NI(0) CATALYSTS

The invention was made with support from grant no. CHE-1265491, awarded by the National Science Foundation. The government has certain rights in this invention.

Previous reports described broad usage of nickel(0) complexes of N-heterocyclic carbene (NHC) ligands that are prepared either in situ from air-sensitive precursors or that are prepared and handled in an inert atmosphere glovebox. Nickel(0) NHC complexes where dimethyl fumarate stabilizes the complex and provides air stability are known, but the stabilizing dimethyl fumarate renders the catalysts too stable and inactive for most applications. Many examples of air-stable Ni(II) catalysts are known, but they typically do not involve NHC ligands, and they require reduction to the active Ni(0) form. To date, there are no examples of moderately air-stable Ni(0) complexes of NHC ligands that display good catalytic reactivity in transformations of broad interest to the pharmaceutical or polymer industries.

Provided herein are Ni(0) catalysts having a structure of formula (I) or (II):

wherein the dashed line is an optional double bond; each R¹is independently selected from the group consisting of H, C_1-8alkyl and C_1-2alkylenearyl; each R²is independently selected from the group consisting of H, halo, C_1-3alkyl, and aryl, or both R²together with the carbons to which they are attached form a 6-membered ring; each R³is the same and is H, C_1-4alkyl, or aryl; each R⁴is the same and is C_1-6alkyl, C_0-2alkylene-aryl or C_0-2alkylene-C_2-8alkene; each R⁵is the same and is H, C_1-6alkyl, aryl, CO₂C_0-2alkylene-aryl, CO₂C_0-2alkylene-C_2-8alkene, or CO₂C_2-6alkyl; and each R⁶is the same and is H, C_1-6alkyl, C_1-6alkoxy, or O-aryl, with the proviso that at least one of R¹and R⁶is not H. In some cases, the dashed line is a double bond. In some cases, each R¹is the same. In some cases, R¹is selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, t-butyl, isobutyl, pentyl, 3-pentyl, and diphenylmethyl. In some cases, each R¹is isopropyl. In some cases, R¹is H. In some cases, each R²is the same. In some cases, each R²is selected from H, chloro, and methyl. In some cases, both R²together with the carbons to which they are attached form a 5- to 7-membered ring. In some cases, R³is aryl. In some cases, R³is phenyl. In some cases, R³is C_1-4alkyl. In some cases, R³is methyl or ethyl. In some cases, R³is H. In some cases, R⁴is C_0-2alkylene-aryl. In some cases, R⁴is C₁alkylene-aryl. In some cases, the aryl of R⁴comprises phenyl or naphthyl. In some cases, R⁴is toluyl, methoxyphenyl, trialkylphenyl (e.g., trimethylphenyl or triisopropylphenyl), MeCO₂-phenyl, or phenyl. In some cases, R⁴is C_0-2alkylene-C_2-8alkene. In some cases, R⁴is C₁alkylene-C_2-8alkene. In some cases, R⁴is C₀alkylene-C_2-8alkene. In some cases, the C_2-8alkene is C₂alkene. In some cases, R⁴is C_2-6alkyl, such as isopropyl or t-butyl. In some cases, R⁵is H. In some cases, R⁵is C_1-6alkyl. In some cases, R⁵is aryl. In some cases, R⁵is CO₂C_0-2alkylene-aryl, CO₂C_0-2alkylene-C_2-8alkene, or CO₂C_2-6alkyl. In some cases, R⁵is CO₂-aryl, and in some cases the aryl is toluyl, methoxyphenyl, trialkylphenyl (e.g., trimethylphenyl or triisopropylphenyl), or CO₂Me-phenyl. In some cases, R⁵is CO₂C_2-6alkyl (e.g., CO₂isopropyl or CO₂t-butyl). In some cases, R⁵is C₀alkylene-C_2-8alkene. In some cases, R⁶is H. In some cases, R⁶is C_1-6alkyl. In some cases, R⁶is C_1-6alkoxy. In some cases, R⁶is O-aryl. In some cases, the catalyst has a structure of formula (I). In some cases, the catalyst has a structure of formula (II).

Further provided are methods of using the catalysts as disclosed herein to catalyze the formation of a C—C, C—N, or C—O bond. In some cases, the bond formation can occur at room temperature or at a temperature of less than 50° C. In some cases, the catalyst can be present in an amount of about 0.1 mol % to 20 mol %. In some cases, the catalyst catalyzes the C—N bond formation in a Buchwald-Hartwig reaction between (a) Ar—X or Het-X and (b) an amine, wherein Ar is aryl, Het is heteroaryl, and X is halide, sulfonate, or C_1-8alkyl-C(O)—O. In some cases, the catalyst catalyzes the C—C bond formation in a Sukuzi reaction between (a) Ar—X or Het-X and (b) a boronic acid, boronic ester, or a trifluoroborate, wherein Ar is aryl, Het is heteroaryl, and X is halide, sulfonate, or C_1-8alkyl-C(O)—O. In some cases, the catalyst catalyzes the C—O bond formation in a Buchwald-Hartwig reaction between (a) Ar—X or Het-X and (b) a hydroxyl compound, wherein Ar is aryl, Het is heteroaryl, and X is halide, sulfonate, or C_1-8alkyl-C(O)—O.

Provided herein are Ni(0) catalysts that can be used in the coupling reaction of a variety of starting materials, to form C—C, C—N, and C—O bonds. These catalysts are stable when exposed to air for short periods of time (e.g., 15 minutes or less) and still exhibit catalytic activity. In some cases, these catalysts are stable when exposed to air for up to three hours. This stability is in contrast to previously reported Ni(0) catalysts. In the past, Ni(0) catalysts would need to be generated in situ due to their instability from the precursor Ni(II) version.

Thus, as provided herein are Ni(0) catalysts of formula (I) or (II):

wherein the dashed line is an optional double bond; each R¹is independently selected from the group consisting of H, C_1-8alkyl and C_1-2alkylenearyl; each R²is independently selected from the group consisting of H, halo, C_1-3alkyl, and aryl, or both R²together with the carbons to which they are attached form a 6-membered ring; each R³is the same and is H, C_1-4alkyl, or aryl; each R⁴is the same and is C_1-6alkyl, C_0-2alkylene-aryl or C_0-2alkylene-C_2-8alkene; each R⁵is the same and is H, C_1-6alkyl, aryl, CO₂C_0-2alkylene-aryl, CO₂C_0-2alkylene-C_2-8alkene, or CO₂C_2-6alkyl; and each R⁶is the same and is H, C_1-6alkyl, C_1-6alkoxy, or O-aryl, with the proviso that at least one of R¹and R⁶is not H.

As used herein, the term “alkyl” refers to refers to straight chained and branched hydrocarbon groups, including but not limited to, methyl, ethyl, n-propyl, i-propyl, n-butyl, sec-butyl, t-butyl, n-pentyl, 3-pentyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, n-hexyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, and 2-ethybutyl. The term C_m-nmeans the alkyl group has “m” to “n” carbon atoms. The term “alkylene” refers to an alkyl group having a substituent. An alkyl, e.g., methyl, or alkylene, e.g., —CH₂—, group can be substituted with one or more, and typically one to three, of independently selected halo, trifluoromethyl, trifluoromethoxy, hydroxy, alkoxy, nitro, cyano, alkylamino, or amino groups, for example. The term “alkene” refers to an alkyl group that has at least one double bond.

As used herein, the term “aryl” refers to a monocyclic or polycyclic aromatic group, preferably a monocyclic or bicyclic aromatic group. Examples of aryl groups include, but are not limited to, phenyl, naphthyl, fluorenyl, azulenyl, anthryl, phenanthryl, pyrenyl, biphenyl, and terphenyl. Aryl also refers to bicyclic and tricyclic carbon rings, where one ring is aromatic and the others are saturated, partially unsaturated, or aromatic, for example, dihydronaphthyl, indenyl, indanyl, or tetrahydronaphthyl (tetralinyl). Unless otherwise indicated, an aryl group can be unsubstituted or substituted with one or more, and in particular one to four, groups independently selected from, for example, halo, alkyl, alkenyl, —OCF₃, —NO₂, —CN, —NC, —OH, alkoxy, amino, alkylamino, —CO₂H, —CO₂alkyl, —OCOalkyl, aryl, heteroaryl, and O-aryl.

