Collective Total Synthesis of 4‐Azafluorenone Alkaloids

Abstract 4‐Azafluorenones are typically obtained by acid‐mediated cyclization of 2‐arylnicotinates. However, this approach fails to give 5‐oxygenated 4‐azafluorenones due lactonization 2‐(2‐alkoxy)phenylnicotinate intermediates. Herein, we report two modifications established approaches 4‐azafluorenone synthesis that, either in combination or themselves, enable the flexible preparation with diverse oxygenation patterns benzenoid ring. Undesired was circumvented via tert ‐butyl hydroperoxide (TBHP)‐mediated radical 2‐aryl‐3‐(hydroxymethyl)pyridines. In absence suitable protecting groups for phenolic intermediates, bromide substituents were regioselectively introduced as latent hydroxy and later converted under palladium catalysis. We present first total syntheses five alkaloids muniranine, darienine, 5,8‐dimethoxy‐7‐hydroxyonychine, 5,6,7,8‐tetramethoxyonychine, 6,8‐dihydroxy‐7‐methoxyonychine addition new six one related pyridocoumarin alkaloid.