Lipase catalyzed acylation of primary alcohols with remotely located stereogenic centres: the resolution of (±)-4,4-dimethyl-3-phenyl-1-pentanol

Abstract Enantioselective acylation of some (±)-3-alkyl-3-phenyl-1-propanols was performed with enzymes as catalysts. Moderate enantiomeric ratios ( E ), ranging up to E  = 11.6, were obtained. In the resolution, some of the lipases selectively acylated the (+)-enantiomer while others acylated the (−)-enantiomer of the γ-substituted primary alcohols 1 – 4 . Thus, it is possible to obtain both enantiomers of the alcohols as remaining substrate with high enantiomeric purity. The resolution of (±)-4,4-dimethyl-3-phenyl-1-pentanol 4 was extensively studied and screening experiments were conducted to select suitable lipase(s), reaction medium, acyl donor and appropriate temperature combinations to increase the enantiomeric ratio. Chirazyme ® L-6/chloroform/vinyl propionate/38 °C and Chirazyme ® L-7/di-iso-propyl ether/vinyl propionate/0 °C were chosen to obtain both enantiomers, ( R )-(+)- 4 and ( S )-(−)- 4 , respectively, via sequential resolutions in excellent enantiomeric excess (>98%) and in 25% and 22% yield, respectively.