As used herein, the term “heteroaryl” refers to a monocyclic or polycyclic ring system (for example, bicyclic) containing one or two aromatic rings and containing at least one nitrogen, oxygen, or sulfur atom in an aromatic ring. Each ring of a heteroaryl group can contain one or two O atoms, one or two S atoms, and/or one to four N atoms, provided that the total number of heteroatoms in each ring is four or less and each ring contains at least one carbon atom. In certain embodiments, the heteroaryl group has from 5 to 20, from 5 to 15, or from 5 to 10 ring atoms. Examples of monocyclic heteroaryl groups include, but are not limited to, furanyl, imidazolyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, thiadiazolyl, thiazolyl, thienyl, tetrazolyl, triazinyl, and triazolyl. Examples of bicyclic heteroaryl groups include, but are not limited to, benzofuranyl, benzimidazolyl, benzoisoxazolyl, benzopyranyl, benzothiadiazolyl, benzothiazolyl, benzothienyl, benzothiophenyl, benzotriazolyl, benzoxazolyl, furopyridyl, imidazopyridinyl, imidazothiazolyl, indolizinyl, indolyl, indazolyl, isobenzofuranyl, isobenzothienyl, isoindolyl, isoquinolinyl, isothiazolyl, naphthyridinyl, oxazolopyridinyl, phthalazinyl, pteridinyl, purinyl, pyridopyridyl, pyrrolopyridyl, quinolinyl, quinoxalinyl, quiazolinyl, thiadiazolopyrimidyl, and thienopyridyl. Unless otherwise indicated, a heteroaryl group can be unsubstituted or substituted with one or more, and in particular one to four, substituents selected from, for example, halo, alkyl, alkenyl, —OCF₃, —NO₂, —CN, —NC, —OH, alkoxy, amino, alkylamino, —CO₂H, —CO₂alkyl, —OCOalkyl, aryl, heteroaryl, and O-aryl.

Some specific catalysts contemplated include

wherein Tol is

The synthesis of the catalysts disclosed herein follows one of the following general procedures dependent on ligand structure.

General Procedure for Ni(NHC)(Acrylate)₂Complexes where Ortho-R₁is not an H:

A solution of Ni(COD)₂(1.0 equiv) and acrylate (4.0 equiv) was stirred in 4.0 mL of toluene for 30 min. In a separate vial, NHC salt (1.0 equiv) and KO-t-Bu (1.1 equiv) was stirred for 30 min in 4.0 mL of toluene. The ligand solution was added dropwise to the nickel solution, and the reaction mixture was stirred overnight at rt. The solution was filtered and the precipitate was washed with toluene. The volatiles were then removed in vacuo. Pentane was added to the resulting crude mixture, and the desired product could be precipitated at −20° C.—rt and isolated by filtration.

General Procedure for Ni(NHC)(Acrylate)₂Complexes where Ortho-R₁is an H:

A solution of Ni(COD)₂(1.0 equiv) and acrylate (4.0 equiv) was stirred in 8.0 mL of toluene for 30 min. A solid mixture of NHC salt (1.0 equiv) and KO-t-Bu (1.1 equiv) was added slowly in portions over the course of 15 min. The resulting reaction mixture was stirred overnight at rt. The solution was filtered and the precipitate was washed with toluene. The volatiles were then removed in vacuo. Pentane was added to the resulting crude mixture, and the desired product could be precipitated at −20° C.—rt and isolated by filtration.

General Procedure for Ni(NHC)(Fumarate)₂Complexes:

A THF solution of NHC (1 equiv.) was added dropwise to a solution of Ni(COD)₂(1 equiv.) in THF at room temperature. The solution was stirred for 30 minutes and a solution of fumarate in THF (2 equiv.) was added dropwise. Afterwards, the system was stirred at room temperature for 2 h. The product could be crystallized from pentane yielding red-orange crystals.

General Procedure for Air-Stability Test:

Catalyst was weighed out into a reaction vessel inside a glove box. It was then removed and exposed to air. Then the reaction vessel was pump/purged with N₂gas three times. After purging the vessel, the general procedure for the reaction indicated was carried out.

The catalysts disclosed herein can be used for form C—C, C—N, and C—O bonds, for example, in a Suzuki coupling, a Buchwald-Hartwig coupling, or a ketone hydrosilylation.

The catalyst can catalyze the reaction of (a) Ar—X or Het-X and (b) an amine, wherein Ar is aryl, Het is heteroaryl, and X is halide, sulfonate, or C_1-8alkyl-C(O)—O.

General Procedure for Ni(IPr)(Benzyl Methacrylate)₂Promoted Buchwald-Hartwig Cross-Coupling:

In a glove box, catalyst Ni(IPr)(benzyl methacrylate) (2 mol %) and NaO-tBu (1.1 equiv) were dissolved in 1.0 mL of THF. Aryl halide (1.0 equiv) was added to the solution containing catalyst and NaO-tBu followed by the addition of amine (1.5 equiv). The reaction was sealed and stirred at 23° C. until no starting material remained. The reaction mixture was quenched with addition of dichloromethane and filtered through a pad of silica gel eluting with 50% v/v EtOAc/hexanes. The solvent was removed in vacuo, and the crude residue was purified via flash chromatography on silica gel to afford desired product.

The catalyst can catalyze the reaction of (a) Ar—X or Het-X and (b) a hydroxyl compound, wherein Ar is aryl, Het is heteroaryl, and X is halide, sulfonate, or C_1-8alkyl-C(O)—O.

The catalyst as disclosed herein can also be used to catalyze the diastereoselective hydrosilylation of ketones which is the reaction of (a) ketone and (b) silane.

General Procedure for Ni(1,3-bis(3,5-di-tert-butylphenyl)imidazolidin-2-yl)(phenyl methacrylate)₂Promoted Aldehyde Hydrosilylation:

In a glove box, Ni(1,3-bis(3,5-di-tert-butylphenyl)imidazolidin-2-yl)(phenyl methacrylate)₂(2 mol %) and silane (1.1 equiv) were weighted out into a vial. A 1 mL solution of ketone (1.0 equiv) was added to the vial and it stirred at 23° C. until no starting material remained. The reaction mixture was quenched with the addition of dichloromethane and filtered through a pad of silica gel eluting with 50% v/v EtOAc/hexanes. The solvent was removed in vacuo, and the crude residue was purified via flash chromatography on silica gel to afford desired product.

The catalyst can catalyze the reaction of (a) Ar—X or Het-X and (b) a boronic acid, boronic ester, or a trifluoroborate, wherein Ar is aryl, Het is heteroaryl, and X is halide, sulfonate, or C_1-8alkyl-C(O)—O.

General Procedure for Ni(NHC)(Acrylate)₂Promoted Suzuki-Miyaura Cross-Coupling:

Ni(NHC)(acrylate)₂(0.05 equiv.), K₃PO₄(3 equiv.) and boronic acid (1.5 equiv) were added to a 1-dram vial with a stir bar. Then THF (0.2 M) was added followed by aryl chloride (1.0 equiv.). Reactions were quenched by a small amount of CH₂Cl₂and air exposure. Reaction crude was pushed through a silica plug and yield was obtained from crude NMR using dibromomethane as an internal standard.

The catalyst can also catalyze the reaction of an aldehyde, alkyne and silane to produce silyl-protected allylic alcohols. In some case this reaction can be performed with high regiocontrol.

General Procedure for Aldehyde-Alkyne Reductive Coupling:

The catalyst (0.005 mmol for a 2 mol % reaction) was dissolved in 1 mL of THF, and then the alkyne (0.25 mmol), the aldehyde (0.25 mmol) and the trialkylsilane (0.50 mmol) were sequentially added to the stirred mixture. Finally, 1 mL of THF is added to achieve 0.125 M concentration and the mixture was stirred for 24 hours. The reaction was quenched opening the vial to air and 2 mL of hexane were added, stirring for 5 minutes. Finally, the crude mixture was filtered through a plug of silica eluting the product with 2% AcOEt in hexanes and product was purified by column chromatography (silica gel, hexanes).

