Bioinspired Total Synthesis of (±)-Chaetophenol C Enabled by a Pd-Catalyzed Cascade Cyclization

A novel
Pd­(II)-catalyzed cascade reaction has been developed that
consists of a highly regio- and stereoselective oxa [4 + 2] cycloaddition
reaction of o-alkynylbenzaldehydes and an intramolecular
carboxylic group quenching of the in situ generated oxonium ion. This
new reaction provides a one-step construction of the tetracyclic core
structure of chaetophenol C from two simple starting materials. The
developed chemistry was successfully applied to the first total synthesis
of chaetophenol C and dozens of its analogues.