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21st August 2013 @ 14:24

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Reaction information

*#Reaction file  
CSRxnsScheme_175.cdx
*Reaction file type CDX
*Procedure  

DMSO (0.36 mL, 5.1 mmol) in dry DCM (0.60 mL) was added dropwise to oxalyl chloride (0.21 mL, 2.5 mmol) in dry DCM (5.3 mL) at −60 °C.  The reaction mixture was stirred at −60 °C for 2 mins.  Alcohol 171a (512 mg, 2.3 mmol) in dry DCM (2.3 mL) was added dropwise to the reaction mixture at ­−60 °C.  The reaction mixture was stirred at −60 °C for 15 mins.  Et3N (1.60 mL, 11.5 mmol) was added dropwise to the reaction mixture at −60 °C.  The reaction mixture was stirred at −60 °C for 15 mins and then left stirring at room temperature for 1 h.  The reaction mixture was poured into water (25 mL).  The aqueous phase was extracted with DCM (3 × 30 mL).  The organic extracts were combined, washed sequentially with brine (50 mL), 1% aq. HCl solution (50 mL) and 5% aq. Na2CO3 solution (50 mL), dried (MgSO4), filtered and the solvent removed in vacuo to give intermediate aldehyde 173 (2-((1S,2R,3aS,7aS)-2-butyl-2,3,3a,4,7,7a-hexahydro-1H-inden-1-yl)acetaldehyde) as an orange oil (501 mg).  Dry DMF (0.48 mL, 6.2 mmol) was added dropwise to CrCl2 (762 mg, 6.2 mmol) in THF (15 mL) at room temperature.  After stirring at room temperature for 45 mins a solution of intermediate aldehyde 173 (171 mg, 0.77 mmol) and diiodide 172 (tert-butyl((5,5-diiodopentyl)oxy)dimethylsilane) (727 mg, 1.6 mmol) in THF (2.5 mL) was added to the reaction mixture.  Stirring was continued at room temperature for 3 h.  The reaction mixture was diluted with pentane (15.0 mL) and poured into water (50 mL).  The aqueous phase was further extracted with pentane (3 × 20 mL).  The organic extracts were combined, washed with brine (100 mL), dried (MgSO4), filtered and the solvent removed in vacuo to give the crude intermediate silane 174 (tert-butyl(((E)-7-((1S,2R,3aS,7aS)-2-butyl-2,3,3a,4,7,7a-hexahydro-1H-inden-1-yl)hept-5-en-1-yl)oxy)dimethylsilane) as a brown oil (976 mg).  Purification by column chromatography (SiO2, hexane→hexane/Et2O 19:1) removed the major impurities to give intermediate silane 174 as a colourless oil (583 mg).  To a solution of intermediate silane 174 (519 mg, 0.69 mmol) in THF (3.0 mL) TBAF (4.8 mL of a 1.0 M solution in THF, 4.8 mmol) was added dropwise.  The reaction mixture was left stirring at room temperature for a further 3 h.  The reaction mixture was poured into water (30 mL) and extracted with ether (3 × 15 mL).  The organic extracts were combined, washed with brine (2 × 30 mL), dried (MgSO4), filtered and the solvent removed in vacuo to give the crude product as a yellow oil (776 mg).  Purification by column chromatography (SiO2, hexane/Et2O 4:1) gave the title compound as a colourless oil (162 mg, 81% over 3 steps).

*Yield (%)  81
*Type of Yield Isolated product yield
Reference(s)  
AH Thesis_2011_pp122.pdf
AH Thesis_2011_pp224-250.pdf
Further information  Compound 175: (E)-7-((1R,2S,3aR,7aR)-2-Butyl-2,3,3a,4,7,7a-hexahydro-1H-inden-1-yl)hept-5-en-1-ol

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
CSRxnsScheme_175.cdx
AH Thesis_2011_pp122.pdf
AH Thesis_2011_pp224-250.pdf