Bidentate Lewis Acids for the Activation of 1,2-Diazines - A New Mode of Catalysis

Bidentate Lewis acids were applied as catalysts for the inverse-electron-demand Diels-Alder (IEDDA) reaction of 1,2-diazines. The concept of catalysis is based on the coordination of the bidentate Lewis acid to both nitrogen atoms of the 1,2-diazine moiety, thereby reducing the electron density and lowering the energy of the LUMO. This should, according to frontier molecular orbital (FMO) theory, facilitate the cycloaddition step. This new concept was successfully applied to a variety of dienophiles and substituted phthalazine substrates. Careful investigations of the mechanism led to the isolation and characterization of key intermediates; all of which support the presented catalytic cycle.