Process for hydrogenating ketones in the presence of ru(ii) catalysts

Abstract

The present invention relates to a process for hydrogenating a substrate including a carbon-heteroatom double bond, the process including the step of reacting the substrate with hydrogen gas in the presence of a hydrogenation catalyst, wherein the hydrogenation catalyst is a complex of formula (I): R 1-10 , A and Hal are as defined in the specification. The present invention also provides processes for the preparation of the complex of formula (I) and intermediates thereof.

1 . A process for hydrogenating a substrate comprising a carbon-heteroatom double bond, the process comprising the step of reacting the substrate with hydrogen gas in the presence of a hydrogenation catalyst, wherein the hydrogenation catalyst is a complex of formula (I): 
       
         
           
           
               
               
           
         
         wherein, 
         R 1 , R 2 , R 3 , R 4  and R 5  are each independently selected from the group consisting of hydrogen, optionally substituted straight, branched or cyclic C 1-20  alkyl, optionally substituted straight, branched or cyclic C 1-20  alkoxy, optionally substituted C 6-20  aryl, optionally substituted C 6-20  aryloxy, —OH, —CN, —NR 20 R 21 , —COOH, COOR 20 , —CONH 2 , —CONR 20 R 21  and —CF 3 , wherein the substituents are selected from the group consisting of one or more straight, branched or cyclic C 1-20  alkyl, straight, branched or cyclic C 1-20  alkoxy, C 6-20  aryl, C 6-20  aryloxy, —OH, —CN, —NR 30 R 31 , —COOR 30 , —CONR 30 R 31  and —CF 3 ; 
         R 1  and R 2 , R 2  and R 3 , R 3  and R 4  or R 4  and R 5  together form an aromatic ring composed of 6 to 10 carbon atoms which is optionally substituted with one or more straight, branched or cyclic C 1-20  alkyl, straight, branched or cyclic C 1-20  alkoxy, C 6-20  aryl, C 6-20  aryloxy, —OH, —CN, —NR 20 R 21 , —COOR 20 , —CONR 20 R 21  and —CF 3 ; 
         R 6 , R 7 , R 8  and R 9  are each independently selected from the group consisting of hydrogen, optionally substituted straight, branched or cyclic C 1-20  alkyl, optionally substituted straight, branched or cyclic C 1-20  alkoxy, optionally substituted C 6-20  aryl and optionally substituted C 6-20  aryloxy wherein the substituents are selected from the group consisting of one or more straight, branched or cyclic C 1-20  alkyl, straight, branched or cyclic C 1-20  alkoxy, C 6-20  aryl, C 6-20  aryloxy, —OH, —CN, —NR 20 R 21 , —COOR 20 , —CONR 20 R 21  and —CF 3 , or 
         R 6  and R 7  together with the carbon atom to which they are bound and/or R 8  and R 9  together with the carbon atom to which they are bound form an optionally substituted C 3-20  cycloalkyl or an optionally substituted C 2-20  cycloalkoxy, wherein the substituents are selected from the group consisting of one or more straight, branched or cyclic C 1-20  alkyl, straight, branched or cyclic C 1-20  alkoxy, C 6-20  aryl, C 6-20  aryloxy, —OH, —CN, —NR 20 R 21 , —COOR 20 , —CONR 20 R 21  and —CF 3 , or 
         one of R 6  and R 7  and one of R 8  and R 9  together form an optionally substituted C 5-10  cycloalkyl or an optionally substituted C 5-10  cycloalkoxy, wherein the substituents are independently selected from the group consisting of one or more straight, branched or cyclic C 1-20  alkyl, straight, branched or cyclic C 1-20  alkoxy, C 6-20  aryl, C 6-20  aryloxy, —OH, —CN, —NR 20 R 21 , —COOR 20 , —CONR 20 R 21  and —CF 3 , or 
         R 10  is an optionally substituted straight, branched or cyclic C 1-10  alkyl, an optionally substituted C 6-10  aryl or —NR 11 R 12  wherein the substituents are selected from the group consisting of one or more straight, branched or cyclic C 1-10  alkyl, straight, branched or cyclic C 1-10  alkoxy, C 6-10  aryl, C 6-10  aryloxy, -Hal, —OH, —CN, —NR 20 R 21 , —COOR 20 , —CONR 20 R 21  and —CF 3 ; 
         R 11  and R 12  are independently selected from the group consisting of hydrogen, optionally substituted straight, branched or cyclic C 1-10  alkyl and optionally substituted C 6-10  aryl, wherein the substituents are selected from the group consisting of one or more straight, branched or cyclic C 1-10  alkyl groups, straight, branched or cyclic C 1-10  alkoxy, C 6-10  aryl, C 6-10  aryloxy, —OH, —CN, —NR 20 R 21 , —COOR 20 , —CONR 20 R 21  and —CF 3 , or 
         R 11  and R 12  together with the nitrogen atom to which they are bound form an optionally substituted C 2-10  cycloalkyl-amino group wherein the substituents are selected from the group consisting of one or more straight, branched or cyclic C 1-10  alkyl, straight, branched or cyclic C 1-10  alkoxy, C 6-10  aryl, C 6-10  aryloxy, —OH, —CN, —NR 20 R 21 , —COOR 20 , —CONR 20 R 21  and —CF 3 ; 
         R 20  and R 21  are independently selected from the group consisting of hydrogen, optionally substituted straight, branched or cyclic C 1-20  alkyl, optionally substituted straight, branched or cyclic C 1-20  alkoxy, optionally substituted C 6-20  aryl, optionally substituted C 6-20  aryloxy, —OH, —CN, —NR 30 R 31 , —COOR 30 , —CONR 30 R 31  and —CF 3 , wherein the substituents are selected from the group consisting of one or more straight, branched or cyclic C 1-20  alkyl, straight, branched or cyclic C 1-20  alkoxy, C 6-20  aryl, C 6-20  aryloxy, —OH, —CN and —CF 3 ; 
         R 30  and R 31  are independently selected from the group consisting of hydrogen, optionally substituted straight, branched or cyclic C 1-20  alkyl, optionally substituted straight, branched or cyclic C 1-20  alkoxy, optionally substituted C 6-20  aryl, optionally substituted C 6-20  aryloxy, —OH, —CN and —CF 3 , wherein the substituents are selected from the group consisting of one or more straight, branched or cyclic C 1-20  alkyl, straight, branched or cyclic C 1-20  alkoxy, C 6-20  aryl, C 6-20  aryloxy, —OH, —CN and —CF 3 ; 
         A is an optionally substituted straight- or branched-chain C 2-5  alkyl wherein the substituents are selected from the group consisting of one or more straight, branched or cyclic C 1-10  alkyl, straight, branched or cyclic C 1-10  alkoxy, C 6-10  aryl and C 6-10  aryloxy, or 
         A is a group of formula (II): 
       