The catalyst can also be used to catalyze the reaction of an alkene and an alkyne. A vast array of catalytic methods have been developed for the union of two g-components via carbon-carbon bond formation. The majority of such methods involve the redistribution of atoms without a net change in the oxidation state in the components. For example, the coupling of an alkene and alkyne to produce a diene (product 1, FIG. 1), the hydrovinyl of alkenes, and the hydroacylation of an alkyne or alkene with an aldehyde are representative examples of processes of this type. The participation of substrates lacking π-bonds in processes of this type have more recently been made possible by sequential hydrogen transfer/C—C coupling events, as illustrated by the coupling of an alcohol and allene to produce a homoallylic alcohol. All of the above-mentioned processes share the characteristic of being completely atom-economical without a net formal change in oxidation state of the reactants.

A second group of processes that similarly enable the union of two π-components involves catalytic methods conducted in the presence of a reductant, wherein a net two-electron reduction of the starting components occurs during the coupling event. Examples of this type of process include the coupling of enones and alkynes to produce γ,δ-unsaturated ketones (product 2, FIG. 1), the coupling of aldehydes and alkynes to produce allylic alcohols, 5 or the coupling of allylic alcohols with alkynes to produce skipped dienes. Each of these processes share the characteristic of a net two-electron reduction accompanying the coupling event. In the course of exploring the development of catalytic reductive coupling methods, an unexpected conversion of enones and alkynes to skipped diene products was observed with complete deoxygenation of the enone substrate (product 3, FIG. 1).

Prior reports described the efficient reductive coupling of enals and alkynes in the presence of silane reductants and Ni(COD)₂with PCy₃to produce Z-enol silanes 4 (FIG. 2). During efforts to extend this reactivity to enones rather than enals, exploration with a range of phosphine and N-heterocyclic carbene (NHC) ligands afforded low yields of the expected trisubstituted enol silanes, with alkyne hydrosilylation being the major side reaction. However, attempting the reaction with the unhindered NHC ligand ITol (5) while using Ti(O-i-Pr)₄as a promoter for the process led to the unexpected production of skipped diene 7 in 37% isolated yield. Omission of Ti(O-i-Pr)₄or replacement of ITol with more common NHC ligands that bear ortho substituents on the N-aryl group such as IMes (N-mesityl) or IPr (N-[2,6-diisopropylphenyl]) failed to produce more than trace quantities of the skipped diene product 7. Replacement of Ti(O-i-Pr)4 with isopropanol did result in production of 7, but in considerably lower isolated yield than when Ti(O-i-Pr)₄was used.

Among the many classes of NHC complexes of nickel explored in various contexts, ligands such as ITol that lack ortho substituents on the N-aryl group typically lead to low-yielding and inconsistent reactions compared with the substantially more robust analogous catalysts derived from IMes or IPr. Given this limitation and the unique behavior of ITol in promoting the formation of skipped diene 7, the preparation of stable pre-catalysts of Ni(0) coordinated with ITol was examined. Among several classes of well-defined catalysts examined, Ni(0) complex 6 derived from methyl methacrylate, ITol.HBF₄, and Ni(COD)₂, had the desirable attributes of ease of preparation, moderate air stability, and high reactivity in the production of skipped dienes, as evidenced by the production of 7a in 90% isolated yield (FIG. 2). Based on this outcome, the utility of catalyst 6 was employed in further exploration of skipped dienes via the four-electron reductive coupling of enones and alkynes.

Utilizing the optimized procedure with catalyst 6, Et3SiH, and Ti(O-i-Pr)₄, the production of skipped diene products from a range of alkynes (2.0 equiv) with enones and enals (1.0 equiv) was examined (Table 1). Utilizing a range of enone substrates, products 7a-7h were obtained in good yield with >95:5 regioselectivity. Within these examples, the enone substrates included phenyl and methyl ketones with aromatic or aliphatic substituents at the enone β-position. The alkyne could be varied to include symmetrical or unsymmetrical alkynes including aromatic alkynes, terminal alkynes, and alkynes bearing phthalimido or silyloxy functionality. Notably, cyclic enones such as cyclohexenone (not shown) were generally ineffective substrates in this transformation. The process was very effective with enal substrates to produce products 8a-8d, including enals that possessed aromatic or aliphatic β-substituents. Notably, an enal that lacked β-substituents (product 8c) was an efficient substrate, whereas enones that lacked a β-substituent were ineffective in the transformation.

Given the novelty of the four-electron reductive coupling and the unusual combination of reactive components, a series of experiments were conducted to better understand the mechanism of this process (FIG. 3). Given the precedent for two-electron reductive couplings to generate enol silane products (i.e. product 4, FIG. 2), enol silane production followed by reductive cleavage of the C—OSiEt₃bond was the likely operative mechanistic pathway. However, attempts to reduce compound 4a under the reaction conditions failed to produce skipped diene 8a. A second alternative considered was that enal 1,2-hydrosilylation was followed by alkyne addition to the resulting silylated allylic alcohol. However, exposure of the silylated allylic alcohol derived from cinnamaldehyde to the reaction conditions also failed to produce skipped diene product 8a.

Important insight was gained in deuterium-labelling studies in the production of d-4a and d-8a from cinnamaldehyde and phenyl propyne (FIG. 4). Using the previously published procedure with PCy₃as ligand and Et₃SiD as reductant, 7a the deuterium label is exclusively introduced on the alkyne-derived terminus of the product d-4a as expected. However, in the skipped diene production using catalyst 6 with Et₃SiD, deuteration of the enal-derived terminal methylene group exclusively cis to the central carbon was observed in product (5-d)-8a, and no label incorporation in the alkyne-derived terminus was observed. Using Ti(O-i-C₃D₇)₄, 91% deuterium incorporation to the alkyne-derived terminus was observed in product (1-d)-8a, and no label incorporation at the enal-derived terminus was observed.

On the basis of these experiments, a mechanism that ex-plains the surprising outcome of these labeling experiments can be formulated (FIG. 5). Oxidative cyclization of the enone and alkyne with Ni(0) provides seven-membered metallacycle 9 with an r 1 nickel O-enolate motif, 12,13 and σ-bond metathesis of the silane with the Ni—O bond provides a nickel hydride intermediate 10 bearing an enol silane functionality. This intermediate serves as a common intermediate leading to two-electron or four-electron reductive coupling pathways. With PCy₃as ligand, reductive elimination of the C—H bond provides the observed enol silane product 4 in analogy to previous reports. However, the unique reactivity illustrated by the unhindered NHC ligand ITol likely suppresses the efficiency of reductive elimination while allowing coordination and insertion of the tethered enol silane functionality via species 11 to provide intermediate 12. Bond-rotation in 12 to produce rotamer 13 is then followed by anti-elimination of the silyloxy group, promoted by the Ti(O-i-Pr)₄Lewis acid, to provide intermediate 14 with isopropoxy transfer from Ti to Ni. Extrusion of acetone to generate 15 and reductive elimination of the C—H bond provides the observed product 7/8.

Several experimental observation support the above postulated mechanistic pathway. The r 1 nickel O-enolate form of metallacycle 9 (FIG. 5) is supported by the observed Z-enol silane stereochemistry of 4 and is consistent with prior crystallographic analysis of the analogous TMEDA and bipyridine metalacycles. While stereoselective formation of the 1,2-trans-alkene generated by enone couplings (product 7, Table 1) could potentially be biased by the thermodynamic stability of the trans alkene, the stereochemical outcome of aldehyde coupling [product (5-d)-8a, FIG. 4] using Et₃SiD with catalyst 6 provides evidence for a pathway consistent with syn addition to the Z-enol silane followed by anti-silyloxy elimination. The overall positional selectivity using Et₃SiD and Ti(O-i-C₃D₇)₄[comparing products (5-d)-8a (1-d)-8a, FIG. 4] are fully consistent with the proposed mechanistic pathway. In particular, the diverging mechanisms from intermediate 10 leading to changes in position of deuterium incorporation explain the labeling outcomes in the production of d-4a and d-8a.

