MX2007011752A - Method for the catalytic production of hydrocodone, hydromorphone, and derivatives thereof. - Google Patents

Abstract

A method for the catalytic production of hydrocodone derivatives and hydromorphone derivatives, respectively, utilizing a transition metal catalyst of the formula [M(PR⁴R⁵R⁶)_nX_m]_p; wherein M is a Group VIII transition metal; R⁴, R⁵ and R⁶ are selected from the group consisting of alkyl, aryl, alkoxyl, phenoxyl and combinations thereof; X is a halide or an anion; n is 1, 2, 3 or 4; m is 1 or 2; and p is at least 1.

Description

METHOD FOR THE CATALYTIC PRODUCTION OF HI ROCODONA, HYDROOMORPHONE AND DERIVATIVES FROM THE S AS FIELD OF THE INVENTION The present invention relates to a method for the catalytic production of hydrocodone derivatives and hydromorphone derivatives.

BACKGROUND OF THE INVENTION Hydrocodone and hydromorphone are opioid analgesics having similar qualities to codeine and morphine. The development of new opioid derivatives is desirable to produce new intermediate products and potential sources of new analgesics. Conventional methods for producing hydrocodone and hydromorphone typically involve a two step oxidation / reduction pathway from codeine and morphine. Unfortunately, these methods are expensive and inefficient. Attempts to improve efficiency have included the use of catalytic methods. Known methods include the use of metal elements, typically Ru, Rh, Pd and Pt on activated carbon as well as metal complexes. The preparation of these catalysts is difficult, the yields are poor and the isolation of the product is very difficult frequently. Other catalytic methods, include the use of REF: 183891 Platinum or palladium finely divided in an acid medium, are undesirable from the environmental point of view. Enzymatic conversion methods have also been tried, but as with the catalysis methods described above, these methods are expensive and difficult to perfect. Therefore, there is a need for an improved method for the production of hydrocodone, hydromorphone and derivatives thereof which is easily refined and which is economical for manufacturing purposes.

BRIEF DESCRIPTION OF THE INVENTION One aspect of the present invention is to provide a method for the catalytic conversion of a compound of the Formula I in a compound of Formula II using at least one transition metal complex as a catalyst, Formula I Formula II wherein R 1 is H, alkyl, aryl or acyl. Another aspect of the present invention is to provide a method for the catalytic conversion of a compound of Formula VI into a compound of Formula VII, Formula VI Formula VII wherein R is selected from but is not limited to H, a benzyl, substituted benzyl, alkyl, aryl, acyl, aryl-sulfonyl, alkylsulfonyl, carboxy ester, carboxyamide, trialkylsilyl, tetrahydropyranyl, and tetrahydrofuranyl group; and R3 is selected from but is not limited to H, an alkyl, allyl, cycloalkylalkyl, benzyl, arylsulfonyl, alkylsulfonyl, aryl, acyl, formyl, hydroxyl, carboxy ester and carboxyamide group. In one aspect of the present invention, the transition metal complex has the formula [M (PR4R5R6) nXm] p wherein M is a transition metal of Group VIII; R4, R5 and R6 are selected from the group consisting of alkyl, aryl, alkoxy, phenoxy and combinations thereof; X is a halide or an anion; n is 1, 2, 3 or 4; m is 1 or 2; and p is at least 1. These are merely illustrative aspects of the present invention and should not be considered a global listing of the innumerable aspects associated with the present invention. These and other aspects will become apparent to those skilled in the field in view of the following description. A method is provided for the conversion of a compound according to Formula I to a compound according to Formula II, Formula I Formula II wherein R1 is H, alkyl, aryl or acyl. The method of the present invention is especially useful where R1 is methyl or H, ie codeine or morphine, respectively, leading to the formation of hydrocodone or hydromorphone, respectively. In an alternative embodiment of the present invention, there is provided a method for the conversion of a compound according to Formula VI into a compound according to Formula VII.

