Continuous kinetic resolution catalysed by cross-linked enzyme aggregates, ‘CLEAs’, in supercritical CO₂

Abstract

We report the use of cross-linked enzyme aggregates (CLEAs 1 ) to catalyse the kinetic resolution of tetralol and 1-phenylethanol in a continuous supercritical carbon dioxide (scCO 2 ) system. We describe the performance of the CLEA from Candida antarctica lipase B (CALB) and compare this to the catalytic activity of Novozym 435 (CALB immobilised on a macroporous acrylic resin). In addition, we report a two-stage reaction with the kinetic resolution of 1-phenylethanol performed in series with the metal (Pd) catalysed hydrogenation of acetophenone. Reactions performed in series have a potential economic advantage as the second, and subsequent reactions do not require additional expenditure of energy for re-pressurization of solvent.

Enzyme Immobilization: The Quest for Optimum Performance

“…The enzymatic resolution could also be combined with the production of the 1-phenylethanol substrate, by palladium-catalyzed hydrogenation of acetophenone, using two separate columns in series (one containing the Pd catalyst and the other the CaLB CLEA), without the need for depressurization ( Figure 15). [103] In the kinetic resolution of 1-phenylethanol and 1-phenylethylamine in the ionic liquids, [bmim] [NO 3 ] and [bmim] [N(CN) 2 ] the best results were observed with CaLB adsorbed and cross-linked on a polypropylene carrier (Accurel EP100). In contrast, the free CaLB or immobilized as Novozym 435 dissolves in these ionic liquids with complete loss of activity.…”

“…[102] Clearly the optimized CaLB CLEAs have activities surpassing those of Nov 435 in both aqueous and organic media. CaLB CLEAs also exhibit excellent activities in supercritical carbon dioxide [103] and ionic liquids. [104] Thus, CaLB CLEA displayed superior activity to that of Novozym 435 in the kinetic resolution of 1-phenylethanol and 1-tetralol, by acylation with vinyl acetate, in scCO 2 .…”

(Bio)Catalytic Continuous Flow Processes in scCO2 and/or ILs: Towards Sustainable (Bio)Catalytic Synthetic Platforms

“…This enables the design of cascade multiple-stage chemocatalytic and biocatalytic processes, and easily increases of the complexity and value of synthesized products. In this regard, Poliakoff and co-workers reported a tandem palladium (Pd)-catalysed hydrogenation of acetophenone followed by a lipase-catalyzed kinetic resolution of the resulting sec-alcohol in scCO 2 [36]. The use of cross-linked enzyme aggregates (CLEAs) was a superior biocatalyst than the classical immobilized enzyme derivative (Novozym 435) (see Fig.…”

“…(4). Pd-catalyzed hydrogenation of acetophenone coupled with CLEAs-catalyzed kinetic resolution (KR) of the resulting rac-1-phenylethanol in scCO2 [36].…”

Asymmetric one-pot reactions using heterogeneous chemical catalysis: recent steps towards sustainable processes

“…214,217,218 The sequential continuous-flow hydrogenation of 33a over Pd/SiO 2 -Al 2 O 3 and KR of 175 by immobilized CALB or crosslinked enzyme aggregates was carried out in supercritical CO 2 using consecutive reactors. 219 Later, in order to catalyse the racemization of the unreacted (S)-175, supported Ru catalyst was also introduced in the batch system, which in the absence of Pd did not promote the hydrogenation of 33a. View Article Online acetoxy-1-indanone 179 resulted in good enantiomeric purity (86-92% ee), however, only up to 50% yield was achieved.…”