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Synlett 2002(2): 0310-0312
DOI: 10.1055/s-2002-19753
LETTER
© Georg Thieme Verlag Stuttgart · New York

Unsaturated 1,2-Amino Alcohols from Dihydropyrrole Epoxides and Organolithiums

David M. Hodgson*a, Timothy J. Milesa, Jason Witheringtonb
a Dyson Perrins Laboratory, Department of Chemistry, University of Oxford, South Parks Road, Oxford OX1 3QY, UK
Fax: +44(1865)275674; e-Mail: david.hodgson@chem.ox.ac.uk;
b GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK
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Publication History

Received 24 October 2001
Publication Date:
02 February 2007 (online)

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Abstract

The alkylative double ring-opening of Bus-protected 2,5-dihydropyrrole epoxide 11 with organolithiums to give 3-substituted 1-aminobut-3-en-2-ols 13-19 is described.

Key words

epoxides - organolithiums - amino alcohols - eliminations - alkenes

11

Typical Procedure for Preparation of an Amino Alcohol: Preparation of N-[3-(trimethylsilylmethyl)-2-hydroxybut-3-enyl]-2-methylpropane-2-sulfonamide (18). A solution of N-Bus epoxide 11 (0.100 g, 0.48 mmol) in Et2O (8 cm3) was added dropwise to a stirred solution of Me3SiCH2Li (1 mol dm-3 in pentane; 1.46 cm3, 1.46 mmol) in Et2O at -78 °C. After 1 h at -78 °C the reaction mixture was warmed to 25 °C over 1 h and then sat. aq NH4Cl (5 cm3) was added. The reaction mixture was extracted with Et2O (3 ¥ 10 cm3) and the combined organic layers were washed with sat. aq NaHCO3 (15 cm3), brine (15 cm3), dried (MgSO4) and then evaporated under reduced pressure. Purification of the residue by column chromatography [SiO2, elution gradient 30% to 60% Et2O in light petroleum (bp 30-40 °C)] gave amino alcohol 18 as a white solid (0.099 g, 69%). Rf = 0.15 [40% Et2O in light petroleum (bp 30-40 °C)]; mp 83.5-84.5 °C; IR: νmax(CHCl3)/cm-1 = 3436 (brs), 2955 (m), 1639 (brm), 1480 (w), 1420 (w), 1366 (w), 1306 (m), 1249 (m), 1159 (w), 1126 (m), 1094 (m) and 1010 (m);1H NMR (400 MHz, CDCl3): δ = 5.04 (1 H, s, H of CH2=), 4.80 (1 H, s, H of CH2=), 4.47-4.42 (1 H, m, NH), 4.12-4.05 (1 H, m, CHOH), 3.43 (1 H, ddd, J = 13.5, 8 and 3, H of CH2N), 3.07 (1 H, ddd, J = 13.5, 7.5 and 4, H of CH2N), 1.66 (1 H, d, J = 14, H of CH2Si), 1.42-1.35 (10 H, m, CMe 3 , H of CH2Si) and 0.05 (9 H, s, J H-Si = 6, SiMe3); 13C NMR (100 MHz, CDCl3): δ = 146.6 (CH2=C), 108.6 (CH2=), 74.8 (CHOH), 60.0 (CMe3), 48.9 (CH2N), 24.3 (CMe 3 ), 23.0 (CH2Si) and -1.4 (SiMe3); MS (CI, NH3): m/z (%) = 311 (100) [M + NH4 +], 294 (28), 278 (16), 240 (22), 223 (60) and 210 (22) (Found: [M + NH4 +], 311.1818. C12H31N2O3SSi requires 311.1825).

12

Yields of amino alcohols from reaction of other organo-lithiums with N-Boc epoxide 7 were unsatisfactory: s-BuLi (16%); t-BuLi (19%); CH2=CHLi (0%); Me3SiCH2Li (17%).