural portion. For example, when R 1 When there is no structural part of the π system that can be conjugated with the carbonyl structural part (e.g., when R... 1 It is C 1-6 (when alkyl), R 2 It is a structural part having a π system that can be conjugated with the carbonyl structural part (e.g., R). 2 It can be aryl or heteroaryl, or R 2 It can be phenyl or ethynyl). Typically, R... 1 and R 2 At least one of them is aryl or heteroaryl (e.g., aryl).

[0088] In a particular implementation scheme, when R 1 and / or R 2 When optionally substituted with a halogenated group, the halogenated group is not located at the α-position of the ketone structural moiety in formula (I). In a particular embodiment, R 1 and R 2 It is not substituted with a halogenated group. For example, R 1and R 2 Each can be independently selected from cyclic C5-C 18 Hydrocarbon groups (such as C6-C) 18 hydrocarbon group), C1-C 17 Heterocyclic group, C 1-6 Alkyl, C 2-6 alkenyl, C 4-6 Dienyl, C6 trienyl, C 2-6 alkynyl group, C 4-6 Diynyl and C6 triynyl, each of which is optionally composed of one or more compounds selected from cyclic C3-C6 groups. 18 Hydrocarbon groups (such as C6-C) 18 Hydrocarbon group), cyclic C1-C 17 heterohydrocarbon group, C 1-4 Alkyl, C 2-6 alkenyl, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Substitution of alkyl)amino groups, wherein the optional cyclic C3-C 18 Hydrocarbon groups (such as C6-C) 18 (hydrocarbon group) and cyclic C1-C 17 The heteroalkyl substituent is optionally C 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Alkyl)amino substitution; and wherein R 1 and R 2 At least one of them contains a π system conjugated with the carbonyl structural portion.

[0089] In a specific implementation scheme, R 1 and R 2 It is not or does not contain unsaturated aliphatic groups. For example, R 1 and R 2 Each can be independently selected from cyclic C5-C 18 Hydrocarbon groups (such as C6-C) 18 hydrocarbon group), C1-C 17 Heterocyclic groups and C 1-6 Alkyl groups, each of which is optionally composed of one or more cyclic C3-C groups. 18 Hydrocarbon groups (such as C6-C) 18 Hydrocarbon group), cyclic C1-C 17 heterohydrocarbon group, C 1-4 Alkyl, Halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Substitution of alkyl)amino groups, wherein the optional cyclic C3-C18 Hydrocarbon groups (such as C6-C) 18 (hydrocarbon group) and cyclic C1-C 17 The heteroalkyl substituent is optionally C 1-4 Alkyl, Halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Alkyl)amino substitution; and wherein R 1 and R 2 At least one of them contains a π system conjugated with the carbonyl structural portion.

[0090] The R 1 and R 2 The group can be attached to the carbonyl structure moiety shown in Figure (I) at any position, provided that it has the correct valence state and is chemically suitable. For example, when R 1 and / or R 2 C1-C is an optional substitute 17 When it is a heterocyclic group, it can be attached to the carbonyl structural moiety through a carbon atom or a heteroatom.

[0091] In a particular embodiment, the annular C5-C of formula (I) 18 The hydrocarbon group is cyclic C6-C 14 Hydrocarbon group. In some embodiments, the cyclic hydrocarbon group is aromatic, for example, selected from any one of phenyl, naphthyl, and fluorenyl. Alternatively, the cyclic C5-C group of formula (I) 18 The hydrocarbon group can be aliphatic, for example, C5-C. 18 Cycloalkyl, for example, is any one selected from cyclopentyl, cyclohexyl and cycloheptyl.

[0092] In a particular implementation, the C1-C of formula (I) 17 The heterocyclic group comprises 1-3 heteroatoms, which are independently selected from N, S, and O, for example, N and S. In a particular embodiment, the C1-C 17 The heterocyclic group contains one or two heteroatoms. Typically, the C1-C... 17 The heterocyclic group has one or more rings that are 5- or 6-membered. Typically, the C1-C 17 The heterocyclic group is a C1-C9 heterocyclic group, which can be monocyclic or bicyclic. In a particular embodiment, the C1-C9 heterocyclic group... 17 The heterocyclic group is selected from pyridinyl, piperidinyl, pyrrolidinyl, thiazolyl, imidazolyl, indolyl, and tetrazolyl, such as pyridinyl.

[0093] In some implementation schemes, R 1 and R 2 Each is independently selected from phenyl, naphthyl, pyridyl, anthraceneyl, phenanthrene, C5-6 cycloalkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 4-6 Dienyl, C6 trienyl, C 2-6 alkynyl group, C 4-6 Diynyl and C6 triynyl, each of which is optionally radicalized by one or more groups selected from phenyl, C6 ... 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 The alkyl)amino group is substituted with a substituent, wherein the optional phenyl substituent is optionally C 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Alkyl)amino substitution; and wherein R 1 and R 2 At least one of them contains a π system conjugated with the carbonyl structural portion.

[0094] In some implementation schemes, R 1 and R 2 Each is independently selected from phenyl, C 1-6 Alkyl, C 2-6 alkenyl, C 4-6 Dienyl, C6 trienyl, C 2-6 alkynyl group, C 4-6 Diynyl and C6 triynyl, each of which is optionally radicalized by one or more groups selected from phenyl, C6 ... 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 The alkyl)amino group is substituted with a substituent, wherein the optional phenyl substituent is optionally C 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Alkyl)amino substitution; and wherein R 1 and R 2 At least one of them contains a π system conjugated with the carbonyl structural portion.

[0095] Typically, R 1 and R 2 Each is independently selected from phenyl, naphthyl, pyridyl, C 5-6 cycloalkyl, C 1-6Alkyl (e.g., C10) 1-4 Alkyl), C 2-6 alkenyl (e.g., C) 2-4 alkenyl) and C 2-6 alkynyl groups (e.g., C) 2-4 (alkynyl groups), each of which is optionally divided by one or more groups selected from phenyl, C 1-4 Alkyl, C 2-6 alkenyl (e.g., C) 2-4 alkenyl), halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 The alkyl)amino group is substituted with a substituent, wherein the optional phenyl substituent is optionally C 1-4 Alkyl, C 2-6 alkenyl (e.g., C) 2-4 alkenyl), halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Alkyl)amino substitution; and wherein R 1 and R 2 At least one of them contains a π system conjugated with the carbonyl structural portion.

[0096] Typically, R 1 and R 2 Each is independently selected from phenyl, C 1-6 Alkyl (e.g., C10) 1-4 Alkyl), C 2-6 alkenyl (e.g., C) 2-4 alkenyl) and C 2-6 alkynyl groups (e.g., C) 2-4 (alkynyl groups), each of which is optionally divided by one or more groups selected from phenyl, C 1-4 Alkyl, C 2-6 alkenyl (e.g., C) 2-4 alkenyl), halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 The alkyl)amino group is substituted with a substituent, wherein the optional phenyl substituent is optionally C 1-4 Alkyl, C 2-6 alkenyl (e.g., C) 2-4 alkenyl), halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Alkyl)amino substitution; and wherein R 1 and R 2 At least one of them contains a π system conjugated with the carbonyl structural portion.

[0097] In some implementation schemes, R1 and R 2 Each is independently selected from phenyl, naphthyl, pyridyl, C 5-6 cycloalkyl and C 1-6 Alkyl (e.g., C10) 1-4 Alkyl groups, each of which is optionally composed of one or more compounds selected from phenyl, C 1-4 Alkyl, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 The alkyl)amino group is substituted with a substituent, wherein the optional phenyl substituent is optionally C 1-4 Alkyl, Halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Alkyl)amino substitution; and wherein R 1 and R 2 At least one of them contains a π system conjugated with the carbonyl structural portion.

[0098] In a specific implementation scheme, R 1 and R 2 Independently selected from phenyl, naphthyl, pyridyl, cyclopentyl, cyclohexyl and C 1-4 Alkyl groups, each of which is optionally substituted as described above. In a particular embodiment, R 1 and R 2 At least one of them is an optionally substituted phenyl, pyridyl, or naphthyl group, such as an optionally substituted phenyl or pyridyl group. In a particular embodiment, R 1 and R 2 Independently selected from optionally substituted phenyl and optionally substituted vinylphenyl.

[0099] In some implementation schemes, R 1 and R 2 Optionally, it is selected from one or more of the following: phenyl, C 1-4 Alkyl, C 2-6 alkenyl (e.g., C) 2-4 alkenyl), halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-6 Substituents of alkyl)amino groups. In more specific embodiments, R 1 and R 2 Optionally, it is selected from one or more of the following: phenyl, C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Alkoxy and di(C 1-6 Substitution of alkyl)amino groups.

[0100] In a specific implementation scheme, R1 and R 2 Optionally selected by one or more of C 1-4 Alkyl, C 2-6 alkenyl (e.g., C) 2-4 alkenyl), halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-6 Substituents of alkyl)amino groups. In more specific embodiments, R 1 and R 2 Optionally selected by one or more of C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Alkoxy and di(C 1-6 Substitution of alkyl)amino groups.

[0101] In more specific implementations, R 1 and R 2 Independently selected from optionally substituted phenyl, optionally substituted pyridyl, C 1-4 Alkyl, optionally substituted cyclopentyl, and optionally substituted cyclohexyl. In some embodiments, R 1 and R 2 At least one of them is an optionally substituted phenyl group (e.g., an unsubstituted phenyl group), and the other is independently selected from an optionally substituted phenyl group, an optionally substituted pyridyl group, or a C-type phenyl group. 1-4 Alkyl, optionally substituted cyclopentyl, and optionally substituted cyclohexyl. For example, Q can be benzophenone, 4-benzoylbiphenyl, phenyl(4-tolyl) methyl ketone, 2-benzoylpyridine, 1'-acetylnaphthalene, isobutyrophenyl, cyclopentylphenyl ketone, or cyclohexylphenyl ketone.

[0102] In a more specific implementation scheme, R 1 and R 2 Each is an optionally substituted phenyl group, for example, each is an unsubstituted phenyl group.

[0103] To avoid doubt, when Q has formula (I), the diol derived from Q has formula (I'):

[0104]

[0105] Where R 1 and R 2 As defined above for equation (I).

[0106] Alternatively, Q may have equation (II):

[0107]

[0108] Where A is a cyclic C6-C 18Hydrocarbon group or C3-C 17 Heterocyclic groups, each optionally surrounded by one or more cyclic C3-C groups. 18 Hydrocarbon groups (e.g., C6-C) 18 Hydrocarbon group), cyclic C1-C 17 heterohydrocarbon group, C 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Substitution of alkyl)amino groups, wherein the optional cyclic C3-C 18 Hydrocarbon groups (e.g., C6-C) 18 (hydrocarbon group) and cyclic C1-C 17 The heteroalkyl substituent is optionally C 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Alkyl)amino substitution; and wherein A comprises a π system conjugated with the carbonyl structural moiety of formula (II). For the avoidance of doubt, and as shown in formula (II), ring A comprises a ketone structural moiety. For example, when ring A is defined as a cyclic C6-C 18 When the hydrocarbon group is fluorene, Q is a cyclic C6-C group containing the ketone moiety. 18 Hydrocarbon groups, such as fluorenone.

[0109] In a particular embodiment, when A is optionally substituted with a halogenated group, the halogenated group is not located at the α-position of the ketone moiety of formula (II). In a particular embodiment, A is not substituted with a halogenated group. For example, A may be a cyclic C6-C 18 Hydrocarbon group or C3-C 17 Heterocyclic groups, each optionally surrounded by one or more cyclic C3-C groups. 18 Hydrocarbon group, cyclic C1-C 17 heterohydrocarbon group, C 1-4 Alkyl, C 2-6 alkenyl, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Substitution of alkyl)amino groups, wherein the optional cyclic C6-C 18 Hydrocarbon groups and cyclic C1-C 17 The heteroalkyl substituent is optionally C 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4Alkyl)amino substitution; and wherein A comprises a π system conjugated with the carbonyl structural portion of formula (II).

[0110] In a particular embodiment, A is not or does not contain an unsaturated aliphatic group. For example, A may be a cyclic C6-C 18 Hydrocarbon group or C3-C 17 Heterocyclic groups, each optionally surrounded by one or more cyclic C3-C groups. 18 Hydrocarbon groups (e.g., C6-C) 18 Hydrocarbon group), cyclic C1-C 17 heterohydrocarbon group, C 1-4 Alkyl, Halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Substitution of alkyl)amino groups, wherein the optional cyclic C3-C 18 Hydrocarbon groups (e.g., C6-C) 18 (hydrocarbon group) and cyclic C1-C 17 The heteroalkyl substituent is optionally C 1-4 Alkyl, Halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Alkyl)amino substitution; and wherein A comprises a π system conjugated with the carbonyl structural portion of formula (II).

[0111] In a particular embodiment, A is an optionally substituted cyclic C6-C 18 Hydrocarbon groups, such as cyclic C6-C 14 Hydrocarbon group, or optionally substituted C5-C 17 Heterocyclic groups, such as cyclic C5-C 13 Heterocyclic groups, each comprising a π system conjugated with the carbonyl structural moiety of formula (II). In some embodiments, the cyclic hydrocarbon group or cyclic heterocyclic group is aromatic. The cyclic hydrocarbon group or cyclic heterocyclic group may be polycyclic and may comprise fused rings. In some embodiments, the cyclic hydrocarbon group or cyclic heterocyclic group is bicyclic or tricyclic. Typically, the cyclic hydrocarbon group or cyclic heterocyclic group is tricyclic, for example, a tricyclic structural moiety comprising three fused rings, such as optionally substituted fluorene or... Tonone.

