Reaction Steps
Step B (4): (S)-Methyl 2-(3-butyl-2-oxopyrrolidin-1-yl)acetate (0.5 g, 2.35 mmol) from step B (3) was dissolved in dry THF (30 mL) and cooled to −78° C. Lithium bis(trimethylsilylamide (1.0M in THF, 2.70 mL, 2.70 mmol, Aldrich) was added while the temperature was maintained below −60° C. The mixture was cooled to −78° C. and stirred for 15 min. A solution of allyl bromide (0.24 mL, 2.72 mmol, Aldrich) in 10 mL of THF was added dropwise and the resulting mixture was stirred for 48 h. The reaction was quenched with acetic acid (0.5 mL) and poured into 75 mL of 0.5 M H2SO4. The aqueous layer was extracted with EtOAc and the organic layers were concentrated in vacuo. The residue was purified by silica gel chromatography (5-35% EtOAc/hexanes linear gradient) to give 170 mg (29% yield) of (s)-methyl 2-((S)-3-butyl-2-oxopyrrolidin-1-yl)pent-4-enoate (diastereomer A, first to elute) as a colorless oil and 130 mg of (R)-methyl 2-((S)-3-butyl-2-oxopyrrolidin-1-yl)pent-4-enoate (diastereomer B, second to elute) as a colorless oil. Data for diastereomer A: LC-MS (M+H)+=254.3; 1H NMR (500 MHz, CDCl3) δ 5.47-5.95 (m, 1H), 4.98-5.20 (m, 2H), 4.87 (dd, J=10.99, 4.88 Hz, 1H), 3.69 (s, 3H), 3.32-3.51 (m, 1H), 3.15-3.34 (m, 1H), 2.60-2.80 (m, 1H), 2.41-2.53 (m, 1H), 2.26-2.40 (m, 1H), 2.05-2.23 (m, 1H), 1.76-1.94 (m, 1H), 1.61-1.77 (m, 1H), 1.18-1.47 (m, 5H), 0.78-0.97 (m, 3H). Data for diastereomer B: LC-MS (M+H)+=254.36; 1H NMR (500 MHz, CDCl3) δ 5.57-5.78 (m, 1H), 4.99-5.18 (m, 2H), 4.88 (dd, J=10.99, 4.88 Hz, 1H), 3.69 (s, 3H), 3.32-3.48 (m, 1H), 3.21-3.32 (m, 1H), 2.64-2.79 (m, 1H), 2.34-2.53 (m, 2H), 2.10-2.30 (m, 1H), 1.74-1.91 (m, 1H), 1.46-1.74 (m, 1H), 1.20-1.40 (m, 5H), 0.78-1.00 (m, 3H).
