The success and stereochemical outcome of the TiCl4-promoted oxa-Pictet–Spengler cyclization of 5-aryl-1, 3-dioxolanes to produce 1, 3-disubstituted-4-hydroxy-isochromans, is influenced by the length and nature of the side chains bound to C-2 and C-4 of the dioxolane. Methyl groups yield a mixture of 4-hydroxy-isochromans in which the 1, 3-trans diastereomer predominates, while bulkier substituents give 1, 3-cis diastereomers. ...