High Resolution Image Download MS PowerPoint Slide A full account of our total synthesis of aleutianamine ( 1 ) is disclosed. An initial α-thioketone derivatization approach was thwarted by a failed enolate functionalization. A second-generation approach employing palladium-catalyzed Barbier addition enabled the successful construction of the 3.3.1bicyclononane moiety of the natural product, but unsuccessful downstream functionalization and poor material throughput led to the abandonment of this approach. Along the way, a one-pot Larock indolization/Buchwald–Hartwig amination cascade was developed for the synthesis of tricyclic diaminoindole derivatives. Eventually, the total synthesis was accomplished via a novel dearomative arylation of an aminothiophene, which allowed rapid access to the molecular skeleton of aleutianamine including the challenging bridgehead sulfide. Following construction of the core, cerium-mediated oxidative amination and palladium-catalyzed decarboxylative pinacol-type rearrangement enabled chemoselective introduction of the C10 aniline and alkenyl bromide, leading to the total synthesis of aleutianamine.
Yu et al. (Thu,) studied this question.