Kinetic and Dynamic Kinetic Resolution by Dual Catalysis

Abstract

Kinetic resolution is one of the most common methods to access enantiomerically enriched compounds. In this method, the resolution is based on the existing difference in reaction rates of the two enantiomers with a chiral catalyst. In the dynamic kinetic resolution, the less reactive enantiomer is racemized and the racemic mixture is further resolved, leading eventually to complete transformation to an enantioenriched compound. This review summarizes the dual catalytic strategies (i. e., modular combinations of distinct catalysts) that have been applied to kinetic resolution and dynamic kinetic resolution. We focus upon the role of the two catalysts, the compatibility between them, and the practical benefits.

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

“…13 Meanwhile, various transition metal catalysts have been used as racemization agents in chemoenzymatic DKR protocols, with ruthenium complexes being particularly well-studied for their effectiveness in redox racemization of sec-alcohols via hydrogen transfer. 7 Novel reaction designs of lipase-metal DKR of secondary alcohols are still needed to meet the demand for more robust methods with readily available and safer catalysts. For example, compartmentalizing the catalysts is a promising option to overcome incompatibility issues and facilitate operational processes.…”

“…In the DKR approach, a kinetic resolution (KR) of the racemate, i.e., preferential conversion of one enantiomer promoted by a chiral catalyst, is combined with a simultaneous racemization of the slower-reacting enantiomer, which allows a theoretical yield of 100% of a chiral product with high enantiomeric excess ( ee ) (Scheme ). , However, achieving an efficient DKR requires effort, such as ensuring a highly enantioselective KR and a racemization rate faster than the resolution reaction rate . Also, the racemization catalyst must not react with the resolution product and must be compatible with the chiral catalyst under the defined reaction conditions …”

“…DKR catalyzed by an enzyme-metal dual system is an attractive route to produce enantiomerically pure secondary alcohols. , Racemic secondary alcohols are frequently resolved by lipase-catalyzed enantioselective acylation due to the ability of these enzymes to discriminate between the enantiomers of a racemic mixture. , This discrimination occurs in their active site, which consists of a catalytic triad: serine (a nucleophilic residue), aspartic or glutamic acid (a catalytic acidic residue), and histidine (a residue hydrogen-bonded to the acidic residue) . Meanwhile, various transition metal catalysts have been used as racemization agents in chemoenzymatic DKR protocols, with ruthenium complexes being particularly well-studied for their effectiveness in redox racemization of sec -alcohols via hydrogen transfer …”

Recent advances in intramolecular kinetic resolution reactions

“…6 Namboothiri et al presented a review of kinetic and dynamic kinetic resolution by dual catalysis in 2022. 7 However, it is obvious that in these reviews the intramolecular KR reactions are still lacking systemic classification and summarization. Therefore, a comprehensive review focusing on the recent advances in intramolecular KR reactions is an urgent need.…”