[408]

I have an electron-poor secondary amine that is protected with a P-methoxylphenyl protecting group.  This stuff is also not soluble in anything except boiling toluene and pyridine.  I know the PMP can be removed with CAN, TCCA, and iodobenzene diacetate, but the general solvent systems for these reactions are much more polar (H2O/MeCN)

Anyone have any other methods of PMP deprotection that would be good in these cases?  Otherwise I will have to go hardcore and attempt oxidative deprotection with HOF on a suspension of the material, and my fluorine cylinder won't be here till Jan or so....

thanks,

[Dan]

That's a tricky one. Do you think a surfactant like SDS would be of any help in aqueous MeCN?

Periodic acid is another option, but also frequently used in aqueous MeCN as well.

[408]

I have periodic acid on order, will give it a shot, but like you say, it is another aqueous acetonitrile reaction.

Regarding surfactants, frankly I have never worked with any in a synthetic capacity, and do not have any associated synthetic intuition regarding its use. The compound contains a zwitterionic core that is already surrounded by grease (PMP), so maybe the surfactant would help.  I have a feeling the solubility is so low as a result of some pretty epic pi-stacking interactions.

[discodermolide]

Why not chuck in some DDQ?
I've never tried it on a protected amine but you never know.

[408]

Never used DDQ before, but I'll check it out.  What conditions and solvents do you usually use with it?

Turns out iodobenzenediacetate is soluble in benzene.  My compound is very slightly soluble in benzene.  Refluxing for a few days and seeing what happens.  Already seeing a slight color change, but that may be resultant from loss of colored impurities from the precursor, and not actual reaction.

[discodermolide]

I'll look my conditions up for you but they are not for amine deprotection, will post them later on.

One of our guys used the following procedure:
Laccase-Mediated Deprotection of para-Methoxyphenyl (PMP)- Protected Amines
by
Jorge M. M. Verkade,a Lieke J. C. van Hemert,a Peter J. L. M. Quaedflieg,b Hans E. Schoemaker,b Martin Schürmann,b Floris L. van Delft,a
and Floris P. J. T. Rutjes
in
Adv. Synth. Catal. 2007, 349, 1332 – 1336.

I have a copy here.

[408]

Thanks!  Just bought some DDQ. if the IBD reaction does not work by monday, I'll give this a shot.

[discodermolide]

good luck

[discodermolide]

How did the deprotection go?

[408]

How did the deprotection go?

It failed harder than me the first time I tried quantum chemistry.
80% SM recovered, tiny bit of unknown product waiting on mass spec. NMR inconclusive.

Trying with TCCA/acid in mixed benzene/MeCN/dil. acid at reflux

[discodermolide]

Sorry to hear that:(
Give the enzymatic method a go.

[408]

Waiting on enzymes.  TCCA may have partially worked!  Mass spec issues currently so no result yet. 

But I got loaded on caffeine one day and went back 5 steps so I could remove a benzyl instead of a PMP.  80% of the way back to protected cpd already!  (408's next thread : "f&#^$*@ debenzylation help plz" )

[jverkade]

Are you still struggling to get the PMP group of? I might be able to give you some help. Please let me know if you're interested.

[408]

Thanks!  let me know any suggestions, I tried everything I could find and think of with no result, so I had to go back a few steps and approach this from another path.  This path is still in process, so any suggestions are still welcome.

[jverkade]

A couple of years too late: has the problem been solved?