PhI(OAc)₂-Promoted Regioselective Cycloaddition of N-Aminopyridinium Ylides with Electron-Deficient Alkenes

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

regioselective - cycloaddition - N-aminopyridinium - alkenes

Publication History

Received: 07 October 2023

Accepted after revision: 22 November 2023

Accepted Manuscript online:
22 November 2023

Article published online:
04 January 2024

• References and Notes.

• 1 Yoshimura A, Zhdankin VV. A. Chem. Rev. 2016; 116: 3328
• 2 Charpentier J, Früh N, Togni A. Chem. Rev. 2015; 115: 650
• 3 Hari DP, Caramenti P, Waser J. Acc. Chem. Res. 2018; 51: 3212
• 4 Lee H.-J, Huang X, Sakaki S, Maruoka K. Green Chem. 2021; 23: 848
• 5 Zhdankin VV, Stang PJ. Chem. Rev. 2008; 108: 5299
• 6 Ballaschka F, Kirsch SF. Green Chem. 2019; 21: 5896
• 7 Cots E, Flores A, Romero MR, Muñiz K, Muñiz A. ChemSusChem 2019; 12: 3028
• 8 Röben C, Souto JA, González Y, Lishchynskyi A, Muñiz K. Angew. Chem. Int. Ed. 2011; 50: 9478
• 9 Dohi T, Maruyama A, Takenaga N, Senami K, Minamitsuji Y, Fujioka H, Caemmerer SB, Kita YA. Angew. Chem. Int. Ed. 2008; 47: 3787
• 10 Li G.-X, Hu X, He G, Chen G. Chem. Sci. 2019; 10: 688
• 11 Wu S, Li J, He R, Jia K, Chen Y. Org. Lett. 2021; 23: 9204
• 12 Wang J, Xie Q, Gao G, Li H, Lu W, Cai X, Chen X, Huang B. Org. Chem. Front. 2023; 10: 4394
• 13 Payne JL, Deng Z, Flach AL, Johnston JN. Chem. Sci. 2022; 13: 7318
• 14 Parra A. Chem. Rev. 2019; 119: 12033
• 15 Huang B, Chen G, Zhang H, Tang X, Yuan J, Lu C, Wang J. Org. Chem. Front. 2023; 10: 3515
• 16 Zhang L, Wang Y, Yang Y, Zhang P, Wang C. Org. Chem. Front. 2020; 7: 3234
• 17 Abdolalian P, Tizhoush SK, Farshadfar K, Ariafard A. Chem. Sci. 2021; 12: 7185
• 18 Wang N, Gu Q.-S, Li Z.-L, Li Z, Guo Y.-L, Guo Z, Liu X.-Y. Angew. Chem. Int. Ed. 2018; 57: 14225
• 19 Tang N, Wu X, Zhu C. Chem. Sci. 2019; 10: 6915
• 20 Wu X, Zhang H, Tang N, Wu Z, Wang D, Ji M, Xu Y, Wang M, Zhu C. Nat. Commun. 2018; 9: 3343
• 21 Hoashi Y, Takai T, Kosugi Y, Nakashima M, Nakayama M, Hirai K, Uchikawa O, Koike T. J. Med. Chem. 2021; 64: 3059
• 22 Lee JW, Park J, Kim J, Choi C, Min KH. Eur. J. Med. Chem. 2021; 216: 113298
• 23 O´Malley DP, Ahuja V, Fink B, Cao C, Wang C, Swanson J, Wee S, Gavai AV, Tokarski J, Critton D, Paiva AA, Johnson BM, Szapiel N, Xie D. ACS Med. Chem. Lett. 2019; 10: 1486
• 24 Devi Priya D, Nandhakumar M, Mohana Roopan S. Synth. Commun. 2020; 50: 3535
• 25 Kendall JD. Curr. Org. Chem. 2011; 15: 2481
• 26 Balkenhohl M, Salgues B, Hirai T, Karaghiosoff K, Knochel P. Org. Lett. 2018; 20: 3114
• 27 Motornov VA, Tabolin AA, Nelyubina YV, Nenajdenko VG, Ioffe SL. Org. Biomol. Chem. 2020; 18: 1436
• 28 Ravi C, Samanta S, Mohan DC, Reddy NN. K, Adimurthy S. Synthesis 2017; 49: 2513
