Process for the hydrogenation of ethylenically unsaturated organic compounds and ruthenium catalysts for carrying out said process
This is a national-phase application filed under 35 USC 371 of PCT application FR 91/01077, filed Dec. 27, 1991. 
     FIELD OF THE INVENTION 
     The invention relates to the hydrogenation of ethylenically unsaturated organic compounds having at least one aliphatic C═C double bond. It comprises a process which makes it possible advantageously to carry out such an operation in a homogeneous medium, in the presence of a catalyst formed by a ruthenium complex. It further relates to a catalyst system of Ru with a phosphorus ligand which is capable of effecting asymmetric hydrogenation with an excellent yield and an enantiomeric excess. 
     PRIOR ART 
     Neutral ruthenium complexes of the structure bis(2-methylallyl)bis(phosphite)ruthenium are known to have been described in the article by M. COOKE et al., J. Chem. Soc. (A), pages 16-20 (1971). More precisely, these are complexes of the formula ##STR1## where compound (C1): L=(MeO) 3  P 
     compound (C2): L=(EtO) 3  P 
     compound (C3): L=MeC(CH 2  O) 3  P 
     compound (C4): L=EtC(CH 2  O) 3  P 
     compound (C5): L=Me 2  PCH 2  CH 2  PMe 2   
     It so happens that said article by M. COOKE et al. neither describes nor suggests the use of these five compounds in the field of the catalytic hydrogenation of ethylenically unsaturated compounds. 
     Furthermore, it is known that ionic ruthenium complexes have been recommended in the past for the catalytic hydrogenation of olefins. In this connection, see on the one hand EP-A-0 366 390, which recommends for this purpose the use of complexes of the formula 
     
         [RuX.sub.l (L).sub.m (R-BINAP)]Y.sub.n                     (C 6) 
    
     in which 
     BINAP is a 2,2&#39;-bis(diphenylphosphino)-1,1&#39;-binaphthyl radical and R is H or CH 3  in the 4-position of each phenyl ring of the bis(diphenylphosphino) fragment, 
     X is F, Cl, Br or I, 
     L is especially benzene, p-cymene or acetonitrile, 
     Y is a halogen atom, ClO 4 , PF 6 , BF 4  or BPh 4 , and 
     when L is other than acetonitrile, l=1, m=1 and n=1, and 
     when L is acetonitrile, if l=1 then m=2 and n=1, and if l=0 then m=4 and n=2, 
     and on the other hand EP-A-0 272 787, which recommends the use of the complexes of the formula 
     
         Ru.sub.x H.sub.y Cl.sub.z (R.sup.4 ---BINAP).sub.2 (S).sub.p(C 7) 
    
     in which 
     BINAP is as defined above in formula C6, 
     R 4  is defined in the same way as R above in formula C6, 
     S is a tertiary amine, and 
     when y=0 then x=2, z=4 and p=1, and 
     when y=1 then x=1, z=1 and p=0. 
     Furthermore, the article by T. OHTA et al., J. Org. Chem., 52, pages 3174-3176 (1987), has disclosed neutral ruthenium catalysts for the hydrogenation of carboxylic acids ethylenically unsaturated in the alpha,beta or beta,gamma-positions. These catalysts, which have the S or R configuration, are represented by the formulae ##STR2## 
     OBJECT OF THE INVENTION 
     There is a need for a novel technical solution for the catalytic hydrogenation of ethylenically unsaturated organic compounds which is different from the technical solutions recommended by the documents EP-A-0 366 390 and EP-A-0 272 787 and the article by T. OHTA et al. cited above. 
     The novel technical solution which has been researched is based on the use of neutral ruthenium complexes which are structurally analogous to the compound C5 according to the article by M. COOKE et al. 
     SUBJECT OF THE INVENTION 
     According to a first feature of the invention, a novel technical solution is recommended for the catalytic hydrogenation of ethylenically unsaturated organic compounds containing at least one aliphatic C═C double bond. In fact, it has so far never been contemplated to use a compound carrying allylic ligands as a catalyst. The references indicated above, and many others, refer to various complexes of Ru with phosphines which are used for the hydrogenation of C═C bonds in a homogeneous medium, but none of the catalysts contains an allylic ligand. 
