Iron-catalyzed cascade synthesis of nitrogen polycycles from alkynoic acids and functionalized amines

Abstract

Catalysis by first-row transition metals is of increasing interest in the context of the scarcity of chemical resources. For instance, iron is promising due to its abundance, low toxicity and unique electronic features. Here we synthesized quinazoline alkaloids from alkynoic acids and functionalized amines in the presence of iron dibromide and pyridine in toluene or, alternatively, in a solventless reaction system. We studied iron sources, reaction media and the effect of additives. Results show 39-99% yields and regioselective preparation of nitrogen- and oxygen-containing scaffolds. This is the first example of a cascade process involving alkynoic acids catalyzed by iron. Fe is more abundant, cheaper and less toxic than other Au, Cu and Ru catalysts previously reported for similar transformations.