| PATENT NUMBER | This data is not available for free |
| PATENT GRANT DATE | May 13, 2003 |
| PATENT TITLE |
Catalyst for aromatic C--O, C--N, and C--C bond formation |
| PATENT ABSTRACT | The present invention is directed to a transition metal catalyst, comprising a Group 8 metal and a ligand having the structure ##STR1## wherein R, R' and R" are organic groups having 1-15 carbon atoms, n=1-5, and m=0-4. The present invention is also directed to a method of forming a compound having an aromatic or vinylic carbon-oxygen, carbon-nitrogen, or carbon-carbon bond using the above catalyst. The catalyst and the method of using the catalyst are advantageous in preparation of compounds under mild conditions of approximately room temperature and pressure |
| PATENT INVENTORS | This data is not available for free |
| PATENT ASSIGNEE | This data is not available for free |
| PATENT FILE DATE | August 3, 2001 |
| PATENT REFERENCES CITED |
"Organic Chemistry, Reaction Between Isoprene and Aniline On Complex", Petrushkina et al., A.N. Nosmeyanov Institute of Organoelemental Compounds, Russian Academy of Sciences, No. 8, Aug. 1992, pp. 1794-1798. Dzhemilev, U.M., et al., "The Reaction of Butadiene With Morpholine As Catalyzed By Nickel Complexes", Bulletin of the Academy of Sciences of the USSR Division of Chemical Science, vol. 25, No. 8, Aug. 1976, pp. 1691-1694. Dzhemilev, U.M., et al., "Reaction of Secondary Amines With Cyclic 1,3-Dienes, Catalyzed By Nickel Complexes", Bulletin of the Academy of Sciences of the USSR Division of Chemical Science, vol. 25, No. 10, Oct. 1976, pp. 2190-2191. Dzhemilev, U.M., et al., "Reaction Of Cycloaliphatic Secondary Amines With Butadiene Catalyzed By Nickel Catalysts", Bulletin of the Academy of Sciences of the USSR Division of Chemical Science, vol. 27, No. 5, Part 1, May 1978, pp. 923-927. Dzhemilev, U.M., et al., "Synthesis Of Unsaturated Amines From Butadiene And Allylamines In Presence Of Palladium And Nickel Complexes", Bulletin of the Academy of Sciences of the USSR Division of Chemical Science, vol. 27, No. 6, Part 2, Jun. 1978, pp. 1230-1232. Zakharkin, L.I., et al., "Telomerization Of Isoprene With Piperidine On Complex Palladium Catalysts", Bulletin of the Academy of Sciences of the USSR Division of Chemical Science, vol. 32, No. 4, Part 2, Apr. 1983, pp. 805-809. Zakharkin, L.I., et al., "Telomerization Of Isoprene With N-Methylaniline On Complex Palladium Catalysts", Bulletin of the Academy of Sciences of the USSR Division of Chemical Science, vol. 35, No. 6, Part 1, Jun. 1986, pp. 1219-1222. Dzhemilev, U.M., et al., "Amination Of Unsaturated Hydrocarbons By Secondary Amines, Catalyzed By Complexes Of Nickel And Palladium", Bashkir Branch, Academy of Sciences of the USSR, vol. 15, No. 6, pp. 1164-1169, Jun. 1979, pp. 1041-1045. Zakharkin, M.I., et al., "Telomerization Of Isoprene With Phthalimide At Complex Palladium Catalysts", A.N. Nesmeyanov Institute of Heteroorganic Compounds Academy of Sciences of the USSR, Moscow, vol. 23, No. 8, Aug. 1987, pp. 1654-1656. |
| PATENT GOVERNMENT INTERESTS |
STATEMENT OF GOVERNMENT SUPPORT This invention was made in part with government support under grant number R29-GM55382 from the National Institutes of Health. The government has certain rights in this invention. |
| PATENT PARENT CASE TEXT | This data is not available for free |
| PATENT CLAIMS |
What is claimed is: 1. A transition metal catalyst, comprising: a Group 8 metal; and a ligand having the structure ##STR391## wherein R, R', and R" are organic groups having 1-15 carbon atoms, n=1-5, and m=0-4. 2. The transition metal catalyst of claim 1, wherein R is t-Bu, R' is phenyl, n=4 or 5, and m=0. 3. The transition metal catalyst of claim 1, wherein R is t-Bu, R' is MeO--C.sub.6 H.sub.4, n=5, and m=0. 4. The transition metal catalyst of claim 1, wherein R is t-Bu, R' is F.sub.3 C--C.sub.6 H.sub.4, n=5, and m=0. 5. The transition metal catalyst of claim 1, wherein R is t-Bu, R' is methyl, n=5, and m=0. 6. The transition metal catalyst of claim 1, wherein R is t-Bu, R" is o-tolyl, n=4, and m=0. 