Chemoenzymatic Synthesis of Enantiomerically Pure syn-Configured 1-Aryl-3-methylisochroman Derivatives



A two-step synthesis of various enantiomerically pure 1-aryl-3-methylisochroman derivatives was accomplished through asymmetric biocatalytic ketone reduction followed by an oxa-Pictet–Spengler reaction. The compounds were obtained in good to excellent yield (47–92 %) in favor of the syn diastereomers [dr (syn/anti) up to 99:1]. Enantiopure arylpropanols serving as pronucleophiles for the C–C bond-formation step were obtained by biocatalytic reduction by employing enantiocomplementary alcohol dehydrogenases, which gave access to the (S) and (R) enantiomer with up to >99 % conversion and up to >99 % ee.