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Late-Stage Direct o-Alkenylation of Phenols by PdII-Catalyzed C?H Functionalization |
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| Authors: | Yandong Dou Kenry Dr Jiang Liu Jianze Jiang Prof Qing Zhu |
| Institution: | 1. College of Biotechnology and Bioengineering, & Collaborative Innovation Center of Yangtze, River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, 310014 China
These authors contributed equally to this work.;2. Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, 117585 Singapore, Singapore These authors contributed equally to this work.;3. College of Biotechnology and Bioengineering, & Collaborative Innovation Center of Yangtze, River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, 310014 China |
| Abstract: | o-Alkenylation of unprotected phenols has been developed by direct C?H functionalization catalyzed by PdII. This work features phenol group as a directing group and realizes highly site-selective C?H bond functionalization of phenols to achieve the corresponding products in moderate to excellent yields at 60 °C. The advantages of this reaction include unprecedented C?H functionalization using phenol as a directing group, high regioselectivity, good substrate scope, mild reaction conditions, and high efficiency. To the best of our knowledge, this is the first example of a regioselective C?H alkenylation of unprotected phenols utilizing phenolic hydroxyl group as a directing group. The alkenylation of unprotected tyrosine and intramolecular cyclization are also successfully carried out under this catalytic system in good yields. Furthermore, this novel method enables a late-stage modification of complex phenol-containing bioactive molecules toward a diversity-oriented drug discovery. |
| Keywords: | alkenylation late-stage modification palladium phenols tyrosine |