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A highly site-selective radical sp³ C-H amination of azaheterocycles.

ABSTRACT: This report describes the development of a novel C-H amination strategy using both a Cu(ii) Lewis acid and an organic hydrogen atom transfer catalyst to activate benzylic C-H bonds adjacent to aromatic N-heterocycles. This simple methodology demonstrates very high selectivity towards azaheterocycles without using exogenous directing groups and affords excellent site selectivity in substrates with more than one reactive position. A wide range of heterocyclic structures not compatible with previously reported catalytic systems have proven to be amenable to this approach. Mechanistic investigations strongly support a radical-mediated H-atom abstraction, which explains the observed contrast to known closed-shell Lewis acid catalyzed processes.

SUBMITTER: Bentley KW

PROVIDER: S-EPMC6115697 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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A highly site-selective radical sp3 C-H amination of azaheterocycles.

Bentley Keith W KW Dummit Krysta A KA Van Humbeck Jeffrey F JF

Chemical science 20180710 30

This report describes the development of a novel C-H amination strategy using both a Cu(ii) Lewis acid and an organic hydrogen atom transfer catalyst to activate benzylic C-H bonds adjacent to aromatic N-heterocycles. This simple methodology demonstrates very high selectivity towards azaheterocycles without using exogenous directing groups and affords excellent site selectivity in substrates with more than one reactive position. A wide range of heterocyclic structures not compatible with previou ...[more]

PMID: 30310574

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