Pyranophane Transannular Diels−Alder Approach to (+)-Chatancin: A Biomimetic Asymmetric Total Synthesis

An asymmetric total synthesis of (+)-chatancin was achieved via a transannular Diels−Alder
(TADA) reaction of an in situ generated macrocyclic pyranophane pseudobase. The presented route
constitutes the second of two proposed biosynthetic pathways that involves a TADA reaction. It
links this diterpene biogenetically to the cembranoids. A set of TADA selection rules that rationalize
the formation of (+)-chatancin from a dynamic equilibrium of four 2-hydroxy-2H-pyrane bicycles
and their 16 potential TADA transition states are also outlined. Beyond the TADA reaction,
highlights of the synthetic work include the assembly of a chiral acyclic macrocyclization substrate
from (S)-citronellol and an efficient macrocyclization via a β-ketosulfoxyde/enone Michael addition.