Remote Nickel-Catalyzed Cross-Coupling Arylation via Proton-Coupled Electron Transfer-Enabled C–C Bond Cleavage

Long Huang, Tengfei Ji, Magnus Rueping
JACS - Journal of American Chemical Society, (2020)

Remote Nickel-Catalyzed Cross-Coupling Arylation via Proton-Coupled Electron Transfer-Enabled C–C Bond Cleavage

Keywords

Aromatic compounds, Alcohols, Cross coupling reaction, Ketones, Nickel

Abstract

​Cross-coupling reactions for carbon–carbon and carbon–heteroatom bond formation are of great importance in modern chemical synthesis. In addition to classical cross-couplings involving preformed or preactivated coupling partners, more recently breakthroughs have been made in the selective, direct coupling of abundant aliphatic carbon–hydrogen bonds using hydrogen atom transfer reactions in which the bond-dissociation energy is the thermodynamic driving force. The more challenging carbon–carbon bond activation is still rather underdeveloped due to the bond inertness. Herein, we report a mild and general strategy for the activation of a diverse set of readily available cyclic alcohols for the remote and site-specific arylation of ketones via the combination of photoredox-mediated multisite concerted proton–electron transfer (MS-PCET) and nickel catalysis. The current cross-coupling proceeds with the generation of an alkoxy radical utilizing bond-dissociation free energy (BDFE) as the thermodynamic driving force. Subsequently, the resulting remote carbon-centered radicals formed by C–C cleavage merge with the nickel catalytic cycle to create the challenging C(sp3)–C(sp2) bonds.

Code

https://doi.org/10.1021/jacs.9b12490

Sources

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