Site-selective remote C(sp3)–H heteroarylation of amides via organic photoredox catalysis

Radical translocation processes triggered by nitrogen-centered radicals (NCRs), such as 1,5-hydrogen atom transfers (1,5-HAT), demonstrated by the well-established Hofmann-Löffler-Freytag (HLF) reaction, provide an attractive approach for the controllable and selective functionalization of remote in...

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Bibliographic Details
Published in:Nature communications 2019-10, Vol.10 (1), p.4743-9, Article 4743
Main Authors: Chen, Hui, Fan, Wenjing, Yuan, Xiang-Ai, Yu, Shouyun
Format: Article
Language:English
Subjects:
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Alkylation
Amides
Benzofuran
Benzothiophene
Carbon
Catalysis
Chemical engineering
Chemistry
Free radicals
Humanities and Social Sciences
Hydrogen
Laboratories
multidisciplinary
Nitrogen
Photoredox catalysis
Polarity
Purines
Quinoxalines
Radicals
Science
Science (multidisciplinary)
Selectivity
Thiazoles
Transition metals
Translocation
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Summary:Radical translocation processes triggered by nitrogen-centered radicals (NCRs), such as 1,5-hydrogen atom transfers (1,5-HAT), demonstrated by the well-established Hofmann-Löffler-Freytag (HLF) reaction, provide an attractive approach for the controllable and selective functionalization of remote inert C(sp 3 )–H bonds. Here we report an amidyl radical-triggered site-selective remote C(sp 3 )–H heteroarylation of amides under organic photoredox conditions. This approach provides a mild and highly regioselective reaction affording remote C(sp 3 )–H heteroarylated amides at room temperature under transition-metal free, weakly basic, and redox-neutral conditions. Non-prefunctionalized heteroarenes, such as purines, thiazolopyridines, benzoxazole, benzothiazoles, benzothiophene, benzofuran, thiazoles and quinoxalines, can be alkylated directly. Sequential and orthogonal C–H functionalization of different heteroarenes by taking advantage pH value or polarity of radicals has also been achieved. DFT calculations explain and can predict the site-selectivity and reactivity of this reaction. This strategy expands the scope of the Minisci reaction and serves as its alternative and potential complement. Nitrogen-centered radicals are valuable intermediates for the controllable and selective functionalization of remote inert C(sp 3 )–H bonds. Here, the authors report an amidyl radical-triggered, metal-free and site-selective C(sp 3 )–H heteroarylation of amides under photoredox conditions.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-019-12722-4