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

Isaac M Blythe; Jingtong Xu; Joaquin S Fernandez Odell; Jeff W Kampf; Miriam A Bowring; Melanie S Sanford

doi:10.1021/jacs.3c00914

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

J Am Chem Soc. 2023 Aug 23;145(33):18253-18259. doi: 10.1021/jacs.3c00914. Epub 2023 Aug 8.

Authors

Isaac M Blythe¹, Jingtong Xu², Joaquin S Fernandez Odell², Jeff W Kampf¹, Miriam A Bowring², Melanie S Sanford¹

Affiliations

¹ Department of Chemistry, University of Michigan, 930 N. University Avenue, Ann Arbor, Michigan 48109, United States.
² Department of Chemistry, Reed College, 3203 Woodstock Boulevard, Portland, Oregon 97202, United States.

PMID: 37552536
DOI: 10.1021/jacs.3c00914

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(sp²)-H functionalization of a fluoroarene substrate. An initial C(sp²)-H activation at Cu^II occurs at room temperature to afford an isolable anionic cyclometalated Cu^II complex. This complex undergoes single-electron oxidation with ferrocenium or Ag^I salts under mild conditions (5 min at room temperature) to afford C(sp²)-C(sp²) or C(sp²)-NO₂ coupling products. Spectroscopic studies implicate the formation of a transient diamagnetic Cu^III-σ-aryl intermediate that undergoes either (i) a second C(sp²)-H activation at Cu^III followed by C-C bond-forming reductive elimination or (ii) reaction with a NO₂^- nucleophile and C(sp²)-NO₂ coupling.