Photoredox-Catalyzed Acylchlorination of α-CF3 Alkenes with Acyl Chloride and Application as Masked Access to β-CF3-enones
Youkang Zhou, Qi Jiang, Yangyang Cheng, Mingyou Hu, Xin-Hua Duan, Le Liu*
*School of Chemistry, Xi'an Key Laboratory of Sustainable Energy Material Chemistry, Xi’an Jiaotong University, Xi’an 710049, China,
Email: le.liu
xjtu.edu.cn
Y. Zhou, Q. Jiang, Y. Cheng, M. Hu, X.-H. Duan, L. Liu, Org. Lett., 2024, 26, 2656-2661.
DOI: 10.1021/acs.orglett.4c00830
Abstract
A photocatalytic strategy simultaneously addresses the construction of trifluoromethylated quaternary carbon centers and the preparation of β-CF3-enones through radical difunctionalization of α-CF3 alkenes with acyl chlorides. This rapid assembly of structurally diverse fluorinated compounds offers broad functional group compatibility, high efficiency, and atom economy.
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Details
The document discusses a novel photocatalytic strategy for the acylchlorination of α-CF3 alkenes using acyl chlorides, which simultaneously constructs trifluoromethylated quaternary carbon centers and prepares β-CF3-enones. This method is notable for its broad functional group compatibility, high efficiency, and atom economy. The trifluoromethyl (CF3) group is significant in pharmaceuticals and agrochemicals due to its properties that enhance lipophilicity, bioavailability, and metabolic stability. Traditional methods for synthesizing β-CF3-enones are limited, often requiring prefunctionalized starting materials. The new approach leverages radical difunctionalization under mild photoredox conditions, using blue LED irradiation and a photocatalyst like Ir(ppy)3. The method has been optimized to achieve high yields and is applicable to a wide range of α-trifluoromethyl styrenes and acyl chlorides. The process also allows for the late-stage functionalization of complex molecules, making it a versatile tool in synthetic chemistry. The study includes gram-scale synthesis and various derivatization reactions, demonstrating the method's practicality and potential for creating structurally diverse fluorinated compounds. The proposed mechanism involves radical addition, single-electron oxidation, and nucleophilic attachment, leading to the formation of acylchlorinated products and subsequent β-CF3-enones.
Key Words
chlorides, ketones, enones, trifluoromethyl alkenes, photochemistry
ID: J54-Y2024