[0112] In a particular embodiment, A is an optionally substituted cyclic C6-C 18 Hydrocarbon groups, such as cyclic C6-C 14A hydrocarbon group comprising a π-system conjugated with the carbonyl structural moiety of formula (II). In some embodiments, the cyclic hydrocarbon group is aromatic. The cyclic hydrocarbon group may be polycyclic and may comprise fused rings. In some embodiments, the cyclic hydrocarbon group is bicyclic or tricyclic. Typically, the cyclic hydrocarbon group is tricyclic, for example, a tricyclic structural moiety comprising three fused rings, such as optionally substituted fluorene. In a particular embodiment, Q is optionally substituted fluorene ketone.

[0113] A may optionally be selected from one or more of the following: phenyl, C 1-4 Alkyl, C 2-6 alkenyl (e.g., C) 2-4 alkenyl), halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 The alkyl)amino group is substituted with a substituent, wherein the optional phenyl substituent is optionally C 1-4 Alkyl, C 2-6 alkenyl (e.g., C) 2-4 alkenyl), halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Alkyl)amino substitution. In some embodiments, A is optionally replaced by one or more molecules selected from phenyl, C 1-4 Alkyl, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 The alkyl)amino group is substituted with a substituent, wherein the optional phenyl substituent is optionally C 1-4 Alkyl, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Alkyl)amino substitution. In some embodiments, A is optionally replaced by one or more molecules selected from phenyl, C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Alkoxy and di(C 1-4 The alkyl)amino group is substituted with a substituent, wherein the optional phenyl substituent is optionally C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Alkoxy and di(C 1-4 Alkyl)amino substitution.

[0114] In a particular implementation, Q has formula (IIa) or (IIb):

[0115]

[0116] in:

[0117] Each ring B is independently selected from benzene, naphthalene, and C3-C. 17 heteroaromatic hydrocarbons, each optionally composed of one or more cyclic C3-C... 18 Hydrocarbon group, cyclic C1-C 17 heterohydrocarbon group, C 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Substitution of alkyl)amino groups, wherein the optional cyclic C3-C 18 Hydrocarbon groups and cyclic C1-C 17 The heteroalkyl substituent is optionally C 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Alkyl)amino substitution;

[0118] Each ring C is arbitrarily selected, and when present, is independently chosen from the cyclic C5-C. 11 Hydrocarbons or C3-C 10 Heterocyclic rings, each optionally separated by one or more rings selected from cyclic C3-C 18 Hydrocarbon group, cyclic C1-C 17 heterohydrocarbon group, C 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Substitution of alkyl)amino groups, wherein the optional cyclic C6-C 18 Hydrocarbon groups and cyclic C1-C 17 The heteroalkyl substituent is optionally C 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Alkyl)amino substitution;

[0119] R f Selected from cyclic C3-C 18 Hydrocarbon group, cyclic C1-C 17 heterohydrocarbon group, C 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Alkyl)amino, wherein the optional cyclic C6-C 18Hydrocarbon groups and cyclic C1-C 17 The heteroalkyl substituent is optionally C 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Alkyl)amino substitution; and

[0120] nf2 is 0 and nf1 is 0;

[0121] nf2 is 1 and nf1 is 0 to 2; or

[0122] nf2 is 2 and nf1 is 0 to 4.

[0123] In a particular embodiment, when the ring C is present and optionally substituted with a halogenated group, the halogenated group is not at the α-position of the ketone moiety in formula (I). In a particular embodiment, the ring C is an optionally substituted aromatic hydrocarbon or an optionally substituted heteroaromatic hydrocarbon, such as benzene, naphthalene, or a C3-C9 heteroaromatic hydrocarbon, each optionally substituted with one or more cyclic C3-C... 18 Hydrocarbon group, cyclic C1-C 17 heterohydrocarbon group, C 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Substitution of alkyl)amino groups, wherein the optional cyclic C6-C 18 Hydrocarbon groups and cyclic C1-C 17 The heteroalkyl substituent is optionally C 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Alkyl)amino substitution. In some embodiments, the ring C is optionally replaced by one or more compounds selected from phenyl, C 1-6 cycloalkyl, C 1-4 Alkyl, Halogenated, C 1-4 Haloalkyl, C 1-4 Alkoxy and di(C 1-4 Substituents of alkyl)amino groups, wherein the phenyl and C 1-6 cycloalkyl groups are optionally C 1-4 Alkyl, Halogenated, C 1-4 Haloalkyl, C 1-4 Alkoxy and di(C 1-4 Alkyl)amino substitution.

[0124] In some embodiments, ring C is present and ring B and ring C are each selected from benzene and naphthalene, such as benzene, each of which is optionally substituted as described above.

[0125] In some embodiments, ring C is present and rings B and C are each selected from benzene and naphthalene, each of which is optionally replaced by one or more components selected from phenyl, C 1-6 cycloalkyl, C 1-4 Alkyl, Halogenated, C 1-4 Haloalkyl, C 1-4 Alkoxy and di(C 1-4 Substituents of alkyl)amino groups, wherein the phenyl and C 1-6 cycloalkyl groups are optionally C 1-4 Alkyl, Halogenated, C 1-4 Haloalkyl, C 1-4 Alkoxy and di(C 1-4 Alkyl)amino substitution. In particular embodiments, B and C are each optionally substituted benzenes.

[0126] In some implementation schemes, R f Selected from phenyl, C 1-6 cycloalkyl, C 1-4 Alkyl, Halogenated, C 1-4 Haloalkyl, C 1-4 Alkoxy and di(C 1-4 alkyl)amino, wherein the phenyl and C 1-6 Each cycloalkyl group is optionally C 1-4 Alkyl, Halogenated, C 1-4 Haloalkyl, C 1-4 Alkoxy and di(C 1-4 Alkyl)amino substitution. In a particular embodiment, R f Selected from C 1-6 cycloalkyl, C 1-4 Alkyl, Halogenated, C 1-4 Haloalkyl, C 1-4 Alkoxy and di(C 1-4 Alkyl)amino.

[0127] In some implementations, nf2 is 0 and nf1 is 0, or nf2 is 1 and nf1 is 0 to 2. In a particular implementation, nf1 is 0. In a more particular implementation, nf2 is 0.

[0128] For the avoidance of doubt, when Q has formula (II) or has formula (IIa) or (IIb), the diol derived from Q has formula (II'), (IIa') or (IIb'):

[0129]

[0130] Among them, rings A, B, C, and R f nf1 and nf2 are defined above for equation (II) or equation (IIa).

[0131] In a specific implementation scheme, Q is fluorenone, Tonone or dibenzocycloheptanone, such as fluorenone, each optionally being oxidized by one or more compounds selected from phenyl, C 1-6 Alkyl, C 2-6 alkenyl, C 4-6 Dienyl, C6 trienyl, C 2-6 alkynyl group, C 4-6 The substituents are diynyl and C6 triynyl, each of which is optionally replaced by one or more substituents selected from phenyl, C6, and C6 triynyl groups. 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 The alkyl)amino group is substituted with a substituent, wherein the optional phenyl substituent is optionally C 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Alkyl)amino substitution. In some embodiments, Q is fluorenone, Tonone or dibenzocycloheptanone, such as fluorenone, each optionally composed of one or more compounds selected from phenyl and C 1-6 Alkyl substituents, wherein the phenyl group is optionally replaced by one or more groups selected from C 1-4 Alkyl, Halogenated, C 1-4 Haloalkyl, C 1-4 Alkoxy and di(C 1-4 Substituents of alkyl)amino groups. In some embodiments, the fluorenone, The optional substituents of tonone or dibenzocycloheptanone are selected from phenyl and C. 1-6 Alkyl groups, wherein the phenyl group is optionally composed of one or more compounds selected from C 1-4 Alkyl, halogenated and C 1-4 Substituents of haloalkyl groups.

[0132] In a specific implementation, Q is 9-fluorenone, 9H- Tun-9-one, 10,10-dimethyl-9-10-dihydroanthraphen-9-one or 10,11-dihydro-5H-dibenzo[a,d][7]cycloen-5-one.

[0133] In a particular embodiment, Q has formula (I) or (II) and the [Ni(L)] n[Q] The complex has formula (IIIa) or (IIIb):

[0134]

[0135] in:

[0136] R 1 R 2 And A is as defined above for equations (I) and (II). In some embodiments, [Ni(L)] n [Q] The complex has formula (IIIc) or (IIId):

[0137]

[0138] in:

[0139] Ring B, Ring C, R f nf2 and nf1 are defined above for equation (IIa) or (IIb).

[0140] In a particular implementation, Q has formula (I) and the [Ni(L)] n The complex (Q) has the formula (IIIa).

[0141] In some implementation schemes, R 1 and R 2 The groups selected independently from phenyl, naphthyl, pyridyl, anthracene, phenanthrene, and C 5-6 cycloalkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 4-6 Dienyl, C6 trienyl, C 2-6 alkynyl group, C 4-6 Diynyl and C6 triynyl, each of which is optionally radicalized by one or more groups selected from phenyl, C6 ... 1-4 Alkyl, C 2-6 alkenyl (e.g., C) 2-4 alkenyl), halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 The alkyl)amino group is substituted with a substituent, wherein the optional phenyl substituent is optionally C 1-4 Alkyl, C 2-6 alkenyl (e.g., C) 2-4 alkenyl), halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Alkyl)amino substitution; and wherein R 1 and R 2 At least one of them contains a π system conjugated with the carbonyl structural portion.

[0142] In some implementation schemes, R 1 and R 2 Each is independently selected from phenyl, naphthyl, pyridyl, anthracene, phenanthrene, C 5-6 cycloalkyl and C 1-6 Alkyl groups, each of which may optionally be substituted. In a more particular embodiment, R 1 and R 2 Each is an optionally substituted phenyl group.

[0143] 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, R f Selected from C 1-4 Alkyl, halogenated and C 1-4 Halogenated alkyl groups.

[0144] As mentioned above, [Ni(L)] n (Q)] and [Ni(L) n The L in (X)2] is a monodentate, bidentate, or tridentate L-type ligand, wherein n is 2 when L is monodentate and n is 1 when L is bidentate or tridentate.

[0145] L-type ligands are neutral ligands capable of donating one or more electron pairs to nickel, thereby forming one or more coordinate bonds with nickel, regardless of the electron counting method used. These electron pairs typically originate from lone pairs of electrons.

[0146] L can bond to nickel via any suitable atom that can donate two electrons to form a coordinate bond. Typically, L bonds to nickel via phosphorus, nitrogen, carbon, and / or oxygen atoms, for example, L bonds to nickel via phosphorus, nitrogen, and / or carbon atoms.

[0147] In some embodiments, L is monodentate and bonded to nickel via a phosphorus atom or a carbon atom. L can be a phosphine, a carbene (such as an N-heterocyclic carbene), an amine, an imine, or an optionally substituted N-heterocyclic compound, such as an optionally substituted N-heteroaryl compound (e.g., pyridine). In certain embodiments, L is a phosphine or a carbene.

[0148] Alternatively, L can be bidentate and chelated to the nickel by two independent bonding atoms selected from phosphorus, nitrogen, carbon, and oxygen. L may comprise two bonding structural motifs, independently selected from phosphine, amine, imine, pyridine, and carbene (e.g., N-heterocyclic carbene) structural motifs. Typically, the two bonding atoms or the two bonding structural motifs are identical. For example, L can be bidentate and comprise two phosphine bonding structural motifs, two amine bonding structural motifs, or two pyridine bonding structural motifs.

[0149] In an alternative embodiment, L is tridentate and chelates to the nickel via nitrogen, phosphorus, and / or carbon atoms. A tridentate L-type ligand is capable of donating three electron pairs to nickel via three distinct bonding atoms. However, when L is tridentate, it typically chelates with nickel via only two of the three available electron pairs, meaning one of the bonding atoms is usually not bonded to nickel. When L is tridentate, it typically comprises three bonding structural moieties, independently selected from phosphine, amine, imine, pyridine, and carbene (e.g., N-heterocyclic carbene) structural moieties.

[0150] L can be or contains phosphine. Suitable phosphine ligands for use as L include those described in the following literature: 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 - Asymmetrictransformations under nickel catalysis, Editor(s): Junliang Zhang, Wenbo Li, "Chiral Phosphorous Based Ligands in Earth-Abundant Transition MetalCatalysis", Elsevier, 2023, 141-186; and Wen et al., Chem. Soc. Rev., 2021, 50, 3211-3237. Ferrocene-based phosphine ligands, such as those described by Bandaru et al. in Coordination Chemistry Reviews, 491, 2023, 215250, are widely used in cross-coupling reactions and are also suitable as L. Particularly useful bidentate phosphine ligands are described by Clevenger et al. Chem.Rev. The polydentate phosphine ligands described in 2020, 120, 13, 6124-6196, and particularly useful ones are described by Pascariu et al. in Journal of Organometallic Chemistry, 694, 25, 2009, 3982-4000. The bidentate and tripentate ligands described in these papers are also suitable for use as L.

[0151] L can be or contains carbenes, such as N-heterocyclic carbenes. A review of nickel N-heterocyclic carbene complexes and their use in homogeneous catalysis is provided by Prakasham and Ghosh in Inorg. Chim. Acta, 431, 2015, 61-100; Henrion et al. in ACS Catal. In 2015, 5, 2, 1283-1302; and Ritleng et al. in ACS Catal. In 2016, 6, 2, 890-906, the N-heterocyclic carbene ligands described in these reviews are suitable for use as L.

