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

TY - JOUR

T1 - Manganese-Mediated C–H Bond Activation of Fluorinated Aromatics and the ortho-Fluorine Effect

T2 - Kinetic Analysis by In Situ Infrared Spectroscopic Analysis and Time-Resolved Methods

AU - Hammarback, L. Anders

AU - Bishop, Amy L.

AU - Jordan, Christina

AU - Athavan, Gayathri

AU - Eastwood, Jonathan B.

AU - Burden, Thomas J.

AU - Bray, Joshua T.W.

AU - Clarke, Francis

AU - Robinson, Alan

AU - Krieger, Jean Philippe

AU - Whitwood, Adrian

AU - Clark, Ian P.

AU - Towrie, Michael

AU - Lynam, Jason M.

AU - Fairlamb, Ian J.S.

N1 - 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

PY - 2022/1/21

Y1 - 2022/1/21

N2 - 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.

AB - 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.

KW - alkynes

KW - catalysis

KW - C−H bond activation

KW - manganese

KW - pyridines

KW - site selectivity

UR - http://www.scopus.com/inward/record.url?scp=85123378468&partnerID=8YFLogxK

U2 - 10.1021/acscatal.1c05477

DO - 10.1021/acscatal.1c05477

M3 - Article

AN - SCOPUS:85123378468

SN - 2155-5435

VL - 12

SP - 1532

EP - 1544

JO - ACS Catalysis

JF - ACS Catalysis

IS - 2

ER -