IE71201B1 - Asymmetrical hydrogenation - Google Patents

Abstract

A process for the asymmetric hydrogenation of (E)-2-methyl-3-phenyl-2-propen-1-ol of the formula <IMAGE> in which R1 has the meaning mentioned herein, to give compounds of the formula <IMAGE> is described. The catalyst used is a neutral or cationic Rh complex of an atropisomeric phosphine.

Description

The present invention relates to an asymmetrical hydrogenation for the preparation of compounds of formula wherein Rx is hydrogen or a group Ζ, Z is the group R2 is methyl, ethyl or chloromethyl and R3 is Cx-Chalky 1, or R2 and R3, together with the carbon atom to which they are jointly attached, are C3 - C7cycloalkyl.

The process comprises asymmetrically hydrogenating a compound of formula in the E form, wherein Rx is as defined above, in the presence of a rhodium catalyst of formula V or VI [Rh(X)(Y)Lotl>2]lt2 V or [Rh(Y)L,|lt2]+A- VI wherein X is a co-ordinating anionic ligand, such as halogen, a carboxylic acid radical, a 1,3-diketonate, an (unsubstituted or substituted) phenolate, hydroxy, nitrate, nitrite, cyanate, thiocyanate, cyanide, hydrogensulfate; Y is a chiral atropisomeric diphosphine ligand of formula VII or VIII; 201 wherein R4 is aryl or cyclohexyl, R5 and Rg are hydrogen, lower alkyl, lower alkoxy, di-lower alkylamino or protected hydroxymethyl, or R5 and Rg together are a group -CH2-0-CH2-, -CH2-NR8-CH2- or -CH2-C(0Rg)2-CH2-, where m is a number from 3 to 5, Rg is lower alkyl, aryl or benzyl, and Re is lower alkyl, or both substituents Rg together are di- or trimethylene, R7 is methyl, lower alkoxy, di-lower alkylamino or halogen, and n is 0, 1, 2 or 3; vm wherein Rlo and Rn are aryl or cyclohexyl, and Ru is methyl, ethyl, halogen, -OH; NH2, acetylamino, nitro, -SO3H, preferably in 5,5' -position, L is a neutral ligand, and 15 A- is an anion, preferably BF^ .

According to the invention VII and VIII are used in the (R)-form. - 3 Compounds of formula I are valuable intermediates for the preparation of optically active fungicides which are known in the form of their racemates e.g. from DE-A-27,52,096.

It is known from EP-A-32,659 that optically active phenylpropanols can be prepared from the correspondingly unsaturated phenylpropenols by microbiological hydrogenation. It is furthermore known from Chemistry Letters 1007-8 (1985) and DE-A-30,18,388 that substituted allyl alcohols can be hydrogenated in the presence of optically active phosphinerhodium catalysts to give the corresponding optically active saturated alcohols. However, the compounds described therein are structurally different from those of the present invention; in addition, the optical yields and the amount of catalyst required are unsatisfactory for industrial use.

The process according to the invention allows the preparation of optically active phenylpropanols in high chemical and optical yields using small amounts of catalyst and with short reaction times.

Within the scope of this invention, halogen means fluoro, chloro, bromo or iodo.

Preferred ligands are those of formula VII. Of these in turn those ligands are preferred wherein R* is unsubs tituted or methylsubstituted phenyl, R5 and R6 are identical and are lower alkyl or alkoxy or together are the group -CH2-O-CH2-, n is 0 or 1, and R7 is methyl, fluoro or di-lower alkylamino. If n is 1, the substituent R7 is preferably in meta-position to the phosphorus atom.

Illustrative examples of especially preferred ligands of formula VII are: R-(6,6' -dimethyl-2,2' -biphenylylene)bis(diphenylphosphine) ; R-(6,6' -dimethyl-2,2' -biphenylylene)bis(di-p-tolylphosphine) ; R- (6,6' -dimethoxy-2,2' -biphenylylene)bis(diphenylphosphine) ; R-(6,6' -dimethoxy-2,2'-biphenylylene)bis(di-p-tolylphosphine). - 4 The ligands of formulae VII and VIII are known compounds or can be prepared in a manner which is known per se.

