Fe-Catalyzed C(sp3)–H Diversification toward γ‑Functionalized Amides via Iron Nitrenoid: Mechanistic Insights and Applications

Access to γ-functionalized amides represents a challenge in organic synthesis. The recent upsurge of biomimetic metal nitrenoid-mediated C–H functionalization offers a method for producing N-containing molecules. Here, we describe an iron-catalyzed γ-C­(sp3)–H diversification of dioxazolones to acce...

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Bibliographic Details
Published inACS catalysis Vol. 13; no. 21; pp. 14023 - 14030
Main Authors Wan, Yanjun, Ramírez, Emmanuel, Ford, Ayzia, Bustamante, Vanessa, Li, Gang
Format Journal Article
LanguageEnglish
Published American Chemical Society 03.11.2023
Subjects
C−H functionalization
reaction mechanisms
nitrene
iron catalysis
radical intermediates
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Summary:Access to γ-functionalized amides represents a challenge in organic synthesis. The recent upsurge of biomimetic metal nitrenoid-mediated C–H functionalization offers a method for producing N-containing molecules. Here, we describe an iron-catalyzed γ-C­(sp3)–H diversification of dioxazolones to access γ-functionalized amides. The C–H activation step proceeds via the formation of an iron nitrenoid species, followed by 1,5-hydrogen atom transfer (1,5-HAT). A crucial dihydrofuranimine species is isolated and characterized. This intermediate undergoes nucleophilic substitution to furnish the desired product through a S N 2 mechanism. This reaction obviates the need for external chemical oxidants and exhibits compatibility with electron-rich substrates and various nitrogen, oxygen, and carbon nucleophiles. The catalyst also offers up to 9500 turnovers on complex natural products, emphasizing its utility in organic synthesis and drug development.
ISSN:2155-5435
2155-5435
DOI:10.1021/acscatal.3c03679