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.