RUTHENIUM-PHOSPHINE COMPLEXES

Abstract: A ruthenium-phosphine complex having a 2,2′bis(diaryl­ phosphino)-6,6′-dimethylbiphenyl ligand (L) is of the general formula: wherein R represents a hydrogen atom or a methyl or methoxy group; and X represents ClO₄, BF₄ or PF₆. 9 specific complexes are shown. Synthesis is by reacting Ru₂Cl₄(L)₂N(C₂H₅)₃ with a salt MX where M is a metal (Na, K, Li, Mg or Ag) in a mixed solvent of water and methylene chloride in a quaternary ammonium or phosphonium salt as phase transfer catalyst. The complex is inexpensive and exhibits excellent performance as a catalyst for various organic syntheses, particularly for asymmetric hydrogenation, e.g. of an α,β-unsaturated carboxylic acid.

Description: This invention relates to a ruthenium-phosphine complex useful as a catalyst for various organic syntheses and asymmetric syntheses, such as asymmetric hydrogenation and asymmetric isomerization. Various organic synthetic reactions using metal complexes have hitherto been developed and utilized for many purposes. In particular, there are a number of reports on asymmetric catalysts to be used in asymmetric syntheses, i.e., asymmetric isomerization, asymmetric hydrogenation, and the like. Of the reported asymmetric catalysts, metal complexes formed between metallic rhodium and an optically active tertiary phosphine are especially well known as catalysts for asymmetric hydrogenation. Such complexes typically include a rhodium-phosphine complex using 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (hereinafter abbreviated as BINAP) as a ligand as disclosed in Japanese Patent Application (OPI) No. 61937/80 (the term "OPI" means an unexamined published Japanese patent application) a rhodium-phosphine complex using 2,2'-bis(diphenylphosphino)-6,6'-dimethylbiphenyl as a ligand as disclosed in Japanese Patent Application (OPI) No. 65051/84, and a ruthenium-phosphine complex having as a ligand a 2,2'-bis9diphenylphosphino)-1,1'-binaphthyl or a substituted derivative thereof as disclosed in our EP-A-0245949 (published 19th November 1987). On the other hand, known ruthenium-optically active phosphine complexes, though there are not so many reports as compared with rhodium complexes, include those having BINAP or 2,2′-bis(di-p-tolylphosphino)-1,1′-binaphthyl (hereinafter abbreviated as T-BINAP) as a ligand, e.g., Ru₂Cl₄(BINAP)₂(NEt₃) (wherein Et represents an ethyl group, thus abbreviated hereinafter), Ru₂Cl₄(T-BINAP)₂(NEt₃), RuHCl(BINAP)₂, and RuHCl(T-BINAP)₂, as reported in Ikariya et al., J. Chem. Soc., Chem. Commun. , p. 922, (1985). However, the known ruthenium complexes are not satisfactory in stability nor in optical yield attained. Although metallic rhodium provides excellent complex catalysts, it is expensive due to limitations in place and quantity of production. When used as a catalyst component, it forms a large proportion in the cost of the catalyst, ultimately resulting in increase in cost of the final commercial products. While metallic ruthenium is cheaper than rhodium and appears promising as a catalyst component for industrial application, it still presents problems in its activity to cope with precision reactions and its range of application. Therefore, it has been much desired to develop a catalyst which is inexpensive, has high activity and durability, and catalyzes asymmetric reactions to attain high optical yields, i.e., to produce reaction products having high optical purity. As a result of extensive investigations with the purpose of meeting the above-described industrial demand, the inventors have discovered a novel ruthenium complex having high catalytic activity, which is usable either for general syntheses when the ligand thereof is optically inactive or for asymmetric syntheses when the ligand thereof is optically active. The present invention thus relates to a ruthenium-phosphine complex represented by the formula (I): wherein R represents a hydrogen atom, a methyl group or a methoxy group; and X represents Cl0₄, BF₄ or PF₆. EP-A-0104376 describes the production of optically active amines wherein there is used a