Within the scope of the present invention, the term lower alkyl by itself or as part of a substituent such as lower alkoxy or di-lower alkylamino means straight-chain or branched alkyl groups of 1 to 9 carbon atoms, such as, for example, methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, and also pentyl, hexyl, heptyl, octyl, nonyl and their isomers. The definition Cj^-C^alkyl radicals covers the first eight of these meanings.

C3-C7cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl.

The Ci-Chalky 1 radicals may also be straight-chain or branched.

The term aryl in the context of the compounds of formulae VII and VIII means within the scope of the present invention unsubstituted phenyl and phenyl which has lower alkyl or lower alkoxy groups, preferably methyl or methoxy groups, or also di-lower alkylamino, preferably dimethylamino groups, in ortho-, para- and/or meta-position.

The term lower alkoxy means groups in which the alkyl moiety is as previously defined. The symbol -H||| means that the radical in question is below the plane of the molecule.

Within the scope of the present invention, the term neutral ligand means a readily exchangeable ligand such as olefins, e.g. ethylene, propylene, cyclooctene, 1,5-hexadiene, norbomadiene, 1,5-cyclooctadiene and the like, nitriles such as acetonitrile or benzonitrile, or also the solvent employed etc. This ligand can he replaced in the course of the hydrogenation. If more than one such ligand is present, they may also differ from one another.

Surprisingly, it has now been found that, compared with the known catalysts for such purposes, the rhodium diphosphine complexes of formulae V and VI are appreciably more active and enantioselective which means in particular that through their use substantially smaller amounts of catalyst can be used, that shorter reaction times are possible, and that optical yields (e.e.) of more than 95 Z can be obtained.

The asymmetrical hydrogenations can be carried out in suitable organic solvents which are inert under the reaction conditions. Such solvents are in particular aromatic hydrocarbons such as benzene or toluene, cyclic ethers such as tetrahydrofuran or dioxane, esters, such as ethyl acetate, or also mixtures thereof, and the like. The ratio of rhodium to ligand Y is conveniently between about 0.05 and about 5 mol, preferably between about 0.5 and about 2 mol, of rhodium per mole of ligand. The ratio of rhodium to the radical X is between about 0.01 and about 20, preferably between about 0.5 and about 10, mol of rhodium per mole of radical X. The molar ratio of rhodium in the complexes of formulae V and VI to the compounds of formula II to be hydrogenated is conveniently between about 0.001 and about 5 mol Z, preferably between about 0.002 and about 0.02 mol Z.

The asymmetrical hydrogenations using complexes of formulae V or VI may conveniently be carried out at temperatures from about 20°C to about 140’C, preferably from about 80°C to about 120"C. It is convenient to carry out these hydrogenations under pressure, in particular under a pressure of about 1 to 100 bar, preferably from 2 to 60 bar.

The compounds of formula I are intermediates.

These are used in particular for preparing the S-isomers of the compounds of formula wherein NR is N-piperidyl, 3,5-cis-dimethylpiperidyl, 3-me thy lpiper idyl or 2,6-dimethyl-4-morpholinyl, into which they can be converted in a manner which is known per se, for example in accordance with - 6 6 in analogy wijfch SP-A2-8686 e.g. 120’C (I'D Thus, for example, conventional replacement of the hydroxyl group of I by chlorine, for example with SOC12, gives initially a compound Cl III which can be converted into IV by treatment with an amine of formula HNR.

The reaction is conveniently carried out at elevated temperature, and 10 the amine is preferably used in excess, as it acts both as reagent and solvent.

The route described in EP-A2 8686 is also possible, i.e. alkylation of the phenyl radical.

The hydroxyl group in I must again initially be activated such that a ' 15 nucleophilic substitution by an amine becomes possible. The customary groups are accordingly halides (Cl, Br, I), but sulfonates (e.g. tosylate, mesylate) are also useful. Ί Examples Abbreviations (R)-BIPHEMP (R)-pTolBINAP (R)-pTolMeOBIPHEP (R)-BIPHOMP AcOEt THF EtOH (R)-(6,6' - dimethyl2,2'-biphenylylenebls(diphenylphosphine)) (((R)-1,1' -binaphthyl)2,2'-ylene]bis(di-p-tolylphosphine) [(R)-6,6' -dimethoxy2,2'-biphenylylene]bis(dip - tolylphosphine) [(R)-5,7-dihydro-dibenz[c,e]oxepine1,11-diyl ]bis (diphenylphosphine) ethyl acetate tetrahydro furan ethanol Determination of the e.e. values To determine the e.e. values the products are converted in methylene chloride with (R)- or (S)-6-methoxy-2,5,7,8-tetramethylchromane2-carboxylic acid, dicyclohexylcarbodiimide and 4-dimethylaminopyridine into the diastereomeric esters and analysed by gas chromatography.

