An efficient synthesis of diquinane-based bis-γ-lactones

Abstract

An efficient stereoselective synthesis of both the diastereomers of diquinane-based conformationally constrained symmetric bis-γ-lactones starting from tricyclic derivative 9 is reported. The key step involves the intramolecular ring opening of an epoxide by the in situ formed hydrate of a diketone leading to the tetracyclic hemiacetal 10, which directly leads to the exo-hydroxy bis-γ-lactone derivatives 2 and 4 under basic hydrogen peroxide cleavage conditions. Conversion to the endo-hydroxy bis-γ-lactone derivatives 1 and 3 was accomplished through lithium hydroxide mediated S_N2 displacements in dimesylate 7, or more expeditiously, via trimesylate 21 through alkaline H₂O₂ mediated cleavage.