Formula VI Formula VII wherein R is selected from, but is not limited to, H, a benzyl, substituted benzyl, alkyl, aryl, acyl, aryl-sulfonyl, alkylsulfonyl, carboxy ester, carboxyamide, trialkylsilyl, tetrahydropyranyl, and tetrahydrofuranyl group; and R3 is selected from, but is not limited to, H, an alkyl, allyl, cycloalkylalkyl, benzyl, arylsulphonyl, alkylsulfonyl, aryl, acyl, formyl, hydroxyl, carboxy ester and carboxyamide group. In yet another embodiment, the method of the present invention can be used with quaternary salts as shown below: Formula VIII Fórimuila IX R 2 is selected from, but is not limited to, H, a benzyl, substituted benzyl, alkyl, aryl, acyl, arylsulphonyl, alkyl sulfonyl, carboxy ester, carboxyamide, trialkylsilyl, tetrahydropyranyl and tetrahydrofuranyl group. R8 and R9 are independently selected from, but are not limited to, H, an alkyl, allyl, benzyl, aryl and alkylenecycloalkane group. Alternatively, R8 and R9 taken together form an oxide. Xi and X2 are typically Cl or Br anions. Alternatively, Xi and X2 are anions selected independently from, but not limited to, BF4, PF6, C104, CH02, C204, CF3C02, CF3S03, CH3C02, ArC02, CH3S03, p-tolylS03, HS0 and H2P04 or mixtures thereof, the anion exchange products. Xi and X2 are subjected to the exchange by means of the catalyst. In one embodiment of the present invention, the transition metal catalysts of the present invention comprise at least one transition metal complex of the formula [M (PR4R5R6) nXm] p; wherein M is a transition metal of Group VIII; R4, R5 and Rd are selected from the group consisting of alkyl, aryl, alkoxy, phenoxy and combinations thereof; X is a halide or an anion; n is 1, 2, 3 or; m is 1 or 2; p is at least 1; In one embodiment of the present invention, the transition metal catalysts of the present invention they comprise a transition metal complex [M (PR4R5R6) nXm] p; wherein, M is preferably a transition metal of Group VIII; R4, R5 and R6 are independently selected from alkyl, aryl, alkoxy and phenoxy groups; X is a halide or an anion; n is 1, 2, 3 or 4; and m is 1 or 2. These complexes have the ability to polymerize, so p is at least 1. When the three R groups are alkoxy, phenoxy or combinations thereof, the ligand of the complex is termed a tertiary phosphite. If at least one of the group R is not alkoxy or phenoxy, then the ligand of the complex is called a tertiary phosphine. Preferred metals include Rh, Ru, Pd and Pt. The halide, X, is typically Cl or Br. The anions include but are not limited to BF4, PF6, C104, CH02, C204, CF3C02, CF3S03, CH3C02, ArC02, CH3S03, p-tolylS03, HS04 and H2P04. Many of these catalysts are commercially available or are easily prepared as is known in the field. In another embodiment of the present invention, the transition metal catalysts of the present invention comprise a transition metal complex of a tertiary phosphide halide, [M (PR73) nXm] p, wherein M is preferably a transition metal. of Group VIII; R7 is alkyl or aryl; X is a halide or an anion; n is 1, 2, 3 or 4; and m is 1 or 2. These complexes have the polymerization capacity, therefore p is at least 1. The metals Preferred include Rh, Ru, Pd and Pt. The halide, X, is typically Cl or Br. The anions include but are not limited to BF4, PF6, C104, CH02, C204, CF3C02, CF3S03, CH3C02, ArC02, CH3S03, p-tolylS03, HS04 and H2P04. R7 is an alkyl or aryl group, with phenyl being preferred. Many of these catalysts are commercially available or are easily prepared as is known in the field. It is observed that the catalysts of the formula [M (PR73) nXm] p are a subgroup of the larger group of catalysts [M (PR4R5R6) nXm] p. The complexes of the present invention can be comprised of phosphines / tertiary phosphites supported by