Total Synthesis of (± plus )-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-gamma-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.