• 29 Ravi C, Mohan DC, Reddy NN. K, Adimurthy S. RSC Adv. 2015; 5: 42961
• 30 Eary CT, Spencer S, Crane Z, Chando K, Asselin S, Liu W, Welch M, Cook A, Kolakowski GR, Metcalf AT, Moreno DA, Tang TP. US10745419B2, 2020
• 31 Mousseau JJ, Fortier A, Charette AB. Org. Lett. 2010; 12: 516
• 32 Tang J, Wang B, Wu T, Wan J, Tu Z, Njire M, Wan B, Franzblauc SG, Zhang T, Lu X, Ding K. ACS Med. Chem. Lett. 2015; 6: 814
• 33 Liao Q, Zhang L, Li S, Xi C. Org. Lett. 2011; 13: 228
• 34 Tang H.-T, Zeng J.-H, Chen J. -J, Zhou Y.-B, Lia R.-H, Zhan Z.-P. Org. Chem. Front. 2017; 4: 1513
• 35 Wen L.-R, Jin X.-J, Niu X.-D, Li M. J. Org. Chem. 2015; 80: 90
• 36 Huang P, Yang Q, Chen Z, Ding Q, Xu J, Peng Y. J. Org. Chem. 2012; 77: 8092
• 37 Zhao Y, Xia W. Chem. Soc. Rev. 2018; 47: 2591
• 38 Yu X.-Y, Chen J.-R, Xiao W.-J. Chem. Rev. 2021; 121: 506
• 39 Yu X.-Y, Zhao Q.-Q, Chen J, Xiao W.-J, Chen J.-R. Acc. Chem. Res. 2020; 53: 1066
• 40 Duan Z, Zhang L, Zhang W, Lu L, Zeng L, Shi R, Lei A. ACS Catal. 2020; 10: 3828
• 41 Lv Z, Wang H, Quan Z, Gao Y, Lei A. Chem. Commun. 2019; 55: 12332
• 42 Hou Z.-W, Mao Z.-Y, Xu H.-C. Org. Biomol. Chem. 2021; 19: 8789
• 43 Hou Z.-W, Xu H.-C. ChemElectroChem 2021; 8: 1571
• 44 Hou Z.-W, Mao Z.-Y, Melcamu YY, Lu X, Xu H.-C. Angew. Chem. Int. Ed. 2018; 57: 1636
• 45 Song C, Liu K, Jiang X, Dong X, Weng Y, Chiang C.-W, Lei A. Angew. Chem. Int. Ed. 2020; 59: 7193
• 46 Huang Q, He D, Han J, Chen J, He W, Deng H, Shao M, Zhang H, Cao W. Synthesis 2018; 50: 3731
• 47 Ding S, Yan Y, Jiao N. Chem. Commun. 2013; 49: 4250
• 48 Wang Z, Li X, Qiu J, Li W, Li H, Weng Z, Li H. Org. Lett. 2022; 24: 6292
• 49 Xiong L, Chen F, Wu Y, Hu X, Ruan Z, Jiang H, Zeng W. Org. Lett. 2022; 24: 7856
• 50 Wang A, Liu Y.-Z, Shen Z, Qiao Z, Ma X. Org. Lett. 2022; 24: 1454
• 51 Jung S, Lee H, Moon Y, Jung H.-Y, Hong S. ACS Catal. 2019; 9: 9891
• 52 Moon Y, Lee W, Hong S. J. Am. Chem. Soc. 2020; 142: 12420
• 53 Kim N, Lee C, Kim T, Hong S. Org. Lett. 2019; 21: 9719
• 54 Im H, Choi W, Hong S. Angew. Chem. Int. Ed. 2020; 59: 17511
• 55 Mendiola J, Rincon JA, Mateos C. Org. Process Res. Dev. 2009; 13: 263
• 56 Bradlow HL, Vanderwerf CA. J. Org. Chem. 1961; 16: 73
• 57 Tamura Y, Sumida Y, Miki Y, Ikeda M. J. Chem. Soc., Perkin Trans. 1 1975; 406
• 58 Yang X.-L, Peng X.-X, Chen F, Han B. Org. Lett. 2016; 18: 2070
• 59 Liu Z, Wu S, Chen Y. ACS Catal. 2021; 11: 10565
• 60 Preparation of Starting Materials: General Procedure A Mesitylene-2-sulfonyl chloride (1.0 equiv.), tert-butyl N-hydroxycarbamate (1.0 equiv.) dissolved in methyl tert-butyl ether (0.2 M), degassed oxygen with N₂ for three times and cooled to 0 °C. 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.