Total Synthesis of (−)-Neocosmosin A via Intramolecular Diels–Alder Reaction of 2‑Pyrone

Abstract

A new synthetic route to (−)-neocosmosin A was devised by elaboration of intramolecular Diels–Alder (IMDA) cycloaddition of 2-pyrone containing a bromopropiolate group as the dienophile. The IMDA reaction was accompanied by cycloreversion of carbon dioxide to give benzannulated macrolide with two bromide groups at C14 and C16. Installation of the pinacolboryl groups and oxidations allowed completion of the total synthesis of (−)-neocosmosin A