Synlett, Table of Contents Synlett 2024; 35(13): 1551-1556DOI: 10.1055/a-2216-4594 letter PhI(OAc)2-Promoted Regioselective Cycloaddition of N-Aminopyridinium Ylides with Electron-Deficient Alkenes Junlei Wang‡ a Guizhou Minzu University, Guiyang 550025, P. R. of China , Guiling Chen‡ a Guizhou Minzu University, Guiyang 550025, P. R. of China , Chengcheng Shi‡ b State Key Lab of Urban Water Resource and Environment School of Science Harbin Institute of Technology (Shenzhen), Shenzhen 518055, P. R. of China , Qinglin Xie a Guizhou Minzu University, Guiyang 550025, P. R. of China , Guocheng Gao a Guizhou Minzu University, Guiyang 550025, P. R. of China , Yanan Li C College of Education for the Future & College of Arts and Sciences, Beijing Normal University, Zhuhai 519087, P. R. of China , Haijun Du a Guizhou Minzu University, Guiyang 550025, P. R. of China , Xiaohua Cai a Guizhou Minzu University, Guiyang 550025, P. R. of China , Hongqing Li∗ a Guizhou Minzu University, Guiyang 550025, P. R. of China , Binbin Huang∗ C College of Education for the Future & College of Arts and Sciences, Beijing Normal University, Zhuhai 519087, P. R. of China › Author Affiliations Recommend Article Abstract Buy Article All articles of this category Abstract Herein, we report a regioselective cycloaddition strategy of N-aminopyridinium ylides with electron-deficient alkenes, in the presence of a hypervalent iodine reagent, PhI(OAc)2. A variety of multifunctionalized pyrazolo[1,5-a]pyridine architectures were smoothly afforded by the reactions of pyridine-, quinoline-, and isoquinoline-based N-ylides with diverse alkenes with or without a halogen atom adjacent to the electron-withdrawing group (EWG) under facile conditions. Key words Key wordsregioselective - cycloaddition - N-aminopyridinium - alkenes Full Text References References and Notes. 1 Yoshimura A, Zhdankin VV. A. Chem. 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The reaction mixture was continuously stirred, triethylamine (1.5 equiv.) was added dropwise, and the reaction was stirred for 2 h. The obtained reaction mixture was filtered and washed with methyl tert-butyl ether (MTBE). Then, the filtrate was concentrated, n-hexane was added to the concentrate solution at room temperature, and after stirring for 5 min, a white solid appeared, washed with 10 mL of n-hexane to give the desired compound as a white solid.55 Preparation of O-Mesitylsulfonylhydroxylamine (MSH) TFA (0.15 M) was cooled to 0 °C, and tert-butyl N-mesitylsulfonyloxycarbamate (MSC, 1.0 equiv.) was added. The reaction mixture was stirred at the same temperature for 1.5 h, then poured into crushed ice. The resulting white-colored precipitate was filtered off, then washed with water (1.5 M), and dried under vacuum, affording the title compound as a white solid and used to the next step without further purification.59 Preparation of N-Aminopyridines Salts Pyridine (1.0 equiv.) was added to the O-mesitylsulfonylhydroxylamine (MSH, 1.0 equiv.) solution (around 0.13 M in CH2Cl2) at 0 °C and stirred for 10 min. The resulted mixture was then allowed to be heated to reflux using an oil bath, monitored by TLC. Upon completion, the solvent was removed by rotary evaporation, and the residue was rinsed with n-hexane. The solid was collected through filtration and dried over vacuum to afford the desired product which was used for the next step without further purification.59 61 General Procedure for Cycloaddition Reactions To a stirring suspension of N-aminopyridines (1.0 equiv.) in CH3CN (0.05 M) was added 2-chloroacrylonitrile (1.2 equiv.). Then PhI(OAc)2 (1.5 equiv.) was added. After being cooled to 0 °C, Et3N (2.0 equiv.) was added dropwise. The resulting mixture was then stirred under nitrogen at room temperature and monitored by TLC. After N-aminopyridine was completely consumed, the product was purified by column chromatography with petroleum ether and ethyl acetate. 62 Selected Typical Cycloaddition Product: 7-Chloro-6-fluoro-4-methylpyrazolo[1,5-a]pyridine-3-carbonitrile (3v) Purified with silica gel chromatography (petroleum ether/ethyl acetate = 20:1), 147–150 °C, 4 h, 28.8 mg, 55% isolated yield. 1H NMR (400 MHz, CDCl3): δ = 8.34 (s, 1 H), 7.22 (d, J = 8.4 Hz, 1 H), 2.78 (s, 3 H). 13C NMR (101 MHz, CDCl3): δ = 150.1 (d, J = 243.3 Hz), 146.6 (d, J = 2.4 Hz), 140.6, 127.7 (d, J = 7.9 Hz), 119.5 (d, J = 24.1 Hz), 114.1, 84.8, 18.0. 19F NMR (376 MHz, CDCl3): δ = –133.15 (d, J = 8.5 Hz). HRMS (ESI): m/z calcd for C9H6ClFN3 + [M + H]+: 210.0229; found: 210.0221. Supplementary Material Supplementary Material Supporting Information
