Widely-used boronic esters as synthetically-versatile directing groups for C–H activation and hydrogen isotope exchange

Abstract

Herein we report the first use of accessible boron-containing compounds as highly effective directing groups for C–H activation and hydrogen isotope exchange. Selective ortho-activation and functionalisation at aromatic C-sp² centres have been achieved across an array of aryl boronic ester species using an iridium-based, NHC/phosphine catalyst system at low loadings. The process is robust, with a wide scope of over 30 substrates, and delivers excellent levels of deuterium incorporation in a selective manner. Further utilisation of the resulting boron-containing isotopologues in cross-coupling chemistry has allowed the late-stage preparation of previously less accessible site-selectively labelled structures. This strategy has been exemplified via the preparation of an isotopically-labelled, biologically-active drug molecule.