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 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 SN2 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.