     In contrast to this state of affairs, the present invention results from the surprising finding that phosphine complexes of Ru in which Ru carries two allylic ligands can catalyze the asymmetric hydrogenation of C═C bonds very effectively. 
     Thus the present invention comprises a process for the hydrogenation of ethylenically unsaturated organic compounds in a homogeneous medium with a (diphosphino)ruthenium complex as a catalyst, wherein, in this catalyst, a ruthenium atom carries two ligands formed by allylic groups. 
     According to a second feature of the invention, the compounds of formula (1) below, in which Q is other than CH 2  CH 2  when R 1  ═R 2  ═R 3  ═R 4  ═methyl, are recommended as novel industrial products useful in the field of the catalytic hydrogenation of olefins and of ethylenically unsaturated organic compounds in general. 
     DETAILED DESCRIPTION OF THE INVENTION 
     The catalyst used according to the invention for the catalytic hydrogenation of ethylenically unsaturated compounds, and belonging to the group consisting of diallylic compounds of (diphosphino)ruthenium, can be represented by the schematic formula ##STR3## in which al is an allylic group, 
     Q is a hydrocarbon bridge containing at least two catenary carbon atoms and capable of containing one to four catenary heteroatoms selected from O, S, N and Si, and 
     R.sup. to R 4  can be identical or different and are each a C 1  --C 18  -alkyl, C 5  --C 7  -cycloalkyl or C 6  --C 4  -aryl group. 
     The above-mentioned allylic groups al here include all allyl groups, the simplest and most economic being more precisely the allyl group itself of the formula CH 2  CH═CH 2  and the methallyl group of the formula CH 2  C(CH 3 )═CH 2 . Thus the allylic group al will advantageously be selected from the group consisting of allyl and methallyl groups. When they are bonded to the ruthenium atom, said allyl and methallyl groups have the following al 2  Ru configurations: ##STR4## in which the allylic C═C double bond is delocalized. 
     The bridge Q is a chain comprising from 2 to 10 catenary atoms, it being possible for one or more fragments of this chain to be included in at least one ring. When a catenary nitrogen atom is present in said bridge Q, this nitrogen atom will be ternary, for example: --N(CH 3 )--, --N(i--C 3  H 7 )--, --N(t--C 4  H 9 )--, --N(C 6  H 5 )-- or --N(CH 2  C 6  H 5 )--. When a catenary silicon atom is present in said bridge Q, this silicon atom will be quaternary, for example: --Si(CH 3 ) 2  --, --Si(CH 2  CH 3 ) 2  --, --Si(C 6  H 5 ) 2  -- or --Si(CH 2  C 6  H 5 )--. 
     Preferably, the bridge Q will contain from 2 to 4 catenary atoms and will advantageously have one of the following structures: ##STR5## in which the dotted lines each denote a substituent other than H or else a C═C double bond on two vicinal carbon atoms included in an aryl ring; thus, when the structure R 1  R 2  P--Q--PR 3  R 4  is the group (+)-BINAP or (-)-BINAP, the above structure (k) of the bridge Q can be ##STR6## 
     As indicated above, the groups R 1 , R 2 , R 3  and R 4 , which are identical or different, are each a C 1  -C 8  -alkyl group (especially methyl, ethyl, isopropyl, propyl, butyl, s-butyl, i-butyl, t-butyl, 2,2-dimethylpropyl or 1,1,3,3-tetramethylbutyl), a C 5  -C 7  -cycloalkyl group (especially cyclopentyl or, preferably, cyclohexyl) or a C 6  -C 12  -aryl group (especially phenyl, tolyl, xylyl, p-methoxyphenyl, p-ethoxyphenyl, p-(t-butoxy)phenyl or naphthyl). 
