WO2001066248A2 - Systeme catalyseur comprenant un metal de transition et de l'imidazoline-2-ylidene ou de l'imidazolidine-2-ylidene et son utilisation dans des reactions de couplage - Google Patents

Systeme catalyseur comprenant un metal de transition et de l'imidazoline-2-ylidene ou de l'imidazolidine-2-ylidene et son utilisation dans des reactions de couplage Download PDF

Info

Publication number
WO2001066248A2
WO2001066248A2 PCT/US2001/005549 US0105549W WO0166248A2 WO 2001066248 A2 WO2001066248 A2 WO 2001066248A2 US 0105549 W US0105549 W US 0105549W WO 0166248 A2 WO0166248 A2 WO 0166248A2
Authority
WO
WIPO (PCT)
Prior art keywords
group
process according
aryl
ylidene
pseudohalide
Prior art date
Application number
PCT/US2001/005549
Other languages
English (en)
Other versions
WO2001066248A3 (fr
Inventor
Steven P. Nolan
Jinkun Huang
Mark L. Trudell
Chunming Zhang
Hon Man Lee
Original Assignee
University Of New Orleans Research And Technology Foundation
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US09/511,122 external-priority patent/US6369265B1/en
Priority claimed from US09/511,654 external-priority patent/US6362357B1/en
Priority claimed from US09/511,420 external-priority patent/US6403802B1/en
Priority claimed from US09/507,958 external-priority patent/US6316380B1/en
Priority claimed from US09/553,542 external-priority patent/US6586599B1/en
Application filed by University Of New Orleans Research And Technology Foundation filed Critical University Of New Orleans Research And Technology Foundation
Publication of WO2001066248A2 publication Critical patent/WO2001066248A2/fr
Publication of WO2001066248A3 publication Critical patent/WO2001066248A3/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
    • C07D295/096—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/22—Organic complexes
    • B01J31/2265—Carbenes or carbynes, i.e.(image)
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/22—Organic complexes
    • B01J31/2265—Carbenes or carbynes, i.e.(image)
    • B01J31/2269—Heterocyclic carbenes
    • B01J31/2273—Heterocyclic carbenes with only nitrogen as heteroatomic ring members, e.g. 1,3-diarylimidazoline-2-ylidenes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B37/00—Reactions without formation or introduction of functional groups containing hetero atoms, involving either the formation of a carbon-to-carbon bond between two carbon atoms not directly linked already or the disconnection of two directly linked carbon atoms
    • C07B37/04—Substitution
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B43/00—Formation or introduction of functional groups containing nitrogen
    • C07B43/04—Formation or introduction of functional groups containing nitrogen of amino groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B49/00—Grignard reactions
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C1/00—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon
    • C07C1/32—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen
    • C07C1/321—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen the hetero-atom being a non-metal atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
    • C07C209/04—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups
    • C07C209/06—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups by substitution of halogen atoms
    • C07C209/10—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups by substitution of halogen atoms with formation of amino groups bound to carbon atoms of six-membered aromatic rings or from amines having nitrogen atoms bound to carbon atoms of six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
    • C07C213/08—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions not involving the formation of amino groups, hydroxy groups or etherified or esterified hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
    • C07C41/01—Preparation of ethers
    • C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
    • C07C41/30—Preparation of ethers by reactions not forming ether-oxygen bonds by increasing the number of carbon atoms, e.g. by oligomerisation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/28—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/293—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
    • C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/02—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements
    • C07D295/023—Preparation; Separation; Stabilisation; Use of additives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/06—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by halogen atoms or nitro radicals
    • C07D295/073—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by halogen atoms or nitro radicals with the ring nitrogen atoms and the substituents separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
    • B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
    • B01J2231/4205—C-C cross-coupling, e.g. metal catalyzed or Friedel-Crafts type
    • B01J2231/4211—Suzuki-type, i.e. RY + R'B(OR)2, in which R, R' are optionally substituted alkyl, alkenyl, aryl, acyl and Y is the leaving group
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/80—Complexes comprising metals of Group VIII as the central metal
    • B01J2531/82—Metals of the platinum group
    • B01J2531/824—Palladium
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/80—Complexes comprising metals of Group VIII as the central metal
    • B01J2531/82—Metals of the platinum group
    • B01J2531/828—Platinum
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/80—Complexes comprising metals of Group VIII as the central metal
    • B01J2531/84—Metals of the iron group
    • B01J2531/847—Nickel

