State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai, 201203, China.
University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing, 100049, China.
Nat Commun. 2023 Apr 26;14(1):2399. doi: 10.1038/s41467-023-38154-9.
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(sp)-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 Na-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.
烯酮是生物活性天然产物和药物中的重要结构基序，但烯酮的γ-羟化是具有挑战性的。在这里，我们展示了一种温和且高效的方法，通过可见光诱导的氢原子转移（HAT）直接对烯酮进行 C(sp)-H 羟化，该方法可促进不同烯酮中伯、仲和叔 C-H 键的γ-羟化，而无需涉及金属和过氧化物。机理研究表明，曙红 Y 钠盐不仅是光催化剂，而且还是 HAT 催化循环中催化溴自由基物种的来源，最终通过氧化降解完全牺牲自身，以环保的方式产生溴自由基和主要产物邻苯二甲酸酐。该可扩展方法通过大量底物（41 个实例）进行了验证，包括 10 种临床药物和 15 种天然产物，这对于烯酮类化合物的后期官能化具有重要意义，特别是在工业上具有大规模生产的应用潜力。
