Stereoselective Formation of Bis(α-hydroxy ketones) via Enzymatic Carboligation

The enzymatic approach to a novel class of chiral bis(α-hydroxy ketones) of type 5 and 8, which enable the synthesis of new multidentate ligands for asymmetric transition metal catalysis, is described. The key step is the second benzoylformate decarboxylase catalyzed C−C-bond formation between an aromatic dialdehyde and acetaldehyde, which proceeds with complete stereocontrol. Transformation of enantiomerically enriched monoadduct (S)-4 (ee 88%) and (S)-7 (ee 79%) resulted in optical pure (S,S)-5 and (S,S)-8 besides minor amounts of the corresponding diastereomeric meso-forms.