[davidjack]

Dear friends...

I am facing some difficulties with wittig reaction...

 In my case, alpha-N-protected Amino aldehyde with methyl triphenyl phosponium bromide and KHMDS.
I tried with several conditions
 for ylide making at 0-25 degree and addition of aldehyde at -78 degree
  same procedure i followed on RT AND 40 degree and upto reflux... but still the reaction not proceeded ,
        J, Org. Chem. 1987,52, 1487-1492.
i followed this article too still it  trouble and product not formed in my case...



i couldnt find the reason,

If anyone help tahnks in advance

[discodermolide]

Dear friends...

I am facing some difficulties with wittig reaction...

 In my case, alpha-N-protected Amino aldehyde with methyl triphenyl phosponium bromide and KHMDS.
I tried with several conditions
 for ylide making at 0-25 degree and addition of aldehyde at -78 degree
  same procedure i followed on RT AND 40 degree and upto reflux... but still the reaction not proceeded ,
        J, Org. Chem. 1987,52, 1487-1492.
i followed this article too still it  trouble and product not formed in my case...



i couldnt find the reason,

If anyone help tahnks in advance

Why not try "instant ylide", a mix of your phosphonium salt and sodium amide. Just add THF and off you go!

[discodermolide]

Another thought; is the KHMDS in toluene? If so shake the bottle as I have had solutions separating out, especially when cool. This caused me severe headaches in a natural product synthesis, until we titrated the base, which we should have done at the start!

[davidjack]

Thanks..

  U r right, we have KHMDS in Toluene but it looks homogeneous and Sure/seal bottle....
 here i didnt find any seperations.
Also while addition time i observed the colour turn to yellow..
 

[discodermolide]

Thanks..

  U r right, we have KHMDS in Toluene but it looks homogeneous and Sure/seal bottle....
 here i didnt find any seperations.
Also while addition time i observed the colour turn to yellow..
 

Are you recovering all of your aldehyde or are you getting decomposition?

[davidjack]

No, i didnt recover aldehyde
Becoz, after reaction TLC shows no Aldehyde spots also in NMR  there is no aldehyde peak.

optically tht aldehyde mild stable but chemically its stable,

[discodermolide]

No, i didnt recover aldehyde
Becoz, after reaction TLC shows no Aldehyde spots also in NMR  there is no aldehyde peak.

optically tht aldehyde mild stable but chemically its stable,

So if there is no aldehyde what product are you isolating, or is it just a mess? Where has the mass gone?

[Dan]

Can you tell us what the N-protecting group is and what the workup procedures are?

I'm thinking that if you cannot account for the mass it may be possible that the N-protecting group is falling off either in the reaction or the workup and you are losing the free amine through aqueous-organic extraction, or on silica gel. No way to be sure without more info though.

[davidjack]

Dear Dan...

   In my aldehyde have two amino groups. one is  protected by BOC and other is benzyl.

Also after work up and NMR analysis i found tht those groups.

Do u think BOC will remove under basic condition??? hope its highly stable..

[davidjack]

Dear discodermolide...

  As i told u i found the rest of peaks in my compound except aldehyde...

  Mass i didnt check, Still i feel tht culprit may be ylide of phosphonium salt..

  But am not sure....

 

[Borek]

i told u tht

Please use plain, correct English.

[discodermolide]

Dear discodermolide...

  As i told u i found the rest of peaks in my compound except aldehyde...

  Mass i didnt check, Still i feel tht culprit may be ylide of phosphonium salt..

  But am not sure....

 

As I suggested use instant ylide. The carbamate may be a problem so use an excess of ylide or perhaps make a bis box (amide) on that nitrogen or use phthalimide.

[discodermolide]

You say you found other peaks except aldehyde, what are the structures of these compounds, apart from the ylide?