Process for preparing chiral diphosphines

Abstract

Compounds of formula VII are described: wherein A represents phenyl or naphthyl and Ar 1 and Ar 2 independently represent a saturated or aromatic carbocyclic group. The compounds may be prepared by reducing the nitrile functions of a compound of formula I:

1 . A process for preparing a compound of formula I:  
       
         
           
           
               
               
           
         
       
       in which: 
 A represents phenyl or naphthyl; and  
 Ar 1  and Ar 2  independently represent a saturated aromatic or carbocyclic group;  
 this process comprising the steps consisting in:  
 i) brominating a diol of formula II:  
                     
 in which A is as defined above, using a suitable brominating agent so as to obtain a dibromo compound of formula III:  
                     
 in which A is as defined above;  
 ii) esterifying the compound of formula III obtained in the preceding step by the action of a sulfonic acid or an activated form thereof, so as to obtain the corresponding disulfonate;  
 iii) substituting the two bromine atoms with cyano groups by reacting the disulfonate obtained in the preceding step with a suitable nucleophilic agent so as to obtain the corresponding nitrile;  
 iv) coupling a phosphine of formula VI:  
 XPAr 1 Ar 2    VI  
 in which X represents a hydrogen atom or a halogen atom and Ar 1  and Ar 2  are as defined above, with the nitrile obtained in the preceding step, in the presence of a catalyst based on a transition metal, so as to obtain the expected compound of formula I.  
 
     
     
         2 . The process as claimed in  claim 1 , characterized in that: 
 A represents naphthyl or phenyl, optionally substituted with one or more radicals chosen from (C 1 -C 6 )alkyl and (C 1 -C 6 )alkoxy; and    Ar 1  and Ar 2  independently represent a phenyl group optionally substituted with one or more (C 1 -C 6 )alkyl or (C 1 -C 6 )alkoxy; or a (C 4 -C 8 )cycloalkyl group optionally substituted with one or more (C 1 -C 6 )alkyl groups.    
     
     
         3 . The process as claimed in either of claims  1  and  2 , characterized in that Ar 1  and Ar 2  are independently chosen from phenyl optionally substituted with methyl or tert-butyl; and (C 5 -C 6 )-cycloalkly optionally substituted with methyl or tert-butyl.  
     
     
         4 . The process as claimed in either of claims  1  and  2 , characterized in that Ar 1  and Ar 2  are identical and preferably represent optionally substituted phenyl.  
     
     
         5 . The process as claimed in any one of the preceding claims, characterized in that A represents naphthyl.  
     
     
         6 . The process as claimed in any one of the preceding claims, for the preparation of an optically active compound of formula I from an optically active diol of formula II.  
     
     
         7 . The process as claimed in any one of the preceding claims, characterized in that the bromination is performed, in step (i) by the action of bromine, at a temperature of between −78° C. and −30° C.  
     
     
         8 . The process as claimed in any one of the preceding claims, characterized in that, in step (ii), the esterification is carried out by the action of trifluoromethanesulfonic anhydride in the presence of a base, the base preferably being chosen from pyridine and 4-dimethylaminopyridine.  
     
     
         9 . The process as claimed in any one of the preceding claims, characterized in that the nucleophilic agent used in step (iii) is CuCN.  
     
     
         10 . The process as claimed in any one of the preceding claims, characterized in that, in step (iv), HPAr 1 Ar 2  is reacted with the nitrile in the presence of [bis(diphenylphosphino)ethane]nickel-dichloride and triethylenediamine at a temperature of from 50 to 200° C. and preferably from 80 to 130° C.  
     
     
         11 . The process as claimed in any one of  claims 1  to  9 , characterized in that, in step (iv), a compound of formula XPAr 1 Ar 2  (in which X is a halogen atom), is reacted with the nitrile in the presence of [bis(diphenylphosphino)ethane]nickeldichloride and zinc, at a temperature of between 50 and 200° C. and preferably between 80 and 180° C.  
     
     
         12 . The process as claimed in either of claims  10  and  11 , characterized in that the molar ratio of compound VI to the nitrile is between 2 and 4.  
     
     
         13 . The process as claimed in any one of  claims 10  to  12 , characterized in that the reaction of the compound of formula VI with the nitrile is carried out in N,N-dimethylformamide as solvent.  
     
     
         14 . A process for preparing a compound of formula VII:  
       
         
           
           
               
               
           
         
       
       in which A, Ar 1 and Ar 2  are as defined in  claim 1  or in  claim 2 , characterized in that it comprises the reduction of the nitrile functions of the corresponding compound of formula I as defined in  claim 1  or in  claim 2 , respectively, by the action of a suitable reducing agent.  
     
     
         15 . The process as claimed in  claim 14 , characterized in that the reducing agent is lithium aluminum hydride, the reduction being carried out in a mixture of toluene and tetrahydrofuran as solvent.  
     
     
         16 . The process as claimed in any one of  claims 1  to  13 , also comprising the step consisting in treating the compound of formula I in a basic medium or in an acidic medium so as to obtain the corresponding carboxylic acid of formula:  
       
         
           
           
               
               
           
         
       
       in which A, Ar 1  and Ar 2  are as defined in  claim 1  or  claim 2 .  
     
     
         17 . A compound of formula VII:  
       
         
           
           
               
               
           
         
       
       in which A, Ar 1  and Ar 2  are as defined in any one of  claims 1  to  5 .  
     
     
         18 . Use of a compound of formula I obtained by carrying out the process as claimed in any one of  claims 1  to  13 , as a ligand for preparing a metal complex which is useful in asymmetric catalysis.  
     
     
         19 . The use of a compound of formula VII as claimed in  claim 17 , as a ligand for preparing a metal complex which is useful in asymmetric catalysis.  
     
     
         20 . The use as claimed in  claim 19 , characterized in that said complex is intended to catalyze the asymmetric hydrogenation of ketones.  
     
     
         21 . The use as claimed in any one of  claims 18  to  20 , characterized in that the metal complex is a ruthenium, rhodium or iridium complex.  
     
     
         22 . A compound of formula IV:  
       
         
           
           
               
               
           
         
       
       in which A is as defined in any one of  claims 1  to  5  and P represents a hydrocarbon-based aliphatic group; an aromatic carbocyclic group; or an aliphatic group substituted with an aromatic carbocyclic group.