Trimethylsulfonium iodide → (-)-(6aR,8R,9R,9aR)-9-Fluoro-2,2,4,4-tetraisopropyl-7-methylenehexahydrocyclopenta[f]-[1,3,5,2,4]trioxadisilocin-8-ol

HRID 522820Notes

Reaction equation

HRID 522820 reaction equation
[I-].C[S+](C)C.[Li][CH2:7]CCC.[F:11][C@H:12]1[C@@H:16]2[O:17][Si:18]([CH:32]([CH3:34])[CH3:33])([CH:29]([CH3:31])[CH3:30])[O:19][Si:20]([CH:26]([CH3:28])[CH3:27])([CH:23]([CH3:25])[CH3:24])[O:21][CH2:22][C@H:15]2[C@H:14]2[O:35][C@@H:13]12>C1COCC1>[F:11][C@H:12]1[C@@H:22]2[O:21][Si:20]([CH:23]([CH3:25])[CH3:24])([CH:26]([CH3:28])[CH3:27])[O:19][Si:18]([CH:29]([CH3:31])[CH3:30])([CH:32]([CH3:33])[CH3:34])[O:17][CH2:16][C@H:15]2[C:14](=[CH2:7])[C@H:13]1[OH:35]

Participants

5

Reactant 3

HCID 75127Trimethylsulfonium iodideHCID 131735545(+)-(6aS,6bR,7aR,8R,8aR)-8-Fluoro-2,2,4,4-tetraisopropylhexahydrooxireno[2',3':3,4]cyclo-penta[1,2-f][1,3,5,2,4]trioxadisilocineHCID 178418339Butyllithium

Product 1

HCID 131735544(-)-(6aR,8R,9R,9aR)-9-Fluoro-2,2,4,4-tetraisopropyl-7-methylenehexahydrocyclopenta[f]-[1,3,5,2,4]trioxadisilocin-8-olYield 81.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a suspension of trimethylsulfonium iodide (30.5 g, 138.4 mmol) in THF (150 mL) at −20° C., n-BuLi (2.5 M solution in hexane) (55.3 mL, 138.4 mmol) was added. After 30 min, the epoxide 13 (6.0 g, 15.5 mmol) in THF (30 mL) was introduced at −20° C. and the reaction mixture allowed slowly to warm to 0° C. over 1 h. The mixture was then stirred at ambient temperature for 2 h, quenched with water and then extracted with ethyl acetate (3×200 ml). The combined organic layer was washed with brine, dried over Na2SO4 and concentrated reduced under pressure. The residues were purified on silica gel column chromatography (10% EtOAc/Hexane) to give the allylic alcohol 14 (5.1 g, 81%) as oil. [α]26D −0.54° (c 0.5, MeOH); 1H NMR (500 MHz, CDCl3) δ 0.93-1.12 (m, 28H), 1.99 (dd, J=2.5, 5.5 Hz, 1H, OH), 2.58 (m, 1H), 3.85 (dd, J=9.5, 11.5 Hz, 1H), 4.08 (dd, J=5.0, 12.0 Hz, 1H), 4.44 (m, 1H) 4.48 (m, 1H), 4.73 (dt, J=5.0, 9.0 Hz, 1H), 5.09 (s, 1H), 5.35-5.34 (m, 1H); 19F NMR (500 MHz, CDCl3) δ −203.0 (m); 13C NMR (125 MHz, CDCl3) δ 12.5, 12.9, 13.4, 13.5, 17.0, 17.03, 17.41, 17.46, 17.5, 17.6, 48.5, 50.2, 65.5, 72.6, 97.4 (d, J=185.0 Hz), 111.8, 146.8; HR-MS Calcd. For (C19H37FO4Si2+H)+ 405.2214. found 405.2202.

Workup

  1. customquenched with water
  2. extractionextracted with ethyl acetate (3×200 ml)
  3. washThe combined organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe residues were purified on silica gel column chromatography (10% EtOAc/Hexane)

Sources & evidence

ORD record
ord-f0b0dbb6d3484039ad8632589d5ff1fb
Source dataset
uspto-grants-2016_05
Patent number
US09334273B1

Reaction notes

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