       
         
           
           
               
               
           
         
         wherein p is an integer selected from 1, 2, 3 or 4; 
         each R 40  is independently selected from the group consisting of straight, branched or cyclic C 1-20  alkyl, straight, branched or cyclic C 1-20  alkoxy, C 6-20 aryl, C 6-20  aryloxy, —OH, —CN or —CF 3 ; 
         q and r are independently integers selected from 0, 1, 2 or 3 wherein q+r=1, 2 or 3; 
         each R 41  is independently selected from the group consisting of hydrogen, straight, branched or cyclic C 1-20  alkyl, straight, branched or cyclic C 1-20  alkoxy, C 6-20  aryl, C 6-20  aryloxy, —OH, —CN and —CF 3 ; and 
         Hal is a halogen. 
       
     
     
         2 . A process according to  claim 1 , wherein R 1 , R 2 , R 3 , R 4  and R 5  are each independently selected from the group consisting of hydrogen, straight-chain C 1-10  alkyl and branched-chain C 1-10  alkyl. 
     
     
         3 . A process according to  claim 2 , wherein R 1 , R 2 , R 3 , R 4  and R 5  are each independently selected from the group consisting of hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl and t-butyl. 
     
     
         4 . A process according to  claim 3 , wherein R 1 , R 2 , R 3 , R 4  and R 5  are each hydrogen. 
     
     
         5 . A process according to  claim 1 , wherein R 6 , R 7 , R 8  and R 9  are each independently selected from the group consisting of hydrogen and optionally substituted C 6-10  aryl. 
     
     
         6 . A process according to  claim 5 , wherein R 6 , R 7 , R 8  and R 9  are each independently selected from the group consisting of hydrogen and phenyl. 
     
     
         7 . A process according to  claim 6 , wherein one of R 6  and R 7  is phenyl and the other of R 6  and R 7  is hydrogen. 
     
     
         8 . A process according to  claim 6 , wherein one of R 8  and R 9  is phenyl and the other of R 8  and R 9  is hydrogen. 
     
     
         9 . A process according to  claim 6 , wherein R 6 , R 7 , R 8  and R 9  are hydrogen. 
     
     
         10 . A process according to  claim 1 , wherein R 10  is methyl or a tolyl group. 
     
     
         11 . A process according to  claim 1 , wherein A is —(CH 2 ) 2 —, —(CH 2 ) 3 —, —(CH 2 ) 4 — or —(CH 2 ) 5 —. 
     
     
         12 . A process according to  claim 1 , wherein Hal is selected from the group consisting of chlorine, bromine and iodine. 
     
     
         13 . A process according to  claim 1 , wherein the substrate to be hydrogenated is a carbonyl or iminyl. 
     
     
         14 . A process according to  claim 1 , further comprising a solvent. 
     
     
         15 . A process according to  claim 14 , wherein the solvent comprises an alcohol. 
     
     
         16 . A process according to  claim 1 , further comprising a silver salt. 
     
     
         17 . A process according to  claim 1 , further comprising a fluorinated sulfonic acid.