Development of a Copper-Catalyzed Thiopyridyl Ester Synthesis and Application to the Total Synthesis of Halichondrin B 1020

We present an efficient coupling of alkyl halides with 2,2'-dithiopyridyl carbonate to synthesize thiopyridyl esters, valuable building blocks in the preparation of ketones, amides and esters. This reaction is catalyzed by low-valent copper-mediated alkyl radical generation and typically proceeds in high yields (up to 96% yield; 26 examples) with good functional group tolerance. This methodology was showcased in the first total synthesis of halichondrin B 1020 and facilitated a divergent synthesis of the latently symmetrical left half spiroketal.