7. A method of forming a compound having an aromatic or vinylic carbon-oxygen, carbon-nitrogen, or carbon-carbon bond, comprising the step of: reacting a first substrate and a second substrate in the presence of a transition metal catalyst, wherein said first substrate comprises an aryl halide reagent or an aryl sufonate reagent, and said second substrate comprises an alcohol reagent, an alkoxide reagent, a silanol reagent, a siloxide reagent, an amine reagent, an organoboron reagent, an organozinc reagent, an organomagnesium reagent, a malonate reagent, a cyanoacetate reagent, or an olefinic reagent, and wherein said transition metal catalyst comprises a Group 8 metal and a ligand having the structure ##STR392## wherein R and R' are organic groups having 1-15 carbon atoms, and n=1-5; under reaction conditions effective to form said compound, wherein said compound has an aromatic carbon-oxygen, carbon-nitrogen, or carbon-carbon bond between said first substrate and said second substrate. 8. The method of claim 7, wherein said first substrate is selected from the group consisting of: ##STR393## wherein X is selected from the group consisting of bromine, chlorine, fluorine, and iodine. 9. The method of claim 7, wherein said second substrate is selected from the group consisting of NaO--C.sub.6 H.sub.4 --OMe, NaO-tBu, NaO--Si-(tBu)Me.sub.2, HO--C.sub.6 H.sub.4 --OMe, HO-tBu, HO--Si-(tBu)Me.sub.2, morpholine, dibutylamine, aniline, n-butylamine, n-hexylamine, methylaniline, aminotoluene, organoboronic acid, indole, and combinations thereof. 10. The method of claim 9, wherein said organoboronic acid is selected from the group consisting of o-tolylboronic acid, phenylboronic acid, p-trifluoromethylphenylboronic acid, p-methoxyphenylboronic acid, o-methoxyphenylboronic acid, 4-chlorophenylboronic acid, 4-formylphenylboronic acid, 2-methylphenylboronic acid, 4-methoxyphenylboronic acid, 1-naphthylboronic acid, and combinations thereof. 11. The method of claim 7, wherein said organozinc reagent is selected from the group consisting of n-butylzinc chloride, secbutylzinc chloride, phenylzinc chloride, and combinations thereof. 12. The method of claim 7, wherein said organomagnesium reagent is selected from the group consisting of butylmagnesium bromide, phenylmagnesium chloride, and combinations thereof. 13. The method of claim 7, wherein said malonate reagent is diethyl malonate. 14. The method of claim 7, wherein said cyanoacetate reagent is ethyl cyanoacetate. 15. The method of claim 7, wherein said olefinic reagent is selected from the group consisting of styrene, n-butyl acrylate, methyl acrylate, and combinations thereof. 16. The method of claim 7, wherein said reacting step further takes place in the presence of a base selected from the group consisting of alkali metal hydroxides, alkali metal alkoxides, metal carbonates, alkali metal amides, alkali metal aryl oxides, alkali metal phosphates, tertiary amines, tetraalkylammonium hydroxides, diaza organic bases, and combinations thereof. 17. The method of claim 7, wherein said Group 8 metal is selected from the group consisting of palladium, platinum, nickel, and combinations thereof. 18. The method of claim 7, wherein in said ligand, R is t-Bu, R' is phenyl, and n=4 or 5. 19. The method of claim 7, wherein in said ligand, R is t-Bu, R' is MeO--C.sub.6 H.sub.4, and n=5. 20. The method of claim 7, wherein in said ligand, R is t-Bu, R' is F.sub.3 C--C.sub.6 H.sub.4, and n=5. 21. The method of claim 7, wherein in said ligand, R is t-Bu, R' is methyl, and n=5. 22. The method of claim 7, wherein in said ligand, R is t-Bu, R" is o-tolyl, and n=4. 23. The method of claim 7, wherein said transition metal catalyst is prepared from an alkene or diene complex of said Group 8 transition metal complex combined with said ligand. 24. The method of claim 23, wherein said alkene complex of the Group 8 transition metal is di(benzylidene)acetone. 25. The method of claim 7, wherein said transition metal catalyst is prepared in situ in said reaction. 26. The method of claim 7, wherein said transition metal catalyst is anchored or supported on a support. 27. The method of claim 7, wherein said reaction conditions comprise reaction times from about 30 minutes to about 24 hours, and reaction temperatures from about 22.degree. C. to about 150.degree. C. 28. The method of claim 7, wherein said reaction conditions further comprise a solvent selected from the group consisting of aromatic hydrocarbons, chlorinated aromatic hydrocarbons, ethers, water, aliphatic alcohols, and combinations thereof. 