Process for the Preparation of (3E, 7E)-Homofarnesol

Abstract

The present invention relates to new types of processes for the improved preparation of homofarnesol, in particular of (3E,7E)-homofarnesol and homofarnesol preparations with an increased content of (3E,7E)-homofarnesol (also referred to as all E-homofarnesol).

1 - 12 . (canceled) 
     
     
         13 . A process for preparing compounds of the general formula I 
       
         
           
           
               
               
           
         
         in which 
         R 1  is a straight-chain or branched, optionally mono- or polyunsaturated hydrocarbyl radical, and R 2  is H or C 1 -C 6 -alkyl, which comprises 
         a) reacting a carbonyl compound of the formula II 
       
       
         
           
           
               
               
           
         
         in which R 1  and R 2  have the meanings given above, 
         by means of Wittig olefination to give a cyclopropane of the general formula (III) 
       
       
         
           
           
               
               
           
         
         in which R 1  and R 2  have the meanings given above, 
         b) reacting the cyclopropane of the formula III with ring opening, to give a compound of the formula IV 
       
       
         
           
           
               
               
           
         
         in which R 1  and R 2  have the meanings given above, and X is halogen or O—R′, in which R′ is H, acyl, Tf-acetyl or SC 2 —R″, in which R″ is alkyl or aryl; 
         and 
         c) converting the compound of the general formula IV to the compound of the general formula I. 
       
     
     
         14 . The process according to  claim 13 , wherein a cyclopropylphosphonium salt is used for the Wittig olefination according to stage a). 
     
     
         15 . The process according to  claim 14 , wherein the cyclopropylphosphonium salt is a triphenylphosphonium compound of the formula V 
       
         
           
           
               
               
           
         
         in which Z −  is the anion of a strong acid. 
       
     
     
         16 . The process according to  claim 15 , wherein Z −  is a halide. 
     
     
         17 . The process according to  claim 15 , wherein Z −  is bromide. 
     
     
         18 . The process according to  claim 15 , wherein the compound of the formula V is prepared by reacting a) bromobutyrolactone with triphenylphosphine and then thermally decarboxylating the reaction product, or b) reacting 1,3-dibromopropane with triphenylphosphine and then cyclizing the reaction product. 
     
     
         19 . The process according to  claim 13 , in which the ring-opening in stage b) takes place in the presence of a Lewis acid or Brönstedt acid/protonic acid and a nucleophile. 
     
     
         20 . The process according to  claim 17 , wherein the ring opening takes place essentially stereoselectively, in particular E-selectively (with respect to R 1 ). 
     
     
         21 . The process according to  claim 13 , wherein, in stage c), the compound of the general formula IV is converted to a compound of the general formula I by, when X is OR′, carrying out an ester cleavage, or when X is halogen, converting the halide to an ester and then cleaving this ester. 
     
     
         22 . The process according to  claim 13 , wherein, in stage c), the compound of the general formula IV is converted to a compound of the general formula I by, when X is OR′, carrying out an ester cleavage, or when X is halogen, converting the halide to a formate ester, and then cleaving this ester. 
     
     
         23 . The process according to  claim 13 , in which a product comprising a (3E,7E)-homofarnesol of the formula Ia 
       
         
           
           
               
               
           
         
         is obtained. 
       
     
     
         24 . The process according to  claim 20 , where, in stage a), E-geranyl acetone of the formula IIa 
       
         
           
           
               
               
           
         
         is reacted with cyclopropylphosphonium halogenide, so that the cyclopropane of the formula IIIa 
       
       
         
           
           
               
               
           
         
         is obtained. 
       
     
     
         25 . A compound of the formula III 
       
         
           
           
               
               
           
         
       
     
     
         26 . A compound of the formula IIIa 
       
         
           
           
               
               
           
         
       
     
     
         27 . A process for preparing enantiomerically pure ambrox or a stereoisomer mixture of ambrox, where (3E,7E)-homofarnesol is prepared by the process according to  claim 13  and the homofarnesol formed in this way is reacted chemically or enzymatically to give enantiomerically pure ambrox or a stereoisomer mixture of ambrox.