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
posted on 2022-01-11, 15:37authored byL. 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
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.