Unless otherwise noted, all reactions were conducted in flame-dried or oven dried (120° C.) glassware with magnetic stirring under an atmosphere of dry nitrogen. Toluene was purified under nitrogen using a solvent purification system (Innovative Technology, Inc., Model # SPS-400-3). Benzylideneactecone (Acros), trans-chalcone (Sigma-Aldrich), (E)-1-phenylbut-2-en-1-one (AstraTech, Inc.), 1-phenyl-1-propyne (Sigma-Aldrich), 3-hexyne (Sigma-Aldrich), 1-octyne (Sigma-aldrich), and N-(2-butynyl)phthalimide (Sigma-Aldrich), and cyclohex-2-en-1-one (Sigma-Aldrich) were used as received. (E)-5-methylhex-3-en-2-one (Sigma-Aldrich), trans-cinnamaldehyde (Sigma-Aldrich), crotonaldehyde (Acros), and methacrolein (Sigma-Aldrich) were distilled prior to use. (E)-3-(4-fluorophenyl)-1-phenylprop-2-en-1-one, (E)-3-(4-methoxyphenyl)-1-phenylprop-2-en-1-one (Wong, L. Eur. J. Org. Chem. 2014, 33, 7343), tert-butyldimethyl((5-phenylpent-4-yn-1-yl)oxy)silane (Six, Y. Eur. J. Org. Chem. 2003, 7, 1157), (cinnamyloxy)triethylsilane (Ikawa, T. Tetrahedron. 2004, 60, 6901), and triethyl(((1Z,4E)-4-methyl-3,5-diphenylpenta-1,4-dien-1-yl)oxy)silane (Montgomery, J. J. Am. Chem. Soc. 2008, 130, 8132) were prepared as per the literature procedure noted. Triethylsilane (Sigma-Aldrich) was passed through basic alumina and stored under nitrogen in Schlenk glassware. Titanium(IV) isopropoxide (Sigma-Aldrich) was distilled and stored under nitrogen in Schlenk glassware. Triethylsilyldeuteride (Sigma-Aldrich) and 2-propanol-d8 (Sigma-Aldrich) were used without further purification. 1,3-Bis(4-methylphenyl)imidazolium chloride (ITol) was prepared as per the literature procedure in Arduengo, A. J., III U.S. Pat. No. 5,007,414, 1991.

Analytical thin layer chromatography (TLC) was performed on Kieselgel 60 F254 (250 μm silica gel) glass plates and compounds were visualized with UV light and p-anisaldehyde or potassium permanganate stains. Flash column chromatography was performed using Kieselgel 60 (230-400 mesh) silica gel. Eluent mixtures are reported as v:v percentages of the minor constituent in the major constituent. All compounds purified by column chromatography were sufficiently pure for use in further experiments unless otherwise indicated.

¹H NMR spectra were collected at 400 MHz on a Varian MR400, at 500 MHz on a Varian Inova 500 or Varian vnmrs 500, or at 700 MHz on a Varian vnmrs 700 instrument. The proton signal of the residual, nondeuterated solvent (δ 7.26 for CHCl3 or 7.15 for C6D6) was used as the internal reference for 1H NMR spectra. 13C NMR spectra were completely heterodecoupled and measured at 125 MHz. Residual chloroform-d3 (δ 77.0) or benzene-d6 (δ 128.0) was used as an internal reference. High resolution mass spectra were recorded on a VG 70-250-s spectrometer manufactured by Micromass Corp. (Manchester UK) at the University of Michigan Mass Spectrometry Laboratory.

A solution of 1,3-Bis(4-methylphenyl)imidazolium chloride (5.82 g, 20.4 mmol) in 100.0 mL of water was allowed to stir. To this was added HBF₄(40% in H₂O, 5.38 mL, 24.5 mmol) and the resulting mixture was stirred at room temperature for 12 hours. The solution was then filtered and the resulting precipitate was washed with water. The volatiles were then removed in vacuo. The resulting orange-brown solid was then recrystallized from CH₂Cl₂and methanol to afford the desired product as a dark-brown solid (4.01 g, 0.12 mmol, 59% yield).¹H-NMR (500 MHz, CDCl₃): δ 9.36 (s, 1H), 7.69 (s, 2H), 7.58 (d, J=8.3 Hz, 4H), 7.35 (d, J=8.1 Hz, 4H), 2.40 (s, 6H).¹³C-NMR (125 MHz, CDCl₃): δ 141.3, 132.6, 131.8, 131.1, 122.17, 122.11, 21.1. HRMS (ESI) m/z: [M-BF₄⁻] calc. for C₁₇H₁₇N₂⁺, 249.1386, found, 249.1387.

Following general procedure for Ni(0) catalyst synthesis: Ni(COD)₂(550 mg, 2.00 mmol), methyl methacrylate (0.84 mL, 8.0 mmol), ITol.HBF₄(672 mg, 2.00 mmol) and KO-t-Bu (246 mg, 2.20 mmol) was stirred for 30 min in 10 mL of toluene. The ligand slurry was added dropwise to the nickel solution, and the reaction mixture was stirred overnight at rt. The solution was filtered and the precipitate was washed with toluene. The volatiles were then removed in vacuo. The crude product was a dark yellow solid. Washing with pentane yielded a pale yellow powder (537 mg, 1.06 mmol, 53% yield). X-ray quality crystals were grown at −20° C. in a solution of toluene and diethyl ether.¹H-NMR (700 MHz, C₆D₆): The¹H NMR peaks reported correspond to the major isomer, although the spectrum also shows the presence of higher symmetry diastereomers. δ 7.59 (d, J=7.7 Hz, 4H), 7.03 (d, J=7.7 Hz, 4H), 6.71 (s, 2H), 3.54 (s, 6H), 3.46 (s, 2H), 2.34 (s, 2H), 2.01 (s, 6H), 1.60 (s, 6H).¹³C-NMR (175 MHz, C₆D₆): Major and minor isomers are reported together. δ 174.0, 138.5, 137.6 137.5, 137.4, 129.9, 129.8, 129.6, 124.5, 123.9, 123.6, 122.0, 121.7, 121.6, 50.6, 20.9, 20.8, 20.1, 18.8. Anal calcd for C₂₇H₃₂N₂NiO₄: C (63.93%), N (5.52%), H (6.36%); found: C (63.32%), N (5.09%), H (6.52%).

Following general procedure for Ni(0) catalyst synthesis: Ni(COD)₂(138 mg, 0.5 mmol), benzyl methacrylate (0.34 mL, 2.0 mmol), IPr HCl (213 mg, 0.5 mmol) and KO-t-Bu (67.3 mg, 0.6 mmol) the desired product was precipitated from pentane at rt and was isolated as a yellow solid (395.4 mg, 99% yield).

Following general procedure for Ni(0) catalyst synthesis: Ni(COD)₂(138 mg, 0.5 mmol), benzyl methacrylate (0.34 mL, 2.0 mmol) and IPr*OMe (473 mg, 0.5 mmol), the desired product was precipitated from toluene and washed with pentane and was isolated as a yellow solid (579 mg, 86% yield).

Following general procedure for Ni(0) catalyst synthesis: Ni(COD)₂(257 mg, 0.9 mmol), phenyl methacrylate (0.58 mL, 3.7 mmol), 1,3-bis(3,5-di-tert-butylphenyl)imidazolinium chloride (500 mg, 0.9 mmol) and KO-t-Bu (126 mg, 1.1 mmol), the desired product was precipitated from pentane at −20° C. and was isolated as an orange solid (149 mg, 20% yield).

Ni(1,3-bis(2,4,6-trimethylphenyl)imidazolidin2-yl)(di(o-PhMe)fumarate)₂

wherein Tol is

Following general procedure for Ni (0) catalyst synthesis: Ni(COD)₂(137 mg, 0.5 mmol), di(o-PhMe)fumarate (282 mg, 1.0 mmol), 1,3-bis(2,4,6-trimethylphenyl)-1,3-dihydro-2H-imidazol-2-ylidene (152 mg, 0.5 mmol), the desired product was isolated as a red crystalline solid (280 mg, 60% yield).

10 mol % of Ni(ITol)(MMA)₂was dissolved in 1.0 mL toluene. Enone or enal (1.0 equiv) and alkyne (2.0 equiv) were added neat to the reaction mixture. Triethylsilane (4.0 equiv) was then added, followed by addition of Ti(O-iPr)₄(2.0 equiv), and the reaction mixture was placed in a heating mantle set to 65° C. and allowed to stir until starting materials were consumed (typically 8 h). The reaction mixture was then filtered through a plug of silica and was washed with a 1:1 mixture of EtOAc:hexanes. The solvent was then removed in vacuo, and the crude reaction mixture was purified via flash chromatography to afford the desired product.

