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

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.

epoxides - organolithiums - amino alcohols - eliminations - alkenes

References

Reviews:

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Allylic alkoxide 5 could also form from α-lithiated epoxide 2 via adjacent C-H insertion. For examples of this process giving allylic alcohols from cyclopentene epoxides see:

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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%). R_f = 0.15 [40% Et₂O in light petroleum (bp 30-40 °C)]; mp 83.5-84.5 °C; IR: ν_max(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%).

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