ASYMMETRIC SYNTHESIS OF ACIDS BY THE PALLADIUM CATALYSED HYDROCARBOXYLATION OF OLEFINS

Abstract: A process for preparing a chiral carboxylic acid or ester thereof, either as a single enantiomer or as a mixture of enantiomers in which the presence of one enantiomer is enhanced relative to the others comprises reacting a prochiral olefinic function and either water or an alcoholic function with carbon monoxide in the presence of a protonic acid other than nitric acid, a single enantiomer of an optically active compound chosen from the class of chiral phosphoric acids or derivatives thereof, and a catalyst comprising (a) at least one of the metals palladium, rhodium, ruthenium, iridium and cobalt and (b) copper. A preferred class of optically active compounds comprises either the (S+) or the (R-) enantiomer of 2,2<1>-(1,1<1>-Binaphthyl) phosphoric acid or its esters or its salts, optionally substituted.

Description: ASYMMETRIC SYNTHESIS OF ACIDS BY THE PALLADIUM CATALYSED HYDROCARBOXYLATION OF OLEFINS The present invention relates to a process for the asymmetric production of carboxylic acid esters and/or carboxylic acids by the catalysed reaction of carbon monoxide, optionally in the presence of oxygen, with a prochiral olefinic substrate. Typically the olefinic substrate can be an aryl substituted olefin e.g. p-isopropylstyrene where a branched product would give a chiral centre adjacent to the benzene ring, or an allylic or homoallylic alcohol where cyclisation results in a chiral centre adjacent to a lactone carbonyl function. Processes for the production of carboxylic acid esters by reacting an olefin with carbon monoxide and an alcohol in the presence of a catalyst and in the presence or absence of oxygen are known. Representative of the published art are US Patent No 4303589, Belgian Patent No 877770, Japanese Patent Publication No 53040709 and US Patent No 3780074. US Patent No 4303589 (Monsanto) describes a process for the production of carboxylate esters by (a) reacting internal olefins with carbon monoxide and an alcohol at 170 to 200*C and 1200-1800 psig in the presence of a cobalt catalyst and a pyridine promoter, (b) diluting the reaction mixture with a large amount of hydrocarbon to cause phase separation, (c) separating the ester from the other phase, which contains more than 90% of the cobalt catalyst and (d) recycling the catalyst to step (a). Belgian Patent No 877770 describes the production of polycarboxylic esters by reacting an olefin containing at least two conjugated double bonds with carbon monoxide and an alcohol in the presence of a base and a palladium/copper catalyst. Japanese Patent Publication No 53040709 describes the production of dicarboxylic acid diesters by reacting an olefin, carbon monoxide, oxygen and an alcohol in the presence of a catalyst containing (a) a palladium group metal or a compound thereof, (b) a copper salt and (c) a tertiary amine. Finally, USP 3,780,075 describes the production of alkadienoic acid esters by reacting a 4-12 carbon acyclic conjugated aliphatic diolefin with a 1 to 20 carbon monohydroxy alcohol and carbon monoxide in the presence of zerovalent palladium and a phosphine activator at 80 to 160'C in the absence of oxygen. Furthermore European application publication No 105704 discloses a process for the production of a carboxylic acid ester which comprises reacting an unsaturated hydrocarbon with carbon monoxide and an alcohol in the presence of a protonic acid and as a catalyst (a) at least one of the metals palladium, rhodium, ruthenium, iridiura and cobalt, and (b) copper. In a more specific example of the above reaction, lactones can be produced by replacing the unsaturated hydrocarbon and the alcohol in the process of European application publication No 105704 by an unsaturated alcohol. This process being disclosed in our copending European application publication No 176370. We have now found that by using a prochiral substrate, asymmetric induction at the resultant chiral centre can be effected by carrying out the hydrocarboxylation reaction in the presence of an optically active compound such as a chiral phosphoric acid or derivative thereof. According to the present invention there is provided a process for preparing a chiral carboxylic acid or ester thereof, either as a single enantiomer or as a mixture of enantiomers in which the presence of one enantiomer is enhanced relative to the others which process comprises reacting a prochiral olefinic function and either water or an alcoholic function with