a solid, including but not limited to tertiary phosphines / phosphites supported by a polymer, tertiary phosphines / phosphites supported by silica and tertiary phosphines / phosphites bonded to resin. In the case of phosphines / tertiary phosphites supported by a solid, one of the R groups typically contains a linking group which connects a phosphine / phosphite and a solid phase, as is well known in the art. A non-limiting example of a tertiary phosphine supported by a solid which is useful in the present invention is the copolymer prepared from the monomer p-styryldiphenylphosphine also known as diphenyl (p-vinylphenyl) phosphine with styrene or tertiary supported phosphines by silica made to from the treatment of silica with (EtO) 3SiCH2CH2PPh2. There are phosphines / phosphites tertiary supported by a solid that are commercially available. In one embodiment of the invention, the metal is Rh and the complex has the formula [Rh (PR4R5R6) nXm] p; wherein R 4, R 5 and R 6 are selected from the group consisting of alkyl, aryl, alkoxy, phenoxy and combinations thereof; X is a halide or an anion; n is 1, 2, 3 or 4; m is 1 or 2; and p is at least 1. In another embodiment of the present invention, the transition metal is Rh and the metal complex has the formula [Rh (PR73) nX] p; wherein R7 is alkyl or aryl, X is a halide, n is 1, 2 or 3 and p is at least 1 or has the formula [Rh (PR73) nY] p wherein R7 is alkyl or aryl, n is 1, 2 or 3, p is at least 1 and Y is an anion, preferably including BF4, PF6, C104, CH02, CF3C02, CF3S03, CH3C02, C20, ArC02, CH3S03, pt? lilS03, HS0 or H2P0. In still another embodiment of the present invention, the transition metal is Ru and the metal complex has the formula [Ru (PR4R5R6) nXm] p; wherein R 4, R 5 and R 6 are selected from the group consisting of alkyl, aryl, alkoxy, phenoxy and combinations thereof; X is a halide or an anion; n is 1, 2, 3 or; m is 1 or 2; and p is at least 1. In another embodiment, the transition metal is Ru and the metal complex has the formula [RuX2 (PR73) n] p wherein R7 is alkyl or aryl, X is a halide, n is 1, 2 , 3 or 4; and p is at least 1 or has the formula [RuYX (PR73) n] p wherein R7 is alkyl or aryl and wherein n = 3, p is at least 1, Y = H and X = C1; n = 3, Y = H and X = H; n = 4, X = H, Y = H; or n = 2, 3 or 4, p is at least 1 and X = Y = C104, CF3S03, PF6 or BF4, CH02, CH3C02 ArC02, CH3S03, p-t? lilS03, HS04 or H2P04. A suitable method for producing an illustrative Ru complex of the present invention involves the reflux of a Ru salt, for example RuClxH20 with an excess of triphenylphosphine in alcohol to form the complex [Ru (P (C6H5) 3) 3 Cl2] p. An illustrative Rh complex of the present invention is also commercially available or can be prepared by refluxing rhodium trichloride with triphenylphosphine in alcohol, typically methanol or ethanol. In another illustrative embodiment of the present invention, the Rh, Ru and / or Ir complex can be linked to a tertiary copolymer of styrene, divinylbenzene and diphenyl (p-vinylphenyl) phosphine also known as p-styryldiphenylphosphine, illustrated below: p-styryldiphenylphosphine Optionally, other monomers can be substituted or added to optimize certain physical properties of the total polymeric catalyst. Illustrative examples include but are not limited to ethylene dimethacrylate, p-bromostyrene and crosslinking agents such as divinylbenzene, butadiene, diallyl maleate, diallyl phthalate, glycol dimethacrylate and other di- or triolefins. Other phosphine-containing monomers bonded to the styrene ring may have, in addition to diaryl, dialkyl, branched and cyclic dialkyl, dialkoxy or mixed substitutions or these substitutions. Illustrative examples using styrene are shown in Formulas 18 and 19.

