Allylic hydroxylation of enones useful for the functionalization of relevant drugs and natural products

Abstract

Enones are privileged structural motifs in bioactive natural products and pharmaceuticals, but the γ-hydroxylation of enones is challenging. Here we show a mild and efficient method for the direct C(sp3)–H hydroxylation of enones via visible-light-induced hydrogen-atom transfer (HAT), which facilitates γ-hydroxylation of primary, secondary, and tertiary C–H bonds of different enones without involving metal and peroxide. The mechanism study shows that Na2-eosin Y serves as both the photocatalyst and the source of catalytic bromine radical species in the HAT-based catalytic cycle, and finally sacrifices itself completely by oxidative degradation to produce bromine radical and a major product phthalic anhydride in an environmentally friendly way. This scalable method was demonstrated by plenty of substrates (41 examples) including 10 clinical drugs and 15 natural products to be useful for the late-stage functionalization of enone-containing compounds, and, in particular, has potential application in industry for large-scale production.