Dinuclear nickel complexes and cross-coupling catalysis precursors

Abstract

We report the synthesis, characterization, and catalytic activity of a family of thermally stable dinuclear Ni(I) complexes supported by commercially available isocyanides as a general solution to this problem. Two classes of Ni(I) isocyanide complexes showing high thermal and solid-state stability have been developed – coordinatively saturated homoleptic compounds and coordinatively unsaturated Ni(I)-halide compounds. The Ni(I) compounds exhibit rapid ligand substitution and are efficient catalysts in Kumada, Suzuki-Miyaura, and Buchwald-Hartwig cross-coupling reactions, suggesting their potential use as either Ni(I) catalysts or pre-catalysts. In addition, bromide-selective functionalization of polyhalogenated arenes with Grignard reagents was achieved for the first time under nickel catalysis. Finally, spectroscopic and mechanistic studies were performed to establish the general use of simple isocyanide ligands as spectator ligands for cross-coupling reactions, representing an untapped chemical space for new reaction discovery.

Description

[0001] DINUCLEAR NICKEL COMPLEXES AND CROSS-COUPLING CATALYSIS PRECURSORS

[0002] RELATED APPLICATIONS

[0003] This application claims priority under 35 U.S.C. §119(e) to U.S. Provisional Patent Application No. 63 / 688,889, filed August 30, 2024, which is incorporated herein by reference.

[0004] GOVERNMENT SUPPORT

[0005] This invention was made with government support under 2155160 awarded by the National Science Foundation. The government has certain rights in the invention.

[0006] BACKGROUND OF THE INVENTION

[0007] Paramagnetic Ni centers are of critical importance to synthetic chemistry and biology, as reflected in a growing recognition of their role as reaction intermediates in Ni-catalyzed crosscoupling reactions and Ni metalloenzymes. In this context, understanding and controlling the radical chemistry involving Ni and Ni oxidation states is key to the development of new reaction chemistry. In the last decade, significant advances have been made in understanding the electronic structure and reactivity of Ni compounds stabilized by N-heterocyclic carbenes (NHCs), phosphines and polypyridyl ligands. However, many of these compounds suffer from a lack of solution stability in common organic solvents, or have ancillary ligands that need further synthetic manipulation to get to Ni-halide species. Thus, despite this recent progress, there is a dearth of a ubiquitously available, easily prepared and handled “Ni in a bottle” source for practitioners of organometallic chemistry. A survey of the literature shows that the most commonly used Ni source in catalysis is the NHC-supported eponymous “Sigman’s dimer” - [(IPr)Ni(p-Cl)]2, (Inorg. Chem. 2005. 44, 3774) which has led to the development of reactivity not accessible to the Ni and Ni counterparts.

[0008] Isocyanides are an integral part of the coordination chemist’s toolkit - they are isoelectronic to CO, yet with better c-donating and poorer ^-accepting properties. Their metal complexes have found extensive use as supporting ligands in organometallic chemistry, but rarely as catalysts, unlike phosphines and NHCs. The key challenge in developing catalysts with isocyanides as ligands is the propensity of isocyanides to form coordinatively saturated compounds. This arises from the linearity of the C-N-C linkage and the small cone angle of these ligands. An elegant solution to this problem has been pioneered by the Figueroa group, using synthetically demanding, sterically encumbered m-terphenyl isocyanides to induce coordinative unsaturation at metal centers (Angew. Chem., Int. Ed. 2009, 48, 3473). In addition, metal-bound isocyanides most commonly act as non-spectator ligands - they participate in reactions with

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[0011] UIUC2024-126-02(PCT) nucleophiles and undergo migratory insertion into metal-carbon bonds to form iminoacyl compounds. These properties have found use in multicomponent reactions (MCRs) or as Cl synthons - but prove to be detrimental for catalysis with metal-isocyanide complexes. The relative ease of synthesis of isocyanides (from a feedstock of primary amines) and their structural diversity suggests the use of isocyanide-ligated coordination compounds as catalysts may allow access to unexplored reactivity. Nickel holds a privileged position in the history of isocyanide chemistry, as dicationic Ni complexes are the premier catalysts for isocyanide polymerization.

[0012] Despite this recent progress, there exists the lack of a ubiquitously available, easily prepared and handled ‘Ni or Ni-halide in a bottle’ for practitioners of organometallic chemistry.

[0013] SUMMARY

[0014] Our group has been generally interested in studying the role of Ni and Ni states supported by multidentate ligands for cross-coupling (Chem 2024, 10, 867) and small molecule activation applications (Nat. Commun. 2023, 14, 905). In this study, we unveil simple, high-yielding and scalable protocols for the synthesis of coordinatively saturated and unsaturated Ni-isocyanide compounds using the commercially available tert-butyl isocyanide (tBuNC) ligand that are active in a range of cross-coupling (i.e., Kumada, Suzuki -Miyaura, and Buchwald-Hartwig) reactions.

[0015] We hypothesized that the key to unlock the potential of isocyanides as spectator ligands may be to ensure they are not bound strongly to the metal center, which usually favors insertion or addition at the isocyanides. The reported stretching frequency of the C=N bond (VCN) of Ni and Ni isocyanide complexes indicates strong ^-accepting and o-donating character of the bound isocyanides, respectively. In contrast, we reasoned that the isocyanide ligands would exhibit counterbalancing ^-accepting and o-donating interactions when bound to Ni, an inherently labile oxidation state of nickel, and thus lead to unique reactivity. Accordingly, our first synthetic target was a homoleptic Ni complex supported by tBuNC.

[0016] Accordingly, this disclosure provides a dinuclear nickel(I) coordination complex comprising isocyanide ligands.

[0017] In some embodiments the coordination complex is represented by Formula I or II: wherein

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[0020] UIUC2024-126-02(PCT) X is halo for Formula II; and

[0021] R is -(Ci-Ci2)alkyl, -(C3-Ci2)cycloalkyl, aryl, or heteroaryl; wherein R is substituted or unsubstituted.

[0022] This disclosure also provides a method for cross-coupling catalysis comprising contacting a coordination complex described above with: a) an organohalide or organotriflate; and b) an organometallic, organoboron, or organoamine; wherein a carbon-carbon bond or a carbon-nitrogen bond is formed in a cross-coupled product.

[0023] The invention provides novel compounds of Formula I and Formula II, intermediates for the synthesis of compounds of Formula I and Formula II, as well as methods of preparing compounds of Formula I and II. The invention also provides compounds of Formula I and II that are useful as intermediates for the synthesis of other useful compounds. The invention provides for the use of compounds of Formula I and Formula II for the manufacture of catalysts useful for the formation of carbon-carbon and carbon-nitrogen bonds.

[0024] BRIEF DESCRIPTION OF THE DRAWINGS

[0025] The following drawings form part of the specification and are included to further demonstrate certain embodiments or various aspects of the invention. In some instances, embodiments of the invention can be best understood by referring to the accompanying drawings in combination with the detailed description presented herein. The description and accompanying drawings may highlight a certain specific example, or a certain aspect of the invention. However, one skilled in the art will understand that portions of the example or aspect may be used in combination with other examples or aspects of the invention.

[0026] Figure 1. Solid-state structures of Ni-isocyanide complexes. Displacement ellipsoid plots of representative Ni isocyanide complexes shown at 50% probability ellipsoids (counteranions and hydrogen atoms have been omitted for clarity): (a) crystal structure of 1-tBu; (b) crystal structure of 1-Xyl; (c) space-filling models of 1-tBu from top-down and side views; (d) comparison of the C-N-C bond angles of the bridging isocyanides of 1-tBu and 1-Xyl; (e) crystal structure of 1-tBu-Br; (f) crystal structure of 1-Xyl-Br; (g) crystal structure of the monomeric form of 1-tBu-Br.

[0027] Figure 2A-E. Spectroscopic characterization and stochiometric reactivity of Ni isocyanide complexes, (a) IR spectra of representative Ni-isocyanide complexes (1) in solution and (2) comparing the solid-state vs solution IR spectra of 1-tBu and 1-tBu-Br. IR spectra showing the solid (b) and solution-state (c) stability of Ni-isocyanide complexes, (d) Stoichiometric reactivity of Ni- isocyanide complexes. The panel shows the displacement ellipsoid plots at 50% probability ellipsoids and electron paramagnetic resonance (EPR) spectra of the products isolated from the reaction of: 1-

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[0030] UIUC2024-126-02(PCT) tBu with terpyridine (1-tBu-terpy), with triphenylphosphine (l-tBu-PPh ), and with triadamantylphosphine (l-tBu-PAd ), recorded at 77 K in 1:3 THF and 2-methyltetrahydrofuran. For l-tBu-PPha, the isolated compound is a dicationic Ni species. Panel (e) shows for the reaction between 1-tBu-Br and 2-mesitylmagnesium chloride, the IR spectrum and EPR spectrum of the reaction mixture (77 K, 1:3 THF and 2-methyltetrahydrofuran) are shown.

[0031] Figure 3. Cross-coupling catalysis. Performance of Ni-isocyanide compounds supported by various alkyl and aryl isocyanides in the model SMC reaction, with 2 mol % catalyst loading.

[0032] Figure 4A-E. Mechanistic studies of reaction between 4-bromobenzotrifluoride and phenylmagnesium chloride, (a) Partial reaction order measurements from the method of initial rates with respect to 4-bromobenzotrifluoride, phenylmagnesium chloride and 1-tBu-Br. (b) Competition Hammett experiments with substituted aryl bromides plotted against Hammett o-values and Creary radical o-values. (c) Reaction progress monitoring for the formation of 4-trifluoromethylbiphenyl by F NMR for 1-tBu, 2-tBu, 1-tBu and 1-tBu-Br. (d,e) Effect of adding 10 mol% tBuNC to the reaction progress with 1-tBu or 1-tBu-Br as catalysts (monitored by F NMR). IR spectral changes observed upon adding 5 equiv tBuNC to 1-tBu-Br. Yields were determined by either GC-MS, H or F NMR spectroscopy with 1,3 -benzodioxole (for GC-MS and H NMR) or hexafluorobenzene (for F NMR) as internal standards, respectively. The errors in the yields or error bars represent standard errors obtained from the average of three independent trials.

[0033] Figure 5. Solution magnetism of Ni isocyanide complexes by Evans Method, calculated with the molar mass of the dimers. Panels show the temperature-dependent values of %T and peff of 1-tBu (in DCM) and 1-tBu-Br (in THF) respectively.

[0034] Figure 6. Electrochemical properties of 1-tBu and 1-tBu-Br. Experimental setup: working electrode - glassy carbon, reference electrode - Ag / AgNCh, and counter electrode - platinum wire. Experiments were performed at 1 mM concentration of the respective complexes in 0.1 M tetrabutylammonium hexafluorophosphate solution (DFB for 1-tBu and THF for 1-tBu-Br).

[0035] DETAILED DESCRIPTION

[0036] Nickel-catalyzed cross-coupling reactions have emerged as a powerful strategy to construct complex molecules. A salient feature of Ni catalysts is their ability to engage in one-electron chemistry involving paramagnetic Ni(I) and Ni(III) intermediates, which has led to development of cross-coupling reactions involving alkyl substrates; however, such reactions generally employ Ni(II) or Ni(0) complexes as pre-catalysts. Although highly desirable, well-defined and catalytically competent Ni(I) sources with exchangeable ancillary ligands are lacking. Here we report on the synthesis, characterization, and catalytic activity of a family of thermally stable dinuclear Ni(I) complexes supported by commercially available isocyanides as a general solution to this problem (Chart 1).

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[0039] UIUC2024-126-02(PCT) Chart 1. The role of Ni in cross-coupling catalysis. Reaction pathways in a canonical Ni-catalyzed cross-coupling reaction, commonly used Ni complexes, and a description of the bonding and reactivity pattern of metal-isocyanide compounds. A. Canonical Ni-catalyzed cross-coupling mechanism. Ni is involved in radical generation, transmetalation, oxidative addition and off-cycle pathways.

[0040] B. Features of metal-isocyanide coordination chemistry: o-donor / n-acceptor ligand. MCN linkage is linear, and steric bulk is far from the metal center. Coordinatively saturated complexes. Transition metal -bound isocyanides typically undergo 1,1 insertion or nucleophilic addition.

[0041] Two classes of Ni(I) isocyanide complexes showing high thermal and solid-state stability have been developed - coordinatively saturated homoleptic compounds and coordinatively unsaturated Ni(I)-halide compounds (Chart 2). The Ni(I) compounds exhibit rapid ligand substitution and are efficient catalysts in Kumada, Suzuki-Miyaura, and Buchwald-Hartwig crosscoupling reactions, suggesting their potential use as either Ni(I) catalysts or pre-catalysts. In addition, bromide-selective functionalization of polyhalogenated arenes with Grignard reagents was achieved for the first time under nickel catalysis. Finally, spectroscopic and mechanistic studies were

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[0043] UIUC2024-126-02(PCT) performed to establish the general use of simple isocyanide ligands as spectator ligands for crosscoupling reactions, representing an untapped chemical space for new reaction discovery.

[0044] Chart 2. Catalytically competent Ni isocyanide complexes.

[0045] Features: Coordinatively unsaturated. Thermally stable. >90% yields. Gram-scale syntheses. Facile, rapid ligand substitution. Catalyzes a range of cross-coupling reactions.

[0046] Definitions.

[0047] The following definitions are included to provide a clear and consistent understanding of the specification and claims. As used herein, the recited terms have the following meanings. All other terms and phrases used in this specification have their ordinary meanings as one of skill in the art would understand. Such ordinary meanings may be obtained by reference to technical dictionaries, such as Hawley ’s Condensed Chemical Dictionary 14 Edition, by R.J. Lewis, John Wiley & Sons, New York, N.Y., 2001.

[0048] References in the specification to "one embodiment", "an embodiment", etc., indicate that the embodiment described may include a particular aspect, feature, structure, moiety, or characteristic, but not every embodiment necessarily includes that aspect, feature, structure, moiety, or characteristic. Moreover, such phrases may, but do not necessarily, refer to the same embodiment referred to in other portions of the specification. Further, when a particular aspect, feature, structure, moiety, or characteristic is described in connection with an embodiment, it is within the knowledge of one skilled in the art to affect or connect such aspect, feature, structure, moiety, or characteristic with other embodiments, whether or not explicitly described.

[0049] The singular forms "a," "an," and "the" include plural reference unless the context clearly dictates otherwise. Thus, for example, a reference to "a compound" includes a plurality of such compounds, so that a compound X includes a plurality of compounds X. It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for the use of exclusive terminology, such as "solely," "only," and the like, in connection with any element described herein, and / or the recitation of claim elements or use of "negative" limitations.

[0050] The term "and / or" means any one of the items, any combination of the items, or all of the items with which this term is associated. The phrases "one or more" and "at least one" are readily

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[0052] UIUC2024-126-02(PCT) understood by one of skill in the art, particularly when read in context of its usage. For example, the phrase can mean one, two, three, four, five, six, ten, 100, or any upper limit approximately 10, 100, or 1000 times higher than a recited lower limit. For example, one or more substituents on a phenyl ring refers to one to five, or one to four, for example if the phenyl ring is disubstituted.

[0053] As will be understood by the skilled artisan, all numbers, including those expressing quantities of ingredients, properties such as molecular weight, reaction conditions, and so forth, are approximations and are understood as being optionally modified in all instances by the term "about." These values can vary depending upon the desired properties sought to be obtained by those skilled in the art utilizing the teachings of the descriptions herein. It is also understood that such values inherently contain variability resulting from the standard deviations found in their respective testing measurements. When values are expressed as approximations, by use of the antecedent "about," it will be understood that the particular value without the modifier "about" also forms a further aspect.

