A Migratory Ether Formation Route to Medium-Sized Sugar Mimetics.

Polyol-substituted cyclic ethers are fundamental building blocks of biomolecules. The position and stereochemistry of multiple hydroxy substituents of cyclic ethers play a central role in their biological function. Current methods for the synthesis of such structures are limited to "naked" ring products with no or few substituents. Here we describe a general route to medium-sized polyol cyclic ethers using a migratory ether formation strategy. In contrast to the common pathway of direct opening of epoxides, Me3 Al was found to promote an unprecedented ether addition reaction, opening a neighboring epoxide. The resulting oxonium intermediate triggers a 1,3-methyl shift to yield 2-deoxyribital products. When the hemiacetal auxiliary is a monosaccharide, the sugar ring is expanded by four atoms to give the corresponding 9- to 11-membered analogues. This method provides an entry into the untapped chemical space of medium-sized sugar mimetics.