     Preferably, R 1 , R 2 , R 3  and R 4 , which are identical or different, will each be a cyclohexyl group, a phenyl group, a phenyl group substituted in the para-position by a C 1  -C 4  -alkyl group, a phenyl group substituted in the para-position by a C 1  -C 4  -alkoxy group, or a 2-naphthyl group. 
     Formula (1) as defined above encompasses the compound C5 described by M. COOKE et al. (Q═CH 2  CH 2  ; R 1  ═R 2  ═R 3  ═R 4  ═CH 3 ). 
     With the exception of said compound C5, all the other catalysts of formula (1) are novel. 
     Apart from the chirality due to the bidentate groups, it is possible to introduce chirality by appropriate choice of the part P--Q--P of the molecule; in particular, it can be present on the phosphorus, in which case formula (1) has the configuration ##STR7## 
     The preparation of the complexes of al 2  Ru is known per se: it is described in the article by M. COOKE et al. cited above and in French patent application no. 89 11 159 of 23rd Aug. 1989 (published as FR-A-2 651 152 of 1st Mar. 1991). 
     Here attention is drawn only to the fact that a practical procedure comprises reacting an Ru salt, for example RuCl 3 .3H 2  O, with a cycladiene, in particular cyclooctadiene. The resulting complex is reacted with an organomagnesium compound of the formula XMg-al (in which al is the allyl or methallyl group, as indicated above, and X is F, Cl, Br or I) to form a complex cyclooctadiene-Ru(al 2 ). The latter is then heated, in general at about 50° to 70° C. for several hours in an appropriate solvent, with a diphosphine ##STR8## to form the complex (1) or (2). 
     This process will advantageously be carried out with an organomagnesium compound XMg-al in which X will be Cl and al will be the methallyl group [i.e. CH 2  ═C--(CH 3 )CH 2  MgCl]. 
     The diphosphines which can be used are the various compounds known in the art by abbreviations such as &#34;DIOP&#34;, &#34;CHIRAPHOS&#34;, &#34;NORPHOS&#34;, &#34;BNPE&#34;, &#34;BINAP&#34;, &#34;DIPAMP&#34;, &#34;BDPP&#34; etc., which replace the cycloalkadiene to form the asymmetric catalyst. 
     As such names are used in the Examples which follow, their compositions are specified below by means of formulae: ##STR9## 
     These phosphines listed above are mentioned here without implying a limitation. 
     By virtue of the mild phosphination conditions, indicated above, which are applied in the preparation of the novel catalysts, various tertiary mono- or di-phosphines carrying chirality on the P atom can be obtained without the ligands of the complex undergoing racemization, which becomes substantial above 80° C. 
     In contrast to the technique of the prior art, which practically only used the rather expensive diphosphine &#34;BINAP&#34; to successfully hydrogenate C═C double bonds (MASATO KITAMURA, J. Org. Chem., 1987, 52, pages 3176-3178), the present invention makes it possible to change ligands easily: this particularly concerns ligands carrying chirality on the phosphorus. As shown in the Examples, the invention permits the economic asymmetric hydrogenation of olefinic bonds with Ru catalysts having different ligands. 
     The invention is illustrated by the following non-limiting Examples, of the hydrogenation of the olefinic double bond, ##STR10## in carboxylic acids. Thus, according to the invention, an olefin can be reduced when it carries one or more functional groups. 
     According to the present invention, the hydrogenation is generally carried out in a solution containing 0.1 to 3 mol of unsaturated compound to be treated per liter of an appropriate solvent, which, depending on the particular case, can be for example an anhydrous alcohol, especially methanol, ethanol, propanol, etc., or a hydrocarbon such as benzene, toluene, xylene, pentane, hexane, heptane or the like, or optionally a mixture of such solvents. An amount of 0.1 to 5 mol % of catalyst, based on the unsaturated compound, is dissolved in the solvent. Proportions of about 0.5 to 2 mol % of catalyst are generally suitable. 
