Enzymatic Kinetic Resolution of Secondary Alcohols Using an Ionic Anhydride Generated In Situ

Abstract

We developed a method for the resolution of secondary alcohols using an ionic anhydride acylating agent prepared directly in the reaction medium containing the biocatalyst Candida antarctica lipase B (CALB). NMR studies showed that mixing all components at the same time does not interfere with the coupling reaction or the enzymatic activity. After optimization of the reaction conditions, the method allowed the resolution of a number of substrates in very high conversions (46-48 %) and enantiomeric ratios (E>170) along with an easy recovery of both enantiomers without the need for preparative chromatographic separation. Additionally, both the starting ionic acid and the biocatalyst could be recovered and reused up to nine cycles without significant loss of enantioselectivity.

From Waste to Value—Direct Utilization of α-Angelica Lactone as a Nonconventional Irreversible Acylating Agent in a Chromatography-Free Lipase-Catalyzed KR Approach toward sec-Alcohols

“…To avoid both aqueous basic and acidic extractive-separation workup, “neutral” selective LLEs have been developed using acyl donors designed on the basis of 1,ω-dicarboxylated poly­(ethylene glycol) (PEG 600 -dicarboxylate diethyl esters), an in situ generated ionic anhydrides, , task-specific ionic liquids (TSILs), and/or fluorous esters , (Figure ). Unfortunately, these methods are stymied by modest yields and low enantiomeric excesses of the resolution products (in the case of PEG-like acyl donor and TSILs), only the partial recovery of the starting ionic acid (in the case of an ionic anhydride acylating agent), or the considerably high costs of reagents as well as their potential adverse environmental and health effects if applied on a large scale (in the case of TSILs and fluorinated esters).…”