Acid-Catalyzed [3+2] Cycloaddition of Enones with Azomethine Imines for Easy Access to Tetrahydropyrazolopyrazolones

Abstract

Aluminum chloride (AlCl₃) or zirconium chloride (ZrCl₄) catalyzes efficiently the [3+2] cycloaddition of N,N′-cyclic azomethine imines with enones which contain the vinyl group. The scope of the reaction towards various azomethine imines and enones has been explored. Access to diastereomerically pure 6-acyl-5-aryltetrahydropyrazolo[1,2-a]pyrazol-1(5H)-ones is provided by easy chromatographic separations.

Key words

dipolar cycloaddition - N,N′-cyclic azomethine imine - enone - N,N′-bicyclic heterocycles - Lewis acid

• References and Notes

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• 13 General Procedure for [3+2] Cycloaddition of N,N′-Cyclic Azomethine Imines 1 and Enones 2 In a 25 mL flask, enone 2 (0.5 mmol) was added to a stirred mixture of N,N′-cyclic azomethine imine 1 (0.6 mmol) and catalyst (AlCl₃ or ZrCl₄, 0.1 mmol) in CH₂Cl₂ (5.0 mL) at r.t. The mixture was stirred for 48 h. The solvent was then removed by distillation, and the crude mixture was separated by silica gel chromatography (hexane–EtOAc = 5:5 to 4:6). Fractions were collected and concentrated in vacuo to provide the pure products 3.
• 14 Selected Data for Products trans-3a 39% yield for AlCl₃-catalyzed reaction (35%yield for ZrCl₄-catalyzed reaction), pale yellow solid; mp 90 °C. ¹H NMR (200 MHz, CDCl₃): δ = 7.50–7.27 (m, 5 H, Ph), 4.13–3.92 (m, 1 H, H-6), 3.74–3.51 (m, 3 H, H-5, H-7a, and H-7b), 3.41 (ddd, J = 11.5, 9.4, 7.6 Hz, 1 H, H-3b), 2.99 (ddd, J = 11.5, 9.0, 6.6 Hz, 1 H, H-3a), 2.84–2.48 (m, 2 H, H-2a, and H-2b), 1.99 (s, 3 H, Me). ¹³C NMR (50 MHz, CDCl₃): δ = 204.1 (CO), 172.9 (C-1), 136.5 (Ph), 128.5 (Ph), 128.2 (Ph), 127.5 (Ph), 70.5 (C-5), 61.7 (C-6), 45.3 (C-3), 42.7 (C-7), 30.7 (C-2), 29.8 (Me). IR (KBr): 3030, 2952, 1713, 1455, 1361, 1169, 750, 703 cm^–1. Anal. Calcd for C₁₄H₁₆N₂O₂ (244.29): C, 68.83; H, 6.60. Found: C, 68.79; H, 6.62. cis-3a 55% yield for AlCl₃-catalyzed reaction (54% yield for ZrCl₄-catalyzed reaction), white solid; mp 160 °C. ¹H NMR (200 MHz, CDCl₃): δ = 7.53–7.26 (m, 5 H, Ph), 4.04–3.71 (m, 4 H, H-5, H-6, H-7a, and H-7b), 3.54 (pseudo dt, J = 11.1, 8.2 Hz, 1 H, H-3b), 2.91 (ddd, J = 11.1, 9.5, 6.9 Hz, H-3a), 2.71 (pseudo t, J = 8.2 Hz, 2 H, H-2a, and H-2b), 1.52 (s, 3 H, Me). ¹³C NMR (50 MHz, CDCl₃): δ = 205.4 (CO), 172.3 (C-1), 134.0 (Ph), 128.8 (Ph), 128.6 (Ph), 127.8 (Ph), 71.1 (C-5), 58.0 (C-6), 46.0 (C-3), 42.0 (C-7), 31.6 (C-2), 30.6 (Me). IR (KBr): 3062, 2966, 1709, 1699, 1458, 1357, 1175, 1090, 776, 712 cm^–1. Anal. Calcd for C₁₄H₁₆N₂O₂ (244.29): C, 68.83; H, 6.60. Found: C, 68.80; H, 6.63.
• 15 CCDC 1497416 contains the supplementary crystallographic data for this paper. The data can be obtained free of charge via www.ccdc.cam.ac.uk/getstructures.
• 16 In the case of sp² hybridization, this sum would be equal or close to 360°.