A Chemo-Enzymatic Approach to the Synthesis of Optically Active 2,4-Disubstituted Aryloxetanes

Functionalized oxetanes are useful building blocks in the preparative chemistry as well as in synthesis of drugs, materials, agrochemicals [1]. In this communication we report the preliminary results of the first chemo-enzymatic synthesis of optically active 2,4-disubstituted oxetanes, prepared by cyclization of optically active 1,3-diols [2], in turn obtained by steroselective reduction of the corresponding 1,3-diketones with yeasts. The stereoselective reduction of symmetrical and nonsymmetrical substituted 1,3-diketones was investigated in the presence of some conventional and non-conventional yeast strains (Saccharomyces cerevisiae, Kluyveromyces marxianus, Baker’s yeast, etc.). Optically active aldols were obtained with high stereopreference by baker’s yeast, and then diastereoselectively converted in the corresponding diols (dr> 95%) which were then cyclized into the corresponding 2,4-disubstituted oxetanes in good yields, with high diastereoisomeric ratio (dr) and enantiomeri excess up to 80 %.