All Notebooks | Help | Support | About
21st August 2013 @ 14:21

This post is compatible for submission to ChemSpider Reactions.

See ChemSpider Reactions template - help and further information for help when using it.

Reaction information

*#Reaction file  
*Reaction file type CDX
*Procedure  

n-BuLi (6.8 mL of a 2.5 M solution in hexanes, 17.0 mmol) was added dropwise to a solution of Cp2ZrCl2 (2.49 g, 8.5 mmol) in dry THF (40 mL) at −78 °C. Triene 140 (1.62 g, 8.5 mmol) in dry THF (25 mL) was added dropwise to the reaction mixture at −78 °C.  After stirring at −78 °C for 20 mins the reaction mixture was warmed to room temperature.  After stirring at room temperature for 2 h the reaction mixture was heated to 65 °C for 30 mins.  The reaction mixture was cooled to −78 °C.  Chloromethyl(dimethyl)phenylsilane (1.50 mL, 8.5 mmol) was added dropwise.  LiTMP [prepared by adding n-BuLi (3.4 mL of a 2.5 M solution in hexanes, 8.5 mmol) to a solution of 2,2,6,6-tetramethylpiperidine (1.40 mL, 8.5 mmol) in THF (25 mL) at 0 °C and stirring at 0 °C for 30 mins] was added dropwise at −78 °C.  After stirring at −78 °C for 1 h the reaction mixture was stirred at room temperature for 2 h.  MeOH (40 mL) and sat. aq. NaHCO3 solution (40 mL) were added and the reaction mixture stirred at room temperature for 16 h.  The reaction mixture was poured into water (300 mL) and extracted with ether (3 × 50 mL).  The organic extracts were combined, washed sequentially with water (300 mL) and brine (300 mL), dried (MgSO4), filtered and the solvent removed in vacuo to give the intermediate silane as a yellow oil (3.08 g).  NMP (26 mL) was added to KH (8.18 g of a 25–35% suspension in mineral oil, washed with hexane (3 × 20 mL), 8.5 mmol).  The reaction mixture was cooled to 0 °C.  t-Butylhydroperoxide (9.3 mL, 51.0 mmol) was added and the reaction mixture warmed to room temperature.  The intermediate silane (2.72 g, 7.5 mmol) in NMP (50 mL) was added and the reaction mixture stirred at room temperature for 10 mins.  TBAF (26 mL of a 1.0 M solution in THF, 26.0 mmol) was added and the reaction mixture heated to 70 °C for 15 h.  Na2S2O3 (17.0 g) and water (50 mL) were added and the reaction mixture stirred for 5 mins.  The reaction mixture was extracted with ether (3 × 50 mL).  The organic extracts were combined, washed sequentially with water (2 × 100 mL), 2 M aq. NaOH solution (100 mL) and brine (100 mL­), dried (MgSO4), filtered and the solvent removed in vacuo to give the crude product as a colourless oil (7.96 g).  Purification by column chromatography (SiO2, DCM) gave a 2.7:1 mixture of diastereoisomers of alcohol 171 as a colourless oil (1.42 g, 75%). Purification by HPLC (hexane/EA 10:1) allowed isolation of the pure required diastereoisomer, 171a.

*Yield (%)  75
*Type of Yield Isolated product yield
Reference(s)  
AH Thesis_2011_pp120.pdf
AH Thesis_2011_pp224-250.pdf
Further information  Compound 171a: 2-((1R,2S,3aR,7aR)-2-Butyl-2,3,3a,4,7,7a-hexahydro-1H-inden-1-yl)ethanol

For multistep reactions (or their steps):

Overall reaction? True
For overall reaction - links to child reaction steps  
For step in multistep reaction - link to previous reaction step  
For step in multistep reaction - link to following reaction step  
Attached Files
AH Thesis_2011_pp120.pdf
AH Thesis_2011_pp224-250.pdf