反応 #50356

反応方程式

LiEt3BH

Super Hydride

KHMDS

18-crown-6

Aldehyde

(2S,3R)-3-(t-butyldimethylsilyloxy)-2-methylhexanal

phosphate

→

alcohol

収率 72.0%

(4R,5R)-(Z)-5-(t-Butyldimethylsilyloxy)-2,4-dimethyl-2-octen-1-ol

収率 72.0%

溶媒

THF

THF

EtOAc

THF

反応条件

後処理

1. 1
   その他flushed with Ar
2. 2
   workup.DISSOLUTIONdissolved in 10 ml of THF
3. 3
   温度the solution cooled to -78° C
4. 4
   その他was recooled to -78° C.
5. 5
   温度The temperature gradually warmed to 25° C. over 4 h
6. 6
   workup.ADDITIONwas added
7. 7
   抽出extracted with 3:1 pentane
8. 8
   洗浄The extracts were washed with 5% NaHCO3 (2×1 ml), brine (1×1 ml )
9. 9
   乾燥dried over MgSO4
10. 10
    濃縮concentrated
11. 11
    その他chromatographed (80 g SiO2, 1% TEA/CH2Cl2)

実験手順

Bis (2,2,2-trifluoroethyl) ethyl 2-phosphonopropionate (173.8 mg, 0.5021 mmol, 1.5 eq) was weighed into a 25 ml Schlenk flask, flushed with Ar, dissolved in 10 ml of THF, cooled to -42° C. It was then treated with 0.75M KHMDS in THF (600 μl, 0.45 mmol, 1.35 eq). After 1 h, 18-crown-6 (439 mg, 1.663 mmol, 5.0 eq) was added and the solution cooled to -78° C. Aldehyde 5 (freshly prepared, 81.3 mg, 0.3326 mmol) in 250 μl THF was added. The reaction was stirred for 4 h at -78° C., at -23° C. for 12 h, then was recooled to -78° C. and 1.0M LiEt3BH in THF was added (2.0 ml, 2.0 mmol, 4.4 eq based on phosphonate). The temperature gradually warmed to 25° C. over 4 h and stirred an additional 8 h when 500 μl of EtOAc was added. The solution was poured onto 10 ml of 0.2 M pH 7 phosphate buffer, and extracted with 3:1 pentane:Et2O (3×10 ml). The extracts were washed with 5% NaHCO3 (2×1 ml), brine (1×1 ml ), dried over MgSO4 , concentrated and chromatographed (80 g SiO2, 1% TEA/CH2Cl2) to give 68.4 mg of isometrically pure alcohol 17 (72%). 1H NMR (CDCl3, 360.134 MHz) δ:5.09 (1H, d J=9.89 Hz), 4.06 (1H, d, J=11.65 Hz), 3.96 (1H, d, J=11.65 Hz), 3.41 (1H,q, J=4.62 Hz), 2.47 (1H, m), 1.74 (3H, d, J=1.45 Hz), 1.60 (1H, br), 1.4-1.15 (4H, m), 0.86 (3H, d, J=6.84 Hz), 0.83 (9H, s), 0.83 (3H, s). 13C NMR (CDCl3 90.55 MHz) δ:134.0, 132.0, 76.6, 61.7, 37.4, 26.0, 21.7, 18.6, 18.3, 17.1, 14.4, -4.3, -4.4. IR (thin film): 3333 (br), 2959 (s), 2932 (s), 2858 (s), 1462 (m), 1377 (w), 1256 (m), 1068 (m), 1032 (s), 1005 (s), 837 (s), and 773 (s) cm-1. High resolution MS (m/z): 229.1613, calcd for C12H25O2Si 229.1624 (M-C4H9). [α]D =+6.25° (c=1.68, CH2Cl2).

出典