A new stereocontrolled method for the formation of trans-anti cyclogeranyl-oxepene systems is described. The demanding stereochemistry is secured by stereoselective coupling of a cyclogeranyl tertiary alcohol with a 1,2-unsymmetrically substituted epoxide, while the formation of the highly strained oxepene is achieved employing ring-closing metathesis. Since the stereochemistry of the trans-fused 6,7-ring system is determined by the epoxide, the method also allows the construction of trans-syn 6,7-ring systems. This approach leads to the synthesis of the AB fragment of Adociasulfate-2 and Toxicol A, for the first time. The flexibility and efficiency of the presented strategy is demonstrated by the total asymmetric synthesis of (-)-Aplysistatin, (+)-Palisadin A, (+)-12-hydroxy-Palisadin B, and (+)-Palisadin B, employing two similar key intermediates.