Concise Synthesis of Polyacyloxy Cyclic Ethers Using the p‐Toluenesulfonic Acid‐Catalyzed Cascade Esterification/Cyclization of Polyols

A p‐toluenesulfonic acid (p‐TsOH)‐catalyzed cascade acylation‐cyclization‐acylation reaction of polyols with carboxylic acids has been developed, which affords polyacyloxy cyclic ethers without the need for the removal of water. The mild reaction conditions in the presence of p‐TsOH•H2O (10 mol%) permitted the use of a variety of carboxylic acids and polyols. In particular, when polyols with 1,4‐dihydroxy moieties were used, the present catalysis efficiently provided the corresponding polyacyloxy tetrahydrofuran derivatives in good‐to‐high yield without loss of optical purity. Furthermore, the concise synthesis of bicyclic isosorbide esters, which are of interest in an industrial and pharmaceutical context, was achieved using commercially available biomass‐derived D‐sorbitol and D‐mannitol via double cascade acylation‐cyclization‐acylation reactions.