A novel and efficient total synthesis of cephalotaxine

[reaction: see text] Total synthesis of cephalotaxine (CET), the parent member of a class of structurally unique antileukemia Cephalotaxus alkaloids, was accomplished on the basis of a conceptually novel strategy featuring transannular reductive skeletal rearrangements as the key transformations for the construction of the pentacyclic ring skeleton of CET. The synthetic potential of the designated Clemmensen-Clemo-Prelog-Leonard reductive rearrangement was demonstrated for the first time in a facile synthesis of the benzazepine subunit of CET. A novel endocyclic enamine (cyclopentenone) annulation was discovered and rationalized as an unusual azo-Nazarov-type cyclization.