Scalable Regio- and Stereoselective Synthesis of Functionalized (E)-4-iodobut-3-en-1-ols: Gram-scale Total Synthesis of Fungal Decanolides and Derivatives

A reliable protocol to synthesize both racemic and chiral ( E )-4-iodobut-3-en-1-ols from aldehydes or epoxides, respectively, containing various aromatic and aliphatic substitutions has been established. The utility of these compounds was then demonstrated by providing access to known fungal decanolides as well as novel aromatic macrocycles. The protocol provided a gram scale route to (–)-aspinolide A and (–)-5- epi -aspinolide A utilizing a catalytic Nozaki-Hiyama-Kishi reaction to close the macrolide in the final step in 65-84% yield.