[0054] The terms "about" and "approximately" are used interchangeably. Both terms can refer to a variation of ± 5%, ± 10%, ± 20%, or ± 25% of the value specified. For example, "about 50" percent can in some embodiments carry a variation from 45 to 55 percent, or as otherwise defined by a particular claim. For integer ranges, the term "about" can include one or two integers greater than and / or less than a recited integer at each end of the range. Unless indicated otherwise herein, the terms "about" and "approximately" are intended to include values, e.g., weight percentages, proximate to the recited range that are equivalent in terms of the functionality of the individual ingredient, composition, or embodiment. The terms "about" and "approximately" can also modify the endpoints of a recited range as discussed above in this paragraph.

[0055] As will be understood by one skilled in the art, for any and all purposes, particularly in terms of providing a written description, all ranges recited herein also encompass any and all possible subranges and combinations of sub-ranges thereof, as well as the individual values making up the range, particularly integer values. It is therefore understood that each unit between two particular units are also disclosed. For example, if 10 to 15 is disclosed, then 11, 12, 13, and 14 are also disclosed, individually, and as part of a range. A recited range (e.g., weight percentages or carbon groups) includes each specific value, integer, decimal, or identity within the range. Any listed range can be easily recognized as sufficiently describing and enabling the same range being broken down into at least equal halves, thirds, quarters, fifths, or tenths. As a non-limiting example, each range discussed herein can be readily broken down into a lower third, middle third and upper third, etc. As will also be understood by one skilled in the art, all language such as "up to", "at least", "greater than", "less than", "more than", "or more", and the like, include the number recited and such terms refer to ranges that can be subsequently broken down into sub-ranges as discussed above. In the same manner, all ratios recited herein also include all sub-ratios falling within the broader ratio. Accordingly, specific values recited for radicals, substituents, and ranges, are for illustration only; they do not exclude other

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[0058] UIUC2024-126-02(PCT) defined values or other values within defined ranges for radicals and substituents. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint.

[0059] This disclosure provides ranges, limits, and deviations to variables such as volume, mass, percentages, ratios, etc. It is understood by an ordinary person skilled in the art that a range, such as “number 1” to “number ”, implies a continuous range of numbers that includes the whole numbers and fractional numbers. For example, 1 to 10 means 1, 2, 3, 4, 5, ... 9, 10. It also means 1.0, 1.1, 1.2. 1.3, ... , 9.8, 9.9, 10.0, and also means 1.01, 1.02, 1.03, and so on. If the variable disclosed is a number less than “number 10”, it implies a continuous range that includes whole numbers and fractional numbers less than number 10, as discussed above. Similarly, if the variable disclosed is a number greater than “number 10”, it implies a continuous range that includes whole numbers and fractional numbers greater than number 10. These ranges can be modified by the term “about”, whose meaning has been described above.

[0060] The recitation of a), b), c), ... or i), ii), iii), or the like in a list of components or steps do not confer any particular order unless explicitly stated.

[0061] One skilled in the art will also readily recognize that where members are grouped together in a common manner, such as in a Markush group, the invention encompasses not only the entire group listed as a whole, but each member of the group individually and all possible subgroups of the main group. Additionally, for all purposes, the invention encompasses not only the main group, but also the main group absent one or more of the group members. The invention therefore envisages the explicit exclusion of any one or more of members of a recited group. Accordingly, provisos may apply to any of the disclosed categories or embodiments whereby any one or more of the recited elements, species, or embodiments, may be excluded from such categories or embodiments, for example, for use in an explicit negative limitation.

[0062] The term "contacting" refers to the act of touching, making contact, or of bringing to immediate or close proximity, including at the cellular or molecular level, for example, to bring about a physiological reaction, a chemical reaction, or a physical change, e.g., in a solution, in a reaction mixture.

[0063] The term “substantially” as used herein, is a broad term and is used in its ordinary sense, including, without limitation, being largely but not necessarily wholly that which is specified. For example, the term could refer to a numerical value that may not be 100% the full numerical value. The full numerical value may be less by about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 15%, or about 20%.

[0064] Wherever the term “comprising” is used herein, options are contemplated wherein the terms “consisting of’ or “consisting essentially of’ are used instead. As used herein, “comprising” is synonymous with "including," "containing," or "characterized by," and is inclusive or open-ended

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[0067] UIUC2024-126-02(PCT) and does not exclude additional, unrecited elements or method steps. As used herein, "consisting of' excludes any element, step, or ingredient not specified in the aspect element. As used herein, "consisting essentially of' does not exclude materials or steps that do not materially affect the basic and novel characteristics of the aspect. In each instance herein any of the terms "comprising", "consisting essentially of' and "consisting of' may be replaced with either of the other two terms. The disclosure illustratively described herein may be suitably practiced in the absence of any element or elements, limitation or limitations which is not specifically disclosed herein.

[0068] This disclosure provides methods of making the compounds and compositions of the invention. The compounds and compositions can be prepared by any of the applicable techniques described herein, optionally in combination with standard techniques of organic synthesis. Many techniques such as etherification and esterification are well known in the art. However, many of these techniques are elaborated in Compendium of Organic Synthetic Methods (John Wiley & Sons, New York), Vol. 1, Ian T. Harrison and Shuyen Harrison, 1971; Vol. 2, Ian T. Harrison and Shuyen Harrison, 1974; Vol. 3, Louis S. Hegedus and Leroy Wade, 1977; Vol. 4, Leroy G. Wade, Jr., 1980; Vol. 5, Leroy G. Wade, Jr., 1984; and Vol. 6; as well as standard organic reference texts such as March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 5th Ed., by M. B. Smith and J. March (John Wiley & Sons, New York, 2001); Comprehensive Organic Synthesis. Selectivity, Strategy & Efficiency in Modem Organic Chemistry. In 9 Volumes, Barry M. Trost, Editor-in-Chief (Pergamon Press, New York, 1993 printing); Advanced Organic Chemistry, Part B: Reactions and Synthesis, Second Edition, Cary and Sundberg (1983); for heterocyclic synthesis see Hermanson, Greg T., Bioconjugate Techniques, Third Edition, Academic Press, 2013.

[0069] The formulas and compounds described herein can be modified using protecting groups. Suitable amino and carboxy protecting groups are known to those skilled in the art (see for example, Protecting Groups in Organic Synthesis, Second Edition, Greene, T. W., and Wuts, P. G. M., John Wiley & Sons, New York, and references cited therein; Philip J. Kocienski; Protecting Groups (Georg Thieme Verlag Stuttgart, New York, 1994), and references cited therein); and Comprehensive Organic Transformations, Larock, R. C., Second Edition, John Wiley & Sons, New York (1999), and referenced cited therein.

[0070] The term "halo" or "halide" refers to fluoro, chloro, bromo, or iodo. Similarly, the term "halogen" refers to fluorine, chlorine, bromine, and iodine.

[0071] The term "alkyl" refers to a branched or unbranched hydrocarbon having, for example, from 1-20 carbon atoms, and often 1-12, 1-10, 1-8, 1-6, or 1-4 carbon atoms; or for example, a range between 1-20 carbon atoms, such as 2-6, 3-6, 2-8, or 3-8 carbon atoms. As used herein, the term “alkyl” also encompasses a “cycloalkyl”, defined below. Examples include, but are not limited to, methyl, ethyl, 1 -propyl, 2-propyl (Ao-propyl), 1 -butyl, 2-methyl-l -propyl (isobutyl), 2-butyl (secbutyl), 2-methyl-2-propyl (Lbutyl), 1 -pentyl, 2-pentyl, 3 -pentyl, 2-methyl-2-butyl, 3-methyl-2-butyl,

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[0074] UIUC2024-126-02(PCT) 3 -methyl- 1 -butyl, 2-methyl-l -butyl, 1 -hexyl, 2-hexyl, 3 -hexyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl,

[0075] 4-methyl-2-pentyl, 3-methyl-3-pentyl, 2-methyl-3 -pentyl, 2,3-dimethyl-2-butyl, 3,3-dimethyl-2-butyl, hexyl, octyl, decyl, dodecyl, and the like. The alkyl can be unsubstituted or substituted, for example, with a substituent described below or otherwise described herein. The alkyl can also be optionally partially or fully unsaturated. As such, the recitation of an alkyl group can include an alkenyl group or an alkynyl group. The alkyl can be a monovalent hydrocarbon radical, as described and exemplified above, or it can be a divalent hydrocarbon radical (i.e., an alkylene).

[0076] An alkylene is an alkyl group having two free valences at a carbon atom or two different carbon atoms of a carbon chain. Similarly, alkenylene and alkynylene are respectively an alkene and an alkyne having two free valences at two different carbon atoms, or an alkenylene can have the two free valences on the same carbon.

[0077] The term "cycloalkyl" refers to cyclic alkyl groups of, for example, from 3 to 10 carbon atoms having a single cyclic ring or multiple condensed rings. Cycloalkyl groups include, by way of example, single ring structures such as cyclopropyl, cyclobutyl, cyclopentyl, cyclooctyl, and the like, or multiple ring structures such as adamantyl, and the like. The cycloalkyl can be unsubstituted or substituted. The cycloalkyl group can be monovalent or divalent and can be optionally substituted as described for alkyl groups. The cycloalkyl group can optionally include one or more cites of unsaturation, for example, the cycloalkyl group can include one or more carbon-carbon double bonds, such as, for example, 1 -cyclopent- 1-enyl, 1 -cyclopent-2-enyl, 1 -cyclopent-3 -enyl, cyclohexyl, 1- cyclohex-l-enyl, 1 -cyclohex-2-enyl, 1 -cyclohex-3 -enyl, and the like.

[0078] The term “heteroatom” refers to any atom in the periodic table that is not carbon or hydrogen. Typically, a heteroatom is O, S, N, P. The heteroatom may also be a halogen, metal or metalloid.

[0079] The term "heterocycloalkyl" or “heterocyclyl” refers to a saturated or partially saturated monocyclic, bicyclic, or polycyclic ring containing at least one heteroatom selected from nitrogen, sulfur, oxygen, preferably from 1 to 3 heteroatoms in at least one ring. Each ring is preferably from 3- to 10-membered, more preferably 4 to 7 membered. Examples of suitable heterocycloalkyl substituents include pyrrolidinyl, tetrahydrofuranyl, tetrahydrothiofuranyl, piperidinyl, piperazinyl, tetrahydropyranyl, morpholinyl, 1,3-diazapanyl, 1,4-diazapanyl, 1 ,4-oxazepanyl, and 1,4- oxathiapanyl. The group may be a terminal group or a bridging group.

[0080] The term "aromatic" refers to either an aryl or heteroaryl group or substituent described herein. Additionally, an aromatic moiety may be a bisaromatic moiety, a trisaromatic moiety, and so on. A bisaromatic moiety has a single bond between two aromatic moieties such as, but not limited to, biphenyl, or bipyridine. Similarly, a trisaromatic moiety has a single bond between each aromatic moiety.

[0081] The term "aryl" refers to an aromatic hydrocarbon group derived from the removal of at least one hydrogen atom from a single carbon atom of a parent aromatic ring system. The radical attachment site can be at a saturated or unsaturated carbon atom of the parent ring system. The aryl

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[0084] UIUC2024-126-02(PCT) group can have from 6 to 30 carbon atoms, for example, about 6-10 carbon atoms. The aryl group can have a single ring (e.g., phenyl) or multiple condensed (fused) rings, wherein at least one ring is aromatic (e.g., naphthyl, dihydrophenanthrenyl, fluorenyl, or anthryl). Typical aryl groups include, but are not limited to, radicals derived from benzene, naphthalene, anthracene, biphenyl, and the like. The aryl can be unsubstituted or optionally substituted with a substituent described below. For example, a phenyl moiety or group may be substituted with one or more substituents R where R is at the ortho-, meta-, or / % / ra-position, and X is an integer variable of 1 to 5.

[0085] The term "heteroaryl" refers to a monocyclic, bicyclic, or tricyclic ring system containing one, two, or three aromatic rings and containing at least one nitrogen, oxygen, or sulfur atom in an aromatic ring. The heteroaryl can be unsubstituted or substituted, for example, with one or more, and in particular one to three, substituents, as described in the definition of "substituted". Typical heteroaryl groups contain 2-20 carbon atoms in the ring skeleton in addition to the one or more heteroatoms, wherein the ring skeleton comprises a 5-membered ring, a 6-membered ring, two 5- membered rings, two 6-membered rings, or a 5 -membered ring fused to a 6-membered ring. Examples of heteroaryl groups include, but are not limited to, 2H-pyrrolyl, 3H-indolyl, 4H- quinolizinyl, acridinyl, benzo[b]thienyl, benzothiazolyl, 0-carbolinyl, carbazolyl, chromenyl, cinnolinyl, dibenzo[b,d]furanyl, furazanyl, furyl, imidazolyl, imidizolyl, indazolyl, indolisinyl, indolyl, isobenzofuranyl, isoindolyl, isoquinolyl, isothiazolyl, isoxazolyl, naphthyridinyl, oxazolyl, perimidinyl, phenanthridinyl, phenanthrolinyl, phenarsazinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolyl, quinoxalinyl, thiadiazolyl, thianthrenyl, thiazolyl, thienyl, triazolyl, tetrazolyl, and xanthenyl. In one embodiment the term "heteroaryl" denotes a monocyclic aromatic ring containing five or six ring atoms containing carbon and 1, 2, 3, or 4 heteroatoms independently selected from non-peroxide oxygen, sulfur, and N(Z) wherein Z is absent or is H, O, alkyl, aryl, or (Ci-C6)alkylaryl. In some embodiments, heteroaryl denotes an ortho-fused bicyclic heterocycle of about eight to ten ring atoms derived therefrom, particularly a benzo-derivative or one derived by fusing a propylene, trimethylene, or tetramethylene diradical thereto.

[0086] As used herein, the term "substituted" or “substituent” is intended to indicate that one or more (for example, in various embodiments, 1-10; in other embodiments, 1-6; in some embodiments 1, 2, 3, 4, or 5; in certain embodiments, 1, 2, or 3; and in other embodiments, 1 or 2) hydrogens on the group indicated in the expression using “substituted” (or “substituent”) is replaced with a selection from the indicated group(s), or with a suitable group known to those of skill in the art, provided that the indicated atom’s normal valency is not exceeded, and that the substitution results in a stable compound. Suitable indicated groups include, e.g., alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, hydroxyalkyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, alkanoyl, alkoxycarbonyl, amino,

[0087] 11

[0088] 500.161W01

[0089] UIUC2024-126-02(PCT) alkylamino, dialkylamino, carboxyalkyl, alkylthio, alkylsulfinyl, and alkylsulfonyl. Substituents of the indicated groups can be those recited in a specific list of substituents described herein, or as one of skill in the art would recognize, can be one or more substituents selected from alkyl, alkenyl, alkynyl, alkoxy, halo, haloalkyl, hydroxy, hydroxyalkyl, aryl, heteroaryl, heterocycle, cycloalkyl, alkanoyl, alkoxycarbonyl, amino, alkylamino, dialkylamino, trifluoromethylthio, difluoromethyl, acylamino, nitro, trifluoromethyl, trifluoromethoxy, carboxy, carboxyalkyl, keto, thioxo, alkylthio, alkylsulfinyl, alkylsulfonyl, and cyano. Suitable substituents of indicated groups can be bonded to a substituted carbon atom include F, Cl, Br, I, OR', 0C(0)N(R')2, CN, CF3, OCF3, R', O, S, C(O), S(O), methylenedioxy, ethylenedioxy, N(R')2, SR', SOR', SO2R', SO2N(R')2, SO3R', C(O)R', C(O)C(O)R', C(O)CH2C(O)R', C(S)R', C(O)OR', OC(O)R', C(0)N(R')2, 0C(0)N(R')2, C(S)N(R')2, (CH2)O-2NHC(0)R', N(R')N(R')C(O)R', N(R')N(R')C(O)OR', N(R')N(R')C0N(R')2, N(R')SO2R', N(R')SO2N(R')2, N(R')C(O)OR', N(R')C(O)R', N(R')C(S)R', N(R')C(0)N(R')2, N(R')C(S)N(R')2, N(COR')COR', N(OR')R', C(=NH)N(R')2, C(O)N(OR')R', or C(=NOR')R' wherein R’ can be hydrogen or a carbon-based moiety (e.g., (Ci-Ce)alkyl), and wherein the carbon-based moiety can itself be further substituted. When a substituent is monovalent, such as, for example, F or Cl, it is bonded to the atom it is substituting by a single bond. When a substituent is divalent, such as O, it is bonded to the atom it is substituting by a double bond; for example, a carbon atom substituted with O forms a carbonyl group, C=O.