[0152] L may contain an N-donor structural moiety, such as an amine, imine, or an optionally substituted N-heterocycle. Loubalová and Kopel provide a review of complexes with dicarboxylic acids and N-donor ligands in Molecules, 2023, 28(3), 1445. Other N-donor ligands are described by Tellis et al. Acc.Chem.Res . 2016, 49, 7, 1429-1439; Huang, Journal of Chemical Research 2022; 46(1); and Tasker et al. Nature As described in 509, 299-309 (2014). L can be one or more of the monodentate ligands described in these papers, as well as any of the bidentate or tripentate ligands.

[0153] As described above, the natural bite angle is the preferred angle for chelation between each of the bonded structural portions of a bidentate ligand or two of the three bonded structural portions of a tripentate ligand and the metal ion. It is obtained using molecular mechanics calculations and is determined solely by the ligand skeleton constraint, not by the metal valence bond angle (see, for example, the bite angle reported by Mansell in Dalton Trans. 2017, 46, 15157 and calculated by the method described by van Leeuwen in Homogeneous Catalysis: Understanding the Art, Springer, Netherlands, 2004). The bite angle of ligands in a complex is known to influence the catalytic activity of the complex.

[0154] The inventors have discovered that the method of the present invention is unexpectedly more efficient when L is a two- or three-toothed tooth and 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 diphenylphosphine methane (dppm). dppm is reported to have a natural bite angle of about 72° and is therefore excluded from the aforementioned bite angle range. In some embodiments, L has a natural bite angle of about 80° to about 140°.

[0155] In a particular implementation, when the method includes making the [Ni(L)]... n [X]2] When the complex comes into contact with reducing metals and ketones, 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 diphenylphosphine ethane (dppe). dppe is reported to have a natural bite angle of about 85°, and is therefore excluded from the bite angle ranges of about 90° to about 140° and about 95° to about 140°. According to some embodiments, L is not diphenylphosphine propane (dppp). It is reported to have a bite angle of about 91°, and is therefore excluded from the range just described.

[0156] In even more specific embodiments, when the method includes making the [Ni(L)]... n When the (X)2] complex comes into contact with a reducing metal and a ketone or diol, L has a natural bite angle of at least about 90° to about 140°, such as about 95° to about 140°.

[0157] As described above, the "Tolman cone angle" is used to measure the size of a monodentate ligand. The inventors have discovered that the method of the present invention is unexpectedly more efficient when L is monodentate and when L has a Tolman cone angle of at least about 125°, such as about 130°, to about 190° or about 180°. According to some embodiments, L is not trimethylphosphine. Trimethylphosphine has reportedly had a Tolman cone angle of about 118°, and is not in the range of at least about 125°, such as about 130°, to about 190° or about 180°.

[0158] In a particular implementation, when the method includes making the [Ni(L)]... n When the [X)2] complex is contacted with a reducing metal and a ketone, L has a Tolman cone angle of about 160° to about 190°, such as about 160° to about 180°. In a more particular embodiment, when the method includes making the [Ni(L)] complex... n When the (X)2] complex comes into contact with reducing metals and ketones, L is bidentate or tridentate.

[0159] In some implementations, when the method includes making the [Ni(L)]... n When the [X)2] complex is contacted with a reducing metal and a ketone or diol, L has a Tolman cone angle of about 160° to about 190°, such as about 160° to about 180°. In a more particular embodiment, when the method includes making the [Ni(L)] complex... n When the (X)2] complex comes into contact with reducing metals and ketones, L is bidentate or tridentate.

[0160] In a particular implementation, L is not dppm, dppe, dppp, or trimethylphosphine.

[0161] In a particular implementation, L is selected from tri-cyclic C 5-6 Hydrophosphine, C 1-4 alkyl-di-cycloC 5-6 Hydrophosphine, tetraC 1-4 Alkyl C 2-4 alkylene diamine, penta-C 1-4 Alkyl C 2-4 alkyltriamines, C containing N,N 10 Heterocyclic bicyclic ligands, C containing N,N 12-14 Heterocyclic tricyclic ligands, bis(di-cyclic C) 5-6 (Hydrocarbon phosphine)C 2-4 Alkylene, bis(di-cycloC) 5-6 (Hydrocarbon-phosphine-) Tons, double (di-C) 1-4 Alkylphosphine Tons, double (two-ring C) 5-6 (Hydrophosphino)ferrocene, bis(di-C) 1-4 Alkylphosphinyl)ferrocene, bis(di-cycloC) 5-6 (Hydrophosphinophenyl) ether and bis(di-C) 1-4 Alkylphosphine phenyl ethers, each of which is optionally composed of one or more compounds selected from C 1-4 Alkyl, Halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Substitution of alkoxy and morpholino groups.

[0162] In some implementations, L is not replaced, i.e., not selected from one or more of C. 1-4 Alkyl, Halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Substitution of alkoxy and morpholino groups.

[0163] In a more specific embodiment, L is selected from triphenylphosphine, bis(diphenylphosphino)propane, bis(diphenylphosphino)butane, bis(diphenylphosphino)ethane, bis(diphenylphosphino)ferrocene, and bis(diphenylphosphino) Ton, N,N,N',N'-tetramethylethylenediamine, N,N,N',N'',N''-pentamethyldiethylenetriamine, bipyridine, di-tert-butylbipyridine, bis(dicyclohexylphosphine)ethane, bis(diisopropylphosphine)ferrocene, bis(di-tert-butylphosphine)ferrocene, diadamantylmorpholinophenylphosphine, methyldiphenylphosphine and tricyclohexylphosphine.

[0164] In some implementations, L is two C 1-4 Alkylphosphine biphenyl or di-cycloC 5-6 Hydroxylphosphine biphenyls, wherein each biphenyl is optionally composed of one or more components selected from C 1-4 Alkyl, di(C) 1-4alkyl)amino and C 1-4 Alkyl group substitution. In some embodiments, L is 2-diC. 1-4 Alkylphosphine biphenyl or 2-di-cycloC 5-6 Hydroxylphosphine biphenyls, wherein each biphenyl is optionally substituted as described above. In some embodiments, L is 2-di-tert-butylphosphine biphenyl or 2-di-cyclohexylphosphine biphenyl, wherein each biphenyl is optionally substituted as described above. In some embodiments, each optional substituent is di(C 1-4 Alkyl)amino, such as dimethylamino. In some embodiments, L is 2-dicyclohexylphosphino-2'-( N,N (-dimethylamino)biphenyl (also known as DavePhos).

[0165] In some embodiments, L is bidentate and comprises a phosphine and carbene bonded structural portion. Typically, in such embodiments, the carbene structural portion is an N-heterocyclic carbene structural portion. For example, L may comprise a bicyclic C 5-6 The alkyl-phosphine-bonded structural portion is, for example, linked to the N-heterocyclic carbene-bonded structural portion via an alkyl linker. In some embodiments, L is a 1-bi-cyclo-C 5-6 Hydroxylphosphine C 1-4 alkyl-3-phenylimidazolium-2-ylene, wherein the ring C 5-6 The hydrocarbon group and the phenyl group are each optionally surrounded by one or more groups selected from C. 1-4 Alkyl, di(C) 1-4 alkyl)amino and C 1-4 Alkyl substituents. In a particular embodiment, L is 1-(2-diphenylphosphinoethyl)-3-(2,4,6-trimethylphenyl)imidazol-2-ylene.

[0166] As mentioned above, [Ni(L)] n In [X]2, X is a monoanionic ligand, which can be monovalent (e.g., a halide or pseudohalide) or divalent (e.g., an acetate or acetylacetonate). In some embodiments, X is selected from halides, trifluoromethanesulfonate, acetate, trifluoroacetate, acetylacetonate, nitrate, and sulfonate. In some embodiments, X is selected from chloride, bromide, iodide, acetate, and nitrate. In some embodiments, X is selected from chloride, bromide, iodide, and nitrate. In particular embodiments, X is chloride, bromide, or iodide, for example, X is chloride.

[0167] When L is bidentate and bonded to nickel through two nitrogen atoms, X can be any of the chloride, bromide, iodide, and acetate groups.

[0168] When L is bidentate and bonded to nickel through two phosphorus atoms, X can be chloride, bromide, or iodide.

[0169] When each L is monodentate and bonded to nickel via a phosphorus atom, X can be any of the chloride, bromide, iodide, nitrate, and sulfate ions.

[0170] The [Ni(L)] n The [X)2] complex can be contacted with a reducing metal and a diol or ketone. The reducing metal can be any metal suitable for reducing a diol or ketone to a carbonyl free anion or a carbonyl free dianion. Typically, the reducing metal comprises a Group I metal, i.e., lithium, sodium, potassium, rubidium, cesium, or francium. In some embodiments, the reducing metal comprises lithium, sodium, potassium, or rubidium, such as lithium, sodium, or potassium. The reducing metal can be provided as an oil or salt dispersion, or as part of a sandwich compound (such as a graphite sandwich compound). In particular embodiments, the reducing metal is provided as a metal or as part of a sandwich compound (such as a graphite sandwich compound). In particular embodiments, the method includes making the [Ni(L)] complex... n The (X)2] complex is contacted with a diol or ketone and any of the following metals selected from sodium, lithium, potassium, cesium, rubidium and graphite sandwich compounds containing potassium or lithium.

[0171] Alternatively and preferably, the [Ni(L)] n [X]2 complexes can contact with bases and glycols. The inventors have discovered that bases (many of which are easier to handle and store than reducing metals) can be used with [Ni(L)2] complexes. n Synthesis of [Ni(L)] complex and diol n [Q] complex, and is unexpectedly effective and adaptable to changes in Q, L and X.

[0172] The base can be any base suitable for reducing a diol to a carbonyl 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-butoxides, phenolates, bis(trimethylsilyl)amides, and various Grignard reagents such as C 1-4 Alkyl magnesium halides and C 5-6 Hydrocarbon-based magnesium halides, various organolithium, organopotassium, and organosodium reagents such as C 1-4 Alkyl lithium, C 1-4 Alkyl potassium, C 1-4 Alkyl sodium, di(C) 1-4 Alkyl)aminolithium, di(C) 1-4 Alkyl)aminopotassium, di(C) 1-4 Sodium alkylamino, tetracarbonyl 1-4 Alkyl C 5-6 Hydrocarbon-based lithium, tetracarbon1-4 Alkyl C 5-6 Hydrocarbon potassium and tetracarbon 1-4 Alkyl C 5-6 Sodium hydrocarbon. Seyferth in Organometallics 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 A review of Grignard reagents is provided in e202102853.

[0173] In some embodiments, the base is selected from potassium tert-butoxide, lithium tert-butoxide, sodium tert-butoxide, sodium phenolate, potassium bis(trimethylsilyl)amino, lithium bis(trimethylsilyl)amino, sodium bis(trimethylsilyl)amino, and C. 1-4 Alkyl magnesium chloride, C 5-6 Hydrocarbon-based magnesium chloride, C 1-4 Alkyl lithium, C 1-4 Alkyl potassium, C 1-4 Alkyl sodium, di(C) 1-4 Alkyl)aminolithium, di(C) 1-4 Alkyl)aminopotassium, di(C) 1-4 Sodium alkylamino, tetracarbonyl 1-4 Alkyl C 5-6 Hydrocarbon-based lithium, tetracarbon 1-4 Alkyl C 5-6 Hydrocarbon potassium, tetracarbon 1-4 Alkyl C 5-6 Hydrocarbon sodium.

[0174] In a more particular embodiment, the base is selected from potassium tert-butoxide, lithium tert-butoxide, sodium phenolate, potassium phenolate, bis(trimethylsilyl)aminopotassium, methyl magnesium chloride, and phenyl magnesium chloride.

[0175] The inventors have discovered that the method is more effective when the contact is carried out in a non-proton solvent (i.e., a solvent that does not have a structural portion capable of supplying protons). Typically, the solvent is anhydrous, i.e., it contains less than about 2 wt% water, for example less than about 1 wt%, about 0.5 wt%, or about 0.1 wt% water.

[0176] The solvent may have a dielectric constant of ≤10⁻⁸ at 20°C. In a particular embodiment, the solvent is selected from one or more of THF, toluene, diethyl ether, dimethoxyethane, hexane, 2-methyltetrahydrofuran, methyl tert-butyl ether, and cyclopentylmethyl ether. Typically, the solvent is selected from one or more of THF, toluene, diethyl ether, dimethoxyethane, and hexane. Typically, only one type of solvent is used, rather than a mixture of solvents.

[0177] Typically, the alkali, reducing metal, ketone, and diol are relative to [Ni(L)]. n The [X)2] complex is in molar excess, which means that relative to the [Ni(L)] complex... n [X]2] Complexes are used in amounts greater than 1 equivalent for each.

[0178] When the [Ni(L)] n When the [X)2] complex comes into contact with a base and a diol, it is typically relative to the [Ni(L)] complex. n The [X)2] complex uses a small excess of diol. In some embodiments, relative to the [Ni(L)] complex... n The [X)2] complex uses a diol in amounts of ≥ about 1 to about 1.5, for example, ≥ about 1 to about 1.2, or ≥ about 1 to about 1.1, for example, about 1.05 equivalents. Typically, this is relative to the [Ni(L)] complex. n The [X)2] complex uses at least 2 equivalents of base. Not limited by theory, it is required that at least 2 molecules of base reduce a nickel(II) complex to nickel(O) via a carbonyl free anionic species. In some embodiments, relative to the [Ni(L)] complex… n The (X)2] complex uses about 2 to about 3, for example about 2 to about 2.5 molar equivalents of base.

