Alternative tandem cyclisation pathways in the reaction between imines and enones

Abstract Dihydroisoquinoline reacts with Danishefsky's diene under Lewis acidic conditions or neat, to give low to moderate yields of the formal aza-Diels–Alder, [4+2]-cycloadduct. However, using methoxyvinyl methylketone with Lewis acid catalysis does not give the aza-Diels–Alder adduct, rather a formal [2+2+2]-cycloaddition occurs to provide access to a diacetyl dihydropyridine. Increased Lewis acid loading results in reduced dihydropyridine formation, and instead, a trimerisation reaction of the methoxyvinyl methyl ketone occurs, to give 1,3,5-triacetylbenzene from a different formal [2+2+2]-cycloaddition. The formal [4+2]-cycloaddition reaction of methoxyvinyl methylketone requires a cyclic imine in order to form the dihydropyridine because the reaction with acyclic imines produced a dihydropyridine from a formal [1+2+1+2]-cycloaddition. Evidence resulting from the isolation of reaction intermediates and in situ spectroscopic studies, shows that the reaction between 3 ,4-dihydroisoquinoline and methyl vinyl ketone, catalysed by oxy-philic Lewis acids, proceeds via a Mannich-Michael pathway and an imminium ion species. All reactions occur by one-pot cascade routes.