Example 1: In a glove box (02 content < 1 ppm), 39.2 mg (0.049 mmol) of tetrabutylammonium hydroxide 30 hydrate, 7.5 mg (0.049 mmol) of 2,6-dihydroxybenzoic acid, 19.9 mg (0.049 mmol) of bis(l,5-cyclooctadiene)rhodium(I) tetrafluoroborate and 33.2 mg (0.049 mmol) of (R)-pTolBINAP are suspended in 50 ml of toluene in a ml graduated flask. The suspension is then stirred for 1.5 hours at 22 °C. A clear, orange-red catalyst solution forms.

Example 2: In a glove box (02 content < 1 ppm) , a 500 ml autoclave is charged with 5.0 g (24.5 mmol) of (E)-dehydroliliol, 145 ml of toluene and 5 ml of the catalyst solution prepared according to Example 1. The hydrogenation is carried out at.lOO’C under a constant hydrogen pressure of 60 bar and with intensive stirring. The conversion'is > 99 X after 6 hours. The pale yellow hydrogenation solution is flushed from the autoclave and evaporated on a rotary evaporator at 60°C/17 mbar. The residue is distilled at 140*0/0.01 mbar, giving 5.0 g (99.0 Z) of (S)-liliol as a, colourless oil in an enantiomeric purity of 92.4 Z e.e. [«law " -46.0° (EtOH, c - 1 Z).

Example 2a-: In analogy to the general procedure described in Example 1, a catalyst solution is prepared and the hydrogenation of (E)-dehydroliliol is carried out as described in Example 2. The results are summarized in Table 1: Table 1: Examples 2a-2i Ho 2 [Hh(X)(Y)(CQD)l X Y s/c Solvant C X P bac I •c Conversion affcss 22 h Liliol ·.·. Z a CH3aCH2COO «Ϊ-Ρ- TolBDUP 5000 tolnHM 3.7 00 100 90.2 93.7 (S) b ci2cacoo (· 5000 M 3.7 so 100 99.¼ 95.3 (S) c CgBsCOO M 5000 M 3.7 60 100 100.0 94.6 (S) d CeCLsOCH2COO M 5000 M 3.7 60 100 80.7 94.9 (S) β (CH3)3CCOO M 5000 W 3.7 60 100 09.7 88.1 (S) £ CeHsO n 5000 M 3.7 60 100 100.0 92.8 (S) 8 CgFjjO M 5000 M 3.7 60 100 04.2 91.7 (S) h CH3C0CH2C0CH3 m 5000 M 3.7 60 100 98.9 91.6 (S) i cf3cocb2ckf3 M 5000 m 3.7 00 100 96.2 93.7 (S) Example 3; In a glove box (02 content < 1 ppm), a catalyst solution is prepared by dissolving 15.9 mg (0.024 mmol) of di-p-trifluoroacetatebis(1,5-cyclooctadiene)dirhodium and 33.2 mg (0.049 mmol) of (R)-p-TolBINAP in 50 ml of toluene in a 50 ml graduated flask. 5 ml of this catalyst solution are added to a solution of 5.0 g (24.47 mmol) of (E)-dehydroliliol in 145 ml of toluene in a 500 ml autoclave. The hydrogenation is carried out at 100C under a constant pressure of 60 bar and with intensive stirring. The conversion is 100 Z after hours. The pale yellow hydrogenation solution is worked up as described in Example 2, giving (S)-liliol in an enantiomeric purity of 91.0 Z e.e.

Evarnnle 4: In a glove box (O2 content < 1 ppm), a catalyst solution is prepared by dissolving 19.9 mg (0.0493 mmol) of bis(l,5-cyclooctadiene)rhodium(I) tetrafluoroborate, 33.2 mg (0.0493 mmol) of (R)-p-TolBINAP and 14.9 mg (0.0493 mmol) of tetrabutylammonium nitrate in 100 ml of toluene in a 100 ml graduated flask. 10 ml of this catalyst solution are added to a solution of 5.0 g ¢24.47 mmol) of (E)-dehydroliliol in 140 ml of toluene in a 500 ml autoclave. The hydrogenation is carried out at 100"C under a constant pressure of 60 bar and with intensive stirring. The conversion is 99.8 Z after 17 hours. The pale yellow hydrogenation solution is worked up as described in Example 2, giving (S)-liliol in an enantiomeric purity of 94.6 Z e.e. [3§§ - -47.6* (EtOH, c - 1 Z) .