((1E,4E)-4-Ethylhepta-1,4-diene-1,3-diyl)dibenzene. Table 1, Compound 7a: Following the general procedure (A), the reaction of Ni(ITol)(MMA)₂(15.3 mg, 0.03 mmol), triethylsilane (139.2 mg, 1.2 mmol), titanium(IV) isopropoxide (93.7 mg, 0.33 mmol), trans-chalcone (62.4 mg, 0.3 mmol), and 3-hexyne (49.3 mg, 0.6 mmol) gave a crude residue, which was purified via flash chromatography (100% hexanes) to afford a single regioisomer in a >98:2 isolated regioselectivity (>98:2 crude regioselectivity) (74.5 mg, 0.27 mmol, 90% yield).¹H-NMR (500 MHz, CDCl₃): δ 7.39-7.21 (m, 10H), 6.51 (dd, J=15.8, 7.6 Hz, 1H), 6.28 (d, J=15.8 Hz, 1H), 5.29 (t, J=7.2 Hz, 1H), 4.21 (d, J=7.5 Hz, 1H), 2.19-2.11 (m, 3H), 1.92 (dq, J=14.6, 7.6 Hz, 1H), 1.02 (t, J=7.5 Hz, 3H), 0.96 (t, J=7.5 Hz, 3H).¹³C-NMR (125 MHz, CDCl₃): δ 142.8, 142.2, 137.7, 132.9, 130.4, 128.9, 128.7, 128.5, 128.3, 127.0, 126.3, 126.2, 54.6, 23.3, 21.1, 14.6, 13.7. IR (film, cm⁻¹): 3024, 2959, 2869, 1599, 1491, 1447. HRMS (EI) m/z: [M+]⁺ calc. for C₂₁H₂₄, 276.1878, found, 276.1866.

((1E,4E)-4-Ethyl-3-methylhepta-1,4-dien-1-yl)benzene. Table 1, Compound 7b: Following the general procedure (A), the reaction of Ni(ITol)(MMA)₂(15.3 mg, 0.03 mmol), triethylsilane (139.2 mg, 1.2 mmol), titanium(IV) isopropoxide (93.7 mg, 0.33 mmol), (E)-1-phenylbut-2-en-1-one (43.8 mg, 0.3 mmol), and 3-hexyne (49.3 mg, 0.6 mmol) gave a crude residue, which was purified via flash chromatography (100% hexanes) to afford a single regioisomer in a >98:2 isolated regioselectivity (>98:2 crude regioselectivity) (34.1 mg, 0.16 mmol, 53% yield).¹H-NMR (400 MHz, CDCl₃): δ 7.33 (d, J=7.8 Hz, 2H), 7.25 (t, J=7.4, 2H), 7.17 (t, J=7.4 Hz, 1H), 6.33 (d, J=15.8 Hz, 1H), 6.13 (dd, J=15.9, 7.2 Hz, 1H), 5.17 (t, J=7.0 Hz, 1H), 2.93 (m, 1H), 2.01 (m, 4H), 1.18 (d, J=7.0 Hz, 3H), 0.96 (dt, J=2.5 7.3 Hz, 6H).¹³C-NMR (125 MHz, CDCl₃): δ 143.7, 137.9, 135.7, 128.5, 128.1, 126.8, 126.02, 126.00, 43.2, 22.5, 21.0, 19.3, 14.7, 14.1. IR (film, cm⁻¹): 2963, 2870, 2164, 1497, 1458. HRMS (EI) m/z: [M+]⁺ calc. for C₁₆H₂₂, 214.1722, found, 214.1723.

((1E,4E)-2-Methylhexa-1,4-diene-1,3-diyl)dibenzene. Table 1, Compound 7c: Following the general procedure (A), the reaction of Ni(ITol)(MMA)₂(15.3 mg, 0.03 mmol), triethylsilane (139.2 mg, 1.2 mmol), titanium(IV) isopropoxide (93.7 mg, 0.33 mmol), benzylideneactecone (43.8 mg, 0.3 mmol), and 1-phenyl-1-propyne (70.2 mg, 0.6 mmol) gave a crude residue, which was purified via flash chromatography (100% hexanes) to afford a single regioisomer in a >98:2 isolated regioselectivity (>98:2 crude regioselectivity) (58.8 mg, 0.24 mmol, 79% yield).¹H-NMR (500 MHz, CDCl₃): δ 7.36-7.21 (m, 10H), 6.46 (s, 1H), 5.85 (dd, J=15.1, 7.5 Hz, 1H), 5.52 (dq, J=15.1, 7.8 Hz), 4.11 (d, J=7.8 Hz, 1H), 1.79 (s, 3H), 1.78, (s, 3H).¹³C-NMR (125 MHz, CDCl₃): δ 142.9, 140.8, 138.4, 132.2, 129.0, 128.4, 128.3, 120.0, 127.0, 126.6, 126.3, 126.1, 57.8, 18.1, 17.3. IR (film, cm⁻¹): 3023, 2913, 2854, 1492, 1447. HRMS (EI) m/z: [M+]⁺ calc. for C₁₉H₂₀, 248.1565, found, 248.1563.

2-((2E,5E)-3-Methyl-4,6-diphenylhexa-2,5-dien-1-yl)isoindoline-1,3-dione. Table 1, Compound 7d: Following the general procedure (A), the reaction of Ni(ITol)(MMA)₂(15.3 mg, 0.03 mmol), triethylsilane (139.2 mg, 1.2 mmol), titanium(IV) isopropoxide (93.7 mg, 0.33 mmol), trans-chalcone (62.4 mg, 0.3 mmol), and N-(2-butynyl)phthalimide (119.5 mg, 0.6 mmol) gave a crude residue, which was purified via flash chromatography (hexanes: ethyl acetate=97:3) to afford a single regioisomer in a >98:2 isolated regioselectivity (>98:2 crude regioselectivity) (93.2 mg, 0.22 mmol, 73% yield).¹H-NMR (500 MHz, CDCl₃): δ 7.86 (dd, J=5.3, 3.1 Hz, 2H), 7.21 (dd, J=5.4, 3.2 Hz, 2H), 7.35-7.20 (m, 10H), 6.45 (dd, J=15.8, 7.5 Hz, 1H), 6.31 (d, J=15.8 Hz, 1H), 5.48 (t, J=6.8 Hz, 1H), 4.40 (d, J=7.1 Hz, 2H), 4.15 (d, J=7.6 Hz, 1H), 1.82 (s, 3H).¹³C-NMR (125 MHz, CDCl₃): δ 168.1, 141.8, 141.7, 137.3, 133.8, 132.3, 131.4, 130.9, 128.46, 128.45, 1128.40, 127.2, 126.5, 126.3, 123.2, 120.7, 57.1, 35.9, 15.9. IR (film, cm⁻¹): 3024, 2165, 1771, 1711 1497. HRMS (EI) m/z: [M+]⁺ calc. for C₂₇H₂₃NO₂, 393.1729, found, 393.1735.

