Development and understanding of iron-catalysed C–H functionalisation reactions

Abstract

C–H functionalisation reactions allow for an efficient and sustainable manner of increasing molecular complexity. The application of Earth-abundant metal-catalysed methods is dependent on systems that are reliable, predictable, and easily accessible. However, current methods typically show limited reaction tolerances, often have little mechanistic understanding, and rely on highly sensitive reagents and pre-catalysts.

An iron-catalysed C–H borylation reaction of arenes has been developed using only commercially available, bench-stable reagents (Scheme A-1). The reaction demonstrates the largest functional group tolerance of any Earth-abundant metalcatalysed C–H borylation reaction and provides insight into observed side reactivity. Mechanistic studies of an iron halide-catalysed system for the directed C–H borylation of 2-phenylpyridine derivatives identified iron to be an initiator in a reaction driven by hidden Brønsted acid catalysis. The development of parallel non-metal-catalysed reaction conditions and methods for main group catalyst activation has also been demonstrated. Mechanistic studies on an iron-catalysed hydrogen isotope exchange (HIE) reaction of heteroarenes and alkenes identified the modes of exchange and a novel method for accessing iron-hydrides in situ. Reaction selectivity and the isolation of catalytic intermediates, including products of C–H metallation, suggested deuterium incorporation was proceeding through a selection of reaction pathways.