Bronsted Acid Catalyzed Addition of Enamides to ortho-Quinone Methide Imines-An Efficient and Highly Enantioselective Synthesis of Chiral Tetrahydroacridines

The direct and highly enantioselective synthesis of tetrahydroacridines was achieved through the phosphoric acid catalyzed addition of enamides to in situ generated orthoquinone methide imines and subsequent elimination. This novel one-step process constitutes a very efficient, elegant, and selective synthetic approach to valuable N-heterocycles with a 1,4-dihydroquinoline motif. By subsequent highly diastereo-selective hydrogenation and N-deprotection the reaction products were easily converted into free hexahydroacridines with a total of three new stereogenic centers.