Total Synthesis of Aaptamine, Demethyloxyaaptamine, and Their 3-Alkylamino Derivatives.

A simple and efficient synthetic route for preparing the benzonaphthyridine framework is reported. Only seven steps are needed for the assembly of 3-alkylamino aaptamine from inexpensive isoquinoline 6 by this route with about 20% overall yield. The two key steps are a novel palladium-catalyzed reductive cyclization with Mo(CO)6 as reductant to form aaptamine and demethyloxyaaptamine and a hydrogen-bond-mediated oxidative alkylamination to account for the complete regioselectivity.