[0090] Definitions of abbreviations: IPr = l,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene, PR3 = trialkylphosphine. tBuNC may also be abbreviated as BuNC. Similarly, 1-tBu may be abbreviated as 1-Bu, and 1-tBuBr may be abbreviated as 1-BuBr.

[0091] Embodiments of the Technology.

[0092] 1. A dinuclear nickel(I) coordination complex comprising isocyanide ligands; or a dinuclear nickel(I) coordination complex consisting of isocyanide ligands; or a dinuclear nickel(I) coordination complex comprising non-bridging isocyanide ligands.

[0093] In some embodiments, the coordination complex comprises at least 2 isocyanide ligands. In some embodiments, the coordination complex comprises at least 3 isocyanide ligands. In some other embodiments, the coordination complex comprises at least 4 isocyanide ligands. In some embodiments, the coordination complex comprises at least 5 isocyanide ligands. In other embodiments, the coordination complex comprises at least 6 isocyanide ligands. In other embodiments, the coordination complex comprises at least 7 isocyanide ligands. In yet other embodiments, the coordination complex comprises at least 8 isocyanide ligands. In some embodiments, the coordination complex comprises non-bridging isocyanide ligands and halide ligands. In some embodiments, the coordination complex comprises bridging isocyanide ligands.

[0094] 12

[0095] 500.161W01

[0096] UIUC2024-126-02(PCT) In additional embodiments, the coordination complex does not comprise aromatic ligands. In other additional embodiments, the coordination complex does not comprise phosphine ligands. In yet other embodiments, the coordination complex consists of non-aromatic ligands. In some other embodiments, the coordination complex comprises additional non-aromatic ligands. In other embodiments the non-aromatic ligands consist of carbon and nitrogen, or halide. In some embodiments, a halide ligand can be bromide or triflate.

[0097] In other additional embodiments, at least one isocyanide ligand bridges the nickel(I) atoms of the coordination complex. In other embodiments, at least two isocyanide ligands bridge the nickel(I) atoms of the coordination complex. In additional embodiments, the coordination complex comprises a Ni(I)-Ni(I) bond. In some other embodiments, the coordination complex comprises both nonbridging isocyanide ligands and bridging isocyanide ligands. In yet other embodiments, the coordination complex further comprises halide ligands.

[0098] 2. The coordination complex of embodiment 1, wherein the dinuclear nickel(I) is coordinatively saturated. In some embodiments, the dinuclear nickel(I) is coordinatively saturated with isocyanide ligands.

[0099] 3. The coordination complex of embodiment 1 , wherein the dinuclear nickel(I) is coordinatively unsaturated.

[0100] 4. The coordination complex of any one of embodiments 1-3, wherein the isocyanide ligands are aliphatic substituted isocyanides.

[0101] 5. The coordination complex of any one of embodiments 1-3, wherein the isocyanide ligands are aromatic substituted isocyanides, such as aryl or heteroaryl substituted isocyanides.

[0102] 6. The coordination complex of any one of embodiments 1-5, wherein the dinuclear nickel(I) is a homoleptic dinuclear nickel(I) isocyanide.

[0103] 7. The coordination complex of embodiment 1, wherein the coordination complex is represented by Formula I: wherein the dashed line between the two Ni atoms (Ni— Ni) indicates a partial covalent bond; and

[0104] R is -(Ci-Ci2)alkyl, -(C3-Ci2)cycloalkyl, aryl such as phenyl, or heteroaryl such as pyridyl; wherein R is substituted or unsubstituted.

[0105] In some embodiments, R is -(C2-Ce)alkyl; or R is -(C3-Cs)alkyl.

[0106] 13

[0107] 500.161W01

[0108] UIUC2024-126-02(PCT) 8. The coordination complex of embodiment 7, wherein R is / e / 7-butyl, cyclohexyl, adamantyl, 2,6-xylyl, or 2,6-diisopropylphenyl.

[0109] 9. The coordination complex of embodiment 7, wherein the coordination complex is:

[0110] [Ni(CNtBu)3(p-CNtBu)]2[BF4]2.

[0111] 10. The coordination complex of embodiment 1, wherein the coordination complex is represented by Formula II: wherein the solid line between the two Ni atoms (Ni-Ni) indicates a covalent bond

[0112] X is halo; and

[0113] R is -(Ci-Ci2)alkyl, -(C3-Ci2)cycloalkyl, aryl such as phenyl, or heteroaryl such as pyridyl; wherein R is substituted or unsubstituted.

[0114] In some embodiments, R is -(C2-Ce)alkyl; or R is -(C3-Cs)alkyl.

[0115] 11. The coordination complex of embodiment 10, wherein X is Br.

[0116] 12. The coordination complex of embodiment 10 or 11, wherein R is / e / 7-butyl, cyclohexyl, adamantyl, 2,6-xylyl, or 2,6-diisopropylphenyl.

[0117] 13. The coordination complex of embodiment 10, wherein the coordination complex is:

[0118] [Ni2(CNtBu)4Br2].

[0119] 14. A composition comprising a coordination complex of any one of embodiments 1-13 and a solvent.

[0120] 15. A method for cross-coupling catalysis comprising contacting a coordination complex of any one of embodiments 1-13 with: a) an organohalide or organotriflate; and b) an organometallic, organoboron, or organoamine; wherein a carbon-carbon bond or a carbon-nitrogen bond is formed in a cross-coupled product.

[0121] 16. The method of embodiment 15, further comprising contacting the coordination complex with an ancillary ligand, wherein the ancillary ligand comprises one or more atom donors. In some embodiments, the one or more atom donors is N, P, C, O, S, or a combination thereof.

[0122] 17. The method of embodiment 16, wherein the ancillary ligand is monodentate, bidentate, tridentate, or tetradentate.

[0123] 14

[0124] 500.161W01

[0125] UIUC2024-126-02(PCT) 18. The method of embodiment 15, wherein the coordination complex is:

[0126] [Ni(CNtBu)3(p-CNtBu)]2[BF4]2.

[0127] 19. The method of embodiment 15, wherein the coordination complex is:

[0128] [Ni2(CNtBu)4Br2].

[0129] 20. The method of any one of embodiments 15-17, wherein the organohalide or organotriflate and the organometallic or organoboron form a carbon-carbon bond in the cross-coupled product.

[0130] 21. The method of any one of embodiments 15-17, wherein the organohalide or organotriflate and the organoamine form a carbon-nitrogen bond in the cross-coupled product.

[0131] 22. A dinuclear nickel(I) coordination complex of any one of embodiments 1-21, comprising ligands selected from group I, II, or II: wherein group I consists of isocyanide ligands; group II consists of isocyanide ligands and halide ligands; group III consists of non-bridging isocyanide ligands and bridging isocyanide ligands; group IV consists of non-bridging isocyanide ligands and halide ligands; wherein the ligands are substituted or unsubstituted.

[0132] Results and Discussion.

[0133] Synthesis and Structural Characterization ofNi-Isocyanide Compounds. The homoleptic isocyanide complexes of Ni and Nican be conveniently prepared on the gram scale by reacting excess tBuNC with Ni(cod)2, or 4 equivalents of tBuNC with [Ni(H2O)e][BF4]2 respectively (Scheme la). During the course of this study, we also developed improved synthetic routes for homoleptic Ni and Ni isocyanide complexes. The dicationic Ni isocyanide complexes were readily prepared from [Ni(NCMe)6][BF4]2 as the Ni precursor (Scheme la), solving the longstanding challenge of synthesizing cationic Ni isocyanide complexes that can readily catalyze isocyanide polymerization. Furthermore, we developed a route to make 0-tBu in moderate yields (45%) from Ni(acac)2 using DIBAL-H as a reducing agent, thus precluding the use of Ni(cod)2 (Scheme la).

[0134] Scheme la. Synthesis of homoleptic Ni and Ni isocyanide complexes.

[0135] EtOH / Et2O up to 80% 95%

[0136] R = alkyl (tBu, Ad) and aryl (2,6-Xylyl, 2,6-Dipp)

[0137] 15

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[0139] UIUC2024-126-02(PCT) Scheme lb. Synthesis of Ni isocyanide complexes.

[0140] R = alkyl (tBu, Ad) and aryl (2,6-Xylyl, 2,6-Dipp)

[0141] 5 equiv RNC

[0142] „ „ THF or DCM

[0143] Ni°(cod)2+ Ni"Br2(dme) - ► 1-R-Bl"

[0144] RT, 15 min up to 95%

[0145] R = alkyl (tBu, Ad, Cyc) and aryl (2,6-Xylyl, 2,6-Dipp)

[0146] Mixing Ni(CNtBu)4 (0-tBu, VCN = 2020 cm) with [Ni(CNtBu)4][BF4]2 (2-tBu, VCN = 2243 cm) in a 1:1 ratio in 1 ,2-difluorobenzene (DFB) results in an immediate color change to dark red (Scheme lb). A crimson solid was isolated from the reaction in yields up to 90%. Single crystal X- ray diffraction (SC-XRD) analysis revealed a dinuclear Ni compound - [Ni(CNtBu)s(p- CNtBu)]2[BF4]2 (1-tBu), with a Ni-Ni bond distance of 2.408 A and two bridging and six terminal tBuNC ligands (Fig. la). Each nickel center is bound to five isocyanide ligands, the C-N bond lengths of the bridging isocyanides (1.177 A) are longer compared to those of the terminal isocyanides (average of 1.148 A), and the C-N-C angle is bent (151 for the bridging ligand vs. 177 for the terminal ligand). These structural parameters suggest a significant donation of electron density into the n-antibonding manifold of the bridging isocyanides. This is consistent with the solid-state vibrational spectroscopic data - the bridging isocyanides showing lowered VCN stretches (1976 cm) compared to the terminal isocyanides (2175 cm). The solid-state structure of this dication bears a striking resemblance to its 34 e, isoelectronic cobalt counterpart Co2(CO)s (vide infra), although no such dinclear Ni-carbonyl analog has been synthesized to date. To establish the generality of the synthetic protocol, we synthesized and fully characterized homoleptic Ni, Ni and Ni complexes with adamantyl isocyanide (0-Ad, 1-Ad, 2-Ad), 2,6-xylyl isocyanide (0-Xyl, 1-Xyl, 2-Xyl) and 2,6- diisopropyl phenylisocyanide (0-Dipp, 1-Dipp, 2-Dipp). The solid-state structure of 1-Xyl (Fig. lb) showed a significantly less bent C-N-C bond (Fig.ld) for the bridging isocyanide (174) compared to that of 1-tBu (151) and a longer Ni-Ni distance (2.4602 A for 1-Xyl compared to 2.4100 A for 1- tBu).We hypothesize that the steric hindrance afforded by the 2, 6-alkyl substituents of the bridging arylisocyanides makes the Ni-Ni interaction weaker.

[0147] 16

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[0149] UIUC2024-126-02(PCT) We then considered the possibility of making coordinatively unsaturated Ni compounds and incorporate halides as X-type ligands, which would allow transmetalation and further derivatization. With these goals in mind, we developed a one-pot comproportionation reaction in which Ni(cod)2, (DME)NiBr2, and four equivalents of tBuNC were reacted to form the neutral Ni-bromide compound [Ni2(tBuNC)4Br2] (1-tBu-Br) in up to 95% yield (Scheme lb), characterized by a single VCN stretch of 2130 cm in THF. The reaction can be performed on a multi-gram scale without loss in yield (92%), and the formally 30 e complex is sensitive to moisture and O2. Surprisingly, SC-XRD analysis revealed an unsupported dinuclear Ni-bromide compound with a nearly linear Br-Ni-Ni-Br unit and an unusually short Ni-Ni distance (-2.32 A) and can be thought to comprise two L2NiBr planes twisted by 90, with a local D2d symmetry (Fig. le). The solid-state structure of this compound is reminiscent of the very first organometallic Ni compound to be isolated - the tetraanionic ‘Bellucci’s salt’ - [Ni2(CN e]. 1-tBu-Br is also structurally similar to the analogous Pd and Pt dimers described by Balch and others (J Am. Chem. Soc. 1976, 98, 4845). The synthetic strategy was extended with slight modifications to a variety of aromatic and aliphatic isocyanides, and we isolated and fully characterized the corresponding Ni-bromide complexes 1-Ad-Br, 1-Cy-Br, 1-Xyl-Br (Fig. le), and 1-Dipp-Br. All of them share similar structural features, including short Ni-Ni contacts (2.30 to 2.34 A) and an approximate D2d symmetry. It is worth noting that comproportionation of Ni(cod)2 with NiCh(dme) or Nil2(dme) in the presence of tBuNC failed to yield the desired Ni-Cl or Ni-I compounds cleanly. However, halide metathesis of 1-tBu-Br with potassium iodide (KI) allowed the isolation of 1-tBu-I, which is structurally similar to its bromide counterpart. Overall, these Ni compounds with sterically unencumbered isocyanides are unusual entries in coordination chemistry, and we were interested in understanding their electronic structure and spectroscopic properties.

[0150] Spectroscopic Characterization of Ni-Isocyanide Compounds. Monitoring the VCN stretch in these isocyanide compounds provides a direct measure of the electron density of the metal center, with lower VCN being consistent with greater 71-backbonding. For example, a difference of approximately 100 cm in the VCN stretch was observed between the oxidation states - Ni: 2020 cm, Ni: 2130 cm (1-tBu-Br) and 2160 cm (1-tBu) and Ni: -2243 cm, making solution IR an effective reporter of the formal oxidation state of the Ni center (Fig. 2a.l). The small difference between the VCN of the free and bound isocyanides for the Ni compounds suggest that the bound isocyanides should be less prone to nucleophilic attack. An interesting divergence was noticed between the solid-state and the solution IR of 1-tBu (Fig. 2a.2). While the ATR-IR showed IR bands corresponding to terminal and bridging isocyanides, a DFB solution of 1-tBu showed a single VCN (2160 cm), suggesting a dynamic behaviour of this compound in solution. We also employed IR spectroscopy to assess the stability of 1-tBu and 1-tBu-Br and keeping the solid powder of 1-tBu open to air at room temperature for over a week led to a negligible increase in the IR stretch corresponding to 2-tBu (Fig. 2b); space filling models of 1-tBu suggest the Ni centers are sterically

[0151] 17

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[0153] UIUC2024-126-02(PCT) protected from attack by O2 (Fig. 1c). In solution, 1-tBu (DFB) and 1-tBu-Br (THF) show remarkable stability for several days under an inert atmosphere at room temperature, as seen by the virtually unchanged VCN values over six days (Fig. 2c). Interestingly, other dinuclear Ni compounds, [(IPr)Ni(p-Cl)]2 and [(PAd2Bu)Ni(p-Br)]2 do not show the same thermal stability.

