Ligand Control Overrides Intrinsic Site Selectivity in C-H Borylation of Phenol and Aniline Derivatives

Controlling the regioselectivity in C-H functionalization is a challenging issue in organic synthesis. Typically, the specific electronic and/or steric character of the substrate leads to intrinsic site selectivity in C-H functionalization. While enhancing intrinsic site selectivity is relatively straightforward, altering and reversing high selectivity is challenging. By the use of a designed ligand for an iridium catalyst, the normally preferred para-selective C-H borylation of sulfated phenol and aniline derivatives has been completely inverted to strong meta-selectivity. This protocol affords a variety of meta-borylated phenols, anilines, and related compounds with excellent regioselectivity under mild reaction conditions. Mechanistic experiments and density functional theory calculations elucidate the origins of this conversion from para- to meta-selectivity.