carbon monoxide in the presence of a protonic acid other than nitric acid, a single enantiomer of an optically active compound selected from the class of chiral phosphoric acids or derivatives thereof and a catalyst comprising (a) at least one of the metals palladium rhodium, ruthenium, indium and cobalt and (b) copper, The olefinic function may suitably be any such function that is prochiral and therefore by virtue of its reaction with carbon monoxide produces a chiral centre. Thus the olefin may suitably be an acyclic olefin containing from 4 to 30 carbon atoms per molecule or a cyclic olefin containing from 5 to 30 carbon atoms per molecule. The olefin may have either 1,2 or 3-olefinic carbon-carbon double bonds per molecule, which double bonds may be internal or terminal and may be conjugated or non-conjugated in olefins containing a plurality of carbon-carbon double bonds. Preferred olefins may be represented by the general formula RCH = CHR^ wherein R and R^ are independently either hydrogen, alkyl, alkenyl, alkadienyl, cycloalkyl, aryl, alkaryl, cycloalkenyl or cycloalkadienyl groups having 4 to 20 carbon atoms. R and R may also be taken together from a cyclic system of 4 to 20 carbon atoms. Examples of such species include 1-butene, 2-butene, 1-pentene, 2-pentene, 1-hexene, 2-hexene, 3-hexene, 1-octene, 1-decene, cyclododecene, 2-methyl-l-undecene, styrene, 4-methylstyrene, 4-isopropylstyrene, and the like. Examples of diolefins falling within the preferred class include 1,4-pentadiene, 1,5-hexadiene, 4-vinyl cyclohexene, 1,7-octadiene, 1,9-decadiene and the like, whilst examples of triolefins include 1,5, -cyclododecatriene, cycloheptatriene and the like. A preferred embodiment of the present invention uses derivatives of styrene, examples of which are p-isopropylstyrene and p-isobutylstyrene or 2-vinyl-6-methoxy naphthalene; the latter two compounds are precursors of ibuprofen and naproxen both of which are pharmacologically important molecules. Considering next the optically active compound employed in the form of a single enantiomer, this is chosen from the class of chiral phosphoric acid or derivatives thereof. Preferred compounds include either the (S+) or the (R-) enantiomer of 2,2* - (l.l 1 - Binaphthyl) phosphoric acid or its esters or its salts, optionally substituted. Further preferred compounds are the acids:- where R or R* can be independently selected from H, C^ to C alkyl, Cl, I, Br or OH. As regards the alcoholic function, monohydric or polyhydric alcohols may be employed. Suitable alcohols may be represented by the formula R2CHOH wherein R is independently hydrogen, alkyl, aryl or hydroxyalkyl, or the two groups R together form a ring. Suitably the alcohol is an alkanol. Examples of suitable alcohols include methanol, ethanol, propanols, butanols, pentanols, hexanols, for example 2-ethylhexanol, benzyl alcohol and 1,4-butanediol. The amount of alcohol employed may suitably be at least the stoichiometric amount required to react with the unsaturated hydrocarbon. It is preferred, however, to employ a substantial excess of alcohol over the stoichiometric amount, the alcohol then performing the dual role of reactant and diluent for the reaction. The alcoholic and olefinic function can be present in the same molecule i.e. it is possible to use an unsaturated alcohol as a reactant. In such cases it is preferred to use an unsaturated alcohol which yields a product which, under the conditions of the process, is capable of forming a lactone ring. Generally, unsaturated alcohols capable of forming 5-, 6- and 7-membered rings will be found most useful in the operation of such a process. Preferably the unsaturated alcohol is an allylic alcohol which may be a primary, secondary or tertiary allylic alcohol. Specific examples of unsaturated alcohols which may be employed in the process of the present invention are 3-buten-l-ol, trans-2-buten-l-ol, 3-buten-2-ol, 2-methyl-2-propen-l-ol, 2-methyl-3-buten-l-ol, 3-penten-2-ol, 4-penten-2-ol, 4-penten-l-ol, l-hexen-3-ol, 5-hexen-2-ol, cis-3-hexen-l-ol, cis-2-hexen-l-ol and trans-2-hexen-l-ol. The carbon monoxide may be derived from any suitable source. Elevated pressures, suitably in the range from 2 to 250 psig above the autogenous pressure at the reaction temperature may be employed. The protonic acid may be either a mineral acid, preferably hydrochloric acid or sulphuric acid (but not nitric acid) or an organic acid which may suitably be a carboxylic acid. With regard to the catalyst, one or more of the metals