Main group metal-mediated strategies for C–H and C–F bond activation and functionalisation of fluoroarenes

Abstract

This Perspective showcases recent advances on the use of specially designed main-group metal complexes to facilitate chemoselective C–H/C–F functionalisation of fluoroarenes.

Cooperative activation of carbon–hydrogen bonds by heterobimetallic systems

“…Hevia and coworkers have considerably extended the alkali–metal - ate chemistry 136–138 and very recently reported the dehydrometallation of fluoroarenes mediated by cobalt alkali–metal amides (Fig. 37).…”

“…134,135 Regioselective functionalization of fluoroarenes can be challenging due to uncontrolled reactivity and unwanted side reactions such as benzyne formation or cascade processes (auto-metalation, multi-metalation). 138 Heterobimetallic amide bases combining an alkali metal with a divalent transition-metal center not only prevent these side reactions but also allow new reaction pathways towards thermally stable metalates under mild conditions. Unlike in many established C–H bond activation processes, the oxidation state of the 3d-transition metal remains unchanged throughout the reaction.…”

Applications of Transition Metal-Catalyzed ortho-Fluorine-Directed C–H Functionalization of (Poly)fluoroarenes in Organic Synthesis

“…41 and Chirik, 64 and by Davies, Macgregor, and McMullin. 65 In addition, a perspective focusing on the activation and functionalization of C−H and C−F bonds in fluoroarenes by main group elements has recently been published by Hevia et al 66 In this section, we address the origins of selectivity between different positions in a particular fluorine-substituted benzene ring for activation by transition metals, for which there is rich experimental evidence. There is little (if any) experimental information about competition between different isomeric fluorobenzenes, e.g., between 1,2-C 6 F 2 H 4 , 1,3-C 6 F 2 H 4 , and 1,4-C 6 F 2 H 4 , although computational studies provide predictions.…”

Stoichiometric and Catalytic Lithium Nickelate-Mediated C–F Bond Alkynylation of Fluoroarenes

“…Motivated by the ability for nickel to functionalize challenging electrophiles, − herein, we explore the stoichiometric and catalytic reactivity of low-valent [formally Ni(0)] nickelate Li 3 (TMEDA) 3 Ni­(CC–Ph) 3 toward aryl fluorides and polyfluoroarenes (Scheme b). While the C–F activation of polyfluorinated arenes is well established for many transition-metal and low-valent main-group complexes, the selective C–F functionalization of monofluorinated arenes is challenging due to the high bond dissociation energy (BDE) of the C­(sp 2 )–F bond (125.6 kcal mol –1 for Ph–F vs 114 kcal mol –1 for C 6 F 6 and 65.1 kcal mol –1 for Ph–I) . The C–F activation of monofluorinated arenes provides opportunities for orthogonal cross-coupling strategies or the late-stage functionalization of substituted arenes, , and numerous stoichiometric, catalytic, and mechanistic studies have been reported to date using nickel complexes. − …”