Lipase/H₂SO₄‐Cocatalyzed Dynamic Kinetic Resolution of Alcohols in Pickering Emulsion

Abstract

This study reports the first chemoenzymatic dynamic kinetic resolution (DKR) of racemic sec‐alcohols by simultaneously using immobilized lipase and aqueous sulfuric acid as catalysts for kinetic resolution and racemization, respectively. The nanoparticle‐stabilized phase separation in a Pickering emulsion enabled the use of these inherently incompatible catalysts in a single vessel. The racemization reaction in the aqueous sulfuric acid solution significantly suppressed the dehydrative side reactions that form alkenes and dimeric ethers, which are often observed in racemization using Brønsted/Lewis acids or oxovanadium compounds in organic solvents. The efficacy of the Pickering emulsion was confirmed by the significantly lower catalytic performance in DKR without emulsification. This method achieved high yields and high optical purities in the production of a wide range of sec‐alcohols.

Recyclable and Scalable Chemoenzymatic Dynamic Kinetic Resolution of Secondary Alcohols Using Rotating Bed Reactors for Catalyst Compartmentalization

“…The compartmentalization approach was applied in chemoenzymatic DKR catalyzed by lipase and acid racemization catalysts in organic media. − The acid racemization proceeds via an addition–elimination mechanism involving the formation of a carbocation intermediate, potentially enabling their application to a broader range of substrates, including tertiary alcohols . However, challenges arise when using this racemization process, including dehydrative side reactions that lead to the formation of alkenes and dimeric ethers, and the mutual catalyst inactivation when combined with enzymes in DKR methods .…”

“…The compartmentalization approach was applied in chemoenzymatic DKR catalyzed by lipase and acid racemization catalysts in organic media. − The acid racemization proceeds via an addition–elimination mechanism involving the formation of a carbocation intermediate, potentially enabling their application to a broader range of substrates, including tertiary alcohols . However, challenges arise when using this racemization process, including dehydrative side reactions that lead to the formation of alkenes and dimeric ethers, and the mutual catalyst inactivation when combined with enzymes in DKR methods . Different compartmentalization strategies have been employed to enhance the compatibility of lipases and acid racemization catalysts in the DKR of sec -alcohols, such as spatial separation of the catalysts in two compartments connected by a pump loop, confinement of the enzyme in a porous stainless-steel basket, DKR under flow conditions, , and phase separation in a Pickering emulsion …”

“…However, challenges arise when using this racemization process, including dehydrative side reactions that lead to the formation of alkenes and dimeric ethers, and the mutual catalyst inactivation when combined with enzymes in DKR methods . Different compartmentalization strategies have been employed to enhance the compatibility of lipases and acid racemization catalysts in the DKR of sec -alcohols, such as spatial separation of the catalysts in two compartments connected by a pump loop, confinement of the enzyme in a porous stainless-steel basket, DKR under flow conditions, , and phase separation in a Pickering emulsion …”

“…24 However, challenges arise when using this racemization process, including dehydrative side reactions that lead to the formation of alkenes and dimeric ethers, and the mutual catalyst inactivation when combined with enzymes in DKR methods. 23 Different compartmentalization strategies have been employed to enhance the compatibility of lipases and acid racemization catalysts in the DKR of sec-alcohols, such as spatial separation of the catalysts in two compartments connected by a pump loop, 18 confinement of the enzyme in a porous stainless-steel basket, 19 DKR under flow conditions, 20,21 and phase separation in a Pickering emulsion. 23 In 2020, our group evaluated for the first time the substrate scope and the catalyst recycling of the DKR of secondary benzyl alcohols catalyzed by immobilized Candida antarctica lipase B (CAL-B, commercial name: Novozyme 435) and hydrated vanadyl sulfate (VOSO 4 ) as acid racemization catalysts.…”

“…23 Different compartmentalization strategies have been employed to enhance the compatibility of lipases and acid racemization catalysts in the DKR of sec-alcohols, such as spatial separation of the catalysts in two compartments connected by a pump loop, 18 confinement of the enzyme in a porous stainless-steel basket, 19 DKR under flow conditions, 20,21 and phase separation in a Pickering emulsion. 23 In 2020, our group evaluated for the first time the substrate scope and the catalyst recycling of the DKR of secondary benzyl alcohols catalyzed by immobilized Candida antarctica lipase B (CAL-B, commercial name: Novozyme 435) and hydrated vanadyl sulfate (VOSO 4 ) as acid racemization catalysts. 22 The catalyst's recyclability was increased by employing a homemade Teflon tube to compartmentalize VOSO 4 , which allowed 8 DKR cycles without significant loss of activity or selectivity.…”