(((E)-4-((E)-Benzylidene)-5,7-diphenylhept-6-en-1-yl)oxy)(tert-butyl) dimethylsilane. Table 1, Compound 7e: Following the general procedure (A), the reaction of Ni(ITol)(MMA)₂(15.3 mg, 0.03 mmol), triethylsilane (139.2 mg, 1.2 mmol), titanium(IV) isopropoxide (93.7 mg, 0.33 mmol), trans-chalcone (62.4 mg, 0.3 mmol), and tert-butyldimethyl((5-phenylpent-4-yn-1-yl)oxy)silane (164.5 mg, 0.6 mmol) gave a crude residue, which was purified via flash chromatography (hexanes: ethyl acetate=99:1) to afford a single regioisomer in a >98:2 isolated regioselectivity (>98:2 crude regioselectivity) (111.0 mg, 0.24 mmol, 79% yield).¹H-NMR (500 MHz, CDCl₃): δ 7.40-7.20 (m, 15H), 6.59 (dd, J=15.9, 7.5 Hz, 1H), 6.43 (s, 1H), 6.34 (d, J=16.0, 1H), 4.39 (d, J=7.3 Hz, 1H), 3.56 (t, J=6.4 Hz, 2H), 2.46 (ddd, J=13.5, 9.4, 6.9 Hz, 1H), 2.15 (ddd, J=13.5, 9.6, 6.7 Hz, 1H), 1.83-1.65 (m, 2H), 0.93 (s, 9H), 0.09 (s, 6H).¹³C-NMR (125 MHz, CDCl₃): δ 144.8, 142.2, 138.1, 137.4, 132.3, 131.2, 128.8, 128.7, 128.51, 128.48, 128.2, 127.9, 127.2, 126.6, 126.28, 126.27, 63.1, 55.0, 31.9, 27.6, 26.0, 18.3, −5.3. IR (film, cm⁻¹): 2929, 2856, 1491, 1104, 832. HRMS (EI) m/z: [M+]⁺ calc. for C₃₂H₄₀OSi, 468.2848, found, 468.2854.

((1E,4E)-3-Isopropyl-2-methylhexa-1,4-dien-1-yl)benzene. Table 1, Compound 7f: Following the general procedure (A), the reaction of Ni(ITol)(MMA)₂(15.3 mg, 0.03 mmol), triethylsilane (139.2 mg, 1.2 mmol), titanium(IV) isopropoxide (93.7 mg, 0.33 mmol), (E)-5-methylhex-3-en-2-one (33.7 mg, 0.3 mmol), and 1-phenyl-1-propyne (70.2 mg, 0.6 mmol) gave a crude residue, which was purified via flash chromatography (100% hexanes) to afford a single regioisomer in a >98:2 isolated regioselectivity (>98:2 crude regioselectivity) (41.8 mg, 0.20 mmol, 65% yield).¹H-NMR (400 MHz, CDCl₃): δ 7.33 (t, J=7.8 Hz, 2H), 7.29 (d, J=5.4 Hz, 2H), 7.19 (t, J=8.6 Hz, 1H), 6.3 (s, 1H), 5.55-5.49 (m, overlapping dd and dq, 2H), 2.36 (dd, J=8.1, 2.9 Hz, 1H), 1.84-1.77 (m, 1H), 1.82 (s, 3H), 1.72 (d, J=4.9 Hz, 3H), 0.93 (d, J=6.6 Hz, 3H), 0.90 (d, J=6.6 Hz, 3H).¹³C-NMR (125 MHz, CDCl₃): δ 141.4, 138.6, 132.5, 128.9, 127.9, 125.8, 125.7, 125.3, 61.3, 29.6, 21.2, 20.8, 18.1, 15.3. IR (film, cm⁻¹): 3021, 2950, 2864, 2356, 1494, 1441. HRMS (EI) m/z: [M+]⁺ calc. for C₁₆H₂₂, 214.1722, found, 214.1722.

1-((1E,4E)-4-Ethyl-1-phenylhepta-1,4-dien-3-yl)-4-methoxybenzene. Table 1, Compound 7g: Following the general procedure (A), the reaction of Ni(ITol)(MMA)₂(15.3 mg, 0.03 mmol), triethylsilane (139.2 mg, 1.2 mmol), titanium(IV) isopropoxide (93.7 mg, 0.33 mmol), (E)-3-(4-methoxyphenyl)-1-phenylprop-2-en-1-one (71.5 mg, 0.3 mmol), and 3-hexyne (49.3 mg, 0.6 mmol) gave a crude residue, which was purified via flash chromatography (hexanes: ethyl acetate=99:1) to afford a single regioisomer in a >98:2 isolated regioselectivity (>98:2 crude regioselectivity) (59.7 mg, 0.20 mmol, 65% yield).¹H-NMR (500 MHz, CDCl₃): δ 7.37 (d, J=7.3 Hz, 2H), 7.30 (t, J=7.6 Hz, 2H), 7.21 (t, J=7.1 Hz, 1H), 7.17 (d, J=8.5 Hz, 2H), 6.87 (d, J=8.5, 2H), 6.47 (dd, J=15.9, 7.6 Hz, 1H), 6.23 (d, J=15.8 Hz, 1H), 5.26 (t, J=7.3, 1H), 4.15 (d, J=7.6 Hz, 1H), 3.82 (s, 3H), 2.16-2.10 (m, 3H), 1.93-1.89 (m, 1H), 1.01 (t, J=7.3 Hz, 3H), 0.95 (t, J=7.3 Hz, 3H).¹³C-NMR (125 MHz, CDCl₃): δ 158.1, 142.5, 137.7, 134.8, 133.2, 130.1, 129.6, 128.7, 128.4, 127.0, 126.2, 113.6, 55.2, 53.7, 23.2, 21.1, 14.6, 13.7. IR (film, cm⁻¹): 2960, 2869, 2054, 1507, 1459. HRMS (EI) m/z: [M+]⁺ calc. for C₂₂H₂₆O, 306.1984, found, 306.1985.

1-((1E,4E)-4-Ethyl-1-phenylhepta-1,4-dien-3-yl)-4-fluorobenzene Table 1, Compound 7h: Following the general procedure (A), the reaction of Ni(ITol)(MMA)₂(15.3 mg, 0.03 mmol), triethylsilane (139.2 mg, 1.2 mmol), titanium(IV) isopropoxide (93.7 mg, 0.33 mmol), (E)-3-(4-fluorophenyl)-1-phenylprop-2-en-1-one (67.9 mg, 0.3 mmol), and 3-hexyne (49.3 mg, 0.6 mmol) gave a crude residue, which was purified via flash chromatography (hexanes: ethyl acetate=99:1) to afford a single regioisomer in a >98:2 isolated regioselectivity (>98:2 crude regioselectivity) (53.0 mg, 0.18 mmol, 60% yield).¹H-NMR (500 MHz, CDCl₃): δ 7.36 (d, J=7.3 Hz, 2H), 7.31 (t, J=7.6 Hz, 2H), 7.20 (m, overlapping t and t, 3H), 7.01 (t, J=8.8 Hz, 2H), 6.45, (dd, J=15.8, 7.6 Hz, 1H), 6.22 (d, J=15.8 Hz, 1H), 5.26 (t, J=7.1 Hz, 1H), 4.18 (d, J=7.3 Hz, 1H), 2.15-2.10 (m, 3H), 1.90 (m, 1H), 1.01 (t, J=7.6 Hz, 3H), 0.95 (t, J=7.8 Hz, 3H).¹³C-NMR (125 MHz, CDCl₃): δ 161.5 (d, J=244.1 Hz), 142.1, 138.3 (d, J=2.8 Hz), 137.5, 132.6, 130.6, 130.1 (d, J=7.6 Hz), 129.1, 128.5, 127.1, 126.2, 115.1 (d, J=21 Hz), 53.7, 23.2, 21.1, 14.6, 13.7. A¹³C spectrum was also acquired at 100 MHz (CDCl₃) in order to elucidate the fluorine coupling assignments. IR (film, cm⁻¹): 3022, 2960, 2869, 1505, 1448. HRMS (EI) m/z: [M+]⁺ calc. for C₂₁H₂₃F, 294.1784, found, 294.1776.

(E)-(2-Methylpenta-1,4-diene-1,3-diyl)dibenzene. Table 1, Compound 8a: Following the general procedure (A), the reaction of Ni(ITol)(MMA)₂(15.3 mg, 0.03 mmol), triethylsilane (139.2 mg, 1.2 mmol), titanium(IV) isopropoxide (93.7 mg, 0.33 mmol), trans-cinnamaldehyde (39.7 mg, 0.3 mmol), and 1-phenyl-1-propyne (70.2 mg, 0.6 mmol) gave a crude residue, which was purified via flash chromatography (100% hexanes) to afford a single regioisomer in a >98:2 isolated regioselectivity (>98:2 crude regioselectivity) (51.3 mg, 0.22 mmol, 73% yield).¹H-NMR (500 MHz, CDCl₃): δ 7.36-7.22 (m, 10H), 6.46 (s, 1H), 6.24 (ddd, J=17.3, 10.2, 7.3 Hz, 1H), 5.24 (d, J=10.2 Hz, 1H), 5.08 (d, J=17.2 Hz, 1H), 4.17 (d, J=7.3 Hz, 1H), 1.80 (s, 3H).¹³C-NMR (125 MHz, CDCl₃): δ 141.9, 140.0, 139.5, 138.3, 129.0, 128.5, 128.4, 128.08, 128.04, 127.8, 127.0, 126.4, 126.2, 116.4, 58.7, 17.4. IR (film, cm⁻¹): 3023, 2193, 2049, 1494, 1332. HRMS (EI) m/z: [M+]⁺ calc. for C₁₈H₁₈, 234.1409, found, 234.1405.

