Remote Regioselective Electrophilic Aromatic Substitutions Using a Tetrafluoropyridyl (TFP) Phenol Protecting Group

Herein, we report the development of remote regioselective electrophilic aromatic substitution reactions enabled by the tetrafluoropyridyl (TFP) protecting group. The TFP group significantly reduces the reactivity of the aromatic ring to which it is attached allowing for substitution selectivity on non-TFP protected rings and in turn access to unsymmetric multi-aryl systems. Yields of the unsymmetric multi-aryl systems ranged between 58-96%. In addition, we disclose that through sequential reactions and protection/deprotection of the TFP group, substitution patterns which do not conform to classical regioselectivity rules can be readily accessed.