Concise Total Synthesis of (+)-Pleiocarpamine and Convergent Total Syntheses of (+)-Voacalgine A and (+)-Bipleiophylline via an Aerobic Oxidative Coupling.

The stereocontrolled total synthesis of (+)-pleiocarpamine and the total syntheses of (+)-voacalgine A and (+)-bipleiophylline have been achieved. The scalable and concise 10-step synthesis of (+)-pleiocarpamine features construction of stereochemistry at the C16 position by radical cyclization and that of the highly strained cage-like structure via Pd-catalyzed intramolecular aromatic C-H functionalization. By modifying the biomimetic aerobic oxidative coupling of tryptophane derivatives catalyzed by FePc(COH), the oxidative coupling of the synthesized (+)-pleiocarpamine with pyrocatechuic acid was established to produce (+)-voacalgine A. The total synthesis of (+)-bipleiophylline was completed by the second coupling of (+)-voacalgine A with (+)-pleiocarpamine or one-pot couplings of 2 equiv of (+)-pleiocarpamine with pyrocatechuic acid.