[kriggy]

Hi guys, im working on synthesis of 15 membered macrocycle. We have 4 step procedure but I stepped upon DCC used in peptide synthesis. It seemes that I could use it, or other carbodiimide, for reaction shown on picture bellow. Could it work? Does anyone has any experience with using carbodiimides to share? Thanks

ps: sry for not the best quality of the picture..couldnt get better with chemsketch :/

[opsomath]

There's no obvious reason you couldn't use a carbodiimide for this coupling. What method of amide coupling is used in your 4-step procedure you mentioned?

[Babcock_Hall]

You have a bifunctional electrophilic intermediate and a bifunctional nucleophile.  Would the macrocycle be favored over polymer formation?  I don't know.

[kriggy]

There's no obvious reason you couldn't use a carbodiimide for this coupling. What method of amide coupling is used in your 4-step procedure you mentioned?

Similar, we reduced acid to dialdehyde  and then just mixture of dialdehyde, 2,2´-(ethylenedioxy)bis(ethylamine) and MnCl2.

My prof told me that it works from ester without carbodiimide just by mixing the 2 reagents to get dipeptide and then reduce the oxygen which is ,according to him the most difficult part, because, reduction by LiAlH4 doesnt give good yields (Im not sure why not, it is used in literature for doing realy similar reductions). Same goes for kirshner-wolf reduction. I guess reduction with zinc amalgame in HCl would be good. Do you know any other metods of reducing carbonyl to CH2?

You have a bifunctional electrophilic intermediate and a bifunctional nucleophile.  Would the macrocycle be favored over polymer formation?  I don't know.

MnCl2 should help with that as it gets coordinated by 2,2´-(ethylenedioxy)bis(ethylamine) and "bends" the shape of the molecule to favor macrocyclization.

[opsomath]

If you are adding the amine to the dialdehyde, it is condensing into the imine which also may be coordinating to the Mn(II) ion. It's not a direct replacement to try to swap that out for an amine coupling.

I'm a little sceptical about the direct condensation of the ester (I assume you mean an ester of that dicarboxylic pyridine thing, you didn't explain) with the bis-amine compound, but I wouldn't be astounded. It is probably a slow reaction anyway.

[Babcock_Hall]

Perhaps it is an active ester?  Just guessing, but active esters can be made into amides, although the reaction is slow in my hands.

[opsomath]

Yes, it would be usual to go from the carbodiimide to an active ester, although OP didn't mention it. I've used this reaction for surfaces quite a bit.

[kriggy]

If you are adding the amine to the dialdehyde, it is condensing into the imine which also may be coordinating to the Mn(II) ion. It's not a direct replacement to try to swap that out for an amine coupling.

I'm a little sceptical about the direct condensation of the ester (I assume you mean an ester of that dicarboxylic pyridine thing, you didn't explain) with the bis-amine compound, but I wouldn't be astounded. It is probably a slow reaction anyway.

1) thx for correction, its obv imine, which we reduce to get the desired macrocysle. I was bit chaotic when I was writing here.
2) Exactly. I will see next monday (stirring for 7 days)