We have described a chemo-, regio-, and stereocontrolled methodology for the simple and efficient synthesis of a large variety of cis-decalins and related fused polycyclic systems with control at up to six stereocenters, based on the sequential ring-opening of dioxacyclic templates. We have established that the most useful feature of the reactivity of the dioxacyclic compounds toward the nucleophilic ring-opening reaction is that the first ring-opening reaction is significantly faster than the second allowing the sequential transformation of the oxabicyclic moieties. The flexibility of the sequential ring-opening process and its limitations have been demonstrated and a new enantioselective mode of opening was reported. The enantioselective base-induced desymmetrization was successfully applied to a thiadioxapentacycle to give the product in >95% ee using a chiral lithium amide base.