[0154] To further elucidate the spin-state and solution structure of these compounds, we turned to variable temperature nuclear magnetic resonance (VT-NMR) studies and measured the temperaturedependent magnetic moment by the Evans Method. The H NMR spectra of 1-tBu and 1-tBu-Br exhibit broad singlets. For 1-tBu, this suggests a rapid interconversion of the terminal and bridging isocyanides on the NMR timescale, confirming its dynamic behaviour. A temperature dependence of the chemical shift corresponding to the / c / 7-butyl protons was observed for 1-tBu, while the chemical shifts did not show remarkable temperature dependence for 1-tBu-Br. For 1-tBu, peff was found to be 2.21 pB at 293 K, which decreased upon cooling to 213 K (peff = 0.93 PB). For 1-tBu-Br, peffremained relatively constant at ~0.9 pB over the measured temperature range. These respective trends held for the other compounds in each class (Fig. 5), although 1-tBu-I showed no observable solution magnetic moment. All these observations are consistent with a high spin-low spin equilibrium for the 1-R compounds. This could be due to a monomer-dimer equilibrium, weak antiferromagnetic coupling, or the existence of a thermally accessible triplet state for the otherwise diamagnetic dimer. The observed moment for the 1-R-Br compounds may be due to some fraction of the compound always existing as a monomer (as evidenced by the serendipitous crystallization of a trigonal planar monomeric form of 1-tBu-Br, Fig. 1g). The solution-state behavior is also consistent with the shorter solid-state Ni-Ni distances for the Ni-halide complexes.

[0155] We then performed density functional theory (DFT) calculations to rationalize the differences in bonding between 1-tBu and 1-tBu-Br. Like Co2(CO)s, the orientation of the two nickel centers does not allow the head-on overlap of any orbitals of appropriate symmetry to form a o-bond in 1- tBu, yet the bridging isocyanides have significant contributions to the frontier molecular orbitals. For 1-tBu-Br, HOMO- 14 shows perfect overlap from two perpendicular Ni dx-yorbitals, as well as overlap from other 71-type orbitals, which is consistent with the short Ni-Ni distances seen for these compounds (see Supporting Information for the full set of molecular orbitals).

[0156] Reactivity ofNi-Isocyanide Compounds. We then studied the reactivity of 1-tBu and 1-tBu- Br towards ligand substitution, as well as their reactions with electrophiles and nucleophiles. In accordance with their lability, both 1-tBu and 1-tBu-Br undergo ligand substitution with a variety of ligands. We found that 1-tBu was less prone to redox perturbations and formed Ni compounds with terpyridine, triphenylphosphine, and triadamantylphosphine (Fig. 2d), reliably delivering a ‘LnNi’ fragment to an appropriate o-donor. 1-tBu-Br was more prone to disproportionation and reactions with phosphines resulted in the formation of Ni-Br compounds. We also surveyed the reactivity of alkyl and aryl halides with the coordinatively unsaturated 1-tBu-Br, and aryl bromides and chlorides

[0157] 18

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[0159] UIUC2024-126-02(PCT) are unreactive, as monitored by EPR, NMR or IR spectroscopy (Fig. 2e, Chart 3). This agrees with the low reduction potentials of the Ni compounds (peak cathodic potentials of -1.22 V and -1.26 V versus Fc for 1-tBu and 1-tBu-Br respectively, Fig. 6). Radical activation of alkyl halides was seen when 1-tBu-Br was reacted with trityl halides (Chart 3), and Gomberg’s dimer was formed along with the corresponding oxidized Ni compound / raw.s-(CNtBu)2NiBr2. This reactivity profile towards organic halides is reminiscent of the “[(tBubpy)NiCl]2” dimer reported by Hazari and coworkers (Angew. Chem., Int. Ed. 2019, 58, 6094). Two-electron oxidative addition with an aryl halide was observed when a pyridinophane-bromide macrocycle was employed, displaying an EPR signal corresponding to a Ni species.

[0160] Chart 3. Reactivity of 1-tBu-Br with electrophiles and nucleophiles. Reactions of 1-tBu-Br with (1) aryl halides, (2) trityl halides, and (3) 2-mesityl magnesium chloride. Monitored by NMR, EPR, IR

[0161] CPh3

[0162] L J- + Ph3CX L rf i) other

[0163] Br— Ni1— H Ni'-Br - ► Br— Ni"-X + |l I] + organic l_ \ X = Br, Cl L || products quantitativeph^ph

[0164] NMR, X-Ray NMR (>99%)

[0165] L

[0166] Finally, we reacted 1-tBu-Br with the mesityl and neosilyl Grignard reagents as model nucleophiles, and an axial EPR spectrum was obtained in -75% yield from the reaction of 1-tBu-Br with mesityl Grignard, consistent with formation of a mononuclear Ni organometallic species (Chart 3). The VCN was red-shifted to -2100 and -2050 cm, as expected for increased back donation due to the carbanion donor. The spectroscopic evidence suggests that a mononuclear Ni organometallic species is likely the kinetically trapped product of the transmetalation reaction. Having structural evidence of an analogous trigonal planar monomeric form of 1-tBu-Br (Fig. 1g) lends further support to the possibility of such a compound existing even with the sterically unencumbered tBuNC.

[0167] 19

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[0169] UIUC2024-126-02(PCT) Catalytic Activity and Mechanistic Investigations. While an extensive reaction discovery campaign is beyond the scope of this study, we explored the efficacy of the Ni compounds in catalyzing model cross-coupling reactions (Scheme 2), without a significant optimization of reaction conditions. We chose to examine the reactivity 1-tBu-Br first as it is coordinatively unsaturated and hence it is expected to be more reactive, and we decided to focus initially on the Kumada-Tamao- Corriu (KTC) cross-coupling, Suzuki-Miyaura cross-coupling (SMC) with boronic acids, and Buchwald-Hartwig amination (BHA). 1-tBu-Br alone was a competent catalyst for CsP2-CsP2 KTC and SMC, furnishing cross-coupled products with varying electronics and sterics in good yields and using low catalyst loadings (1-2%, Scheme 2). Excitingly, for SMC, heterocyclic coupling partners were tolerated as well. For CsP2-CsP3 KTC, moderate yields could be obtained with alkyl Grignard reagents. For BHA of aryl halides with morpholine, 1-tBu-Br alone did not result in cross-coupling - but adding dppf as a supporting ligand yielded cross-coupled products in good yields, highlighting the modularity of 1-tBu-Br as a precatalyst. Moreover, addition of pybox to as the supporting ligand to 1-tBu-Br enabled CsP3-CsP3 Negishi cross-coupling (Scheme 2; 28). We also tested 1-tBu as a catalyst for some KTC and SMC couplings, good yields were obtained for CsP2-CsP2and CsP2-CsP3 couplings, suggesting its viability as a precatalyst. Excitingly, we also found that 1-tBu acts as a precatalyst with bpy (4,4’-di-tert-butyl-2,2’-dipyridyl) as a supporting ligand for the SMC of both primary and secondary alkyl halides with arylboronic acids in good yields (Scheme 2; 26 and 27).

[0170] Scheme 2. Cross-coupling catalysts with 1-tBu-Br and 1-tBu Kumada Coupling.

[0171] 500.161W01

[0172] UIUC2024-126-02(PCT) Bromide Selective Kumada Coupling.

[0173] Suzuki-Miyaura Coupling. Buchwald-Hartwig Coupling ,

[0174] Csp-C Cross-Coupling Reactions

[0175] 2 equiv. 70 C, 18 hrs from Hep-Br from Cyp-I

[0176] 26 74 ± 1 27 76 ± 4

[0177] 21

[0178] 500.161W01

[0179] UIUC2024-126-02(PCT) Substrate scope for cross-coupling catalysis. Yields were determined by either GC-MS, H or F NMR spectroscopy with 1,3 -benzodioxole (for GC-MS and H NMR) or hexafluorobenzene (for F NMR) as internal standards respectively. NMR reactions were run at 0.1 mmol scale with respect to the electrophile. Reactions for isolating the products were run at 1 mmol scale. Isolated yields are given in parentheses; denotes that the reaction was performed in dioxane; * denotes that 3 mol% catalyst was used instead of 2 mol%; denotes that the reaction was run in isopropanol.

[0180] To further benchmark the catalytic performance of these new Ni compounds, we performed extensive comparisons with other Ni catalysts as well as various Ni-isocyanide compounds discussed in this study (Table 1 and Fig. 3). Under the optimized reaction conditions for the SMC reaction, 1- tBu-Br outperformed all other systems employed at low catalyst loadings (1-2 mol%). We also tested a range of oxidation states and nuclearity of the nickel (pre)catalysts as well as the nature and denticity of ligands. Notably, other Ni dinuclear compounds and Ni precatalysts showed reduced yields, while Ni precatalysts showed slightly higher yields. When comparing the various Ni- isocyanide compounds as catalysts in the same reaction, we found that Ni compounds showed slightly higher yields than Ni or Ni analogs. Remarkably, significant ablation of yields was noticed for Ni complexes bound to 2,6-xylyl isocyanide irrespective of their oxidation state. We hypothesize that this is due to the stronger ^-accepting properties or competing insertion reactions for aryl isocyanides. In addition, we found that [(IPr)Ni(p-Cl)]2, which can readily facilitate Csp-Csp couplings in non-polar solvents, furnished negligible or no yields of cross-coupled product with alkyl halides as electrophiles (Scheme 2; 26, 27 and 28).

[0181] Table 1. Comparison with other Ni-based catalytic systems for SMC. Performance of various Ni catalysts in a model SMC reaction; denotes that the reaction was run with 1 mol % catalyst loading, while denotes that the reaction was run with 2 mol% Ni precursor and 4 mol % ligand.

[0182] UIUC2024-126-02(PCT)

[0183] Table 2. Chemoselectivity comparisons. Comparative performance of Ni, Ni and Ni sources in two chemoselective Kumada coupling reactions. The errors in the yields or error bars represent standard errors obtained from the average of two or three independent trials.

[0184] 1.5 equiv 13 SiMe331

[0185] We were also interested in discovering new reactivity that is enabled by these Ni complexes. Importantly, 1-tBu-Br proved to be a competent catalyst for the bromide-selective Kumada coupling of polyhalogenated arenes containing chloride and fluoride, which has not been reported previously for Ni systems (Scheme 2; 8-13). Good to excellent yields were obtained in aryl halides containing the chloride para or meta to the bromide; when the chloride is ortho to the bromide, selective coupling was not possible. Both aliphatic and aromatic Grignard reagents were tolerated under the reaction conditions (including the bulky mesityl Grignard reagent). In contrast, we found that traditional Ni and Ni systems like Ni(cod)2 / PPh3 and NiBr2(dme) / PPh3 could not discriminate between chloride and bromide groups in polyhalogenated arenes, highlighting the exquisite chemoselectivity afforded by 1-tBu-Br. In addition, bona fide dinuclear Ni precatalysts like

[0186] 23

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[0188] UIUC2024-126-02(PCT) [(IPr)Ni(|i-Cl)]2 and [(PAd2tBu)Ni(p-Br)]2 did not display the same selectivity (Table 2). Overall, these new transformations at Ni highlight the scope of the powerful complementary, chemoselective reactivity that can be achieved with the new Ni-isocyanide compounds.

[0189] Having established the viability of the Ni-isocyanide compounds as (pre)catalysts, we sought to probe the mechanism for the CsP2-CsP2 KTC reaction, to inform future reactivity development. Reaction order measurements reveal a complex, fractional order in 1-tBu-Br, a first-order dependence on PhMgCl and saturation kinetics in 4-bromobenzotrifluoride (Fig. 4a). In addition, the reaction of 1-tBu-Br with PhMgCl yields an axial EPR signal with g = [2.093 2,013 2.066], indicating the formation of a mononuclear Nispecies after transmetalation. Conversely, spectroscopic monitoring of the reaction with 4-bromobenzotrifluoride showed that 1-tBu-Br was unreactive with the aryl halide. EPR analysis of the reaction of the aryl halide with a mixture of 1-tBu-Br and PhMgCl did not reveal the formation of any paramagnetic Nispecies. When the reaction was carried out in the presence of the fast radical trap l-bromo-2-(but-3-enyl)benzene as the electrophile, cyclized products were detected by GC-MS and implying the involvement of aryl radicals (Scheme 3). Stoichiometric reactions with the same electrophile showed that cyclized products are only formed in the presence of the Grignard reagent, suggesting that only the nucleophilic Ni-aryl species (and not 1-tBu-Br) can generate an aryl radical.

[0190] Scheme 3. Reaction with an aryl radical trap. Stoichiometric and catalytic reactions conducted with l-bromo-2-(but-3-enyl)benzene as an aryl radical trap.

[0191] In addition, a competition Hammett analysis with electronically divergent aryl bromides yielded a small, positive value of = 0.64(1), suggesting a slight buildup of negative charge in the transition state (Fig. 4b). Strong correlation was also found with the radical o* from Creary and coworkers. This data suggests that the reaction involves the radical cleavage of an aryl halide by a nucleophilic Ni center, similar to previous observations for the radical activation of alkyl halides by Co and Ni species by Sigman and Diao, respectively. IR monitoring of the catalytic reaction mixture

[0192] 24

[0193] 500.161W01

[0194] UIUC2024-126-02(PCT) revealed the growth of a peak at 2109 cm, indicating that the lowest oxidation state attained during catalysis is not a Ni species, which would have a lower energy VCN stretch. From these experiments, we propose that catalysis is initiated by the reaction of PhMgCl with 1-tBu-Br to form a more reducing mononuclear Ni-aryl species. This step suggests that pre-activation of 1-tBu-Br is necessary (also corroborated by single-turnover experiments with limiting Grignard reagent, Table 3) and correlates with the fractional order in catalyst. This Ni-aryl species can generate an aryl radical from the aryl bromide to form a caged radical species [NiAr], which can then undergo radical capture to form a transient Ni species Ni-a (Scheme 4). We propose that this step is the pre-equilibrium that gives rise to the saturation kinetics in aryl halide. A second transmetalation step (consistent with the first order behavior in Grignard) may occur to generate a Ni intermediate Ni-b, which can either reductively eliminate the cross-coupled product or the nucleophile-derived homocoupled product and regenerate the active organometallic Ni species (Scheme 4).

[0195] Table 3. Single turnover experiment with limiting electrophile or nucleophile.

[0196] Finally, reaction progress monitoring by F NMR spectroscopy was employed to evaluate the differences in reactivity of the various Ni oxidation states. A quick initiation and saturation within two hours were observed for 1-tBu-Br. For 1-tBu and 0-tBu, longer induction periods were observed, while saturation took six hours for 2-tBu, and all three conditions gave lower product yields (Fig. 4c). Notable, the superior reactivity of the Ni-isocyanide compounds compared to the Ni and Ni counterparts stands in contrast to the observations by Hazari and Doyle, and points towards different reactivity profiles versus the polypyridyl- and phosphine-Ni compounds. Addition of excess isocyanide inhibits the reaction for 1-tBu and introduces an induction period for 1-tBu-Br (Fig. 4d), suggesting that the former may operate via a mechanism requiring isocyanide dissociation, while the latter can form 1-tBu with excess isocyanide added to the reaction, as confirmed independently by IR spectroscopy (Fig. 4e).

[0197] 25

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[0199] UIUC2024-126-02(PCT) Scheme 4. Mechanism studies of CsP2-CsP2 Kumada cross-coupling catalyzed by 1-tBu-Br.