complex of a metal of Group VIII such as rhodium, and wherein the product contains diphenyl phosphino legands of similar type of those used herein. The 2,2'-bis(diarylphosphino)-6,6'-dimethylbiphenyl used as a ligand of the complex of the present invention can be synthesized according to the process reported in Miyashita et al., The Chemical Society of Japan, Collected Drafts II for Lectures in the 52th Spring Annual Meeting , IT06, p. 1267 (1986). More specifically, o-toluidine is reacted with nitric acid to form 2-amino-3-methylnitrobezene, which is then converted to 2-iodo-3-methylnitrobenzene making use of the process described in P.B. Carlin et al., J. Am. Chem. Soc. , Vol. 78, p. 1997 (1956). A copper powder is reacted on the resulting product to obtain 2,2′-dinitro-6,6′-dimethylbiphenyl, which is then subjected to hydrogenation using a Raney nickel as a catalyst to obtain 2,2′-diamino-6,6′-dimethylbiphenyl. The product is treated with a 47% hydrobromic acid aqueous solution to obtain 2,2′-dibromo-6,6′-dimethylbiphenyl. A Grignard reagent is prepared from the product according to a process generally employed therefor, for example, by using magnesium. The resulting Grignard reagent is condensed with a diarylphosphinyl chloride selected from diphenylphosphinyl chloride, di-p-tolylphosphinyl chloride and di-p-anisylphosphinyl chloride to obtain a (±)-2,2′-bis(diarylphosphinyl)-6,6′-dimethylbiphenyl. The product is resolved by using dibenzoyl tartaric acid and then reduced with trichlorosilane to obtain an optically active 2,2′-bis(diarylphosphino)-6,6′-dimethylbiphenyl. Starting with the thus prepared optically active 2,2′-bis(diarylphosphino)-6,6′-dimethylbiphenyl, there can be obtained the ruthenium-phosphine complex of the present invention having the corresponding optical activity. The ruthenium-phosphine complex of formula (I) according to the present invention can be prepared starting from Ru₂Cl₄(L)₂NEt₃ (wherein L represents a 2,2′-bis(diarylphosphino)-6,6′-dimethylbiphenyl, hereinafter the same), which is obtained by reacting [RuCl₂(COD)] n (wherein COD represents cyclooctadiene, hereinafter the same) and the above-described 2,2′-bis(diarylphosphino)-6,6′-dimethylbiphenyl. The previous starting material, [RuCl₂(COD)] n , can be prepared by reacting ruthenium chloride and cycloocta-1,5-diene in an ethanol solvent as taught in M.A. Bennett et al., Chemistry and Ind. , p. 1516 (1959). Ru₂Cl₄(L)₂NEt₃ can be obtained in a good yield by reacting 1 mole of [RuCl₂(COD)] n , about 1.2 moles of 2,2′-bis(diarylphosphino)-6,6′-dimethylbiphenyl, and about 4 moles of triethylamine in a solvent, e.g., toluene, under heating. The novel ruthenium-phosphine complex of formula (I) according to the present invention can be prepared by reacting Ru₂Cl₄(L)₂NEt₃ with a salt represented by formula (II) MX (II) wherein X is as defined above; and M represents a metal element selected from Na, K, Li, Mg and Ag, in a mixed solvent of water and methylene chloride in the presence of, as a phase transfer catalyst, a quaternary ammonium salt or quaternary phosphonium salt represented by formula (III) R¹R²R³R⁴QZ (III) wherein R¹, R², R³, and R⁴ each represents an alkyl group having from 1 to 16 carbon atoms, a phenyl group, or a benzyl group; Q represents a nitrogen atom or a phosphorus atom; and Z represents a halogen atom. The reaction between Ru₂Cl₄(L)₂NEt₃ and the salt of formula (II) is carried out by adding these two reactants and the phase transfer catalyst of formula (III) to a mixed solvent of water and methylene chloride and stirring the mixture. The amount of the salt of formula (II) to be added ranges from 2 to 10 moles, preferably 5 moles, per mole of the ruthenium, and the amount of the phase transfer catalyst of formula (III) ranges from 1/100 to 1/10 mole per mole of the ruthenium. The reaction sufficiently proceeds by stirring at a temperature of from 5 to 30°C for a period of from 6 to 18 hours, usually 12 hours, while optimum conditions are determined depending on the kinds of the starting complex and the salt of formula (II). As a solvent system, water and