Definitions

  • This invention relates to reactions involving carbon-to-carbon or carbon-to-nitrogen bond formation, which can be used for chemical synthesis in the polymer and the fine chemical industry.
  • aryl bromides aryl iodides
  • aryl pseudohalides e.g. , triflates
  • Prior art methods generally cannot employ aryl chlorides as feedstock for these chemical transformations, and require the use of more expensive aryl bromides and aryl iodides.
  • aryl chlorides as chemical feedstock in coupling chemistry has proven difficult but would economically benefit a number of industrial processes.
  • the few prior art methods that can employ aryl chlorides use expensive, air-sensitive phosphine ligands. See in this comiection Old et al., J. Am. Chem.
  • Nucleophilic N-heterocyclic carbenes the imidazoline-2-ylidenes (sometimes commonly called imidazol-2-ylidenes) or so-called "phosphine mimics", have attracted considerable attention as possible alternatives for the widely used phosphine ligands in homogeneous catalysis.
  • a primary advantage of these ligands is that an excess ofthe ligand is not required. It appears that these ligands do not dissociate from the metal center, thus preventing aggregation of the catalyst to yield the bulk metal. Further, these imidazoline-2-ylidene carbenes also appear to be more thermally stable than phosphines.
  • this invention provides new and highly advantageous catalyst compositions and processes for carrying out reactions to form C-C and C-N bonds.
  • this invention provides a process which comprises mixing, in a liquid medium, i) at least one strong base; ii) at least one aryl halide or aryl pseudohalide, wherein the aryl halide has, directly bonded to the aromatic ring(s), at least one halogen atom selected from the group consisting of a chlorine atom, a bromine atom, and an iodine atom; iii) ' at least one transmetalating agent; iv) at least one metal compound comprising at least one metal atom selected from nickel, palladium, and platinum, wherein the formal oxidation state of the metal is zero or two; and v) at least one N-heterocyclic carbene.
  • the transmetalating agent is selected from the group consisting of at least one arylboronic acid in which all substituents are other than chlorine atoms, bromine atoms, iodine atoms, or pseudohalide groups; at least one primary amine and/or at least one secondary amine; at least one Grignard reagent; at least one organotin compound wherein the tin atom is quaternary, wherein one group bound to the tin atom is unsaturated at the alpha or beta position, and wherein each ofthe remaining groups bound to the tin atom is a saturated group; and at least one silane wherein the silicon atom is quaternary, wherein one group bound to the silicon atom is unsaturated at the alpha or beta position, and wherein each ofthe remaining groups bound to the silicon atom is a saturated hydrocarbyl or a saturated hydrocarbyloxy group; all with the proviso that (A) if the transmetalating agent is the arylboronic acid, all substitu
  • the carbene is selected from the group consisting of an imidazoline-2-ylidene wherein the 1 and 3 positions are each, independently, substituted by a secondary or tertiary group which has at least three atoms, or aprotonated salt thereof; an imidazolidine-2-ylidene wherein the 1 and 3 positions are each, independently, substituted by a secondary or tertiary group which has at least three atoms, or aprotonated salt thereof; abis(imidazoline-2-ylidene) wherein a bridging moiety is bound to one nitrogen atom of each ring, and wherein the remaining two mtrogen atoms are each, independently, substituted by a secondary or tertiary group which has at least three atoms, or a protonated salt thereof; and a bis(imidazolidine-2-ylidene) wherein abridging moiety is bound to one mtrogen atom of each ring, and wherein the remaining two nitrogen
  • this invention provides a process for conducting Suzuki coupling reactions, wherein the transmetalating agent is at least one arylboronic acid in which all substituents are other than chlorine atoms, bromine atoms, iodine atoms, or pseudohalide groups.
  • the catalyst system used in this embodiment of the invention exhibits the fastest reaction rate for Suzuki coupling observed to date, 3 times faster than the best reported rate for a phosphine-based catalyst system.
  • the catalyst system of this embodiment also permits the use of aryl chlorides as substrates in Suzuki coupling reactions while eliminating the need for phosphine ligands.
  • this invention provides a process for conducting animation reactions, wherein the transmetalating agent is at least one primary amine and/or at least one secondary amine.
  • This process uses a catalyst system comprising nickel, palladium, or platinum and imidazoline-2-ylidene or imidazolidine-2-ylidene, and permits the use of aryl chlorides as substrates in amination reactions while eliminating the need for phosphine ligands.
  • both electron-donating and electron-withdrawing substituents on the aryl halide or pseudohalide, the amine, or both, in the amination reaction are tolerated by the catalyst system used in the present invention, and provide the corresponding amination products in good yields.
  • this invention provides a process for conducting Kumada coupling reactions, wherein the transmetalating agent is at least one Grignard reagent.
  • the catalyst system used in this embodiment ofthe mvention permits the use of aryl chlorides as substrates in Kumada coupling reactions while eliminating the need for phosphine ligands. Furthermore, both electron-donating and electron-withdrawing substituents on the aryl halide or pseudohalide, the Grignard reagent, or both, in the Kumada coupling reaction are tolerated by the catalyst system used in the present invention, and provide the corresponding Kumada coupling products in excellent yields. Homocoupling of aryl pseudohalides is also feasible using the processes of this invention.
  • Still another apect of this invention provides a process for conducting Stille coupling reactions, wherein the transmetalating agent is at least one organotin compound wherein the tin atom is quaternary, wherein one group bound to the tin atom is unsaturated at the alpha or beta position, and wherein each ofthe remaining groups bound to the tin atom is a saturated group.
  • This embodiment of the present invention permits the use of aryl chlorides as substrates in Stille coupling reactions while eliminating the need for phosphine ligands.
  • this invention provides provides a process for conducting coupling reactions of aryl halides using unsaturated silanes as the transmetalating agent.
  • the catalyst system of this embodiment permits the use of aryl chlorides as substrates in these coupling reactions while eliminating the need for phosphine ligands.
  • both electron-donating and electron-withdrawing substituents on the aryl halide or pseudohalide, the silane, or both, in the coupling reaction are well tolerated by the catalyst system of the present invention, and provide the corresponding heterocoupled products in excellent yields.
  • This invention also provides a catalyst system useful in all ofthe coupling reactions noted in this description.
  • a feature of this aspect of the invention is the use of an imidazoline-2-ylidene, an imidazolidine-2-ylidene, a bis(imidazoline-2-ylidene), and/or a bis(imidazolidine-2-ylidene) as part ofthe catalyst system.
  • These N-heterocyclic carbenes and their corresponding salts are inexpensive and readily synthesized.
  • another embodiment of this invention is a composition which comprises at least one metal compound comprising at least one transition metal atom and at least one N-heterocyclic carbene or protonated salt of an N-heterocyclic carbene.
  • the N-heterocyclic carbene is selected from the group consisting of i) an imidazoline-2-ylidene wherein the 1 and 3 positions are each, independently, substituted by an aromatic group in which each ortho position is, independently, substituted by a secondary or tertiary group which has at least three atoms, or a protonated salt of such an imidazoline-2-ylidene; ii) an imidazolidine-2-ylidene wherein the 1 and 3 positions are each, independently, substituted by an aromatic group in which each ortho position is, independently, substituted by a secondary or tertiary group having at least three atoms, or a protonated salt of such an imidazolidine-2-ylidene; iii) a bis(
  • N-heterocyclic carbene is selected from the group consisting of i) an imidazoline-2-ylidene wherein the 1 and 3 positions are each, independently, substituted by an aromatic group in which each ortho position is, independently, substituted by a secondary or tertiary group which has at least three atoms, or aprotonated salt of such an imidazoline-2-ylidene; ii) an imidazolidine-2-ylidene wherein the 1 and 3 positions are each, independently, substituted by an aromatic group in which each ortho position is, independently, substituted by a secondary or tertiary group having at least three atoms, or a protonated salt of such an imidazolidine-2-ylidene; iii) a bis(imidazoline-2-ylidene) wherein
  • the liquid medium for the processes of this embodiment ofthe invention can include any of a wide range of solvents, and mixtures of solvents are also usable.
  • the exclusion of water is not necessary, but is preferred.
  • Types of solvents that can be used include hydrocarbons, ethers, amides, ketones, and alcohols. Polar solvents are preferred; ethers are a more preferred solvent type.
  • Ethers that may be used include, for example, diethyl ether, di-n-propyl ether, diisopropyl ether, tert-butyl ethyl ether, diheptyl ether, 1,3-dioxolane, 1,4-dioxane, tetrahydrofuran, methyltetrahydrofuran, glyme (the dimethyl ether of ethylene glycol), diglyme (the dimethyl ether of diethylene glycol), and the like. Cyclic ethers and polyethers are preferred; a highly preferred ether is 1,4-dioxane.
  • Alkali metal salts are a preferred group of inorganic bases.
  • suitable alkali metal salts include, but are not limited to, sodium acetate, sodium bicarbonate, sodium tert-butoxide, sodium oxide, sodium tetrafluoroborate, potassium acetate, potassium carbonate, potassium tert-butoxide, potassium nitrite, potassium phosphate, potassium sulfite, potassium hexafluorophosphate, cesium acetate, cesium bicarbonate, cesium carbonate, cesium fluoride, cesium nitrate, and cesium sulfate.
  • Alkali metal salts of carboxylic acid anions are also suitable for use as the inorganic base in this invention. More preferred are salts of potassium and cesium; most preferred are cesium salts. The most highly preferred inorganic base is cesium carbonate. Choice(s) of inorganic base will vary with the particular system of aryl halide or pseudohalide and arylboronic acid involved. Amine bases are generally not preferred because, to date, they appear to poison the catalyst system ofthe invention.
  • aryl halide or pseudohalide Directly bonded to the aromatic ring(s) ofthe aryl halide or pseudohalide (i.e., aryl halide or aryl pseudohalide) is at least one halogen atom selected from a chlorine atom, a bromine atom, and an iodine atom, or at least one pseudohalide group.
  • pseudohalide group includes such groups as j?-toluenesulfonate (tosylate), and trifluoro- methanesulfonate (triflate).
  • the aryl halide or pseudohalide can have two or more such halogen atoms with an atomic number greater than nine and/or pseudohalide groups, including combinations of halogen atoms and pseudohalide groups.
  • the halogen atoms with an atomic number greater than nine and/or pseudohalide groups should all be different from each other.
  • substituents when two such substituents are present, they may be a chlorine atom and a bromine atom, or an iodine atom and a tosylate group, or etc.
  • the aryl moiety for the aryl halide or pseudohalide can be homocyclic or heterocyclic.
  • suitable homocyclic aryl moieties include, but are not limited to, benzene, naphthalene, anthracene, phenanthrene, pyrene, biphenyl, acenaphthalene, fluorene, and indene.
  • Heterocyclic aryl moieties that can be used include, for example, furan, thiophene, oxathiolane, thianthrene, isobenzofuran, phenoxathiin, and the like.
  • Nitrogen-containing heterocycles such as pyridine, indole, and isoxazole may have an effect on the catalyst system similar to that of amine bases, as described above, and thus are not preferred.
  • Benzene is a preferred aryl moiety for the aryl halide or pseudohalide.
  • substituents other than a chlorine atom, a bromine atom, an iodine atom, and or a pseudohalide group that may be present on the aromatic ring(s) include, but are not limited to, hydrogen atoms, fluorine atoms, nitro groups, hydrocarbyl groups, alkoxy groups, perfluorohydrocarbyl groups, silyl groups, ether groups, ketone groups, and ester groups.
  • hydrocarbyl groups are present, they are preferably to C 18 alkyl groups or C 6 to C 20 aryl or aralkyl groups.
  • hydrocarbyl groups examples include methyl, ethyl, isopropyl, tert-butyl, cyclopentyl, methylcyclohexyl, decyl, phenyl, tolyl, xylyl, benzyl, naphthyl, and tetrahydronaphthyl.
  • Alkoxy group substituents preferably have to C 6 alkyl moieties. Some examples of alkoxy groups are methoxy, ethoxy, isopropoxy, methylcyclopentoxy, and cyclohexoxy.
  • Perfluorohydrocarbyl groups include alkyl and aryl perfluorocarbons; suitable perfluorohydrocarbyl groups are, for example, trifluoromethyl, pentafluoroethyl, pentafluorophenyl, and heptafluoronaphthyl.
  • Substituent silyl groups preferably have to C 18 alkyl groups or C 6 to C 20 aryl or aralkyl groups, and examples include trimethylsilyl, triisopropylsilyl, ter/-butyl(dimethyl)silyl, tridecylsilyl, and triphenylsilyl.
  • the substituents preferred for the aryl halide or pseudohalide will depend on the product that is desired.
  • the arylboronic acid contains only one boronic acid group directly bonded to the aromatic ring(s), which may prevent mixtures of products from forming. It is recognized that more than one boronic acid group may be present when a mixture of products is desired. To prevent self-reaction, it is also preferred that chlorine atoms, bromine atoms, iodine atoms, and/or pseudohalide groups are not present on the aromatic ring(s) of the arylboronic acid. In other words, the arylboronic acid is preferably devoid of halogen atoms with an atomic number greater than nine, and is also preferably devoid of pseudohalide groups. However, one or more fluorine atoms can be present on the aromatic ring(s).
  • the aryl moiety of the arylboronic acid can be homocyclic or heterocyclic, as described for the aryl halide or pseudohalide.
  • the preferred aryl moieties are benzene and naphthalene.
  • Substituents on the aryl ring, again as described for the aryl halide or pseudohalide, can be hydrogen atoms, fluorine atoms, nitro groups, hydrocarbyl groups, alkoxy groups, perfluorohydrocarbyl groups, silyl groups, ether groups, etone groups, and ester groups. Preferred substituents for the arylboronic acid depend on the desired product.
  • the metal compound comprises at least one metal atom selected from nickel, palladium, and platinum having a formal oxidation state of zero or two, and is sometimes referred to hereinafter as the metal compound.
  • Inorganic salts of nickel, palladium, or platinum that can be used include the bromides, chlorides, fluorides, iodides, cyanides, nitrates, sulfides, sulfites, and sulfates.
  • Organic nickel, palladium, or platinum compounds that may be used include complexes and salts such as the carboxylates, e.g., the acetates or propionates, etc.
  • Suitable nickel compounds include bis(l,5-cyclooctadiene)nickel, nickel acetate, nickel oxalate, nickel phosphate, nickel stearate, nickel acetylacetonate, nickel tetrafluoroborate, nickel thiocyanate, nickel carbonate, and nickel sulfamate.
  • Examples of palladium compounds include Pd(OAc) 2 , palladium(II) chloride, Pd(CH 3 CN) 4 (BF 4 ) 2 , tris(dibenzylideneacetone)dipalladium(0) [which is also referred to herein as dipalladium tris(dibenzylideneacetone)], and palladium trifluoroacetate.
  • Platinum compounds that can be used include platinum acetylacetonate and platinum chloride. Nickel and palladium compounds are preferred; more preferred are compounds of palladium. Palladium compounds such as palladium acetate and tris(dibenzylideneacetone)dipalladium(0) are most preferred.
  • N-heterocyclic carbenes are imidazoline-2-ylidenes ofthe formula
  • R 1 and R 2 are each, independently, alkyl or aryl groups having at least 3 carbon atoms
  • R 3 and R 4 are each, independently, a hydrogen atom, a halogen atom, or a hydrocarbyl group
  • R 1 , R 2 , R 3 , and R 4 are as defined for the imidazoline-2-ylidenes; bis(imidazoline-2-ylidene)s ofthe formula
  • R 1 , R 2 , R 3 , and R 4 are as defined for the imidazoline-2-ylidenes, wherein R 3 ' and R 4 ' are as defined for R 3 and R 4 for the imida- zoline-2-ylidenes, and wherein R 5 is a bridging group that links the two imidazoline rings; bis(imidazolidine-2-ylidene)s ofthe formula
  • R 1 , R 2 , R 3 , and R 4 are as defined for the imidazoline-2-ylidenes, wherein R 3 ' and R 4 ' are as defined for R 3 and R 4 for the imidazoline-2-ylidenes, and wherein R 5 is a bridging group that links the two imidazolidine rings.
  • R 1 and R 2 are preferably sterically bulky groups. Suitable groups include, but are not limited to, isopropyl, sec-butyl, tert-butyl, 2,2-dimethylpropyl (neopentyl), cyclohexyl, norbornyl, adamantyl, tolyl, 3,5-dimethylphenyl, 2,4,6-trimethylphenyl, 2,6-diisopropylphenyl, and triphenylmethyl. Preferred groups are tert-butyl, 2,4,6-trimethylphenyl, 2,6-diisopropylphenyl, and triphenylmethyl. Most preferred for both R 1 and R 2 are the 2,4,6-trimethylphenyl and 2,6-diisopropylphenyl groups.
  • R 3 , R 4 , R 3 ', and R 4 ' groups include chlorine atoms, bromine atoms, hydrogen atoms, hydrocarbyl groups, and the like.
  • hydrocarbyl groups When hydrocarbyl groups are present, they are preferably C ⁇ to C !8 alkyl groups or C 6 to C 20 aryl or aralkyl groups.
  • suitable hydrocarbyl groups are methyl, ethyl, isopropyl, tert-butyl, cyclopentyl, methylcyclohexyl, decyl, phenyl, tolyl, xylyl, benzyl, naphthyl, and tetrahydronaphthyl.
  • Chlorine atoms and hydrogen atoms are preferred groups. Most preferred for all substituents R 3 , R 4 , R 3 ', and R 4 ' are hydrogen atoms.
  • R 5 in both the formula for the bis(imidazoline-2-ylidene)s and the bis(imidazo ⁇ idine-2- ylidene)s of this invention can be selected from a large variety of moieties, including alkylene groups, arylene groups, and silylene groups. Atoms that can form the bridge include, but are not limited to, carbon, nitrogen, oxygen, silicon, and sulfur.
  • Suitable bridging moieties include methylene (-CH 2 -), substituted methylene, ethylene (-CH 2 CH 2 -), substituted ethylene, silylene (>SiR 2 ), benzo (C 6 H 4 ⁇ ), substituted benzo, biphenylene, substituted biphenylene, binaphthylene, and substituted binaphthylene.
  • Heterocyclic aromatic moieties such as, for example, pyridine, pyrimidine, pyrazine, pyridazine, furan, thiophene, oxathiolane, thianthrene, isobenzofuran,phenoxathiin, isothiazole,phenoxazine, and the like, can also form the bridge.
  • Preferred R 5 moieties include biphenylene, binaphthylene, and substituted benzo, with substituted benzo being more preferred. Highly preferred is benzo substituted with methyl groups.
  • the bridge preferably has at least four atoms, and more preferably has from four to eight atoms. While better results have been observed with longer bridges, it is possible that judicious choices for R 1 , R 2 , R 3 , R 4 , R 3 ', and R 4 ' may improve results for short bridges.
  • a highly preferred embodiment of this invention involves generation of the imidazoline-2-ylidene in situ from the corresponding imidazolinium salt (similarly so for the imidazolidine-2-ylidene and the corresponding imidazolidinium salt); this removes the need to handle the N-heterocyclic carbene ligands in an inert atmosphere.
  • Protonated salts of the imidazoline-2-ylidene carbenes and imidazolidine-2-ylidene carbenes are monoprotonated, while the protonated salts of the bis(imidazoline-2-ylidene)s andthebis(imidazolidine-2-ylidene)s are diprotonated.
  • Suitable counterions for the protonated salts are virtually limitless, but halides are preferred counterions. The most preferred counterions are chloride and bromide.
  • the imidazolinium salts are straightforward to synthesize and are air-stable. While the absence of oxygen is not necessary when using a protonated salt of an imidazoline-2-ylidene carbene or an imidazolidine-2-ylidene carbene, it is preferred. When using a neutral carbene, the absence of oxygen is necessary. In any instance where oxygen is excluded, the presence of an inert gas such as mtrogen, helium, or argon is preferred.
  • the aryl halide or pseudohalide and the arylboronic acid may be employed in an ideal molar ratio of about 1 : 1 when using an aryl halide or pseudohalide that has only one halogen atom (other than a fluorine atom) or pseudohalide group; or either reagent may be used in excess. It is preferred to use the arylboronic acid in an excess such that the molar ratio of aryl halide or pseudohalide to arylboronic acid is in the range of from about 1 : 1 to about 1 :3 when using an aryl halide or pseudohalide that has only one halogen atom (other than a fluorine atom) or pseudohalide group.
  • aryl halide or pseudohalide has more than one halogen atom (other than fluorine) and or pseudohalide group
  • reactions may be carried out in sequence.
  • An arylboronic acid will react first at the site ofthe more reactive substituent, e.g. , at iodine before bromine. Reaction at only the site ofthe more reactive substituent(s) can be performed.
  • a suitable molar ratio of aryl halide or pseudohalide to strong base is in the range of from about 1 : 1 to about 1 :5.
  • a more preferred molar ratio of aryl halide or pseudohalide to strong base is in the range of from about 1:1 to about 1:3.
  • the molar ratio of metal atoms of the metal compound to aryl halide or pseudohalide molecules is in the range offroin about 0.01:1 to about0.05:l; apreferredmolar ratio of metal atoms of metal compound to aryl halide or pseudohalide molecules is in the range of from about 0.02: 1 to about 0.04: 1.
  • the molar ratio of metal atoms ofthe metal compound to carbene molecules is in the range of from about 1:0.5 to about 1:5, and more preferably in the range of from about 1:1 to about 1:3.
  • the order of addition ofthe various components to a reaction vessel is not of particular importance. Premixing ofthe components ofthe catalyst system is not necessary; however, it is preferred that the catalyst system is premixed.
  • the metal compound, the N-heterocyclic carbene (salt or neutral compound), and the strong base are mixed together after being added in no particular order to a reaction vessel.
  • the mixing time (activation period) for these components on the laboratory scale may be very short, e.g., five minutes or less, but a preferred mixing time is in the range of from about fifteen minutes to about sixty minutes.
  • the aryl halide or pseudohalide and the arylboronic acid may be added to the same reaction vessel, or the premixed catalyst system can be transferred to a different vessel in which the reaction is to take place. Use ofthe same vessel for premixing the catalyst system and conducting the reaction is preferred.
  • the strong base, aryl halide or pseudohalide, the arylboronic acid, the metal compound, the liquid medium, and the N-heterocyclic carbene (salt or neutral compound) are added in any order to the reaction vessel.
  • the mixture may be heated, provided that the temperature does not exceed the thermal decomposition temperature ofthe catalyst system or the products ofthe reaction.
  • Preferred temperatures are in the range of from about 20 ° C to about 150 ° C; more preferred temperatures are in the range of from about 20 °C to about 110°C.
  • the aryl halide or pseudohalide is an aryl chloride, an aryl triflate, or an aryl tosylate
  • heat is usually necessary to drive the reaction.
  • Preferred temperatures when the aryl halide or pseudohalide is an aryl chloride, an aryl triflate, or an aryl tosylate are in the range of from about 40 ° C to about 150 ° C.
  • the reaction(s) proceeds easily at room temperature, although heat may speed the reaction.
  • aryl bromides and aryl iodides preferred temperatures are in the range of from about 20 °C to about 70 °C.
  • the reaction mixture is normally agitated.
  • a preferred contact time for the components of the reaction is in the range of from about one hour to about forty-eight hours. More preferably, the contact time is from about one hour to about twenty-four hours.
  • the base (2.00 mmol) was either Cs 2 CO 3 or K 2 CO 3 ; the metal compound was either Pd(CH 3 CO 2 ) 2 (5.8mg, 0.025 mmol) orPd 2 (dibenzylideneacetone) 3 (18.8mg, 0.01 mmol); and the N-heterocyclic carbene was l,3-bis(2,6-diisopropylphenyl)imidazolinium chloride (106 mg, 0.03 mmol).
  • the aryl halide or pseudohalide in all runs was 4-methylphenyl p- toluenesulfonate (1.0 mmol).
  • Reagents, analyses, and procedures were as described in Example 1 , except as follows.
  • the base was Cs 2 CO 3 (652 mg, 2.00 mmol);
  • the metal compound was bis(l,5- cyclooctadiene)nickel (8.3mg, 0.03 mmol, or 16.7mg, 0.06 mmol); and
  • the N-heterocyclic carbene was l,3-bis(2,6-diisopropylphenyl)imidazolinium chloride (106 mg, 0.03 mmol).
  • aryl chlorides 1.0 mmol each
  • aryl triflates 1.0 mmol each
  • the arylboronic acid for all runs was phenylboronic acid (1.5 mmol).
  • N-(2,4,6-trimethylphenyl)imidazoline (2.0 mmol) was heated in xylene (5 mL) at 120 °C for
  • EXAMPLE 7 The procedure used in all runs of this example are as follows: A Schlenk tube was charged with Pd(CH 3 CO 2 ) 2 (5.6 mg, 0.025 mmol), one ofthe carbenes prepared in Example 6 (0.025 mmol), Cs 2 CO 3 (2.00 equivalents), and a magnetic stirring bar. After a 30 minute catalyst activation period, 1,4-dioxane (3 mL), 4-chlorotoluene (1.0 mmol), and phenylboronic acid (1.5 mmol) were added in turn to the Schlenk tube. The Schlenk tube was placed in a 80 °C oil bath and stirred for a number of hours. The mixture was then allowed to cool to room temperature. The bis(imidazoline-2-ylidene) used in each run are listed in Table 6. All ofthe yields reported in Table 6 are ofthe heterocoupling product, and are the average of two runs. TABLE 6
  • the liquid medium for the processes of this mvention can include any of a wide range of solvents, and mixtures of solvents are also usable.
  • the exclusion of water is not necessary, but is preferred.
  • Types of solvents that can be used include hydrocarbons, ethers, amides, ketones, and alcohols. Polar solvents are preferred; ethers are a preferred solvent type.
  • Ethers that may be used include, for example, diethyl ether, di- ⁇ -propyl ether, diisopropyl ether, tert-butyl ethyl ether, diheptyl ether, 1,3-dioxolane, 1,4-dioxane, tetrahydrofuran, methyl tetrahydrofuran, glyme (the dimethyl ether of ethylene glycol), diglyme (the dimethyl ether of diethylene glycol), and the like. Cyclic ethers and polyethers are preferred; a highly preferred ether is 1,4-dioxane.
  • Alkali metal salts are a preferred group of inorganic bases.
