Total Synthesis of (±)-Maistemonine, (±)-Stemonamide, and (±)-Isomaistemonine

A full account of the total synthesis of (±)-maistemonine,
(±)-stemonamide, and (±)-isomaistemonine is presented. Two
approaches have been developed to construct the basic pyrrolo­[1,2-a]­azepine core of the Stemona alkaloids,
featuring a tandem semipinacol/Schmidt rearrangement of a secondary
azide and a highly stereoselectively desymmetrizing intramolecular
Schmidt reaction, respectively. To build the common spiro-γ-butyrolactone,
a new protocol was carried out by utilizing an intramolecular ketone-ester
condensation as the key transformation. The vicinal butyrolactone
moiety of (±)-maistemonine was stereoselectively introduced via
a one-pot procedure involving the epimerization at C-3 and carbonyl
allylation/lactonization. Moreover, (±)-stemonamide was divergently
synthesized from a common intermediate, and (±)-isomaistemonine
was obtained via the epimerization of (±)-maistemonine at C-12.