[0200] Conclusions. Much progress has been made in expanding the repertoire of low-valent nickel complexes that are used as catalysts, starting with the seminal discovery of Ni(cod)2 by Gunther Wilke 60 years ago. Innovations in coordination chemistry has led to the development of air-stable Ni complexes by the Engle and Cornelia groups, as well as Ni oxidative addition complexes that act as in situ sources of Ni. Compared to the rich history of catalytically active Ni precursors, our understanding of Ni chemistry is still in its infancy. By looking beyond ligands traditionally used for cross-coupling catalysis, we have successfully developed a general method of synthesizing well- defined Ni-isocyanide compounds that are active catalysts or pre-catalysts for a range of crosscoupling reactions. In addition, the comparative reactivity studies showcased here suggest that alkyl isocyanides impose a ligand field that is distinct from polypyridyl ligands or strongly o-donating phosphines and NHCs. This is highlighted in their ability to function as a catalyst for CsP2- CsP2Couplings at very low catalyst loadings, as well as their activity as precatalysts with CsP3Substrates. Among other aspects, future work will focus on understanding the differences in reactivity between complexes supported by alkyl and aryl isocyanides, which display divergent catalytic activity.

[0201] We anticipate that the remarkable thermal stability of these complexes and their ability to catalyze a range of cross-coupling reactions will lead to their widespread adoption as a reliable Ni source. This work also represents a significant advance in isocyanide coordination chemistry and the synthesis of catalytically active base metal-isocyanide compounds. Moreover, the structural diversity of isocyanides suggests that much is left to be unearthed about the behavior of these molecules as spectator ligands, which should lead to the discovery of new reactions.

[0202] 500.161W01

[0203] UIUC2024-126-02(PCT) The following Examples are intended to illustrate the above invention and should not be construed as to narrow its scope. One skilled in the art will readily recognize that the Examples suggest many other ways in which the invention could be practiced. It should be understood that numerous variations and modifications may be made while remaining within the scope of the invention.

[0204] EXAMPLES

[0205] Example 1. Synthesis and Spectroscopic Characterization of Ligands and Metal Complexes.

[0206] Reagents and Materials. All reagents, unless stated otherwise were commercially available from Sigma- Aldrich, Fisher Scientific, Combi-Blocks or Strem Chemicals and were used as received without further purification. Solvents were purified prior to use by passing through a column of activated alumina using an M Braun solvent purification system. In the case of NMR solvents and liquid compounds used for catalysis they purified prior to use by distillation followed by freeze- pump-thaw and storing over 3 A molecular sieves for 48 hours prior to use. The synthesis of xylNC and DippNC was performed following literature protocols. The synthesis of the Ni precursor [Ni(MeCN)6][BF4]2 was adapted from a literature procedure and is described below.

[0207] Physical Measurements. H NMR spectra were recorded on a Bruker 500 spectrometer (500 MHz) or Varian 600 MHz spectrometer at UIUC School of Chemical Sciences NMR Lab. Chemical shifts are reported in ppm and referenced to residual solvent resonance peaks. UV-vis spectra were recorded on a Varian Cary 50 Bio spectrophotometer and are reported as / .max, nm (s, M cm). EPR spectra were recorded on a JEOL JES-FA X-band (9.2 GHz) or a Bruker 10" EMXPlus X-band Continuous Wave EPR spectrometer at 77 K. EPR spectra simulation and analysis were performed using Bruker WINEPR SimFonia program, version 1.25. Elemental analysis was carried out by the Microanalysis Laboratory at UIUC using an Exeter Analytical Model CE440 CHN Analyzer. Solid- state infrared spectra were measured using a PerkinElmer Frontier FT-IR spectrophotometer equipped with a KRS5 thallium bromide / iodide universal attenuated total reflectance accessory. Cyclic voltammetry (CV) was performed using a CHI Electrochemical Analyzer 660D. Measurements were taken in a glove box under nitrogen. Glassy carbon disk electrode (d = 1.6 mm) was used as the working electrode for cyclic voltammetry and the auxiliary electrode was a platinum wire. Ag / AgNO3 (0.1 M in acetonitrile) was used as the reference electrode. The reference was calibrated against ferrocene after each experiment. ESI-MS experiments were performed by the Mass Spectrometry Lab at UIUC using a Waters Q- TOF Ultima ESI mass spectrometer with an electron spray ionization source.

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[0210] UIUC2024-126-02(PCT) Synthesis of 2, 6 dimethylphenyl isocyanide (XylNC) and 2, 6 diisopropylphenyl isocyanide (DippNC).

[0211] The synthesis of DippNC and XylNC was adapted from previously reported synthetic procedures and are described below, along with spectral characterization.

[0212] 2, 6 dimethylphenyl isocyanide. Step 1: A solution of 2,6-dimethylaniline (12.1 g, 100 mmol) and 98% formic acid (7.7 ml, 200 mmol) in 60 ml toluene was refluxed for 12 hours. Volatiles were removed by rotary evaporation to obtain 2,6-dimethyl-l -formanilide in near quantitative yield as a feathery white solid.

[0213] Step 2: POC13 (5.39 mL, 57.8 mmol, 1.2 equiv) was added to the solution of the formanilide (6 g, 49 mmol, 1 equiv) and Et3N (20.2 mL, 145 mmol, 2.9 equiv) in THF (100 mL) at 0 °C. The reaction mixture was stirred at 0 °C. The reaction mixture was basified with a saturated aqueous solution of NaHCO3, after stirring for 2h. The reaction mixture was extracted with Et2O, and the combined extracts were washed with brine. The ether was dried over MgSO4 and concentrated the residue under reduced pressure. The obtained residue was filtered through a silica plug to obtain 2,6- dimethylphenylisocyanide (3.3 g, 52%). H NMR (499 MHz, CDC13) 8 (ppm): 7.18 (t, 1 H, Ar), 7.09 (d, 2 H, Ar), 2.41 (s, 6H, C / 73). C NMR (151 MHz, CDC13) 8 (ppm): 167.68, 134.94, 128.72, 127.81, 18.98

[0214] 2, 6 diisopropylphenyl isocyanide. Step 1 : To a 500 mL three-necked flask, 10 g of 2,6- diisopropyl aniline (10 g, 10.64 mL, 56.4 mmol, 1 equiv) is dissolved in toluene (210 mL) and added to a three-necked flask fitted with a Dean-Stark trap full of toluene, itself fitted with a reflux condenser. The flask is then flushed with nitrogen and kept under nitrogen for subsequent reagent additions. 97% formic acid in water (38.93 g, 31.9 mL, 846 mmol, 15 equiv) was added and the solution was heated and allowed to reflux for three hours. The flask and Dean-Stark trap were covered in aluminum foil to ensure uniform heating. After three hours, more formic acid (12.97 g, 10.64 mL, 282 mmol, 5 eq.) was added to the reaction mixture, and the reaction was allowed to reflux overnight. The next day, the solvent was removed in vacuo yielding a colorless solid (10.5 g, 91%).

[0215] Step 2: N-(2,6-diisopropylphenyl)formamide (5 g, 24.35 mmol, 1 equiv) to a 1 L threenecked round bottom flask fitted with a reflux condenser attached to the Schlenk line. To this, diisopropylamine (11.8 mL, 84.75 mmol, 3.5 equiv) and DCM was added (50 mL) and the flask was filled with nitrogen and cooled to 0 C. To the solution, phosphoryl chloride (2.8 mL, 29.9 mmol, 1.2 equiv) dissolved in DCM (-100 mL) was added dropwise and the solution was allowed to warm to room temperature and stirred for four hours. Then, 250 mL of 1.5M sodium carbonate solution was added to the reaction mixture and was allowed to stir at room temperature overnight. The organic layer was extracted from the aqueous layer with three 100 mL DCM extractions and the pale- yellow solution was dried with sodium sulfate. The solution was passed through a silica plug and was removed in vacuo to yield a pale-yellow oil (3g, 65%). H NMR (499 MHz, CD2C12) 8 (ppm): 7.36

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[0218] UIUC2024-126-02(PCT) (t, 1H, Ar), 7.21 (d, 2H, Ar), 3.41 (septet, 2H, CH3CHCH3), 1.30 (d, 12H, CH3CHCH3). C NMR (151 MHz, CD2CI2) 8 (ppm): 145.36, 129.75, 123.71, 30.29, 22.81.

[0219] Synthesis of [Ni(MeCN)6][BF4]2. [Ni(MeCN)e][BF4]2 was prepared by refluxing an acetonitrile solution of [Ni(H2O)e][BF4]2 for a week. Removal of the solvent in vacuo, followed by adding an excess of ether led to the formation of a pale blue solid that was dried under vacuum for 12 hours. The resulting solid was analytically pure, and the characterization matched previously reported data. [Ni(MeCN)6][BF4]2 is extremely moisture-sensitive and should be stored and handled in a N2- filled glovebox.

[0220] Synthesis ofNi Isocyanide complexes with tert-butyl isocyanide (tBuNCf General notes: The synthesis of all nickel isocyanide complexes should be carried out in a glovebox or a fumehood for the compounds that are not air-sensitive to avoid the unpleasant smell of the free ligands. It should be noted that the metal complexes do not bear the same unpleasant odor. For all complexes described below, the synthesis, NMR characterization, and elemental analysis data are included. The solution IR spectra and UV-vis spectra of all new compounds are described in subsequent sections. Nomenclature: The compounds described herein are named as a set of numbers and characters separated by a hyphen, such that the number represents the formal oxidation state of the Ni center, and the character is a shorthand for the substituent on the isocyanide ligand.

[0221] Synthesis and Characterization of 0-tBu. The synthesis of 0-tBu was adapted from a procedure reported by Otsuka and coworkers (J. Am. Chem. Soc. 1969, 91, 6994). tBuNC (1 mL, 7.23 mmol, 5 equiv) was added to a toluene (2 mL) solution of Ni(cod)2 (0.5 g, 1.82 mmol, 1 equiv). When not stirred properly, portions of the solution turned red, most likely owing to the formation of nanoclusters, as noted by Muetterties and coworkers. Using excess tBuNC avoids this issue. The original procedure calls for using 10 equivalents of tBuNC, but we found that 5 equivalents is sufficient for the reaction to proceed without the formation of cluster side products. After stirring for an hour, the solution was reduced in volume (~0.5 mL) and excess pentane (-10 mL) was added to it. Bright yellow crystals crashed out after storing the vial at -35 C overnight (0.64 g, 90% yield). Alternatively, the reaction can also be done in hexane - 0-tBu crashes out as a pale yellow powder as the reaction progresses. The spectral data obtained for this compound was identical to the literature reported values. H NMR (500 MHz, THF-d) 8 (ppm): 1.35 (s, 36H). C NMR (126 MHz, THF-d) 8 (ppm): 31.39, 54.76, 169.85. Elemental Analysis found, C 62.79, H 9.43, N 13.4%; calculated for C20H36N4N1 . 0.5 C5H12, C 63.24, H 9.91, N 13.11%.

[0222] Synthesis and Characterization of 2-tBu. The synthesis of 2-tBu was adapted from the procedure reported by Drenth and coworkers (Reel. Trav. Chim. Pays-Bas 1973, 92, 788). Exactly four equivalents of tBuNC (0.66 mL, 5.88 mmol) was added to a 1:1 EtOH:Et2O solution containing 1 equiv [Ni(H2O)e][BF4]2 (0.5 g, 1.47 mmol). The solution turns to a skin colored slurry within 30 minutes. It was filtered under in vacuo and the pale skin colored powder was washed with copious

[0223] 29

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[0225] UIUC2024-126-02(PCT) amounts of ether. Consistent with the observation of Drenth and coworkers, on applying high vacuum for 12 hours the color of the solid changed to off-white, signifying the loss of bound water molecules (0.78 g, 94%). Elemental analysis performed with this solid was consistent with a Ni center without bound water. Note: Ni is known to catalyze the polymerization of isocyanides, hence using precisely four equivalents of tBuNC is essential for successfully synthesizing 2-tBu. C NMR (151 MHz, DMSO-d) 8 (ppm): 152.57, 54.27, 29.92. Elemental Analysis found, C 42.36, H 6.44, N 9.83%; calculated for C20H36N4N1B2F8, C 42.53, H 6.42, N 9.92%.

[0226] Synthesis and Characterization of 1-tBu. To a 1,2 difl urobenzene (DFB) solution of 0-tBu (bright yellow), 1 equivalent 2-tBu was added. The solution turns to a dark red color immediately. After stirring for approximately 30 minutes, the solution was filtered through a pad of celite. In all synthetic attempts, no Ni black was seen. After reduction in volume, excess ether was added to crash out a crimson red crystalline powder (85-90% yield across various trials - for the gram-scale reaction 1.1 g of 1-tBu was obtained starting from 0.5 g of 0-tBu and 0.72 g of 2-tBu). Pentane can also be used to crash out 1-tBu - however a noticeable difference in the nature of the solid so obtained can be seen. When ether is used for the trituration, the solid obtained is crystalline and dark red. When pentane is used for trituration, the solid obtained is an amorphous powder and a lighter brick red. We recommend using diethyl ether to crash out 1-tBu. The ATR-IR of the powder show no observable difference. X-ray quality crystals were grown by the vapor diffusion of pentane into a DFB solution containing 1-tBu. H NMR (500 MHz, CD2CI2) 8 (ppm): 2.57 (s, 72H). Elemental Analysis: found, C 49.68, H 7.46, N 11.54%; calculated for C40H72N8N12B2F8, C 50.25, H 7.59, N 11.72%.

[0227] Synthesis and Characterization of 1-tBu-Br (General Procedure 1, abbreviated as GP-1). For the synthesis of 1-tBu-Br, we found that making the Ni in situ gives the most consistent results. Hence, Ni(cod)2 and 4.2 equivalents of tBuNC were mixed in THF and allowed to stir for 5 minutes. To this yellow solution, (DME)NiBr2 was added in portions over one minute. The solution turns dark purple. After 20 minutes, the solution was filtered through celite, and excess pentane was added to crash out a shiny purple solid. It was dried in vacuo and recrystallized by the vapor diffusion of pentane into a saturated THF solution (90-95% yield across several runs - for a representative trial, reacting 0.6 g Ni(cod)2, 0.67 g (DME)NiBr2 and 1.1 mL tBuNC yielded 1.22 g of 1-tBu-Br, representing a 92% yield). X-ray quality crystals were obtained from several solvent combinations like THF / pentane and DFB / ether at -35 C.

[0228] Detailed characterization of the solution behavior of 1-tBu-Br are described in the subsequent sections. The solid is indefinitely stable at room temperature under an inert atmosphere. However, it is extremely air and moisture-sensitive and turns into a sticky brown solid as soon as it is exposed to air. A THF solution of 1-tBu-Br is purple under inert atmosphere and turns into a golden- yellow color when exposed to air. Spectral characterization of the product formed when exposed to ambient conditions is provided later in the supporting information. H NMR (500 MHz, CD2CI2) 8

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[0231] UIUC2024-126-02(PCT) (ppm): 1.60 (s, 36 H). C NMR (126 MHz, CD2C12) 8 (ppm): 26.36. Elemental Analysis found, C 40.31, H 6.12, N 9.29%; calculated for C2oH36N4Ni2Br2, C 39.4, H 6.4, N 9.19%.

[0232] Synthesis and Characterization of 1-tBu-I. A solution of 1-tBu-Br (100 mg, 0.164 mmol, 1 equiv) in 2 mL THF was stirred with 2.2 equivalents of KI (60 mg). KI is not initially soluble in THF, but the solution turns dark green overnight. In case the reaction did not proceed at room temperature, the reaction mixture was heated gently at 30 C. The green solution was then filtered through a pad of celite. The solution was reduced in volume to ~ 1 mL, excess pentane was added to crash out a darkcolored powder (97 mg, 85% yield) which was dried in vacuo. X-Ray diffraction quality crystals were obtained by slow evaporation of pentane into a saturated solution of 1-tBu-I in THF. H NMR (500 MHz, THF-d) 8 (ppm): 1.54 (s, 36H). C NMR (126 MHz, THF-d) 8 (ppm): 30.23. Elemental Analysis found C 34.35, H 5.17, N 7.75%; calculated for C2OH36N4NI2I2, C 34.13, H 5.16, N 7.75%.