(E)-(2,3-Dimethylpenta-1,4-dien-1-yl)benzene. Table 1, Compound 8b: Following the general procedure (A), the reaction of Ni(ITol)(MMA)₂(15.3 mg, 0.03 mmol), triethylsilane (139.2 mg, 1.2 mmol), titanium(IV) isopropoxide (93.7 mg, 0.33 mmol), crotonaldehyde (39.7 mg, 0.3 mmol), and 1-phenyl-1-propyne (70.2 mg, 0.6 mmol) gave a crude residue, which was purified via flash chromatography (100% hexanes) to afford a single regioisomer in a >98:2 isolated regioselectivity (>98:2 crude regioselectivity) (37.7 mg, 0.22 mmol, 73% yield).¹H-NMR (500 MHz, CDCl₃): δ 7.34 (t, J=7.6 Hz, 2H), 7.28 (d, J=6.8 Hz, 2H), 7.21 (t, 7.3 Hz, 1H), 6.37 (s, 1H), 5.92 (ddd, J=17.0, 10.3, 6.5 Hz, 1H), 5.13-5.07 (m, 2H), 3.09-2.88 (m, 1H), 1.84 (s, 3H), 1.26 (d, J=7.1, 3H).¹³C-NMR (125 MHz, CDCl₃): δ 142.2, 141.8, 138.5, 128.9, 128.0, 125.9, 124.5, 113.6, 46.8, 18.1, 15.7. IR (film, cm⁻¹): 2962, 2175, 2016, 1278, 1027. HRMS (EI) m/z: [M+]⁺ calc. for C₁₃H₁₆, 172.1252, found, 172.1246.

(E)-(2,4-dimethylpenta-1,4-dien-1-yl)benzene. Table 1, Compound 8c: Following the general procedure (A), the reaction of Ni(ITol)(mma)₂(15.3 mg, 0.03 mmol), triethylsilane (139.2 mg, 1.2 mmol), titanium(IV) isopropoxide (93.7 mg, 0.33 mmol), methacrolein (39.7 mg, 0.3 mmol), and 1-phenyl-1-propyne (70.2 mg, 0.6 mmol) gave a crude residue, which was purified via flash chromatography (100% hexanes) to afford a single regioisomer in a >98:2 isolated regioselectivity (>98:2 crude regioselectivity) (42.3 mg, 0.25 mmol, 82% yield).¹H-NMR (500 MHz, CDCl₃): δ 7.35 (t, J=7.6 Hz, 2H), 7.30 (d, J=7.6 Hz, 2H), 7.22 (t, J=7.3 Hz, 1H), 6.36 (s, 1H), 4.88 (s, 1H), 4.84 (s, 1H), 2.90 (s, 2H), 1.85 (s, 3H), 1.76 (s, 3H).¹³C-NMR (125 MHz, CDCl₃): δ 143.7, 138.5, 136.7, 128.8, 128.1, 126.8, 126.0, 112.3, 49.6, 21.9, 17.3. IR (film, cm⁻¹): 3072, 2970, 2909, 2163, 1497. HRMS (EI) m/z: [M+]⁺ calc. for C₁₃H₁₆, 172.1252, found, 172.1245.

(E)-Undeca-1,4-dien-3-ylbenzene. Table 1, Compound 8d: Following the general procedure (A), the reaction of Ni(ITol)(MMA)₂(15.3 mg, 0.03 mmol), triethylsilane (139.2 mg, 1.2 mmol), titanium(IV) isopropoxide (93.7 mg, 0.33 mmol), trans-cinnamaldehyde (39.7 mg, 0.3 mmol), and 1-octyne (66.1 mg, 0.6 mmol) gave a crude residue, which was purified via flash chromatography (100% hexanes) to afford a single regioisomer in a >98:2 isolated regioselectivity (>98:2 crude regioselectivity) (49.3 mg, 0.22 mmol, 72% yield). The spectral data matches that previously reported in the literature (Table VII, Compound 16 in J. Org. Chem. 1980, 45, 1640).¹H-NMR (500 MHz, CDCl₃): δ 7.31 (dt, J=8.1 Hz, 1.7 Hz, 2H), 7.22-7.19 (m, 3H), 6.02 (ddd, J=17.0, 10.2, 6.8 Hz, 1H), 5.61 (dd, J=15.3, 7.0 Hz, 1H), 5.51-5.46 (ddt, 15.4, 6.7, 0.8 Hz, 1H), 5.10 (ddd, J=10.2, 1.4, 1.4 Hz, 1H), 5.04 (ddd, J=17.1, 1.4, 1.4 Hz, 1H), 4.01 (dd, J=7.0, 6.9 Hz, 1H), 2.04 (dt, J=7.1, 7.0 Hz, 2H), 1.39-1.24 (m, 8H), 0.88 (t, 7.1 Hz, 3H).¹³C-NMR (125 MHz, CDCl₃): δ 143.4, 140.9, 131.8, 131.4, 128.4, 127.9, 126.2, 114.8, 52.2, 32.6, 31.7, 29.3, 28.9, 22.6, 14.1. IR (film, cm⁻¹): 3025, 2956, 2924, 2854, 2036, 1495. HRMS (EI) m/z: [M+]⁺ calc. for C₁₇H₂₄, 228.1878, found, 228.1884.

triethyl(((1Z,4E)-4-methyl-3,5-diphenylpenta-1,4-dien-1-yl-5-d)oxy)silane. Entry d-4a: Following a previously published modified procedure from Montgomery, J. Am. Chem. Soc. 2008, 130, 8132, utilizing triethyl(silane-d), a crude residue was obtained, which was purified via flash chromatography (100% hexanes) to afford a single regioisomer in a >98:2 isolated regioselectivity (>98:2 crude regioselectivity) with >95% deuterium incorporation at the proton shown above (36.1 mg, 0.10 mmol, 33% yield). The undeuterated standard was previously reported (Table 2, entry 3 of J. Am. Chem. Soc. 2008, 130, 8132.)¹H-NMR (400 MHz, CDCl₃): δ 7.34-7.18 (m, 10H), 6.40 (d, J=5.6 Hz, 1H), 4.88 (dd, J=5.6, 9.6 Hz, 1H), 4.75 (d, J=9.6 Hz, 1H), 1.78 (d, J=1.2 Hz, 3H), 0.99 (t, J=8.0 Hz, 9H), 0.67 (q, J=8.0 Hz, 6H).

