Novel phosphine ligands

Abstract

The invention is concerned with new phosphine ligands of the formula I wherein R 1 and R 2 are independently of each other alkyl, aryl, cycloalkyl or heteroaryl, said alkyl, aryl, cycloalkyl or heteroaryl may be substituted by alkyl, alkoxy, halogen, hydroxy, amino, mono- or dialkylamino, aryl, —SO 2 —R 7 , —SO 3 − , —CO—NR 8 R 8′ , carboxy, alkoxycarbonyl, trialkylsilyl, diarylalkylsilyl, dialkylarylsilyl or triarylsilyl; R 3 is alkyl, cycloalkyl, aryl or heteroaryl; R 4′ and R 4 signify independently of each other hydrogen, alkyl or optionally substituted aryl; or R 4′ and R 4 together with the C-atom they are attached to form a 3-8-membered carbocyclic ring; dotted line is absent or is present and forms a double bond; R 5 and R 6 are independently of each other hydrogen, alkyl or aryl; or linked together to form a 3-8-membered carbocyclic ring or an aromatic ring; R 7 is alkyl, aryl or NR 8 R 8′ ; and R 8 and R 8′ are independently of each other hydrogen, alkyl or aryl; metal complexes with such ligands as well as the use of such metal complexes as catalysts in asymmetric reactions.

1 . A Transition metal complex of formula II
   M m L n X p A q   II   wherein   M is a transition metal,   L is the diphosphine compound of formula I;   wherein   X is a coordinating anion selected from Cl, Br or I,   m, n and p are each 1,   with the proviso that   a) q is 0, if M is Rh;   or   b) X is acyloxy   m and n are each 1,   p is 2,   and   c) q is 0, if M is Ru;   or   d) X is Cl,   m and n are each 2,   p is 4,   q is 1, and   A is triethylamine, if M is Ru;   or   e) X is a π-methallyl group,   m and n are each 1,   p is 2,   and   q is 0, if M is Ru;   or   f) X is a coordinating anion selected from Cl, Br or I,   m, n and p are each 1,   and   q is 0, if M is Ir;   or   g) X is Cl,   m and n are each 1,   p is 2,   and   q is 0, if M is Pd;   or   h) X is Cl, Br or I,   m and n are each 1,   p is 2,   and   q is 0, if M is Ni.   
     
     
         2 . The transition metal complex of  claim 1   wherein   M is Rh,   L is the diphosphine compound of formula I; and   wherein   X is a coordinating anion selected from Cl, Br or I,   m, n and p are each 1, and   q is 0.   
     
     
         3 . A Metal complex of the formula
   [M m L n X p A q ]D r   III   wherein   M is a transition metal,   L is the diphosphine compound of formula I;   wherein   X is a diene ligand,   D is a non-coordinating anion selected from BF 4 , ClO 4 , PF 6 , SbF 6 , CF 3 SO 3 , BPh 4 , or BARF,   m, n, p and r are each 1,   with the proviso that   a) q is 0, if M is Rh;   or   b) X is an olefinic ligand such as e.g. cyclooctene or ethylene,   D is a non-coordinating anion selected from BF 4 , ClO 4 , PF 6 , SbF 6 , CF 3 SO 3 , BPh 4 , or BARF,   m, n and r are each 1,   p is 2   and   q is 0, if M is Rh;   or   c) X is Cl, Br or I,   A is benzene or p-cymene,   D is Cl, Br or I,   and   m, n, p, q and r are each 1, if M is Ru;   or   d) D is a non-coordinating anion selected from BF 4 , ClO 4 , PF 6 , SbF 6 , CF 3 SO 3 , BPh 4 , or BARF,   m and n are each 1,   p and q are each 0, and   r is 2, if M is Ru;   or   e) X is a diene ligand,   D is a non-coordinating anion selected from BF 4 , ClO 4 , PF 6 , SbF 6 , CF 3 SO 3 , BPh 4 , or BARF,   m, n, p and r are each 1, and   q is 0, if M is Ir;   or   f) X is an olefinic ligand,   D is a non-coordinating anion selected from BF 4 , ClO 4 , PF 6 , SbF 6 , CF 3 SO 3 , BPh 4 , or BARF,   m, p and r are each 1,   n is 2 and   q is 0, if M is Ir;   or   g) X is a π-allyl group,   D is a non-coordinating anion selected from BF 4 , ClO 4 , PF 6 , SbF 6 , CF 3 SO 3 , BPh 4 , or BARF,   m, n, p and r are each 1, and   q is 0, if M is Pd.   
     
     
         4 . The metal complex of  claim 3   wherein   M is Rh,   L is the diphosphine compound of formula I; and   wherein   a) X is a diene ligand,   D is a non-coordinating anion selected from BF 4 , ClO 4 , PF 6 , SbF 6 , CF 3 SO 3 , BPh 4 , or BARF,   m, n, p and r are each 1, and   q is 0;   or   b) X is an olefinic ligand such as e.g. cyclooctene or ethylene,   D is a non-coordinating anion selected from BF 4 , ClO 4 , PF 6 , SbF 6 , CF 3 SO 3 , BPh 4 , or BARF,   m, n and r are each 1,   p is 2 and   q is 0.   
     
     
         5 . A process for the asymmetric hydrogenation of a prochiral olefinic or ketonic compound comprising carrying out the hydrogenation in presence of metal complex of formula II as defined in  claim 1 . 
     
     
         6 . A process for the asymmetric hydrogenation of a prochiral olefinic or ketonic compound comprising carrying out the hydrogenation in presence of metal complex of formula III as defined in  claim 3 . 
     