Example 4a-: In analogy to the general procedure described in Example 4, a catalyst solution is prepared and the hydrogenation of (E)-dehydroliliol is carried out. The results are an—rtxed in Table 2: Table 2: Examples 4a-41 Ho 4 [Bh(X)(Y)(COO)l X T s/c Solvent c Z P bar T •c Convecaion after 22 h (2) Liliol e.e. 2 a CH3COO (R)-p- IolBINAP 10000 toluene 11.0 60 100 36.2 82.6 (S) b F M 10000 n 11.0 60 100 S3 83.2 (S) c Bz W 10000 H 11.0 60 100 86.8 86.2 (S) d I « 10000 M. 11.0 60 100 87.8 8S.8 CS) • 1103 n 3000 N 3.7 60 100 88.8 84.6 (S) £ ho2 H sooo - 3.7 60 100 88.7 81.7 (S) S OH 1« 3000 n 3.7 60 100 88.3 88.7 (S) Ho 4 (Hh(X)(Y)(C0D)] X Y s/c Solvent c Z P bar T •c Coaversion after 22 b Liliol ·.·. Z h CH M 5000 w 3.7 so 100 87.8 85.5 (8) i sen n 5000 w 3.7 so 100 84.8 85.4 (S) J OCH M 5000 M 3.7 so 100 88.5 83.7 (8) k sso4 W 5000 « 3.7 so 100 48.8 88.0 (S) 1 H2K>4 M 5000 M 3.7 so 100 88.0 88.2 (8) Exaipple 5; in a glove box (02 content < 1 ppm) , a catalyst solution is prepared by dissolving 24.3 mg (0.0493 mmol) of dichlorobis(1,5-cyclooctadiene)dirhodium and 66.9 mg (0.0986 mmol) of (R)-p-TolBINAP in 50 ml of toluene in a 50 ml graduated flask. 2 ml of this catalyst solution are added to a solution of 16.1 g (78.85 mmol) of (E)-dehydroliliol in 148 ml of toluene in a 500 ml autoclave. The hydrogenation is carried out at 100°C under a constant pressure of bar and with intensive stirring. The conversion is 99.6 Z after 21 hours. The pale yellow hydrogenation solution is worked up as described in Example 2, giving (S)-liliol in an enantiomeric purity of 95.1 Z e.e. - -47.0’ (EtOH, c - 1 Z) .

Exampl e 5a- : The catalyst solution is prepared in analogy to the general procedure described in Example 5, and the hydrogenation is carried out under the conditions shown in Table 3. The hydrogenation solution is worked up as described in Example 2. The results are summarized in Table 3: - 11 Table 3 Examples 5a-5j No S [Rh(X)(T)(COO>] X T S/C Solvant c Z P bar T •c Conversion after 22 h (Z) Liliol e.e. Z a Cl - BIFBEMP 200 toluene 11 60 20 100.0 93.0 (S) b Cl M 200 ·» 11 60 60 100.0 93.7 (S) . c Cl (R)" p-TolBINAF 20000 11 60 120 00.0 01.0 (S) d Cl w 20000 ·» 11 30 100 00.5 06.4 (S) • Cl n 20000 »1 11 5 100 25.6 04.6 (S) £ Cl N 20000 *1 30 60 100 S3.0 00.0 (S) β Cl - pTolMe- CBXEBEP 20000 11 60 100 100 04.2 (S) h Cl 00- BIPHDMP 20000 N 11 60 100 100 02.6 (S) i Cl oo- BIBBEMP 200 XBF 11 60 60 100 03.7 (S) J Cl (R)-p- TolBIHAP 10000 AeQEt 11 60 100 OS 05.2 (S) Example 6: In a glove box (02 content < 1 ppm) , a catalyst solution is prepared by dissolving 32.0 mg (0.079 mmol) of bis(l,5-cyclooctadiene)rhodium(I) tetrafluoroborate and 53.5 mg (0.079 mmol) of (R)-p-TolBINAP in 50 ml of toluene in a 50 ml graduated flask. 5 ml of this catalyst solution are added to a solution of 16.1 g (78.85 mmol) of (E)-dehydroliliol in 145 ml of toluene in a 500 ml autoclave. The hydrogenation is carried out at 100°C uxider a constant pressure of 60 bar and with intensive stirring. The conversion is 99.8 Z after 22 hours. The pale yellow.hydrogenation solution is worked up as described in Example 2, giving (S)-liliol in an enantiomeric purity of 95.4 Z e.e. [a]3g§ - -47.5°C (EtOH, c = 1 %).

