Remarkably chemoselective indium-mediated coupling en route to the C21–C40 acyclic portion of the azaspiracids

A densely functionalized acyclic intermediate representing the C21–C40 portion of the novel marine natural product azaspiracid was prepared via a chemoselective indium-mediated coupling between C21–C27 and C28–C40 intermediates. Although the coupling partners contained aldehyde, azide, ketone, enone, and lactone functionalities, the C21–C27 allylic species added selectively to the aldehyde of a C28–C40 intermediate under aqueous indium-mediated conditions. The C21–C27 and C35–C40 fragments were prepared in a divergent fashion from a common syn-1,3-dimethyl synthon 9.