[0179] When the [Ni(L)] n When the [X)2] complex comes into contact with a reducing metal and a diol or ketone, two different reaction pathways may exist. As mentioned above, the carbonyl free anion is typically the dominant carbonyl free species formed when about 1 or less equivalent of reducing metal is used relative to the ketone or about 2 or less equivalents of reducing metal is used relative to the diol. The carbonyl dianion is typically the dominant carbonyl free species formed when about 2 or more equivalents of reducing metal is used relative to the ketone or about 4 or more equivalents of reducing metal is used relative to the diol. One process may be superior to the other; for example, one process may be better suited for the synthesis of nickel complexes than another. Since the carbonyl dianion is a better reducing agent, therefore, in the [Ni(L)] complex... n When the (X)2] complex is more difficult to reduce, the carbonyl dianion pathway is preferred. Alternatively, when using more sensitive starting materials, the carbonyl radical process is preferred.

[0180] Relative to [Ni(L)] n [X)2] complex, about 2 to about 5 molar equivalents of reducing metal can be used, for example about 2 to about 4 molar equivalents of reducing metal. When using ketones, relative to the [Ni(L)] complex... n [X]2] The complex uses a ketone in greater than about 2 molar equivalents, for example, about 2.05 to about 8 molar equivalents of a ketone. When a diol is used, relative to the Ni(L) n [X]2] Complexes typically use about ≥1.01 to about 1.5 moles of diol, for example about ≥1.01 to about 1.2 molar equivalents of diol, for example about 1.05 molar equivalents of diol.

[0181] To facilitate the carbonyl anion pathway, when the reducing metal is used with the diol, relative to the [Ni(L)]... n The [X]2] complex uses a small excess of a diol, for example, ≥ about 1 to about 2 equivalents, or ≥ about 1 to about 1.5 equivalents of a diol. Typically, a reducing metal of ≥ about 1 equivalent and ≤ about 2 equivalents is used relative to the diol. In some embodiments, a reducing metal of about 1.2 to about 1.8, for example about 1.6 equivalents, is used relative to the diol. To facilitate the carbonyl anion pathway, when the reducing metal is used with a ketone, the [Ni(L)] complex is used in excess of a small amount of a diol. n [X]2] Complexes typically use an excess of ketone, for example, ≥ about 2 to about 4 equivalents, or ≥ about 2 to about 3 equivalents of ketone. Typically, ≤ about 1 equivalent of reducing metal is used relative to the ketone. In some embodiments, about 0.5 to about 1, for example, about 0.8 equivalents of reducing metal are used relative to the ketone.

[0182] To facilitate the carbonyl dianion pathway, when the reducing metal is used with the diol, relative to the [Ni(L)]... n [X)2] Complexes typically use less than 1 equivalent of a diol, for example, about 0.5 to about 0.9 equivalents of a diol. Typically, ≥ about 2 equivalents of a reducing metal are used relative to the diol, for example, about 3 to about 5 equivalents (e.g., about 4 equivalents) of a reducing metal. When the reducing metal is used with a ketone, to favor the carbonyl dianion pathway, the amount of [Ni(L)] complex is increased relative to the dianion. n [X]2] complexes typically use a small excess of ketone, for example, about 1.2 to about 1.8 equivalents of ketone. Typically, about 1.5 to about 2.5 equivalents of reducing metal, such as about 2 equivalents, are used relative to the ketone.

[0183] The method of the present invention can be carried out at any convenient temperature, provided that the carbonyl free anion or dianion species can be formed. Those skilled in the art can assess which temperature is suitable without causing undue burden. In some embodiments, the contact is carried out at a temperature of about 240 K to about 305 K. Advantageously, the inventors have found that the reaction is carried out at ambient temperature. Therefore, the contact can be carried out at a temperature of about 240 K to about 298 K, for example, about 285 K to about 298 K.

[0184] The contact can be carried out for the length of time required to produce a suitable amount of product, for example, the time required for the reaction to complete, i.e., [Ni(L)]. n (Q)] from [Ni(L) n (X)2] The time required for complete conversion. Techniques well known to those skilled in the art can be used to monitor the reaction process and assess when a suitable amount of product has been prepared or when the reaction is complete. Methods also known to those skilled in the art can be used to accelerate the reaction rate and thus reduce the time required for the reaction to complete. Examples include increasing the temperature, increasing the pressure, and using microwave heating. In some embodiments, the contact lasts for a period of approximately 3 to 12 hours.

[0185] As mentioned above, the second aspect provides [Ni(L)] n [Q] complex, wherein:

[0186] Q is a ketone complexed with nickel, wherein the ketone contains a carbonyl structural moiety conjugated with the π system;

[0187] L is a monodentate, bidentate, or tridentate L-type ligand selected from tri-C 1-6 Alkylphosphine (e.g., tri-n-butylphosphine), tri-cyclic C 5-6 Hydrophosphine, C 1-4 alkyl-di-cycloC 5-6 Hydroxyphosphine, N,N,N',N'-tetrachlorophosphine 1-4 Alkyl C 2-4 alkylene diamine, N,N,N',N'',N''-pentacarbonyl 1-4 Alkyl C 2-4 alkyltriamines, C containing N,N 12-14 Heterocyclic tricyclic ligands, bis(di-cyclic C) 5-6 (Hydrocarbon phosphine)C 2-4 Alkylene, bis(di-cycloC) 5-6 (Hydrocarbon-phosphine-) Tons, double (di-C) 1-4 Alkylphosphine Tons, double (two-ring C) 5-6 (Hydrophosphino)ferrocene, bis(di-C) 1-4 Alkylphosphinyl)ferrocene, bis(di-cycloC)5-6 (Hydrophosphinophenyl) ether and bis(di-C) 1-4 Alkylphosphine phenyl ethers, each of which is optionally composed of one or more compounds selected from C 1-4 Alkyl, Halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Substitution of alkoxy and morpholino groups,

[0188] L is a C that includes N, N 10 Heterocyclic bicyclic ligands, optionally using one or more selected from C 1-4 Alkyl, Halogenated, C 1-4 Halogenated alkyl, hydroxyl and C 1-4 Substitution of alkoxy groups,

[0189] L is two C 1-4 Alkyl-phosphino-biphenyl or di-cyclic C 5-6 Hydroxylphosphine-biphenyl, wherein each biphenyl is optionally made of one or more compounds selected from C 1-4 Alkyl, di(C) 1-4 alkyl)amino and C 1-4 Substitution of alkoxy groups, or

[0190] L contains bicyclic C 5-6 The alkylphosphine-bonded structural portion is optionally linked to the N-heterocyclic carbene-bonded structural portion via an alkyl linker; and

[0191] When L is a single tooth, n is 2, and when L is a double or triple tooth, n is 1.

[0192] In some implementations, L is a monodentate, bidentate, or tridentate L-type ligand selected from tricyclic C 5-6 Hydrophosphine, C 1-4 alkyl-di-cycloC 5-6 Hydroxyphosphine, N,N,N',N'-tetrachlorophosphine 1-4 Alkyl C 2-4 alkylene diamine, N,N,N',N'',N''-pentacarbonyl 1-4 Alkyl C 2-4 alkyltriamines, C containing N,N 12-14 Heterocyclic tricyclic ligands, bis(di-cyclic C) 5-6 (Hydrocarbon phosphine)C 2-4 Alkylene, bis(di-cycloC) 5-6 (Hydrocarbon-phosphine-) Tons, double (di-C) 1-4 Alkylphosphine Tons, double (two-ring C) 5-6 (Hydrophosphino)ferrocene, bis(di-C) 1-4 Alkylphosphinyl)ferrocene, bis(di-cycloC) 5-6(Hydrophosphinophenyl) ether and bis(di-C) 1-4 Alkylphosphine phenyl ethers, each of which is optionally composed of one or more compounds selected from C 1-4 Alkyl, Halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Substitution of alkoxy and morpholino groups, or

[0193] L is a C containing N, N 10 Heterocyclic bicyclic ligands, optionally ligands selected from one or more C... 1-3 Alkyl, Halogenated, C 1-4 Halogenated alkyl, hydroxyl and C 1-4 Substitution of alkoxy groups.

[0194] For the avoidance of doubt, each embodiment of the embodiments described in relation to Q and L in the first aspect may be applied to the second aspect with any necessary changes. For example, Q may have formula (I) or formula (II), or more particularly may be an optionally substituted fluorenone or an optionally substituted benzophenone. L may be any one selected from the following: triphenylphosphine, bis(diphenylphosphino)propane, bis(diphenylphosphino)butane, bis(diphenylphosphino)ethane, bis(diphenylphosphino)ferrocene, bis(diphenylphosphino) Ton, N,N,N',N'-tetramethylethylenediamine, N,N,N',N'',N''-pentamethyldiethylenetriamine, bipyridine, bis(dicyclohexylphosphino)ethane, bis(diisopropylphosphino)ferrocene, bis(di-tert-butylphosphino)ferrocene, diadamantylmorpholinophenylphosphine, methyldiphenylphosphine and tricyclohexylphosphine.

[0195] For example, Q can have equation (I) or equation (II), and when R 1 R 2 When A is optionally substituted with a halogenated group, the halogenated group is not at the α-position of the ketone structural portion of formula (I) or (II).

[0196] In some embodiments, when L is triphenylphosphine or 2,2'-bipyridine, Q is not benzophenone. In some embodiments, when L is optionally composed of one or more compounds selected from C... 1-4 Alkyl, Halogenated, C 1-4 Halogenated alkyl, hydroxyl and C 1-4 Alkoxy substituents of N,N-containing C 10 Heterocyclic bicyclic ligands or tricyclic C 5-6 When it is a hydrocarbon phosphine, Q is not benzophenone.

[0197] In a specific implementation scheme, R 1 and R 2 Each is independently selected from phenyl, naphthyl, pyridyl, C 5-6cycloalkyl and C 1-6 Alkyl (e.g., C10) 1-4 Alkyl groups, each of which is optionally composed of one or more compounds selected from phenyl, C 1-4 Alkyl, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 The alkyl)amino group is substituted with a substituent, wherein the optional phenyl substituent is optionally C 1-4 Alkyl, Halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Alkyl)amino substitution; and wherein R 1 and R 2 At least one of them contains a π system conjugated with the carbonyl structural portion. Alternatively, Q may have formula (IIa) or (IIb).

[0198] In some implementations, L is a monodentate, bidentate, or tridentate L-type ligand selected from tri-C 1-6 Alkylphosphine (e.g., tri-n-butylphosphine), N,N,N',N'-tetra-C 1-4 Alkyl C 2-4 Alkylene diamines (e.g., N,N,N',N'-tetramethylethylenediamine (TMEDA) or N,N,N',N'-tetraethylethylenediamine (TEEDA)), N,N,N',N'',N''-pentacarbonylamine (TPED) 1-4 Alkyl C 2-4 alkylene triamines (e.g., N,N,N',N'',N''-pentamethyldiethylenetriamine (PMDTA)), bis(di-cyclohexane-3-methyltriamine) 5-6 (Hydrocarbon phosphine)C 3-4 Alkylenes (e.g., 1,3-bis(diphenylphosphino)propane (DPPP) or 1,4-bis(diphenylphosphino)butane (DPPB)), bis(di-cyclocarbonyl)propane (C2-C4 ... 5-6 (Hydrocarbon-phosphine-) Tons (e.g., 4,5-bis(diphenylphosphino)-9,9-dimethyl) XantPhos (ton), double (di-cyclic C) 5-6 (Hydrophosphino)ferrocene (e.g., 1,1'-bis(diphenylphosphino)ferrocene (DPPF)), each of which is optionally composed of one or more compounds selected from C 1-4 Alkyl, Halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Substitution of alkoxy and morpholino groups,

[0199] L is selected from one or more of C 1-4 Alkyl, Halogenated, C 1-4 Halogenated alkyl, hydroxyl and C 1-4Alkoxy substituents of N,N-containing C 10 Heterocyclic bicyclic ligands (e.g., L is 4,4'-di-tert-butyl-2,2'-bipyridine (d t BuBIPY) or 4,4'-dimethoxy-2,2'-bipyridine (dMeOBIPY)

[0200] L is two C 1-4 Alkylphosphine biphenyl or di-cyclo-C 5-6 Hydroxylphosphine biphenyls, wherein each biphenyl is optionally composed of one or more components selected from C 1-4 Alkyl, di(C) 1-4 alkyl)amino and C 1-4 Alkyl substituents (e.g., L is 2-dicyclohexylphosphine-2'-( N,N (-dimethylamino)biphenyl), or

[0201] L contains bicyclic C 5-6 The alkylphosphine-bonded structural portion, optionally linked by an alkyl linker (e.g., C10), 1-4 The alkyl linker is connected to the N-heterocyclic carbene bonded structure (e.g., L is 1-(2-diphenylphosphinoethyl)-3-(2,4,6-trimethylphenyl)imidazol-2-ylide).

