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Synlett 2006(2): 239-242  
DOI: 10.1055/s-2005-922791
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Broadened Scope for the Use of Hydrazones as Neutral Nucleophiles in the Presence of H-Bonding Organocatalysts

Daniel Pettersen*a, Raquel P. Herrera*a, Luca Bernardia, Franscesco Finia, Valentina Sgarzania, Rosario Fernandezb, José M. Lassalettac, Alfredo Riccia
a Dipartimento di Chimica Organica ‘A. Mangini’, Università di Bologna, Viale Risorgimento N°4, 40136 Bologna, Italy
Fax: +39(051)2093654; e-Mail: dap@chem.gu.se, rph@alu.ua.es;
b Dpto. de Quimica Organica, Universidad de Sevilla, Apdo. de Correos 553, 41071 Seville, Spain
c Instituto de Investigaciones Quimicas (CSIC-Use), Isla de la Cartuja, Americo Vespucio s/n, 41092 Seville, Spain
Further Information

Publication History

Received 2 November 2005
Publication Date:
23 December 2005 (online)

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Abstract

Using thioureas as H-bonding organocatalysts, nitro­alkenes can be activated for the conjugate addition of hydrazones as neutral nucleophiles. Formaldehyde derivatives react at the azo­methine carbon as expected, whereas hydrazones from enolizable aldehydes behave as ene-hydrazines and react at the α-carbon ­instead. Ionic liquids were found to decrease the reaction times ­considerably compared to commonly used solvents, whereas alternative activation by Lewis acids resulted in decomposition of ­reactants.

Key words

catalysis - ionic liquids - hydrazones - nucleophiles - ­addition reactions

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Experimental Procedure.
To a mixture of thiourea 1 (0.02 mmol, 10 mg) and nitroalkene (0.1 mmol) in CH2Cl2 (100 µL) was added hydrazone (0.15 mmol). The reaction was then stirred for the time stated at ambient temperature. The product was isolated as an oil using column chromatography (EtOAc-hexane, 1:4). All compounds gave satisfactory analytical and spectral data.
Typical data for representative compounds:
Compound 4ca (19.2 mg, 77%): Major diastereomer: 1H NMR (300 MHz, CDCl3): δ = 0.85 (3 H, d, J = 6.87 Hz, CH3), 2.62 (1 H, m, J = 6.87, 7.11, 10.2 Hz, CH3CH), 2.75 [6 H, s, N(CH3)2], 3.41 (1 H, dt-like, J = 5.27, 10.20 PhCH), 4.53 (1 H, dd, J = 9.87, 12.9 Hz, CHNO2), 4.76 (1 H, dd, J = 5.07, 12.9 Hz, CHNO2), 6.39 (1 H, d, J = 7.11, HC=N), 7.08-7.37 (5 H, m, Ph). 13C NMR (75 MHz, CDCl3): δ = 17.96, 41.14, 43.18, 48.79, 79.94, 127.9, 128.3, 129.1, 136.7, 138.7. ESI-MS: m/z = 272 [M + Na+]. HRMS: m/z calcd for C13H19N3O2: 249.1477; found: 249.1475.
Compound 4de (24.7 mg, 82%): Major diastereomer: 1H NMR (300 MHz, CDCl3): δ = 2.80 [6 H, s, N(CH3)2], 3.89 (1 H, dd, J = 5.84, 10.3 Hz, PhCH), 4.26 (1 H, m, CH), 4.77 (1 H, dd, J = 8.96, 12.9, CHNO2), 4.95 (1 H, dd, J = 5.01, 12.9, CHNO2), 5.83 (1 H, m, furyl), 6.08 (1 H, m, furyl), 6.62 (1 H, d, J = 5.84 Hz, HC=N), 7.05-7.38 (5 H, m, Ph and 1H, furyl). 13C NMR (75 MHz, CDCl3): δ = 41.99, 43.11, 51.07, 77.25, 108.8, 110.3, 127.2, 128.3, 128.4, 129.3, 139.6, 142.1, 151.2. ESI-MS: m/z = 324 [M + Na+]. HRMS: m/z calcd for C16H19N3O3: 301.1426; found: 301.1424.

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Formation of adducts derived from attack by the azo-methine carbon was not observed for any of the studied hydrazones 2b-f.

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Other H-bonding catalysts such as tartaric acid or mandelic acid were unsuccessfully tried. Furthermore, no decomposition of hydrazones or nitroalkenes in presence of thiourea 1 was observed after one week in CH2Cl2.