     
         7 . A process for the manufacture of compounds of formula Ia, Ib, Ic and Id 
       
         
           
           
               
               
           
         
         wherein 
         R 1  and R 2  are independently selected from the group consisting of alkyl, aryl, cycloalkyl or heteroaryl, said alkyl, aryl, cycloalkyl or heteroaryl being unsubstituted or substituted by alkyl, alkoxy, halogen, hydroxy, amino, mono- or dialkylamino, aryl, —SO 2 —R 7 , —SO 3   − , —CO—NR 8 R 8′ , carboxy, alkoxycarbonyl, trialkylsilyl, diarylalkylsilyl, dialkylarylsilyl or triarylsilyl; 
         R 3  is selected from the group consisting of alkyl, cycloalkyl, aryl and heteroaryl; 
         R 4′  and R 4  are independently selected from the group consisting of hydrogen, alkyl and aryl; or 
         R 4′  and R 4  together with the C-atom they are attached to form a 3-8-membered carbocyclic ring; 
         the dotted line is absent or is present and forms a double bond; 
         R 5  and R 6  are independently selected from the group consisting of hydrogen, alkyl and aryl; 
         R 7  is selected from the group consisting of alkyl, aryl and NR 8 R 8′ ; and 
         R 8  and R 8′  are independently selected from the group consisting of hydrogen, alkyl and aryl; 
         which comprises the steps of 
         1) reacting phospholane borane complex 1 with a non-chiral or an optically active epoxide EP to produce trans-2-hydroxyethyl-phospholanes as a mixture of isomers 2a and 2b. 
       
       
         
           
           
               
               
           
         
         2) converting compounds of formula 2a and 2b to a mixture of sulfonates of formula 3a and 3b 
       
       
         
           
           
               
               
           
         
         3) reacting compounds 3a and 3b with a phosphine R 1 R 2 PH and then treating with a borane delivering agent to produce the bis(borane) complex 4a and 4b. 
       
       
         
           
           
               
               
           
         
         4) deboronating the bis(borane) complex 4a and 4b with an amine to produce the free 1,3-diphosphines Ia and Ib. 
       
       
         
           
           
               
               
           
         
         5) treating the trans-configurated diphosphines Ia and Ib at elevated temperatures in an organic solvent to obtain cis-configurated diphosphines Ic and Id. 
       
       
         
           
           
               
               
           
         
       
     
     
         8 . The process of  claim 7 , wherein the separation of the isomeric compounds a and b is carried out in any of the steps 1) to 5). 
     
     
         9 . The process of  claim 7  for the manufacture of compounds of formula Ia, Ib, Ic or Id 
       
         
           
           
               
               
           
         
         which comprises the steps of 
         1) reacting phospholane borane complex I with a non-chiral or an optically active epoxide EP to produce trans-2-hydroxyethyl-phospholanes as a mixture of isomers 2a and 2b; 
       
       
         
           
           
               
               
           
         
         2) converting compounds of formula 2a and 2b to a mixture of sulfonates of formula 3a and 3b; 
       
       
         
           
           
               
               
           
         
         3) separating the mixture of compounds 3a and 3b to produce diastereomerically and enantiomerically pure sulfonates 3a and 3b; 
       
       
         
           
           
               
               
           
         
         4) reacting compounds 3a and 3b separately with a phosphine R 1 R 2 PH and then treating with a borane delivering agent to produce the bis(borane) complex 4a or 4b; 
       
       
         
           
           
               
               
           
         
         5) deboronating the bis(borane) complex 4a or 4b with an amine to produce the free 1,3-diphosphines Ia or Ib; 
       
       
         
           
           
               
               
           
         
         6) treating the trans-configurated diphosphines Ia or Ib at elevated temperatures in an organic solvent to obtain cis-configurated diphosphines Ic or Id. 
       
       
         
           
           
               
               
           
         
       
     
     
         10 . The process of  claim 9 , wherein the substituents R 4  and R 4′  are hydrogen and the separation of the isomeric compounds a and b is carried out in step 1) by a method comprising an enzymatic resolution step. 
     
     
         11 . A process for the manufacture of compounds of formula Ia, Ib, Ic and Id 
       
         
           
           
               
               
           
         
         wherein R 1 , R 2 , R 3 , R 4 , R 4′ , R 5 , R 6 , R 7 , R 8 , and R 8′  are as defined in  claim 7 , which comprises as the steps of 
         1) reacting phospholane-1-sulfide 1′ with a non-chiral or an optically active epoxide EP to produce trans-2-hydroxyethyl-phospholanes as a mixture of isomers 2′a and 2′b; 
       
       
         
           
           
               
               
           
         
         2) separating the mixture of compounds 2′a and 2′b to produce diastereomerically and enantiomerically enriched compound of 2′a and 2′b; 
       
       
         
           
           
               
               
           
         
         3) converting separately compounds of formula 2′a and 2′b to sulfonates of formula 3′a and 3′b; 
       
       
         
           
           
               
               
           
         
         4) reacting compounds 3′a and 3′b separately with a phosphine R 1 R 2 PH and then treating with a borane delivering agent to produce the borane complex 4′a or 4′b; 
       
       
         
           
           
               
               
           
         
         5) removing the sulfur group of the borane complex 4′a or 4′b with a reducing agent and then treating with a borane delivering agent to produce bis(borane) complex 4a or 4b; 
       
       
         
           
           
               
               
           
         
         6) deboronating the bis(borane) complex 4a or 4b with an amine to produce the free 1,3-diphosphines Ia or Ib; 
       
       
         
           
           
               
               
           
         
         7) treating the trans-configurated diphosphines Ia or Ib at elevated temperatures in an organic solvent to obtain cis-configurated diphosphines Ic or Id. 
       
       
         
           
           
               
               
           
         
       
     
     
         12 . A process according to  claim 11 , wherein the separation of the isomeric compounds a and b is carried out in any of the steps 1 to 6.