Photoinduced Iron-Catalyzed LMCT Enables Propargylic C(sp3)-H Activation to Access Polysubstituted α-Bromoenones

Abstract

α-Bromoenones are highly valuable scaffolds with broad synthetic utility in organic synthesis. Conventional approaches to access these important motifs mostly rely on pre-functionalized substrates, stoichiometric electrophilic halogenating agents (e.g., X2, NXS, HX), and nucleophilic oxygen sources (e.g., DMSO, N-oxides), often suffering from poor atom economy, limited substrate scope, and inadequate stereocontrol. Therefore, the development of sustainable methods for the synthesis of α-bromoenones from simple, readily available starting materials remains a significant challenge. Herein, we report a photoinduced iron-catalyzed ligand-to-metal charge transfer (LMCT)/hydrogen atom transfer (HAT) strategy that enables direct propargylic C(sp3)–H functionalization of internal alkynes using atmospheric O2 as the sole oxygen source and terminal oxidant. The reaction proceeds via bromine radical-mediated hydrogen atom transfer, followed by O2 trapping and iron-assisted oxygenation, delivering a broad range of α-bromoenones with excellent stereoselectivity (>20:1 Z/E). A bipyridine ligand plays a crucial role in directing the radical pathway and ensuring high geometric purity. This protocol represents the first example of propargylic C–H activation via iron-LMCT photocatalysis, operating under mild, oxidant-free conditions with minimal waste generation. The combination of O2 as a green oxidant and ZnBr2/FeBr3 as an atom-economic nucleophilic bromine source (100% atom utilization) underscores the alignment of this method with key green chemistry principles, including atom economy, waste minimization, and the use of sustainable reagents.