METHOD FOR THE PRODUCTION OF CHIRAL, SECONDARY ALCOHOLS

摘要

Disclosed is a method for producing chiral, secondary alcohols of formula (I), wherein A represents an aromatic, heterocyclic, or alicyclic ring or a ring system with 4 to 20 C atoms, n represents 0, 1, 2, 3, 4, or 5, R represents halogen, OH, an O- protective group, NO₂, N,N-R2,R3 amine, R2 and R3 representing C1-C6 alkyl, phenyl, or benzyl, N,N-R2,R3-amino-C₁-C₆ alkyl, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₁-C₆ alkoxy, C₁-C₄ alkoxycarbonyl, or CN, and R1 represents N,N-R2,R3 amine, N,N-R2,R3-amino-C₁-C₆ alkyl, C₁-C₁₂ alkyl, C₁-C₆-haloalkyl, C₁-C₄ alkoxycarbonyl, C₁-C₆ alkoxy-C₁-C₆ alkyl, or a C₂-C₅ alkylene radical that forms a ring system along with the A radical. According to the inventive method, a) a ketone of formula (II) is optionally reduced to the corresponding racemic alcohol of formula (III) by means of an aliphatic C₁-C₆ alcohol in the presence of a transition metal catalyst and a base, and b) the alcohol of formula (III) is reacted to a mixture of (R) ester of formula (IV), wherein R4 represents H or C₁-C₅ alkyl, and (S) alcohol of formula (I) in the presence of an esterification catalyst and an acyl donor, whereupon the (S) alcohol is isolated from the reaction mixture by means of crystallization or distillation according to the aggregate state thereof.