C-C bond formation via C-H bond activation: synthesis of the core of teleocidin B4

Abstract

The core of teleocidin B4, a complex fragment of a natural product containing two quaternary stereocenters and a penta-substituted benzene ring, was synthesized in four C-C bond-forming steps starting from tert-butyl derivative 1. The first step involved alkenylation of the tert-butyl group with a vinyl boronic acid, followed by the successful annulation of the cyclohexane ring to the benzene nucleus via an intramolecular Friedel-Crafts reaction. The third step required a diastereoselective oxidative carbonylation of the geminal dimethyl group, followed at last by indole assembly via the alkenylation of the phenol nucleus, to afford the teleocidin B4 core. Noteworthy is the fact that steps 1 and 3 critically depended on the directing role of the aniline nitrogen (directed C-H bond functionalization).