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Radical Acylfluoroalkylation of Olefins through N-Heterocyclic Carbene Organocatalysis |
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| Authors: | Prof Dr Jun-Long Li Yan-Qing Liu Wen-Lin Zou Rong Zeng Xiang Zhang Dr Yue Liu Prof Dr Bo Han Yu He Hai-Jun Leng Prof Dr Qing-Zhu Li |
| Institution: | 1. Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, Chengdu University, Chengdu, 610052 China
Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu, 610041 China These authors contributed equally to this work.;2. State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137 China These authors contributed equally to this work.;3. Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, Chengdu University, Chengdu, 610052 China;4. Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, Chengdu University, Chengdu, 610052 China Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu, 610041 China;5. State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137 China |
| Abstract: | Fluorinated ketones are widely prevalent in numerous biologically interesting molecules, and the development of novel transformations to access these structures is an important task in organic synthesis. Herein, we report the multicomponent radical acylfluoroalkylation of a variety of olefins in the presence of various commercially available aromatic aldehydes and fluoroalkyl reagents through N-heterocyclic carbene organocatalysis. With this protocol, over 120 examples of functionalized ketones with diverse fluorine substituents have been synthesized in up to 99 % yield with complete regioselectivity. The generality of this catalytic strategy was further highlighted by its successful application in the late-stage functionalization of pharmaceutical skeletons. Excellent diastereoselectivity could be achieved in the reactions forging multiple stereocenters. In addition, preliminary results have been achieved on the catalytic asymmetric variant of the olefin difunctionalization process. |
| Keywords: | Fluorketone Mehrkomponenten-Reaktionen NHC-Organokatalyse Olefin-Difunktionalisierung Radikalische Acylfluoralkylierung |