Manganese-Mediated C–H Bond Activation of Fluorinated Aromatics and the ortho-Fluorine Effect: Kinetic Analysis by In Situ Infrared Spectroscopic Analysis and Time-Resolved Methods

L. Anders Hammarback, Amy L. Bishop, Christina Jordan, Gayathri Athavan, Jonathan B. Eastwood, Thomas J. Burden, Joshua T.W. Bray, Francis Clarke, Alan Robinson, Jean Philippe Krieger, Adrian Whitwood, Ian P. Clark, Michael Towrie, Jason M. Lynam*, Ian J.S. Fairlamb

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Insights into the factors controlling the site selectivity of transition metal-catalyzed C–H bond functionalization reactions are vital to their successful implementation in the synthesis of complex target molecules. The introduction of fluorine atoms into substrates has the potential to deliver this selectivity. In this study, we employ spectroscopic and computational methods to demonstrate how the “ortho-fluorine effect” influences the kinetic and thermodynamic control of C–H bond activation in manganese(I)-mediated reactions. The C–H bond activation of fluorinated N,N-dimethylbenzylamines and fluorinated 2-phenylpyridines by benzyl manganese(I) pentacarbonyl BnMn(CO)5 leads to the formation of cyclomanganated tetracarbonyl complexes (2a–b and 4a–e), which all exhibit C–H bond activation ortho-to-fluorine. Corroboration of the experimental findings with density functional theory methods confirms that a kinetically controlled irreversible σ-complex-assisted metathesis mechanism is operative in these reactions. The addition of benzoic acid results in a mechanistic switch, so that cyclomanganation proceeds through a reversible AMLA-6 mechanism (kinetically and thermodynamically controlled). These stoichiometric findings are critical to catalysis, particularly subsequent insertion of a suitable acceptor substrate into the C–Mn bond of the regioisomeric cyclomanganated tetracarbonyl complex intermediates. The employment of time-resolved infrared spectroscopic analysis allowed for correlation of the rates of terminal acetylene insertion into the C–Mn bond with the relative thermodynamic stability of the regioisomeric complexes. Thus, more stable manganacycles, imparted by an ortho-fluorine substituent, exhibit a slower rate of terminal acetylene insertion, whereas a para-fluorine atom accelerates this step. A critical factor in governing C–H bond site selectivity under catalytic conditions is the generation of the regioisomeric cyclomanganated intermediates, rather than their subsequent reactivity toward alkyne insertion.

Original languageEnglish
Pages (from-to)1532-1544
Number of pages13
JournalACS Catalysis
Issue number2
Early online date11 Jan 2022
Publication statusPublished - 21 Jan 2022

Bibliographical note

Funding Information:
We are grateful to Dr. Jessica Milani for assistance with the synthesis of the fluorinated amine starting materials. We thank Professors Robin N. Perutz, Paul H. Walton, and Andrew S. Weller (York) for discussion of our findings. We are grateful to the ERASUMS exchange scheme for funding C.J. and the Wild fund for supporting a PhD scholarship for G.A. Syngenta and EPSRC are thanked for funding an iCASE PhD studentship for L.A.H. We acknowledge EPSRC grants (EP/H011455, EP/K031589/1, and EP/N509413/1).

© 2022 American Chemical Society. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details


  • alkynes
  • catalysis
  • C−H bond activation
  • manganese
  • pyridines
  • site selectivity

Cite this