Stereoselective Reduction of 2‐Hydroxy Ketones towards <i>syn</i>‐ and <i>anti</i>‐1,2‐Diols

Abstract

Abstract Stereoselective reduction of 2‐hydroxy ketones should in principle give access to syn ‐ and anti ‐1,2‐diols. anti ‐1,2‐Diols are accessible in a highly selective way using zinc borohydride [Zn(BH 4 ) 2 ] under chelation control ( dr &gt;20:1). Diastereoselective reduction of unprotected or even protected 2‐hydroxy ketones towards syn ‐1,2‐diols could be achieved only with moderate selectivity of dr ≤5:1. Even when using sterically demanding protecting groups and/or polymer‐supported borohydride reagents high selectivity could not be achieved. A new ionic liquid‐dependent borohydride reduction method, although highly attractive with respect to reaction engineering, resulted in only moderate to good selectivity. An efficient two‐step biocatalytic method for the synthesis of syn ‐1,2‐diols is described. The method relies on the whole‐cell Pichia glucozyma ‐catalyzed stereoselective reduction of the unprotected ( R )‐2‐hydroxy ketones ( dr &gt;10:1). The latter are accessible through thiamine diphosphate‐dependent enzyme‐catalyzed synthesis starting from simple aldehydes. Thus, biocatalytic transformations enable a process which is hardly accessible through present non‐enzymatic methods.