Acid-Catalyzed Oxy-aminomethylation of Styrenes.

We report a strong Brønsted acid-catalyzed three-component oxy-aminomethylation of styrenes with sym-trioxane and sulfonamides or carbamates. This transformation provides a variety of 1,3-oxazinanes in moderate to good yields under mild reaction conditions. The obtained heterocycles can be readily transformed into the corresponding 1,3-amino alcohols, which are useful building blocks for the synthesis of pharmaceutically relevant molecules. Mechanistic studies suggest the intermediacy of an in situ formed 1,3,5-dioxazinane and a subsequent reaction with the olefin.

The Catalytic Asymmetric Intermolecular Prins Reaction.

Despite their significant potential, catalytic asymmetric reactions of olefins with formaldehyde are rare and metal-free approaches have not been previously disclosed. Here we describe an enantioselective intermolecular Prins reaction of styrenes and paraformaldehyde to form 1,3-dioxanes, using confined imino-imidodiphosphate (iIDP) Brønsted acid catalysts. Isotope labeling experiments and computations suggest a concerted, highly asynchronous addition of an acid-activated formaldehyde oligomer to the olefin. The enantioenriched 1,3-dioxanes can be transformed into the corresponding optically active 1,3-diols, which are valuable synthetic building blocks.