Synthesis of the Madangamine Alkaloid Core by a C–C Bond Activation Cascade

The diazatricyclic core of the madangamine alkaloids was synthesized from a densely functionalized cyclohexane derivative. An alkene and two cyanoformamide groups are used to form two new rings and a new quaternary stereocenter in a cascade reaction, which involves two Pd-catalyzed C–C bond activation steps. The synthesis of the cascade precursor involves an intramolecular Staudinger reaction of a vicinal diester that gives a [3.2.1]­azabicyclooctane derivative, allowing the regioselective introduction of a monosubstituted alkene.