Synlett, Table of Contents Synlett 2022; 33(04): 381-385DOI: 10.1055/a-1705-0247 letter A Mild and Efficient Synthesis of Pyrazolo[1,5-a]pyridines Mediated by Triphenylphosphine/Diiodine Authors Kai Jia‡ Wenchao Ma‡ Yintao Yan Chenming Zhang Chao Jiang ∗ Recommend Article Abstract Buy Article(opens in new window) All articles of this category(opens in new window) Abstract A synthesis of 2,3-diaryl-substituted pyrazolo[1,5-a]pyridines in moderate to good yields under metal-free and mild conditions is described. The intramolecular cyclization of the oxime substrates is mediated by PPh3/I2, which leads directly to pyrazolo[1,5-a]pyridines without the formation of a 2H-azirine intermediate. Various substituents on the aryl rings are compatible with the method. Key words Key wordspyrazolopyridines - oximes - metal-free synthesis - iodine - triphenylphosphine Full Text References References and Notes For selected examples, see: 1a Shultz MD, Cao X, Chen CH, Cho YS, Davis NR, Eckman J, Fan J, Fekete A, Firestone B, Flynn J, Green J, Growney J, Holmqvist DM, Hsu M, Jansson D, Jiang L, Kwon P, Liu G, Lombardo F, Lu Q, Majumdar D, Meta C, Perez L, Pu M, Ramsey T, Remiszewski S, Skolnik S, Traebert M, Urban L, Uttamsingh V, Wang P, Whitebread S, Whitehead L, Yan-Neale Y, Yao Y.-M, Zhou L, Atadja P. J. Med. Chem. 2011; 54: 4752 1b Balkenhohl M, Salgues B, Hirai T, Karaghiosoff K, Knochel P. Org. Lett. 2018; 20: 3114 1c Nirogi R, Mohammed AR, Shinde AK, Gagginapally SR, Kancharla DM, Middekadi VR, Bogaraju N, Ravella SR, Singh P, Birangal SR, Subramanian R, Palacharla RC, Benade V, Muddana N, Jayarajan P. J. Med. 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Lett. 2005; 7: 4753 12 6-Methyl-2,3-diphenylpyrazolo[1,5-a]pyridine (2c); Typical ProcedureA mixture of oxime 1c (60 mg, 0.2 mmol), PPh3 (79 mg, 0.3 mmol), I2 (76 mg, 0.3 mmol), imidazole (27 mg, 0.4 mmol), and THF (2.0 mL) was added under air to a high-pressure tube. The tube was sealed and the mixture was stirred at 30 °C for 40 min, then cooled to R.T., and filtered through a pad of silica gel that was subsequently washed with 1:1 EtOAc–PE (100 mL). The solvents were removed under reduced pressure, and the residue was purified by chromatography [silica gel, EtOAc–PE (1:20)] to give a white solid; yield: 29 mg (52%); mp 110.1 °C.1H NMR (500 MHz, CDCl3): δ = 8.31 (s, 1 H), 7.62–7.57 (m, 2 H), 7.48 (d, J = 9.0 Hz, 1 H), 7.41–7.34 (m, 4 H), 7.32 (d, J = 6.1 Hz, 4 H), 6.98 (d, J = 9.1 Hz, 1 H), 2.36 (s, 3 H). 13C NMR (126 MHz, CDCl3): δ = 150.3, 138.3, 133.4, 133.4, 129.9, 128.9, 128.7, 128.4, 128.0, 126.9, 126.5, 126.3, 122.1, 116.6, 109.9, 18.2. HRMS (ESI-TOF): m/z [M + H]+ calcd for C20H16N2: 285.1392; found: 285.1388. 13a Appel R. Angew. Chem. Int. Ed. 1975; 14: 801 13b Desmaris L, Percina N, Cottier L, Sinou D. Tetrahedron Lett. 2003; 44: 7589 13c Baughman TW, Sworen JC, Wagener KB. Tetrahedron 2004; 60: 10943 13d Årstad E, Barrett AG. M, Hopkins BT, Köbberling J. Org. Lett. 2002; 4: 1975 Supplementary Material Supplementary Material Supporting Information (PDF)
