PDF《(+)-Isomethoxystemofoline》

1 Electronic Supplementary Information Enantioselective Total Synthesis of (+)-Methoxystemofoline and (+)-Isomethoxystemofoline Pei-Qiang Huang,a,b, * Su-Yu Huang,a Long-Hui Gao,a Zhong-Yi Mao,a Zong Chang,a Ai-E Wanga a Department of Chemistry and Fujian Provincial Key Laboratory of Chemical Biology, and Collaborative Innovation Centre of Chemistry for Energy Materials, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005, P.

R. China. b State Key Laboratory of Applied Organic Chemistry Lanzhou University, Lanzhou 730000, P.R. China. E-mail: [email protected] Contents (38 pages): ? Experimental procedures for the synthesis of compounds 2, 3, 7-10 (pp. 2-7) ? Table

1 and 2,

1 H and

13 C NMR data for methoxystemofoline (2) and isomethoxystemofoline (3) (pp. 8-9) ? References (pp. 10) ?

1 H and

13 C NMR spectra of compounds 2, 3, 5~7, 9~25 (pp. 11-36) ? NOESY spectra of compounds trans-7 and (Z)-14 (pp. 37-38) ? X-ray structure of compound

20 (pp. 38)

2 General Methods. Melting points were uncorrected. Infrared spectra were measured using film KBr pellet techniques.

1 H NMR spectra were recorded in CDCl3 with tetramethylsilane as an internal standard. Chemical shifts are expressed in δ (ppm) units downfield from TMS. Mass spectra were obtained using electrospray ionization and an ICR analyzer (ESI-MS) for high resolution mass spectra (HRMS). Silica gel (300-400 mesh) was used for flash column chromatography, eluting (unless otherwise stated) with ethyl acetate/hexane. Ether and THF were distilled over sodium benzophenone ketyl under N2. Dichloromethane was distilled over calcium hydride under N2. (S)-2-(Benzyloxy)-N-(2-(tert-butyldimethylsilyloxy)ethyl)-4-hydroxybutanamide (9) NH OTBDMS OH O BnO

9 To a cooled solution (? ?C) of the known (S)-?-benzyloxy-?-lactone1 S-8 (9.77 g, 50.9 mmol) in methanol (230 mL) under N2 was added 2-((tert-butyldimethylsilyl)oxy)ethanamine (13.36 g, 76.3 mmol) in methanol (30 mL). The reaction mixture was stirred at room temperature for

3 days. Then the solvent was removed under reduced pressure. The residue was purified by flash chromatography (EtOAc/PE = 1/1) to give hydroxy amide

9 (16.8 g, yield: 90%) as a white solid. M.p. 52-57 ?C;

[?]D

20 ?45.2 (c 1.0, CHCl3);

IR (film) vmax: 3417, 2952, 2927, 2855, 1661, 1530, 1470, 1454, 1381, 1255, 1094, 836, 777,

696 cm-1 ;

1 H NMR (400 MHz, CDCl3) ? 0.04 (s, 6H), 0.86 (s, 9H), 1.95-2.08 (m, 2H), 2.92 (br s, 1H), 3.34-3.47 (m, 2H), 3.65-3.71 (m, 2H), 3.75 (t, J = 5.6 Hz, 2H), 4.05 (t, J = 6.3 Hz, 1H), 4.55 (d, J = 11.4 Hz, 1H), 4.61 (d, J = 11.4 Hz, 1H), 7.09 (br s, 1H), 7.28-7.39 (m, 5H);

13 C NMR (100 MHz, CDCl3) ???5.4 (2C), 18.2, 25.8 (3C), 35.5, 41.2, 59.6, 61.7, 72.8, 78.7, 128.0 (2C), 128.3, 128.7 (2C), 136.9, 172.7;

HRMS calcd for C19H33NO4Si [M+Na+ ]: 390.2071;

found: 390.2075.

3 (4S)-4-(Benzyloxy)-1-[2-(tert-butyldimethylsilyloxy)ethyl]-5-oxopyrrolidin-2-yl acetate (10) To a cooled (? ?C) suspension of Dess-Martin periodinane (7.94 g, 18.90 mmol) in anhydrous CH2Cl2 (50 mL), a solution of hydroxy amide

9 (5.31 g, 14.54 mmol) in CH2Cl2 (20 mL) was added. Then reaction mixture was warmed to room temperature and stirred for

2 h. The reaction was quenched with a saturated aqueous NaHCO3 (30 mL) and a saturated aqueous Na2S2O3 (30 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 diluted with MeOH (50 mL), and then silicon gel (2 g) was added. The suspension was refluxed at