[0202] In a particular embodiment, L is a monodentate, bidentate, or tridentate L-type ligand selected from tri-C 1-6 Alkylphosphine (e.g., tri-n-butylphosphine), N,N,N',N'-tetra-C 1-4 Alkyl C 2-4 Alkylene diamines (e.g., N,N,N',N'-tetramethylethylenediamine (TMEDA) or N,N,N',N'-tetraethylethylenediamine (TEEDA)), N,N,N',N'',N''-pentacarbonylamine (TPED) 1-4 Alkyl C 2-4 alkylene triamines (e.g., N,N,N',N'',N''-pentamethyldiethylenetriamine (PMDTA)), bis(di-cyclohexane-3-methyltriamine) 5-6 (Hydrocarbon phosphine)C 3-4 Alkylenes (e.g., 1,3-bis(diphenylphosphino)propane (DPPP) or 1,4-bis(diphenylphosphino)butane (DPPB)), bis(di-cyclocarbonyl)propane (C2-C4 ... 5-6 (Hydrocarbon-phosphine-) Tons (e.g., 4,5-bis(diphenylphosphino)-9,9-dimethyl) XantPhos (ton), double (di-cyclic C) 5-6 (Hydrophosphino)ferrocene (e.g., 1,1'-bis(diphenylphosphino)ferrocene (DPPF)), each of which is optionally composed of one or more compounds selected from C 1-4 Alkyl, Halogenated, C1-4 Halogenated alkyl, hydroxyl, C 1-4 Substitution of alkoxy and morpholino groups, or

[0203] L is selected from one or more of C 1-4 Alkyl, Halogenated, C 1-4 Halogenated alkyl, hydroxyl and C 1-4 Alkoxy substituents of N,N-containing C 10 Heterocyclic bicyclic ligands (e.g., L is 4,4'-di-tert-butyl-2,2'-bipyridine (d t (BuBIPY) or 4,4'-dimethoxy-2,2'-bipyridine (dMeOBIPY)).

[0204] In some implementations, L is a monodentate, bidentate, or tridentate L-type ligand selected from tri-C 1-6 Alkylphosphine (e.g., tri-n-butylphosphine), N,N,N',N'-tetra-C 1-4 Alkyl C 2-4 Alkylene diamines (e.g., N,N,N',N'-tetramethylethylenediamine (TMEDA) or N,N,N',N'-tetraethylethylenediamine (TEEDA)), N,N,N',N'',N''-pentacarbonylamine (TPED) 1-4 Alkyl C 2-4 alkylene triamines (e.g., N,N,N',N'',N''-pentamethyldiethylenetriamine (PMDTA)), bis(di-cyclohexane-3-methyltriamine) 5-6 (Hydrocarbon phosphine)C 3-4 Alkylenes (e.g., 1,3-bis(diphenylphosphino)propane (DPPP) or 1,4-bis(diphenylphosphino)butane (DPPB)), bis(di-cyclocarbonyl)propane (C2-C4 ... 5-6 (Hydrocarbon-phosphine-) Tons (e.g., 4,5-bis(diphenylphosphino)-9,9-dimethyl) XantPhos (ton), double (di-cyclic C) 5-6 (Hydrophosphino)ferrocene (e.g., 1,1'-bis(diphenylphosphino)ferrocene (DPPF)), or

[0205] L is selected from one or more of C 1-4 Alkyl, Halogenated, C 1-4 Halogenated alkyl, hydroxyl and C 1-4 Alkoxy (optionally C) 1-4 Alkyl and C 1-4 Alkoxy) substituents of N,N-containing C 10 Heterocyclic bicyclic ligands (e.g., L is 4,4'-di-tert-butyl-2,2'-bipyridine (d t (BuBIPY) or 4,4'-dimethoxy-2,2'-bipyridine (dMeOBIPY)).

[0206] In a more specific embodiment, L is selected from tri-n-butylphosphine, N,N,N',N'-tetramethylethylenediamine (TMEDA), N,N,N',N'-tetraethylethylenediamine (TEEDA), N,N,N',N'',N''-pentamethyldiethylenetriamine (PMDTA), 1,3-bis(diphenylphosphine)propane (DPPP), 1,4-bis(diphenylphosphine)butane (DPPB), 4,5-bis(diphenylphosphine)-9,9-dimethyl XantPhos, 1,1'-bis(diphenylphosphino)ferrocene (DPPF), 4,4'-di-tert-butyl-2,2'-bipyridine (d t BuBIPY) and 4,4'-dimethoxy-2,2'-bipyridine (dMeOBIPY).

[0207] In a particular implementation, the [Ni(L)] n (Q)] The complex is selected from any of the following structures:

[0208]

[0209]

[0210] .

[0211] In a more specific implementation, the [Ni(L)] n (Q)] The complex is selected from any of the following structures:

[0212] .

[0213] To avoid any doubt, the compounds depicted in the structures disclosed herein are not limited to the bond angles and bond lengths schematically depicted herein. For example, depending on the specific identities of the L and Q ligands, the shapes of the compounds of the present invention can vary from tetrahedral to planar square.

[0214] This also includes solvates and isotope-labeled compounds of the present invention. The isotope-labeled compounds are the same as those described herein, except that one or more atoms are replaced by atoms with atomic masses or mass numbers different from those predominantly found in nature. Examples of isotopes that can be incorporated into the compounds of the present invention include isotopes of hydrogen, carbon, nitrogen, oxygen, sulfur, fluorine, and chlorine, for example... 2 H (i.e., deuterium) 3 H, 13 C 14 C 15 N、 18 O、 17O、 35 S, 18 F and 36 Cl.

[0215] The protium atom (H) is a hydrogen atom with zero neutrons. The deuterium atom (D or...) 2 H) is a hydrogen atom with one neutron. Naturally occurring hydrogen contains approximately 0.02 mol% deuterium and 99.98% protium. The physicochemical properties between protium and deuterium are small but measurable. Deuterium is slightly less lipophilic than protium, has a smaller molar volume, and the carbon-deuterium bond is shorter than the carbon-protium bond. Compared to H, deuterium retains the 3D surface, shape, and spatial flexibility of the molecule. A deuterium:protium ratio greater than 1:99 in a compound is considered greater than the ratio naturally found in hydrogen. In a particular embodiment, when the structural moiety is designated as "H", the deuterium:protium ratio at that position is greater than the natural isotopic abundance of deuterium, i.e., the percentage of deuterium found at that position in the compound of the present invention is greater than its natural isotopic abundance in hydrogen (approximately 0.02 mol%).

[0216] The compounds of this invention also include all amorphous and crystalline forms.

[0217] As stated above, the inventors have discovered that the complex of the second aspect is active in catalysis including cross-coupling reactions, and the third aspect provides the use of the complex as a catalyst, such as a cross-coupling catalyst, as defined in the second aspect. For examples of nickel-catalyzed cross-coupling reactions, see the following literature: Henrion 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.

[0218] To avoid doubt, each embodiment described in relation to Q and L of the first and second aspects may be applied to the third aspect with any necessary modifications. For example, the complex may be selected from formulas IVa to IVk.

[0219] Every patent and non-patent document mentioned in this article is incorporated herein in its entirety by reference, just as the entire content of each document is presented in its entirety in this article.

[0220] The invention can be further understood by referring to the following terms.

[0221] Clause 1. By [Ni(L)] n [X)2] complex formation [Ni(L)] n A method for producing a [Ni(L)] complex, the method comprising: […]. n [X]2] complexes come into contact with the following substances:

[0222] (iii) (a) Reducing metals or bases; and

[0223] (d) A diol comprising a tertiary or ortho-hydroxyl structural moiety, wherein at least one of the hydroxyl structural moiety is conjugated with a π system;

[0224] or

[0225] (iv) (a) Reduction of metals; and

[0226] (d) Ketones containing a carbonyl structural moiety conjugated with the π system;

[0227] in:

[0228] Q is the ketone complexed with nickel or a ketone derived from the diol;

[0229] L is a monodentate, bidentate, or tridentate L-type ligand, wherein when L is monodentate, n is 2, and when L is bidentate or tridentate, n is 1; and

[0230] X is a monovalent or divalent monoanion ligand.

[0231] Clause 2. The method described in Clause 1, wherein:

[0232] (i) Q has equation (I):

[0233]

[0234] in:

[0235] R 1 and R 2 Each is independently selected from cyclic C6-C 18 Hydrocarbon group, C1-C 17 Heterocyclic group, C 1-6 Alkyl, C 2-6 alkenyl, C 4-6 Dienyl, C6 trienyl, C 2-6 alkynyl group, C 4-6 Diynyl and C6 triynyl, each of which is optionally composed of one or more compounds selected from cyclic C6-C 18 Hydrocarbon group, cyclic C3-C 17 heterohydrocarbon group, C 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Substitution of alkyl)amino groups, wherein the optional cyclic C6-C 18 Hydrocarbon groups and cyclic C3-C 17 The heteroalkyl substituent is optionally C 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Alkyl)amino substitution;

[0236] or

[0237] (ii) Q has equation (II):

[0238]

[0239] Where A is a cyclic C6-C 18 Hydrocarbon group or C3-C 17 Heterocyclic groups, each optionally surrounded by one or more cyclic C6-C groups. 18 Hydrocarbon group, cyclic C1-C 17 heterohydrocarbon group, C 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Substitution of alkyl)amino groups, wherein the optional cyclic C6-C 18 Hydrocarbon groups and cyclic C1-C 17 The heteroalkyl substituent is optionally C 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Alkyl)amino substitution; and wherein A comprises a π system conjugated with the carbonyl structural portion of formula (II).

[0240] Clause 3. The method according to Clause 1, wherein [Ni(L)] n (Q)] The complex has formula (II):

[0241]

[0242] in:

[0243] R 1 and R 2 Independently selected from phenyl, C 1-6 Alkyl, C 2-6 alkenyl, C4-6 Dienyl, C6 trienyl, C 2-6 alkynyl group, C 4-6 Diynyl and C6 triynyl, each of which is optionally radicalized by one or more groups selected from phenyl, C6 ... 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 The alkyl)amino group is substituted with a substituent, wherein the optional phenyl substituent is optionally C 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Alkyl)amino substitution.

[0244] Clause 4. The method described in accordance with Clause 2 or Clause 3, wherein R 1 and R 2 Each is an optionally substituted phenyl group.

[0245] Clause 5. The method described in Clause 4, wherein R 1 and R 2 Optionally selected by one or more of C 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Substitution of alkyl)amino groups.

[0246] Clause 6. The method described in Clause 3, wherein R 1 and R 2 It is phenyl.

[0247] Clause 7. The method according to any of the preceding clauses, wherein L is bonded to the nickel via phosphorus, nitrogen, oxygen and / or carbon atoms, for example, L is bonded to the nickel via phosphorus, nitrogen and / or oxygen atoms.

[0248] Clause 8. The method according to any one of Clauses 1-6, wherein:

[0249] L is monodentate and is bonded to the nickel via a phosphorus atom or a carbon atom;

[0250] L is bidentate and chelated with the nickel via phosphorus, nitrogen, carbon, and / or oxygen atoms; or

[0251] L is tridentate and chelated with the nickel via nitrogen, phosphorus and / or carbon atoms.

[0252] Clause 9. The method described in accordance with Clause 8, wherein:

[0253] L is monodentate and is selected from phosphine ligands and carbene ligands;

[0254] L is bidentate and contains two independent bonded structural moieties selected from phosphine, amine, imine, pyridine, and carbene; or

[0255] L is tridentate and contains three independent bonded structural moieties selected from phosphine, amine, imine, pyridine, and carbene.

[0256] Clause 10. The method according to any of the preceding clauses, wherein L is two-toothed or three-toothed and has a natural bite angle of at least 75°, for example, from 75° to 140°.

[0257] Clause 11. The method according to any one of Clauses 1-9, wherein L is a single tooth and has a Tolman cone angle of at least 120°, for example, 120° to 190°.

[0258] Clause 12. The method according to any of the preceding clauses, wherein L is selected from tri-ring C 5-6 Hydrophosphine, C 1-4 alkyl-di-cycloC 5-6 Hydrophosphine, tetraC 1-4 Alkyl C 2-4 alkylene diamine, penta-C 1-4 Alkyl C 2-4 alkyltriamines, C containing N,N 10 Heterocyclic bicyclic ligands, C containing N,N 12-14 Heterocyclic tricyclic ligands, bis(di-cyclic C) 5-6 (Hydrocarbon phosphine)C 2-4 Alkylene, bis(di-cycloC) 5-6 (Hydrocarbon-phosphine-) Tons, double (di-C) 1-4 Alkylphosphine Tons, double (two-ring C) 5-6 (Hydrophosphino)ferrocene, bis(di-C) 1-4 Alkylphosphinyl)ferrocene, bis(di-cycloC) 5-6 (Hydrophosphinophenyl) ether and bis(di-C) 1-4 Alkylphosphine phenyl ethers, each of which is optionally composed of one or more compounds selected from C 1-4 Alkyl, Halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Substitution of alkoxy and morpholino groups.

[0259] Clause 13. The method according to Clause 12, wherein L is selected from triphenylphosphine, bis(diphenylphosphino)propane, bis(diphenylphosphino)butane, bis(diphenylphosphino)ethane, bis(diphenylphosphino)ferrocene, bis(diphenylphosphino) Ton, tetramethylethylenediamine, pentamethyldiethylenetriamine, bipyridine, di-tert-butyl-bipyridine, bis(dicyclohexylphosphine)ethane, bis(diisopropylphosphine)ferrocene, bis(di-tert-butylphosphine)ferrocene, diadamantylmorpholinophenylphosphine, methyldiphenylphosphine and tricyclohexylphosphine.

[0260] Clause 14. The method described in any of the preceding clauses, wherein X is chloride, bromide or iodide, such as chloride.

[0261] Clause 15. The method according to any of the preceding clauses, wherein the reducing metal comprises a Group I metal.

[0262] Clause 16. The method according to Clause 14, wherein the method includes contacting with any one of sodium metal, lithium metal, potassium metal, cesium metal, rubidium metal and a graphite interlayer compound containing potassium or lithium.

[0263] Clause 17. The method according to any of the preceding clauses, wherein the base has a conjugate acid with a pKa of ≥9.5 or ≥15.