  • suitable alkali metal salts include, but are not limited to, lithium carbonate, lithium tert-butoxide, sodium acetate, sodium bicarbonate, sodium tert-butoxide, sodium oxide, sodium tetrafluoroborate, potassium acetate, potassium carbonate, potassium tert-butoxide, potassium nitrite, potassium phosphate, potassium sulfite, potassium hexafluorophosphate, cesium acetate, cesium bicarbonate, cesium carbonate, cesium fluoride, cesium nitrate, and cesium sulfate.
  • Alkali metal salts of carboxylic acid anions are also suitable for use as the inorganic base in this invention. More preferred are salts of potassium and cesium; most preferred are potassium salts.
  • the most highly preferred inorganic base is potassium tert- butoxide. Choice(s) of inorganic base will vary with the particular system of aryl halide or pseudohalide and amine involved.
  • aryl halide or pseudohalide Directly bonded to the aromatic ring(s) ofthe aryl halide or pseudohalide (i.e., aryl halide or aryl pseudohalide) is at least one halogen atom selected from a chlorine atom, a bromine atom, and an iodine atom, or at least one pseudohalide group.
  • aryl halide group includes such groups as /j-tomenesulfonate (tosylate), trifluoromethanesulfonate (triflate), methanesulfonate (meslyate), nonaflate (ON f ), and aryl diazonium salts (ArN 2 + X , where X ⁇ is halide, BF 4 , etc.).
  • the aryl halide or pseudohalide can have two or more such halogen atoms with an atomic number greater than nine and/or pseudohalide groups, including combinations of halogen atoms and pseudohalide groups.
  • the halogen atoms with an atomic number greater than nine and/or pseudohalide groups should all be different from each other.
  • substituents when two such substituents are present, they may be a chlorine atom and a bromine atom, or an iodine atom and a tosylate group, or etc. It is preferred that there is only one chlorine atom, bromine atom, iodine atom, or pseudohalide group directly bound to the aryl ring of the aryl halide or pseudohalide.
  • Aryl chlorides are more preferred as the aryl halide reactants. To prevent self-reaction, it is preferred that amino groups are not present on the aryl halide or pseudohalide.
  • the aryl moiety for the aryl halide or pseudohalide can be homocyclic or heterocyclic.
  • suitable homocyclic aryl moieties include, but are not limited to, benzene, naphthalene, anthracene, phenanthrene, pyrene, biphenyl, acenaphthalene, fluorene, and indene.
  • Heterocyclic aryl moieties that can be used include, for example, furan, thiophene, oxathiolane, thianthrene, isoberizofuran, phenoxathiin, and the like.
  • Nitrogen-containing heterocycles, that can be used include, for example, pyridine, indole, isoxazole,and the like- Benzene is a preferred aryl moiety for the aryl halide or pseudohalide.
  • substituents other than a chlorine atom, a bromine atom, an iodine atom, and/or a pseudohalide group that may be present on the aromatic ring(s) include, but are not limited to, hydrogen atoms, fluorine atoms, nitro groups, hydrocarbyl groups, alkoxy groups, perfluorohydrocarbyl groups, silyl groups, amide groups, nitrile groups, ether groups, ketone groups, and ester groups.
  • hydrocarbyl groups are present, they are preferably C ⁇ to C 18 alkyl groups or C 6 to C 20 aryl or arylalkyl groups.
  • hydrocarbyl groups examples include methyl, ethyl, isopropyl, tert-butyl, cyclopentyl, methylcyclohexyl, decyl, phenyl, tolyl, xylyl, benzyl, naphthyl, and tetrahydronaphthyl.
  • Alkoxy group substituents preferably have Cj to C 6 alkyl moieties. Some examples of alkoxy groups are methoxy, ethoxy, isopropoxy, methylcyclopentoxy, and cyclohexoxy.
  • Perfluorohydrocarbyl groups include alkyl and aryl perfluorocarbons; suitable perfluorohydrocarbyl groups are, for example, trifluoromethyl, pentafluoroethyl, pentafluorophenyl, and heptafluoronaphthyl.
  • Substituent silyl groups preferably have to C 18 alkyl groups or C 6 to C 20 aryl or aralkyl groups, and examples include trimethylsilyl, triisopropylsilyl, tert-butyl(dimethyl)silyl, tridecylsilyl, and triphenylsilyl.
  • the substituents preferred for the aryl halide or pseudohalide will depend on the product that is desired.
  • Amines suitable for use in this invention include primary and secondary amines.
  • the group(s) of the amine may be saturated, unsaturated, branched, straight-chain, cyclic, or aromatic. Heteroatoms, such as oxygen, sulfur, and silicon, and/or functional groups including ethers, esters, and ketones can be present in the group(s) of the amine.
  • the two groups on a particular amine may be the same or different.
  • the aryl moiety can be homocyclic or heterocyclic, as described for the aryl halide or pseudohalide.
  • the preferred aryl moieties are benzene and naphthalene.
  • Substituents on the aryl ring, again as described for the aryl halide or pseudohalide, can be hydrogen atoms, fluorine atoms, nitro groups, hydrocarbyl groups, alkoxy groups, perfluorohydrocarbyl groups, silyl groups, ether groups, ketone groups, and ester groups.
  • chlorine atoms, bromine atoms, iodine atoms, and/or pseudohalide groups are not present on aromatic ring(s) in the amine.
  • the aromatic rings in the amine are preferably devoid of halogen atoms with an atomic number greater than nine, and are preferably also devoid of pseudohalide groups.
  • one or more fluorine atoms can be present on the aromatic ring(s).
  • Examples of primary amines include, but are not limited to, methylamine, cyclopropylamine, n-butylamine, tert-butylamine, cyclobutylamine, 2-pentylamine, hexylamine, heptylamine, octylamine, 4-methylcyclooctylamine, decylamine, phenylamine (aniline), 2,4,6-trimethylphenylamine (2,4,6-trimethylaniline), and benzylamine.
  • Suitable secondary amines include dimethylamine, ethylmethylamine, diisopropylamine, di-n- butylamine, di-sec-butylamine, dicyclopentylamine, dihexylamine, di(methylcyclohexyl)amine, piperidine, morpholine, (ethyl)(octyl)amine, (nonyl)( «- propyl)amine, didodecylamine, N-methylphenylamine (N-methylaniline), (methyl)phenylamine, and the like.
  • Primary or secondary amines may be preferred, depending on the product desired; similarly, preferred groups for the amine also depend on the desired product.
  • the metal compound comprises at least one metal atom selected from nickel, palladium, and platinum having a formal oxidation state of zero or two, and is sometimes referred to hereinafter as the metal compound.
  • Inorganic salts of nickel, palladium, or platinum that can be used include the bromides, chlorides, fluorides, iodides, cyanides, nitrates, sulfides, sulfites, and sulfates.
  • Organic nickel, palladium, or platinum compounds that may be used include complexes and salts such as the carboxylates, e.g., the acetates or propionates, etc.
  • Suitable nickel compounds include bis(l,5-cyclooctadiene)nickel, nickel acetate, nickel oxalate, nickel phosphate, nickel stearate, nickel acetylacetonate, nickel tetrafluoroborate, nickel thiocyanate, nickel carbonate, and nickel sulfamate.
  • Examples of palladium compounds include Pd(OAc) 2 , palladmm(H) chloride, Pd(CH 3 CN) 4 (BF 4 ) 2 , PdCl 2 (CH 3 CN) 2 , PdCl 2 (PhCN) 2 , PdCl 2 (PPh 3 ) 2 , tris(dibenzylideneacetone)dipalladium(0) [which is also referred to herein as dipalladium tris(dibenzylideneacetone)], and palladium trifluoroacetate.
  • Platinum compounds that can be used include platinum acetylacetonate and platinum chloride. Nickel and palladium compounds are preferred; more preferred are compounds of palladium. Palladium compounds such as palladium acetate and tris(dibenzylideneacetone)dipalladium(0) are most preferred.
  • N-heterocyclic carbenes are imidazoline-2-ylidenes ofthe formula
  • R 1 and R 2 are each, independently, alkyl or aryl groups having at least 3 carbon atoms
  • R 3 andR 4 are each, independently, a hydrogen atom, a halogen atom, or a hydrocarbyl group
  • R 1 , R 2 , R 3 , and R 4 are as defined for the imidazoline-2-ylidenes; bis(imidazoline-2-ylidene)s ofthe formula
  • R 1 , R 2 , R 3 , and R 4 are as defined for the imidazoline-2-ylidenes, wherein R 3 ' and R 4 ' are as defined for R 3 and R 4 for the imidazoline-2-ylidenes, and wherein R 5 is a bridging group that links the two imidazoline rings; bis(imidazolidine-2-ylidene)s ofthe formula
  • R 1 , R 2 , R 3 , and R 4 are as defined for the imidazoline-2-ylidenes, wherein R 3 ' and R 4 ' are as defined for R 3 and R 4 for the imidazoline-2-ylidenes, and wherein R 5 is a bridging group that links the two imidazolidine rings.
  • R 1 and R 2 are preferably sterically bulky groups. Suitable groups include, but are not limited to, isopropyl, sec-butyl, tert-butyl, 2,2-dimethylpropyl (neopentyl), cyclohexyl, norbornyl, adamantyl, tolyl, 3,5-dimethylphenyl, 2,4,6-trimethylphenyl, 2,6-diisopropylphenyl, and triphenylmethyl.
  • Preferred groups are tert-butyl, 2,4,6-trimethylphenyl, 2,6-diisopropylphenyl, 2,4,6-triisopropylphenyl, 2,4,6- triisopropylphenylmethyl, and triphenylmethyl.
  • Most preferred for both R 1 and R 2 are the 2,4,6-trimethylphenyl 2,6-diisopropylphenyl, and 2,4,6-triisopropylphenyl, groups.
  • suitable R 3 , R 4 , R 3 ', and R 4 ' groups include chlorine atoms, bromine atoms, hydrogen atoms, hydrocarbyl groups, and the like.
  • hydrocarbyl groups When hydrocarbyl groups are present, they are preferably Cj to Cj 8 alkyl groups or C 6 to C 20 aryl or aralkyl groups.
  • suitable hydrocarbyl groups are methyl, ethyl, isopropyl, tert-butyl, cyclopentyl, methylcyclohexyl, decyl, phenyl, tolyl, xylyl, benzyl, naphthyl, and tetrahydronaphthyl.
  • Chlorine atoms and hydrogen atoms are preferred groups. Most preferred for all substituents
  • R 3 , R 4 , R 3 ', and R 4 ' are hydrogen atoms.
  • R 5 in both the formula for the bis(imidazoline-2-ylidene)s and the bis(imidazolidine-2- ylidene)s of this invention can be selected from a large variety of moieties, including alkylene groups, arylene groups, and silylene groups. Atoms that can form the bridge include, but are not limited to, carbon, nitrogen, oxygen, silicon, and sulfur.
  • Suitable bridging moieties include methylene (-CH 2 -), substituted methylene, ethylene (-CH 2 CH 2 -), substituted ethylene, silylene (>SiR 2 ), benzo (C 6 H 4 ⁇ ), substituted benzo, biphenylene, substituted biphenylene, binaphthylene, and substituted binaphthylene.
  • Heterocyclic aromatic moieties such as, for example, pyridine, pyrimidine, pyrazine, pyridazine, furan, thiophene, oxathiolane, thianthrene, isobenzofuran, phenoxathiin, isothiazole, phenoxazine, and the like, can also form the bridge.
  • Preferred R 5 moieties include biphenylene, binaphthylene, and substituted benzo, with substituted benzo being more preferred. Highly preferred is benzo substituted with methyl groups.
  • the bridge has at least one atom, and more preferably has from four to eight atoms. While better results have been observed with longer bridges, it is possible that judicious choices for R 1 , R 2 , R 3 , R 4 , R 3 ', and R 4 ' may improve results for short bridges.
  • a highly preferred embodiment of this invention involves generation of the imidazoline-2-ylidene in situ from the corresponding imidazolinium salt (similarly so for the imidazolidine-2-ylidene and the corresponding imidazolidinium salt); this removes the need to handle the N-heterocyclic carbene ligands in an inert atmosphere.
  • Protonated salts of the imidazolme-2-ylidene carbenes and imidazolidine-2-ylidene carbenes are monoprotonated, while the protonated salts of the bis(imidazoline-2-ylidene)s and the bis(imidazolidine-2-ylidene)s are diprotonated.
  • Suitable counterions for the protonated salts are virtually limitless, but halides are preferred counterions. The most preferred counterions are chloride and bromide.
  • the imidazolinium salts are straightforward to synthesize and are air-stable. While the absence of oxygen is not necessary when using a protonated salt of an imidazoline-2-ylidene carbene or an imidazolidine-2-ylidene carbene, it is preferred. When using a neutral carbene, the absence of oxygen is necessary. In any instance where oxygen is excluded, the presence of an inert gas such as nitrogen, helium, or argon is preferred.
  • the aryl halide or pseudohalide and the amine may be employed in an ideal molar ratio of about 1 : 1 when using an aryl halide or pseudohalide that has only one halogen atom (other than a fluorine atom) or pseudohalide group; or either reagent may be used in excess. It is preferred to use the amine in an excess such that the molar ratio of aryl halide or pseudohalide to amine is in the range of from about 1 : 1 to about 1:3 when using an aryl halide or pseudohalide that has only one halogen atom (other than a fluorine atom) or pseudohalide group.
  • aryl halide or pseudohalide has more than one halogen atom (other than fluorine) and/or pseudohalide group
  • reactions may be carried out in sequence.
  • An amine will react first at the site ofthe more reactive substituent, e.g. , at iodine before bromine. Reaction at only the site ofthe more reactive substiruent(s) can be performed.
  • a suitable molar ratio of aryl halide or pseudohalide to strong base is in the range of from about 1 : 1 to about 1 : 5.
  • a more preferred molar ratio of aryl halide or pseudohalide to strong base is in the range of from about 1:1 to about 1:3.
  • the molar ratio of metal atoms of the metal compound to aryl halide or pseudohalide molecules is in the range offrom about 0.01:1 to about 0.05:1; apreferredmolar ratio of metal atoms of metal compound to aryl halide or pseudohalide molecules is in the range offrom about 0.01:1 to about 0.03 : 1.
  • the molar ratio of metal atoms ofthe metal compound to carbene molecules is in the range of from about 1 :0.5 to about 1:5, and more preferably in the range of from about 1:1 to about 1:3.
  • the order of addition ofthe various components to a reaction vessel is not of particular importance. Premixing ofthe components ofthe catalyst system is not necessary; however, it is preferred that the catalyst system is premixed.
  • the metal compound and the N-heterocyclic carbene salt or neutral compound
  • the mixing time (activation period) for these components on the laboratory scale may be very short, e.g. , five minutes or less, but a preferred mixing time is in the range offrom about fifteen minutes to about sixty minutes.
  • the aryl halide or pseudohalide, the amine, and the strong base may be added to the same reaction vessel, or the premixed catalyst system can be transferred to a different vessel in which the reaction is to take place. Use ofthe same vessel for premixing the catalyst system and conducting the reaction is preferred.
  • the strong base, aryl halide or pseudohalide, the amine, the metal compound, the liquid medium, and the N- heterocyclic carbene (salt or neutral compound) are added in any order to the reaction vessel.
  • the mixture may be heated, provided that the temperature does not exceed the thermal decomposition temperature ofthe catalyst system or the products ofthe reaction.
  • Preferred temperatures are in the range offrom about 20 °C to about 150 °C; more preferred temperatures are in the range offrom about 20 ° C to about 120 ° C.
  • the aryl halide or pseudohalide is an aryl chloride, an aryl triflate, an aryl tosylate, aryl mesylate, aryl trifluoromethanesulfone, aryl nonaflate, or aryl diazonium salt, heat is usually necessary to drive the reaction.
  • aryl halide or pseudohalide is an aryl chloride, an aryl triflate, or an aryl tosylate are in the range offrom about 40°C to about 150°C.
  • the reaction(s) proceeds easily at room temperature, although heat may speed the reaction.
  • preferred temperatures are in the range offrom about 20 °C to about 70 °C.
  • the reaction mixture is normally agitated.
  • a preferred contact time for the components of the reaction is in the range of from about one hour to about seventy-two hours. More preferably, the contact time is from about one hour to about forty-eight hours.
  • One aspect is the provision of exceedingly efficient catalyzed Kumada coupling reactions.
  • the other aspect involves the discovery of catalyzed homocoupling reactions in which aryl triflates or aryl tosylates are caused to homocouple even in the presence of a Grignard reagent.
  • the liquid medium for the processes of this invention can include any of a wide range of solvents, and mixtures of solvents are also usable.
  • the exclusion of water is necessary because the processes of this mvention use Grignard reagents.
  • "exclusion of water” as used here is intended to mean that no addition of water should be undertaken and that necessary steps should be taken to avoid unintended introduction of water into the reaction.
  • inconsequential amounts of water which have no meaningful effect upon the reaction may be present.
  • the reaction is carried out in the substantial absence of water.
  • Types of solvents that can be used include hydrocarbons, ethers, and amides. Polar solvents are preferred.
  • Ethers are a preferred solvent type. Ethers that may be used include, for example, diethyl ether, di-n-propyl ether, diisopropyl ether, tert-butyl ethyl ether, diheptyl ether, 1,3-dioxolane, 1,4-dioxane, tefrahydrofuran, methyl tetrahydrofuran, glyme (the dimethyl ether of ethylene glycol), diglyme (the dimethyl ether of diethylene glycol), and the like.
  • Cyclic ethers and polyethers are preferred, especially 1,4-dioxane and tetrahydrofuran. Mixtures comprising tetrahydro-furan are more preferred; a highly preferred liquid medium is a mixture of 1,4-dioxane and tetrahydrofuran.
  • aryl halide or pseudohalide Directly bonded to the aromatic ring(s) ofthe aryl halide or pseudohalide (i.e., aryl halide or aryl pseudohalide) is at least one halogen atom selected from a chlorine atom, a bromine atom, and an iodine atom, or at least one pseudohalide group.
  • pseudohalide group includes such groups as ⁇ -toluene sulfonate (tosylate), trifluoromethanesulfonate (triflate), methanesulfonate (meslyate), nonaflate (ON f ), and aryl diazonium salts (ArN 2 + X , where X y is halide, BF 4 , etc.).
  • the aryl halide or pseudohalide can have two or more such halogen atoms with an atomic number greater than nine and/or pseudohalide groups, including combinations of halogen atoms and pseudohalide groups.
  • the halogen atoms with an atomic number greater than nine and/or pseudohalide groups should all be different from each other.
  • substituents when two such substituents are present, they may be a chlorine atom and a bromine atom, or an iodine atom and a tosylate group, or etc. It is preferred that there is only one chlorine atom, bromine atom, iodine atom, or pseudohalide group directly bound to the aryl ring of the aryl halide or pseudohalide.
  • Aryl chlorides are more preferred as the aryl halide reactants.
  • the aryl moiety for the arylhalide or pseudohalide can be homocyclic or heterocyclic.
  • suitable homocyclic aryl moieties include, but are not limited to, benzene, naphthalene, anthracene, phenanthrene, pyrene, biphenyl, acenaphthalene, fluorene, and indene.
  • Heterocyclic aryl moieties that can be used include, for example, furan, thiophene, pyridine, indole, oxathiolane, isoxazole, thianthrene, isobenzofuran, phenoxathiin, and the like.
  • Benzene is a preferred aryl moiety for the aryl halide or pseudohalide.
  • substituents other than a chlorine atom, a bromine atom, an iodine atom, and/or a pseudohalide group that may be present on the aromatic ring(s) include, but are not limited to, hydrogen atoms, fluorine atoms, nitro groups, hydrocarbyl groups, alkoxy groups, perfluorohydrocarbyl groups, silyl groups, amino groups, ether groups, ketone groups, and ester groups.
  • hydrocarbyl groups are present, they are preferably Ci to C 18 alkyl groups or C 6 to C 20 aryl or aralkyl groups.
  • hydrocarbyl groups examples include methyl, ethyl, isopropyl, tert-butyl, cyclopentyl, methylcyclohexyl, decyl, phenyl, tolyl, xylyl, benzyl, naphthyl, and tetrahydronaphthyl.
  • Alkoxy group substituents preferably have Cj to C 6 alkyl moieties. Some examples of alkoxy groups are methoxy, ethoxy, isopropoxy, methylcyclopentoxy, and cyclohexoxy.
  • Perfluorohydrocarbyl groups include alkyl and aryl perfluorocarbons; suitable perfluorohydrocarbyl groups are, for example, trifluoromethyl, pentafluoroethyl, pentafluorophenyl, and heptafluoronaphthyl.
  • Substituent silyl groups preferably have to C 18 alkyl groups or C 6 to C 20 aryl or aralkyl groups, and examples include trimethylsilyl, triisopropylsilyl, tert-butyl(dimethyl)silyl, tridecylsilyl, and triphenylsilyl.
  • the substituents preferred for the aryl halide or pseudohalide will depend on the product that is desired.
  • the Grignard reagent can be an organomagnesium chloride, an organomagnesium bromide, or an organomagnesium iodide, and is preferably an organomagnesium bromide.
  • the organic group ofthe Grignard reagent may be saturated, unsaturated, branched, straight- chain, cyclic, or aromatic. Heteroatoms, such as oxygen, sulfur, and silicon can be present in the organic group ofthe Grignard reagent.
  • the organic group ofthe Grignard reagent is preferably an aromatic group.
  • the aryl moiety ofthe aromatic group can be homocyclic or heterocyclic, as described for the aryl halide or pseudohalide.
  • the preferred aryl moieties are benzene and naphthalene.
  • Substituents on the aryl ring, as described for the aryl halide or pseudohalide, can be hydrogen atoms, fluorine atoms, nitro groups, hydrocarbyl groups, alkoxy groups, perfluorohydrocarbyl groups, and silyl groups. Preferred substituents for the Grignard reagent depend on the desired product.
  • the metal compound comprises at least one metal atom selected from nickel, palladium, and platinum having a formal oxidation state of zero or two, and is sometimes referred to hereinafter as the metal compound.
  • Inorganic salts of nickel, palladium, or platinum that can be used include the bromides, chlorides, fluorides, iodides, cyanides, nitrates, sulfides, sulfites, and sulfates.
  • Organic nickel, palladium, or platinum compounds that may be used include complexes and salts such as the carboxylates, e.g., the acetates or propionates, etc.
  • Suitable nickel compounds include bis(l,5-cyclooctadiene)nickel, nickel acetate, nickel oxalate, nickel phosphate, nickel stearate, nickel acetylacetonate, nickel tetrafluoroborate, nickel thiocyanate, nickel carbonate, and nickel sulfamate.
  • palladium compounds examples include Pd(OAc) 2 , palladium(II) chloride, Pd(CH 3 CN) 4 (BF 4 ) 2 , PdCl 2 (CH 3 CN) 2 , PdCl 2 (PhCN) 2 , PdCl 2 (PPh 3 ) 2 , tris(dibenzylideneacetone)dipalladium(0) [which is also referred to herein as dipalladium tris(dibenzylideneacetone)], and palladium trifluoroacetate.
  • Platinum compounds that can be used include platinum acetylacetonate and platinum chloride. Nickel and palladium compounds are preferred; more preferred are compounds of palladium. Palladium compounds such as palladium acetate and tris(dibenzylideneacetone)dipalladium(0) are most preferred.
  • N-heterocyclic carbenes are imidazoline-2-ylidenes ofthe formula
  • R 1 and R 2 are each, independently, alkyl or aryl groups having at least 3 carbon atoms
  • R 3 andR 4 are each, independently, a hydrogen atom, a halogen atom, or a hydrocarbyl group
  • R 1 , R 2 , R 3 , and R 4 are as defined for the imidazoline-2-ylidenes; bis(imidazoline-2-ylidene)s ofthe formula
  • R 1 , R 2 , R 3 , and R 4 are as defined for the imidazoline-2-ylidenes, wherein R 3 ' and R 4 ' are as defined for R 3 and R 4 for the imidazoline-2-ylidenes, and wherein R 5 is a bridging group that links the two imidazoline rings; bis(imidazolidine-2-ylidene)s ofthe formula
  • R 1 , R 2 , R 3 , and R 4 are as defined for the imidazoline-2-ylidenes, wherein R 3 ' and R 4 ' are as defined for R 3 and R 4 for the imidazoline-2-ylidenes, and wherein R 5 is a bridging group that links the two imidazolidine rings.
  • R 1 and R 2 are preferably sterically bulky groups. Suitable groups include, but are not limited to, isopropyl, _?ec-butyl, tert-butyl, 2,2-dimethylpropyl (neopentyl), cyclohexyl, norbornyl, adamantyl, tolyl, 3,5-dimethylphenyl, 2,4,6-trimethylphenyl, 2,6-diisopropylphenyl, and triphenylmethyl.
  • Preferred groups are tert-butyl, 2,4,6-trimethylphenyl, 2,6-diisopropylphenyl, 2,4,6-triisopropylphenyl, 2,4, 6-triisopropylphenylmethyl and triphenylmethyl.
  • Most preferred for both R 1 and R 2 are the 2,4,6-trimethylphenyl and 2,6-diisopropylphenyl groups.
  • suitable R 3 , R 4 , R 3 ', and R 4 ' groups include chlorine atoms, bromine atoms, hydrogen atoms, hydrocarbyl groups, and the like. When hydrocarbyl groups are present, they are preferably to C 18 alkyl groups or C 6 to C 20 aryl or aralkyl groups.
  • hydrocarbyl groups examples include methyl, ethyl, isopropyl, tert-butyl, cyclopentyl, methylcyclohexyl, decyl, phenyl, tolyl, xylyl, benzyl, naphthyl, and tetrahydronaphthyl.
  • Chlorine atoms and hydrogen atoms are preferred groups. Most preferred for all substituents R 3 , R 4 , R 3 ', and R 4 ' are hydrogen atoms.
  • R 5 in both the formula for the bis(imidazoline-2-ylidene)s and the bis(imidazolidine-2- ylidene)s of this invention can be selected from a large variety of moieties, including alkylene groups, arylene groups, and silylene groups. Atoms that can form the bridge include, but are not limited to, carbon, nitrogen, oxygen, silicon, and sulfur.
  • Suitable bridging moieties include methylene (-CH 2 -), substituted methylene, ethylene (-CH 2 CH 2 -), substituted ethylene, silylene (>SiR 2 ), benzo (C 6 H 4 ⁇ ), substituted benzo, biphenylene, substituted biphenylene, binaphthylene, and substituted binaphthylene.
  • Heterocyclic aromatic moieties such as, for example, pyridine, pyrimidine, pyrazine, pyridazine, furan, thiophene, oxathiolane, thianthrene, isobenzo furan, phenoxathiin, isothiazole, phenoxazine, and the like, can also form the bridge.
  • Preferred R 5 moieties include biphenylene, binaphthylene, and substituted benzo, with substituted benzo being more preferred. Highly preferred is benzo substituted with methyl groups.
  • the bridge has at least one atom, and preferably has from four to eight atoms. While better results have been observed with longer bridges, it is possible that judicious choices for R 1 , R 2 , R 3 , R 4 , R 3 ', and R 4 ' may improve results for short bridges.
  • a highly preferred embodiment of this invention involves generation of the imidazoline-2-ylidene in situ from the corresponding imidazolinium salt (similarly so for the imidazolidine-2-ylidene and the corresponding imidazolidinium salt); this removes the need to handle the N-heterocyclic carbene ligands in an inert atmosphere.
  • Protonated salts of the imidazoline-2-ylidene carbenes and imidazolidine-2-ylidene carbenes are monoprotonated, while the protonated salts of the bis(imidazoline-2-ylidene)s andthebis(imidazolidine-2-ylidene)s are diprotonated.
  • Suitable counterions for the protonated salts are virtually limitless, but halides are preferred counterions. The most preferred counterions are chloride and bromide.
  • the imidazolinium salts are straightforward to synthesize and are air-stable. While the absence of oxygen is not necessary when using a protonated salt of an imidazoline-2-ylidene carbene or an imidazolidine-2-ylidene carbene, it is preferred. When using a neutral carbene, the absence of oxygen is necessary. In any instance where oxygen is excluded, the presence of an inert gas such as nitrogen, helium, or argon is preferred.
