Quantitative Improvements and Insights into CALB‐Catalyzed Resolution of trans‐ and cis‐2‐Phenylcyclopropyl Azolides

Abstract

AbstractWith trans‐2‐phenylcyclopropyl azolides as the model substrate for hydrolytic or alcoholic resolution in methyl tert‐butyl ether (MTBE) via Novozym 435 as an immobilized Candida antarctica lipase B (CALB), quantitative improvements of the enzyme activity and enantioselectivity were reported. At the best reaction conditions of 35oC, leading to k2RRKmRR−1=5.185 L/h⋅g and Etrans=97.2, for hydrolysis of trans‐2‐phenylcyclopropyl 1,2,4‐azolide (trans‐2‐PCPT), (1R,2R)‐2‐PCPCA of high optical purity was obtained. Insights into CALB performance via kinetic and thermodynamic analysis for trans‐ and cis‐2‐phenylcyclopropyl 1,2,4‐triazolide (cis‐2‐PCPT) were furthermore addressed, showing the prospect of present kinetic resolution process for synthesizing other optically pure 2‐arylcyclopropane‐1‐carboxylic acids.