29. A method of forming a compound having an aromatic carbon-oxygen, carbon-nitrogen, or carbon-carbon bond, comprising the step of: reacting a first substrate and a second substrate in the presence of a transition metal catalyst, wherein said first substrate comprises an aryl halide reagent or an aryl sufonate reagent selected from the group consisting of: ##STR394## wherein X is selected from the group consisting of bromine, chlorine, fluorine, iodine, and sulfonate; and said second substrate is selected from the group consisting of NaO--C.sub.6 H.sub.4 --OMe, NaO-tBu, NaO--Si-(tBu)Me.sub.2, HO--C.sub.6 H.sub.4 --OMe, HO-tBu, HO--Si-(tBu)Me.sub.2, morpholine, dibutylamine, aniline, n-butylamine, n-hexylamine, methylaniline, aminotoluene, organoboron reagents, organozinc reagents, organomagnesium reagents, indoles, ethyl cyanoacetate, diethyl malonate, methyl acrylate, and combinations thereof; and wherein said transition metal catalyst comprises a Group 8 metal selected from the group consisting of palladium, platinum, and nickel, and a ligand having the structure ##STR395## in a solvent selected from the group consisting of aromatic hydrocarbons, chlorinated aromatic hydrocarbons, ethers, water, aliphatic alcohols, and combinations thereof, under reaction conditions effective to form said compound, wherein said compound has an aromatic carbon-oxygen, carbon-nitrogen, or carbon-carbon bond between said first substrate and said second substrate. 30. The method of claim 29, wherein said organoboron reagent is an organoboronic acid selected from the group consisting of o-tolylboronic acid, phenylboronic acid, p-trifluoromethylphenylboronic acid, p-methoxyphenylboronic acid, o-methoxyphenylboronic acid, 4-chlorophenylboronic acid, 4-formylphenylboronic acid, 2-methylphenylboronic acid, 4-methoxyphenylboronic acid, 1-naphthylboronic acid, and combinations thereof. 31. The method of claim 29, wherein said organozinc reagent is selected from the group consisting of n-butylzinc chloride, secbutylzinc chloride, phenylzinc chloride, and combinations thereof. 32. The method of claim 29, wherein said organomagnesium reagent is selected from the group consisting of butylmagnesium bromide, phenylmagnesium chloride, and combinations thereof. 33. The method of claim 29, wherein said transition metal catalyst is prepared from an alkene or diene complex of said Group 8 transition metal complex combined with said ligand. 34. The method of claim 33, wherein said alkene complex of the Group 8 transition metal is di(benzylidene)acetone. 35. The method of claim 29, wherein said reacting step further takes place in the presence of a base selected from the group consisting of alkali metal hydroxides, alkali metal alkoxides, metal carbonates, alkali metal amides, alkali metal aryl oxides, alkali metal phosphates, tertiary amines, tetraalkylammonium hydroxides, diaza organic bases, and combinations thereof. 36. The method of claim 29, wherein said transition metal catalyst is prepared in situ in said reaction. 37. The method of claim 29, wherein said transition metal catalyst is anchored or supported on a support. 38. The method of claim 29, wherein said reaction conditions comprise reaction times from about 30 minutes to about 24 hours, and reaction temperatures from about 22.degree. C. to about 150.degree. C. |
| PATENT DESCRIPTION |
BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to transition metal catalysts for aromatic or vinylic C--O, C--N, and C--C bond formation, and more particularly to transition metal catalysts for aromatic or vinylic C--O, C--N, and C--C bond formation that include ferrocenyl ligands and a transition metal atom such as platinum, palladium, or nickel. The present invention also relates to method of forming compounds containing aromatic C--O, C--N, and C--C bonds using the transition metal catalysts. 2. Brief Description of the Related Art Mild, aromatic or vinylic substitution to form C--O, C--N, and C--C bonds is a difficult transformation. For reactions of unactivated aryl halides, direct, uncatalyzed substitutions and copper-mediated couplings typically require temperatures of 100.degree. C. or greater (Bacon, R. G. R.; Rennison, S. C. J. Chem. Soc. (C) 1969, 312-315; Marcoux, J. F.; Doye, S.; Buchwald, S. L. J. Amn. Chem. Soc. 1997, 119, 10539-10540; Kalinin, A. V.; Bower, J. F.; Riebel, P.; Snieckus, V. J. Org. Chem. 1999, 64, 2986-2987). Alternative approaches have suffered similar drawbacks and disadvantages. For example, diazotization and displacement with oxygen or nitrogen nucleophiles is generally limited in scope and uses stoichiometric amounts of copper in its mildest form (March, J. In Advanced Organic Chemistry John Wiley and Sons: New York, 1985; pp 601). Recently, palladium catalysts for the formation of diaryl and alkyl aryl ethers from unactivated aryl halides have been shown to be useful in these reactions (Mann, G.; Incarvito, C.; Rheingold, A. L.; Hartwig, J. F. J. Am. Chem. Soc. 1999, 121, 3224-3225). However, this system for C--O bond-formation as well as similar systems (Aranyos, A.; Old, D. W.; Kiyomori, A.; Wolfe, J. P.; Sadighi, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1999, 121, 4369-4378) required temperatures similar to those for copper-mediated processes (Bacon, R. G. R.; Rennison, S. C. J. Chem. Soc. (C) 1969, 312-315; Marcoux, J. F.; Doye,. S.; Buchwald, S. L. J. Am. Chem. Soc. 1997, 119, 10539-10540; Kalinin, A. V.; Bower, J. F.; Riebel, P.; Snieckus, V. J. Org. Chem. 1999, 64, 2986-2987; Boger, D. L.; Yohannes, D. J. Org. Chem. 1991, 56, 1763; Fagan, P. J.; Hauptman, E.; Shapiro, R.; Casalnuovo, A. J. Am. Chem. Soc. 2000, 122, 5043-5051). In addition, several catalysts have been shown to induce aromatic C--N bond-formation from aryl halides and sulfonates. Yet, the termperatures, for general reactions remain high in many cases, and the selectivities for formation of the desired aniline derivative instead of the undesired arene or diarylamine are often lower than optimal for synthetic applications.(Wolfe, J. P.; Buchwald, S. L. J. Org. Chem. 2000, 65, 1444; Wolfe, J. P.; Buchwald, S. L. J. Org. Chem. 2000, 65, 1158; Huang, J.; Grassa, G.; Nolan, S. P. Org. Lett. 1999, 1, 1307; Hartwig, J. F.; Kawatsura, M.; Hauck, S. I.; Shaughnessy, K. H.; Alcazar-Roman, L. M. J. Org. Chem. 1999, 64, 5575; Stauffer, S. I.; Hauck, S. I.; Lee, S.; Stambuli, J.; Hartwig, J. F. Org. Lett. 2000, 2, 1423) Finally, catalysts have been developed for aromatic or vinylic C--C bond formation, but again the conditions for these reactions are often harsh.(Suzuki, A. J. Organomet. Chem. 1999, 576, 147; Buchwals, S. L.; Fox, J. M. The Strem Chemiker, 2000, 18, 1; Zhang, C; Huang, J.; Trudell, M. L.; Nolan, S. P. J. Org. Chem. 1999, 64, 3804; Beletskaya, I. P. Cheprakov, A. V. Chem. Rev. 2000, 100, 3009; Littke, A. F.; Fu, G. C. J. Org. Chem. 1999, 64, 10; Shaughnessy, K. H.; Hartwig, J. F. J. Am. Chem. Soc. 1999, 121, 2123) In particular for each of these three classes of reactions, the bond-forming processes are especially difficult to conduct under mild conditions with high selectivity when using chloroarenes. Unfortunately, reaction conditions such as those described above are quite harsh and require special equipment and techniques to accomplish even small scale syntheses. In addition, larger scale reactions of these reactions, such as those used in large-scale pharmaceutical manufacturing, are generally impractical and expensive due to these extreme reaction conditions. What is needed in the art is a catalytic method of aromatic or vinylic carbon-oxygen, carbon-nitrogen, and carbon-carbon bond formation that occurs under mild conditions (e.g., room temperature and atmospheric pressure) and that is easily scalable for large-scale synthesis, for example, in the pharmaceutical industry. The present invention is believed to be an answer to that need. SUMMARY OF THE INVENTION In one aspect, the present invention is directed to a transition metal catalyst, comprising a Group 8 metal and a ligand having the structure ##STR2## wherein R, R' and R" are organic groups having 1-15 carbon atoms, n=1-5, and m=0-4. In another aspect, the present invention is directed to a method of forming a compound having an aromatic or vinylic carbon-oxygen, carbon-nitrogen, or carbon-carbon bond, comprising the step of reacting a first substrate and a second substrate in the presence of a transition metal catalyst, wherein the first substrate comprises an aryl halide reagent or an aryl sufonate reagent, and the second substrate comprises an alcohol reagent, an alkoxide reagent, a silanol reagent, a siloxide reagent, an amine reagent, an organoboron reagent, an organozinc reagent, an organomagnesium reagent, a malonate reagent, a cyanoacetate reagent, or an olefinic reagent, and wherein the transition metal catalyst comprises a Group 8 metal and a ligand having the structure ##STR3## wherein R and R' are organic groups having 1-15 carbon atoms, and n=1-5; under reaction conditions effective to form the compound, wherein the compound has an aromatic carbon-oxygen, carbon-nitrogen, or carbon-carbon bond between the first substrate and the second substrate. In yet another aspect, the present invention is directed to a method of forming a compound having an aromatic carbon-oxygen, carbon-nitrogen, or carbon-carbon bond, comprising the step of reacting a first substrate and a second substrate in the presence of a transition metal