A convergent synthesis of (+)-asteltoxin (1) has been achieved by the Horner−Emmonsolefination of bis(tetrahydrofuran) aldehyde 53 and α-pyrone phosphonate 5. A key step features thestereoselective construction of a sterically congested quaternary center embedded in the denselyfunctionalized bis(tetrahydrofuran) subunit by a Lewis acid-catalyzed, pinacol-type rearrangement of anepoxy silyl ether. This pivotal rearrangement methodology parallels the proposed biosynthetic pathway of1 and is ripe for applications to the stereocontrolled synthesis of structurally complex natural products.