methylene chloride are suitably used in approximately equal amounts, and the salt and the phase transfer catalyst are added to the reaction system as dissolved in water. Examples of the salt of formula (II) to be used include perchlorates, borofluorides, and hexafluorophosphates of Na, K, Li, Mg or Ag, whose anionic group is introduced into the ruthenium complex. The phase transfer catalyst of formula (III) which can be used in the present method include those described in the literature, e.g., W.P. Weber and G.W. Gokel, Phase Transfer Catalysts in Organic Synthesis , 1st Ed., Kagaku Dojin (1978). Specific examples of these phase transfer catalysts are quaternary ammonium salts, e.g., tetramethylammonium bromide, tetrapropylammonium bromide, tetrabutylammonium chloride, tetrabutylammonium iodide, octyltrimethylammonium bromide, lauryltrimethylammonium bromide, lauryltriphenylammonium bromide, cetyltrimethylammonium chloride, methyltrioctylammonium chloride or benzyltriethylammonium bromide, and quaternary phosphonium salts, e.g., tetrabutylphosphonium chloride, tetrabutylphosphonium bromide, tetrabutylphosphonium iodide, lauryltriethylphosphonium bromide, lauryltributylphosphonium bromide, trioctylethylphosphonium bromide, butyltriphenylphosphonium chloride, lauryltributylphosphonium bromide or benzyltributylphosphonium bromide. After completion of the reaction, the reaction mixture is allowed to stand, followed by liquid separation to remove the aqueous layer. The methylene chloride solution is then washed with water, and the methylene chloride is removed by distillation under reduced pressure to obtain the desired product. The ruthenium-phosphine complex of formula (I) according to the present invention can also be prepared by starting with Ru(O₂CCH₃)₂(L) as follows. The starting material, Ru(O₂CCH₃)₂(L), is obtained by reacting Ru₂Cl₄(L)₂NEt₃ with sodium acetate in an alcohol solvent, e.g., methanol, ethanol, t-butanol, at a temperature of from about 20 to 110°C for a period of from 3 to 15 hours, removing the solvent by distillation, extracting the desired complex with a solvent, e.g., diethyl ether, ethanol, and then evaporating the extract to dryness. The resulting Ru(O₂CCH₃)₂(L) is then reacted with an acid represented by formula (IV) HX (IV) wherein X is as defined above, in a mixed solvent of methylene chloride and methanol while stirring. The acid of formula (IV) is used in an amount of from 2 to 6 moles, preferably 4 moles, per mole of the ruthenium. This reaction is carried out at a temperature of from 5 to 30°C for a period of from 6 to 18 hours, usually 12 hours, while stirring, though the optimum reaction conditions are determined depending on the kind of the acid of formula (IV). The methylene chloride and methanol are suitably used at an approximately equivalent ratio. Specific examples of the ruthenium-phosphine complexes according to the present invention are shown below. The thus obtained ruthenium-phosphine complex of formula (I) according to the present invention contains a biphenyl basic structure as a ligand that exhibits higher structural flexibility and higher solubilities to various solvents and is, therefore, more applicable to various reactions as compared with a BINAP ligand. The ruthenium-phosphine complex of the invention exhibits excellent performance as a catalyst for asymmetric hydrogenation or the like reaction. For example, when it is applied to asymmetric hydrogenation reaction of α,β-unsaturated carboxylic acids, such as tiglic acid, i.e., (E)-2-methyl-2-butenoic acid, etc., the reaction rapidly proceeds in the presence of the complex of formula (I) at a temperature of from 10 to 50°C to produce an optically active carboxylic acid derivative, i.e., a hydrogenation product, at a selectivity reaching almost 100%. Further, the thus produced carboxylic acid has an optical purity of from 90 to 95%. Thus, the ruthenium-phosphine complexes according to the present invention show very excellent results as industrially useful catalysts. The present invention will hereinafter be illustrated in greater detail with reference