[0233] Synthesis ofNi Isocyanide complexes with adamantyl isocyanide (AdNC).

[0234] Synthesis and Characterization of O-Ad. The synthesis of 0-Ad followed the same protocol as 0-tBu. Stirring AdNC (0.29 g, 1.8 mmol, 5 equiv) with Ni(cod)2 (0.1 g, 0.364 mmol, 1 equiv) in pentane results in the formation of a beige solid over time. Excess pentane was added to the above mixture and stored at -35 C overnight. The beige solid was separated by filtration and dried in vacuo (0.214 g, 84%). THF can also be used as a solvent for this reaction - excess pentane needs to be added to crash out the product completely. H NMR (500 MHz, THF-d) 8 (ppm): 2.02, 1.98 (36H), 1.66 (24 H). C NMR (126 MHz, THF-d) 8 (ppm): 169.41, 45.13, 36.81, 30.41. Elemental Analysis found C 74.75, H 8.65, N 7.87%; calculated for C44H60N4N1, C 75.1, H 8.59, N 7.96%.

[0235] Synthesis and Characterization of 2-Ad. The synthetic route with [Ni(H2O)e][BF4]2as the Ni source did not work for the synthesis of 2-Ad. It led to an intractable dark mixture that could not be purified easily. We hypothesized that a different source of Ni with less labile ligands could assist the synthesis. Hence we used [Ni(MeCN)6][BF4]2as a Ni source. Thus, a solution of AdNC (0.23 g, 1.44 mmol, 4 equiv) was added to [Ni(MeCN)6][BF4]2(172 mg, 0.36 mmol, 1 equiv) in THF or DCM, which resulted in the formation of a light orange precipitate. The reaction was stirred for two hours, and excess pentane was added to the reaction. Vigorous stirring was found to be necessary as the Ni precursor is insoluble in THF. The pale orange solid formed was separated from the solution by filtration, washed vigorously with pentane and ether and dried in vacuo to give 2-Ad (0.24 g, 0.30 mmol, 77%). X-ray quality crystals were grown by the slow evaporation of pentane into a DCM solution of 2-Ad. H NMR (500 MHz, CD2C12) 8 (ppm): 2.19, 2.16 (s, 36H), 1.71 (s, 24H). C NMR (126 MHz, CD2C12) 8 (ppm): 42.38, 35.31, 29.18. Elemental Analysis found C 59.66, H 6.89, N 7.07%; calculated for C44H6oN4NiB2F8 + 0.5 CH3CN, C 60.2, H 6.9, N 7.02%.

[0236] Synthesis and Characterization of 1-Ad. To a 1,2 difl urobenzene (DFB) solution of 0-Ad (pale yellow, 70 mg, 0.1 mmol, 1 equiv), 1 equivalent 2-Ad (87.6 mg, 0.1 mmol, 1 equiv) was added.

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[0239] UIUC2024-126-02(PCT) The solution turns to a dark brown color immediately. After stirring for approximately 30 minutes, the solution was filtered through a pad of celite. In all synthetic attempts, no Ni black was seen. After reduction in volume, excess ether was added to crash out a crimson red powder (126 mg, 80% yield). X-ray quality crystals were grown by the vapor diffusion of pentane into a THF solution containing 1-Ad. H NMR (500 MHz, CD2CI2) 8 (ppm): 3.06 (s, 24H), 2.14 (48H), 1.94, 1.91 (s, 24H), 1.68, 1.66 (s, 24H). C NMR (126 MHz, CD2C12) 8 (ppm): 43.71, 34.85, 31.66. Elemental Analysis found C 67.58, H 7.34, N 6.56%; calculated for C88H120N8N12B2F8 + 1 THF, C 66.85, H 7.81, N 6.78%.

[0240] Synthesis and Characterization of 1-Ad-Br. GP-1 was followed for the synthesis of 1-Ad-Br. The key difference from the synthesis of 1-tBu-Br is that the pale purple product crashed out of the THF solution over the course of an hour. Excess pentane was added, and the light purple solid was separated from the solution by filtration and dried in vacuo (up to 87% yield across various runs). X- ray quality crystals were grown by the slow evaporation of pentane into a saturated DFB solution. H NMR (500 MHz, CD2C12) 8 (ppm): 2.19 (br s, 36H), 1.72 (br s, 24H). C NMR (126 MHz, CD2C12) 8 (ppm): 134.85, 68.08, 43.40, 35.68, 29.37. Elemental Analysis found C 57.39, H 6.97, N 5.77%; calculated for C44H6oN4Ni2Br2, C 57.31, H 6.56, N 6.08%.

[0241] Synthesis ofNi Isocyanide complexes with 2, 6 dimethylphenyl isocyanide (xylNC).

[0242] Synthesis and Characterization of O-Xyl. The synthesis of 0-Xyl was adapted from a previous synthetic protocol for synthesizing homoleptic Ni complexes with aryl isocyanides. To a solution of Ni(cod)2 (100 mg, 0.364 mmol, 1 equiv) in 3 mL toluene, was added 5 equivalents of xylNC (240 mg, 1.82 mmol, 5 equiv). The yellow solution was stirred for 2 hours, filtered through celite, and reduced in volume to ~1 mL. -15 mL pentane was added to the solution, kept at -35 C overnight. Bright yellow crystals formed overnight. The solution was decanted, the solids were washed with cold pentane twice and dried. (190 mg, 90% yield). H NMR (500 MHz, CD2CI2) 8 (ppm): 7.06 (s, Ar, 12H), 2.44 (s, ArCft, 24H). C NMR (126 MHz, CD2CI2) 8 (ppm): 134.31, 127.90, 126.72, 19.23. Elemental Analysis found C 74.39, H 6.25, N 9.62%; calculated for C36H36N4N1, C 74.12, H 6.22, N 9.6%.

[0243] Synthesis and Characterization of 2-Xyl. 4 equivalents of xylNC (192 mg, 1.46 mmol, 4 equiv) were added to one equivalent of [Ni(MeCN)e][BF4]2 (172 mg, 0.36 mmol, 1 equiv) in -2 mL DFB. The solution was stirred vigorously overnight and turned dark brown. It was filtered through celite and reduced in volume to ~0.5 mL. Then -10 mL ether was added to crash out a beige powder (190 mg, 70% yield). It was dried in vacuo, and x-ray quality crystals were grown by the slow evaporation of ether into a saturated solution of 2-Xyl in DFB. H NMR (500 MHz, CD2CI2) 8 (ppm): 7.37 (t, Ar, 4H), 7.20 (d, Ar, 8H), 2.53 (s, Ar-C / L, 24H). C NMR (126 MHz, CD2CI2) 8 (ppm). Elemental Analysis found C 56.37, H 4.89, N 7.33%; calculated for C36H36N4N1B2F8, C 57.12, H 4.79, N 7.4%.

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[0246] UIUC2024-126-02(PCT) Synthesis and Characterization of 1-Xyl. To a 1,2 diflurobenzene (DFB) solution of O-Xyl (58 mg, 0.1 mmol, 1 equiv), 1 equivalent 2-Xyl (76 mg, 0.1 mmol, 1 equiv) was added. The solution turns to a dark brown color immediately. After stirring for approximately 30 minutes, the solution was fdtered through a pad of celite. After reduction in volume, excess ether was added to crash out a dark blue powder (90 mg, 72% yield). X-ray quality crystals were grown by the vapor diffusion of pentane into a DFB solution containing 1-Xyl. H NMR (500 MHz, CD2C12) 8 (ppm): 7.88 (Ar, br s, 16H), 6.00 (Ar, br s, 8H), 3.45 (ArCH3, br s, 3H). C NMR (126 MHz, CD2C12) 8 (ppm): 137.71, 136.58, 124.30, 19.11. Elemental Analysis found C 63.97, H 5.07, N 8.28%; calculated for C72H72N8N12B2F8, C 64.52, H 5.41, N 8.36%.

[0247] Synthesis and Characterization of 1-Xyl-Br. The GP-1 was followed for the synthesis of 1- Xyl-Br. Unlike the aliphatic isocyanides, the color of the solution turned dark brown. The solution was dried completely and triturated with pentane three times, till the pentane washes ran clear. After drying under vacuum for 12 hours, a dark brown powder was isolated in 78% yield. X-ray quality crystals were grown by the vapor diffusion of pentane into a saturated THF solution of 1-Xyl-Br. H NMR (500 MHz, CD2C12) 8 (ppm): 7.24 (Ar, br s, 1H), 7.13 (Ar, br s, 2H), 2.53 (ArCH3, br s, 6H). C NMR (126 MHz, CD2C12) 8 (ppm): 127.71, 128.96, 128.43, 28.37, 19.43. Elemental Analysis found C 53.59, H 4.87, N 6.95%; calculated for C36H36N4Ni2Br2, C 53.92, H 4.52, N 6.99%.

[0248] Synthesis ofNi Isocyanide complexes with 2, 6 diisopropylphenyl isocyanide (DippNC).

[0249] Synthesis and Characterization of O-Dipp. The synthesis of 0-Dipp was adapted from a previous synthetic protocol for synthesizing homoleptic Ni complexes with aryl isocyanides. To a solution of Ni(cod)2 (100 mg, 0.364 mmol, 1 equiv) in 3 mL toluene, was added 5 equivalents of DippNC (340 mg, 1.82 mmol, 5 equiv). The yellow solution was stirred for 2 hours, filtered through celite, and reduced in volume to ~1 mL. -15 mL pentane was added to the solution, kept at -35 C overnight. Bright yellow crystals formed overnight. The solution was decanted, the solids were washed with cold pentane twice and dried. (255 mg, 88% yield). H NMR (500 MHz, C6D6) 8 (ppm): 7.02 (t, Ar, 4H), 6.96 (d, Ar, 8H), 3.71 (sep, CH3C / 7CH3, 8H), 1.27 (d, CH3CHCH3, 48H). C NMR (126 MHz, C6D6) 8 (ppm): 176.76, 144.19, 128.97, 126.93, 123.49, 30.32, 22.86. Elemental Analysis found, C 77.02, H 8.25, N 6.99%; calculated for C52H68N4N1, C 77.31, H 8.48, 6.94%.

[0250] Synthesis and Characterization of2-Dipp. 4 equivalents of DippNC (270 mg, 1.46 mmol, 4 equiv) were added to one equivalent of [Ni(MeCN)6][BF4]2 (172 mg, 0.36 mmol, 1 equiv) in -2 mL DFB. The solution was stirred vigorously overnight and turned dark brown. It was filtered through celite and reduced in volume to ~0.5 mL. Then -10 mL ether was added to crash out a beige powder (285 mg, 81% yield). It was dried in vacuo, and x-ray quality crystals were grown by the slow evaporation of ether into a saturated solution of 2-Dipp in THF. H NMR (500 MHz, CD2C12) 8 (ppm): 7.50 (t, Ar, 4H), 7.27 (d, Ar, 8H), 3.44 (sep, CH3C / 7CH3, 8H), 1.23 (d, CH3CHCH3, 48H).

[0251] 33

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[0253] UIUC2024-126-02(PCT) C NMR (126 MHz, CD2C12) 8 (ppm): 147.71, 132.91, 124.33, 30.11, 22.85. Elemental Analysis found, C 63.22, H 6.76, N 5.77%; calculated for C52H68N4N1B2F8, C 63.64, H 6.98, N 5.71%.

[0254] Synthesis and Characterization of 1-Dipp. To a 1,2 difl urobenzene (DFB) solution of 0-Dipp (41 mg, 0.05 mmol, 1 equiv), 1 equivalent 2-Dipp (48 mg, 0.049 mmol, 0.98 equiv) was added. The solution turns to a dark brown color immediately. After stirring for approximately 30 minutes, the solution was filtered through a pad of celite. Various attempts were made to crystallize 1-Dipp, but 0- Dipp was crystallized instead. This indicates that 1-Dipp undergoes disproportionation during the crystallization process. Unlike the other dimeric homoleptic Ni compounds, 1-Dipp was found to be monomeric based on EPR evidence. H NMR (500 MHz, CD2C12) 8 (ppm): 7.36 (br s, Ar, 4H), 7.20 (br s, Ar, 8H), 3.76 (br s, CH3C / 7CH3, 8H), 1.29 (br s, CH3CHCH3, 48H). Elemental Analysis found C 68.85, H 7.35, N 6.12%; calculated for C88H120N8N12B2F8 + 1 DFB, C 69.06, H 7.19, N 5.55%.

[0255] Synthesis and Characterization of 1-Dipp-Br. The GP-1 was followed for the synthesis of 1- Dipp-Br. Like 1-Xyl-Br, the color of the solution turned dark brown. The solution was dried completely and triturated with pentane three times. After drying under vacuum for 12 hours, a dark brown powder was isolated in 70% yield. X-ray quality crystals were grown by the vapor diffusion of pentane into a saturated THF solution of 1-Dipp-Br. H NMR (500 MHz, CD2C12) 8 (ppm): 7.37 (br s, Ar, 4H), 7.20 (br s, Ar, 8H), 3.75 (br s, CH3C / 7CH3, 8H), 1.28 (br s, CH3CHCH3, 48H). C NMR (126 MHz, CD2C12) 8 (ppm): 148.11, 130.42, 123.95, 30.41, 22.83. Elemental Analysis Elemental Analysis found C 59.75, H 6.65, N 5.22%; calculated for C52H68N4Ni2Br2 + 1 DFB, C 60.85, H 6.68, N 5.46%.

[0256] Synthesis ofNi Isocyanide complexes with cyclohexyl isocyanide (CycNC).

[0257] Synthesis and Characterization of 1-Cyc-Br. GP-1 was followed for the synthesis of 1-Cyc- Br in 72% yield. X-ray quality crystals were grown by the slow evaporation of pentane into a saturated THF solution of 1-Cyc-Br. The H NMR of this compound was paramagnetically broadened, and significantly downfield resonances were observed as characteristic for paramagnetic complexes. H NMR (500 MHz, CD2C12) 8 (ppm): 22.42, 16.58, 10.45, 9.37, 3.98, 3.69, 1.89, 1.50. C NMR (500 MHz, CD2C12) 8 (ppm): 134.43, 55.67, 33.20, 25.10, 22.69. Elemental Analysis found C 47.18, H 6.23, N 7.49%; calculated for C28H44N4Ni2Br2, C 47.11, H 6.21, N 7.85%.

[0258] Table 4. Molecular masses of the homoleptic Ni, Ni, and Ni isocyanide compounds.

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[0261] UIUC2024-126-02(PCT)

[0262] Ligand substitution reactions of Ni Isocyanide Complexes.

[0263] General considerations for ligand substitution reactions with 1-tBu or 1-tBu-Br. For ligand substitution reactions, our goal was to show that both the coordinatively saturated and unsaturated Ni complexes underwent rapid and facile ligand substitution. To that end, we chose to examine the reactivity of various catalytically relevant N, P, and C donor ligands. These studies establish the modularity of 1-tBu or 1-tBu-Br as viable options for a Ni source in high-throughput screening, as they underwent ligand substitution rapidly. This was further validated during the catalytic trials, as the Ni complexes alone catalyzed Kumada and Suzuki couplings but needed an equimolar amount of dppf to effectively catalyze Buchwald-Hartwig amination.