     In the Examples which follow, the hydrogenation procedure was carried out as indicated below. 1 mmol of olefinic substrate to be hydrogenated and 3 ml of degassed dry methanol are introduced into a reactor containing an argon atmosphere. 1 mol % of catalyst, consisting of a phosphine complex of Ru, is added. The argon atmosphere is then replaced with hydrogen and a hydrogen pressure with a value of 1 to 100 bar is established. The mixture is stirred for 24 to 64 hours at 20° C. Experience has moreover shown that the preferred temperatures for such hydrogenations range from 0° to 50° C. 
     After evaporation of the solvent, the degree of conversion of the olefinic product to the corresponding saturated compound is determined by NMR. 
     The Examples whose results are given below correspond to the use of the catalysts according to the invention, containing two methallyl groups bonded to the Ru atom. 
    
    
     EXAMPLES 1 to 7 
     2-Methylbut-2-enoic acid: ##STR11## is hydrogenated by the procedure stated above to give 2-methylbutanoic acid: ##STR12## at 20° C., under different pressures and for variable times. 
     The catalyst DIOP-Ru(methallyl) 2  had the following characteristics: 
       1  H NMR (250 MHz, C 6  D 6 ): 1.0 (m, 2H); 1.3 (s, 6H); 1.32 (q, J=14.5 Hz, 4H); 2.04 (s, 6H); 2.55 (m, 2H); 2.79 (dd, J 1  =8.5 Hz, J 2  =13 Hz, 6H); 3.25 (t, J=13 Hz, 6H); 4.15 (m, 2H); 6.8-8.0 (m, 20H, aromatic).  13  C NMR (62 MHz, C 6  D 6 ): 25.77; 27.2; 31.5 (m); 42.5; 48.31 (m); 78.8; 95.7; 107.9; 127-140 (aromatic).  31  P NMR (100 MHz, C 6  D 6 ): 36 (ref. 75% H 3  PO 4 ). IR (Nujol): 1595, 1240 cm -1 . α D   25  =+202° (c=0.43, toluene). Melting point: 204° C. (decomposition). 
     The characteristics of the catalyst CHIRAPHOS-Ru(methallyl) 2  were as follows: 
       1  H NMR (250 MHz, C 6  D 6 ): 1.06 (d, J=6.5 Hz, 2H); 1.12 (d, J=6.5 Hz, 2H); 1.24 (q, J=2.5 Hz, 6H); 1.61 (d, J=2.5 Hz, 2H); 1.74 (d, J=2.5 Hz, 2H); 2.15 (J, 6H); 6.8-8.0 (m, 20H, aromatic). IR (Nujol): 1580, 1085, 1015, 760, 720 cm -1 . α D   25  =+60° (c=0.2, toluene). Melting point: 183° C. (decomposition). (See Table 1 below.) 
     EXAMPLE 8 
     Hydrogenation of 2-methylhex-2-enoic acid of the formula ##STR13## to 2-methylhexanoic acid of the formula ##STR14## at 20° C., under a hydrogen pressure of 15 bar, for 24 hours. 
     The catalyst CHIRAPHOS-Ru(methallyl) 2  gives an enantiomeric excess (ee) of 17% with a yield of 100%. 
     EXAMPLE 9 
     Hydrogenation of 3-phenyl-2-methylprop-2-enoic acid of the formula ##STR15## to 3-phenyl-2-methylpropanoic acid of the formula ##STR16## 
     The reaction is carried out at 20° C. under a hydrogen pressure of 95 bar for 24 hours. The catalyst CHIRAPHOS-Ru(-)(methallyl) 2  gives the saturated acid with a yield of 70%. 
     EXAMPLE 10 
     Hydrogenation of 2-(6-methoxy-2-naphthyl)prop-2-enoic acid to 2-(6-methoxy-2-naphthyl)propionic acid, which is known in pharmacy as &#34;NAPROXENE&#34; and possesses antiinflammatory properties. 
     The operation takes place at room temperature, under a hydrogen pressure of 30 bar, for 64 hours, in the presence of the complex DIPAMP-Ru(methallyl) 2  as the catalyst and 10% of triethylamine. 
