Synthesis of bridged inside-outside bicyclic ethers through oxidative transannular cyclization reactions.

The classical geometry of the 6-endo transition state for nucleophilic additions into oxocarbenium ions can be perturbed by incorporating the reactive groups into medium-sized rings, leading to the formation of 2,6-trans-dialkyl tetrahydropyrans. The bicyclic products exhibit inside-outside stereoisomerism, as seen in numerous macrolide natural products.