[0264] Clause 18. The method according to any of the preceding clauses, wherein the base is selected from potassium tert-butoxide, lithium tert-butoxide, sodium tert-butoxide, sodium phenolate, potassium bis(trimethylsilyl)amino, lithium bis(trimethylsilyl)amino, sodium bis(trimethylsilyl)amino, C 1-4 Alkyl magnesium chloride, C 5-6 Hydrocarbon-based magnesium chloride, C 1-4 Alkyl lithium, C 1-4 Alkyl potassium, C 1-4 Alkyl sodium, di(C) 1-4 Alkyl)aminolithium, di(C) 1-4 Alkyl)aminopotassium, di(C) 1-4 Sodium alkylamino, tetracarbonyl 1-4 Alkyl C 5-6 Hydrocarbon-based lithium, tetracarbon 1-4 Alkyl C 5-6 Hydrocarbon potassium, tetracarbon 1-4 Alkyl C 5-6 Hydrocarbon sodium.

[0265] Clause 19. The method according to any of the preceding clauses, wherein the contact is in an aprotic solvent.

[0266] Clause 20. The method according to Clause 19, wherein the aprotic solvent is selected from THF, toluene, diethyl ether, dimethoxyethane, hexane, 2-methyltetrahydrofuran, methyl tert-butyl ether, and cyclopentylmethyl ether.

[0267] Clause 21. The method according to any of the preceding clauses, wherein the base, reducing metal, ketone, and diol are relative to [Ni(L)] n [X]2] complex is in molar excess.

[0268] Clause 22. The method according to any of the preceding clauses, wherein, relative to the [Ni(L)] n The (X)2] complex uses about 2 to about 3 molar equivalents of base.

[0269] Clause 23. The method according to any of the preceding clauses, wherein, relative to the [Ni(L)] n The (X)2] complex uses about 2 to about 5 molar equivalents of reducing metal.

[0270] Clause 24. The method according to any of the preceding clauses, wherein, relative to the [Ni(L)] n The (X)2] complex uses a ketone in greater than about 2 molar equivalents, for example, about 2.05 to about 8 molar equivalents of the ketone.

[0271] Clause 25. The method according to any of the preceding clauses, wherein, relative to the [Ni(L)] n The (X)2] complex uses about ≥1.01 to about 1.5 molar equivalents of the diol, for example about 1.05 molar equivalents of the diol.

[0272] Clause 26. The method described pursuant to any of the preceding clauses, wherein:

[0273] (i) the diol and the reducing metal or base;

[0274] or

[0275] (ii) the ketone and the reducing metal.

[0276] In relation to the [Ni(L)] n [X]2] Contact is performed before contact with the complex.

[0277] Clause 27. The method according to any of the preceding clauses, wherein [Ni(L)] n The (X)2] complex is contacted with the diol.

[0278] Clause 28. [Ni(L)] n [Q] complex, wherein:

[0279] Q is a ketone that is complexed with nickel;

[0280] L is a monodentate, bidentate, or tridentate L-type ligand selected from tricyclic C 5-6 Hydrophosphine, C 1-4 alkyl-di-cycloC 5-6Hydrophosphine, tetraC 1-4 Alkyl C 2-4 alkylene diamine, penta-C 1-4 Alkyl C 2-4 alkyltriamines, C containing N,N 12-14 Heterocyclic tricyclic ligands, bis(di-cyclic C) 5-6 (Hydrocarbon phosphine)C 2-4 Alkylene, bis(di-cycloC) 5-6 (Hydrocarbon-phosphine-) Tons, double (di-C) 1-4 Alkylphosphine Tons, double (two-ring C) 5-6 (Hydrophosphino)ferrocene, bis(di-C) 1-4 Alkylphosphinyl)ferrocene, bis(di-cycloC) 5-6 (Hydrophosphinophenyl) ether and bis(di-C) 1-4 Alkylphosphine phenyl ethers, each of which is optionally composed of one or more compounds selected from C 1-4 Alkyl, Halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Substitution of alkoxy and morpholino groups,

[0281] Alternatively, L is a C that contains N,N 10 Heterocyclic bicyclic ligands, optionally using one or more selected from C 1-3 Alkyl, Halogenated, C 1-4 Halogenated alkyl, hydroxyl and C 1-4 Alkoxy substituents, and

[0282] When L is a single tooth, n is 2, and when L is a double or triple tooth, n is 1.

[0283] Clause 29. The complex as described in Clause 28, wherein Q is as defined in any one of Clauses 2-6.

[0284] Clause 30. Use of complexes as catalysts, such as cross-coupled catalysts, as defined in Clause 28 or Clause 29. Detailed Implementation

[0285] Example

[0286] The invention can be further understood by referring to the following embodiments.

[0287] General considerations

[0288] The following experiments are sensitive to air and moisture; therefore, degassed anhydrous solvents are used. Reactions are carried out in a glove box or using Schlenk wire techniques and related equipment.

[0289] NMR codes beginning with B and D are used on different spectrometers. The differences between the two spectrometers are typically... 1 H ~ 0.5-1ppm adjustment and 31 P ~ 1-5ppm.

[0290] synthesis

[0291] Typical pathway (free radical anion pathway)

[0292] 1) Ketone + Reduced Metal

[0293]

[0294] Ketones (e.g., benzophenone, relative to [(L)]) n [NiX2] (3 equivalents) was added together with a solvent (e.g., anhydrous tetrahydrofuran (THF)) into a reaction vessel containing a magnetic stir bar, followed by the slow addition of a reducing metal (e.g., sodium, relative to [(L)]). n [NiX2] (2.4 equivalents) was used to generate blue radical anionic species. Once stirred at room temperature for at least 10 minutes, [(L)] n NiX2] was added to the container and stirred at room temperature for 3–12 hours (until the reaction endpoint was confirmed). The resulting reaction mixture was then filtered, and the components containing [(L)] were separated. n The filtrate of Ni(Q)].

[0295] 2) Diol + Reduced Metal

[0296]

[0297] Diols (e.g., pinacol, relative to [(L)]) n [NiX2] (1.05 equivalent) was added together with a solvent (e.g., anhydrous THF) to a reaction vessel containing a magnetic stir bar. The reaction vessel was then stirred at a suitable temperature for >10 minutes to suspend and dissolve the relevant materials. A reducing metal (relative to [(L)]) was added to the resulting reaction mixture. n [NiX2] was 2.4 equivalents), and the reaction was stirred for 3-12 hours (until the endpoint of the reaction was confirmed). Then, [(L)] was separated from the resulting reaction mixture. n Ni(Q)] complex.

[0298] 3) Diol + Base

[0299]

[0300] Diols (e.g., pinacol, relative to [(L)]) n[NiX2] (1.05 equivalent) was added together with a solvent (e.g., anhydrous THF) to a reaction vessel containing a magnetic stir bar. The reaction vessel was then stirred at a suitable temperature for >10 minutes to suspend and dissolve the material. An alkaline solution (e.g., a metal alkoxide base, relative to [(L)]) was then added. n [NiX2] is 2.2 equivalents), and the reaction is stirred for 3-12 hours (until the endpoint of the reaction is confirmed). Then, [(L)] is separated from the resulting reaction mixture. n Ni(Q)] complex.

[0301] Typical procedure (dianion pathway)

[0302] 4) Ketones + reducing metals

[0303]

[0304] Ketones (e.g., benzophenone, relative to [(L)]) n [NiCl2] (1.5 equivalents) was added together with a solvent (e.g., anhydrous THF) to a reaction vessel containing a magnetic stir bar, followed by the slow addition of a reducing metal (e.g., sodium, relative to [(L)]). n [NiCl2] (3 equivalents) to produce a purple dianionic species. Once stirred at room temperature for at least 10 minutes, [(L)] n NiCl2] was added to the container and stirred at room temperature for 3–12 hours (until the reaction endpoint was confirmed). The resulting reaction mixture was then filtered, and the components containing [(L)] were separated. n The filtrate of Ni(Q)].

[0305] 5) Diol + Reduced Metal

[0306]

[0307] The diol (e.g., pinacol, 0.55 equivalents, relative to [(L)]) n NiCl2]), [(L) n NiCl2 was added along with a solvent (e.g., anhydrous THF) to a reaction vessel containing a magnetic stir bar. The reaction vessel was then stirred at a suitable temperature for >10 minutes to suspend and dissolve the materials. A reducing metal (relative to [(L)]) was added to the resulting reaction mixture. n [NiCl2] (3 equivalents) was used, and the reaction was stirred for 3-12 hours (until the endpoint of the reaction was confirmed). Then, [(L)] was separated from the resulting reaction mixture. n Ni(Q)] complex.

[0308] result

[0309] Initial results were obtained using method 1) described above, along with benzophenone (BP) and sodium metal in THF and various L-ligands. These results are shown in Table 1. Various nickel(O) ketone complexes were successfully synthesized and characterized.

[0310] Table 1 - Initial results using benzophenone (BP) and sodium metal in Method 1).

[0311]

[0312] Using the same method, but with a reducing metal:ketone ratio (sodium metal:benzophenone in this case) of 2.4:6, additional complexes were synthesized, and the results are shown in Table 2.

[0313] Table 2 - Results of using benzophenone (BP) and sodium metal in a 2.4:6 ratio in Method 1).

[0314]

[0315] Then reaction method 1 is used, where [(L)] n The L in [NiCl2] represents different bis(diphenylphosphine) alkane ligands. The results are shown in Table 3.

[0316] Table 3 - Results of using method 1) and benzophenone (BP) and sodium metal in a 2.4:5 ratio, LT = low Temperature approximately -30°C, SA = slow addition, i.e., adding the nickel complex in 4-5 equal portions over 15-20 minutes, ON = overnight, and S' A = Slowly add Ni(II) to the free radical solution, that is, add the nickel complex in 8-10 equal portions over 30-40 minutes.

[0317]

[0318] Synthetic route 3)

[0319] This work involved using a suitable base (e.g., pKa > 15) with benzimidol (BPL) and allowing for the formation of more nickel(0) ketone complexes. The results are shown in Table 4.

[0320] Table 4 - Results of using method 3), the reaction was carried out at different scales (1 mmol or less, with exceptions). [(dtBuBIPY)NiCl 2 ] and [(PPh 3 ) 2 NiCl 2 (The concentrations were 10 mmol and 30 mmol, respectively.)

[0321]

[0322] Different reducing metals and benzophenone, method 1)

[0323] The formation of the desired product was evaluated using different reducing metals (Li metal (2.4 equivalents = 8.4 mg), K metal (2.4 equivalents = 47 mg), KC8 (2.4 equivalents = 163 mg)) with benzophenone (550 mg) and [(PPh3)2NiCl2] (383 mg). The reducing metal was added to a solution containing the desired equivalent of benzophenone, which was stirred at room temperature before the addition of the starting complex. The results are shown in Table 5.

[0324] Table 5 - Results using method 1) and various reducing metals. The reaction was carried out in THF at a scale of 0.5 mmol. Okay. Through the reaction mixture 31 P NMR analysis of the target complex [(PPh)] 3 ) 2 The product formation of Ni(BP)].

[0325]

[0326] Different reducing metals and benzinolide, method 2)

[0327]

[0328]

[0329] The formation of the desired products was evaluated when different reducing metals were used. The metals used were: Li metal (2 equivalents = 2.8 mg, 4 equivalents = 5.6 mg), Na metal (2 equivalents = 9.2 mg, 4 equivalents = 18.4 mg), K metal (2 equivalents = 15.6 mg, 4 equivalents = 31.2 mg), KC8 (2 equivalents = 54 mg, 4 equivalents = 108 mg), and benzipineol (74 mg) and [(PPh3)2NiCl2] (153 mg). The reducing metals were added to a THF solution containing [(PPh3)2NiCl2] and benzipineol under magnetic stirring in an argon-filled glove box at room temperature. The results are shown in Table 6.

[0330] Table 6 - Results using method 2) and various reducing metals. The reaction was carried out in THF at a scale of 0.2 mmol. Okay. Through the reaction mixture 31 P NMR analysis of the target complex [(PPh)] 3 ) 2 The product formation of Ni(BP)].

[0331]

[0332] Different strong bases and benzinolide, method 3)

[0333]

[0334] The formation of the desired product was evaluated using different strong bases with benzipineol (74 mg) and [(PPh3)2NiCl2] (153 mg). The bases were added to a THF solution containing [(PPh3)2NiCl2] and benzipineol under magnetic stirring in an argon-filled glove box at room temperature. The results are shown in Table 7.

[0335] Table 7 - Results using method 3) and various reducing metals. The reaction was carried out in THF at a scale of 0.2 mmol. Okay. Through the reaction mixture 31 P NMR analysis of the target complex [(PPh)] 3 ) 2 The product formation of Ni(BP)].

[0336]

[0337] Product characterization

[0338] The following materials were separated from the various reactions using methods 1) to 3).

[0339] N-coordinated complexes

[0340]

[0341] Separation was achieved from a reaction using 3 equivalents of sodium metal and 1.5 equivalents of benzophenone at 3 mmol (yield 34%).

[0342]

[0343] Obtain the crystal structure and confirm the identity of the product.

[0344]

[0345] Separation was achieved by reacting 4 equivalents of sodium metal and 2 equivalents of benzophenone at 1 mmol (yield approximately 25%).

[0346]

[0347] Obtain the crystal structure and confirm the identity of the product.

[0348]

[0349] Separation was achieved by reacting 2.4 equivalents of sodium metal and 3 equivalents of benzophenone at 0.5 mmol (yield 10%).

