Protecting Group-Controlled Remote Regioselective Electrophilic Aromatic Halogenation Reactions

Being able to utilize a protecting group to influence remote regiocontrol offers a simple alternative approach to direct late-stage functionalization of complex organic molecules. However, protecting groups that have the ability to influence reaction regioselectivity remote to their local chemical environment are not widely reported in the literature. Herein, we report the development of remote regioselective electrophilic aromatic substitution (S E Ar) reactions that are enabled via the application of the tetrafluoropyridyl (TFP) phenol-protecting group. We demonstrate that through sequential reactions and protection/deprotection of the TFP group, substitution patterns that do not conform to classical S E Ar regioselectivity rules can be readily accessed.