A method of preparing an intermediate in the synthesis of eribulin, said method comprising performing a macrocyclization reaction on a non-macrocyclic intermediate, said macrocyclization reaction producing said intermediate in the synthesis of eribulin by forming a C.2-C.3 bond in the structure of eribulin, wherein performing said macrocyclization reaction comprises contacting said non-macrocyclic intermediate with an organic base and a Lewis acid, and wherein said non-macrocyclic intermediate is a compound of formula (IIA) or a salt thereof: wherein each R is independently optionally substituted alkyl or optionally substituted aryl; (i) R 1 is H or a hydroxyl protecting group, and R 2 and R 3 combine to form a double bond; or (ii) R 1 and R 2 combine to form a bond, and R 3 is H; each P 3 is independently H or a hydroxyl protecting group, and X 2 is oxo; or both P 3 groups and X 2 , together with the atoms to which each is attached, combine to form ketal; P 4 is H or a hydroxyl protecting group; and X is O, and each of P 1 and P 2 is independently H or a hydroxyl protecting group, or P 1 and P 2 , together with the atoms to which each is attached, combine to form a cyclic protected diol; or X is N, and P 1 is H or a hydroxyl protecting group, and X and P 2 combine to form optionally masked amino; or P 1 and P 2 , together with the atoms to which each is attached, combine to form an aminal or 1,3-oxazolidin-2-one-5-yl; and wherein said intermediate in the synthesis of eribulin is a compound of formula (IIB) or a salt thereof: wherein performing said macrocyclization reaction comprises contacting said non-macrocyclic intermediate with an organic base and a Lewis acid, and wherein said non-macrocyclic intermediate is a compound of formula (IIA) or a salt thereof: wherein each R is independently optionally substituted alkyl or optionally substituted aryl; (i) R 1 is H or a hydroxyl protecting group, and R 2 and R 3 combine to form a double bond; or (ii) R 1 and R 2 combine to form a bond, and R 3 is H; (i) R 1 is H or a hydroxyl protecting group, and R 2 and R 3 combine to form a double bond; or (ii) R 1 and R 2 combine to form a bond, and R 3 is H; each P 3 is independently H or a hydroxyl protecting group, and X 2 is oxo; or both P 3 groups and X 2 , together with the atoms to which each is attached, combine to form ketal; P 4 is H or a hydroxyl protecting group; and X is O, and each of P 1 and P 2 is independently H or a hydroxyl protecting group, or P 1 and P 2 , together with the atoms to which each is attached, combine to form a cyclic protected diol; or X is N, and P 1 is H or a hydroxyl protecting group, and X and P 2 combine to form optionally masked amino; or P 1 and P 2 , together with the atoms to which each is attached, combine to form an aminal or 1,3-oxazolidin-2-one-5-yl; and X is O, and each of P 1 and P 2 is independently H or a hydroxyl protecting group, or P 1 and P 2 , together with the atoms to which each is attached, combine to form a cyclic protected diol; X is N, and P 1 is H or a hydroxyl protecting group, and X and P 2 combine to form optionally masked amino; or P 1 and P 2 , together with the atoms to which each is attached, combine to form an aminal or 1,3-oxazolidin-2-one-5-yl; and wherein said intermediate in the synthesis of eribulin is a compound of formula (IIB) or a salt thereof: <EOS>