Chemo‐Enzymatic Dynamic Kinetic Resolution of Symmetric and Non‐Symmetric α‐Hydroxy Ketones for Industrial Application

• Published in: ChemistrySelect (Weinheim) 2019-06, Vol.4 (21), p.6469-6472
• Main Authors: Petrenz‐Beck, Annika, Kühn, Jasmin, Zuhse, Ralf, Ansorge‐Schumacher, Marion B.
• Format: Article
• Language: English
• Subjects: 2-hydroxy ketone; biocatalysis; dynamic kinetic resolution; immobilization; S-PAC
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.201900740

α‐Hydroxy ketones are important intermediates in various drugs and fine chemicals. Stereoselective synthesis of both symmetric and asymmetric compounds is demonstrated involving benzoin, 2–2’‐furoin, phenylacetyl carbinol (PAC) and 2‐hydroxy‐1‐phenylpropan‐1‐one (HPP) as representatives. Dynamic kinetic resolution of the racemic preparations was achieved in one‐pot combining transesterification catalyzed by immobilized lipases from Pseudomonas stutzeri and Pseudozyma antarctica, respectively, and racemization mediated by the heterogeneous chemo‐catalyst Zr‐TUD‐1 in water‐free organic solvent. (S)‐benzoin, (S)‐2,2’‐furoin, (S)‐PAC and (R)‐HPP were obtained with both high efficiency and high enantiomeric excess. Within 90 minutes, 2,45 g (S)‐PAC butyrate (ee 88%) yielded from a 130 mL batch reaction demonstrating both technical feasibility and relevance for application. Stereoselective synthesis of the synthetically important α‐hydroxy ketones benzoin, 2–2’‐furoin, phenylacetyl carbinol (PAC) and 2‐hydroxy‐1‐phenylpropan‐1‐one (HPP) was achieved by one‐pot combination of immobilized enzyme and heterogeneous chemo‐catatyst. Products were obtained with high efficiency and enantiomeric excess. Technical feasibility and relevance for application were demonstrated at the synthesis of (S)‐PAC butyrate on preparative scale.