[Babcock_Hall]

Good Morning Everyone,

A few years ago, we were using the para-methoxybenzyl group (4-methoxybenzyl) to protect a carboxylic acid in the form of an ester.  The deprotections we tried in the literature were based on acid cleavage in the presence of phenol.  Phenol presumably captures the benzylic carbocation.  In our hands, deprotection was slower than in the literature, or it was incomplete.  We were working with BOC-protected lysine or ornithine derivatives bearing an isonicotinamide group at the time, and in at least one case, the BOC group was removed, but the PMB group was not.  The PMB ester was part of an N-alkyl chain, starting at the pyridine nitrogen atom.

IIRC Discodermolide made the sensible suggestion of trying oxidative conditions to remove the PMB group.  I recall seeing oxidative removal protocols when PMB was used in the form of an ether but not an ester.  We turned our attention to other things, but we may return to this project shortly.  Does anyone have any thoughts about which oxidative conditions would work best?  The only thing that I can think of at the moment is that it might be prudent to remove the PMB group before the BOC group if possible.

[rolnor]

I think its best just to try in small scale, DDQ for example.

[pgk]

Please, take a look at the reference, bellow:
Mild, selective deprotection of PMB ethers with triflic acid/1,3-dimethoxybenzene, Tetrahedron Letters, 52, (2011), 6051–6054
http://www.chem.ucla.edu/~jung/pdfs/288.pdf
Question: why not using trifflic acid (pKa = −14.7) instead of any other acid, in the ordinary protocol of PMB/acid cleavage in the presence of phenol? As being a superacid, it will accelerate the cleavage and might lead to a more complete reaction (with a probable risk of simultaneous deBOCylation).

[rolnor]

Would catalytic hydrogenation be useful?

[Babcock_Hall]

There is a pyridinium ring present; therefore, I worried that it would be reduced if we deprotected by hydrogenation.

[TheUnassuming]

In theory the same conditions for the ether should work for the ester.  For the oxidative PMB removal, in addition to rolnor's suggestion of DDQ, you could also try CAN. 

[pgk]

The presence of pyridinium salt is not a big problem because its hydrogenation with Pd/C demands either high pressure or long reaction times in highly polar solvents.
1). Chemistry of Heterocyclic Compounds, 2001, 37(7), 797–821
2). Tetrahedron, 2009, 65(41), 8538-8541
Another option is hydrogenolysis with hydrosilane + Pd/C and using polymethylhydrosiloxane (PMHS) that is a safe reagent instead of Et3SiH, which is highly flammable.
J. Org. Chem., 2007, 72(17), pp 6599-6601
This method seems selective because PMHS reduction of pyridinium salt demands exotic organometallic catalysts.
Organometallics, 2013, 32(16), 4457-4464
Besides, PMHS reduction of esters demands catalysis by fluoride salts.
1). Synthesis, 1982; 1982(11), 981-984
2). Synlett, 1997, iss.8, 989-991
3). Molecules, 2003, 8, 873-881

[clarkstill]

Scifinder gives about 125 hits for PMB removal in the presence of a Boc, including:

JOC 2003 4574 (ZrCl4)
Synthesis 2010 1712 (O2 and flavin photocatalysis)
BMC 2003 1901 (Rh/Al2O3, H2)
RSC Advances 2013 14814 (POCl3, DCE)
TL 2015 1080 (oxalyl chloride)
... and lots of H2, Pd/C examples.

I didnt spot anything oxidative though. I suppose by making an ester you reduce the electron density on the PMB and make it less susceptible to oxidation?

[Babcock_Hall]

Thank you.  I regret being unable to reply to all of the thoughtful comments at this time.  I will comment as soon as I have finished with a pressing professional matter.