  • the aryl halide or pseudohalide and the Grignard reagent may be employed in an ideal molar ratio of about 1 : 1 when using an aryl halide or pseudohalide that has only one halogen atom (other than a fluorine atom) or pseudohalide group; or either reagent may be used in excess. It is preferred to use the Grignard reagent in an excess such that the molar ratio of aryl halide or pseudohalide to Grignard reagent is in the range offrom about 1 : 1 to about 1 :5 when using an aryl halide or pseudohalide that has only one halogen atom (other than a fluorine atom) or pseudohalide group.
  • reaction may be carried out in sequence.
  • a Grignard reagent will react first at the site ofthe more reactive substituent, e.g., at iodine before bromine. Reaction at only the site of the more reactive substituent(s) can be performed. In reactions carried out in sequence where the Grignard reagents are different, each should be added separately. It is preferred to allow one reaction to finish before the addition of the next Grignard reagent.
  • Grignard reagents When different Grignard reagents are used, it is preferred to use close to the ideal molar ratio of aryl halide or pseudohalide to Grignard reagent to minimize undesirable side products. The presence of a Grignard reagent is not necessary in a homocoupling reaction.
  • the molar ratio of metal atoms ofthe metal compound to carbene molecules is in the range of from about 1 :0.5 to about 1 :5, and more preferably in the range offrom about 1 :0.5 to about 1:2.5.
  • the order of addition ofthe various components to a reaction vessel is not of particular importance for either heterocoupling or homocoupling reactions. Premixing of the components of the catalyst system is not necessary; however, it is preferred for both heterocoupling and homocoupling reactions that the catalyst system is premixed.
  • the metal compound and the N-heterocyclic carbene salt or neutral compound
  • the mixing time (activation period) for these components on the laboratory scale may be very short, e.g., five minutes or less, but a preferred mixing time is in the range offrom about fifteen minutes to about sixty minutes.
  • the aryl halide or pseudohalide and the Grignard reagent may be added to the same reaction vessel, or the premixed catalyst system can be transferred to a different vessel in which the reaction is to take place. Use ofthe same vessel for premixing the catalyst system and conducting the reaction is preferred.
  • the mixture may be heated, provided that the temperature does not exceed the thermal decomposition temperature ofthe catalyst system or the products ofthe reaction.
  • Preferred temperatures for both heterocoupling and homocoupling reactions are in the range offrom about 20 ° C to about 150°C; more preferred temperatures are in the range of from about 20°C to about 120°C.
  • the aryl halide is an aryl chloride, or when the aryl pseudohalide is an aryl triflate or an aryl tosylate, heat is usually necessary to drive the reaction.
  • Preferred temperatures when the aryl halide is an aryl chloride, or when the aryl pseudohalide is an aryl triflate or an aryl tosylate are in the range offrom about 40°C to about 150°C.
  • the reaction(s) proceeds easily at room temperature, although heat may speed the reaction.
  • preferred temperatures are in the range offrom about 20°C to about 70°C.
  • Patent No.5,077,414, and/or Arduengo A. J. III., Dias, H.V.R.; Harlow, R.L. and Kline, M. J. Am. Chem. Soc, 1992, 114, 5530-5534.
  • the synthesis of l,3-bis(2,6-diisopropylphenyl)imidazolinium chloride was carried out in a similar fashion, except that it was done in two steps (rather than in one pot).
  • the mixture was hydrolyzed either with aqueous HC1 (1.0 moles per liter) or H 4 NC1 solution.
  • the solvent was removed under vacuum and the residue was purified by flash cliromatography using hexane or a mixture of hexane and ethyl acetate.
  • Reagents, analyses, and procedures were as described in Example 13, except as follows.
  • the solvent was a mixture of 1,4-dioxane and tetrahydrofuran; the l ,3 -bis(substituted)imidazolinium chloride used was l ,3-bis(2,6- diisopropylphenyl)imidazolinmm chloride. All runs were performed at 80 °C. Several different aryl halides (1.0 mmol each) and Grignard reagents (1.2 mmol each) were used.
  • Run B Pd(CH 3 CO 2 ) 2 (4.5mg, 0.02 mmol) was used as the metal compound; in Run F, 1.8 mmol of the Grignard reagent was used, and in Runs H and I, 2.5 mmol of the Grignard reagent was used.
  • Example 16 demonstrates that the process of this invention is useful in the homocoupling of aryl triflates and aryl tosylates.
  • the liquid medium for the processes of this invention can include any of a wide range of solvents, and mixtures of solvents are also usable.
  • the exclusion of water is not necessary, but is preferred.
  • Types of solvents that can be used include hydrocarbons, ethers, amides, ketones, and alcohols. Polar solvents are preferred; ethers are a more preferred solvent type.
  • Ethers that may be used include, for example, diethyl ether, di-n-propyl ether, diisopropyl ether, tert-butyl ethyl ether, diheptyl ether, 1,3-dioxolane, 1,4-dioxane, tetrahydrofuran, methyl tetrahydrofuran, glyme (the dimethyl ether of ethylene glycol), diglyme (the dimethyl ether of diethylene glycol), and the like. Cyclic ethers and polyethers are preferred; a highly preferred ether is 1,4-dioxane.
  • Alkali metal salts are a preferred group of inorganic bases.
  • suitable alkali metal salts include, but are not limited to, lithium carbonate, litl-ium tert-butoxide, sodium acetate, sodium bicarbonate, sodium tert-butoxide, sodium oxide, sodium tetrafluoroborate, potassium acetate, potassium carbonate, potassium tert-butoxide, potassium nitrite, potassium phosphate, potassium sulfite, potassium hexafluorophosphate, cesium acetate, cesium bicarbonate, cesium carbonate, cesium fluoride, cesium nitrate, and cesium sulfate.
  • Alkali metal salts of carboxylic acid anions are also suitable for use as the inorganic base in this invention. More preferred are salts of potassium and cesium; most preferred are cesium salts.
  • the most highly preferred inorganic base is cesium fluoride. Choice(s) of inorganic base will vary with the particular system of aryl halide or pseudohalide and organotin compound involved. Amine bases are generally not preferred because, to date, they appear to poison the catalyst system ofthe invention.
  • aryl halide or pseudohalide Directly bonded to the aromatic ring(s) ofthe aryl halide or pseudohalide (i.e., aryl halide or aryl pseudohalide) is at least one halogen atom selected from a chlorine atom, a bromine atom, and an iodine atom, or at least one pseudohalide group.
  • pseudohalide group includes such groups as -toluenesulfonate (tosylate), and trifluoromethanesulfonate (triflate), methanesulfonate (meslyate), nonaflate (ON f ), and aryl diazonium salts (ArN 2 + X , where x" is halide, BF 4 , etc.).
  • the aryl halide or pseudohalide can have two or more such halogen atoms with an atomic number greater than nine and/or pseudohalide groups, including combinations of halogen atoms and pseudohalide groups.
  • the halogen atoms with an atomic number greater than nine and/or pseudohalide groups should all be different from each other.
  • substituents when two such substituents are present, they may be a chlorine atom and a bromine atom, or an iodine atom and a tosylate group, or etc. It is preferred that there is only one chlorine atom, bromine atom, iodine atom, or pseudohalide group directly bound to the aryl ring of the aryl halide or pseudohalide.
  • Aryl chlorides are more preferred as the aryl halide reactants. To prevent self-reaction, it is preferred that stannyl groups are not present on the aryl halide or pseudohalide.
  • the aryl moiety for the aryl halide or pseudohalide can be homocyclic or heterocyclic.
  • suitable homocyclic aryl moieties include, but are not limited to, benzene, naphthalene, anthracene, phenanthrene, pyrene, biphenyl, acenaphthalene, fluorene, and indene.
  • Heterocyclic aryl moieties that can be used include, for example, furan, thiophene, oxathiolane, thianthrene, isobenzofuran, phenoxathiin, and the like.
  • Nitrogen-containing heterocycles that can be used include, for example, pyridine, indole, and isoxazole, and the like.
  • Benzene is a preferred aryl moiety for the aryl halide or pseudohalide.
  • substituents other than a chlorine atom, a bromine atom, an iodine atom, and/or a pseudohalide group that may be present on the aromatic ring(s) include, but are not limited to, hydrogen atoms, fluorine atoms, nitro groups, hydrocarbyl groups, alkoxy groups, perfluorohydrocarbyl groups, silyl groups, ether groups, ketone groups, and ester groups.
  • hydrocarbyl groups are present, they are preferably C t to Cj 8 alkyl groups or C 6 to C 20 aryl or aralkyl groups.
  • hydrocarbyl groups examples include methyl, ethyl, isopropyl, tert-butyl, cyclopentyl, methylcyclohexyl, decyl, phenyl, tolyl, xylyl, benzyl, naphthyl, and tetrahydronaphthyl.
  • Alkoxy group substituents preferably have to C 6 alkyl moieties. Some examples of alkoxy groups are methoxy, ethoxy, isopropoxy, methylcyclopentoxy, and cyclohexoxy.
  • Perfluorohydrocarbyl groups include alkyl and aryl perfluorocarbons; suitable perfluorohydrocarbyl groups are, for example, trifluoromethyl, pentafluoroethyl, pentafluorophenyl, and heptafluoronaphthyl.
  • Substituent silyl groups preferably have Cj to C 1S alkyl groups or C 6 to C 20 aryl or aralkyl groups, and examples include trimethylsilyl, triisopropylsilyl, tert-butyl(dimethyl)silyl, tridecylsilyl, and triphenylsilyl.
  • the substituents preferred for the aryl halide or pseudohalide will depend on the product that is desired.
  • the aryl moiety when an aryl moiety is the unsaturated group of the organotin compound, the aryl moiety can be homocyclic or heterocyclic, as described for the aryl halide or pseudohalide.
  • the preferred aryl moieties are benzene and naphthalene.
  • Substituents on the aryl ring, again as described for the aryl halide or pseudohalide, can be hydrogen atoms, fluorine atoms, nitro groups, hydrocarbyl groups, alkoxy groups, perfluorohydrocarbyl groups, silyl groups, ether groups, ketone groups, and ester groups.
  • chlorine atoms, bromine atoms, iodine atoms, and/or pseudohalide groups are not present on aromatic ring(s) in the organotin compound.
  • the aryl moiety ofthe organotin compound is preferably devoid of halogen atoms with an atomic number greater than nine, and preferably is also devoid of pseudohalide groups.
  • one or more fluorine atoms can be present on the aromatic ring(s).
  • Preferred unsaturated groups for the organotin compound depend on the desired product.
  • the unsaturated group ofthe organotin compound when not an aryl moiety, may be a vinyl, allyl, alkenyl, or benzyl moiety.
  • Suitable unsaturated groups are vinyl, allyl, benzyl, butenyl, cyclobutenyl, 2-pentenyl, cyclohexenyl, hexenyl, 1 -heptenyl, 2-octenyl, and the like.
  • a large variety of substituents, as described for the aryl moieties, can be present in the unsaturated group.
  • the saturated groups ofthe organotin compound may be the same or different, and are preferably saturated hydrocarbyl groups. These hydrocarbyl groups can be branched, straight chain, or cyclic. More preferred are hydrocarbyl groups containing from one to ten carbon atoms. Examples of suitable groups include, but are not limited to, methyl, ethyl, isopropyl, .--butyl, sec-butyl, 2-pentyl, cyclopentyl, methylcyclohexyl, heptyl, octyl, nonyl, and decyl. Especially preferred saturated groups for the organotin compound are methyl groups and n- butyl groups; it is also preferred that all ofthe saturated groups are the same.
  • Organotin compounds suitable for use in this invention include, but are not limited to, phenyl(trimethyl)tin, trimethyl(3-methylbenzyl)tin, triethyl( ⁇ entafluorophenyl)tin, triethyl(vinyl)tin, (allyl)tripropyltin, tripropyl(o-tolyl)tin, trin-butyl(vinyl)fm, trin-butyl(l- ethoxyvinyl)tin, and trin-butyl(3-methyl-2-butenyl)tin.
  • the metal compound comprises at least one metal atom selected from nickel, palladium, and platinum having a formal oxidation state of zero or two, and is sometimes referred to hereinafter as the metal compound.
  • Inorganic salts of nickel, palladium, or platinum that can be used include the bromides, chlorides, fluorides, iodides, cyanides, nitrates, sulfides, sulfites, and sulfates.
  • Organic nickel, palladium, or platinum compounds that may be used include complexes and salts such as the carboxylates, e.g., the acetates or propionates, etc.
  • Suitable nickel compounds include bis(l,5-cyclooctadiene)nickel, nickel acetate, nickel oxalate, nickel phosphate, nickel stearate, nickel acetylacetonate, nickel tetrafluoroborate, nickel thiocyanate, nickel carbonate, and nickel sulfamate.
  • palladium compounds examples include Pd(OAc) 2 , palladium(II) chloride, Pd(CH 3 CN) 4 (BF 4 ) 2 , PdCl 2 (CH 3 CN) 2 , PdCl 2 (PhCN) 2 , PdCl 2 (PPh 3 ) 2 , tris(dibenzylideneacetone)dipalladium(0) [which is also referred to herein as dipalladium tris(dibenzylideneacetone)], and palladium trifmoroacetate.
  • Platinum compounds that can be used include platinum acetylacetonate and platinum chloride. Nickel and palladium compounds are preferred; more preferred are compounds of palladium. Palladium compounds such as palladium acetate and tris(dibenzylideneacetone)dipalladium(0) are most preferred.
  • N-heterocyclic carbenes are imidazoline-2-ylidenes ofthe formula
  • R 1 and R 2 are each, independently, alkyl or aryl groups having at least 3 carbon atoms
  • R 3 and R 4 are each, independently, a hydrogen atom, a halogen atom, or a hydrocarbyl group
  • R 1 , R 2 , R 3 , and R 4 are as defined for the imidazoline-2-ylidenes ; bis(imidazoline-2-ylidene)s ofthe formula
  • R 1 , R 2 , R 3 , and R 4 are as defined for the imidazoline-2-ylidenes, wherein R 3 ' and R 4 ' are as defined for R 3 and R 4 for the imidazoline-2-ylidenes, and wherein R 5 is a bridging group that links the two imidazoline rings; bis(imidazolidine-2-ylidene)s ofthe formula
  • R 1 , R 2 , R 3 , and R 4 are as defined for the imidazoline-2-ylidenes, wherein R 3 ' and R 4 ' are as defined for R 3 and R 4 for the imidazoline-2-ylidenes, and wherein R 5 is a bridging group that links the two imidazolidine rings.
  • R 1 and R 2 are preferably sterically bulky groups. Suitable groups include, but are not limited to, isopropyl, -?ec-butyl, tert-butyl, 2,2-dimethylpropyl (neopentyl), cyclohexyl, norbornyl, adamantyl, tolyl, 3,5-dimethylphenyl, 2,4,6-trimethylphenyl, 2,6-diisopropylphenyl, 2,4,6-triisopropylphenyl, and triphenylmethyl. Preferred groups are tert-butyl, 2,4,6-trimethylphenyl, 2,6-diisopropylphenyl, and triphenylmethyl. Most preferred for both R 1 and R 2 are the 2,4,6-trimethylphenyl, 2,6-diisopropylphenyl, and 2,4,6-triisopropylphenyl groups.
  • R 3 , R 4 , R 3 ', and R 4 ' groups include chlorine atoms, bromine atoms, hydrogen atoms, hydrocarbyl groups, and the like.
  • hydrocarbyl groups When hydrocarbyl groups are present, they are preferably Cj to C ]8 alkyl groups or C 6 to C 20 aryl or aralkyl groups.
  • suitable hydrocarbyl groups are methyl, ethyl, isopropyl, tert-butyl, cyclopentyl, methylcyclohexyl, decyl, phenyl, tolyl, xylyl, benzyl, naphthyl, and tetrahydronaphthyl.
  • Chlorine atoms and hydrogen atoms are preferred groups. Most preferred for all substituents R 3 , R 4 , R 3 ', and R 4 ' are hydrogen atoms.
  • R 5 in both the formula for the bis(imidazoline-2-ylidene)s and the bis(imidazolidine-2- ylidene)s of this invention can be selected from a large variety of moieties, including alkylene groups, arylene groups, and silylene groups. Atoms that can form the bridge include, but are not limited to, carbon, nitrogen, oxygen, silicon, and sulfur.
  • Suitable bridging moieties include methylene (-CH 2 -), substituted methylene, ethylene (-CH 2 CH 2 -), substituted ethylene, silylene (>SiR 2 ), benzo (C 6 H 4 ⁇ ), substituted benzo, biphenylene, substituted biphenylene, binaphthylene, and substituted binaphthylene.
  • Heterocyclic aromatic moieties such as, for example, pyridine, pyrimidine, pyrazine, pyridazine, furan, thiophene, oxathiolane, thianthrene, isobenzofuran, phenoxathiin, isothiazole, phenoxazine, and the like, can also form the bridge.
  • Preferred R 5 moieties include biphenylene, binaphthylene, and substituted benzo, with substituted benzo being more preferred. Highly preferred is benzo substituted with methyl groups.
  • the bridge has at least one atom, and preferably has from four to eight atoms. While better results have been observed with longer bridges, it is possible that judicious choices for R 1 , R 2 , R 3 , R 4 , R 3 ', and R 4 ' may improve results for short bridges.
  • a highly preferred embodiment of this invention involves generation ofthe imidazoline-2-ylidene in situ from the corresponding imidazolinium salt (similarly so for the imidazolidine-2-ylidene and the corresponding imidazolidinium salt); this removes the need to handle the N-heterocyclic carbene ligands in an inert atmosphere.
  • Protonated salts of the imidazoline-2-ylidene carbenes and imidazolidine-2-ylidene carbenes are monoprotonated, while the protonated salts of the bis(imidazoline-2-ylidene)s andthebis(imidazolidine-2-ylidene)s are diprotonated.
  • Suitable counterions for the protonated salts are virtually limitless, but halides are preferred counterions. The most preferred counterions are chloride and bromide.
  • the imidazolinium salts are straightforward to synthesize and are air-stable. While the absence of oxygen is not necessary when using a protonated salt of an imidazoline-2-ylidene carbene or an imidazolidine-2-ylidene carbene, it is preferred. When using a neutral carbene, the absence of oxygen is necessary. In any instance where oxygen is excluded, the presence of an inert gas such as nitrogen, helium, or argon is preferred.
  • the aryl halide or pseudohalide and the organotin compound may be employed in an ideal molar ratio of about 1:1 when using an aryl halide or pseudohalide that has only one halogen atom (other than a fluorine atom) or pseudohalide group; or either reagent may be used in excess. It is preferred to use the organotin compound in an excess such that the molar ratio of aryl halide or pseudohalide to organotin compound is in the range of from about 1 : 1 to about 1 :3 when using an aryl halide or pseudohalide that has only one halogen atom (other than a fluorine atom) or pseudohalide group.
  • aryl halide or pseudohalide has more than one halogen atom (other than fluorine) and/or pseudohalide group
  • reactions may be carried out in sequence.
  • An organotin compound will react first at the site of the more reactive substituent, e.g., at iodine before bromine. Reaction at only the site of the more reactive substituent(s) can be performed.
  • a suitable molar ratio of aryl halide or pseudohalide to strong base is in the range of from about 1 : 1 to about 1:5.
  • a more preferred molar ratio of aryl halide or pseudohalide to strong base is in the range of from about 1:1 to about 1:3.
  • the molar ratio of metal atoms of the metal compound to aryl halide or pseudohalide molecules is in the range of from about 0.01:1 to about0.10:l; apreferredmolar ratio of metal atoms of metal compound to aryl halide or pseudohalide molecules is in the range offrom about 0.03 : 1 to about 0.07: 1.
  • the molar ratio of metal atoms ofthe metal compound to carbene molecules is in the range of from about 1:0.5 to about 1:5, and more preferably in the range of from about 1:1 to about 1:3.
  • the order of addition ofthe various components to a reaction vessel is not of particular importance.
  • Premixing ofthe components ofthe catalyst system is not necessary; however, it is preferred that the catalyst system is premixed.
  • the metal compound, the N-heterocyclic carbene (salt or neutral compound), and the strong base are mixed together after being added in no particular order to a reaction vessel.
  • the mixing time (activation period) for these components on the laboratory scale may be very short, e.g., five minutes or less, but a preferred mixing time is in the range of from about fifteen minutes to about sixty minutes.
  • the aryl halide or pseudohalide and the organotin compound may be added to the same reaction vessel, or the premixed catalyst system can be transferred to a different vessel in which the reaction is to take place. Use ofthe same vessel for premixing the catalyst system and conducting the reaction is preferred.
  • the strong base, aryl halide or pseudohalide, the organotin compound, the metal compound, the liquid medium, and the N-heterocyclic carbene (salt or neutral compound) are added in any order to the reaction vessel.
  • one or more salt additives may be included in the reaction mixture.
  • a salt additive may speed the reaction and/or increase the yield ofthe reaction.
  • Suitable compounds for use as a salt additive include alkali metal halides and alkaline earth halides. Alkali metal halides are preferred; examples of alkali metal halides include lithium chloride, lithium bromide, lithium iodide, sodium chloride, sodium bromide, sodium iodide, potassium chloride, potassium bromide, potassium iodide, cesium chloride, cesium bromide, and cesium iodide. Lithium salts and sodium salts are preferred, especially lithium chloride and sodium iodide.
  • the mixture may be heated, provided that the temperature does not exceed the thermal decomposition temperature ofthe catalyst system or the products ofthe reaction.
  • Preferred temperatures are in the range offrom about 20 ° C to about 150 ° C; more preferred temperatures are in the range offrom about 20°C to about 120°C.
  • the arylhalide or pseudohalide is an aryl chloride, an aryl triflate, or an aryl tosylate
  • heat is usually necessary to drive the reaction.
  • Preferred temperatures when the aryl halide or pseudohalide is an aryl chloride, an aryl triflate, or an aryl tosylate are in the range offrom about 40 °C to about 150°C.
  • the reaction(s) proceeds easily at room temperature, although heat may speed the reaction.
  • aryl bromides and aryl iodides preferred temperatures are in the range offrom about 20 °C to about 70 °C.
  • the reaction mixture is normally agitated.
  • a preferred contact time for the components of the reaction is in the range of from about one hour to about seventy-two hours. More preferably, the contact time is from about one hour to about forty-eight hours.
  • the Schlenk tube was placed in a 100° C oil bath and stirred for 48 hours. The mixture was then allowed to cool to room temperature. The mixture was washed with diethyl ether. The organic layer and the diethyl ether extracts were combined, washed with saturated saline solution, and then dried over MgSO 4 . The solvent was removed under vacuum and the residue was purified by flash chromatography using hexane or a mixture of hexane and ethyl acetate.
  • the liquid medium for the processes of this invention can include any of a wide range of solvents, and mixtures of solvents are also usable.
  • the exclusion of water is not necessary, but is preferred.
  • Types of solvents that can be used include hydrocarbons, ethers, amides, ketones, and alcohols. Polar solvents are preferred; ethers are a more preferred solvent type.
  • Ethers that may be used include, for example, diethyl ether, di-n-propyl ether, diisopropyl ether, tert-butyl ethyl ether, diheptyl ether, 1,3-dioxolane, 1,4-dioxane, tetrahydrofuran, methyltefrahydrofuran, glyme (the dimethyl ether of ethylene glycol), diglyme (the dimethyl ether of diethylene glycol), and the like. Cyclic ethers and polyethers are preferred; a highly preferred ether is 1,4-dioxane.
  • Fluoride salts are a preferred group of bases.
  • Preferable counterions for the fluoride anion are alkali metal cations and ammonium cations.
  • an alkali metal fluoride can be lithium fluoride, sodium fluoride, potassium fluoride, rubidium fluoride, or cesium fluoride, and is preferably cesium fluoride. It is more preferable to use an ammonium fluoride.
  • Suitable substituents for the ammonium cation include hydrogen atoms and hydrocarbyl groups, whether straight chain, branched, or cyclic. Preferred hydrocarbyl substituents have from 1 to about 10 carbon atoms.
  • ammonium fluoride salts that can be used in this mvention include, but are not limited to, ammonium fluoride (NH 4 F), trimethylammonium fluoride, tetramethylammonium fluoride, phenyltrimethylammonium fluoride, berizyltrimethylammoi-ium fluoride, tetraethylammonium fluoride, tetrapropylammonium fluoride, diisopropylammonium fluoride, isopropylcyclohexylammonium fluoride, tetrabutylammonium fluoride, diisobutylammonium fluoride, cyclopentylammonium fluoride, dicyclohexylammonium fluoride, heptylammonium fluoride, tetraoctylammonium fluoride, dinonylammonium fluoride, «-decylammonium fluoride, and triben
  • ammonium fluoride salts are tetramethylammonium fluoride, tetrabutylammonium fluoride, and tetraoctylammonium fluoride, especially tetrabutylammonium fluoride.
  • Choice(s) of base will vary with the particular system of aryl halide or pseudohalide and silane involved.
  • aryl halide or pseudohalide Directly bonded to the aromatic ring(s) ofthe aryl halide or pseudohalide (i.e., aryl halide or aryl pseudohalide) is at least one halogen atom selected from a chlorine atom, a bromine atom, and an iodine atom, or at least one pseudohalide group.
  • pseudohalide group includes such groups as j-i-toluenesulfonate (tosylate), trifluoromethanesulfonate (triflate), methanesulfonate (mesylate), nonaflate (ON f ), and aryl diazonium salts (ArN 2 X , where X y is halide, BF 4 , etc.).
  • the aryl halide or pseudohalide can have two or more such halogen atoms with an atomic number greater than nine and/or pseudohalide groups, including combinations of halogen atoms and pseudohalide groups.
  • the halogen atoms with an atomic number greater than nine and/or pseudohalide groups should all be different from each other.
  • substituents when two such substituents are present, they may be a chlorine atom and a bromine atom, or an iodine atom and a tosylate group, or etc. It is preferred that there is only one chlorine atom, bromine atom, iodine atom, or pseudohalide group directly bound to the aryl ring of the aryl halide or pseudohalide.
  • Aryl chlorides are more preferred as the aryl halide reactants. To prevent self-reaction, it is preferred that silyl groups are not present on the aryl halide or pseudohalide.
  • the aryl moiety for the aryl halide or pseudohalide can be homocyclic or heterocyclic.
  • suitable homocyclic aryl moieties include, but are not limited to, benzene, naphthalene, anthracene, phenanthrene, pyrene, biphenyl, acenaphthalene, fluorene, and indene.
  • Heterocyclic aryl moieties that can be used include, for example, furan, thiophene, pyridine, indole, oxathiolane, isoxazole, thianthrene, isobenzofuran, phenoxathiin, and the like.
  • Benzene is a preferred aryl moiety for the aryl halide or pseudohalide.