((1E,4Z)-2-methylpenta-1,4-diene-1,3-diyl-5-d)dibenzene. Entry (5-d)-8a: Following the general procedure (A), the reaction of Ni(ITol)(MMA)₂(15.3 mg, 0.03 mmol), triethyl(silane-d) (140.2 mg, 1.2 mmol), titanium(IV) isopropoxide (93.7 mg, 0.33 mmol), trans-cinnamaldehyde (39.7 mg, 0.3 mmol), and 1-phenyl-1-propyne (70.2 mg, 0.6 mmol) gave a crude residue, which was purified via flash chromatography (100% hexanes) to afford a single regioisomer in a >98:2 isolated regioselectivity (>98:2 crude regioselectivity) with >95% deuterium incorporation at the proton shown above (51.3 mg, 0.22 mmol, 63% yield).¹H-NMR (500 MHz, CDCl₃): δ 7.36-7.21 (m, 10H), 6.46 (s, 1H), 6.22 (m, 1H), 5.21 (d, J=10.2 Hz, 1H), 4.16 (d, J=7.1 Hz, 1H), 1.80 (s, 3H).¹³C-NMR (125 MHz, CDCl₃): δ 141.9, 140.0, 139.4, 138.3, 128.4, 128.5, 128.4, 128.0, 127.0, 126.4, 126.2, 116.1 (t, J=23.8 Hz), 58.6, 17.4.

tetrakis((propan-2-yl-d₇)oxy)titanium. Titanium(IV) isopropoxide (1.0 ml, 3.4 mmol) was added to a flame dried round bottom under a nitrogen atmosphere. To this was added 2-propanol-ds (99.5%) (2.0 ml, 26.1 mmol) and the mixture was allowed to stir for 2 h. The reaction mixture was then concentrated, and the addition of 2-propanol-ds (99.5%) (2.0 ml, 26.1 mmol) and subsequent concentration after stirring for two hours was repeated two more times to afford the desired product with 99% deuterium incorporation. Standard Titanium(IV) isopropoxide, MS (EI) m/z: [M-CH₃]⁺ calc. for C₁₂H₂₈O₄Ti, 269.12, found, 269.1. Titanium(IV) isopropoxide-d₂₈MS (EI) m/z: [M-CD₃]⁺ calc. for C₁₂D₂₈O₄Ti, 294.28, found, 294.3. No d₂₁, d₁₄, or d₇products detected. Characteristic peaks at m/z 290.3, 287.2, 283.2, 280.2, 276.2, and 273.1 indicate incomplete deuterium incorporation.

(E)-(2-methylpenta-1,4-diene-1,3-diyl-1-d)dibenzene. Entry (1-d)-8a: Following the general procedure (A), the reaction of Ni(ITol)(MMA)₂(15.3 mg, 0.03 mmol), triethylsilane (140.2 mg, 1.2 mmol), titanium(IV) isopropoxide-d₂₈(99%) (93.7 mg, 0.33 mmol), trans-cinnamaldehyde (39.7 mg, 0.3 mmol), and 1-phenyl-1-propyne (70.2 mg, 0.6 mmol) gave a crude residue, which was purified via flash chromatography (100% hexanes) to afford a single regioisomer in a >98:2 isolated regioselectivity (>98:2 crude regioselectivity) with 91% deuterium incorporation at the proton shown above (35.6 mg, 0.15 mmol, 51% yield).¹H-NMR (500 MHz, CDCl₃): δ 7.36-7.22 (m, 10H), 6.46 (s, 0.09H), 6.24 (ddd, J=17.3, 10.2, 7.3 Hz, 1H), 5.24 (d, J=10.2 Hz, 1H), 5.08 (d, J=17.2 Hz, 1H), 4.17 (d, J=7.3 Hz, 1H), 1.80 (s, 3H).¹³C-NMR (125 MHz, CDCl₃): δ 141.9, 140.0, 139.5, 138.2, 128.9, 128.5, 128.4, 128.1, 128.0, 127.8, 127.0, 126.4, 126.2, 116.3, 58.7, 17.3.

Following the general procedure for Buchwald-Hartwig cross-coupling: Ni(IPr*^OMe)(benzyl methacrylate) (5.0 mg, 0.004 mmol), NaO-tBu (23 mg, 0.24 mmol), 2-chloro-1,3-dimethylbenzene (28 mg, 0.2 mmol) and aniline (28 mg, 0.3 mmol) were stirred for 24 h at 50° C. yield obtained from crude NMR using dibromomethane as an internal standard (99% yield).

Following the general procedure for Buchwald-Hartwig cross-coupling: Ni(IPr*^OMe)(benzyl methacrylate) (5.0 mg, 0.004 mmol), NaO-tBu (23 mg, 0.24 mmol), 2-chlorotoluene (25 mg, 0.2 mmol) and 2,4,6-trimethylaniline (41 mg, 0.3 mmol) were stirred for 16 h at 23° C. yield obtained from crude NMR using dibromomethane as an internal standard (76% yield).

Following the general procedure for Buchwald-Hartwig cross-coupling: Ni(IPr)(benzyl methacrylate) (8.0 mg, 0.01 mmol), NaO-tBu (58 mg, 0.6 mmol), 1-chloro-4-(trifluoromethyl)benzene (67 μL, 0.5 mmol) and morpholine (66 μL, 0.75 mmol) stirred for 15 hr followed by column chromatography (109 mg, 95% yield).

Following general procedure for air stability test, Ni(IPr)(benzyl methacrylate) (8.0 mg, 0.01 mmol), NaO-tBu (58 mg, 0.6 mmol), 1-chloro-4-(trifluoromethyl)benzene (67 μL, 0.5 mmol) and morpholine (66 μL, 0.75 mmol) stirred for 15 hr followed by column chromatography (98.2 mg, 85% yield).

Following general procedure for aldehyde hydrosilylation, Ni(1,3-bis(3,5-di-tert-butylphenyl)imidazolidin-2-yl)(phenyl methacrylate)₂(8.3 mg, 0.01 mmol), Ph₃SiH (156 mg, 0.6 mmol), and (−) menthone (77 mg, 0.5 mmol) stirred for 6 hr and produced a crude residue that could be purified by column chromatography on silica gel (201 mg, dr=5:1, 97% yield)

Following general procedure for air stability test followed by the general procedure for aldehyde hydrosilylation: Ni(1,3-bis(3,5-di-tert-butylphenyl)imidazolidin-2-yl)(phenyl methacrylate)₂(8.3 mg, 0.01 mmol), Ph₃SiH (156 mg, 0.6 mmol), and (−) menthone (77 mg, 0.5 mmol) stirred for 6 hr and produced a crude residue that could be purified by column chromatography on silica gel (203 mg, dr=5:1, 98% yield)

Following general procedure for air stability test followed by the general procedure for aldehyde hydrosilylation: Ni(1,3-bis(3,5-di-tert-butylphenyl)imidazolidin-2-yl)(phenyl methacrylate)₂(8.3 mg, 0.01 mmol), Ph₃SiH (156 mg, 0.6 mmol), and trans-dehydroandrosterone (144.2 mg, 0.5 mmol) stirred for 6 hr and produced a crude residue that could be purified by column chromatography on silica gel (258 mg, dr=4:1, 94% yield)

Following general procedure for air stability test followed by the general procedure for aldehyde hydrosilylation: Ni(1,3-bis(3,5-di-tert-butylphenyl)imidazolidin-2-yl)(phenyl methacrylate)₂(8.3 mg, 0.01 mmol), Ph₃SiH (156 mg, 0.6 mmol), and (1R)-(−)-Fenchone (80.3 μL, 0.5 mmol) stirred for 6 hr and produced a crude residue that could be purified by column chromatography on silica gel (204 mg, dr=15:1, 99% yield.

Following general procedure for aldehyde-alkyne reductive coupling, Ni(IMes)(di(o-PhMe) fumarate)₂(3.7 mg, 0.0 mmol), benzaldehyde (21 mg, 0.2 mmol), 1-phenyl propyne (23.2 mg, 0.2 mmol) and triethylsilane (46.5 mg, 0.4 mmol). Product could be purified by column chromatography on silica gel using pure hexanes (58 mg, 98:2, 85% yield).

Following general procedure for Suzuki-Miyaura cross couplings: Ni(ITol)(methyl methacrylate)₂(2.5 mg, 0.005 mmol), K₃PO₄(64 mg, 0.3 mmol), phenyl boronic acid (18 mg, 0.15 mmol), 4-chlorobenzotrifluoride (18 mg, 0.1 mmol). The reaction was stirred for 16 h at 23° C. (63% yield).

Following general procedure for Suzuki-Miyaura cross couplings: Ni(SIPr)(benzyl methacrylate)₂(4.0 mg, 0.005 mmol), K₃PO₄(64 mg, 0.3 mmol), phenyl boronic acid (18 mg, 0.15 mmol), 4-chlorobenzotrifluoride (18 mg, 0.1 mmol). The reaction was stirred for 16 h at 23° C. (90% yield).

Following general procedure for Suzuki-Miyaura cross couplings: Ni(ITol)(methyl methacrylate)₂(2.5 mg, 0.005 mmol), K₃PO₄(64 mg, 0.3 mmol), phenyl boronic acid (18 mg, 0.15 mmol), 2-chlorotoluene (13 mg, 0.1 mmol). The reaction was stirred for 4 h at 80° C. (31% yield).

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