Furanophane Transannular Diels−Alder Approach to (+)-Chatancin:  An Asymmetric Total Synthesis of (+)-Anhydrochatancin

(+)-Anhydrochatancin was synthesized while attempting an enantioselective total synthesis of (+)-chatancin. The presented route constitutes the furanophane approach, one of the two ways of proposed biosynthesis which may involve transannular Diels−Alder (TADA) reaction to link this diterpene biogenetically to the furanocembranoids. Highlights of the synthetic work include the assembly of chiral, acyclic, trisubstituted furan 28 via a coupling of aldehyde 10 and dilithiofuroic acid 11, a macrocyclization to furanophane 29E via ring-closing metathesis, a TADA reaction to reach tetracyclic intermediate 4, and a hydride shift mediated oxygen transposition as a final rearrangement to the target. Unfortunately, the strongly acidic condition required for the last step allows only the isolation of anhydrochatancin 30 due to the acid sensitivity of chatancin 1.