Formula IV Formula V The polymer complex constitutes a composition of material consisting essentially of a solid, inherently porous organic styrene-divinylbenzene copolymer; a substituent phosphine group guanically linked through phosphorus to a carbon atom of the polymer; and a Group VIII metal chemically bonded to the phosphine substituent, which composition is substantially insoluble in the solvent (s). In an illustrative embodiment, the polymeric support it is composed of a styrene-divinylbenzene copolymer containing from 2 to 20 mole percent of divinylbenzene, in which from 0.5 to 7 mole percent, preferably from 5 to 6 mole percent of the pendant phenyl groups of styrene copolymerized contain the diphenylphosphine portion in the para position. The composition of the polymeric support is from 75 to 97.6 mol percent styrene, from 2 to 20 percent divinylbenzene and from 0.4 to 6 percent p-diphenylphosphotostyrene. As for the amount of ruthenium complex in the catalyst, typically the ratio of Ru / atom to slope is preferably at least 0.001 and more preferably is from about 0.5 to an upper limit established by the point at which the polymeric support will not absorb the complex for a longer time, for example about 1.2. The polymer complex can be made by contacting a solution of the Group's metal salt complexVIII in solution with the polymeric support. For a practical application, the metal complex is dissolved in a suitable solvent which includes but is not limited to water, methanol, ethanol, isopropanol, isobutyl alcohol, t-butyl alcohol, chloroform, dichloromethane, fluorobenzene, chlorobenzene, toluene, N- methylpyrrolidone, N, N-dimethylformamide, N, N-dimethylacetamide, methyl sulfoxide, methyl sulfone, tetrahydrofuran and mixtures thereof. The Solution of the Group VIII metal complex should be at least 10 ~ 6 M in the ruthenium complex but preferably is approximately 10 ~ 3 M in the ruthenium complex. In this illustrative embodiment, the polymer portion of the catalyst is inherently porous. The porosity of the polymer portion of the catalyst gives increased activity to the catalyst. With the catalysts having an organic polymer portion which is not inherently porous, the porosity can be induced in the polymer portion by means of solvent swelling. The combinations of the solvents observed above can be manipulated to produce various degrees of swelling of the polymer portion of the catalyst, as is well known in the art. The catalytic conversion of the present invention has the additional economic advantage of being able to convert a codeine or morphine salt, for example codeine hydrochloride or morphine hydrochloride, to hydrocodone or hydromorphone, respectively. In addition, the catalysts of the present invention facilitate the recovery of high value metal from solid metal-containing catalyst. When recovered by conventional methods that are known in the field, the metal of the present catalyst results in an improved recovery rate. This reduces additionally the material and labor costs, as well as simplifying processing / development. For the purposes of this document, it is proposed that the term recovery includes recovery, recycling and / or regeneration of the metal. In embodiments wherein the catalyst is on a fixed support, the catalyst / support can be placed in a column or vessel as part of a circuit reactor. In a non-limiting illustrative example, codeine in alcohol that is heated in a reactor can be pumped or fed by gravity through a catalyst bed and can be alternated back to the reactor until the desired conversion to hydrocodone occurs. The advantages of this method include that many cycles (perhaps several batches) of product can be obtained with a given bed. The value of the catalyst is then easily recovered and sent again for reprocessing. The development of the purification is simplified because the catalyst is not present in the solution. For practical reasons, the concentration of Group VIII metals should be less than about 10 ppm in the product. In cooling, the product would crystallize out of the solution with a high purity, to be recovered by means of filtration or centrifugation. Many process designs, as they are well known in the field, they could be used with the process of the present invention. The reaction of the present invention can be carried out by means of any conventional process. A suitable process includes dissolving the reagent of Formula I in a suitable solvent in a reaction vessel. Suitable solvents include but are not limited to alcohols, preferably to primary or secondary lower alkyl alcohols. The reaction vessel is then flooded with an inert atmosphere, typically nitrogen. The catalyst is added and the reaction mixture is heated to reflux under the inert atmosphere until the conversion is essentially complete, typically at least about one hour. The reaction mixture is cooled and the crystals of the product are collected. The product can be purified by recrystallization from a suitable solvent as is well known in the field or by any other conventional purification method, suitable. In an alternative embodiment, a tertiary amine, for example triethylamine, is added to the reaction mixture when the preferred Ru-complex catalyst is used. The tertiary amine reduces the formation of side products, mainly the alkaloid neopine, a potential by-product in reactions of the present invention using the preferred Ru catalyst.

