Enantioselective Total Synthesis of (+)-Arboridinine

The
enantioselective total synthesis of cage-shaped alkaloid (+)-arboridinine
is reported. The synthesis takes advantage of the stereoselective
double-Mannich reaction to rapidly construct the aza[3.3.1]­bicyclic
core along with two quaternary stereocenters of the alkaloid. Key
steps for the present synthesis include an enantioselective Michael
addition establishing the original chiral center at C10 and intramolecular
dearomative alkylation forging the cage-shaped ring system found in
arboridinine, as well as creating the requisite quaternary carbon
center at C3. The bridgehead hydroxyl moiety at C11 was installed
through a late-stage cobalt-catalyzed decarboxylative acetoxylation
reaction. This strategy enables a 14-step asymmetric total synthesis
of (+)-arboridinine from the readily available starting materials
with most of the transformations performed on the decagram scale.