Pd-catalyzed coupling of arylamines and 2-bromo-3,3,3-trifluoropropene

Palladium-catalyzed coupling of arylamines and 2-bromo-3,3,3-trifluoropropene (BTP) was investigated. When a toluene solution of aniline and BTP was heated at 110 °C in the presence of Pd2(dba)3·CHCl3, 1,1′-diphenylphosphinoferrocene and Cs2CO3 under an argon atmosphere, N-(1,1,1-trifluoro-2-propylidene)aniline was obtained in excellent GC and 19F NMR yields (99%) and isolated yield (92%). Cs2CO3 was exclusively effective in the coupling reaction among the bases tested. The coupling using 2-aminobenzonitriles as substrates provided not only 2-N-(1,1,1-trifluoro-2-propylidene)aminobenzonitriles but also 4-amino-2-trifluoromethylquinolines and 2-trifluoromethyl-4-N-(1,1,1-trifluoro-2-propylidene)aminoquinolines. The strong electron-withdrawing character of CF3 will enhance the acidity of the methyl proton in the N-(1,1,1-trifluoromethyl-2-propylidene)amino group, resulting in the attack of the methyl proton to the carbon in the cyano group to give 4-amino-2-trifluoromethylquinolines. Moreover, the one-pot synthesis of 2-trifluoromethylindoles with 2-bromoanilines and BTP was achieved by use of Pd(OAc)2, 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbipenyl and Cs2CO3. The Pd-catalyzed intramolecular Heck coupling of the vinyl group in 2-bromo-N-(1-trifluoromethyl)vinylanilines, which is the tautmeric isomer of 2-bromo-N-(1,1,1-trifluoro-2-propylidene)anilines, and the CBr bond presumably furnished indole rings. The CN double bond of N-(1,1,1-trifluoro-2-propylidene)amino group obtained here was smoothly hydrogenated to N-(1-methyl-2,2,2-trifluoro)ethylamino group using LiAlH4 or H2 with Pd/C.

Graphical abstractPd-catalyzed amination of 2-bromo-3,3,3-trifluoropropene with arylamines to provide (1,1,1-trifluoro-2-propylidene)amine was achieved. By use of 2-aminobenzonitriles and 2-bromoanilines, 4-amino-2-trifluoromethylquinolines and 2-trifluoromethylindoles were obtained, respectively. 1,1,1-trifluoro-2-propylidene group was readily hydrogenated to 1,1,1-trifluoro-2-propyl group by LiAlH4, etc.Figure optionsDownload full-size imageDownload as PowerPoint slide