  • substituents other than a chlorine atom, a bromine atom, an iodine atom, and/or a pseudohalide group that may be present on the aromatic ring(s) include, but are not limited to, hydrogen atoms, fluorine atoms, nitro groups, hydrocarbyl groups, alkoxy groups, perfluorohydrocarbyl groups, ether groups, ketone groups, and ester groups.
  • hydrocarbyl groups are present, they are preferably to C 18 alkyl groups or C 6 to C 20 aryl or aralkyl groups.
  • hydrocarbyl groups examples include methyl, ethyl, isopropyl, tert-butyl, cyclopentyl, methylcyclohexyl, decyl, phenyl, tolyl, xylyl, benzyl, naphthyl, and tetrahydronaphthyl.
  • Alkoxy group substituents preferably have to C 6 alkyl moieties. Some examples of alkoxy groups are methoxy, ethoxy, isopropoxy, methylcyclopentoxy, and cyclohexoxy.
  • Perfluorohydrocarbyl groups include alkyl and aryl perfluorocarbons; suitable perfluorohydrocarbyl groups are, for example, trifluoromethyl, pentafluoroethyl, pentafluorophenyl, andheptafluoronaphthyl.
  • the substituents preferred for the aryl halide or pseudohalide will depend on the product that is desired.
  • the aryl moiety when an aryl moiety is the unsaturated group of the silane, the aryl moiety can be homocyclic or heterocyclic, as described for the aryl halide or pseudohalide.
  • the preferred aryl moieties are benzene and naphthalene.
  • Substituents on the aryl ring, again as described for the aryl halide or pseudohalide, can be hydrogen atoms, fluorine atoms, nitro groups, hydrocarbyl groups, alkoxy groups, perfluorohydrocarbyl groups, ether groups, ketone groups, and ester groups.
  • chlorine atoms, bromine atoms, iodine atoms, and/or pseudohalide groups are not present on aromatic ring(s) in the silane.
  • the aryl moiety ofthe silane is preferably devoid of halogen atoms with an atomic number greater than nine, and preferably is also devoid of pseudohalide groups.
  • one or more fluorine atoms can be present on the aromatic ring(s).
  • Preferred unsaturated groups for the silane depend on the desired product.
  • the unsaturated group ofthe silane when not an aryl moiety, may be a vinyl, allyl, alkenyl, benzyl, or aryloxy moiety.
  • Suitable unsaturated groups are vinyl, allyl, benzyl, 1- butenyl, l-cyclobutenyl,2-pentenyl, cyclohexenyl, 1-hexenyl, l-heptenyl,2-octenyl,phenoxy, naphthoxy, biphenyloxy, phenantliroxy, fluorenoxy, and the like.
  • a large variety of substituents, as described for the aryl moieties, can be present in the unsaturated group.
  • the saturated groups ofthe silane may be the same or different, and are preferably saturated hydrocarbyl or saturated hydrocarbyloxy groups.
  • the saturated hydrocarbyl groups can be branched, straight chain, or cyclic. More preferred are hydrocarbyl groups containing from one to ten carbon atoms. Examples of suitable groups include, but are not limited to, methyl, ethyl, isopropyl, .--butyl, sec-butyl, 2-pentyl, cyclopentyl, methylcyclohexyl, heptyl, octyl, nonyl, and decyl.
  • the hydrocarbyl portion ofthe saturated hydrocarbyloxy groups can be branched, straight chain, or cyclic. Similarly, hydrocarbyl portions ofthe saturated hydrocarbyloxy groups containing from one to ten carbon atoms are more preferred.
  • Suitable saturated hydrocarbyloxy groups include methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, tert-butoxy, cyclobutoxy, 3- pentoxy, 4-methylcyclohexoxy, 4-heptoxy, 1-octoxy, 2-nonoxy, and 1-decoxy.
  • Especially preferred saturated groups for the silane are methyl groups and methoxy groups; it is also preferred that all ofthe saturated groups are the same.
  • Silanes suitable for use in this invention include, but are not limited to, vinyltrimethylsilane, phenyl(trimethyl)silane, frimethyl(3-methylbenzyl)silane, (6-methoxy-2- naphthyl)trimethylsilane, triethyl(vinyl)silane, triethyl(pentafluorophenyl)silane, (allyl)tripropylsilane, tripropyl( ⁇ -toly ⁇ )silane, tri-?.-butyl(3-methyl-2-butenyl)silane, tri-n- butyl(vinyl)silane, vinyltrimethoxysilane, phenyltrimethoxysilane, (6-methoxy-2- naphthyl)trimemoxysilane,naphmyltriisopropoxysilane,phenyldimethoxyisopropoxysilane, phenoxytriisopropylsilane,
  • the metal compound comprises at least one metal atom selected from nickel, palladium, and platinum having a formal oxidation state of zero or two, and is sometimes referred to hereinafter as the metal compound.
  • Inorganic salts of nickel, palladium, or platinum that can be used include the bromides, chlorides, fluorides, iodides, cyanides, nitrates, sulfides, sulfites, and sulfates.
  • Organic nickel, palladium, or platinum compounds that may be used include complexes and salts such as the carboxylates, e.g., the acetates or propionates, etc.
  • Suitable nickel compounds include bis(l,5-cyclooctadiene)nickel, nickel acetate, nickel oxalate, nickel phosphate, nickel stearate, nickel acetylacetonate, nickel tetrafluoroborate, nickel thiocyanate, nickel carbonate, and nickel sulfamate.
  • Examples of palladium compounds include Pd(OAc) 2 , palladium(II) chloride, Pd(CH 3 CN) 4 (BF 4 ) 2 , tris(dibenzylideneacetone)dipalladium(0) [which is also referred to herein as dipalladium tris(dibenzylideneacetone)], and palladium trifluoroacetate.
  • Platinum compounds that can be used include platinum acetylacetonate and platinum chloride. Nickel and palladium compounds are preferred; more preferred are compounds of palladium. Palladium compounds such as palladium acetate and tris(dibenzylideneacetone)dipalladium(0) are most preferred.
  • N-heterocyclic carbenes are A) imidazoline-2-ylidenes ofthe formula
  • R 1 or R 2 is an alkyl or aryl group having at least 3 carbon atoms
  • R 3 and R 4 are each, independently, a hydrogen atom, a halogen atom, or a hydrocarbyl group
  • R 1 , R 2 , R 3 , and R 4 are as defined for the imidazoline-2-ylidenes;
  • R 1 , R 2 , R 3 , and R 4 are as defined for the imidazoline-2-ylidenes, wherein R 3 ' and R 4 ' are as defined for R 3 and R 4 for the imidazoline-2-ylidenes, and wherein R 5 is a bridging group that links the two imidazoline rings;
  • R 1 , R 2 , R 3 , and R 4 are as defined for the imidazoline-2-ylidenes, wherein R 3 ' and R 4 ' are as defined for R 3 and R 4 for the imidazoline-2-ylidenes, and wherein R 5 is a bridging group that links the two imidazolidine rings.
  • both R 1 and R 2 are secondary or tertiary groups. More preferably, R 1 and R 2 are sterically bulky groups. Suitable groups include, but are not limited to, isopropyl, sec-butyl, tert-butyl, 2,2-dimethylpropyl (neopentyl), cyclohexyl, norbornyl, adamantyl, tolyl, 3,5-dimethylphenyl, 2,4,6-trimethylphenyl, 2,6-diisopropylphenyl, and triphenylmethyl. Preferred groups are tert-butyl, 2,4,6-trimethylphenyl, 2,6-diisopropylphenyl, and triphenylmethyl. Most preferred for both R 1 and R 2 are the 2,4,6-trimethylphenyl and 2,6-diisopropylphenyl groups.
  • R 3 , R 4 , R 3 ', and R 4 ' groups include chlorine atoms, bromine atoms, hydrogen atoms, hydrocarbyl groups, and the like.
  • hydrocarbyl groups When hydrocarbyl groups are present, they are preferably to C 18 alkyl groups or C 6 to C 20 aryl or aralkyl groups.
  • suitable hydrocarbyl groups are methyl, ethyl, isopropyl, tert-butyl, cyclopentyl, methylcyclohexyl, decyl, phenyl, tolyl, xylyl, benzyl, naphthyl, and tetrahydronaphthyl.
  • Chlorine atoms and hydrogen atoms are preferred groups. Most preferred for all substituents R 3 , R 4 , R 3 ', and R 4 ' are hydrogen atoms.
  • R 5 in both the formula for the bis(imidazoline-2-ylidene)s and the bis(imidazolidine-2- ylidene)s of this invention can be selected from a large variety of moieties, including alkylene groups, arylene groups, and silylene groups. Atoms that can form the bridge include, but are not limited to, carbon, nitrogen, oxygen, silicon, and sulfur.
  • Suitable bridging moieties include methylene (-CH 2 -), substituted methylene, ethylene (-CH 2 CH 2 -), substituted ethylene, silylene (>SiR 2 ), benzo (C 6 H 4 ⁇ ), substituted benzo, biphenylene, substituted biphenylene, binaphthylene, and substituted binaphthylene.
  • Heterocyclic aromatic moieties such as, for example, pyridine, pyrimidine, pyrazine, pyridazine, furan, thiophene, oxathiolane, thianthrene, isobenzofuran, phenoxathiin, isothiazole, phenoxazine, and the like, can also form the bridge.
  • Preferred R 5 moieties include biphenylene, binaphthylene, and substituted benzo, with substituted benzo being more preferred. Highly preferred is benzo substituted with methyl groups.
  • the bridge preferably has at least four atoms, and more preferably has from four to eight atoms. While better results have been observed with longer bridges,it is possible that judicious choices for R 1 , R 2 , R 3 , R 4 , R 3 ', and R 4 ' may improve results for short bridges.
  • a highly preferred embodiment of this invention involves generation of the imidazoline-2-ylidene in situ from the corresponding imidazolinium salt (similarly so for the imidazolidine-2-ylidene and the corresponding imidazolidinium salt); this removes the need to handle the N-heterocyclic carbene ligands in an inert atmosphere.
  • Protonated salts of the imidazoline-2-ylidene carbenes and imidazolidine-2-ylidene carbenes are monoprotonated, while the protonated salts of the bis(imidazoline-2-ylidene)s and the bis(imidazolidine-2-ylidene)s are diprotonated.
  • Suitable counterions for the protonated salts are virtually limitless, but halides are preferred counterions. The most preferred counterions are chloride and bromide.
  • the imidazolinium salts are straightforward to synthesize and are air-stable. While the absence of oxygen is not necessary when using a protonated salt of an imidazoline-2-ylidene carbene or an imidazolidine-2-ylidene carbene, it is preferred. When using a neutral carbene, the absence of oxygen is necessary. In any instance where oxygen is excluded, the presence of an inert gas such as nitrogen, helium, or argon is preferred.
  • the aryl halide or pseudohalide and the silane may be employed in an ideal molar ratio of about 1 : 1 when using an aryl halide or pseudohalide that has only one halogen atom (other than a fluorine atom) or pseudohalide group; or either reagent may be used in excess. It is preferred to use the silane in an excess such that the molar ratio of aryl halide or pseudohalide to silane is in the range of from about 1:1.5 to about 1:4 when using an aryl halide or pseudohalide that has only one halogen atom (other than a fluorine atom) or pseudohalide group.
  • reaction may be carried out in sequence.
  • a silane will react first at the site ofthe more reactive substituent, e.g. , at iodine before bromine. Reaction at only the site ofthe more reactive substiruent(s) can be performed.
  • a suitable molar ratio of aryl halide or pseudohalide to strong base is in the range of from about 1 : 1 to about 1:5.
  • a more preferred molar ratio of aryl halide or pseudohalide to strong base is in the range of from about 1 : 1 to about 1:3.
  • the molar ratio of metal atoms of the metal compound to aryl halide or pseudohalide molecules is in the range offrom about 0.01:1 to about0.05:l; apreferredmolar ratio of metal atoms of metal compound to aryl halide or pseudohalide molecules is in the range offrom about 0.02: 1 to about 0.04: 1.
  • the molar ratio of metal atoms ofthe metal compound to carbene molecules is in the range of from about 1:0.5 to about 1:5, and more preferably in the range offrom about 1:1 to about 1:3.
  • the order of addition ofthe various components to a reaction vessel is not of particular importance. Premixing ofthe components ofthe catalyst system is not necessary; however, it is preferred that the catalyst system is premixed.
  • the metal compound, the N-heterocyclic carbene (salt or neutral compound), and the strong base are mixed together after being added in no particular order to a reaction vessel.
  • the mixing time (activation period) for these components on the laboratory scale may be very short, e.g., five minutes or less, but a preferred mixing time is in the range of from about fifteen minutes to about sixty minutes.
  • the aryl halide or pseudohalide and the silane may be added to the same reaction vessel, or the premixed catalyst system can be transferred to a different vessel in which the reaction is to take place. Use of the same vessel for premixing the catalyst system and conducting the reaction is preferred.
  • the strong base, aryl halide or pseudohalide, the silane, the metal compound, the liquid medium, and the N- heterocyclic carbene (salt or neutral compound) are added in any order to the reaction vessel.
  • the mixture may be heated, provided that the temperature does not exceed the the ⁇ nal decomposition temperature ofthe catalyst system or the products ofthe reaction.
  • Preferred temperatures are in the range offrom about 20 ° C to about 150 ° C; more prefe ⁇ ed temperatures are in the range of from about 20 °C to about 110°C.
  • the aryl halide or pseudohalide is an aryl chloride, an aryl triflate, or an aryl tosylate, heat is usually necessary to drive the reaction.
  • Prefe ⁇ ed temperatures when the aryl halide or pseudohalide is an aryl chloride, an aryl triflate, or an aryl tosylate are in the range offrom about 40 °C to about 150°C.
  • the reaction(s) usually proceeds at room temperature, although heat may speed the reaction.
  • prefe ⁇ ed temperatures are in the range offrom about 20 °C to about 90 °C.
  • the reaction mixture is normally agitated.
  • a prefe ⁇ ed contact time for the components of the reaction is in the range of from about one hour to about forty-eight hours. More preferably, the contact time is from about one hour to about twenty-four hours.
  • Toluene (500 mL) and l,4-Bis(2,6-diisopropylphenyl)diazabutadiene (25g, 66 mol) were added to a reaction vessel, followed by solid paraformaldehyde (2.0g, 66 mmol).
  • the reaction mixture was heated to 100 ° C until most ofthe parafo ⁇ naldehyde had dissolved.
  • the mixture was then cooled to 40°C, and HC1 (16.5mL, 4 moles per liter in dioxane, 66 mmol) was added via syringe.
  • the reaction mixture turned brown in color, and a white precipitate appeared after a few hours.
  • the reaction mixture was sti ⁇ ed at room temperature for another 36 hours.
  • Imidazolidine-2-ylidenes can be prepared by hydrogenation of the co ⁇ esponding imidazolinium salt, for example, with KH in tetrahydrofuran. See in this connection Arduengo et al, J. Am. Chem. Soc, 1995, 117, 11027.
  • the vial was placed in a 80 ° C oil bath and the mixture was sti ⁇ ed for a number of hours. The mixture was then allowed to cool to room temperature. The reaction mixture was quenched with water (30 mL), and extracted with diethyl ether (4 x 30 mL). The combined diethyl ether extractions were dried over MgSO 4 , concentrated in v ⁇ cuo, and purified by flash chromatography.
  • the metal compound was either Pd(CH 3 CO 2 ) 2 (6.7mg, 0.03 mmol) or Pd 2 (dibenzyl- ideneacetone) 3 (56.4mg, 0.03 mmol); and the N-heterocyclic carbene was l,3-bis(2,6-diiso- propylphenyl)imidazolinium chloride (13 mg, 0.03 mmol) or l,3-bis(2,4,6-trimethyl- phenyl)imidazolinium chloride (10 mg, 0.03 mmol). Two phosphine ligands were also used.
  • the amount of phenyltrimethoxysilane used in each run was different.
  • the aryl halide used in all runs was 4-bromotoluene (1.0 mmol).
  • the metal compound, ligand, temperature, amount of phenyltrimethoxysilane, and reaction time for each run are listed in Table 21. All ofthe yields reported in Table 20 are ofthe heterocoupling product.
  • the transition metal ofthe metal compound may be any of those in Groups 4-11 of the Periodic Table.
  • the metal compound can be in the form of an inorganic salt or an organic metal compound.
  • Inorganic salts that can be used include the bromides, chlorides, fluorides, iodides, cyanides, nitrates, sulfides, sulfites, and sulfates.
  • Organic metal compounds that may be used include complexes and salts such as the carboxylates, e.g., the acetates or propionates, etc.
  • Prefe ⁇ ed are metals from Groups 8-11, especially ruthenium, osmium, rhodium, nickel, palladium, platinum, and copper. More prefe ⁇ ed transition metals are the Group 10 metals, particularly nickel and palladium, and especially compounds in which the formal oxidation state of nickel or palladium is zero or two. Examples of ruthenium compounds are dichloro(l,5- cyclooctadiene)ruthenium, ruthenium acetate, ruthenium iodide, and the like. Osmium compounds that can be used include osmium chloride.
  • Suitable rhodium compounds include bis(l,5-cyclooctadiene)rhodium trifluoromethanesulfonate and rhodium chloride.
  • Suitable copper compounds include, but are not limited to, copper chloride, copper bromide, and copper cyanide.
  • Suitable nickel compounds include bis(l,5-cyclooctadiene)nickel, nickel acetate, nickel oxalate, nickel phosphate, nickel stearate, nickel acetylacetonate, nickel tetrafluoroborate, nickel thiocyanate, nickel carbonate, and nickel sulfamate.
  • palladium compounds examples include Pd(OAc) 2 , palladium(II) chloride, Pd(CH 3 CN) 4 (BF 4 ) 2 , PdCl 2 (CH 3 CN) 2 , PdCl 2 (PhCN) 2 , PdCl 2 (PPh 3 ) 2 , tris(dibenzylideneacetone)di ⁇ alladium(0) [which is also refe ⁇ ed to herein as dipalladium tris(dibenzylideneacetone)], and palladium trifluoroacetate.
  • Platinum compounds that can be used include platinum acetylacetonate and platinum chloride. More prefe ⁇ ed are compounds of palladium. Palladium compounds such as palladium acetate and tris(dibenzylideneacetone)dipalladium(0) are most prefe ⁇ ed.
  • the aryl moiety ofthe aromatic group at the 1 and 3 positions can be, but is not limited to, phenyl, biphenylyl, naphthyl, and anthracenyl.
  • the aryl moiety is not a phenyl group, the requirement for ortho substitution is fulfilled, for example, by a 1,3-disubstituted 2- naphthyl moiety (where the naphthyl group is bound to the nitrogen atom at the 2 position of the naphthyl group).
  • Prefe ⁇ ed as the aryl moiety is a phenyl group.
  • the secondary or tertiary group having at least three atoms at the ortho positions can be, for example, isopropyl, cyclopropyl, sec-butyl, tert-butyl, cyclobutyl, 3-pentyl, cyclo- pentyl, cyclohexyl, 2,5-dimethylhex-2-yl, norbornyl, and adamantyl.
  • the secondary or tertiary group has from three to about twelve carbon atoms, and more preferably has from three to about eight carbon atoms.
  • Prefe ⁇ ed groups are isopropyl and tert-butyl, especially isopropyl; preferably, both ortho groups are the same.
  • prefe ⁇ ed aromatic groups are 2,6-diisopropylphenyl, 2,6-di(tert-butyl)phenyl, and 2,4,6-triisopropylphenyl.
  • imidazoline-2-ylidenes examples include l,3-bis(2,6-diisopropyl- phenyl)imidazolme, 1 ,3-bis(2-isopropyl-6-tert-butylphenyl)imidazoline, 1 ,3-bis(2,6-ditert- butylphenyl)imidazoline, 1 ,3-bis(2,6-di(cyclohexyl)phenyl)imidazoline, 1 ,3-bis(2,4,6-triiso- propylphenyl)imidazoline, l,3-bis(2,6-dicyclopropylphenyl) ⁇ nidazoline, l,3-bis(2-isopropyl- 6-cyclohexyl)phenyl)imidazoline, l,3-bis(2,6-ditert-butyl-4-methylphenyl)imidazoline, l,3-bis(2,6-di(sec
  • a highly prefe ⁇ ed N-heterocyclic carbene is a protonated salt of an imidazoline-2-ylidene ofthe formula R4 R3
  • R 1 and R 2 are 2,6-diisopropylphenyl groups or 2,4,6-triisopropylphenyl groups
  • R 3 and R 4 are each, independently, a hydrogen atom, a halogen atom, or a hydrocarbyl group. Most preferably, R 3 and R 4 are both hydrogen atoms.
  • the bridging moiety can be selected from a large variety of moieties, including alkyl groups, aryl groups, and silyl groups, so long as the bridge has at least five atoms.
  • the bridge has five to about eight atoms. Atoms that can form the bridge include, but are not limited to, carbon, nitrogen, oxygen, silicon, and sulfur.
  • Suitable bridging moieties include 1,5-pentylene, 1,6-hexylene, 1,5- hexylene, benzo (C 6 H 4 ⁇ ), substituted benzo, biphenylene, substituted biphenylene, binaphthylene, and substituted binaphthylene.
  • Heterocyclic aromatic moieties such as, for example, pyridine, pyrimidine, pyrazine, pyridazine, furan, thiophene, oxathiolane, thianthrene, isobenzofuran, phenoxathiin, isothiazole, phenoxazine, and the like, can also form the bridge.
  • the bridging moiety preferably is hydrocarbylene.
  • the bridging moiety has from about eight to about thirty carbon atoms, and more preferably has from about ten to about twenty-five carbon atoms.
  • Prefe ⁇ ed bridging moieties include biphenylene, binaphthylene, and substituted benzo, with substituted benzo being more prefe ⁇ ed. Highly prefe ⁇ ed is benzo substituted with methyl groups.
  • the two nitrogen atoms that are not bound to the bridging moiety are each, independently, substituted by a secondary or tertiary group which has at least three atoms, preferably sterically bulky groups.
  • Suitable groups include, but are not limited to, isopropyl, cyclopropyl, sec-butyl, tert-butyl, cyclobutyl, 3-pentyl, cyclopentyl, cyclohexyl, norbornyl, 2,5-dimethylhex-2-yl, adamantyl, tolyl, 3,5-dimethylphenyl, 2,4,6-trimethylphenyl, 2,6- diisopropylphenyl, 2,4,6-triisopropylphenyl, and2,4,6-triisopropylphenylmethyl.
  • the secondary or tertiary group has from three to about twelve carbon atoms, and more preferably has from three to about eight carbon atoms.
  • both secondary or tertiary groups are the same.
  • Prefe ⁇ ed groups are tert-butyl, 2,4,6-trimethylphenyl, 2,6-ditert- butylphenyl, 2,6-diisopropylphenyl, and 2,4,6-triisopropylphenyl.
  • the 2,4,6-trimethylphenyl group is most prefe ⁇ ed as the secondary or tertiary group for both ofthe nitrogen atoms that are not bound to the bridging moiety.
  • bis(imidazoline-2-ylidene)s examples include 3,3'-bis[3-(2,4,6- trimethylphenyl)imidazoline-2-ylidene]biphenyl and 2,7-bis [3 -(2,6- diisopropyl ⁇ henyl)imidazoline-2-ylidene]naphthalene.
  • a highly prefe ⁇ ed N-heterocyclic carbene is a protonated salt of a bis(imidazoline-2-ylidene) ofthe formula
  • R 1 and R 2 are 2,4,6-trimethylphenyl groups
  • R 3 , R 4 , R 3 ', R 4 ' are hydrogen atoms
  • R 5 is a biphenylene, binaphthylene, or substituted benzo moiety, and the bridge formed by the moiety has at least five atoms.
  • Particularly prefe ⁇ ed protonated salts of bis(imidazoline-2-ylidene)s include
  • Imidazoline-2-ylidene carbenes and imidazolidine-2-ylidene carbenes are considerably less stable to air and moisture than their co ⁇ esponding protonated imidazolinium and imidazolidinium salts.
  • a highly prefe ⁇ ed embodiment of this invention involves use of the co ⁇ esponding imidazolinium salt to generate the imidazoline-2-ylidene in situ (similarly so for the imidazolidine-2-ylidene and the co ⁇ esponding imidazolidinium salt) to form the catalyst system; this removes the need to handle the N-heterocyclic carbene ligands in an inert atmosphere.
  • Protonated salts of the imidazoline-2-ylidene carbenes and imidazolidine-2-ylidene carbenes are monoprotonated, while the protonated salts of the bis(imidazoline-2-ylidene)s andthebis(imidazolidine-2-ylidene)s are diprotonated.
  • Suitable counterions for the protonated salts are virtually limitless, but halides are prefe ⁇ ed counterions. The most prefe ⁇ ed counterions are chloride and bromide.
  • the imidazolinium salts are straightforward to synthesize and are air-stable.
  • abase is included when aprotonated salt of an N-heterocyclic carbene is used.
  • a large variety of strong bases are suitable for use in this invention with the protonated carbene salts.
  • these are inorganic bases.
  • Alkali metal salts are a prefe ⁇ ed group of inorganic bases.
  • alkali metal salts include, but are not limited to, lithium carbonate, lithium tert-butoxide, sodium bicarbonate, sodium carbonate, sodium tert-butoxide, sodium oxide, sodium tetrafluoroborate, potassium acetate, potassium carbonate, potassium fluoride, potassium tert-butoxide, potassium nitrite, potassium phosphate, potassium sulfite, potassium hexafluorophosphate, cesium acetate, cesium bicarbonate, cesium carbonate, cesium fluoride, cesium nitrate, and cesium sulfate.
  • Alkali metal salts of carboxylic acid anions are also suitable for use as the inorganic base in this invention. More prefe ⁇ ed are salts of potassium and cesium. Choice(s) of inorganic base will vary with the particular catalyst system involved. Amine bases have been observed to poison the catalyst system ofthe invention in some instances, and thus are not prefe ⁇ ed.
  • the molar ratio of metal atoms ofthe metal compound to N-heterocyclic carbene molecules is in the range offrom about 1 :0.5 to about 1 :5, and more preferably in the range offrom about 1 : 1 to about 1:3.
  • the base is preferably used in excess.
  • Toluene (500 mL) and l,4-Bis(2,6-diisopropylphenyl)diazabutadiene (25g, 66 mol) were added to a reaction vessel, followed by solid paraformaldehyde (2.0g, 66 mmol).
  • the reaction mixture was heated to 100 ° C until most ofthe paraformaldehyde had dissolved.
  • the mixture was then cooled to 40°C, and HC1 (16.5mL, 4 moles per liter in dioxane, 66 mmol) was added via syringe.
  • the reaction mixture turned brown in color, and a white precipitate appeared after a few hours.
  • the reaction mixture was sti ⁇ ed at room temperature for another 36 hours.
  • Imidazolidine-2-ylidenes can be prepared by hydrogenation of the co ⁇ esponding imidazolinium salt, for example, with KH in tetrahydrofuran. See in this connection Arduengo et al., J. Am. Chem. Soc, 1995, 117, 11027.
  • the Schlenk tube was placed in a 100° C oil bath and the mixture was sti ⁇ ed for 3 hours. The mixture was then allowed to cool to room temperature. The mixture was washed with diethyl ether. The organic layer and the diethyl ether extracts were combined, washed with saturated saline solution, and then dried over MgSO 4 . The solvent was removed under vacuum and the residue was purified by flash chromatography using hexane or a mixture of hexane and ethyl acetate.
  • the mixture was then allowed to cool to room temperature.
  • the mixture was hydrolyzed either with aqueous HCl (1.0 moles per liter) or H 4 NC1 solution.
  • the solvent was removed under vacuum and the residue was purified by flash cliromatography using hexane or a mixture of hexane and ethyl acetate.
  • Bis(imidazolidine-2-ylidene)s can be prepared by hydrogenation ofthe co ⁇ esponding imidazolimum salt, for example, with KH in tetrahydrofuran. See in this connection Arduengo et al., J. Am. Chem. Soc, 1995, 117, 11027.
  • the Schlenk tube was placed in a 80 ° C oil bath and sti ⁇ ed for a number of hours. The mixture was then allowed to cool to room temperature.
  • the bis(imidazoline-2-ylidene) salt used in each run is listed in Table 24. All of the yields reported in Table 24 are ofthe heterocoupling product, and are the average of two runs.
  • reactants and components are identified as ingredients to be brought together in connection with performing a desired chemical reaction or in forming a mixture to be used in conducting a desired reaction. Accordingly, even though the claims hereinafter may refer to substances, components and or ingredients in the present tense ("comprises”, “is”, etc), the reference is to the substance, component or ingredient as it existed at the time just before it was first contacted, blended or mixed with one or more other substances, components and/or ingredients in accordance with the present disclosure. Whatever transfo ⁇ nations, if any, that occur in situ as a reaction is conducted is what the claim is intended to cover.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Inorganic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

