We are grateful for the financial support from the National Natural Science Foundation of China (GZ-1645), the Key Research & Development Project in Shaanxi Province (2022GY-195, 2023-YBGY-183), the Basic Research Project of Natural Science of Shaanxi Province (2021JLM-30), and Shaanxi Provincial Department of Education Science and Technology Project (23JC035).
N-(Difluoropropenyl)amides/amines are an important class of fluorinated compounds. Here, we report an efficient method for synthesizing these compounds without the use of transition metals. Under simple base-promoted conditions, 3-bromo-3,3-difluoroprop-1-ene reacts with N-methylanilines or N-arylacrylamides, with the elimination of one molecule of HBr, to give the target compound. Another efficient method for synthesizing difluoroalkenes is the reaction of 2-bromo-3,3,3-trifluoroprop-1-ene with indole or its analogues.
29 CCDC 2323785 contains the supplementary crystallographic data for compound 7e. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures.
30N-(3,3-Difluoroprop-2-en-1-yl)-N-(4-methoxyphenyl)acrylamide; Typical Procedure A 35.0 mL glass reaction tube was charged with N-(4-methoxyphenyl)acrylamide (1a; 1.0 mmol), 3-bromo-3,3-difluoropropene (2; 2.0 mmol) t-BuOK (2.0 mmol), and MeCN (2.0 mL), and the tube was placed in an autoclave. The autoclave was sealed, purged three times with N2, and heated in an oil bath at 100 °C for 8 h. The autoclave was then cooled to r.t. and the crude product was purified by column chromatography [silica gel, PE–EtOAc (30:1 to 10:1)] to give a yellow liquid; yield: 39.2 mg (55%). 1H NMR (400 MHz, CDCl3): δ = 7.05–6.70 (m, 4 H), 6.28 (d, J = 16.8 Hz, 1 H), 6.02–5.80 (m, 1 H), 5.44 (d, J = 10.3 Hz, 1 H), 4.48–4.30 (m, 1 H), 4.25 (d, J = 7.9 Hz, 2 H), 3.76 (s, 3 H). 13C NMR (101 MHz, CDCl3): δ = 165.7, 159.2, 157.7 (t, J = 289.0 Hz), 133.9, 129.2, 128.4, 127.8, 114.8, 74.9 (dd, J = 18.8, 23.2 Hz), 55.5, 42.7 (d, J = 7.4 Hz). 19F NMR (376 MHz, CDCl3): δ = –85.75 (d, J = 38.09 Hz, 1 F), –88.17 (dd, J = 24.52, 37.41 Hz). HRMS (ESI): m/z [M + Na]+ calcd for C13H13F2NNaO2: 276.0812; found: 276.0810.
