Lactonization reactions through hydrolase-catalyzed peracid formation. Use of lipases for chemoenzymatic Baeyer–Villiger oxidations of cyclobutanones

Abstract

Abstract:A one-pot chemoenzymatic method has been described for the synthesis of -butyrolactones starting from the corresponding ketones through a Baeyer-Villiger reaction.The approach is based on a lipase-catalyzed perhydrolysis for the formation of peracetic acid, which is the responsible for the ketone oxidation. Optimization studies have been performed in the oxidation of cyclobutanone, finding Candida antarctica lipase type B, ethyl acetate and urea-hydrogen peroxide complex as the best system. The relative ratio of these reagents has also been analyzed in depth. This synthetic approach has been successfully extended to a family of 3-substituted cyclobutanones in high substrate concentration, yielding the corresponding lactones with excellent isolated yields and purities, under mild reaction conditions and after a simple extraction protocol.

Optimization of chemoenzymatic Baeyer–Villiger oxidation of cyclohexanone to ε‐caprolactone using response surface methodology

“…In the present work, in order to improve the stability of lipase, T. laibacchii lipase was immobilized on diatomite supports using glutaraldehyde as a crosslinker. In this study, the initial concentration of cyclohexanone was 1.22 M and the concentration of the target product ε‐CL reached about 1.2 M according to the yield of 98.06%, being much higher than that (0.225–0.37 M) with a conversion of 80–90% in the previous other studies . Among them, the highest concentration of 0.37 M was achieved when an ionic liquid was used as solvent, and the yield of caprolactone reached 98.06% because the T. laibacchii lipase used in this study was immobilized by cross‐linking technology, glutaraldehyde was used as a crosslinking agent for T. laibacchii lipase and diatomite support to improve the stability of lipase.…”

“…Although it is generally believed that the present system only consists of two reactions including Reactions (1) and (2), it can be concluded from the above discussion that Reaction (3) in which recycling acetic acid formed reacts with UHP to generate peracetic acid. This indicates that there are three reactions in this reaction system rather than two reactions …”

“…At the optimum molar ratio of cyclohexanone to UHP, which was 1:1.3, the response yield of ε‐CL reached 98.06%. González‐Martínez et al carried out a chemoenzymatic synthesis of butyrolactones starting through a Baeyer–Villiger reaction, in which the range of the molar ratio of cyclobutanone to UHP was from 1:0 to 1:2. The yield reached 99% when the molar ratio was 1:1.5, in which the initial concentration of cyclobutanone was 0.66 M. In their study, an extreme conversion rate was obtained at a relatively high substrate cyclobutanone concentration because cyclobutanone seems to inhibit enzymes less than cyclohexanone.…”

“…ε‐Caprolactone (ε‐CL) has attracted a great deal of attention as an important intermediate of a series of synthetic materials and also a monomer of the new polymer polycaprolactone . In the current industrial production, the traditional chemical Baeyer–Villiger (BV) oxidation is used to synthesize ε‐CL from cyclohexanone.…”

Novel chemoenzymatic oxidation of amines into oximes based on hydrolase-catalysed peracid formation

“…These are the use of ethyl acetate (EtOAc) as both solvent and peracid precursor, 30 and alternatively the combination of lauric acid as peracid precursor and acetonitrile (MeCN) as solvent. 21 For simplicity, benzylamine (1a) was again selected as model substrate, finding in all cases the oxime 2a as the main product (Scheme 2).…”