Multiheterocyclic Motifs via Three-Component Reactions of Benzynes, Cyclic Amines, and Protic Nucleophiles

A broadly general, three-component reaction strategy for the construction of compounds containing multiple heterocycles is described. Thermal benzyne formation (by the hexadehydro-Diels-Alder (HDDA) reaction) in the presence of tertiary cyclic amines and a protic nucleophile (HNu) gives, via ring-opening of intermediate ammonium ion/Nu^- ion pairs, heterocyclic products. Many reactions are efficient even when the stoichiometric loading of the three reactants approaches unity. Use of HOSO₂CF₃ as the HNu gives ammonium triflate intermediates, which can then be ring opened by an even wider variety of nucleophiles.