In another alternative embodiment, the alkaloid compound is added to the reactants that form the catalyst and the catalyst formation reaction takes place in the presence of the alkaloid. The ability to form the catalyst and to subsequently perform the catalytic conversion in the same reaction vessel further improves the economy of the reaction.

DETAILED DESCRIPTION OF THE INVENTION Ex emplos Example 1 Codeine, 50.00 g, was dissolved in 200 ml of methanol in a three neck flask at room temperature. The flask was equipped with a condenser and nitrogen. The flask was flushed with nitrogen for five minutes with an open neck. The catalyst, 0.50 g of RhCl (P (C6H5) 3) 3 was added to the solution. The flask was then flushed with nitrogen for another five minutes and the open neck was closed. The reaction mixture was stirred under nitrogen and heated to reflux for four hours, then cooled to 0 ° C for 30 minutes. The resulting crystals were removed by filtration. The collected crystals were washed four times with 10 ml of cold methanol (5 ° C) and air dried for one hour producing pale yellow crystals (41.50 g, 83% yield). The filtrate was pumped to dryness to provide 6.14 g of a solid yellow color. The solid residue was dissolved in 40 ml of refluxing methanol and cooled to 0 ° C for 30 minutes and filtered. The collected crystals were washed four times with 3 ml portions of cold methanol (5 ° C) and dried in air for 2 hours yielding 3.41 g (6.8%) of white crystals. The analysis of CLAR and the NMR spectra confirm that the product is pure hydrocodone.

Example 2 Morphine, 50.00 g, was suspended in 500 ml of methanol in a three-necked flask equipped with a condenser and nitrogen inlet and outlet. After heating to reflux under nitrogen for five minutes, a neck of the flask was opened. A catalyst, 0.50 g of RhCl (P (C6H5) 3) 3 was added to the vessel. The open neck was closed with a stopper. The reaction mixture was stirred under nitrogen and heated to reflux for 6 hours, cooled to 0 ° C for 30 minutes and filtered. The collected solid was washed four times with cold methanol (5 ° C) and air dried for 20 minutes. The solid was kept under vacuum (15 mm Hg) at room temperature for 1 hour, yielding a white powder (38.83 g, 77.7% yield). The filtrate was distilled under nitrogen until only 200 ml of solution remained. It was cooled to 0 ° C for 30 minutes and filtered, yielding a white powder. He The product was washed twice with 20 ml each and then once with 10 ml of cold methanol (5 ° C) air-dried for 40 minutes to yield 3.48 g of a white powder product. The analysis of CLAR and the NMR spectra confirm that the product is pure hydromorphone.

Example 3 The ruthenium dimer was prepared by refluxing 1 g of RuCl3xH20 with 3 equivalents of P (C6H5) 3 in EtOH (100 ml) overnight. The resulting catalyst, [Ru (P (C6H5) 3) 2C12] 2 was obtained as a black precipitated product after filtration, yield 63%.

Example 4 The catalyst of Example 3 was reacted with codeine in MeOH in the presence of triethylamine in the ratios shown in the following table. The reaction mixtures were flooded with N for 5 minutes, heated to reflux under N2, cooled to 0 ° C and filtered. The recovered crystals were washed twice with 5 ml of MeOH and air dried to produce white crystals.

