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Synlett 2003(14): 2258-2260  
DOI: 10.1055/s-2003-42101
LETTER
© Georg Thieme Verlag Stuttgart · New York

An Efficient Acid-Catalysed 5-endo-dig Cyclisation Method for Pyrrole Synthesis

David W. Knight*, Christopher M. Sharland
Cardiff School of Chemistry, Cardiff University, P.O. Box 912, Cardiff, CF10 3TB, UK
e-Mail: knightdw@cardiff.ac.uk;
Further Information

Publication History

Received 14 August 2003
Publication Date:
29 October 2003 (online)

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Abstract

Exposure of the γ-ynyl-β-hydroxy-α-amino esters 14 and 16, derived from condensations between conjugated ynals and ynones 11 and the tin(II) enolate of N-tosylglycinate 12, to 0.5 equivalents of toluenesulfinic or sulfonic acid in hot toluene induces smooth 5-endo-dig cyclisation and dehydration to give good to excellent yields of the pyrroles 15 and 17.

Key words

pyrrole - 5-endo-dig cyclisation - γ-ynyl-β-hydroxy-α-amino esters

    References

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8

Ethyl 5-(propen-2-yl)-1-(4-toluenesulfonyl)pyrrole-2-carboxylate ( 15c). A typical procedure is as follows: The amino-ester 14c (0.100 g, 0.29 mmol) was dissolved in toluene (10 mL) containing p-toluenesulfinic acid (0.027 g, 0.15 mmol) and the resulting solution stirred at reflux for 6 h. The cooled solution was then diluted with water (20 mL) and evaporated. The residue was dissolved in Et2O (50 mL) and the resulting solution washed with 2 M aq KOH (2 × 10 mL) and brine (10 mL) then dried (MgSO4), filtered and evaporated. Column chromatography of the residue (SiO2; 10-15% Et2O-hexanes) separated the pyrrole 15c as a viscous oil (0.072 g, 76%), which showed the following spectroscopic data. IR (film): 1732, 1598, 1495, 1446, 1304, 1192, 1020, 914, 815 cm-1. 1H NMR (400 MHz, CDCl3):
δ = 1.28 (t, J = 7.1 Hz, 3 H, OCH2CH 3), 1.91 (br. app. s, 3 H, CH3), 2.34 (s, 3 H, Ar-CH3), 4.26 (q, J = 7.1 Hz, 2 H, OCH 2CH3), 4.86 (app. s, 1 H, =CH), 5.11 (app. s, 1 H, =CH), 5.96 (d, 1 H, J = 3.5 Hz, 4-H), 6.75 (d, 1 H, J = 3.5 Hz, 3-H), 7.19 (d, J = 8.3 Hz, 2 H, 2 × ArCH), 7.72 (d, J = 8.3 Hz, 2 H, 2 × ArCH). 13C NMR (100 MHz, CDCl3): δ = 14.3, 20.9, 22.9 (all CH3), 62.6 (OCH2), 114.2 (4-CH), 119.4 (=CH2), 122.8 (3-CH), 128.2, 129.8 (both 2 × ArCH) and 160.9 (CO). MS (APcI): m/z (%) = 334 (100) [M+ H+]. HRMS: m/z [M ] calcd for C17H20NO4S: 334.1113; found [M + H+]: 334.1114.