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

被引：0
作者：
Cheng-Yu Zheng
Jian-Min Yue
机构：
[1] Chinese Academy of Sciences,State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica
[2] University of Chinese Academy of Sciences,Research Units of Discovery of New Drug Lead Molecules
[3] Chinese Academy of Medical Sciences,undefined
来源：
Nature Communications | / 14卷
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摘要：
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.
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[1]  
Genovino J(2016)Accessing drug metabolites via transition-metal catalyzed C–H oxidation: the liver as synthetic inspiration Angew. Chem. Int. Ed. 55 14218-14238
[2]  
Sames D(2021)Late-stage C–H functionalization offers new opportunities in drug discovery Nat. Rev. Chem. 5 522-545
[3]  
Hamann LG(2020)Late-stage functionalization Chem 6 1877-1887
[4]  
Toure BB(2017)Ruthenium-catalyzed C–H hydroxylation in aqueous acid enables selective functionalization of amine derivatives J. Am. Chem. Soc. 139 9503-9506
[5]  
Guillemard L(2017)Remote, late-stage oxidation of aliphatic C–H bonds in amide-containing molecules J. Am. Chem. Soc. 139 14586-14591
[6]  
Kaplaneris N(2020)Chemoselective tertiary C–H hydroxylation for late-stage functionalization with Mn(PDP)/chloroacetic acid catalysis Adv. Synth. Catal. 362 417-423
[7]  
Ackermann L(2020)Enantioselective C–H lactonization of unactivated methylenes directed by carboxylic acids J. Am. Chem. Soc. 142 1584-1593
[8]  
Johansson MJ(2021)N-ammonium ylide mediators for electrochemical C–H oxidation J. Am. Chem. Soc. 143 7859-7867
[9]  
Börgel J(2020)Divergent synthesis of complex diterpenes through a hybrid oxidative approach Science 369 799-806
[10]  
Ritter T(2021)Enzymatic hydroxylations of sp ACS Catal. 11 9168-9203
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