An entirely chromium-free synthesis of eribulin, a fully synthetic macrocyclic ketone analogue of the marine natural product halichondrin B, was achieved through iterative sulfone fragment couplings followed by an intramolecular Prins reaction involving a C.26 homoallenyl alcohol and a C.27 aldehyde acetal. A notable feature of this new macrocyclization is the employment of a β-ketosulfone at C.15/14 as an acid-stable progenitor of the notoriously acid-sensitive polycyclic ketal moiety, characteristic of the halichondrins.