Synthesis of (±)-Angustatin A: Assembly of the Phenanthrene Moiety Despite Increasing Ring Strain.

Abstract

The synthesis of (±)-angustatin A, a phenanthrene-containing cyclophane that possesses conformational chirality, is reported. Key steps include a Pd-catalyzed Negishi coupling to assemble the necessary terphenyl intermediate, its closure into a 14-membered macrocycle via a catalytic-in-phosphine Wittig olefination, and finally a Pt-catalyzed alkyne hydroarylation, which is able to assemble the phenanthrene unit despite the thermodynamic cost of significantly bending arene A from the ideal plane.