Characterization and Reactivity of Copper(II) and Copper(III) σ-Aryl Intermediates in Aminoquinoline-Directed C–H Functionalization

Abstract

Over the past decade, numerous reports have focused on the development and applications of Cu-mediated C−H functionalization reactions; however, to date, little is known about the Cu intermediates involved in these transformations. This paper details the observation and characterization of Cu II and Cu III intermediates in aminoquinoline-directed C(sp 2 )−H functionalization of a fluoroarene substrate. An initial C(sp 2 )−H activation at Cu II occurs at room temperature to afford an isolable anionic cyclometalated Cu II complex. This complex undergoes singleelectron oxidation with ferrocenium or Ag I salts under mild conditions (5 min at room temperature) to afford C(sp 2 )−C(sp 2 ) or C(sp 2 )−NO 2 coupling products. Spectroscopic studies implicate the formation of a transient diamagnetic Cu III -σ-aryl intermediate that undergoes either (i) a second C(sp 2 )−H activation at Cu III followed by C−C bond-forming reductive elimination or (ii) reaction with a NO 2 − nucleophile and C(sp 2 )−NO 2 coupling.

Copper–Carbon Homolysis Competes with Reductive Elimination in Well-Defined Copper(III) Complexes

“…6 More recently, Sanford has reported the characterization of Cu III −aryl intermediates in aminoquinoline-directed C−H functionalization. 7 Despite significant progress in understanding the reductive elimination step in Cu catalysis, the involvement of Cu III species in Cu catalysis remains speculative. Particularly in Cu-catalyzed C(sp 3 ) cross-coupling reactions with alkyl radicals, an ongoing debate persists regarding the formation of Cu III species in these transformations.…”

“…Additionally, Tilley recently published a study on Cu III metalla­cyclo­penta­diene dimer complexes, which can undergo reductive elimination to generate phenanthro­cyclo­buta­diene in quantitative yield . More recently, Sanford has reported the characterization of Cu III –aryl intermediates in amino­quinoline-directed C–H functionalization …”

C–N Bond Formation at Discrete CuIII–Aryl Complexes

“…, amides, imides, and sulfonamides (Scheme A,B). ,,, However, the aryl motif must be tethered to the Cu III center as a part of the macrocyclic ligand, which does not reflect the dynamic nature of copper–aryl bonds during coupling reactions. Likewise, Sanford et al recently reported a Cu II aryl complex with the aryl moiety linked to an aminoquinoline chelate . Treatment with oxidants results in aryl–aryl coupling or, when AgNO 2 is utilized as the oxidant, aryl–NO 2 coupling.…”

“…Likewise, Sanford et al recently reported a Cu II aryl complex with the aryl moiety linked to an aminoquinoline chelate. 23 Treatment with oxidants results in aryl−aryl coupling or, when AgNO 2 is utilized as the oxidant, aryl−NO 2 coupling. Warren et al reported a discrete copper(II) aryl complex capable of coupling with PhOH to generate Ar−OPh (Scheme 2C).…”

Photoredox-Catalyzed C(sp2)–H Bond Functionalization Reactions: A Short Account

“…9 This approach, which allows for selectively replacing the hydrogen atoms on C-H bonds with more reactive functional groups (FG), has found wide applications in diverse fields such as pharmaceuticals and materials science. 10 Notable pioneers in C-H bond activation include Yu, 11 Murai, 12 White, 13 Sanford, 14 Fagnou, 15 and many others. Our group has focused on alkenyl C(sp 2 )-H bond functionalization.…”