AbstractIn view of the described results in acid‐induced polyepoxide cyclizations, the biosynthesis of fused polyether toxins may be better explained by a stepwise mechanism through oxonium ion intermediates acting on the enzyme‐bonded polyepoxide precursor. A new synthetic strategy for the regio‐ and stereospecific synthesis of heterosubstituted oxolane and oxane rings involving intramolecular iodoetherification of 2,3‐epoxy‐cycloalken‐1‐ols was studied. Cyclization/solvolysis of 2,3‐epoxy‐cycloalk‐5‐en‐1‐ols proceed with complete regio‐ and stereoselectivity to yield cis‐2,6‐dialkyl‐3,5‐oxygenated oxane rings and thus assemble in two steps the key structural units present in marine syn‐trans fused polyether toxins. A highly efficient cyclization reaction of 2,3‐epoxycyclonon‐6‐en‐1‐one leading to the oxepane system is described. The silver(I)‐induced solvolysis occurs in high yield under mild conditions and the resulting cyclic system may be manipulated via oxidative carbon‐carbon bond cleavage leading to a functionalized α, α′‐dialkyl β,β′‐oxygenated oxepane ring with defined cis‐syn‐cis stereochemistry.