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Yield in a Horner Wadsworth Emmons reaction
Babcock_Hall:
I am attempting to convert an aldehyde into a vinylsulfone using Horner-Wadsworth-Emmons chemistry with lithium hexamethyldisilazane as the base (28.7%). The number in parentheses is the yield of a closely related, purified product, as reported in the paper I am following. With respect to the HWE reaction, the protocol specified stirring for an hour at 0 °C followed by two hours at room temperature. The other reactant is a diethyl β-sulfonylphosphonate.
Although the important thing is just to get the product, I am somewhat concerned about the low yield in the HWE reaction, given that this is a multistep synthesis. The only idea that I can think of as a possible improvement is to monitor the HWE reaction by TLC or by P-31 NMR (there should be a difference in chemical shifts of roughly 10 ppm). I have previously found P-31 NMR to be useful in that it is relatively sensitive yet ideally there are only two molecules present, reactant and product. However, I do not presently know whether or not incompleteness of the reaction was the reason for the relatively low yield in the step. I have not yet surveyed other similar reactions for yield, although I have seen a variety of bases used.
Babcock_Hall:
One thing I just thought about: the paper I am following uses FMOC to protect nitrogen. I wonder whether or not there might be some loss of the FMOC group during the HWE reaction.
TheUnassuming:
If you have an FMOC group in HWE conditions I would guess you are getting relatively high levels deprotection of the amine since it can usually be done with much weaker amine bases. Have you been able to shoot the crude through LCMS to go back and check?
Out of curiosity are you seeing full conversion of your starting material?
Babcock_Hall:
Thank you. I have not run the HWE reaction yet, but it is coming up the step after next. I have a BOC-protected nitrogen, and I am hoping that this will work at least as well as FMOC, possibly better for the reason that you suggested. For my purposes, BOC-protection is fine.
pgk:
FmocN- is described to be incompatible with aldehydes but BocN- is described as compatible.
Anyway, the Horner-Wadsworth-Emmons reaction might have a higher yield by slow addition of diluted reagents (say 1 drop/sec) at -5oC (NaCl/ice), left to react at -5oC for 1 h, followed by reaction at 0oC for another 1 h and then at room temperature for 2 hours (or something else like that).
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