Synthesis of (E)‐4‐Methylhexa‐3,5‐dien‐1‐ol and Its Diels–Alder Reaction with Thioester Dienophiles: A Short Enantioselective Synthesis of Bicyclic Lactones

Abstract

The preparation of (E)‐4‐methylhexa‐3,5‐dien‐1‐ol has been achieved in a single step from 3‐methylpenta‐1,4‐diene through deprotonation with BuLi, alkylation with paraformaldehyde and metal‐counterion exchange in situ to promote oxy‐anion‐accelerated [1,3]‐sigmatropic shift. This alcohol is shown to undergo intermolecular Diels–Alder reaction with 3‐isopropyl acrylate thioesters; the so‐formed exclusive endo‐adduct may then be closed to the bicyclic lactone, the product of formal intramolecular Diels–Alder reaction (a much more difficult process). Use of chiral thioesters results in an enantioselective synthesis of this bicyclic lactone, an intermediate with application to eunicellane (cladiellane) diterpene synthesis.