L'invention concerne un procédé destiné à conduire des réactions de formation de liaisons carbone-carbone ou carbone-azote. Les procédés de l'invention font utilisation de carbènes hétérocycliques azotés comme ligands auxiliaires dans différents types de couplages d'halogénures d'aryle ou de pseudohalogénures d'aryle. Une réaction de couplage de Suzuki, par exemple, peut être réalisée par mélange, dans un milieu liquide, d'au moins une base forte, d'au moins un halogénure ou d'un pseudohalogénure d'aryle dans lequel tous les substituants sont autres que des groupes d'acide boronique, et dans lequel l'halogénure d'aryle comporte, directement lié au noyau(x) aromatique, au moins un atome d'halogène sélectionné dans le groupe comprenant un atome de chlore, un atome de brome et un atome d'iode; au moins un acide arylboronique dans lequel tous les substituants sont autres que des atomes de chlore, de brome et d'iode ou des groupes de pseudohalogénures, au moins un composé métallique comprenant au moins un atome métallique sélectionné parmi le nickel, le palladium, et le platine, dans lequel l'état d'oxydation réel du métal est zéro ou deux, et au moins un carbène hétérocyclique azoté. Un type préféré de carbène hétérocyclique azoté est l'imidazoline-2-ylidène de formule (I) dans laquelle R1 et R2 représentent chacun, de manière indépendante, des groupes alkyle ou aryle possédant au moins 3 atomes de carbone, et R3 et R4 représentent chacun, de manière indépendante, un atome d'hydrogène, un atome d'halogène ou un groupe hydrocarbyle.
PCT/US2001/005549 2000-02-22 2001-02-22 Systeme catalyseur comprenant un metal de transition et de l'imidazoline-2-ylidene ou de l'imidazolidine-2-ylidene et son utilisation dans des reactions de couplage WO2001066248A2 (fr)