Example 7: In a glove box (02 content < 1 ppm) , a catalyst solution is prepared by dissolving 9.15 mg (0.0186 mmol) of dichlorobis(l,5-cyclooccadiene)dirhodium and 25.18 mg (0.0371 mmol) of (R) -p-TolBINAP in 50 ml of toluene. This catalyst solution is added to a solution of 5.5 g (37.1 mmol) of (E)-2-methyl-3-phenyl-2-propen-l-ol in 35 ml of toluene in a 500 ml autoclave. The hydrogenation is carried out at 100**C under a constant pressure of 60 bar and with intensive stirring. The conversion is 100 Z after 22 hours. The pale yellow hydrogenation solution is worked up as described in Example 2, giving (S) -2-methyl-3-phenylpropan-1-ol in an enantiomeric purity of 89.1 Z e.e., [a]3g§ - -57.9' (EtOH, c - 1 Z).

Ex.amp.l9-8: (a) (S)-1-tert-Butyl-4-[3-chloro-2-methylpropyl]benzene .9 g (0.15 mol) of (S)-3-(p-tert-butylphenyl)-2-methyl-l-propanol (S-liliol) are charged to the rector and, with stirring, 20.2 g (0.17 mol) of thionyl chloride are added at 120°C over 5 hours. The gaseous products which form (S02, HCl) are destroyed by passing them into a wash tower filled with 10 Z sodium hydroxide solution. When the dropwise addition is complete, the reaction mixture is stirred for another half hour at 120°C and then cooled. The crude product is distilled under a high vacuum (b.p. about 80°C), giving (a) as a colourless oil. (b) (S)-2-Methyl-3-phenylpropyl chloride In analogy to the general procedure described in (a), 22.5 g (0.15 mol) of (S)-2-methyl-.3-phenylpropanol are reacted with 20.2 g (0.17 mol) of thionyl chloride, and the crude product is distilled under a water-jet vacuum (18 torr) to give (b) (b.p. 110-112°C); colourless oil.

Product (b) can then be converted in known manner into product (a) by a Friedel-Crafts alkylation, e.g. with isobutylene in cone, sulfuric acid.

The reaction of (a) with piperidine gives the novel compound (S)-fenpropidine. - 13 The reaction of (a) with cis-2,6-dime thy lmorpholine gives the known (S)- fenpropimorph.

(S)-l-f3-(p-tert - Butylphenyl) - 2 -me thylnronvl 1 piperidine ( ( S )fenoropidine1 With intensive stirring, 27 g (0.12 mol) of (S)-l-tert-butyl4-[3-chloro-2-methylpropyl]benzene in 70 ml (0.708 mol) of piperidine are heated for 16 hours to reflux temperature. Then a further 30 ml (0.303 mol) of piperidine are poured in. The reaction course is monitored by gas chromatography. The reaction mixture is stirred for a further hour at reflux temperature and allowed to cool. The reaction mixture is poured into 350 ml of sodium hydroxide solution and extracted with altogether 600 ml of n-hexane in 3 portions. The organic phases are combined, dried over anhydrous sodium sulfate and concentrated. The residue is chromatographed on 700 g of silica gel 60 (MERCK, granular size, 0.040-0.063 mm) with ethyl acetate/n-hexane (1:1). The pure fractions are combined and distilled under a high vacuum (b.p. about 140’C), giving a colourless oil. Optical rotation (c-1 Z, C2Hs0H 96 Z): 365 nm + 11.1’ 436 nm + 9.0’ 546 nm + 6.0’ 578 pm + 5.5’ 589 pm + 5.4’ The epaptiomeric purity cap be determined ip the NMR spectrum (CDC13) by additiop of the chiral solveut* (R)-(-)-2,2,2-trifluoro-l-(9-anthryl) ethanol (TAE) . The shifts in the signals of the methyl group at the centre of chirality depends on the relative amount of TAE in the solution. No indication of racemization is found.

