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N-Directed fluorination of unactivated Csp³-H bonds.

ABSTRACT: Site-selective fluorination of aliphatic C-H bonds remains synthetically challenging. While directed C-H fluorination represents the most promising approach, the limited work conducted to date has enabled just a few functional groups as the arbiters of direction. Leveraging insights gained from both computations and experimentation, we enabled the use of the ubiquitous amine functional group as a handle for the directed C-H fluorination of Csp³-H bonds. By converting primary amines to adamantoyl-based fluoroamides, site-selective C-H fluorination proceeds under the influence of a simple iron catalyst in 20 minutes. Computational studies revealed a unique reaction coordinate for the catalytic process and offer an explanation for the high site selectivity.

SUBMITTER: Pinter EN

PROVIDER: S-EPMC8146735 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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N-Directed fluorination of unactivated Csp3-H bonds.

Pinter Emily N EN Bingham Jenna E JE AbuSalim Deyaa I DI Cook Silas P SP

Chemical science 20191216 4

Site-selective fluorination of aliphatic C-H bonds remains synthetically challenging. While directed C-H fluorination represents the most promising approach, the limited work conducted to date has enabled just a few functional groups as the arbiters of direction. Leveraging insights gained from both computations and experimentation, we enabled the use of the ubiquitous amine functional group as a handle for the directed C-H fluorination of Csp3-H bonds. By converting primary amines to ...[more]

PMID: 34084366

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