catalyst, wherein the first substrate comprises a selected aryl halide reagent or an aryl sufonate reagent and the second substrate is selected from the group consisting of NaO--C.sub.6 H.sub.4 --OMe, NaO-tBu, NaO--Si-(tBu)Me.sub.2, HO--C.sub.6 H.sub.4 --OMe, HO-tBu, HO--Si-(tBu)Me.sub.2, primary amines, secondary amines, alkyl amines, benzylic amines, aryl amines including morpholine, dibutylamine, aniline, n-butylamine, n-hexylamine, methylaniline, aminotoluene; organoboron reagents, organozinc reagents, organomagnesium reagents, indoles, ethyl cyanoacetate, diethyl malonate, methyl acrylate, and combinations thereof, and wherein the transition metal catalyst comprises a Group 8 metal selected from the group consisting of palladium, platinum, and nickel, and a ligand having the structure ##STR4## in a solvent selected from the group consisting of aromatic hydrocarbons, chlorinated aromatic hydrocarbons, ethers, water, aliphatic alcohols, and combinations thereof, under reaction conditions effective to form the compound, wherein the compound has an aromatic carbon-oxygen, carbon-nitrogen, or carbon-carbon bond between the first substrate and the second substrate. These and other aspects will become apparent upon reading the following detailed description of the invention. DETAILED DESCRIPTION OF THE INVENTION It now has been surprisingly found, in accordance with the present invention, that a solution is provided to the problem of providing a general and efficient catalytic method of aromatic or vinylic carbon-oxygen, carbon-nitrogen, and carbon-carbon bond formation between two substrates that occurs under mild conditions (e.g., room temperature and atmospheric pressure). The present inventors have solved this problem by utilizing a catalyst that includes a transition metal catalyst comprising a Group 8 metal and a substituted ferrocenylphosphineligand. The catalyst is useful in a general and efficient process of formation of reaction products containing an aromatic carbon-oxygen, carbon-carbon, or carbon-nitrogen bond. Production of carbon-oxygen, carbon-carbon, or carbon-nitrogen bonds between substrates under mild conditions is particularly advantageous in the pharmaceutical industry where active starting substrates can be rapidly degraded by harsh chemical coupling conditions. The aromatic carbon-oxygen, carbon-carbon, or carbon-nitrogen bonds are formed under mild conditions and in the presence of the catalyst using a variety of starting substrates, most notably aryl halide reagents, aryl sulfonate reagents, alkoxide reagents, siloxide reagents, alcohol reagents, silanol reagents, amine reagents, organoboron reagents, organomagnesium reagents, organozinc reagents, malonate reagents, cyanoacetate reagents, and olefinic reagents. In addition to forming an aromatic carbon-oxygen bond between two distinct substrates, the catalyst and method of the present invention is also useful in intramolecular reactions, such as intramolecular etherification, amination, or vinylation where a single compound comprises each of the two substrates. As defined herein, the term "substrate" includes distinct compounds possessing the above reactive groups (for example, aryl halides, aryl sulfonates, alkoxides, alcohols, siloxides, silanols, amines or related compounds with an N--H bond, organoborons, organomagnesiums, organozincs, malonates, cyanoesters, and olefinic compounds) as well as a single compound that includes reactive groups such as aryl halides, aryl sulfonates, alkoxides, alcohols, siloxides, silandls, amines or related compounds with an N--H bond, organoboron, organomagnesium, organozinc, malonate, cyanoester, and olefinic groups, such that an intramolecular reaction can take place in the presence of the catalyst of the present invention. As defined herein, the term "aromatic" refers to a compound whose molecules have the ring structure characteristic of benzene, naphthalene, phenanthroline, anthracene, related heterocycles such as pyridines, pyrimidines, thiophenes, furans, pyrroles, and the like. The phrase "aromatic carbon-oxygen, carbon-nitrogen, or carbon-carbon bond" refers to a covalent bond between a carbon atom of an aromatic or heteroaromatic ring of a first substrate, and an oxygen, nitrogen, or carbon atom of a second substrate. The terms "amine" and "amine reagent" are broadly defined herein to encompass primary amines, secondary amines, alkyl amines, benzylic amines, aryl amines, as well as related compounds with N--H bonds, including carbamates and cyclic or