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Nucleophilic Aromatic Substitution of Unactivated Fluoroarenes Enabled by Organic Photoredox Catalysis.

ABSTRACT: Nucleophilic aromatic substitution (S_NAr) is a classical reaction with well-known reactivity toward electron-poor fluoroarenes. However, electron-neutral and electron-rich fluoro(hetero)arenes are considerably underrepresented. Herein, we present a method for the nucleophilic defluorination of unactivated fluoroarenes enabled by cation radical-accelerated nucleophilic aromatic substitution. The use of organic photoredox catalysis renders this method operationally simple under mild conditions and is amenable to various nucleophile classes, including azoles, amines, and carboxylic acids. Select fluorinated heterocycles can be functionalized using this method. In addition, the late-stage functionalization of pharmaceuticals is also presented. Computational studies demonstrate that the site selectivity of the reaction is dictated by arene electronics.

SUBMITTER: Pistritto VA

PROVIDER: S-EPMC7720250 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Nucleophilic Aromatic Substitution of Unactivated Fluoroarenes Enabled by Organic Photoredox Catalysis.

Pistritto Vincent A VA Schutzbach-Horton Megan E ME Nicewicz David A DA

Journal of the American Chemical Society 20200928 40

Nucleophilic aromatic substitution (SNAr) is a classical reaction with well-known reactivity toward electron-poor fluoroarenes. However, electron-neutral and electron-rich fluoro(hetero)arenes are considerably underrepresented. Herein, we present a method for the nucleophilic defluorination of unactivated fluoroarenes enabled by cation radical-accelerated nucleophilic aromatic substitution. The use of organic photoredox catalysis renders this method operationally simple under mild con ...[more]

PMID: 32986412

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