palladium, rhodium, ruthenium, iridium and cobalt is employed as component (a). The metal(s) may either be in the form of the elemental metal(s), such as a finely divided powder, or in the form of a compound of the metal(s). Suitable compounds of the metal(s) include the chlorides, iodides, acetates, trifluoroacetates and nitrates, preferably the chlorides. It is preferred to use palladium either as a metal or as compound, e.g. palladium (II) chloride. Copper, which constitutes component (b) of the catalyst may suitably be added as a cuprous or a cupric compound or as a mixture thereof. A wide variety of copper compounds may be used in the process of the invention. Examples of suitable copper compounds include copper (I) acetate, copper (II) acetylacetonate, copper (I) bromide, copper (I) chloride, copper (II) chloride, copper (I) iodide, copper (II) nitrate, copper (II) trifluoroacetate and the like. As regards the ratios of the catalyst components, the molar ratio of copper component (b) to metal(s) component (a) may suitabl be in the range 1:1 to 200:1, preferably from 2:1 to 50:1. The molar ratio of unsaturated hydrocarbon to the metal(s) component (a) may suitably be in the range from 1:1 to 1000:1, preferably from 5:1 to 250:1. Oxygen may be present or absent. However, it is preferred to operate in the presence of oxygen because by doing so the product yields can be improved. Oxygen may be supplied to the reaction either as essentially pure oxygen or admixed with other gases which are substantially inert under the reaction conditions. Air may conveniently be used as the source of oxygen. The oxygen pressure may suitably be the autogenous pressure at the reaction temperature employed. Alternatively elevated pressures may be employed if desired. Other non gaseous oxidants including hydrogen peroxide, t-butyl hydro peroxide and benzoquenone may also be employed. A solvent may be additionally employed if desired. The particular solvent employed may form a single phase with the alcohol reactant. Alternatively a solvent which is capable of forming a second liquid phase may be employed. The particular solvent employed should be inert under the reaction conditions. Suitable solvents which form a single phas.e with the alcohol reactant include oxygenated hydrocarbons, for example tetrahydrofuran. Suitable solvents capable of forming a second liquid phase include aliphatic hydrocarbons, cycloaliphatic hydrocarbons, aromatic hydrocarbons, alkyl-substituted aromatic hydrocarbons or halogenated aliphatic or aromatic hydrocarbons. Examples of suitable solvents capable of forming a second liquid phase include benzene, toluene, hexane, cyclohexane, chlorobenzene, bromobenzene, a xylene, dichloromethane, chloroform and 1,2-dichloroethane. It will be appreciated by those skilled in the art that the solvent should be chosen having regard to the difference in boiling points between the products of the reaction and the solvent so as to facilitate separation of the reaction mixture into its individual components. The amount of solvent based on the olefin reactant may vary over a wide range, suitably from 20 to 0.2, preferably from 5 to 1, volumes of solvent per volume of olefin reactant. If, in a modification of the invention, the alcoholic function is replaced by water, provided that the amount of water is less than 8 mole equivalents based on the olefinic function and a solvent other than an alcohol is employed, then instead of carboxylic acid ester, there is formed the corresponding carboxylic acid. Preferably the amount of water employed is less than 5, even more preferably about 1 mole equivalent based on the unsaturated hydrocarbon reactant. When water is employed, any suitable solvent other than an alcohol may be used. Suitable solvents include ethers and hydrocarbons, for example paraffinic and aromatic hydrocarbons. Preferably the solvent is an ether. Examples of suitable ethers include tetrahydrofuran, dioxan, glymes and the crown ethers, of which tetrahydrofuran is preferred. The process may suitably be operated at ambient temperature though elevated temperatures, for example in the range 20 to 150*C or even higher may be employed. The reaction time may vary over a wide range, suitably from about 30 minutes to 8 hours, though longer reaction times may be employed if desired. The process may be carried out batchwise or continuously, preferably continuously. The invention will now be described in greater detail by reference to the following Examples. Example 1 Carbon monoxide was