heterocyclic amine compounds. As indicated above, the transition metal catalyst of the present invention includes a transition metal atom complexed with a ferrocenyl ligand. In one embodiment, the ferrocenyl ligand portion of the catalyst is represented by the formula: ##STR5## wherein R, R', and R" are organic groups having 1-15 carbon atoms, n=1-5, and m=0-4. Within the ferrocenyl ligand, R can be any organic group possessing 1-15 carbon atoms, preferably 2-8 carbon atoms, and more preferably 2-5 carbon atoms. In one preferred embodiment, R possesses 4 carbon atoms, and is a tertiary butyl group (tBu). R' can also be any organic group possessing 1-15 carbon atoms, with or without additional substitutents such as halides, and the like. More preferably, R' possesses 1-10 carbon atoms, and most preferably 2-8 carbon atoms. In one embodiment, R' may be phenyl, MeO--C.sub.6 H.sub.4, F.sub.3 C--C.sub.6 H.sub.4, methyl, or o-tolyl. In addition, the number of R' groups preferably ranges from 1-5, most preferably either 4 or 5. R" can also be any organic group possessing 1-15 carbon atoms. Preferable substituents for R" include methyl, ethyl, propyl, aminoalkyl, 1-dialkylaminoethyl, 1-alkoxyethyl, phenyl, methoxyphenyl, halophenyl, naphthyl, and the like. The number of R" groups ranges from 0-4. In one preferred embodiment, the transition metal catalyst is a palladium complex with a ferrocenyl ligand having the formula: ##STR6## wherein R' is phenyl, MeO--C.sub.6 H.sub.4, F.sub.3 C--C.sub.6 H.sub.4, methyl, or o-tolyl, R is tert-butyl, and n is 4 or 5. In one particularly preferred embodiment, the transition metal catalyst is a palladium complex with a ferrocenyl ligand having the formula: ##STR7## The transition metal atom or ion is required to be a Group 8 transition metal, that is, a metal selected from iron, cobalt, nickel, ruthenium, rhodium, palladium, osmium, iridium, and platinum. More preferably, the Group 8 metal is palladium, platinum, or nickel, and most preferably, palladium. The Group 8 metal may exist in any oxidation state ranging from the zero-valent state to any higher variance available to the metal. The catalyst may be formed from a mixture of P(C.sub.5 H.sub.4 FeC.sub.5 H.sub.5)(t-Bu).sub.2, Pd(OAc).sub.2, NaO-t-Bu and PhCl according to Equation 1. ##STR8## In the presence of a Group 8 metal, such as iron, cobalt, nickel, ruthenium, rhodium, palladium, osmium, iridium, or platinum, the ferrocenyl ligand is formed into an active catalyst that is useful in catalyzing reactions that form carbon-oxygen, carbon-nitrogen, or carbon-carbon bonds between the substrates. The transition metal catalyst may be synthesized first and thereafter employed in the reaction process. Alternatively, the catalyst can be prepared in situ in the reaction mixture. If the latter mixture is employed, then a Group 8 catalyst precursor compound and the ferrocenyl ligand are independently added to the reaction mixture wherein formation of the transition metal catalyst occurs in situ. Suitable precursor compounds include alkene and diene complexes of the Group 8 metals, preferably, di(benzylidene)acetone (dba) complexes of the Group 8 metals, as well as, monodentate phosphine complexes of the Group 8 metals, and Group 8 carboxylates or halides. In the presence of the ferrocenyl ligand, in situ formation of the transition metal catalyst occurs. Non-limiting examples of suitable precursor compounds include [bis-di(benzylidene)acetone]palladium (0) as shown in Eq. 1, tetrakis-(triphenylphosphine)-palladium (0), tris-[di(benzylidene)acetone]palladium (0), tris-[di(benzylidene)acetone]-dipalladium (0), palladium acetate, palladium chloride, and the analogous complexes of iron, cobalt, nickel, ruthenium, rhodium, osmium, iridium, and platinum. Any of the aforementioned catalyst precursors may include a solvent of crystallization. Group 8 metals supported on carbon, preferably, palladium on carbon, can also be suitably employed as a precursor compound. Preferably, the catalyst precursor compound is bis-[di(benzylidene)acetone]palladium(0). As indicated above, the present invention is also directed to a method of forming a compound having an aromatic carbon-oxygen, carbon-carbon, or carbon-nitrogen bond, comprising the step of reacting a first substrate and a second substrate in the presence of the transition metal catalyst described above. Each of these steps and components are described in more detail below. Aryl halides that are useful as reagents include any compounds in which a halide