Lipase-Catalyzed Kinetic Resolution of 1-(2-Hydroxycyclohexyl)Indoles in Batch and Continuous-Flow Systems

The lipase catalyzed kinetic resolution of three trans-1-(2-hydroxycyclohexyl)-indoles in both batch and continuousflow systems is reported. Ring opening of cyclohexene oxide by the corresponding indole followed by enzymatic acylation with vinyl acetate resulted in novel, highly enantioenriched indole-substituted cyclohexanols and cyclohexyl acetates. The effect of the temperature on enantiomeric ratio (E) and productivity (specific reaction rate, rflow) in the continuous-flow mode acylation was studied at analytical scale in the 0–70 °C range. Preparative scale kinetic resolution of the three indole derivatives was performed in mixed continuous- and recirculation-flow mode resulting in almost complete conversion and good to excellent enantiomeric purity of the products.