[0350] Obtain the crystal structure and confirm the identity of the product.

[0351]

[0352] Separation was achieved by using 2.4 equivalents of sodium metal and 3 equivalents of benzophenone in a reaction at 1 mmol (yield 67%).

[0353]

[0354] P-coordinated complexes

[0355]

[0356]

[0357] Obtain the crystal structure and confirm the identity of the product.

[0358]

[0359]

[0360] Obtain the crystal structure and confirm the identity of the product.

[0361]

[0362]

[0363] Obtain the crystal structure and confirm the identity of the product.

[0364]

[0365]

[0366] Obtain the crystal structure and confirm the identity of the product.

[0367]

[0368] Separation was achieved from a reaction using 2.4 equivalents of sodium metal and 3 equivalents of benzophenone at 5 mmol (yield 90-95%).

[0369]

[0370] Obtain the crystal structure and confirm the identity of the product.

[0371]

[0372] Separation was achieved from a reaction using 2.4 equivalents of sodium metal and 3 equivalents of benzophenone at 0.8 mmol (yield 90-95%).

[0373]

[0374] In-situ detection and characterization of products

[0375] For some reactions, 31 P NMR was used to detect product formation in situ.

[0376]

[0377]

[0378] Cross-coupling reaction of (hetero)aryl halides with magnesium aryl halide reagents catalyzed by the nickel complex

[0379] Overview

[0380] All reactions were prepared under anhydrous and oxygen-free conditions using an inert atmosphere glove box with argon as the working gas; typical oxygen and water contents were less than 1 ppm. Anhydrous tetrahydrofuran was obtained by solvent purification system (<10 ppm water according to Karl-Fischer titration). Aryl magnesium bromide reagents were prepared from the corresponding aryl bromide and elemental magnesium, and their concentrations were determined by iodine titration in THF solution.

[0381] Reaction setup

[0382] A known concentration of feedstock solutions of [Ni(Ph2CO)(PPh3)2] and aryl halides is prepared by dissolving the corresponding material of known mass or volume in anhydrous THF.

[0383] The vials (4 mL) were filled with anhydrous THF in a selected volume to achieve a final reaction volume of 1 mL. Then, appropriate volumes of: aryl halide feedstock solution to achieve a final concentration in the range of 0.15–0.3 mol / L; catalyst feedstock solution to achieve a final concentration in the range of 0.003–0.03 mol / L; and aryl magnesium halide feedstock solution to achieve a final concentration in the range of 0.15–0.3 mol / L.

[0384] The vials were capped with screw caps fitted with diaphragms, removed from the glove box, and heated for 18 hours in a planetary mixing environment within a machined 24-well aluminum block connected to a Thermomixer C set to 30°C. Each reaction was then quenched by the addition of ethanol; a known volume of aliquots was diluted in ethyl acetate with a known amount of dodecane, and the solution was analyzed by gas chromatography-flame ionization detection (GC-FID). Each reaction was performed in duplicate.

[0385] analyze

[0386] All analyses were performed using an Agilent 7890A gas chromatography (GC) system equipped with an HP-5 30m × 0.320mm × 0.25μm column.

[0387] Real samples of each product were prepared independently, and their identity and purity were verified through [method / method / etc.]. 1 H and 13 C{ 1 H NMR analysis and GC-FID analysis confirmed the results.

[0388] The real standard is used to calibrate GC-FID relative to the dodecane standard.

[0389] The reaction results were determined by integrating the peaks corresponding to dodecane (of known concentration) and the analyte under consideration, and applying a response factor determined by the calibration process to obtain the concentration of the analyte. This information, along with the known initial concentration of the aryl halogen, enabled the calculation of the reaction yield.

[0390] reaction results

[0391]

[0392]

[0393]

[0394]

[0395] [Ni(Ph2CO)(PPh3)2] has thus been shown to be an effective catalyst for representative cross-coupling reactions involving aryl halides or heteroaryl halides with magnesium aryl halides, yielding high yields in both reactions.

[0396] Additional examples

[0397] Note - All J values ​​are averaged to the nearest integer value.

[0398] Reduction reactions using different X anion ligands

[0399] Two different procedures were used for the reduction of various Ni(II) species, as described below.

[0400] 1. Using the radical anionic pathway of ketones and reducing metals: 40% Na / oil dispersion (70 mg) was added to a 14 mL flask containing benzophenone (270 mg) in 8 mL of anhydrous tetrahydrofuran (THF) under magnetic stirring. Then, 0.5 mmol of [(PPh3)2Ni(X)2]X=Br (372 mg), I (419 mg), or NO3 (354 mg) was added to the mixture under stirring. The color change was recorded, and aliquots (~0.3 mL) were obtained and mixed with 0.3 mL of deuterated solvent C6D6, followed by NMR analysis.

[0401] 2. Radical anion pathway using diols and bases: Add 0.5 mmol of [(PPh3)2Ni(X)2]X=Br (372 mg), I (419 mg), or NO3 (354 mg) to a 14 mL vial containing benzinolide (275 mg) in 7 mL of anhydrous tetrahydrofuran (THF) with magnetic stirring. Then add sodium tert-butoxide (0.8 mL–2 M) to the mixture with stirring. Record the color change and obtain aliquots (~0.3 mL), which are then mixed with 0.3 mL of deuterated solvent C6D6 and analyzed by NMR.

[0402] The reduction of [(PPh3)2NiBr2] by procedures 1 and 2 generates [(PPh3)2Ni(BP)]:

[0403] 1. (E81835): 31 P{ 1 H} NMR (C6D6); dd 36.28-36.04, 30.82-30.58 (J = 50Hz)

[0404] 2. (E81839) 31 P{ 1 H} NMR (C6D6); dd 36.28-36.04, 30.82-30.58 (J = 50 Hz)

[0405] The reduction of [(PPh3)2NiI2] in procedure 2 generates [(PPh3)2Ni(BP)].

[0406] 2. (E81840) 31 P{ 1 H} NMR (C6D6); dd 36.28-36.04, 30.82-30.57 (J = 50 Hz)

[0407] [(PPh3)2Ni(NO3)2] is generated by the reduction of [(PPh3)2Ni(BP)] through procedures 1 and 2.

[0408] 1. (E81835) 31 P{ 1 H} NMR (C6D6); dd 36.22-35.97, 30.78-30.58 (J = 50 Hz)

[0409] 2. (E81839) 31 P{ 1H} NMR (C6D6); dd 36.25-36.00, 30.79-30.55 (J = 50 Hz)

[0410] [(TMEDA)Ni(OAc)2] is generated by the reduction of [(TMEDA)Ni(BP)] in program 1. 1 H NMR analysis and detection.

[0411] Reduction reactions using different L-ligands

[0412] The reduction of [(DavePhos)NiCl2] was carried out by mixing sodium metal (60 mg) and benzophenone (365 mg) in a 14 mL vial containing 8 mL of tetrahydrofuran (THF), where DavePhos is 2-dicyclohexylphosphino-2'-( N,N (-dimethylamino)biphenyl. After complete dissolution of sodium metal and formation of the corresponding free radical anion, [(DavePhos)NiCl2] (523 mg) was added in a single-part batch with stirring. The color change was recorded, and aliquots (~0.3 mL) were obtained and mixed with 0.3 mL of deuterated solvent C6D6, followed by NMR analysis.

[0413] [(DavePhos)Ni(BP)](E82093) was formed. 31 P{ 1 H NMR (C6D6); s, 35.38.

[0414] The reduction of [(CP)NiCl2] was successful, and the product was confirmed by comparison with the NMR spectrum of the corresponding product (obtained by replacing the CP ligand with [(PPh3)2Ni(BP)]). The substitution involved mixing CP BArF salt and KO in a deuterated solvent. t Bu and [(PPh3)2Ni(BP)]. In this reaction, a free CP ligand is generated, and the triphenylphosphine ligand is substituted from the Ni(0) complex. CP is 1-(2-diphenylphosphinoethyl)-3-(2,4,6-trimethylphenyl)imidazolium-2-ylidene (ylide), as shown below:

[0415] .

[0416] The reduction process was carried out "in situ". Under magnetic stirring, [(Lut)₂NiCl₂](68mg) and [(CP)(HBArF) were mixed. 24[(CP)NiCl2] was generated by reacting sodium tert-butoxide (245 mg) with sodium tert-butoxide (0.3 mL–2 M) in anhydrous THF (2 mL). This is the 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) under magnetic stirring. This is the second reaction mixture. The first reaction mixture was drawn up using a syringe and needle and added to the second reaction mixture.

[0417] [(CP)Ni(BP)] reduces (E82091) 31 P{ 1 H NMR (C6D6); s, 29.89

[0418] [(CP)Ni(BP)] replaces (D394192) 31 P{ 1 H NMR (C6D6); s, 30.17

[0419] General reduction procedure for screening Q-ligands

[0420] Prior to reaction with [(PPh3)2NiCl2], ketones were screened for reaction with sodium metal to generate radical anionic species. 2 mmol of each ketone was reacted with sodium (40% Na / oil (138 mg) or Na metal (60 mg)) and the mixture was magnetically stirred in 8 mL of tetrahydrofuran (THF). After observing a color change and complete dissolution of the sodium metal (which had reacted to form the corresponding radical anion), the mixture was reacted with [(PPh3)2NiCl2] (654 mg) (unless otherwise noted). The color change was recorded, and aliquots (~0.3 mL) were obtained and mixed with 0.3 mL of deuterated solvent C6D6 for NMR analysis.

[0421] Screening for different ketones to generate [(L)] n Ni(ketone)]

[0422] 4-Benzoylbiphenyl: Successful reduction of [(PPh3)2NiCl2] yielded [(PPh3)2Ni(4-benzoylbiphenyl)] (E81985). 31 P{ 1 H} NMR (C6D6); dd 36.03-35.79, 31.15-30.91 (J = 49 Hz).

[0423] Phenyl(4-tolyl)methyl ketone: Successful reduction of [(PPh3)2NiCl2] yielded [(PPh3)2Ni(phenyl(4-tolyl)methyl ketone)] (E81986). 31P{ 1 H} NMR (C6D6); dd 36.19-35.93, 30.72-30.46 (J = 53 Hz).

[0424] 2-Benzoylpyridine: [(DPPF)NiCl2] was successfully reduced to give [(DPPF)Ni(2-benzoylpyridine)] (E82066). 31 P{ 1 H NMR (C6D6); two singlets at 30.74 and 24.84 (1:1 integral).

[0425] 1'-acetylnaphthalene: [(PPh3)2NiCl2] was successfully reduced to [(PPh3)2Ni(1'-acetylnaphthalene)] (E82003). 31 P{ 1 H NMR (C6D6); two broad singlets at 30.13 and 26.96.

[0426] Isobutyrobenzene: Successful reduction of [(PPh3)2NiCl2] yielded [(PPh3)2Ni(isobutyrobenzene)] (E82067). 31 P{ 1 H} NMR (C6D6); dd 38.32-38.11, 28.27-28.06 (J=42Hz).

[0427] Cyclopentylphenyl ketone: Successful reduction of [(PPh3)2NiCl2] yielded [(PPh3)2Ni(cyclopentylphenyl ketone)] (E82068). 31 P{ 1 H} NMR (C6D6); dd 38.46-38.24, 28.18-27.93 (J=45Hz).

[0428] Cyclohexylphenyl ketone: Successful reduction of [(PPh3)2NiCl2] yielded [(PPh3)2Ni(cyclohexylphenyl ketone)] (E82069). 31 P{ 1 H} NMR (C6D6); dd 37.88-37.65, 27.74-27.49 (J=51Hz).

[0429] 9-fluorenone: [(PPh3)2NiCl2] was successfully reduced to [(PPh3)2Ni(9-fluorenone)] (E81909). 31 P{ 1 H} NMR (C6D6); dd 40.04-39.84, 33.43-33.23 (J=42Hz).

[0430] 9H- Ton-9-one: Successful reduction of [(PPh3)2NiCl2] yielded [(PPh3)2Ni(9H- ] [Ton-9-one](E82004). 31 P{ 1 H NMR (C6D6); two broad singlets at 35.92 and 31.64.

[0431] 10,10-Dimethyl-9-10-dihydroanthraphen-9-one: Successful reduction of [(PPh3)2NiCl2] yielded [(PPh3)2Ni(10,10-dimethyl-9-10-dihydroanthraphen-9-one)] (E82006). 31 P{ 1 H} NMR (C6D6); dd 36.39-36.13, 33.49-33.27 (J=49Hz).

[0432] 10,11-Dihydro-5H-Dibenzo[a,d][7]cycloen-5-one: Successful reduction of [(PPh3)2NiCl2] yielded [(PPh3)2Ni(10,11-Dihydro-5H-Dibenzo[a,d][7]cycloen-5-one)] (E82007). 31 P{ 1 H} NMR (C6D6); dd37.07-36.82, 33.51-33.27 (J=50Hz).

Claims

1. From [Ni(L) n [X)2] complex formation [Ni(L)] n A method for producing a [Ni(L)] complex, the method comprising: […]. n [X]2] complexes come into contact with the following substances: (v) (a) Reducing metals or bases; and (e) A diol containing a tertiary or ortho-hydroxyl structural moiety, wherein at least one of the carbon atoms bonded to the tertiary or ortho-hydroxyl structural moiety is adjacent to the π system. or (vi) (a) reducing metals; and (e) Ketones containing a carbonyl moiety conjugated with the π system; in: Q is the ketone complexed with nickel or a ketone derived from the diol; L is a monodentate, bidentate, or tridentate L-type ligand, wherein when L is monodentate, n is 2, and when L is bidentate or tridentate, n is 1; and X is a monovalent or divalent monoanion ligand.

