Alpha-substituted alpha, beta-unsaturated e- or z-aldehydes, use thereof, and processes for their preparation alpha, beta

Abstract

This invention relates to novel alpha-substituted α,β-unsaturated E- or Z-aldehydes, or isomer mixture thereof, of the formula in which R 1 and R 2 may be identical or different and are each H or a hydrocarbon, in which the hydrocarbon may have one or more heteroatoms and R 3 and R 4 may be identical or different and are each a hydrocarbon, in which the hydrocarbon may have one or more heteroatoms, and R 5 may be identical or different and is H or a hydrocarbon, in which the hydrocarbon may have one or more heteroatoms, to the use thereof, and to processes for their preparation. The invention further relates to the preparation of further intermediates for pharmaceuticals and to the preparation of the pharmaceuticals.

1 . A process for preparing a compound of the formula (IX) 
       
         
           
           
               
               
           
         
         wherein the process comprises reacting, for example reducing, the alpha,beta-carbon-carbon double bond of a compound of the formula (I) 
       
       
         
           
           
               
               
           
         
         in the presence of an addition compound HY in which Y is H or the conjugated base of HY, where Y is preferably selected from H, Cl, Br, I, F, SiR x R y R z , SR x , NR x R y , in which R x , R Y  and R z  are each independently selected from H and hydrocarbon groups, which hydrocarbon groups may especially be selected from H, optionally substituted C 1 -C 12  alkyl and optionally substituted C 2 -C 12  alkenyl, more especially from H, optionally substituted C 1 -C 6  alkyl and optionally substituted alkenyl, and wherein 
         R 1  and R 2  may be identical or different and are each H or an optionally substituted hydrocarbon which optionally has one or more heteroatoms, in which the hydrocarbon may especially be an oxygen protecting group, and in which R 1  and R 2  may optionally be bonded to one another to form a ring structure; and 
         R 3  and R 4  may be identical or different and are each an optionally substituted hydrocarbon with 1-6 C atoms, which optionally has one or more heteroatoms, and in which R 3  and R 4  may be bonded to form a ring structure. 
       
     
     
         2 . A process as in  claim 1 , comprising catalytically hydrogenating the alpha,beta-carbon-carbon double bond of a compound of the formula (I) in the presence of a catalyst, especially an enzyme, or a homogeneous catalyst prepared from a metal and a ligand. 
     
     
         3 . A process according to  claim 2 , wherein a compound of the formula (IX) is prepared enantioselectively, hence with the R enantiomer or the S enantiomer in excess, especially with R enantiomer in excess. 
     
     
         4 . A process for preparing a compound of the formula (XVIII) 
       
         
           
           
               
               
           
         
         wherein the process comprises reducing a compound of the formula (I) 
       
       
         
           
           
               
               
           
         
         wherein 
         R 1  and R 2  may be identical or different and are each H or an optionally substituted hydrocarbon which optionally has one or more heteroatoms, in which the hydrocarbon may especially be an oxygen protecting group, and in which R 1  and R 2  may optionally be bonded to one another to form a ring structure; and 
         R 3  and R 4  may be identical or different and are each an optionally substituted hydrocarbon with 1-6 C atoms, which optionally has one or more heteroatoms, and in which R 3  and R 4  may be bonded to form a ring structure, and 
         Y is the aldehyde group of a compound of the formula (I) and is preferably selected from H. CI, Br, I, F. SiR x R y R z , SR x , NR x R y , in which R x . R y  and R z  are each independently selected from H and hydrocarbon groups, which hydrocarbon groups may especially be selected from H, optionally substituted C 1 -C 12  alkyl and optionally substituted C 2 -C 12  alkenyl, more especially from H, optionally substituted C 1 -C 6  alkyl and optionally substituted alkenyl. 
       
     
     
         5 . A process for preparing a compound of the formula (II) 
       
         
           
           
               
               
           
         
         in which R 1 , R 2 , R 3  and R 4  and Y is as defined in  claim 1 , in which this compound is prepared from an aldehyde of the formula (I) by addition of a compound HY onto the alpha,beta-carbon-carbon double bond, or a reduction of the alpha,beta-carbon-carbon double bond and reduction of the aldehyde group, or 
         in which this compound is prepared from a compound of the formula (IX) by reduction of the aldehyde group, or 
         in which this compound is prepared from a compound of the formula (XVIII) by reduction of the alpha,beta-carbon-carbon double bond. 
       
     
     
         6 . A process according to  claim 1 , for preparing a compound of the formula (IX) or (II), respectively, or a mixture thereof, from an aldehyde of the formula (I) where both the E and Z isomers are converted to the compound of the formula (IX) or (II), or a mixture thereof, especially in the presence of chiral hydrogenation catalysts from the group of enzymes or homogeneous catalysts, or a mixture thereof. 
     
     
         7 . The processes according to  claim 6  carried out under reaction conditions causing isomerization. 
     
     
         8 . The process according to  claim 4 , wherein the compound of the formula (II) or formula (IX) is prepared enantioselectively, especially with R configuration. 
     
     
         9 . The process according to  claim 4 , carried out under reaction conditions causing racemization. 
     
     
         10 . A process for preparing a compound of the formula (X) 
       
         
           
           
               
               
           
         
         in which R 1 , R 2 , R 3  and R 4  are each as defined in  claim 1  and Y is preferably selected from H. Cl, Br, I, F. SiR x R y R z , SR x , NR x R y , in which R x , R y  end R z  are each independently selected from H and hydrocarbon groups, which hydrocarbon groups may especially be selected from H, optionally substituted C 1 -C 12  alkyl and optionally substituted C 2 -C 12  alkenyl, more especially from H, optionally substituted C 1 -C 6  alkyl and optionally substituted alkenyl, Hal is a halogen atom, preferably chlorine, and 
         in which this compound is prepared from a compound of the formula (II). 
       
     
     
         11 . Use of a compound as an intermediate compound for preparing a compound according to the formula (XVII) or a suitable salt thereof, in particular a fumerate salt, 
       
         
           
           
               
               
           
         
         wherein R 1 , R 2 , R 3  and R 4  and Y are as defined in  claim 1  and R a  is —CH 2 —[CH(CH 3 ) 2 ]—CO—NH 2 .