A formal synthesis of marine-derived antitumor natural product varitriol from a 5-oxabicyclo[2.1.1]hexane derivative is described. A tetrahydrofuran unit of varitriol embedded with four contiguous stereocenters was synthesized with an overall yield of 10.2% in 11 steps from an oxa-bicyclic system. An unprecedented oxidative cleavage reaction involving scissoring of two CC bonds at oxa-quaternary carbon of THFs leading to γ-butyrolactones was reported and a plausible mechanism has been proposed. © 2014 Elsevier Ltd. All rights reserved.