Iron-catalysed alkene and heteroarene H/D exchange by reversible protonation of iron-hydride intermediates. Issue 35 (19th August 2022)

• Record Type: Journal Article
• Authors: Britton, Luke; Docherty, Jamie H.; Sklyaruk, Jan; Cooney, Jessica; Nichol, Gary S.; Dominey, Andrew P.; Thomas, Stephen P.
• Is Part Of: Chemical science. Volume 13:Issue 35(2022)
• Page Start: 10291
• Page End: 10298
• Publication Date: 2022-08-19
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d2sc03802a
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : The iron-catalysed C(sp 2 )–H bond H/D exchange reaction using CD3 OD is reported for both heterocycles and alkenes. Characterisation of the key C–H metallation intermediates provided evidence for reversible protonation of the iron hydride catalyst. 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(sp 2 )–H bond hydrogen/deuterium exchange reaction using CD3 OD 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 C6 D6, D2, or D2 O 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.