The invention provides methods for the synthesis of a halichondrin macrolides through a macrocyclization strategy. The macrocyclization strategy of the present invention involves subjecting a non macrocyclic intermediate to a carbon carbon bond forming reaction (e.g. an olefination reaction (e.g. Horner Wadsworth Emmons olefination) catalytic Ring Closing Olefin Metathesis or Nozaki Hiyama Kishi reaction) to afford a macrocyclic macrolide. The invention also provides compounds useful as intermediates in the synthesis of a halichondrin macrolides and methods for preparing the same.