[0264] For all of the reactions, we recorded the EPR spectrum by freeze-quenching a 1 : 1 mixture of the ligand and 1-tBu or 1-tBu-Br in an appropriate glassing solvent. Due to the paramagnetic nature of the complexes, NMR spectroscopy is not an effective reporter of solution speciation, so no NMR studies were attempted. For many of the ligand substitution reactions, we were able to obtain the solid-state structure of the compound as determined by XRD. In addition, we also observed that complicated mixtures of products were obtained from the crystallization attempts - so no Evans Method experiments were performed as an accurate estimation of the solution speciation for these ligand-substituted species was not possible.

[0265] General procedure for EP R-scale reactions. 1-tBu or 1-tBu-Br (1-2 mg, 1 equiv) and the ligand (2.1 equiv) were mixed at room temperature in 0.5 mL of either 1:1 DFB:toluene for reactions with 1-tBu or 1:3 THF:2-Me THF for reactions with 1-tBu-Br. The reaction mixture was then flash- frozen in liquid N2 (77 K). All warmups were done at room temperature.

[0266] General procedure for synthetic scale reactions. 1-tBu or 1-tBu-Br (15 mg, 1 equiv) and an appropriate amount of the ligand (2.1 equiv) were mixed at room temperature in 1 mL of either DFB for reactions with 1-tBu or THF for reactions with 1-tBu-Br. The reaction mixture was then stirred for 15 minutes, fdtered through a celite pad and reduced to ~0.5 mL. Then diethyl ether was added to 35

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[0268] UIUC2024-126-02(PCT) crash out the complexes as solids. Crystals suitable for SC-XRD were grown from the solvent systems specified for each case.

[0269] Ligand substitution reactions of 1-tBu.

[0270] Ligand substitution with terpyridine (1-tBu-terpy). 1-tBu (15 mg, 1 equiv) and terpyridine (2.1 equiv) were mixed at room temperature in 1 mL DFB. The reaction mixture was then stirred for 15 minutes, filtered through a celite pad and reduced to ~0.5 mL. Then diethyl ether was added to crash out the complex as a solid. Crystals were grown by vapor diffusion of pentane into a saturated THF solution of 1-tBu-terpy.

[0271] Ligand substitution with neocuproine (1-tBu-neocuproine). 1-tBu (15 mg, 1 equiv) and neocuproine (2.1 equiv) were mixed at room temperature in 1 mL DFB. The reaction mixture was then stirred for 15 minutes, filtered through a celite pad and reduced to -0.5 mL. Then diethyl ether was added to crash out the complex as a solid. Crystals were grown by vapor diffusion of pentane into a saturated THF solution of 1-tBu-neocuproine.

[0272] Ligand substitution with (S,S)-2,6-Bis(4-isopropyl-2-oxazolin-2-yl)pyridine (iPrpyBOX). 1- tBu (15 mg, 1 equiv) and pyBOX (2.1 equiv) were mixed at room temperature in 1 mL DFB. The reaction mixture was then stirred for 15 minutes, filtered through a celite pad and reduced to -0.5 mL. Then diethyl ether was added to crash out the complex as a solid. Despite several attempts, X- ray quality crystals could not be obtained.

[0273] Ligand substitution with tris(l-adamantyl)phosphine. 1-tBu (15 mg, 1 equiv) and PAd3 (2.1 equiv) were mixed at room temperature in 1 mL DFB. The reaction mixture was then stirred for 15 minutes, filtered through a celite pad and reduced to -0.5 mL. Then diethyl ether was added to crash out the complex as a solid. Crystals were grown by vapor diffusion of pentane into a saturated THF solution of l-tBu-PAds.

[0274] Ligand substitution with diphenylphosphinoferrocene (dppf). 1-tBu (15 mg, 1 equiv) and dppf (2.1 equiv) were mixed at room temperature in 1 mL DFB. The reaction mixture was then stirred for 15 minutes, filtered through a celite pad and reduced to -0.5 mL. Then diethyl ether was added to crash out the complex as a solid. Crystals were grown by vapor diffusion of pentane into a saturated THF solution of 1-tBu-dppf.

[0275] Ligand substitution with triphenylphosphine. 1-tBu (15 mg, 1 equiv) and PPh3 (2.1 equiv) were mixed at room temperature in 1 mL DFB. The reaction mixture was then stirred for 15 minutes, filtered through a celite pad and reduced to -0.5 mL. Then diethyl ether was added to crash out the complex as a solid. Crystals were grown by vapor diffusion of pentane into a saturated THF solution of l-tBu-PPh3.

[0276] 36

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[0278] UIUC2024-126-02(PCT) Ligand substitution with IPr. 1-tBu (15 mg, 1 equiv) and IPr (2.1 equiv) were mixed at room temperature in 1 mL THF. The reaction mixture was then stirred for 15 minutes, filtered through a celite pad and reduced to ~0.5 mL. Then diethyl ether was added to crash out the complex as a solid.

[0279] Ligand substitution reactions of 1-tBu-Br.

[0280] Ligand substitution with diphenylphosphinoferrocene (dppf). 1-tBu (15 mg, 1 equiv) and dppf (2.1 equiv) were mixed at room temperature in 1 mL THF. The reaction mixture was then stirred for 15 minutes, filtered through a celite pad and reduced to -0.5 mL. Then pentane was added to crash out the complex as a solid. Crystals were grown by vapor diffusion of pentane into a saturated THF solution of 1-tBu-Br-dppf.

[0281] Ligand substitution with diphenylphosphinoethane (dppe). 1-tBu (15 mg, 1 equiv) and dppe (2.1 equiv) were mixed at room temperature in 1 mL THF. The reaction mixture was then stirred for 15 minutes, filtered through a celite pad and reduced to -0.5 mL. Then pentane was added to crash out the complex as a solid. Crystals were grown by vapor diffusion of pentane into a saturated THF solution of 1-tBu-Br-dppe.

[0282] Example 2. Synthesis of nickel complexes.

[0283] Synthesis of 1-tBu [Ni(CNtBu)s(p-CNtBu)]2[BF4]2. To a 1,2 diflurobenzene (DFB) solution of 0-tBu (bright yellow), 1 equivalent 2-tBu was added. The solution turns to a dark red color immediately. After stirring for approximately 30 minutes, the solution was filtered through a pad of celite. In all synthetic attempts, no Ni black was seen. After reduction in volume, excess ether was added to crash out a crimson red crystalline powder (85-90% yield across various trials - for the gram-scale reaction 1.1 g of 1-tBu was obtained starting from 0.5 g of 0-tBu and 0.72 g of 2-tBu, representing a 90% yield). H NMR (500 MHz, CD2CI2) 8 (ppm): 2.57 (s, 72H). C NMR (500 MHz, CD2CI2) 8 (ppm): 30.87 (other C peaks could not be seen, presumably due to the paramagnetic nature of the compound). Elemental Analysis: found, C 49.68, H 7.46, N 11.54%; calculated for C40H72N8N12B2F8, C 50.25, H 7.59, N 11.72%.

[0284] 37

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[0286] UIUC2024-126-02(PCT) 5 equiv RNC n „ THF or DCM

[0287] Ni°(cod)2+ Ni"Br2(dme) - >-

[0288] RT, 15 min up to 95% t

[0289] R = 'Bu

[0290] Synthesis of 1-tBu-Br [Ni2(CNtBu)4Br2]. Ni(cod)2 and 4.2 equivalents of tBuNC were mixed in THF and allowed to stir for 5 minutes. To this yellow solution, (DME)NiBr2 was added in portions over one minute. The solution turns dark purple. After 20 minutes, excess pentane was added to crash out a shiny purple solid. It was dried in vacuo and recrystallized by the vapor diffusion of pentane into a saturated THF solution (90-95% yield across several runs - for a representative trial, 0.6 g Ni(cod)2, 0.67 g (DME)NiBr2 and 1.1 mL tBuNC yielded 1.22 g of 1-tBu-Br, representing a 92% yield). X-ray quality crystals were obtained from several solvent combinations like THF / pentane and DFB / ether. H NMR (500 MHz, CD2CI2) 8 (ppm): 2.57 (s, 36H), C NMR (125 MHz, THF-d) 8 (ppm): 28.36. Elemental Analysis: found, C 40.31, H 6.12, 9.29%; calculated for C2oH36Br2N4Ni2, C 39.4, H 5.95, N 9.29%.

[0291] Example 3. Catalytic Reactions. Cross-coupling catalysis by Ni(I) isocyanide complexes. General procedures for isolation of products from cross-coupling reactions.

[0292] Csp2-CSp3 Kumada Coupling. All reactions were performed in the following conditions unless otherwise noted. In a N2- fdled glovebox, 1-tBu-Br (1 mol%, 0.01 mol), was dissolved in THF (1.0 mL) and added to the solution of aryl halide solution (1.0 mol). The Grignard reagent (1.5 equiv, 1.5 mmol) was then added to the mixture in one portion at room temperature. The reaction mixture was then stirred for 4 to 18 hours. Subsequently, the mixture was then taken out from the glovebox and quenched with saturated ammonium chloride solution and the solution was extracted with dichloromethane and dried over MgSO4. The product was then purified by column chromatography. Then the sample was analyzed by H, C, F NMRs or GC. l-cyclohexyl-4-(trifluoromethyl)benzene. The reaction was done at 3 mmol scale. After the Grignard was quenched by saturated ammonium chloride solution, dichloromethane was added to the reaction mixture and the combined organic layers were dried over MgSO4. The crude was purified by flash chromatography (hexane) to afford a clear oil (346 mg, 49%). Spectroscopic data is consistent with the previous report. (Org. Lett. 2019, 21, 8, 2947-2951). H NMR (499 MHz, CDC13) 8 7.54 (d, 2H, J= 9.0 Hz), 7.32 (d, 2H, J= 9.0 Hz), 2.57 (m, 1H), 1.87 (m, 4H), 1.79 (d, 1H), 1.42 (m, 4H),

[0293] 38

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[0295] UIUC2024-126-02(PCT) 1.28 (m, 1H). C NMR (151 MHz, CDC13) 8 152.18, 128.21 (quartet, J = 32 Hz), 127.29, 125.37 (quartet, J= 3.8 Hz), 123.66, 44.65, 34.36, 26.88, 26.16. F NMR (565 MHz, CDC13) 8 -62.24. HRMS (El): m / z Calcd. for C13H15F3: 228.1126. Found: 228.1122. l-octyl-4-(trifluoromethyl)benzene. The reaction was done at 1 mmol scale. After the Grignard was quenched by saturated ammonium chloride solution, diethyl ether was added to the reaction mixture and the combined organic layers were dried over MgSO4. The crude was purified by flash chromatography (hexane : ethyl acetate = 50 : 1) to afford a clear oil (99 mg, 38%). Spectroscopic data is consistent with the previous report. (D. A. Everson, R. Shrestha and D. J. Weix, J. Am. Chem. Soc., 2010, 132, 920-921). H NMR (499 MHz, CDC13) 8 7.53 (d, 2H, J= 8.0 Hz), 7.29 (d, 2H, J= 8.0 Hz), 2.66 (t, 2H, J= 7.5 Hz), 1.62 (m, 2H), 1.31 - 1.26 (m, 10H), 0.89 (t, 3H, J =

[0296] 6.5 Hz). C NMR (151 MHz, CDCH) 8 147.18, 128.82, 128.19, 127.98, 125.47, 125.28 (quartet, J =

[0297] 3.6 Hz), 35.95, 32.01, 31.36, 29.56, 29.37, 22.80, 14.25. F NMR (470 MHz, CDC13) 8 -62.66. HRMS (El): Calcd. for C15H21F3, 258.1595. Found: 258.1601.

[0298] 1 -cyclohexylquinoline. The reaction was done at 1 mmol scale. After the Grignard was quenched by saturated ammonium chloride solution, diethyl ether was added to the reaction mixture and the combined organic layers were dried over MgSO4. The crude was purified by flash chromatography (hexane : ethyl acetate = 9 : 1) to afford a yellow oil (87 mg, 41%). Spectroscopic data is consistent with the previous report (Eur. J. Org. Chem., 2015, 9, 1910-1914). H NMR (600 MHz, CDC13) 8 8.08 (d, 1H, J= 8.4 Hz), 8.05 (d, 1H, J = 8.4 Hz), 7.77 (d, J= 8.4 Hz), 7.67 (m, 1H), 7.47 (m, 1H), 7.33 (d, 1H, J= 9.0 Hz), 2.92 (tt, 1H, J= 12,2 Hz, 3.5 Hz), 2.03 (m, 2H), 1.90 (m, 2H), 1.79 (m, 1H), 1.63 (qd, 2H, J= 12.6 Hz, 3.4 Hz), 1.48 (qt, 2H, J= 12.9 Hz, 3.4 Hz), 1.34 (qd, 1H, J = 12.9 Hz, 3.7 Hz). 13C NMR (151 MHz, CDCh) 8 166.97, 147.92, 136.44, 129.35, 129.09, 127.56, 127.09, 125.72, 119.70, 47.78, 32.97, 26.67, 26.22. HRMS (El): Calcd. for C15H17N, 211.1361. Found: 211.1367.

[0299] Csp2-C3p2 Kumada Coupling. All reactions were performed in the following conditions unless otherwise noted. In a N2- fdled glovebox, 1-tBu-Br (1 mol%, 0.01 mol), was dissolved in THF (1.0 mL) and added to the solution of aryl halide solution (1.0 mol). The Grignard reagent (1.5 equiv, 1.5 mmol) was then added to the mixture in one portion at room temperature. The reaction mixture was then stirred for 4 to 18 hours. Subsequently, the mixture was then taken out from the glovebox and quenched with saturated ammonium chloride solution and the solution was extracted with

[0300] 500.161W01

[0301] UIUC2024-126-02(PCT) dichloromethane and dried over MgSO4. The product was then purified by column chromatography.

[0302] Then the sample was analyzed by H, C, F NMRs and HR- MS.

[0303] 4-methoxy-l,l'-biphenyl. The reaction was done at 1 mmol scale. After the Grignard was quenched by saturated ammonium chloride solution, di chloromethane was added to the reaction mixture and the combined organic layers were dried over MgSO4. The crude was purified by flash chromatography (5% EtOAc / hexane) to afford a beige solid (150 mg, 82%). Spectroscopic data is consistent with the previous report. H NMR (600 MHz, CDC13) 8 7.63 - 7.59 (m, 4H), 7.48 (t, J = 7.8 Hz, 2H), 7.38 - 7.35 (m, 1H), 7.05 - 7.03 (m, 2H), 3.89 (s, 3H). C NMR (151 MHz, CDC13) 8 159.24, 140.91, 133.84, 128.83, 128.24, 126.82, 126.76, 114.30, 55.39.