bubbled through a solution of tetrahydrofuran (15ral) for 15 minutes. Palladium chloride (0.07g, 0.39 ramol) was added, followed several minutes later by 0.5ral of concentrated hydrochloric acid. After 10 minutes, cupric chloride (O.lOg) was added to the magnetically stirred solution. Oxygen was then bubbled into the solution simultaneously with the carbon monoxide. The (S+) enantiomer of 1,1^-binaphthyl -2,2^ hydrogen phosphate (BNPPA) (0.056g, 0.16 ramol) was then added, followed by 0.50g of p-isobutylstyrene (3.1 ramol). The overall molar ratio of p-isobutylstyrene/BNPPA/PdCl2 is 10/0.5/1.0. The reaction mixture was stirred at room temperature overnight. Distilled water (15ml) was added and the reaction mixture filtered. The filtrate was extracted with hexane (3 x 50ml) and the extract concentrated by rotary evaporation. The aqueous base was treated with ether (3 x 50ml) and the ether extracts then discarded. The aqueous solution was acidified to pH2 using concentrated hydrochloric acid and then extracted with ether (3 x 50ml). The ether extracts were dried (MgSO^.) and concentrated to give ibuprofen. Pure acid was obtained in 92% yield and 78% (S+) enantiomeric excess. Example 2 The method of Example 1 was repeated except that the p-isobutylstyrene was replaced by 2-vinyl-6-methoxy-naphthalene (0.57g, 3.1 ramol), providing a yield of 88% (S+) naproxen and 83% enantiomer excess. Example 3 The method of Example 1 was repeated wherein the ratio of p-isobutylstyrene/(S)-BNPPA/PdCl is 7.7/0.38/1.0. A yield of 89% pure acid with 83% (S+) enantiomeric excess was obtained. Example 4 The method of Example 1 was repeated wherein the ratio of p-isobutylstyrene/(S)-BNPPA.PdCl 2 is 7.7/0.77/1.0. A yield of 80% pure acid with 55% (S+) enantiomeric excess was obtained. Example 5 The method of Example 1 ws repeated wherein the ratio of p-isobutylstyrene/(R-)-BNPPA/PdCl 2 is 7.7/0.38/1.0. A yield of 81% pure acid with 84% (R-) enantiomeric excess was obtained. Comparative Example 1 The method of Example 1 was repeated except that (S+)-BNPPA was replaced by (S+)-BINAP. A yield of 80% pure acid with 9% (S+) enantiomeric excess was obtained. Comparative Example 2 The method of Example 1 was repeated except that (S+)-BNPPA was • replaced by D-menthol and the ratio of p-isobutylstyrene/D-menthol/PdCl2 was 10/3.8/1.0. A yield of 94% pure acid and 2% (S+) enantiomeric excess was obtained. Comparative Example 3 The method of Example 1 was repeated except that (S+)-BNPPA was replaced by D-menthol and the ratio of p-isobutylstyrene/D-menthol/PdCl2 was 10/10/1.0. A yield of 88% pure acid and 3% (S+) enantiomeric excess was obtained.

Claims: CLAIMS 1. A process for preparing a chiral carboxylic acid or ester thereof, either as a single enantiomer or as a mixture of enantioraers in which the presence of one enantiomer is enhanced relative to the others which process comprises reacting a prochiral olefinic function and either water or an alcoholic function with carbon monoxide in the presence of a protonic acid other than nitric acid, a single enantiomer of an optically active compound chosen from the class of chiral phosphoric acids or derivatives thereof, and a catalyst comprising (a) at least one of the metals palladium, rhodium, ruthenium, indium and cobalt and (b) copper. 2. A process as claimed in claim 1 wherein an alcoholic function is used and wherein the prochiral olefinic function and the alcoholic function are provided by an unsaturated alcohol. 3. A process as claimed in claim 2 wherein the unsaturated alcohol is one yielding a product capable of forming a lactone ring. 4. A process as claimed in claim 1 wherein the optically active compound is a chiral phosphoric acid. 5. A process as claimed in claim 4 wherein the optically active compound is either the (S+) or the (R-) enantiomer of a 2,2*-(l, l^-Binaphthyl) phosphoric acid, or esters or salts thereof, the acid having the formula:- where R and R can be independently selected from H, C^ to C alkyl, Cl, I,Br or OH. 6. A process as claimed in claim 1 where component (a) of the catalyst is either palladium metal or a palladium compound. 7. A process as claimed in claim 1 which is carried out in the presence of essentially pure oxygen or air. 8. A process as claimed in claim 1 wherein the olefin is either p-isobutylstyrene or 2-vinyl-6-methoxy napththalene.

Inventors: ALPER HOWARD, ALPER, HOWARD
Applicants: BRITISH PETROLEUM CO PLC, THE BRITISH PETROLEUM COMPANY PLC
Application year: 1990
Main classification: C07C51
IPC codes: C07C51