Photoinduced FeCl3-catalyzed Cross-Dehydrogenative Alkylation of Benzoxazin-2-ones with Alkanes

Homogeneous visible-light photoredox catalysis has emerged as a powerful tool in modern organic synthesis, which utilizes inexhaustible light to facilitate carbon-carbon and carbon-heteroatom bond formation under eco-friendly and mild conditions. Due to the incapablity of most organic compounds to absorb visible light, homogeneous photocatalysts such as precious metals (rhodium and iridium-complexes) and elaborate organic dyes were often employed through their visible light-driven electron/energy transfer to sensitize organic molecules in photoredox catalysis. However, these photocatalysts are not conducive to large-scale production due to the relatively high cost. Iron is an ideal candidate for economical and eco-friendly catalysis because of its abundant availability and nontoxicity. Recently, iron-photocatalyzed bond formation reactions via ligand-to-metal charge transfer (LMCT) have attracted huge attention. Functionalized benzoxazin-2-ones are important N-heterocycles found in many natural products, bioactive molecules and pharmaceuticals. Among these benzoxazin-2-one derivatives, alkylated benzoxazin-2-ones have received significant attention due to their valuable biological and pharmacological activities. From a synthetic point of view, the direct C-H alkylation of benzoxazin-2-ones represents one of the most straightforward and efficient methods for producing alkylated benzoxazin-2-ones due to its high atom and step economy. Alkanes are low cost and abundant feedstock materials, which have been widely used as the alkylation reagents in organic synthesis. In the present work, we report the development of iron-catalyzed C-H alkylation of benzoxazin-2-ones with alkanes via photoinduced LMCT. With FeCl3 as the photocatalyst, ambient air as the oxidant, tetrabutylammonium chloride as the promoter, a series of 3-alkylbenzoxazin-2-ones were efficiently synthesized under mild and eco-friendly conditions. The chlorine radical generated in situ serves as a hydrogen atom-transfer reagent. In addition, the present reaction can be smoothly scaled-up to gram level, which indicates it could be applied in industrial synthesis of pharmaceuticals.