Continuous flow dynamic kinetic resolution of rac-1-phenylethanol using a single packed-bed containing immobilized CAL-B lipase and VOSO₄as racemization catalysts

Abstract

Herein, we report a method for the continuous flow DKR of rac-1-phenylethanol catalyzed by CAL-B and VOSO4, using a single packed-bed containing both catalysts.

Lipase‐oxovanadium heterogeneous catalysis system: a robust protocol for the dynamic kinetic resolution of sec‐alcohols

“…These results indicate that the incompatibility between CAL−B and VOSO 4 is an issue for substrates that require extended reaction times. In these cases, better conversions and selectivities can be obtained by physically separating CAL−B and VOSO 4 , which has been mentioned in previous works . On the other hand, no conversions were observed in the substitution of the side chain with groups larger than ethyl (substrates 11 – 13 , Table ).…”

“…Decreasing the temperature resulted in better selectivity with acceptable racemization rates. The optimum conditions disclosed in this study, heptane at 50 °C (Table , entry 6), in addition to being greener than the conditions previously reported in the literature, are closer in those required by enzymes, which will be crucial in the DKR.…”

“…Our study began by examining the VOSO 4 ‐catalysed racemization step using ( S )‐1‐phenylethanol (( S )‐ 1 ) as a model substrate aiming to increase the selectivity of the process previously reported by Jacobs et al and Souza et al . As shown in Table , fast racemization was achieved at 80 °C in all the evaluated solvents, but with low selectivity (high by‐product formation).…”

“…However, most are expensive, not eco‐friendly or not readily available and, in some cases, they require conditions that are harmful to lipases, such as high temperatures or the presence of strong bases. Therefore, substantial effort has been devoted to developing biocompatible and more environmentally benign racemization catalysts, such as solid acids, zeolites and vanadium compounds …”

“…Souza et al . also described the DKR of rac ‐1‐phenylethanol catalysed by VOSO 4 and CAL−B using a continuous flow approach that enabled catalyst compartmentalization . In this work, the DKR was performed in toluene (70 °C) and the ( R )‐product was obtained with 96 % yield and 99 % ee .…”