Enantioselective Total Synthesis of (−)-Caldaphnidine O via a Radical Cyclization Cascade

The synthetically
challenging, diverse chemical skeletons and promising
biological profiles of the Daphniphyllum alkaloids have generated intense interest from the synthetic chemistry
community. Herein, the first and enantioselective total synthesis
of (−)-caldaphnidine O, a complex bukittinggine-type Daphniphyllum alkaloid, is described. The key transformations
in this concise approach included an intramolecular aza-Michael addition,
a ring expansion reaction sequence, a Sm­(II)/Fe­(III)-mediated Kagan–Molander
coupling, and the rapid formation of the entire hexacyclic ring skeleton
of the target molecule via a radical cyclization cascade reaction,
which was inspired by an unexpected radical detosylation observed
in our recent dapholdhamine B synthesis.