     The reaction ##STR17## gives a yield of 100% and the product has an ee of 55%. 
     The characteristics of the catalyst DIPAMP-Ru-(methallyl) 2  employed are as follows: 
       1  H NMR (250 MHz): 0.25 (d, J=15, 2H); 1.1 (dd, J 1  =15, J 2  =5, 2H); 1.7 (s, 2H); 2.2 (d, J=2 Hz, 2H); 2.31 (s, 6H); 2.92 (s, 6H); 3.4 (m, 2H); 6.5-8.1 (m, 18H). 
       13  C NMR (CDCl 3 ): 26.6; 32.5 (dd, J 1  =J 2  =27 Hz); 42.4 (d, J=25 Hz); 44.3; 54.6; 96.1; 110.6; 120.6; 126-130; 134.6; 142.3; 159.9. Color: yellow. M.p.=183°-185° (decomposition). α D  =-43.5° (c=0.23, toluene). 
     EXAMPLE 11 
     A hydrogenation similar in all respects to that of Example 10 is carried out with the complex DIPAMP-Ru(AcO) 2  as the catalyst. The yield is again 100% but the ee is only 22%, which shows the advantage of the allylic groups in the catalyst of Example 10. 
     It may be advantageous in some cases to use an Ru complex having allylic ligands together with a corresponding complex without allylic groups; the preferred relative proportions are then 10 to 90 parts by weight of the one to 90 to 10 parts of the other. 
     
                                           TABLE I                                 
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 ##STR18##                                                                
                      Pressure                                            
                           Time                                           
                              Yield                                       
                                  ee                                      
Ex. no.                                                                   
    CATALYST          (bar)                                               
                           (h)                                            
                              %   % Configuration                         
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1   DIOPRu(-)(methallyl).sub.2                                            
                      50   24 100 46                                      
                                    R                                     
2   &#34;                 15   &#34;  100 46                                      
                                    R                                     
3   &#34;                 5    &#34;  100 48                                      
                                    R                                     
4   &#34;                 1.5  36 100 51                                      
                                    R                                     
5   CHIRAPHOSRu(-)(methallyl).sub.2                                       
                      15   24 100 30                                      
                                    S                                     
6   NORPHOSRu(+)(methallyl).sub.2                                         
                      1.5  60 100  4                                      
                                    S                                     
7   BINAPRu(+)(methallyl).sub.2                                           
                      15   24 100 87                                      
                                    R                                     
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     EXAMPLE 12 
     Hydrogenation of α-acetamido-2-phenylprop-2-enoic acid of the formula ##STR19## to N-acetylphenylalanine of the formula ##STR20## 
     The reaction is carried out at 20° C. under a hydrogen pressure of 100 bar for 24 hours, the catalyst being DIPAMP-Ru(methallyl) 2 . The N-acetylphenylalanine is obtained with a yield of 70%. 
     EXAMPLES 13 to 21. 
     9 chiral ruthenium complexes of formula (1) according to the invention were prepared from ruthenium chloride trihydrate and cyclooctadiene in accordance with the following reaction mechanisms, where met is the methallyl group. ##STR21## 
     The chiral compounds obtained from different diphosphines according to equation III are shown in Table II below. 
