Asymmetric Formal Total Syntheses of (+)- and (−)-Limaspermidine from Chirally Resolved 2-Pyrone Diels–Alder Cycloadducts via Aromatic C–H Amidation and Imino-Diels–Alder Reaction

A new asymmetric synthetic route to (+)- and (−)-limaspermidine was devised, starting with chirally resolved enantiomerically pure 2-pyrone Diels–Alder cycloadducts. This route utilizes intramolecular Pd-catalyzed aromatic C–H amidation and imino-Diels–Alder reactions to construct the key indoline and indolizidine subunits onto the central cyclohexane core, allowing the straightforward formal total syntheses of both (+)- and (−)-limaspermidine.