Oxidative Ring Expansion of Cyclobutanols: Access to Functionalized 1,2-Dioxanes

Cyclobutanols undergo an oxidative ring expansion into 1,2-dioxanols by using Co(acac)2 and triplet oxygen (3O2) as radical promoters. The formation of an alkoxy radical drives to the regioselective break of the strained ring with stabilization of a new radical on the most substituted side. The radical traps then oxygen to form 1,2-dioxanols. The reaction is particularly effective on secondary cyclobutanols but can work also on tertiary alcohols. Further acetylation generates peroxycarbenium species under catalytic Lewis acid conditions, which react with neutral nucleophiles. Many original 1,2-dioxanes, which would be difficult to prepare by another method, were then obtained with a preferred 3,6-cis-configuration. This method provides an interesting access to the total synthesis of many natural endoperoxides.