A three-component coupling approach to the ACE-ring substructure of C19-diterpene alkaloids.

C19-diterpene alkaloids are a class of alkaloids with pharmacologically important activities having an intricately fused hexacyclic ABCDEF-ring system. Here we report expeditious assembly of the ACE-ring substructure 4a by applying a three-component coupling strategy. A radical-polar crossover reaction between an AE-ring radical precursor, a C-ring radical acceptor and an aldehyde was realized by the actions of Et3B and O2, resulting in the installation of three new stereocenters and extension of the carbon chain corresponding to the B-ring. As the ACE-ring 4a possesses the correct C4,11-quaternary and C10-tertiary carbons, 4a would serve as an advanced intermediate for constructing the entire C19-diterpene alkaloid structures.