Combination of Asymmetric Organo‐ and Biocatalysis in Flow Processes and Comparison with their Analogous Batch Syntheses

Abstract

AbstractA sequential‐type as well as a tandem‐type chemoenzymatic flow cascade combining an organocatalytic aldol reaction and a biocatalytic reduction to form stereoselectively a 1,3‐diol with two stereogenic centers were developed. Initially, a comprehensive screening of 24 alcohol dehydrogenases was carried out and the identified candidates were applied in different multi‐step flow cascades. All four stereoisomers of the desired 1,3‐diol product are accessible via a sequential flow approach with product formation‐related conversions of up to 76 % over two steps, isolated yields of up to 64 % and enantiomeric excess of >99 % in all cases. In addition, a tandem‐type flow process, performing both reaction steps simultaneously, was established leading to 51 % conversion with >99 % ee and 8 : 1 d.r. and representing a combination of the fields of asymmetric chemocatalysis, biocatalysis and flow chemistry.