A proof of concept for the combination of an asymmetric organocatalytic reaction with a biotransformation toward a “one-pot like” process for 1,3-diols based on immobilized organo- and biocatalysts, which are utilized in different compartments, is demonstrated. This process which runs completely in organic media consists of an initial proline-derivative-catalyzed aldol reaction and a subsequent reduction of the aldol adduct catalyzed by an alcohol dehydrogenase (ADH) without the need for intermediate isolation. Economically attractive superabsorber-based coimmobilization for the ADH and its cofactor NAD+ turned out to give a highly efficient biocatalyst with excellent reusability and simple product separation from the immobilizate under avoidance of any tedious extraction steps during the overall process.

No abstract

The combination of an asymmetric organocatalytic aldol reaction with a subsequent biotransformation toward a "one-pot-like" process for the synthesis of (R)-pantolactone, which to date is industrially produced by a resolution process, is demonstrated. This process consists of an initial aldol reaction catalyzed by readily available l-histidine followed by biotransformation of the aldol adduct by an alcohol dehydrogenase without the need for intermediate isolation. Employing the industrially attractive starting material isobutanal, a chemoenzymatic three-step process without intermediate purification is established allowing the synthesis of (R)-pantolactone in an overall yield of 55% (three steps) and high enantiomeric excess of 95%.

An acid formed autoxidatively from an aldehyde substrate as a side product was found to alter the reaction kinetics and selectivity significantly in the direct asymmetric aldol reaction between an aldehyde and acetone, both in aqueous media and cyclohexane. Furthermore, this side‐product catalysis (“impurity catalysis”) was also observed upon using commercial samples of aldehydes without purification prior to their use (owing to the presence of the acid formed therein during storage), which thus underlines the impact of substrate purity on the reaction course of the catalytic process.