     
                                           TABLE II                                
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LIGAND                             COMPLEX                                
__________________________________________________________________________
Ex. 13                                                                    
     ##STR22##          (-)BDPP (2S, 4S)-2,4- bis(diphenyl- phosphino)pent
                        ane- (S,S) M = 440.50                             
                                   (-)PDPPRu(met).sub.2 M = 649.76        
                                   (Green) Yield = 60%                    
Ex. 14                                                                    
     ##STR23##          (+)DIOP (S, S)O,O-iso- propylidene-2,3- dihydroxy-
                        1,4- bis(diphenyl- phosphino)-butane M            
                                   (+)DIOPRu(met).sub.2 M = 707.80        
                                   (Yellow) Yield = 90%                   
Ex. 15                                                                    
     ##STR24##          (-)DIPAMP (R, R)-1,2-bis- (phenylorthoanisyl-     
                        phosphino)ethane M = 458.48                       
                                   (-)DIPAMP- Ru(met).sub.2 M = 667.74    
                                   (Yellow) Yield = 40%                   
Ex. 16                                                                    
     ##STR25##          (-)CHIRAPHOS (S, S)-2,3-bis- (diphenylphos-       
                        phino)butane M = 426.48                           
                                   (-)CHIRAPHOS- Ru(met).sub.2 M = 635.74 
                                   Yellow) Yield = 55%                    
Ex. 17                                                                    
     ##STR26##          (-)BPPM (2S, 4S)NBOC-4- diphenylphosphino-        
                        2-diphenylphos- phino-2-methyl- pyrrolidine M =   
                        553.63     (-)BPPMRu(met).sub.2 M = 762.88 (Pale  
                                   green) Yield = 67%                     
Ex. 18                                                                    
     ##STR27##          (+)NORPHOS (S, S)-1,2-bis(di- phenylphosphino)-   
                        bicyclo[2.2.1]hept- 4-ene M = 462.61              
                                   (+)NORPHOS- Ru(met).sub.2 M = 671.77   
                                   (Brown) Yield = 71%                    
Ex. 19                                                                    
     ##STR28##          (+)BINAP  (R)-2,2&#39;-bis(di- phenylphosphino)-      
                        1,1&#39;-binaphthyl M = 622.69                        
                                   (+)BINAP- Ru(met).sub.2 M = 831.95     
                                   (Brown) Yield = 32%                    
Ex. 20                                                                    
     ##STR29##          (-)BNPE Bis(naphthyl- phenylphosphino)- ethane M  
                        = 498.54   (-)BNPERu(met).sub.2 M = 606.73        
                                   (Bright yellow) Yield 45%              
Ex. 21                                                                    
     ##STR30##          &#34;BNPPMDS&#34; Bis(naphthylphenyl- phosphinomethano)-  
                        diphenylsilane M = 684.88                         
                                   &#34;BNPPMDS&#34;- Ru(met).sub.2 M = 898.17    
                                   (Brown) Yield = 74%                    
__________________________________________________________________________
 These complexes are kept in a refrigerator under an argon atmosphere.    
 EXAMPLES 22 to 29
 
    
     8 of the chiral ruthenium complexes shown in Table II above (those of Examples 13 to 20) were studied as catalysts in the preparation of tiglic acid by catalytic hydrogenation. 
     This was done by carrying out the reaction of equation IV below using 1% of each chiral complex in methanol, with hydrogen under a pressure of 8.1 bar (8 atmospheres), at 25° C., for 24 h. 
     The results obtained have been collated in Table III below, where met denotes the methallyl group. 
     
                       TABLE III                                                   
______________________________________                                    
 ##STR31##                    (IV)                                        
Experiment  Catalyst        Yield %.sup.(1)                               
______________________________________                                    
22          BDPPRu(met).sub.2                                             
                            100                                           
23          DIOPRu(met).sub.2                                             
                            100                                           
24          DIPAMPRu(met).sub.2                                           
                            100                                           
25          CHIRAPHOSRu(met).sub.2                                        
                            100                                           
26          BPPMRu(met).sub.2                                             
                            100                                           
27          NORPHOSRu(met).sub.2                                          
                            100                                           
28          BINAPRu(met).sub.2                                            
                            100                                           
29          BNPERu(met).sub.2                                             
                            100                                           
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 .sup.(1) Determined by .sup.1 H NMR.                                     
 
    
     For practical reasons, it is preferable according to the invention to use chiral ruthenium complexes of formula (1) in which the group R 1  R 2  P--Q--PR 3  R 4  contains a total of more than 6 carbon atoms, preferably more than 12 carbon atoms and particularly preferably from 24 to 50 carbon atoms.