Total Synthesis of the Lycopodium Alkaloid Serratezomine A Using Free Radical-Mediated Vinyl Amination to Prepare a β‑Stannyl Enamine Linchpin

Serratezomine A is a member of the structurally diverse
class of
compounds known as the Lycopodium alkaloids. The
key supporting studies and successful total synthesis of serratezomine
A are described in this account. Significant features of the synthesis
include the first application of free radical mediated vinyl amination
and Hwu’s oxidative allylation in a total synthesis and an
intramolecular lactonization via a transannular SNi reaction.
Minimal use of protecting groups and the highly diastereoselective
formation of a hindered, quaternary stereocenter using an umpolung
allylation are also highlights from a strategy perspective. Observation
of quaternary carbon epimerization via a retro-Mannich/Mannich
sequence highlights the additional challenge presented by the axial
alcohol at C8 in serratezomine A.