atom is covalently bound to an aryl ring structure, such as a benzene ring or a heteroaromatic ring. Nonlimiting examples of suitable aryl halide reagents include bromobenzene, chlorobenzene, methoxy bromo- or chlorobenzene, bromo- or chloro toluene, bromo- or chloro benzophenone, bromo- or chloro nitrobenzene, halopyridines, halopyrazines, halopyrimidines, and the like. The structures of several examples of useful aryl halides are shown in Table A below: TABLE A ##STR9## ##STR10## ##STR11## ##STR12## ##STR13## ##STR14## ##STR15## ##STR16## ##STR17## ##STR18## ##STR19## ##STR20## ##STR21## ##STR22## ##STR23## ##STR24## ##STR25## ##STR26## ##STR27## ##STR28## ##STR29## ##STR30## ##STR31## In each of the structures shown in Table A, X may be any halogen, for example, bromine, chlorine, flourine, or iodine. Additionally, X may be a sulfonate group, such that aryl sulfonates may also be used in the method of the present invention. As indicated above, the second substrate may be an alcohol reagent, an alkoxide reagent, a silanol reagent, a siloxide reagent, an amine reagent, an organoboron reagent, an organozinc reagent, an organomagnesium reagent such as a Grignard reagent, a malonate reagent, a cyanoacetate reagent, an olefinic reagent, or combinations of these. Nonlimiting examples of useful alkoxide reagents include NaO--C.sub.6 H.sub.4 --OMe and NaO-tBu. Nonlimiting examples of useful siloxide reagents include NaO--Si-(tBu)Me.sub.2. Nonlimiting examples of amine reagents include compounds with N--H bonds, including carbamates and cyclic or heterocyclic amine compounds such as pyrrole, indole, and the like. Examples of amine and related N--H reagents that are useful in the method of the present invention include, but are not limited to, morpholine, dibutylamine, aniline, n-butylamine, n-hexylamine, methylaniline, aminotoluene, t-butylcarbamate, indole, benzophenone hydrazone and benzophenone imine. Useful organoboron reagents include arylboronic acids, such as o-tolylboronic acid, phenylboronic acid, p-trifluoromethylphenylboronic acid, p-methoxyphenylboronic acid, o-methoxyphenylboronic acid, 4-chlorophenylboronic acid, 4-formylphenylboronic acid, 2-methylphenylboronic acid, 4-methoxyphenylboronic acid, 1-naphthylboronic acid, and the like. Useful organozinc reagents include n-butylzinc chloride, secbutylzinc chloride and phenylzinc chloride. Useful organomagnesium reagents include butylmagnesium bromide and phenylmagnesium chloride. Useful olefinic reagents include vinylarenes such as styrene and acrylic acid derivatives such as n-butyl acrylate and methyl acrylate. All of these reagents may be used as the limiting substrate or in excess quantities and are preferably used in quantities of 0.2-5 equivalents relative to the aromatic halide or sulfonate. The method of the present invention optionally takes place in the presence of a base. Any base may be used so long as the process of the invention proceeds to the product. Non-limiting examples of suitable bases include alkali metal hydroxides, such as sodium and potassium hydroxides; alkali metal alkoxides, such as sodium t-butoxide; metal carbonates, such as potassium carbonate, cesium carbonate, and magnesium carbonate; phosphates such as trisodium or tripotassium phosphate; alkali metal aryl oxides, such as potassium phenoxide; alkali metal amides, such as lithium amide; tertiary amines, such as triethylamine and tributylamine; (hydrocarbyl)ammonium hydroxides, such as benzyltrimethylammonium hydroxide and tetraethylammonium hydroxide; and diaza organic bases, such as 1,8-diazabicyclo[5.4.0]-undec-7-ene and 1,8-diazabicyclo-[2.2.2.]-octane, and organic or alkali metal fluorides such as tetrabutylamonium fluoride or potassium fluoride. Preferably, the base is an alkali hydroxide, alkali alkoxide, alkali carbonate, alkali phosphate or alkali fluoride, more preferably, an alkali alkoxide, and most preferably, an alkali metal C.sub.1-10 alkoxide. The quantity of base which may be used can be any quantity which allows for the formation of the product. Preferably, the molar ratio of base to arylating compound ranges from about 1:1 to about 5:1, and more preferably between about 1:1 and 3:1. As an alternative embodiment of this invention, the catalyst may be anchored or supported on a catalyst support, including a refractory oxide, such as silica, alumina, titania, or magnesia; or an aluminosilicate clay, or molecular sieve or zeolite; or an organic polymeric resin. The quantity of transition metal catalyst which is employed