<i>para</i>-C–H Borylation of Benzene Derivatives by a Bulky Iridium Catalyst

A highly <i>para</i>-selective aromatic C–H borylation has been accomplished. By a new iridium catalyst bearing a bulky diphosphine ligand, Xyl-MeO-BIPHEP, the C–H borylation of monosubstituted benzenes can be affected with <i>para</i>-selectivity up to 91%. This catalytic system is quite different from the usual iridium catalysts that cannot distinguish <i>meta</i>- and <i>para</i>-C–H bonds of monosubstituted benzene derivatives, resulting in the preferred formation of <i>meta</i>-products. The <i>para</i>-selectivity increases with increasing bulkiness of the substituent on the arene, indicating that the regioselectivity of the present reaction is primarily controlled by steric repulsion between substrate and catalyst. Caramiphen, an anticholinergic drug used in the treatment of Parkinson’s disease, was converted into five derivatives via our <i>para</i>-selective borylation. The present [Ir­(cod)­OH]<sub>2</sub>/Xyl-MeO-BIPHEP catalyst represents a unique, sterically controlled, <i>para</i>-selective, aromatic C–H borylation system that should find use in streamlined, predictable chemical synthesis and in the rapid discovery and optimization of pharmaceuticals and materials.