A unified synthesis of the C1-C19 building blocks 8-10 of halichondrins A-C was developed from the common synthetic intermediates 26a,b. Acetylenic ketones 26a,b were in With synthesized via selective activation/coupling of polyhalogenated nudeophiles 23a,b with aldehyde 11 in a (Ni)/Cr-mediated coupling reaction. Compared with Ni/Cr-mediated couplings Of vinyl iodides and aldehydes, this (Ni)/Cr-mediated coupling exhibited two unique features: First, the coupling was found to proceed with a trace amount or no added Ni-catalyst. Second, TES-Cl, a dissociating agent to regenerate the Cr-catalyst, was found to give a better yield than Zr(Cp)(2)Cl-2. An adjustment of the oxidation state was required to transform acetylenic ketones 26a,13 into C1-C19 building blocks 8 and 9 of halichondrins A and B, respectively. In the halichondrin B series, a hydroxyl-directed (Me)(4)NBH(OAc)(3) reduction of E- and Z-beta-alkoxy-enones 30 was found cleanly to achieve the required transformation, whereas a DMDO oxidation of E-vinylogous ester 21 allowed to introduce the C13 hydroxyl group with a high stereoselectivity in the halichondrin A series. In the halichondrin C series, Hf(OTf)(4) was used to convert the double oxy-Michael product 28 into C1-C19 building block 10.