[0304] 4-fluoro-l, 1 '-biphenyl. The reaction was done at 1 mmol scale. After the Grignard was quenched by saturated ammonium chloride solution, di chloromethane was added to the reaction mixture and the combined organic layers were dried over MgSO4. The crude was purified by flash chromatography (5% EtOAc / hexane) to afford a white solid (124 mg, 74%). Spectroscopic data is consistent with the previous report. H NMR (600 MHz, CDC13) 8 7.64 (d, J = 7.7 Hz, 2H), 7.62 - 7.50 (m, 2H), 7.47 (q, J = 7.1 Hz, 3H), 7.39 (t, J = 7.5 Hz, 1H), 7.16 (t, J = 8.3 Hz, 1H). C NMR (151 MHz, CDC13) 8 163.41, 161.78, 141.37, 140.38, 128.95, 128.89, 127.39, 127.30, 127.15, 115.82, 115.67. F NMR (565 MHz, CDC13) 8 -115.78

[0305] 2-methyl-l, 1 '-biphenyl. The reaction was done at 1 mmol scale. After the Grignard was quenched by saturated ammonium chloride solution, di chloromethane was added to the reaction mixture and the combined organic layers were dried over MgSO4. The crude was purified by flash chromatography (hexanes) to afford a white solid (132 mg, 79% crude, 71% yield of cross-coupled product). This compound was isolated as an inseparable mixture with the homocoupled product derived from the electrophile. The yield reported is based on the integrations of the methyl protons of the respective protons in the NMR. Spectroscopic data is consistent with the previous report. H NMR (600 MHz, CDC13) 8 7.64 (d, J = 8.4 Hz, 3H), 7.48 (t, J = 6.9 Hz, 3H), 7.44 (d, J = 6.7 Hz, 2H), 7.38 (d, J = 8.3 Hz, 3H), 7.30 (d, J = 4.2 Hz, 2H), 7.28 (s, 2H), 2.31 (s, 3H), 2.10 (s, 1H). C NMR (151

[0306] 40

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[0308] UIUC2024-126-02(PCT) MHz, CDC13) 5 141.98, 141.29, 135.39, 130.35, 129.85, 129.27, 128.81, 128.11, 127.31, 127.22, 126.81, 125.81, 20.53, 19.88.

[0309] 3 -phenylpyridine. The reaction was done at 1 mmol scale. After the Grignard was quenched by saturated ammonium chloride solution, dichloromethane was added to the reaction mixture and the combined organic layers were dried over MgSO4. The crude was purified by flash chromatography (10% DCM / hexanes) to afford a beige solid (76 mg, 49%). Spectroscopic data is consistent with the previous report. H NMR (600 MHz, CDC13) 8 8.85 (s, 1H), 8.59 (s, 1H), 7.87 (d, J = 6.9 Hz, 1H), 7.58 (d, J = 7.1 Hz, 2H), 7.48 (t, J = 7.7 Hz, 2H), 7.40 (t, J = 7.4 Hz, 1H), 7.36 (s, 1H). C NMR (151 MHz, CDC13) 8 148.58, 148.45, 137.96, 136.76, 134.46, 129.19, 128.21, 127.28, 123.67.

[0310] Csp2-Csp2 Suzuki-Miyaura Coupling. All reactions were performed in the following conditions unless otherwise noted. In a N2-filled glovebox, 1-tBu-Br (2 mol%, 0.01 mol), was dissolved in dioxane (1.0 mL) and added to the the aryl halide solution (1.0 mol), the boronic acid (2 equiv, 2 mmol), and K3PO4 (3.5 equiv, 3.5 mmol). The reaction mixture was then stirred at 80 oC for 12 to 18 hours. Subsequently, the mixture was then taken out from the glovebox and quenched with distilled water and the solution was extracted with dichloromethane and dried over MgSO4. The product was then purified by column chromatography. Then the sample was analyzed by 1H, 13C, 19F NMRs or GC.

[0311] 4-(trifluoromethyl)- 1 , l'-biphenyl. The reaction was done at 1 mmol scale. After cooling down the reaction mixture, DI water was added to quench the nickel catalyst. Then di chloromethane was added to reaction mixture and the combined organic layers were dried over MgSO4. The crude was purified by flash chromatography (20% ethyl acetate / hexanes) to afford a white solid as the product (179 mg, 81%). H NMR (600 MHz, CDC13) 5 7.71 (s, 4H), 7.61 (d, J = 7.5 Hz, 2H), 7.49 (t, J = 7.5 Hz, 2H), 7.42 (t, J = 7.4 Hz, 1H). C NMR (151 MHz, CDC13) 8 144.87, 139.91, 129.13, 128.33, 127.56, 127.42, 125.88, 125.86, 125.83, 125.81. 19F NMR (565 MHz, CDC13) 8 -62.36.

[0312] 41

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[0314] UIUC2024-126-02(PCT) 2-methyl-4'-(trifluoromethyl)- 1 , 1 '-biphenyl. The reaction was done at 1 mmol scale. After cooling down the reaction mixture, DI water was added to quench the nickel catalyst. Then dichloromethane was added to reaction mixture and the combined organic layers were dried over MgSO4. The crude was purified by flash chromatography (hexanes) to afford a tan solid as the product (186 mg, 79% crude, 74% of the cross-coupled product based on the NMR integration). This compound was isolated as an inseparable mixture with the homocoupled product derived from the electrophile. The yield reported is based on the integrations of the methyl protons of the respective protons in the NMR. Spectroscopic data is consistent with the previous report. H NMR (600 MHz, CDC13) 8 7.74 (d, J = 7.9 Hz, 2H), 7.51 (d, J = 8.6 Hz, 2H), 7.40 - 7.31 (m, 3H), 7.28 (d, J = 7.2 Hz, 1H), 2.34 (s, 3H). C NMR (151 MHz, CDC13) 8 145.79, 140.66, 135.35, 130.68, 129.69, 128.10, 125.24, 125.22, 125.20, 125.17. 19F NMR (565 MHz, CDC13) 8 -62.31.

[0315] 3-(4-(trifluoromethyl)phenyl)pyridine. The reaction was done at 1 mmol scale. After cooling down the reaction mixture, DI water was added to quench the nickel catalyst. Then di chloromethane was added to reaction mixture and the combined organic layers were dried over MgSO4. The crude was purified by flash chromatography (40% ethyl acetate / hexanes) to afford a yellow oil as the product (158 mg, 71%). H NMR (600 MHz, CDC13) 8 8.85 (s, 1H), 8.64 (s, 1H), 7.89 (d, J = 8.0 Hz, 1H), 7.73 (d, J = 8.0 Hz, 2H), 7.68 (d, J = 8.0 Hz, 2H), 7.44 - 7.37 (m, 1H). C NMR (151 MHz, CDC13) 8 149.41, 148.38, 141.46, 135.44, 134.70, 127.61, 126.20, 126.18, 126.15, 126.13, 123.85. F NMR (565 MHz, CDC13) 8 -62.57.

[0316] 2-(4-(trifluoromethyl)phenyl)quinoline. The reaction was done at 1 mmol scale. After cooling down the reaction mixture, DI water was added to quench the nickel catalyst. Then dichloromethane was added to reaction mixture and the combined organic layers were dried over MgSO4. The crude was purified by flash chromatography (10% dichloromethane / hexanes) to afford a yellow oil as the product (226 mg, 83%). H NMR (600 MHz, Acetone) 8 8.52 (d, J = 8.0 Hz, 2H), 8.46 (d, J = 8.6 Hz, 1H), 8.18 (d, J = 8.6 Hz, 1H), 8.15 (d, J = 8.5 Hz, 1H), 8.00 (d, J = 7.4 Hz, 1H), 7.89 (d, J = 7.4 Hz, 2H), 7.83 - 7.80 (m, 1H), 7.65 - 7.62 (m, 1H).

[0317] C NMR (151 MHz, Acetone) 8 155.83, 149.08, 143.91, 140.37, 138.23, 131.55, 130.87, 130.56, 129.14, 128.83, 128.65, 128.58, 127.81, 126.54, 126.52, 126.49, 126.47, 123.19, 119.55.

[0318] 500.161W01

[0319] UIUC2024-126-02(PCT)

[0320] 2-(pyridin-3-yl)quinoline. The reaction was done at 1 mmol scale. After cooling down the reaction mixture, DI water was added to quench the nickel catalyst. Then di chloromethane was added to reaction mixture and the combined organic layers were dried over MgSO4. The crude was purified by flash chromatography (10% ethyl acetate / hexanes) to afford a yellow crystalline solid as the product (127 mg, 62%). H NMR (600 MHz, CD2C12) 5 9.38 (d, J = 3.0 Hz, 1H), 8.68 (dd, J = 4.8, 1.7 Hz, 1H), 8.55 (dt, J = 7.9, 2.0 Hz, 1H), 8.30 (d, J = 9.7 Hz, 1H), 8.15 (d, J = 9.6 Hz, 1H), 7.93 (d, J = 8.5 Hz, 1H), 7.89 (d, J = 8.1 Hz, 1H), 7.77 (ddd, J = 8.4, 6.8, 1.5 Hz, 1H), 7.58 (ddd, J = 8.1, 6.8, 1.2 Hz, 1H), 7.48 (dd, J = 7.9, 5.7 Hz, 1H). C NMR (151 MHz, CD2C12) 8 154.81, 150.30, 148.89, 148.73, 137.54, 135.41, 135.30, 130.35, 130.03, 128.01, 127.85, 127.16, 124.08, 118.80. l-(4-(pyridin-3-yl)phenyl)ethan-l-one. The reaction was done at 1 mmol scale. After cooling down the reaction mixture, DI water was added to quench the nickel catalyst. Then di chloromethane was added to reaction mixture and the combined organic layers were dried over MgSO4. The crude was purified by flash chromatography (40% ethyl acetate / hexanes) to afford the product as a white crystalline solid (167 mg, 85%).

[0321] H NMR (499 MHz, CDCh) 8 8.84 (s, 1H), 8.60 (d, J= 4.8 Hz, 1H), 8.02 (d, J= 8.4 Hz, 2H), 7.87 (d, J= 7.9 Hz, 1H), 7.64 (d, J= 8.4 Hz, 2H), 7.36 (dd, J= 7.9, 4.8 Hz, 1H), 2.60 (s, 3H). C NMR (126 MHz, CDCH) 8 197.57, 149.17, 148.38, 142.30, 136.54, 135.45, 134.60, 134.51, 129.19, 129.12, 129.06, 127.29, 123.65, 26.78, 26.63.

[0322] Table 5. Control experiments for Csp2-Csp2 Kumada Coupling with 1-tBu-Br. All reported yields are from H or F NMR measurements against an internal standard. , ,

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[0326] Table 6. Control experiments for Csp2-Csp2 Kumada Coupling catalyzed by 1-tBu. , , Table 7. Csp2-Csp3 Kumada Coupling catalyzed by 1-tBu.

[0327] Csp2-CSp2 Suzuki-Miyaura Coupling. All reactions were performed in the following conditions unless otherwise noted. In a N2-fdled glovebox, 1-tBu-Br (2 mol%, 0.01 mol), was dissolved in dioxane (1.0 mL) and added to the the aryl halide solution (1.0 mol), the boronic acid (2 equiv, 2 mmol), and K3PO4 (3.5 equiv, 3.5 mmol). The reaction mixture was then stirred at 80 C for 12 hours. Subsequently, the mixture was then taken out from the glovebox and quenched with distilled water and the solution was extracted with dichloromethane and dried over MgSO4. The product was then purified by column chromatography. Then the sample was analyzed by H, C, F NMRs or GC.

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[0330] UIUC2024-126-02(PCT) Table 8. Control experiments for Suzuki-Miyaura coupling catalyzed by 1-tBu-Br. All reported yields are from F NMR measurements against an internal standard.

[0331] B(OH)2x mol% catalyst

[0332] Dioxane, K3PO4(3.5 equiv)

[0333] 2 equiv. 80 °C 12 hrs General procedure for Buchwald-Hartwig coupling. All reactions were performed in the following conditions unless otherwise noted. In a N2-filled glovebox, 1-tBu-Br (5 mol%, 0.01 mol) and diphenylphosphinoferrocene (dppf) (5 mol%, 0.01 mol) was dissolved in toluene (2.0 mL) and added to the the aryl halide solution (1.0 mol), morpholine (1.5 equiv, 1.5 mmol), and NaOtBu (1.5 equiv, 1.5 mmol). The reaction mixture was then stirred at 100 C for 12 hours. Subsequently, the mixture was then taken out from the glovebox and quenched with distilled water and the solution was extracted with dichloromethane and dried over MgSOi. The product was then purified by column chromatography. Then the sample was analyzed by H, C, F NMRs or GC.

[0334] Table 7. Control experiments for Buchwald-Hartwig coupling catalyzed by 1-tBu-Br. x mol% catalyst

[0335] 5 mol% dppf NaOfBu (1.5 equiv)

[0336] 1 .5 equiv Toluene, 100 °C

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[0339] UIUC2024-126-02(PCT) All publications, patents, and patent documents cited herein are incorporated by reference as though individually incorporated by reference. No limitations inconsistent with this disclosure are to be understood therefrom. The invention has been described with reference to various specific and preferred embodiments and techniques. However, many variations and modifications may be made while remaining within the spirit and scope of the invention.

[0340] While specific embodiments have been described above with reference to the disclosed embodiments and examples, such embodiments are only illustrative and do not limit the scope of the invention. Changes and modifications can be made in accordance with ordinary skill in the art without departing from the invention in its broader aspects as defined in the following claims.

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Claims

1. CLAIMSWhat is claimed is:

1. A dinuclear nickel(I) coordination complex comprising non-bridging and bridging isocyanide ligands; or isocyanide ligands and halide ligands.

2. The coordination complex of claim 1, wherein the dinuclear nickel(I) is coordinatively saturated.

3. The coordination complex of claim 1 , wherein the dinuclear nickel(I) is coordinatively unsaturated.

4. The coordination complex of any one of claims 1-3, wherein the isocyanide ligands are aliphatic substituted isocyanide ligands.

5. The coordination complex of any one of claims 1-3, wherein the isocyanide ligands are aromatic substituted isocyanide ligands.

6. The coordination complex of any one of claims 1-3, wherein the dinuclear nickel(I) is a homoleptic dinuclear nickel(I) isocyanide.

7. The coordination complex of claim 1, wherein the coordination complex is represented byFormula I:whereinR is -(Ci-Ci2)alkyl, -(C3-Ci2)cycloalkyl, aryl, or heteroaryl; wherein R is substituted or unsubstituted.

8. The coordination complex of claim 7, wherein R is / e / 7-butyl, cyclohexyl, adamantyl, 2,6- xylyl, or 2,6-diisopropylphenyl.47500.161W01UIUC2024-126-02(PCT)9. The coordination complex of claim 7, wherein the coordination complex is:[Ni(CNtBu)3(p-CNtBu)]2[BF4]2.

10. The coordination complex of claim 1, wherein the coordination complex is represented by Formula II:whereinX is halo; andR is -(Ci-Ci2)alkyl, -(C3-Ci2)cycloalkyl, aryl, or heteroaryl; wherein R is substituted or unsubstituted.

11. The coordination complex of claim 10, wherein X is Br.

12. The coordination complex of claim 10 or 11, wherein R is / e / -butyl, cyclohexyl, adamantyl, 2,6-xylyl, or 2,6-diisopropylphenyl.

13. The coordination complex of claim 10, wherein the coordination complex is:[Ni2(CNtBu)4Br2].

14. A composition comprising a coordination complex of any one of claims 1, 7 or 10 and a solvent.

15. A method for cross-coupling catalysis comprising contacting a coordination complex of any one of claims 1, 7 or 10 with: a) an organohalide or organotriflate; and b) an organometallic, organoboron, or organoamine; wherein a carbon-carbon bond or a carbon-nitrogen bond is formed in a cross-coupled product.

16. The method of claim 15, further comprising contacting the coordination complex with an ancillary ligand, wherein the ancillary ligand comprises one or more atom donors.48500.161W01UIUC2024-126-02(PCT)17. The method of claim 16, wherein the ancillary ligand is monodentate, bidentate, tri dentate, or tetradentate.

18. The method of claim 15, wherein the coordination complex is:[Ni(CNtBu)3(p-CNtBu)]2[BF4]2.

19. The method of claim 15, wherein the coordination complex is:[Ni2(CNtBu)4Br2].

20. The method of claim 15, wherein the organohalide or organotriflate and the organometallic or organoboron form a carbon-carbon bond in the cross-coupled product.

21. The method of claim 15, wherein the organohalide or organotriflate and the organoamine form a carbon-nitrogen bond in the cross-coupled product.49500.161W01UIUC2024-126-02(PCT)

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