Continuous‐Flow Dynamic Kinetic Resolution of Racemic Alcohols by Lipase–Oxovanadium Cocatalysis

Abstract

A continuous‐flow dynamic kinetic resolution of racemic secondary alcohols was carried out using a single column reactor packed with a mixture of immobilized lipase and an immobilized oxovanadium species, VMPS4. As a result, optically pure esters were produced in 88–92 % yields. Problems encountered in this study were overcome by using fillers that efficiently maintained the initial distribution of the catalysts in the reactor and by using a packing method in which the mixing ratio of the two catalysts was varied in a stepwise fashion. The flow process led to an increased turnover number of each catalyst compared to those of batch reactions.

Expanding the Synthetic Toolbox through Metal–Enzyme Cascade Reactions

“…For instance, Groger, Akai, and co-workers have described the use of the oxovanadium catalyst V-MPS4 52 and CAL-B (Novozym 435) to develop a DKR process of secondary alcohols in flow mode. 57 First, the DKR study of (E)-4-phenylbut-3-en-2-ol (0.1 M) was carried out in a packed column with CAL-B and V-MPS4 in the presence of vinyl acetate (4 equiv) at 35 °C. Unfortunately, a change in the distribution of both catalysts was observed during the process, resulting in a biotransformation efficiency decrease.…”

“…This has not gone unnoticed for the biocatalysis community, − especially when considering the development of DKR processes to circumvent the bio- and metal catalyst incompatibilities. For instance, Gröger, Akai, and co-workers have described the use of the oxovanadium catalyst V-MPS4 and CAL-B (Novozym 435) to develop a DKR process of secondary alcohols in flow mode . First, the DKR study of ( E )-4-phenylbut-3-en-2-ol (0.1 M) was carried out in a packed column with CAL-B and V-MPS4 in the presence of vinyl acetate (4 equiv) at 35 °C.…”

Kinetic and Dynamic Kinetic Resolution by Dual Catalysis

“…[40] In 2020, the same group developed a continuous flow method for the resolution of racemic allylic alcohols (Table 7). [41] In this protocol, VMPS4 was used as a racemization catalyst, in which the covalent bond formation between oxovanadium species with immobilized silica improved the compatibility with lipase. The main advantage of these continuous flow reactions is that scale-up is easy and turnover number (TON) is high.…”

Progress on the Stereoselective Synthesis of Chiral Molecules Based on Metal-Catalyzed Dynamic Kinetic Resolution of Alcohols with Lipases

“…In 2020, the groups of Gröger and Akai developed the continuous-flow DKR of allylic alcohols. A three-layer packed column containing DualPore silica beads as a filler, and both catalysts with increasing ratio of V-MPS4/CAL-B was used (Scheme 11) [48]. Alcohols were con-verted after 30-60 min of residence time and the corresponding (R)-esters were isolated in 88-92% yield and 96-99% ee.…”