Fe-Catalyzed C(sp<sup>3</sup>)–H Diversification toward γ-Functionalized Amides via Iron Nitrenoid: Mechanistic Insights and Applications
Yanjun Wan, Emmanuel Ramírez, Ayzia Ford, Vanessa Bustamante, Gang Li
Abstract
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(sp 3 )–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.