Acid-Catalyzed Oxy-aminomethylation of Styrenes

Abstract

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.