Example 5 Codeine, 5.0 g and 0.117 g of catalyst, Ru (P (C6H5) 3) 3C12, were dissolved in 25 ml of EtOH. The mixture was flushed with nitrogen for 5 minutes. After heating under reflux under nitrogen for 2 hours, the reaction mixture was cooled to 0 ° C and filtered. The crystals collected were washed twice with 5 ml of MeOH each and dried in the air for 1 hour to produce white crystals, 70% yield of hydrocodone.

Example 6 Morphine, 1.0 g and 80 mg of [Ru (P (CeHs) 3) 2C12] 2 was suspended in 10 ml of MeOH. The reaction mixture was flooded with N2 for 3 minutes, after which 0.25 ml of triethylamine was added and the mixture was flooded with N2 for another 3 minutes. The reaction mixture was heated to reflux with stirring under N2 for 72 hours. It was found that the resulting solid was hydromorphone.

Example 7 Codeine, 5.09 g, 25.4 mg of RuCl3xH20 and 95.9 mg of P (CeH5) 3 were added to 25 ml of ethanol in a three-necked flask. The flask was flooded with N for 5 minutes. The mixture was heated until the reagents dissolved and then heated to reflux, under nitrogen, overnight. The resulting solution was washed twice with 5 ml of MeOH each and air dried to yield 3.31 g of product. The analysis determined the presence of hydrocodone and Ru catalyst.

Example 8 The codeine HCl, 1.1 g and 0.1 g of RuCl2 (P (C6H5) 3) 3 were stirred in 10 ml of MeOH and were flooded with N2 for 5 minutes. The reaction mixture was refluxed overnight under N2, cooled to room temperature and dried under vacuum to yield 1.16 g of a brown solid containing hydrocodone.

Example 9 Conversion of Polymeric Catalyst from Ru to Hydrocodone: Codeine, 50.00 g, is added to 200 ml of methanol contained in a three-necked flask equipped with a condenser and nitrogen inlet and outlet. The mixture is refluxed under nitrogen. 5 g of a polymeric Ru catalyst firmly fixed to phosphine (1% in mol of Ru) are added to the vessel. The reaction mixture is stirred under nitrogen at reflux for several hours. An additional 800 ml of methanol are added and the heating is continued for 30 minutes. The polymeric catalyst is recovered for recycling by filtering the hot liquor. Approximately 800 ml of methanol are removed from the filtrate by means of distillation. The liquor is then cooled to 0 ° C and maintained at that temperature for at least about 30 minutes. The product is collect by filtration, wash four times with cold methanol (5 ° C) and air dry. The product is placed under vacuum (<15 mm Hg) at room temperature for at least one hour. The product is obtained as a white powder weighing more than 38 grams for a yield > 75% The purity and identity of the hydrocodone is confirmed by means of the analysis of CLAR, H1 and C13 NMR and MS.

Example 10 Formula IX Codeine 10 g, Rh (PPh3) 3 Cl, 0.1 g, 0.1 mmol, PPh3, 0.1 mmol and AgBF4, 0.1 g, 0.1 mmol, were placed in a flask and the flask was purged with N2. The MeOH, 100 ml, was purged with N2 and then added to the flask. The reaction mixture was stirred at room temperature. In 15 minutes, the HPLC analysis showed that the reaction was more than 95% complete. The resulting product was recrystallized to provide a pure product with a 90% yield.

Example 11 The N-codeine metobromide, 50 g, is dissolved in 200 ml of methanol in a three neck flask at room temperature. The flask is equipped with a condenser and nitrogen. The flask is flooded with nitrogen for five minutes with an open neck. The catalyst, 0.50 g of RhCl (P (C6H5) 3) 3 is added to the solution. The flask is then flushed with nitrogen for another five minutes and the open neck is closed. The reaction mixture is stirred under nitrogen and heated to reflux for six hours, then cooled. The methanol, 100 ml, is removed by distillation. 100 ml of ethyl acetate are added and the cooling is continued at -10 ° C for one hour. The resulting crystals are removed by filtration. The collected crystals are washed four times with 10 ml of cold ethyl acetate (5 ° C) and dried under a nitrogen flow for one hour producing yellow crystals (~40 g). The analysis of CLAR and the NMR spectra confirm that the product is N-hydrocodone methobromide. From the above description, those skilled in the art will appreciate that economic and efficient methods are provided for catalytic reactions that form hydrocodone derivatives and hydromorphone derivatives. Having described the invention in detail, those skilled in the art will appreciate that modifications can be made to the invention without departing from its spirit and scope. Therefore, it is not proposed that the scope of the invention be limited to the specific embodiments described. Preferably it is proposed that the appended claims and their equivalents determine the scope of the invention. It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims (21)

