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 .