Free Radical Cyclizations in Alkaloid Total Synthesis: (±)-21-Oxogelsemine and (±)-Gelsemine

Total syntheses of (±)-21-oxogelsemine ( 3 ) and (±)-gelsemine ( 1 ) are described. Free radical cyclizations play important roles in constructing the tricyclic core ( 40 → 41 ) and oxindole ( 93 → 96 ) substructures of the target alkaloids, and an isomerization−cyclization strategy ( 101 → 102 ) was used to complete construction of the gelsemine cage. Observations made along the way include intramolecular 1,4- and 1,6-hydrogen atom transfers ( 64 → 65 and 40 → 47 ) and a free radical cyclization-fragmentation sequence ( 85 → 86 + 87 ). A retroaldol−aldol strategy for adjusting oxindole stereochemistry in gelsemine-like structures is also described ( 72 → 74 and 86 → 87 ).