2. The method according to claim 1, wherein: (iii) Q has equation (I): in: R 1 and R 2 Each is independently selected from cyclic C5-C 18 Hydrocarbon group, C1-C 17 Heterocyclic group, C 1-6 Alkyl, C 2-6 alkenyl, C 4-6 Dienyl, C6 trienyl, C 2-6 alkynyl group, C 4-6 Diynyl and C6 triynyl, each of which is optionally composed of one or more compounds selected from cyclic C3-C6 groups. 18 Hydrocarbon group, cyclic C3-C 17 heterohydrocarbon group, C 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Substitution of alkyl)amino groups, wherein the optional cyclic C3-C 18 Hydrocarbon groups and cyclic C3-C 17 The heteroalkyl substituent is optionally C 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Alkyl)amino substitution; or (iv) Q has equation (II): Where A is a cyclic C6-C 18 Hydrocarbon group or C3-C 17 Heterocyclic groups, each optionally surrounded by one or more cyclic C3-C groups. 18 Hydrocarbon group, cyclic C1-C 17 heterohydrocarbon group, C 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Substitution of alkyl)amino groups, wherein the optional cyclic C3-C 18 Hydrocarbon groups and cyclic C1-C 17 The heteroalkyl substituent is optionally C 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Alkyl)amino substitution; and wherein A comprises a π system conjugated with the carbonyl structural portion of formula (II).

3. The method according to claim 1, wherein [Ni(L)] n [Q] The complex has formula (IIIa), (IIIc) or (IIId): in: R 1 and R 2 Independently selected from phenyl, naphthyl, pyridyl, anthraceneyl, phenanthrene, C 5-6 cycloalkyl, C 1-6 Alkyl, C 2-6 alkenyl, C 4-6 Dienyl, C6 trienyl, C 2-6 alkynyl group, C 4-6 Diynyl and C6 triynyl, each of which is optionally radicalized by one or more groups selected from phenyl, C6 ... 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 The alkyl)amino group is substituted with a substituent, wherein the optional phenyl substituent is optionally C 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Alkyl)amino substitution; Each ring B is independently selected from benzene, naphthalene, and C3-C. 17 heteroaromatic hydrocarbons, each optionally composed of one or more cyclic C3-C... 18 Hydrocarbon group, cyclic C1-C 17 heterohydrocarbon group, C 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Substitution of alkyl)amino groups, wherein the optional cyclic C3-C 18 Hydrocarbon groups and cyclic C1-C 17 The heteroalkyl substituent is optionally C 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Alkyl)amino substitution; Each ring C is arbitrarily selected, and when present, is independently chosen from the cyclic C5-C. 11 Hydrocarbons or C3-C 10 Heterocyclic rings, each optionally separated by one or more rings selected from cyclic C3-C 18 Hydrocarbon group, cyclic C1-C 17 heterohydrocarbon group, C 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Substitution of alkyl)amino groups, wherein the optional cyclic C3-C 18 Hydrocarbon groups and cyclic C1-C 17 The heteroalkyl substituent is optionally C 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Alkyl)amino substitution; R f Selected from cyclic C3-C 18 Hydrocarbon group, cyclic C1-C 17 heterohydrocarbon group, C 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Alkyl)amino, wherein the optional cyclic C3-C 18 Hydrocarbon groups and cyclic C1-C 17 The heteroalkyl substituent is optionally C 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Alkyl)amino substitution; 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 according to claim 2 or 3, wherein: (i) R 1 and R 2 Each is independently selected from phenyl, naphthyl, pyridyl, anthraceneyl, phenanthrene, C 5-6 cycloalkyl and C 1-6 Alkyl groups, each of which may optionally be substituted; and / or (ii) Ring C is present and rings B and C are each selected from benzene and naphthalene, for example, benzene, each of which is optionally substituted; and R f Selected from C 1-4 Alkyl, halogroup and C 1-4 Halogenated alkyl groups.

5. The method according to any one of claims 2-4, wherein R 1 and R 2 Optionally selected by one or more of C 1-4 Alkyl, C 2-6 alkenyl, halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Alkoxy and di(C 1-4 Substitution of alkyl)amino groups.

6. The method according to any one of claims 2-4, wherein R 1 and R 2 One is phenyl or pyridyl and the other is selected from phenyl, naphthyl, pyridyl, cyclopentyl, cyclohexyl and C 1-4 Alkyl groups, each of which may be optionally substituted; and B and C are each benzene.

7. The method according to any of the preceding claims, wherein L is bonded to the nickel via phosphorus, nitrogen, oxygen and / or carbon atoms, for example, L is bonded to the nickel via phosphorus, nitrogen and / or oxygen atoms.

8. The method according to any one of claims 1-6, wherein: L is monodentate and is bonded to the nickel via a phosphorus atom or a carbon atom; L is bidentate and chelated with the nickel via phosphorus, nitrogen, carbon, and / or oxygen atoms; or L is tridentate and chelated with the nickel via nitrogen, phosphorus and / or carbon atoms.

9. The method according to claim 8, wherein: L is monodentate and is selected from phosphine ligands and carbene ligands; L is bidentate and contains two independent bonded structural moieties selected from phosphine, amine, imine, pyridine, and carbene; or L is tridentate and contains three independent bonded structural moieties selected from phosphine, amine, imine, pyridine, and carbene.

10. The method according to any of the preceding claims, wherein L is bidental or tridental and has a natural bite angle of at least 75°, for example, from 75° to 140°.

11. The method according to any one of claims 1-9, wherein L is a single tooth and has a Tolman cone angle of at least 120°, for example, 120° to 190°.

12. The method according to any of the preceding claims, wherein L is selected from tri-C 1-6 Alkylphosphine, tri-cyclic C 5-6 Hydrophosphine, C 1-4 alkyl-di-cycloC 5-6 Hydroxyphosphine, N,N,N',N'-tetrachlorophosphine 1-4 Alkyl C 2-4 alkylene diamine, N,N,N',N'',N''-pentacarbonyl 1-4 Alkyl C 2-4 alkyltriamines, C containing N,N 10 Heterocyclic bicyclic ligands, C containing N,N 12-14 Heterocyclic tricyclic ligands, bis(di-cyclic C) 5-6 (Hydrocarbon phosphine)C 2-4 Alkylene, bis(di-cycloC) 5-6 (Hydrocarbon phosphine) Tons, double (di-C) 1-4 Alkylphosphine Tons, double (two-ring C) 5-6 (Hydrophosphino)ferrocene, bis(di-C) 1-4 Alkylphosphinyl)ferrocene, bis(di-cycloC) 5-6 (Hydrophosphinophenyl) ether and bis(di-C) 1-4 Alkylphosphine phenyl ethers, each of which is optionally composed of one or more compounds selected from C 1-4 Alkyl, Halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Substitution of alkoxy and morpholino groups; L is two C 1-4 Alkyl-phosphino-biphenyl or di-cyclic C 5-6 Hydroxylphosphine-biphenyl, wherein each biphenyl is optionally made of one or more compounds selected from C 1-4 Alkyl, di(C) 1-4 alkyl)amino and C 1-4 Substitution of alkoxy groups; L is two C 1-4 Alkyl-phosphino-biphenyl or di-cyclic C 5-6 Hydroxylphosphine-biphenyl, wherein each biphenyl is optionally made of one or more compounds selected from C 1-4 Alkyl, di(C) 1-4 alkyl)amino and C 1-4 Substitution of alkoxy groups; or L contains bicyclic C 5-6 The alkylphosphine-bonded portion is optionally linked to the N-heterocyclic carbene-bonded portion via an alkyl linker.

13. The method according to claim 12, wherein L is selected from triphenylphosphine, bis(diphenylphosphino)propane, bis(diphenylphosphino)butane, bis(diphenylphosphino)ethane, bis(diphenylphosphino)ferrocene, bis(diphenylphosphino) Ton, Tetramethylethylenediamine, Pentamethyldiethylenetriamine, Bipyridine, Di-tert-butyl-bipyridine, Bis(dicyclohexylphosphine)ethane, Bis(diisopropylphosphine)ferrocene, Bis(di-tert-butylphosphine)ferrocene, Diadamantylmorpholinophenylphosphine, Methyldiphenylphosphine, Tricyclohexylphosphine, Dicyclohexylphosphine-2′-( N,N -dimethylamino)biphenyl and 1-(2-diphenylphosphinoethyl)-3-(2,4,6-trimethylphenyl)imidazol-2-ylene.

14. The method according to any of the preceding claims, wherein X is selected from halogen, acetate and nitrate, and optionally, wherein X is chloride, bromide or iodide, such as chloride.

15. The method according to any of the preceding claims, wherein the reducing metal comprises a Group I metal.

16. The method of claim 14, wherein the method comprises contacting with any one of sodium metal, lithium metal, potassium metal, cesium metal, rubidium metal and a graphite interlayer compound containing potassium or lithium.

17. The method according to any of the preceding claims, wherein the base has a conjugate acid with a pKa of ≥9.5 or ≥15.

18. The method according to any of the preceding claims, wherein the base is selected from potassium tert-butoxide, lithium tert-butoxide, sodium tert-butoxide, sodium phenolate, potassium bis(trimethylsilyl)amino, lithium bis(trimethylsilyl)amino, sodium bis(trimethylsilyl)amino, C 1-4 Alkyl magnesium chloride, C 5-6 Hydrocarbon-based magnesium chloride, C 1-4 Alkyl lithium, C 1-4 Alkyl potassium, C 1-4 Alkyl sodium, di(C) 1-4 Alkyl)aminolithium, di(C) 1-4 Alkyl)aminopotassium, di(C) 1-4 Sodium alkylamino, tetracarbonyl 1-4 Alkyl C 5-6 Hydrocarbon-based lithium, tetracarbon 1-4 Alkyl C 5-6 Hydrocarbon potassium, tetracarbon 1-4 Alkyl C 5-6 Hydrocarbon sodium.

19. The method according to any of the preceding claims, wherein the contact 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 cyclopentylmethyl ether.

20. The method according to any of the preceding claims, wherein the alkali, reducing metal, ketone, and diol are relative to [Ni(L)] n [X]2] complex is in molar excess, optionally, wherein: (i) relative to the [Ni(L)] n [X]2] The complex is made using about 2 to about 3 molar equivalents of base; or (ii) relative to the [Ni(L)] n The (X)2] complex uses about 2 to about 5 molar equivalents of reducing metal.

21. The method according to any of the preceding claims, wherein: (i) relative to the [Ni(L)] n [X]2] The complex uses a ketone in greater than about 2 molar equivalents, for example, about 2.05 to about 8 molar equivalents of the ketone; or (ii) relative to the [Ni(L)] n The (X)2] complex uses about ≥1.01 to about 1.5 molar equivalents of the diol, for example about 1.05 molar equivalents of the diol.

22. The method according to any of the preceding claims, wherein: (iii) the diol and the reducing metal or base; or (iv) the ketone and the reducing metal. In relation to the [Ni(L)] n [X]2] Contact is performed before contact with the complex.

23. The method according to any of the preceding claims, wherein [Ni(L)] n The (X)2] complex is contacted with the diol.

24. [Ni(L)] n [Q] complex, wherein: Q is a ketone complexed with nickel, wherein the ketone contains a carbonyl structural moiety conjugated with the π system; L is a monodentate, bidentate, or tridentate L-type ligand selected from tri-C 1-6 Alkylphosphine (e.g., tri-n-butylphosphine), tri-cyclic C 5-6 Hydrophosphine, C 1-4 alkyl-di-cycloC 5-6 Hydroxyphosphine, N,N,N',N'-tetrachlorophosphine 1-4 Alkyl C 2-4 alkylene diamine, N,N,N',N'',N''-pentacarbonyl 1-4 Alkyl C 2-4 alkyltriamines, C containing N,N 12-14 Heterocyclic tricyclic ligands, bis(di-cyclic C) 5-6 (Hydrocarbon phosphine)C 2-4 Alkylene, bis(di-cycloC) 5-6 (Hydrocarbon phosphine) Tons, double (di-C) 1-4 Alkylphosphine Tons, double (two-ring C) 5-6 (Hydrophosphino)ferrocene, bis(di-C) 1-4 Alkylphosphinyl)ferrocene, bis(di-cycloC) 5-6 (Hydrophosphinophenyl) ether and bis(di-C) 1-4 Alkylphosphine ethers, each of which is optionally composed of one or more compounds selected from C 1-4 Alkyl, Halogenated, C 1-4 Halogenated alkyl, hydroxyl, C 1-4 Substitution of alkoxy and morpholino groups, L is a C that includes N, N 10 Heterocyclic bicyclic ligands, optionally using one or more selected from C 1-4 Alkyl, Halogenated, C 1-4 Halogenated alkyl, hydroxyl and C 1-4 Substitution of alkoxy groups, L is two C 1-4 Alkyl-phosphino-biphenyl or di-cyclic C 5-6 Hydroxylphosphine-biphenyl, wherein each biphenyl is optionally made of one or more compounds selected from C 1-4 Alkyl, di(C) 1-4 alkyl)amino and C 1-4 Substitution of alkoxy groups, or L contains bicyclic C 5-6 The alkylphosphine-bonded structural portion is optionally connected to the N-heterocyclic carbene-bonded structural portion via an alkyl linker; and wherein when L is monodentate, n is 2, and when L is bidentate or tripentate, n is 1; Optionally, Q is defined as in any one of claims 2-6.

25. Use of the complex as defined in claim 24 as a catalyst, such as a cross-coupled catalyst.

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