Synlett, Table of Contents Synlett 2021; 32(03): 316-320DOI: 10.1055/s-0040-1707262 letter Palladium-Catalyzed Synthesis of Polysubstituted Pyrazoles by Ring-Opening Reactions of 2H-Azirines with Hydrazones Jiaan Shao‡ a School of Medicine, Zhejiang University City College, Hangzhou, 310015, P. R. of China , Ke Shu‡ b College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, P. R. of China , Shuangrong Liu b College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, P. R. of China , Huajian Zhu a School of Medicine, Zhejiang University City College, Hangzhou, 310015, P. R. of China , Jiankang Zhang a School of Medicine, Zhejiang University City College, Hangzhou, 310015, P. R. of China , Chong Zhang a School of Medicine, Zhejiang University City College, Hangzhou, 310015, P. R. of China , Ling-Hui Zeng a School of Medicine, Zhejiang University City College, Hangzhou, 310015, P. R. of China , Wenteng Chen∗ b College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, P. R. of China› Author AffiliationsRecommend Article Abstract Buy Article All articles of this category Abstract A palladium–catalyzed ring-opening reaction of 2H-azirines with hydrazones has been developed. This protocol provides an alternative route for the construction of various polysubstituted pyrazoles with a wide substrate scope. Moreover, a plausible mechanism is proposed for this reaction, which should further enrich the chemical conversion of 2H-azirines. Key words Key wordspalladium catalysis - ring opening - azirines - hydrazones - pyrazoles Full Text References References and Notes For reviews on 2H-azirine chemistry, see: 1a Nakamura S. Chem. Asian J. 2019; 14: 1323 1b Huang C.-Y, Doyle AG. Cm. Rev. 2014; 114: 8153 1c Khlebnikov AF, Novikov MS. Tetrahedron 2013; 69: 3363 1d Palacios F, Ochoa de Retana AM, Martínez de Marigorta E, de los Santos JM. Eur. J. Org. 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Determination of Total Nitrogen in Natural Waters by Means of Persulfate Oxidation, International Council for the Exploration of the Sea (ICES), Council Meeting (2nd ed.), Paper C:8 1969. 1970 ; ICES: Copenhagen; (accesed Aug 24, 2020) http://ices.dk/sites/pub/CM%20Doccuments/1969/C/1969_C8.pdf 17 Polysubstituted Pyrazoles 3a–t; General ProcedureThe appropriate 2H-azirine (1; 1.05 mmol), hydrazone 2 (1.0 mmol), Pd(OAc)2 (10 mol%), K2S2O8 (2.0 mmol), CsF (1.0 mmol), and anhyd 1,4-dioxane (6 mL) were sequentially added to a sealed tube under N2, and the mixture was stirred at 100 °C for about 12 h until the reaction was complete (TLC). The mixture was then filtered through diatomite, and the filter cake was washed with EtOAc(10 mL). The filtrate was collected and concentrated under reduced pressure, and the crude product was purified by chromatography [silica gel, PE–EtOAc (40:1)].3-(4-Bromophenyl)-1,4-diphenyl-1H-pyrazole (3a)Yellow solid; yield: 281 mg (75%); mp 113.4–114.7 °C. 1H NMR (500 MHz, DMSO-d 6): δ = 8.78 (s, 1 H), 7.95 (d, J = 7.8 Hz, 2 H), 7.59 (d, J = 8.5 Hz, 2 H), 7.54 (t, J = 7.9 Hz, 2 H), 7.45 (d, J = 8.5 Hz, 2 H), 7.41–7.31 (m, 6 H). 13C NMR (125 MHz, DMSO-d 6): δ = 148.2, 139.3, 132.2, 132.1, 131.4, 129.9, 129.5, 128.6, 128.3, 128.3, 127.1, 126.5, 122.2, 121.3, 118.4. HRMS (ESI): m/z [M+ H]+ calcd for C21H16BrN2: 375.0491; found: 375.0492. Supplementary Material Supplementary Material Supporting Information
