Y(OTf)₃-Catalyzed Cascade Propargylic Substitution/Aza-Meyer–Schuster Rearrangement: Stereoselective Synthesis of α,β-Unsaturated Hydrazones and Their Conversion into Pyrazoles

Abstract

A straightforward and concise method for the highly stereoselective synthesis of α,β-unsaturated hydrazones by the Y(OTf)₃-catalyzed cascade propargylic substitution/aza-Meyer–Schuster rearrangement reaction of tertiary propargylic alcohols and p-toluenesulfonyl hydrazide under an air atmosphere is developed. A series of α,β-unsaturated hydrazones have been synthesized from simple and readily available starting materials in good yields. Furthermore, the obtained α,β-unsaturated hydrazones are converted into pyrazoles in the presence of LiOt-Bu.

Keywords

propargylic alcohols - aza-Meyer–Schuster rearrangement - Y(OTf)₃ - α,β-unsaturated hydrazones - pyrazoles

• References and Notes


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• 12 General Procedure for the Synthesis of Pyrazoles from the Corresponding α,β-Unsaturated Hydrazones To a solution of α,β-unsaturated hydrazones (0.3 mmol) in toluene (2.0 mL) was added LiOt-Bu (0.45 mmol) under an air atmosphere. The resulting mixture was heated at 80 °C for the indicated time. After completion of the reaction, the solvent was removed in a vacuum. The resulting residue was purified on a silica gel column (EtOAc–PE) to provide the desired pyrazole products 4 and 5. Representative Spectroscopic DataCompound 4a: yellow solid; mp 68–71 °C. ¹H NMR (500 MHz, CDCl₃): δ = 1.83 (s, 3 H), 7.28–7.36 (m, 4 H), 7.39–7.44 (m, 3 H), 7.48 (t, J = 7.5 Hz, 2 H), 8.12–8.05 (m, 2 H). ¹³C NMR (125 MHz, CDCl₃): δ = 22.2, 100.3, 126.5, 127.3, 128.1, 128.8, 128.9, 129.3, 130.7, 136.34, 136.6, 154.9. ESI-HRMS: m/z calcd for C₁₆H₁₅N₂ [M + H]⁺: 235.1230; found: 235.1230. Compound 4f: yellow solid; mp 84–87 °C. ¹H NMR (500 MHz, CDCl₃): δ = 1.80 (s, 3 H), 7.29 (d, J = 8.5 Hz, 2 H), 7.41–7.51 (m, 5 H), 8.07 (d, J = 8.0 Hz, 2 H). ¹³C NMR (125 MHz, CDCl₃): δ = 22.2, 99.7, 122.1, 127.3, 128.2, 129.0, 129.5, 130.4, 131.9, 135.4, 135.8, 155.3. Anal. Calcd for C₁₆H₁₃BrN₂: C, 61.36; H, 4.18; N, 8.94. Found: C, 61.29; H, 4.31; N, 8.95.

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