to Reference Examples, Examples, and a Use Example. REFERENCE EXAMPLE 1 [Bis(µ,µ′-dichloro)bis{2,2′-bis(diphenylphosphino)-6,6′-dimethylbiphenyl}]diruthenium-Triethylamine To 50 ml of toluene were added 0.5 g (1.8 mmoles) of [RuCl₂(COD)] n , 1 g (1.82 mmoles) of 2,2′-bis(diphenylphosphino)-6,6′-dimethylbiphenyl, and 1.0 ml (7.2 mmoles) of triethylamine under a nitrogen atmosphere, and the mixture was stirred while heating under toluene refluxing for 6 hours to effect reaction. The solvent was removed from the reaction mixture by distillation, and the residue was dried under reduced pressure. The solid was dissolved in methylene chloride, followed by filtration through Celite. The filtrate was concentrated to dryness under reduced pressure to obtain 1.35 g of the titled compound as deep red crystals. The yield was 97%. Elemental Analysis for C₈₂H₇₉P₄NCl₄Ru₂: Calcd. (%): Ru 13.07, P 8.01, C 63.69, H 5.15 Found (%): Ru 12.71, P 7.64, C 64.07, H 5.52 ³¹P NMR (CDCl₃) δ ppm: 51.63 (d, J=40.0 Hz), 52.52 (d, J=41.5 Hz) ¹H NMR (CDCl₃) δ ppm: 1.27 (s, 12H), 1.30 (br. s, 9H), 2.91-3.08 (m, 6H), 6.58-8.18 (m, 52H) REFERENCE EXAMPLE 2 [2,2′-Bis(diphenylphosphino)-6,6′-dimethylbiphenyl]ruthenium-Diacetate In a 80 ml-volume Schlenk's tube were charged 0.66 g (0.85 mmole) of the [bis(µ,µ′-dichloro)bis{2,2′-bis(diphenylphosphino)-6,6′-dimethylbiphenyl}]diruthenium-triethylamine as prepared in Reference Example 1 and 0.70 g (8.54 mmoles) of sodium acetate. After the atmosphere had been thoroughly displaced with nitrogen, 40 ml of t-butanol was added thereto, followed by heat-refluxing for 14 hours. After completion of the reaction, the t-butanol was removed by distillation under reduced pressure, and the residue was evaporated to dryness and extracted three times with 5 ml portions of diethyl ether. The diethyl ether was removed by distillation to dryness, and the solid was further extracted three times with 5 ml portions of ethanol. The extract was concentrated to dryness to obtain 0.65 g of the titled compound as a yellowish brown solid. The yield was 98.6%. Elemental Analysis for C₄₂H₄₄O₄P₂Ru: Calcd. (%): Ru 13.03; P 7.98; C 65.02; H 5.72 Found (%): Ru 12.69; P 7.78; C 65.41; H 6.08 ³¹P NMR (CDCl₃) δ ppm: 61.18 (s) ¹H NMR (CDCl₃) δ ppm: 1.32 (s, 6H), 1.72 (s, 6H), 6.61-7.72 (m, 26H) EXAMPLE 1 [2,2′-Bis(diphenylphosphino)-6,6′-dimethylbiphenyl]ruthenium-Diperchlorate In a 250 ml-volume Schlenk's tube was charged 0.23 g (0.3 mmole) of the [bis(µ,µ′-dichloro)bis{2,2′-bis(diphenylphosphino)-6,6′-dimethylbiphenyl}]diruthenium-triethylamine as prepared in Reference Example 1. After the atmosphere had been thoroughly displaced with nitrogen, 60 ml of methylene chloride was added thereto, and a solution of 0.73 g (6.0 mmoles) of sodium perchlorate in 60 ml of water and a solution of 16 mg (0.06 mmole) of triethylbenzylammonium bromide in 3 ml of water were added thereto, followed by stirring at room temperature for 12 hours. After completion of the reaction, the reaction mixture was allowed to stand, followed by liquid separation to remove the aqueous layer. The methylene chloride solution was washed with 50 ml of water, followed by liquid separation. The methylene chloride was removed by distillation under reduced pressure, and the residue was dried under reduced pressure to obtain 0.25 g of the titled compound as a deep brown solid. The yield was 98%. Elemental Analysis for C₃₈H₃₂Cl₂O₈P₂Ru: Calcd. (%): Ru 11.88; P 7.28; C 53.66; H 3.79 Found (%): Ru 11.47; P 6.93; C 53.91; H 4.10 ³¹P NMR (CDCl₃) δ ppm: 46.27 (d, J=47.95 Hz), 69.09 (d, J=47.95 Hz) EXAMPLE 2 [2,2′-Bis(diphenylphosphino)-6,6′-dimethylbiphenyl]ruthenium-Ditetrafluoroborate In a Schlenk's tube was charged 0.23 g (0.3 mmole) of the [2,2′-bis(diphenylphosphino)-6,6′-dimethylbiphenyl]ruthenium-diacetate as prepared in Reference Example 2. After the atmosphere had been thoroughly displaced with nitrogen, 5 ml of methylene chloride, 5 ml of methanol, and 0.25 ml (1.2 mmoles) of a 42 wt% borofluoric acid were added thereto, followed by stirring at room temperature for 12 hours. The reaction mixture was concentrated