Selective Oxidative Homo- and Cross-Coupling of Phenols

The efforts described in this dissertation initially focus on the asymmetric coupling of phenols. We have developed Schiff base vanadium catalyst for the oxidative coupling of phenols with high reactivity and enantioselectivity. To the best of our knowledge, this example constitutes the first highly selective asymmetric coupling of phenols. Several substrates were coupled with our vanadium catalyst with good enantioselectivity (72-89% ee). The first simple catalystic system that uses atom-economical oxygen as the terminal oxidant to accomplish selective ortho−ortho, ortho−para, or para−para homo-couplings of phenols was developed. Chromium salen catalysts have been discovered and verified as uniquely effective in the cross-coupling of different phenols with high chemo- and regio-selectivity. A broad scope of phenol substrates was found for these reaction conditions giving cross-coupling products with good yield (up to 88%). In order to understand the mechanism of cross-coupling reaction, spectroscopic methods, additive experiments, SAR studies, and kinetic experiments were performed and a mechanism was postulated. Finally, we established an efficient route for the total synthesis of honokiol by utilizing a novel disconnection that transits new structures. This five step (six chemical reactions) synthesis was initiated by oxidative cross-coupling of inexpensive commercial phenols with high yield (91%). Following retro Friedel-Crafts alkylation, a protection reaction proceeded smoothly with excellent yield (89% for three steps). The remaining steps of radical bromination, Kumada coupling and demethylation were each optimized. The total yield over five steps was 34% and gram-scale reactions were conducted for each step.