Concise and Highly Stereoselective Synthesis of the C20–C26 Building Block of Halichondrins and Eribulin

A concise, stereoselective, and scalable synthesis of the C20–C26 building block of halichondrins and Eribulin is reported. The synthesis relies on three key transformations: regiospecific Ru-catalyzed intramolecular hydrosilylation, highly stereoselective SN2′ substitution, and selective conversion of a C–Si to C–I bond. It is carried out in a 5-pot/4-workup operation without chromatographic purification, except for filtration through a silica-gel plug, to give the C20–C26 building block (dr > 200:1; ee > 99%) in ca. 60% overall yield from epoxide 1.