Applications Claiming Priority (11)

Application Number Priority Date Filing Date Title
US09/511,122 US6369265B1 (en) 1999-09-16 2000-02-22 Use of a catalyst system comprising nickel, palladium, or platinum and imidazoline-2-ylidene or imidazolidine-2-ylidene in kumada coupling reactions
US09/507,958 2000-02-22
US09/507,959 2000-02-22
US09/511,654 US6362357B1 (en) 1999-02-22 2000-02-22 Use a catalyst system comprising nickel palladium or platinum and imidazoline-2-ylidene or imidazolidine-2-ylidene in stille coupling reactions
US09/511,420 2000-02-22
US09/511,420 US6403802B1 (en) 1998-09-10 2000-02-22 Use of catalyst system comprising nickel, palladium, or platinum and imidazoline-2-ylidene or imidazolidine-2-ylidene in amination reactions
US09/511,122 2000-02-22
US09/507,958 US6316380B1 (en) 1998-09-10 2000-02-22 Catalyst system comprising transition metal and imidazoline-2-ylidene or imidazolidine-2-ylidene
US09/511,654 2000-02-22
US09/553,542 US6586599B1 (en) 2000-04-20 2000-04-20 Catalyzed coupling reactions of aryl halides with silanes
US09/553,542 2000-04-20