The reaction of (a) with cis-3,5-dimethylpiperidine leads to the novel compound cis-l-[(S)-3-(p-tert-hutylphenyl)-2-methylpropyl]30 3,5-dimethylpiperidine, colourless oil. Optical rotation in 1 Z ethanol: [a]s«6 " +6.1’.

The reaction of (a) with racemic 3-methylpiperidine leads to the novel fungicide (RS) -1- [ (S) -3-p-tert-butylphenyl)-2-methylpropyl] - 14 3-methylpiperidine (epimer ratio 1:1); colourless oil.

Example 9: Starting from (S)-2-methyl-3-phenylpropan-l-ol prepared in Example 7, the following novel fungicidally active compounds are prepared in accordance with the above reaction scheme: (S)-l-[3-(p-tert-amylphenyl)-2-methylpropyl]piperidine, as a colourless oil; cis-1- [ (S) -3- (p-tert-amylphenyl) -2-methylpropyl] -3,5-dime thy lpiperidine, as a colourless oil; (RS) -1- [ (S) -3- (p-tert-amylphenyl) -2-methylpropyl] -3-me thy lpiperidine, as 10 a colourless oil.

Claims (5)

1. A process for the preparation of a compound of formula wherein R x is hydrogen or a group Z, Z is the group CH3 -+-¾ , R z is methyl, ethyl or chloromethyl and Rg is C x - Chalky 1, or R2 and R 3 , together with the carbon atom to which they are jointly attached, are C 3 -C 7 cycloalkyl, by asymmetrically hydrogenating a compound of formula IQ in the E form, wherein R x is as defined above, which comprises carrying out the hydrogenation in the presence of a rhodium catalyst of formula V or VI iRhWOOlD.i.ah.a V or [Rh(Y)Lo, 1(2 ] + A- VI 15 wherein X is a co-ordinating anionic ligand, such as halogen, a carboxylic acid radical, a 1,3-diketonate, an (unsubstituted or substituted) phenolate, hydroxy, nitrate, nitrite, cyanate, thiocyanate, cyanide, hydrogensulfate; 20 Y is a chiral atropisomeric diphosphine ligand of formula VII or VIII; wherein R« is aryl or cyclohexyl, Rs and Rg are hydrogen, lower alkyl, lower alkoxy, di-lower alkylamino or protected hydroxymethyl, or R s and Re together are a group 5 (-CH 2 )-) b , -CH 2 -O-CH 2 -, -CH 2 -NR e -CH 2 - or -CH 2 -C(ORg) 2 -CH 2 -, where m is a number from 3 to 5, Rg is lower alkyl, aryl or benzyl, and Rg is lower allyl, or both substituents Rg together are di- or trimethylene, R 7 is methyl, lower alkoxy, di-lower ally lamino or halogen, and n is 0, 1, 2 or 3; wherein R 10 and R 1X are aryl or cyclohexyl, and R^ is methyl, ethyl, halogen, -OH; NH 2 , acetylamino, nitro, -SO 3 H, preferably in 5,5'-position, L is a neutral ligand, and 15 A - is an anion, preferably BF^ .

2. A process according to claim 1, wherein the asymmetrical hydrogenation is carried out at a temperature from 20°C to 140“C, preferably from 80“C to 120®C.

3. A process according to claim 1, wherein the diphosphine ligand of 17 formula VII is R-(6,6' -dimethyl-2,2* -biphenylene)bis(diphenylphosphine) ; j R-(6,6'-dimethyl-2,2' -biphenylene)bis(di-p-tolylphosphine) ; R- (6,6 '-dimethoxy-2,2'-biphenylene)bis(diphenylphosphine ); or 5 R-(6,6'-dimethoxy-2,2'-biphenylene)bis(di-p-tolylphosphine).

4. A process according to claim 1 for the preparation of a conpound of formula (I) given and defined therein, substantially as hereinbefore described and exenplified.

5. A conpound of formula (I) given and defined in claim 1, whenever 10 prepared by a process claimed in a preceding claim.