A general stereoselective method for the synthesis of cis:anti:cis polycyclic ethers containing six-, seven-, and eightmembered rings from a simple precursor has been reported. The methodology involves oxonium ion mediated intramolecular cyclization, carbon-carbon bond formation and ring-closing metathesis as key features.Polycyclic ethers containing fused six-, seven-, and eightmembered cyclic ethers are present in a large number of marine natural products such as brevetoxins, hemibrevetoxin B, and ciguatoxins. 1 Many of these polycyclic ethers possess important biological properties. 2 The complex molecular architecture containing an array of fused cyclic ethers coupled with their biological properties have stimulated significant interest in development of strategies and methodologies for the synthesis of polycyclic ethers. 2,3 Most of the methods deal with synthesis of trans-fused polycyclic ethers since a majority of the naturally occurring polycyclic ethers contain trans-fused cyclic ethers. There are only a few methods leading to cisfused polycyclic ethers 4 though motifs containing cisfused cyclic ether ring systems are present in the framework of (Z)-and (E)-dactomelyenes 5a (1a,b, Figure 1) and several subunits of polycyclic ethers such as halichondrin and maitotoxin. 5b Figure 1 Structure of dactomelynesIn view of the above, we considered developing a general methodology for the synthesis of polycyclic ethers containing fused [6,6,6], [6,6,7], and [6,6,8] ring systems from a simple and readily available precursor. The oxocarbenium ion mediated cyclization, alkylation, 6,7 and ring-closing metathesis 8,9 are the key features of our methodology. Our strategy is outlined in Scheme 1. We envisioned that oxocarbenium ion mediated intramolecular cyclization in the precursor 4 followed by further manipulation would give the bicyclic ether 3. Subsequent introduction of oxy-allyl chain and alkoxy group across vinyl ether group in 3 followed by cyclization and further manipulation would afford the tricyclic ether 2. The precursor 4, in turn, was thought to be readily accessible from dihydropyran (Scheme 1). In addition, it was also contemplated that the precursor 3 would be readily elaborated to O O H H Br Cl (3E)-dactomelyne (1a) (3Z)-dactomelyne (1b)