in the method of this invention is any quantity which promotes the formation of the desired product. Generally, the quantity is a catalytic amount, which means that the catalyst is used in an amount which is less than stoichiometric relative to either of the substrates. Typically, the transition metal catalyst ranges from about 0.01 to about 20 mole percent, based on the number of moles of either the first substrate or the second substrate used in the reaction. Preferably, the quantity of transition metal catalyst ranges from about 0.01 to about 2 mole percent, and more preferably from about 0.1 to about 2 mole percent, based on the moles of either substrate. In addition, the ratio of ferrocenyl ligand to Group 8 metal is preferably in the range from about 3:1 to about 0.25:1, more preferably from about 0.5:1 to about 2:1, and most preferably from about 0.8:1 to about 3:1. The method described herein may be conducted in any conventional reactor designed for catalytic processes. Continuous, semi-continuous, and batch reactors can be employed. If the catalyst is substantially dissolved in the reaction mixture as in homogeneous processes, then batch reactors, including stirred tank and pressurized autoclaves, can be employed. If the catalyst is anchored to a support and is substantially in a heterogeneous phase, then fixed-bed and fluidized bed reactors can be used. In the typical practice of this invention, the substrates, the catalyst, and any optional base are mixed in batch, optionally with a solvent, and the resulting mixture is maintained at a temperature and pressure effective to prepare the aromatic product containing a C--O, C--C, or C--N covalent bond. Any solvent can be used in the process of the invention provided that it does not interfere with the formation of the product. Both aprotic and protic solvents and combinations thereof are acceptable. Suitable aprotic solvents include, but are not limited to, aromatic hydrocarbons, such as toluene and xylene, chlorinated aromatic hydrocarbons, such as dichlorobenzene, and ethers, such as dimethoxyethane, tetrahydrofuran or dioxane. Suitable protic solvents include, but are not limited to, water and aliphatic alcohols, such as ethanol, isopropanol, and cyclohexonol, as well as glycols and other polyols. The amount of solvent which is employed may be any amount, preferably an amount sufficient to solubilize, at least in part, the reactants and base. A suitable quantity of solvent typically ranges from about 1 to about 100 grams solvent per gram reactants. Other quantities of solvent may also be suitable, as determined by the specific process conditions and by the skilled artisan. Generally, the reagents may be mixed together or added to a solvent in any order. Air is preferably removed from the reaction vessel during the course of the reaction, however this step is not always necessary. If it is desirable or necessary to remove air, the solvent and reaction mixture can be sparged with a non-reactive gas, such as nitrogen, helium, or argon, or the reaction may be conducted under anaerobic conditions. The process conditions can be any operable conditions which yield the desired product. Beneficially, the reaction conditions for this process are mild. For example, a preferred temperature for the process of the present invention ranges from about ambient, taken as about 22.degree. C., to about 150.degree. C., and preferably, from about 25.degree. C. to about 70.degree. C. The process may be run at subatmospheric pressures if necessary, but typically proceeds sufficiently well at about atmospheric pressure. The process is generally run for a time sufficient to convert as much of the substrates to product as possible. Typical reaction times range from about 30 minutes to about 24 hours, but longer times may be used if necessary. The product can be recovered by conventional methods known to those skilled in the art, including, for example, distillation, crystallization, sublimation, and gel chromatography. The yield of product will vary depending upon the specific catalyst, reagents, and process conditions used. For the purposes of this invention, "yield" is defined as the mole percentage of product recovered, based on the number of moles of starting reactants employed. Typically, the yield of product is greater than about 25 mole percent. Preferably, the yield of product is greater than about 60 mole percent, and more preferably, greater than about 75 mole percent. |
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