Synthesis of Bridged Inside–Outside Bicyclic Ethers through Oxidative Transannular Cyclization Reactions

The classical geometry of the 6-<i>endo</i> 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-<i>trans</i>-dialkyl tetrahydropyrans. The bicyclic products exhibit inside–outside stereoisomerism, as seen in numerous macrolide natural products