The atomistic transformation of C(sp³)–H to C(sp³)–O via direct oxidation has emerged as an effective tactic for designing and synthesizing oxygen-containing valuable molecules. This approach enables synthetic chemists to mimic nature’s pathways and diversify complex structures without the need for separate de novo synthesis. Among the various C–H bonds in organic molecules, the benzylic C–H bond stands out as a pivotal target for selective oxidation, as oxygenated benzylic structures are prevalent in natural products and biologically active compounds. Over the past few decades, benzylic C–H functionalization, particularly enantioselective C–C bond formation, has become a powerful tool for synthetic chemists. Recent progress has also been made in enantioselective C–N bond formation from benzylic C–H bonds. However, the enantioselective construction of C–O bonds via benzylic C–H bond oxidation remains a challenge.

Recently, Qi-Lin Zhou’s group have developed a method for the enantioselective oxidation of benzylic C(sp³)–H bonds in alkylarenes by combining copper catalysis with photocatalysis and using NHPI as the oxygenating source. The method does not require excess substrate or oxidant and is carried out under mild conditions. Using this method, a variety of chiral compounds with benzylic C(sp³)–O bonds have been synthesized in good to high yield and high enantioselectivity. The products can be easily converted into chiral benzylic alcohols and hydroxylamines. Mechanistic studies suggest that the oxidation occurs through a free radical mechanism. These findings offer a new approach to exploring enantioselective functionalization reactions of unactivated C–H bonds. Relevant achievements were published in J. Am. Chem. Soc., 2025. DOI: 10.1021/jacs.5c04142.