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 (SEAr) 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
SEAr regioselectivity rules can be readily accessed.