under reduced pressure to obtain 0.24 g of the titled compound as a yellowish brown solid. The yield was 97%. Elemental Analysis for C₃₈H₃₂B₂F₈P₂Ru: Calcd. (%): Ru 12.25; P 7.51; C 55.30; H 3.91 Found (%): Ru 11.89; P 7.23; C 55.67; H 4.12 ³¹P NMR (CDCl₃) δ ppm: 46.17 (d, J=47.95 Hz), 69.08 (d, J=47.95 Hz) EXAMPLE 3 [2,2′-Bis(diphenylphosphino)-6,6′-dimethylbiphenyl]ruthenium-Dihexafluorophosphate In a 250 ml-volume Schlenk's tube was charged 0.23 g (0.3 mmole) of the [bis(µ,µ′-dichloro)bis{2,2′-bis(diphenylphosphino)-6,6′-dimethylbiphenyl}]diruthenium-triethylamine as prepared in Reference Example 1. After the atmosphere had been thoroughly displaced with nitrogen, 60 ml of methylene chloride was added thereto, and subsequently, a solution of 1.10 g (6.0 mmoles) of potassium hexafluorophosphate in 60 ml of water and a solution of 16 mg (0.06 mmole) of triethylbenzylammonium bromide in 3 ml of water were added thereto. The reaction mixture was stirred at room temperature for 12 hours. After completion of the reaction, the reaction mixture was allowed to stand, followed by liquid separation to remove the aqueous layer. The methylene chloride solution was washed with 50 ml of water, followed by liquid separation. The methylene chloride was removed by distillation under reduced pressure, and the residue was dried under reduced pressure to obtain 0.27 g of the titled compound as a deep brown solid. The yield was 96%. Elemental Analysis for C₃₈H₃₂F₁₂P₄Ru: Calcd. (%): Ru 10.76; P 12.94; C 48.60; H 3.43 Found (%): Ru 10.44; P 12.61; C 48.91; H 3.81 ³¹P NMR (CDCl₃) δ ppm: 46.15 (d, J=47.95 Hz), 69.08 (d, J=47.95 Hz) USE EXAMPLE Preparation of (2R)-(-)-2-Methylbutyric Acid In a 300 ml-volume stainless steel autoclave whose atmosphere has been displaced with nitrogen, 1 g (10 mmoles) of (E)-2-methyl-2-butenoic acid and 50 ml of methanol were charged, and 16.5 mg (0.02 mmole) of the (+)-[2,2′-bis(diphenylphosphino)-6,6′-dimethylbiphenyl]ruthenium-ditetrafluoroborate as prepared in Example 2 was added thereto. The mixture was subjected to hydrogenation at 20°C and at a hydrogen pressure of 4 kg/cm² for 20 hours. After the completion of the reaction, the solvent was removed by distillation to obtain 1 g of 2-methylbutyric acid. The yield was 100%. Boiling Point: 50°C/0.07 mm Hg Optical Rotation: [α] 23 / D -18.09° (neat) ¹H NMR (CDCl₃) δ ppm: 0.95 (t, 3H), 1.17 (d, 3H), 1.15-2.00 (m, 2H), 2.4 (m, H), 9.76 (s, 1H) The resulting carboxylic acid was reacted with (R)-(+)-1-(1-naphthyl)ethylamine to synthesize an amide compound. High performance liquid chromatography of the amide revealed that the above obtained carboxylic acid comprised 97.2% of (2R)-(-)-2-methylbutyric acid and 2.8% of (2S)-(+)-2-methylbutyric acid and had an optical purity of 94.4 % ee. The present invention provides a novel ruthenium-phosphine complex exhibiting excellent performance as a catalyst for various organic syntheses, and particularly asymmetric hydrogenation, and shows industrially superior results in catalytic activity. Further, the complex according to the present invention can be produced at low cost, making a contribution to reductian of product price and, thus, has a high industrial value.

Claims: A ruthenium-phosphine complex represented by the general formula: wherein R represents a hydrogen atom, a methyl group or a methoxy group; and X represents ClO₄, BF₄ or PF₆. [2,2′-Bis(diphenylphosphino)-6,6′-dimethylbiphenyl]ruthenium-diperchlorate. [2,2′-Bis(diphenylphosphino)-6,6′-dimethylbiphenyl]ruthenium-ditetrafluoroborate. [2,2′-Bis(diphenylphosphino)-6,6′-dimethylbiphenyl]ruthenium-dihexafluorophosphate. A process of asymmetric hydrogenation, wherein an α,β -unsaturated carboxylic acid is hydrogenated in the presence of a complex as claimed in any preceding claim as catalyst. A process as claimed in Claim 5, wherein the reaction is at a temperature of 10 to 50°C.

Inventors: AKUTAGAWA, SUSUMU, KUMOBAYASHI, HIDENORI, SAYO, NOBORU, TAKETOMI, TAKANAO
Applicants: TAKASAGO INTERNATIONAL CORPORATION
Application year: 1987
Main classification: C07F15
IPC codes: B01J31, C07C51, C07F15, C07B61