1. CLAIMS Having described the invention as above, the content of the following claims is claimed as property: 1. A process for the conversion of a composition according to formula VI to the composition according to formula VII, characterized in that it comprises catalytically converting the composition according to formula VI in the composition of formula VII in the presence of at least one catalyst, wherein the catalyst is at least one transition metal complex of the formula [M (PR4R5R6) nX] P; wherein M is a transition metal of group VIII; R4, R5 and R6 are selected from the group consisting of alkyl, aryl, alkoxy, phenoxy and combinations thereof; X is a halide or an anion; n is 1, 2, 3 or 4; m is 1 or 2; and p is at least 1; Formula VI Formula VII wherein R is selected from the group consisting of H, a benzyl group, substituted benzyl, alkyl, aryl, acyl, aryl sulfonyl, alkyl sulfonyl, carboxy ester, carboxyamide, trialkylsilyl, tetrahydropyranyl and tetrahydrofuranyl; and R3 is selected from the group consisting of H, an alkyl, allyl, cycloalkylalkyl, benzyl, aryl-sulfonyl, alkylsulfonyl, aryl, acyl, formyl, hydroxyl, carboxyester, and carboxyamide group.
2. 2. The method according to claim 1, characterized in that (PRR5R6) n is supported by a solid.
3. 3. The method according to claim 1, characterized in that (PRR5R6) n is selected from the group consisting of (PR4R5R6) n supported by polymer, (PR4R5R6) n supported by silica, (PRR5R6) n bonded to resin and mixtures of the same.
4. The method according to claim 1, characterized in that the metal complex is linked to a tertiary copolymer selected from the group consisting of styrene, divinylbenzene and diphenyl (p-vinylphenyl) phosphine.
5. The method according to claim 4, characterized in that the copolymer is replaced by a monomer selected from the group consisting of ethylene-dimethacrylate, p-bromostyrene, divinylbenzene, butadiene, diallyl maleate, diallyl phthalate, glycol dimethacrylate, diolefins and triolefins.
6. 6. The method according to claim 1, characterized in that the metal complex has the formula [Rh (PRR5R6) nXm] p; wherein M is a transition metal of group VIII; R4, R5 and R5 are selected from the group consisting of alkyl, aryl, alkoxy, phenoxy and combinations thereof; X is a halide or an anion; n is 1, 2, 3 or 4; m is 1 or 2; and p is at least 1.
7. 7. The method according to claim 6, characterized in that n is 1, 2 or 3; p is at least 1; and X is selected from the group consisting of BF4, PFß, C10, CH0, CF3C02, CF3S03, CH3C02, ArC02, CH3S03, p-tolylS03, HS04 and H2P04.
8. 8. The method of compliance with the claim 1, characterized in that the metal complex has the formula [RuXY (PRR5R6) n] p; wherein M is a transition metal of group VIII; R4, R5 and R5 are selected from the group consisting of alkyl, aryl, alkoxy, phenoxy and combinations thereof; X is an H, halide or anion; And it is H, halide or anion; n is 1, 2, 3 or 4; m is 1 or 2; and p is at least 1.
9. The method according to claim 8, characterized in that n = 3, p is at least 1, Y = H and X = C1; or n = 3, p is at least 1, Y = H and X = H; or n = 4, p is at least 1, X = H, Y = H; or n = 2, 3 or 4 and X = Y is selected from the group consisting of C104, PF6, BF4, CH02, CF3C02, CF3S03, CH3C02, ArC02, CH3S03, p-t? lilS03, HS04 and H2P0.
