Atroposelective biocatalysis employing alcohol dehydrogenases

The biocatalytic synthesis of axially chiral heterobiaryl compounds is an area of great interest. A particularly valuable approach involves the atroposelective transformation of achiral, configurationally labile, or racemic heterobiaryl molecules using biocatalysis. By judicious designing the structure of the starting material, Dynamic Kinetic Resolutions (DKR) have been developed to produce higablehly enantioenriched atropisomers with excellent yields and selectivities. Thus, indole- and quinoline-based aldehydes with a precise structure have been prepared. The non-covalent Lewis interaction between the carbonyl group and a nitrogen atom is responsible for the atropoisomerization (dynamization) of the stereogenic axis. The employment of commercially available alcohol dehydrogenases (ADHs) led to the enantiodivergent synthesis of a variety of heterobiaryl alcohols with high yields and excellent enantiomeric excesses. For the substrate in which the DKR led to optical purities lower than 90 %, solvent engineering was performed, thus being possible to obtain both atropoisomers of the final alcohol with high enantiomeric excesses by using methyl tert-butyl ether or tetrahydrofuran as cosolvents.