[mirro]

Hey,
I’m trying to make the methylidene wittig product starting from 4-oxo-proline methyl ester.
First I tried a procedure of JOC 1992, 57, 2060-2065. They add methyltriphenylphosphonium bromide to potassium tert-butoxide at 3°C. after 15 min they add oxo-proline, reflux 3h, done. I tried it with dry THF instead of dry ether, it did not work. Tried twice
Then I tried procedure from  J. Comb. Chem. 2007, 9, 143 157
Methyltriphenylphosphonium bromide (505.7 g, 1.42 mol) was placed in a 3-L round-
bottom flask, and the flask was put into an ice bath.
Potassium tert-butoxide (1.49 L of a 1.0 M solution in THF,
1.49 mol) was added to the reaction mixture, which was then
allowed to stir at 0 °C for 30 min. The reaction mixture was
warmed to room temperature and allowed to stir for 30 min,
followed by refluxing for 1 h, after which the reaction
mixture was cooled in an ice bath, and 3 (172 g, 707.8 mmol)
was added via pipet. The reaction mixture was removed from
the ice bath and brought to reflux until TLC showed the
reaction to be complete.


Did not work either. I think I am doing something wrong, but I have no idea what.
maybe the solvent is not dry enough. I just use dry solvent bottles from Aldrich. I tried different bottles and no improvement.  Maybe I should distill my dry solvents first?
Maybe my starting material is not pure enough? But then I expect some yield and not nothing.
Any ideas how to get better yield?

thanks

[StarvinMarvin]

I always use freshly distilled THF for any anion-type chemistry. Try distilling some from CaH2. Moreover, I used to use n-BuLi to form the phosphonium ylide. I don't know if it would help you, but judging from what you described, the base might just not be working.

[OC pro]

Potassium tert-butoxide is fine as long it is fresh. It readily decomposes to give potassium carbonate. THF should be distilled from CaH2, LiAlH4 or Na.
You should see a yellowish solution/suspension first (upon treating MePPh3Br with base) indicating the methylidene wittig-reagent has been formed.
Did not work means you have only unreacted starting material?

[mirro]

I see a yellowish suspension,  but the bottle of the Potassium tert-butoxide looked quite old...
after reaction i still see starting material.

[OC pro]

So if the conversion to the product is slow, heat for a longer period of time. Or you can add more of the Wittig reagent. 3.1equiv of MePPh3Br and 3.0equiv of base. And I would order a new bottle of KOtBU. Otherwise, NaH will also do the job.
If prolonged heating is not enough, you can switch to Toluene as solvent. Wittig reagent will work the same as in THF.

Best of luck

[napoleon79]

Hi you,
I am also this trouble with heptanal, 5-hydroxypentyl triphenylphosphonium and t-BuOK. It doesn't work. Phosphonium salt doesn't dissolution in THF because I see white soild in THF when I stopped stirring.

Please give me some advices

[sjb]

Hi you,
I am also this trouble with heptanal, 5-hydroxypentyl triphenylphosphonium and t-BuOK. It doesn't work. Phosphonium salt doesn't dissolution in THF because I see white soild in THF when I stopped stirring.

Please give me some advices

thanks

How many equivalents of base are you using?

[discodermolide]

Hey,
I’m trying to make the methylidene wittig product starting from 4-oxo-proline methyl ester.
First I tried a procedure of JOC 1992, 57, 2060-2065. They add methyltriphenylphosphonium bromide to potassium tert-butoxide at 3°C. after 15 min they add oxo-proline, reflux 3h, done. I tried it with dry THF instead of dry ether, it did not work. Tried twice
Then I tried procedure from  J. Comb. Chem. 2007, 9, 143 157
Methyltriphenylphosphonium bromide (505.7 g, 1.42 mol) was placed in a 3-L round-
bottom flask, and the flask was put into an ice bath.
Potassium tert-butoxide (1.49 L of a 1.0 M solution in THF,
1.49 mol) was added to the reaction mixture, which was then
allowed to stir at 0 °C for 30 min. The reaction mixture was
warmed to room temperature and allowed to stir for 30 min,
followed by refluxing for 1 h, after which the reaction
mixture was cooled in an ice bath, and 3 (172 g, 707.8 mmol)
was added via pipet. The reaction mixture was removed from
the ice bath and brought to reflux until TLC showed the
reaction to be complete.


Did not work either. I think I am doing something wrong, but I have no idea what.
maybe the solvent is not dry enough. I just use dry solvent bottles from Aldrich. I tried different bottles and no improvement.  Maybe I should distill my dry solvents first?
Maybe my starting material is not pure enough? But then I expect some yield and not nothing.
Any ideas how to get better yield?

thanks

1, Have you protected the nitrogen atom?
2, I don't think this will work with the Wittig, try the Peterson olefination.
3, If you persist with the Wittig use t-Butyl lithium, KOtBu is usually quite heavily contaminated with potassium carbonate, purify it first by sublimation. Or try LiHMDS or the like

[napoleon79]

I used

5-hydroxypentyl triphenylphosphonium = 2 mmole (0,858 g) + 8 ml THF

t-BuOK = 2,2 mmole ( 0,2464 g) + 10 ml THF
Mixture reaction was stirring at room temperature for 30 min.

Next. It was cold to zero dre C. Then heptanal was dropwise into reactive bottle.
heptanal = 2,5 mmole (0,285 g) + 5 ml THF

Next. It was stirring at room temperature for 10h.



- If I have a few of heptanal. I use more phosphonium salt than heptanal. What is happen ?

Please give me some advices  
thanks

[sjb]

How does the pKa of the hyroxyl proton compare to that of the one you're trying to take off to form the ylid?

[napoleon79]

"First I tried a procedure of JOC 1992, 57, 2060-2065. They add methyltriphenylphosphonium bromide to potassium tert-butoxide at 3°C."

Then I tried procedure from  J. Comb. Chem. 2007, 9, 143 157
Methyltriphenylphosphonium bromide (505.7 g, 1.42 mol) was placed in a 3-L round-
bottom flask, and the flask was put into an ice bath.
Potassium tert-butoxide (1.49 L of a 1.0 M solution in THF,
1.49 mol) was added to the reaction mixture,

What different is ? when you added phosphonium salt into t-BuOK solution or t-BuOK in THF solution into a 3-L round (phosphonium salt in THF solution) ??


I don't know "pKa of the hyroxyl proton compare to that of the one you're trying to take off to form the ylid"

who was made wittig reaction with CH3CN solution ? Was it Z more than E isomer or reverse ? How did it do ?

thanks for your advices. 

[sjb]

Can you draw your reaction scheme out, I think there may be something I am missing in translation here?

[napoleon79]

What different is ? when you added phosphonium salt into t-BuOK solution or t-BuOK in THF solution into a 3-L round (phosphonium salt in THF solution) Huh??



http://imageshack.us/f/37/68063631.jpg/





http://imageshack.us/photo/my-images/829/16737916.jpg/

who was made wittig reaction with CH3CN solution ? Was it Z more than E isomer or reverse ? How did it do ?



http://imageshack.us/photo/my-images/827/41653374.jpg/

thanks  

[sjb]

OK, http://imageshack.us/photo/my-images/827/41653374.jpg/ is what I meant, not necessarily pictures of your apparatus.

Is there a danger that you may be producing the potassium salt of the alcohol, rather than the ylid. Does your reaction mixture change colour after addition of the KOtBu?

[discodermolide]

What happened to the original poster's question? I don't see many answers to that one!