Publications (2)

Publication Number Publication Date
WO2001066248A2 true WO2001066248A2 (fr) 2001-09-13
WO2001066248A3 WO2001066248A3 (fr) 2002-02-14

Family

ID=27541799

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2001/005549 WO2001066248A2 (fr) 2000-02-22 2001-02-22 Systeme catalyseur comprenant un metal de transition et de l'imidazoline-2-ylidene ou de l'imidazolidine-2-ylidene et son utilisation dans des reactions de couplage

Country Status (1)

Country Link
WO (1) WO2001066248A2 (fr)

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1308157A1 (fr) * 2001-10-26 2003-05-07 Bayer Aktiengesellschaft Complexes de carbènes N-heterocycliques et leur utilisation
EP1312605A1 (fr) * 2001-11-19 2003-05-21 Sumitomo Chemical Company, Limited Procédé de préparation des composés biaryles
WO2003066570A1 (fr) * 2002-02-04 2003-08-14 Massachusetts Institute Of Technology Procedes de formation de liaison carbone-azote catalysee par un metal de transition a l'aide de ligands carbenes
EP1439157A2 (fr) * 2003-01-17 2004-07-21 Sumitomo Chemical Co.,Ltd. Procédé de préparation d'un composé de couplage Suzuki catalysé par un composé du nickel
WO2006024616A1 (fr) 2004-08-28 2006-03-09 Oxeno Olefinchemie Gmbh Procede de telomerisation d'olefines non cycliques
US7091373B2 (en) 2002-03-18 2006-08-15 Sumitomo Chemical Company, Limited Production method for biarylalanine
WO2006110198A1 (fr) 2005-04-11 2006-10-19 Wisconsin Alumni Research Foundation Carbenes heterocycliques a sept chainons et leurs complexes metalliques
WO2007114793A1 (fr) * 2006-04-05 2007-10-11 Agency For Science, Technology And Research Sels de polyimidazolium et complexes poly-nhc-metal
WO2008070014A2 (fr) * 2006-12-04 2008-06-12 Neurogen Corporation Pipéridines à substitution cétonique de biaryle
CN102643372A (zh) * 2008-02-12 2012-08-22 可隆工业株式会社 选择性氢化方法
CN102942429A (zh) * 2012-11-26 2013-02-27 大连理工大学 一种钯碳催化的制备氮杂或硫杂芳基联芳化合物的方法
CN105061124A (zh) * 2015-07-27 2015-11-18 苏州大学 一种制备二芳基甲烷类化合物的方法
CN111116596A (zh) * 2018-10-30 2020-05-08 中国科学院大连化学物理研究所 一类轴手性联咪唑化合物及其合成方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998000399A1 (fr) * 1996-07-01 1998-01-08 E.I. Du Pont De Nemours And Company Addition catalysee par nickel de composes contenant du -nh- a des halogenures de vinyle et d'aryle

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998000399A1 (fr) * 1996-07-01 1998-01-08 E.I. Du Pont De Nemours And Company Addition catalysee par nickel de composes contenant du -nh- a des halogenures de vinyle et d'aryle

Non-Patent Citations (8)

* Cited by examiner, † Cited by third party
Title
B\HM ET AL: "Nickel-catalyzed cross-coupling of aryl chlorides with aryl grignard reagents" ANGEW. CHEM. INT. ED., vol. 39, no. 9, 2 May 2000 (2000-05-02), pages 1602-4, XP002178608 *
B\HM V P W ET AL: "N-Heterocyclic carbenes - Part 26. N-Heterocyclic carbene complexes of palladium(0): synthesis and application in the Suzuki cross-coupling reaction" JOURNAL OF ORGANOMETALLIC CHEMISTRY, ELSEVIER-SEQUOIA S.A. LAUSANNE, CH, vol. 595, no. 2, February 2000 (2000-02), pages 186-190, XP004187387 ISSN: 0022-328X *
BAKER ET AL.: "Palladium carbene complexes derived from imidazolium-linked ortho-cyclophanes" J. CHEM. SOC. DALTON TRANS., 21 January 2001 (2001-01-21), pages 111-20, XP002178609 *
CADDICK ET AL.: "An improved synthesis of bis(1,3-di-N-tert-butylimidazol-2-ylidene) palladium(0) and its use in C-C and C-N coupling reactions" J. ORGANOMETALLIC CHEM., vol. 617-18, 15 January 2001 (2001-01-15), pages 635-9, XP002178610 *
HERMANN ET AL.: "Synthesis, structure and catalytic aplication of Pd(II)complexes bearing N-heterocyclic carbenes and phosphines" J. ORGANOMETALIC CHEM., vol. 617, no. 18, 15 January 2001 (2001-01-15), pages 616-28, XP002178611 *
HERMANN ET AL: "Chelating N-heterocyclic carbene ligands in palladium-catalyzed heck-type reactions" JOURNAL OF ORGANOMETALLIC CHEMISTRY, ELSEVIER-SEQUOIA S.A. LAUSANNE, CH, vol. 557, no. 1, 20 April 1998 (1998-04-20), pages 93-96, XP004122368 ISSN: 0022-328X cited in the application *
WESKAMP T ET AL: "Combining N-heterocyclic carbenes and phosphines: improved palladium(II) catalysts for aryl coupling reactions" JOURNAL OF ORGANOMETALLIC CHEMISTRY, ELSEVIER-SEQUOIA S.A. LAUSANNE, CH, vol. 585, no. 2, 15 August 1999 (1999-08-15), pages 348-352, XP004177479 ISSN: 0022-328X *
WOLFGANG A. HERRMANN, CHRISTIAN K\CHER: "N-Heterocyclic Carbenes" ANGEW. CHEM. INT. ED. ENGL., vol. 36, 1997, pages 2162-87, XP002178612 *

Cited By (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1308157A1 (fr) * 2001-10-26 2003-05-07 Bayer Aktiengesellschaft Complexes de carbènes N-heterocycliques et leur utilisation
EP1312605A1 (fr) * 2001-11-19 2003-05-21 Sumitomo Chemical Company, Limited Procédé de préparation des composés biaryles
US7122711B2 (en) 2001-11-19 2006-10-17 Sumitomo Chemical Company, Limited Method for producing biaryl compound
WO2003066570A1 (fr) * 2002-02-04 2003-08-14 Massachusetts Institute Of Technology Procedes de formation de liaison carbone-azote catalysee par un metal de transition a l'aide de ligands carbenes
US6888029B2 (en) 2002-02-04 2005-05-03 Massachusetts Institute Of Technology Transition-metal-catalyzed carbon-nitrogen bond-forming methods using carbene ligands
US7091373B2 (en) 2002-03-18 2006-08-15 Sumitomo Chemical Company, Limited Production method for biarylalanine
US7553988B2 (en) 2003-01-17 2009-06-30 Sumitomo Chemical Company, Limted Method for producing coupling compound
EP1439157A2 (fr) * 2003-01-17 2004-07-21 Sumitomo Chemical Co.,Ltd. Procédé de préparation d'un composé de couplage Suzuki catalysé par un composé du nickel
EP1439157A3 (fr) * 2003-01-17 2004-10-20 Sumitomo Chemical Co.,Ltd. Procédé de préparation d'un composé de couplage Suzuki catalysé par un composé du nickel
US7217677B2 (en) 2003-01-17 2007-05-15 Sumitomo Chemical Company, Limited Method for producing coupling compound
WO2006024616A1 (fr) 2004-08-28 2006-03-09 Oxeno Olefinchemie Gmbh Procede de telomerisation d'olefines non cycliques
US8163900B2 (en) 2005-04-11 2012-04-24 Wisconsin Alumni Research Foundation Seven-membered heterocyclic carbenes and their metal complexes
US7750149B2 (en) 2005-04-11 2010-07-06 Wisconsin Alumni Research Foundation Seven-membered heterocyclic carbenes and their metal complexes
WO2006110198A1 (fr) 2005-04-11 2006-10-19 Wisconsin Alumni Research Foundation Carbenes heterocycliques a sept chainons et leurs complexes metalliques
WO2007114793A1 (fr) * 2006-04-05 2007-10-11 Agency For Science, Technology And Research Sels de polyimidazolium et complexes poly-nhc-metal
WO2007114792A1 (fr) * 2006-04-05 2007-10-11 Agency For Science, Technology And Research Sels polymeriques et complexes de metaux polymeriques
US8163851B2 (en) 2006-04-05 2012-04-24 Institute Of Bioengineering And Nanotechnology Polymeric salts and poly-NHC-metal complexes
CN102850544B (zh) * 2006-04-05 2015-04-15 新加坡科技研究局 聚咪唑盐和聚n-杂环卡宾金属配合物
WO2008070014A3 (fr) * 2006-12-04 2009-04-02 Neurogen Corp Pipéridines à substitution cétonique de biaryle
WO2008070014A2 (fr) * 2006-12-04 2008-06-12 Neurogen Corporation Pipéridines à substitution cétonique de biaryle
CN102643372A (zh) * 2008-02-12 2012-08-22 可隆工业株式会社 选择性氢化方法
CN102643372B (zh) * 2008-02-12 2014-09-10 可隆工业株式会社 选择性氢化方法
CN102942429A (zh) * 2012-11-26 2013-02-27 大连理工大学 一种钯碳催化的制备氮杂或硫杂芳基联芳化合物的方法
CN105061124A (zh) * 2015-07-27 2015-11-18 苏州大学 一种制备二芳基甲烷类化合物的方法
CN111116596A (zh) * 2018-10-30 2020-05-08 中国科学院大连化学物理研究所 一类轴手性联咪唑化合物及其合成方法
CN111116596B (zh) * 2018-10-30 2021-04-23 中国科学院大连化学物理研究所 一类轴手性联咪唑化合物及其合成方法

Also Published As

Publication number Publication date
WO2001066248A3 (fr) 2002-02-14

Similar Documents

Publication Publication Date Title
US6316380B1 (en) Catalyst system comprising transition metal and imidazoline-2-ylidene or imidazolidine-2-ylidene
EP1625133B1 (fr) Phosphines monodentelées contenant de l'azote et leur utilisation dans une catalyse
Sadighi et al. A highly active palladium catalyst system for the arylation of anilines
WO2001066248A2 (fr) Systeme catalyseur comprenant un metal de transition et de l'imidazoline-2-ylidene ou de l'imidazolidine-2-ylidene et son utilisation dans des reactions de couplage
US8492552B2 (en) N-heterocyclic carbene metallacycle catalysts and methods
US20050154205A1 (en) Complexes of N-heterocyclic carbenes and the use thereof
US7442800B2 (en) Nucleophilic heterocyclic carbene derivatives of Pd(acac)2 for cross-coupling reactions
KR101017881B1 (ko) 포스핀 화합물, 중간체, 팔라듐-착체, 및 그의 용도
US6362357B1 (en) Use a catalyst system comprising nickel palladium or platinum and imidazoline-2-ylidene or imidazolidine-2-ylidene in stille coupling reactions
US6403802B1 (en) Use of catalyst system comprising nickel, palladium, or platinum and imidazoline-2-ylidene or imidazolidine-2-ylidene in amination reactions
US6369265B1 (en) Use of a catalyst system comprising nickel, palladium, or platinum and imidazoline-2-ylidene or imidazolidine-2-ylidene in kumada coupling reactions
CA2556850A1 (fr) Complexes de metaux de transition et de carbenes n-heterocycliques, methode de preparation connexe et utilisation desdits complexes dans des relations chimiques organiques catalyses par des metaux de transition
CN103748065B (zh) 2－烯基胺化合物的制造方法
US20010056190A1 (en) Immobilized palladium complexes
US6586599B1 (en) Catalyzed coupling reactions of aryl halides with silanes
Oguro et al. Alkoxycarbene complexes of nickel (II)
EP3204351A1 (fr) Procédé de couplage d'un fluorosulfonate avec une amine
US6403801B1 (en) Use of a catalyst system comprising nickel, palladium, or platinum and imidazoline-2-ylidene of imidazolidine-2-ylidene in suzuki coupling reactions
Zhang et al. The use of palladium chloride as a precatalyst for the amination of aryl bromides
US20030181688A1 (en) Coupling of nucleophiles, vinyl compounds or CO with water, alcohols or amines to organic compounds
US20020107426A1 (en) Process for the preparation of mono-, bi- or poly- functional biaryls
US6353136B1 (en) Process for preparing aromatic amines in the presence of palladaphosphacyclobutane catalysts
KR101660390B1 (ko) 2-알케닐아민 화합물의 제조 방법
US6878850B2 (en) Catalysis using halophosphine compounds
JP2005320332A (ja) モノアリールピペラジンの製造方法

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): CA JP US US US US US US

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR

121 Ep: the epo has been informed by wipo that ep was designated in this application
AK Designated states

Kind code of ref document: A3

Designated state(s): CA JP US US US US US US

AL Designated countries for regional patents

Kind code of ref document: A3

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR

122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP