Divergent Total Syntheses of Pyrroloiminoquinone Alkaloids Ena-bled by the Development of a Larock/Buchwald–Hartwig Annula-tion/Cyclization

ABSTRACT: Pyrroloiminoquinone alkaloids are a large class of natural products that display a wide range of biologi-cal activities. Synthetic approaches to these natural products typically rely on a common late-stage C10-oxygenated pyrroloiminoquinone intermediate, but these strategies often lead to lengthy synthetic sequences that are not ame-nable to divergent syntheses. We devised an alternative approach aimed at the early introduction of the C10 nitro-gen, which we hypothesized would enable late-stage diversification. This strategy hinged upon a Larock/Buchwald–Hartwig annulation/cyclization to quickly access the core of these alkaloids. We report the development of this cas-cade process, which was facilitated by a dual ligand system in addition to selective functionalization of the key inter-mediate, to provide the shortest total syntheses to date of makaluvamines A, C, and D and isobatzelline B, and the first total synthesis of makaluvamine N.