An Air-Stable, Single-Component Iridium Precatalyst for the Borylation of C–H Bonds on Large to Miniaturized Scales

Abstract

The functionalization of C–H bonds enables the modification of complex molecules, often with the intention of forming compound libraries. The borylation of aryl C–H bonds is a widely used class of C–H bond functionalization, and conventional catalyst systems for the borylation of C–H bonds consist of an iridium source and an N,N-ligand, in conjunction with pinacolborane, to form the active iridium(III) tris(boryl) catalyst. These multicomponent catalyst systems complicate borylation reactions at large and small scales, due to the air sensitivity of the most common iridium precursor [Ir(cod)OMe]₂, and, particularly on small scale, the challenges associated with dispensing multiple components with differing solubilities or that are air-sensitive. We describe the discovery of an air-stable, single-component iridium precatalyst, [(tmphen)Ir(coe)₂Cl], that generates the same active iridium(III) tris(boryl) catalyst and reacts with higher turnovers, comparable selectivity, and similar scope to those of known catalyst systems for the borylation of aryl and heteroaryl C–H bonds. We show how the development of this precatalyst enables reactions to be run on submicromole scale in a high-throughput experimentation format in conjunction with ChemBead technology, and with a second diversification step that illustrates the potential to diversify structures by chemical sequences involving catalytic reactions, including C–H bond functionalizations, on submicromole scales in the same reaction vessel.