PDF《(+)-Isomethoxystemofoline》

75 ?C for

2 h, then silicon gel was filtered and solvent was removed under reduced pressure to give hemiaminal which was used in the next step without purification. The hemiaminal and DMAP (50 mg) was dissolved in CH2Cl2 (70 mL) under N2, and cooled down to ? ?C. Then Et3N (6.07 mL, 43.6 mmol) and Ac2O (3.42 mL, 36.4 mmol) were added successively. After being stirred at room temperature overnight, the reaction was quenched with a saturated aqueous NaHCO3 (50 mL). The organic layer was separated and the aqueous layer was extracted with CH2Cl2 (3 *

50 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography (EtOAc/PE = 1/6) to give compound

10 (4.38 g, yield: 73% from 9) as an inseparable diastereomeric mixture in a ratio of

57 :

43 (1 H NMR). Colorless oil. IR (film) vmax: 2953, 2929, 2856, 1716, 1453, 1423, 1362, 1237, 1192, 1102, 1010, 923, 836, 778, 736,

698 cm-1 ;

1 H NMR (400 MHz, CDCl3, data read from the diastereoisomeric mixture) ?major diastereomer: 0.03 (s, 6H), 0.86 (s, 9H), 1.94-2.01 (m,

4 1H), 2.08 (s, 3H), 2.57-2.69 (m, 1H), 3.60-3.81 (m, 4H), 4.02 (dd, J = 3.0, 8.3 Hz, 1H), 4.75 (d, J = 12.0 Hz 1H), 4.93 (d, J = 12.0 Hz, 1H), 6.21 (dd, J = 1.7, 6.4 Hz, 1H), 7.24-7.40 (m, 5H);

?minor diastereomer: 0.04 (s, 6H), 0.88 (s, 9H), 2.02 (s, 3H), 2.14-2.28 (m, 1H), 2.35 (dd, J = 7.8, 14.0 Hz, 1H), 3.10-3.20 (m, 2H), 3.60-3.81 (m, 2H), 4.32 (dd, J = 8.2, 8.2 Hz, 1H), 4.77 (d, J = 11.9 Hz, 1H), 5.01 (d, J = 11.9 Hz, 1H), 6.30 (d, J = 5.7 Hz, 1H), 7.24-7.40 (m, 5H);

13 C NMR (100 MHz, CDCl3 data read from the diastereoisomeric mixture) ?major diastereomer: ?5.6 (2C), 18.0, 21.0, 25.7 (3C), 33.8, 42.9, 60.5, 72.0, 73.2, 83.1, 127.7, 127.9 (2C), 128.3 (2C), 137.5, 170.3, 172.6;

?minor diastereomer: ?5.5 (2C), 18.0, 21.0, 25.7 (3C), 34.6, 43.2, 60.8, 72.2, 72.9, 83.0, 127.8, 127.9 (2C), 128.3 (2C), 137.5, 170.3, 174.3;

HRMS calcd for C21H33NO5Si [M+Na+ ]: 430.2020;

found: 430.2023. (3S,5S)-3-(Benzyloxy)-1-[2-(tert-butyldimethylsilyloxy)ethyl]-5-(2-oxopropyl)pyrr olidin-2-one (cis-7) and (3S,5R)-3-(Benzyloxy)-1-[2-(tert-butyldimethylsilyloxy)ethyl]-5-(2-oxopropyl)pyr rolidin-2-one (tran-7) N O OTBDMS BnO O cis-7 To a cooled solution (?78 ?C) of acetate

10 (8.06 g, 19.8 mmol) in CH2Cl2 (200 mL) under N2 was added dropwise TMSOTf (1.8 mL, 9.9 mmol). After being stirred for

15 min at ?78 ?C, trimethyl(prop-1-en-2-yloxy)silane (6.6 mL, 39.6 mmol) was added dropwise into the reaction mixture. After being stirred for

2 h at ?78 ?C, the reaction was warmed slowly to room temperature and stirred overnight. The reaction was quenched with a saturated aqueous NaHCO3 (30 mL) at 0-5 ?C. The organic layer was separated and the aqueous layer was extracted with CH2Cl2 (3 *

30 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was used in the next

5 step without further purification. The crude partially O-desilylation keto-lactam and imidazole (2.69 g, 39.6 mmol) was dissolved in CH2Cl2 (90 mL) and cooled down to ? ?C, then a solution of t-butyldimethylsilyl chloride (3.58g, 23.8 mmol) in CH2Cl2 (10 mL) was added. The reaction mixture was warmed to room temperature and stirred for

4 h. Then the reaction was quenched with a saturated aqueous solution of NaHCO3 (30 mL) under an ice-bath. The organic layer was separated and the aqueous layer was extracted with CH2Cl2 (3 *