Trifluoromethylation of Benzoic Acids: An Access to Aryl Trifluoromethyl Ketones
Xue Liu, Long Liu, Tianzeng Huang, Jingjing Zhang, Zhi Tang, Chunya Li and Tieqiao Chen*
*Hainan Provincial Key Lab of Fine Chem, Hainan Provincial Fine Chemical Engineering Research Center, Hainan University, Haikou 570228, China, Email: chentieqiaohnu.edu.cn
X. Liu, L. Liu, T. Huang, J. Zhang, Z. Tang, C. Li, T. Chen, Org. Lett., 2021, 23, 4930-4934.
DOI: 10.1021/acs.orglett.1c01720 (free Supporting Information)
see article for more reactions
The use of anhydrides as in situ activating reagents enables an efficient and convenient trifluoromethylation of a wide range of benzoic acids with TMSCF3 through addition-elimination to provide aryl trifluormethyl ketones in very good yields.
see article for more examples
proposed reaction pathway
General Experimental Procedure for the Synthesis of Trifluoromethyl ketones
An oven dried 25 mL Schlenk tube was charged with carboxylic acid (0.2 mmol), DMAP (0.5 mmol, 2.5 equiv.), CsF (0.5 mmol, 2.5 equiv.). Subsequently, TMSCF3 (0.6 mmol, 3.0 equiv.), TFAA (0.4 mmol, 2.0 equiv.) and PhOMe (2 mL) were added under a N2 atmosphere. The reaction mixture was reacted at 120 °C for 15 hours. Then the mixture was cooled to room temperature, water (10 mL) was added, and the mixture was extracted with EtOAc (5 mL×3). The combined organic phases were dried over anhydrous Na2SO4, filtered and concentrated under vacuum. Further purification by flash column chromatography on silica gel (eluting with petroleum ether/ethyl acetate) provided the product.