A Short Synthesis of (±)-3-Demethoxyerythratidinone by Ligand Controlled Selective Heck Cyclization of Equilibrating Enamines

A short, 5-step total synthesis of (±)-3-demethoxyerythratidinone from a simple pyrrole derivative is described. Features include the formation of gram quantities of a key tricylic aziridine from a challenging photochemical cascade reaction through the use of flow photochemistry. The final step involved a highly unusual Heck cyclization whereby ligand control enabled efficient formation of the natural product in 69% yield from the minor isomer present in an equilibrating mixture of labile enamines.