10. 10. A process for the conversion of a composition according to formula VIII to a composition according to formula IX, characterized because it comprises catalytically converting the composition according to formula VIII into the composition of formula IX in the presence of at least one catalyst, wherein the catalyst is at least one transition metal complex of the formula [(PR4R5R6) nXm] p; wherein M is a transition metal of group VIII; R4, R5 and R6 are selected from the group consisting of alkyl, aryl, alkoxy, phenoxy and combinations thereof; X is halide or an anion; n is 1, 2, 3 or 4; m is 1 or 2; and p is at least 1; Formula VIII Formula IX wherein R is selected from the group consisting of H, a benzyl, substituted benzyl, alkyl, aryl, acyl, aryl-sulfonyl, alkylsulfonyl, carboxy ester, carboxyamide, trialkylsilyl, tetrahydropyranyl, and tetrahydrofuranyl group; R8 and R9 are independently selected from the group consisting of H, an alkyl, allyl, benzyl, aryl and alkylenecycloalkane group; and Xi and X2 are anions.
11. 11. The method according to the claim 10, characterized in that Xi and X2 are Br or Cl.
12. The method according to claim 10, characterized in that Xx and X2 are anions selected from the group consisting of BF4, PF6, C104, CH02, C204, CF3C02, CF3S03, CH3C02, ArC02, CH3S03, pt? LilS03, HS04 and H2P0.
13. The method according to claim 10, characterized in that R8 and R9 taken together form an oxide.
14. The method according to claim 10, characterized in that (PRR5R6) n is supported by a solid.
15. The method according to claim 10, characterized in that (PR4R5R6) n is selected from the group consisting of (PR4R5R6) n supported by polymer, (PR4R5R6) n supported by silica, (PR4R5R6) n bonded to resin and mixtures of the same.
16. The method according to claim 10, characterized in that the metal complex is linked to a tertiary copolymer selected from the group consisting of styrene, divinylbenzene and diphenyl (p-vinylphenyl) phosphine.
17. 17. The method of compliance with the claim 14, characterized in that the copolymer is replaced by a monomer selected from the group consisting of ethylene dimethacrylate, p-bromostyrene, divinylbenzene, butadiene, diallyl maleate, diallyl phthalate, glycol dimethacrylate, diolefins and triolefins.
18. 18. The method according to claim 10, characterized in that the metal complex has the formula [Rh (PR4R5R6) nXm] p; wherein M is a transition metal of group VIII; R4, R5 and R6 are selected from the group consisting of alkyl, aryl, alkoxy, phenoxy and combinations thereof; X is a halide or an anion; n is 1, 2, 3 or 4; m is 1 or 2; and p is at least 1.
19. The method according to claim 16, characterized in that n is 1, 2 or 3; p is at least 1; and X is selected from the group consisting of BF4, PF6, C10, CH02, CF3C02, CF3S03, CH3C02, ArC02, CH3S03, p-tolylS03, HS04 and H2P04.
20. The method according to claim 10, characterized in that the metal complex has the formula [RuXY (PRR5R6) n] p; wherein M is a transition metal of group VIII; R4, R5 and R6 are selected from the group consisting of alkyl, aryl, alkoxy, phenoxy and combinations thereof; X is H, halide or an anion; And it is H, halide or anion; n is 1, 2, 3 or 4; m is 1 or 2; and p is at least 1.
21. 21. The method according to the claim 18, characterized in that n = 3, p is at least 1, Y = H and X = C1; or n = 3, p is at least 1, Y = H and X = H; or n = 4, p is at least 1, X = H, Y = H; or n = 2, 3 or 4 and X = Y is selected from the group consisting of C104, PF6, BF4, CH02, CF3C02, CF3S03, CH3C02, ArC02, CH3S03, p-tolylS03, HS04 and H2P04.