Studies on the intramolecular oxa-Pictet–Spengler rearrangement of 5-aryl-1,3-dioxolanes to 4-hydroxy-isochromans

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. Functional groups in the C-2 side chain of the dioxolane ring may hinder cyclization by complexation with the promoter.