Iron-catalysed alkene and heteroarene H/D exchange by reversible protonation of iron-hydride intermediates

Britton, Luke and Docherty, Jamie H. and Sklyaruk, Jan and Cooney, Jessica and Nichol, Gary S. and Dominey, Andrew P. and Thomas, Stephen P. (2022) Iron-catalysed alkene and heteroarene H/D exchange by reversible protonation of iron-hydride intermediates. Chemical Science, 13 (35). pp. 10291-10298. ISSN 2041-6520

Text (Thomas)
Thomas.pdf - Published Version
Available under License Creative Commons Attribution-NonCommercial.
Download (1MB)

Abstract

C-H functionalisation reactions offer a sustainable method for molecular construction and diversification. These reactions however remain dominated by precious metal catalysis. While significant interest in iron-catalysed C-H activation reactions has emerged, the isolation, characterisation and mechanistic understanding of these processes remain lacking. Herein the iron-catalysed C(sp2)-H bond hydrogen/deuterium exchange reaction using CD3OD is reported for both heterocycles and, for the first time, alkenes (38 examples). Isolation and characterisation, including by single-crystal X-ray diffraction, of the key iron-aryl and iron-alkenyl C-H metallation intermediates provided evidence for a reversible protonation of the active iron hydride catalyst. Good chemoselectivity was observed for both substrate classes. The developed procedure is orthogonal to previous iron-catalysed H/D exchange methods which used C6D6, D2, or D2O as the deuterium source, and uses only bench-stable reagents, including the iron(ii) pre-catalyst. Further, a new mechanism of iron-hydride formation is reported in which β-hydride elimination from an alcohol generates the iron hydride. The ability to produce, isolate and characterise the organometallic products arising from C-H activation presents a basis for future discovery and development.