[taurean]

Is there any good reagent apart from BH3.THF, BH3.Me2S or aminoborane which can selectively reduce amide in the presence of an enol (keto-enol eq'm possible)?

Please help.

taurean

[movies]

Possibly an amalgam like Na/Hg, but the ones you named are the best.

What about LAH reduction and then reoxidation of the alcohol?

[taurean]

Possibly an amalgam like Na/Hg, but the ones you named are the best.

What about LAH reduction and then reoxidation of the alcohol?

LAH reduction is a big mess with the formation of more than one product.(diastereomers), which is not desirable.

[movies]

If the diastereomers are just a consequence of the alcohol, then you will eliminate them in the oxidation step.

[taurean]

If the diastereomers are just a consequence of the alcohol, then you will eliminate them in the oxidation step.

I am at the verge of completing the total synthesis.  I would like to finish it in an elegant way.  That is one reason I was looking for a selective reagent.  The other reason is it is pain to increase couple of more steps at the end of the synthesis.


what is your opinion about LAB's?

[movies]

You mean the lithium amino trihydroborates?  That might work too, but I don't think that they are all that much different than the boranes you already mentioned.  Worth a shot though.

[taurean]

You mean the lithium amino trihydroborates?  That might work too, but I don't think that they are all that much different than the boranes you already mentioned.  Worth a shot though.

How about sulfurization of amide carbonyl using Lawesson's? Do you have any idea if it sulfurizes ketone carbonyl of beta-ketoester?

Which is the best way to reduce thioamide to amine?

[movies]

That's a good idea!  I think that Lawesson's reagent is pretty selective for amides.  I've seen examples where it has reacted with an amide in the presence of an ester, so that's a good sign.  Certainly ketones are slower than esters.

As for the reduction, Raney nickel will do the job, but that might be a little harsh.  It can be a very selective reagent, but you may have to deactivate it some by refluxing with alcohol for a couple of hours before adding your susbstrate or else other things might get reduced too (e.g., olefins).

That might also be a good candidate for an amalgam reduction since sulfur is so soft.  How about other radical reductions?  I think that Bu₃SnH or zinc dust might do the job too.

[taurean]

That's a good idea!  I think that Lawesson's reagent is pretty selective for amides.  I've seen examples where it has reacted with an amide in the presence of an ester, so that's a good sign.  Certainly ketones are slower than esters.

As for the reduction, Raney nickel will do the job, but that might be a little harsh.  It can be a very selective reagent, but you may have to deactivate it some by refluxing with alcohol for a couple of hours before adding your susbstrate or else other things might get reduced too (e.g., olefins).

Thanks for your insight.

That might also be a good candidate for an amalgam reduction since sulfur is so soft.  How about other radical reductions?  I think that Bu₃SnH or zinc dust might do the job too.

I haven't seen any examples of radical reductions.  If you know of any references, could you please let me know.

[/b]

[movies]

I was thinking along the lines of a Barton-McCombie deoxygenation, where a tin radical adds to a thiocarbonyl.

[taurean]

I was thinking along the lines of a Barton-McCombie deoxygenation, where a tin radical adds to a thiocarbonyl.

I don't know if it serves my purpose of forming an secondary amine.  I will first try boranes and Lawesson's.  Thank you for your valuable suggestions.

[movies]

Let me know how it goes.  I'm curious!

[taurean]

Let me know how it goes.  I'm curious!

I will surely let you know.  It will take sometime before I set up that reaction.

[taurean]

Let me know how it goes.  I'm curious!

As we talked about it before, I tried Lawesson's and also boranes.  Lawesson's and BTHF did not work in my case.  BDMS worked giving a single spot reaction.  However my NMR appears little weird, I do not see the amine peak which usually comes ~3 ppm, instead, a huge blob appears in that region.  I suspect that it is due to amine (formed after the reduction) complexed with borane.  Can you suggest some procedure to break the amine borane complex, avoiding acidic or basic workup?  Usually, the acidic workup is followed by addition of base (NaOH).  I do not want to add base because I have a betaketo ester in the molecule, which would deprotonate and will go in to the water layer.

[movies]

Hmmm...usually base (aq KOH) is the way that I have broken up B-heteroatom junk.  Maybe methanol would be nucleophilic enough to get rid of the boron.