Kinetic Resolution of (±)‐1‐Phenylbutan‐1‐ol by Means of CALB‐Catalyzed Aminolyses: A Study on the Role of the Amine in the Alcohol Resolution

The kinetic resolution of (±)‐1‐phenylbutan‐1‐ol [(±)‐1] by means of CALB‐catalyzed aminolysis of its acetyl derivative [(±)‐2] using (±)‐1‐phenylethanamine [(±)‐3] as nucleophile is a slower but more enantioselective process (E= 50) than the corresponding CALB‐catalyzed transesterification of (±)‐1with vinyl acetate (E= 19). The use of triethylamine and acetanilide as additives in the transesterification of (±)‐1enhanced the enantiomeric ratio (E= 43 and 38, respectively), thus showing that both the basic character of the amine as well as its structural nature could be responsible for the enantioselectivity differences observed between the transesterification and aminolysis reactions. We have also carried out the aminolysis of (±)‐2using different chiral and non‐chiral amines. Enantiomeric ratio values varied significantly with the amine employed, but the enzyme always remained more selective towards the R‐enantiomer of the substrate. Among all the amines tested, (±)‐1‐phenylpropan‐1‐amine [(±)‐5] was the nucleophile of choice. Analysis of the conversion values for each enantiomer of (±)‐2showed that the selectivity differences exhibited by the lipase in the aminolysis reactions were due to the different stabilization of the fast‐reacting enantiomer of the substrate [(R)‐2] during the catalytic process. The CALB behavior in these reactions could be explained on the basis of substrate imprinting effects, which were corroborated by means of enzyme recycling experiments. Finally, a solvent screening allowed the kinetic resolution of this alcohol for synthetic purposes.