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

Wenfei Liu; Han Wang; Haiying Zhao; Baoguo Li; Shufeng Chen

doi:10.1055/s-0034-1381057

Synlett, Table of Contents

Synlett 2015; 26(15): 2170-2174
DOI: 10.1055/s-0034-1381057

letter

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

Authors

Wenfei Liu

Inner Mongolia Key Laboratory of Fine Organic Synthesis, Department of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot 010021, P. R. of China Email: shufengchen@imu.edu.cn Email: baoguol@sohu.com
Han Wang

Inner Mongolia Key Laboratory of Fine Organic Synthesis, Department of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot 010021, P. R. of China Email: shufengchen@imu.edu.cn Email: baoguol@sohu.com
Haiying Zhao

Inner Mongolia Key Laboratory of Fine Organic Synthesis, Department of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot 010021, P. R. of China Email: shufengchen@imu.edu.cn Email: baoguol@sohu.com
Baoguo Li*

Inner Mongolia Key Laboratory of Fine Organic Synthesis, Department of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot 010021, P. R. of China Email: shufengchen@imu.edu.cn Email: baoguol@sohu.com
Shufeng Chen*

Inner Mongolia Key Laboratory of Fine Organic Synthesis, Department of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot 010021, P. R. of China Email: shufengchen@imu.edu.cn Email: baoguol@sohu.com

Abstract

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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

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References

References and Notes

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8 For the crystal structure of 3a, please see the Supporting Information.
9 General Procedure for the Y(OTf)₃-Catalyzed Reaction of Tertiary Propargylic Alcohols with p-Toluenesulfonyl Hydrazide To a solution of propargylic alcohols (0.3 mmol) and p-toluenesulfonyl hydrazide (0.6 mmol) in MeCN (2.0 mL) was added Y(OTf)₃ (0.06 mmol) under an air atmosphere. The resulting mixture was heated at 80 °C for the indicated time. After completion of the reaction, the mixture was cooled to r.t. The solvent was removed in a vacuum, and the resulting residue was purified on a silica gel column (PE–EtOAc) to provide the desired α,β-unsaturated hydrazone products 3. Representative Spectroscopic Data Compound 3b: white solid; mp 128–130 °C. ¹H NMR (500 MHz, CDCl₃): δ = 1.86 (s, 3 H), 2.43 (s, 3 H), 6.19 (s, 1 H), 7.00–7.07 (m, 2 H), 7.33 (d, J = 8.0 Hz, 2 H), 7.39–7.44 (m, 3 H), 7.53–7.55 (m, 2 H), 7.63–7.68 (m, 2 H), 7.84 (s, 1 H), 7.89 (d, J = 8.5 Hz, 2 H). ¹³C NMR (125 MHz, CDCl₃): δ = 18.2, 21.6, 115.5, 125.9, 128.0, 128.8, 128.8, 129.1, 129.7, 131.9, 135.6, 139.5, 144.2, 146.6, 150.9, 162.9, 164.8. ESI-HRMS: m/z calcd for C₂₃H₂₂FN₂O₂S [M + H]⁺: 409.1381; found: 409.1379. Compound 3q: white solid; mp 114–117 °C. ¹H NMR (500 MHz, CDCl₃): δ = 1.29 (s, 6 H), 2.43 (s, 3 H), 3.65 (s, 1 H), 6.07 (s, 1 H), 7.30 (d, J = 7.0 Hz, 5 H), 7.36–7.39 (m, 2 H), 7.83(d, J = 8.0 Hz, 2 H). ¹³C NMR (125 MHz, CDCl₃): δ = 21.6, 27.0, 83.3, 91.6, 122.4, 128.3, 128.3, 128.4, 129.4, 131.7, 135.3, 143.8. Anal. Calcd for C₁₈H₂₀N₂O₂S: C, 65.83; H, 6.14; N, 8.53. Found: C, 65.81; H, 6.20; N, 8.41.

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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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Supplementary Material

Supporting Information (PDF)