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Final published version
Licence: CC BY-NC: Creative Commons Attribution-NonCommercial 4.0 International License
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Iron-catalysed alkene and heteroarene H/D exchange by reversible protonation of iron-hydride intermediates
AU - Britton, Luke
AU - Docherty, Jamie H.
AU - Sklyaruk, Jan
AU - Cooney, Jessica
AU - Nichol, Gary S.
AU - Dominey, Andrew P.
AU - Thomas, Stephen P.
PY - 2022/9/14
Y1 - 2022/9/14
N2 - 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.
AB - 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.
U2 - 10.1039/d2sc03802a
DO - 10.1039/d2sc03802a
M3 - Journal article
C2 - 36277640
AN - SCOPUS:85136843532
VL - 13
SP - 10291
EP - 10298
JO - Chemical Science
JF - Chemical Science
SN - 2041-6520
IS - 35
ER -