Horner-Wadsworth-Emmons (HWE) reaction
To the phosphonate (7.74 mmol) in 50 mL anhydrous diethyl ether cooled to 0 oC was added barium oxide (4.22 mmol) followed by water (8.44 mmol) and the mixture was stirred for 15 min. Aldehyde (7.04 mmol) in 10 mL ether (then 2 x 5 mL wash) was added dropwise. The resulting turbid reaction mixture was stirred at 0 oC for 1 h, and then quenched with 100 mL of 0.1 M HCl solution. The mixture was partitioned, and the aq. layer was extracted with ethyl ether (3 × 35 mL). The combined organics were washed with brine, dried (MgSO4), filtered, concentrated and the residue was purified by silica gel column chromatography (10:1 hexanes/ethyl acetate) to give the desired enone as colorless oil (82 %).
Source: Toste, Radosevich, Chan and Shih, ACIEE, 2008, EarlyView. DOI: 10.1002/anie.200800554.
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Points for discussion:
Why barium oxide and water was used (instead of NaH or BuLi) ?
Hey! I like your concept.
Hmm….I once used calcium oxide in water to generate calcium hydroxide in situ to ensure that the concentration was high enough…..solubility issues. Is it something like that?
anniechem
May 17, 2008 at 1:04 am
Thanks. I think you are right, barium hydroxide is the preferred base here (NaH or BuLi would deprotonate the aldehyde).
pmgb
May 17, 2008 at 5:38 am
Thanks for the wonderful method. I could not understand why you have used “anhydrous” ether when you are adding water in the reactions!
Mandar Deodhar
September 19, 2008 at 1:00 am
The Ba(OH)2 procedure is the more classic approach to deprotonation of the phosphonate. It’s a very strange procedure when looking into the details; the Ba(OH)2 is normally dried vigorously by heating under vacuum and the deprotonation is normally carried out in dry THF. However, the aldehyde is often added in wet THF (40:1 THF-H2O). Deviations from the procedure seem to give lower yields. A reference for the Ba(OH)2 prep (which, I think is the more conventional method) is:
http://pubs.acs.org/doi/abs/10.1021/ol802769e
Chris Cordier
March 3, 2009 at 12:20 pm