Visible-Light-Induced Decarboxylative Fluorination of Aliphatic Carboxylic Acids Catalyzed by Iron
Yu Zhang, Jiahui Qian, Miao Wang, Yahao Huang and Peng Hu*
*Lehn Institute of Functional Materials, School of Chemistry, Sun Yat-sen
University, Guangzhou 510006, China, Email: hupeng8mail.sysu.edu.cn
Y. Zhang, J. Qian, M. Wang, Y. Huang, P. Hu, Org. Lett., 2022, 24, 5972-5976.
DOI: 10.1021/acs.orglett.2c02242
Abstract
Iron salts catalyze an efficient and inexpensive protocol for the direct decarboxylative fluorination of aliphatic carboxylic acids under visible light irradition. This method allows the facile fluorination of a diverse array of carboxylic acids even on gram scale using a Schlenk flask without loss of efficiency.
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The document discusses a study on the visible-light-induced decarboxylative fluorination of aliphatic carboxylic acids using iron salts as catalysts. This method is efficient, cost-effective, and environmentally friendly, allowing for the fluorination of various carboxylic acids on a gram scale without losing efficiency. The process involves the photoinduced ligand-to-metal charge transfer (LMCT) to generate carboxyl radical intermediates. The study highlights the broad applicability of fluorinated molecules in pharmaceuticals, agrochemicals, and polymers. The optimized reaction conditions include using Fe(OAc)2 and a methoxy-substituted bipyridine ligand under blue LED irradiation, achieving up to 82% yield. The method tolerates a wide range of functional groups and is effective for primary, secondary, and tertiary carboxylic acids. Mechanistic studies confirm a free-radical process and the essential role of visible light. The reaction's scalability and robustness make it practical for large-scale applications, providing a straightforward and economical approach to synthesizing alkyl fluorides. The study's findings contribute to the development of user-friendly and efficient decarboxylative fluorination methods using non-noble metal catalysts.
General procedure for the substrate scope
An oven-dried 25 mL Schlenk-tube equipped with a magnetic stir bar was charged with alkyl carboxylic acid (0.4 mmol), ligand (10 mol%, 8.8 mg), Selectfluor (2.1 equiv. for secondary and tertiary carboxylic acids, 6.3 equiv. for primary carboxylic acids). Then the Schlenk-tube was transferred to a nitrogen-filled glovebox and Fe(OAc)2 (10 mol%, 6.9 mg) added. After that, the Schlenk-tube was sealed with a rubber plug and taken out of the glovebox. To the reaction mixture was added degassed MeCN (2 mL), degassed H2O (2 mL) and 2,6-lutidine (84 μl, 1.8 equiv.) via syringe or microsyringe, respectively. Finally, the reaction mixture was stirred and irradiated for 2 h under LEDs (6 W, 400 nm), cooling with a fan. To get accurate isolated yields, an average of two runs on 0.4 mmol scale were conducted in most cases. The reaction solution was then washed with water and extracted with DCM (3×20 mL), the organic layer was dried over Na2SO4, filtered, and concentrated by rotary evaporation. The residue was purified by chromatography on silica gel to obtain the final product.
Key Words
fluorination, photochemistry, selectfluor
ID: J54-Y2022