[Oxime]

I've got a system wherein I'm trying to find a way to reduce an oxime to the corresponding aminooxy ether - that is, take R-O-N=C-R' to R-O-N-C-R' through reduction of the double bond. Although the reaction is precedented and has worked well in my hands under a number of conditions (see below), I can't find a way to make it work in aqueous solution and/or at low (millimolar to sub-millimolar) concentrations.

Reaction conditions that have worked for similar oxime reduction typically occurs in polar organic solvent (MeOH, EtOH, THF), acid (I've personally used HCl, acetic acid, and TFA) and a range of reducing agents (in my hands: NaBH4, NaCNBH3, NaBH(OAc)3; in literature: BH3-pyridine or BH3-THF as well).

However, due to the low concentration of the oxime under my conditions and the aqueous solution present, none of the conditions that work in organic solvent have worked, regardless of the equivalents of reducing agent used or the pH of the solution.

One possibility is to use a water-soluble silane (I've tried triethylsilane, but with limited success due to immiscibility with water), but I'm coming up empty in looking for water-soluble silanes that don't polymerize. I'm wondering if anyone on these forums has alternative suggestions - either of reducing agents (including silanes) or changing the conditions totally?

[Archer]

If I may ask, why are aqueous conditions so important and why do you have to use such low concentrations?

[Oxime]

I'm working with biomolecules. Due to their precious nature (in addition, conditions typical in the field for characterization), lower concentrations are used. Not to mention it can be difficult to get millimolar concentrations of biomolecules in reasonable volumes to work with (i.e., more than a few to tens of microliters).

In working towards the biomolecule reduction, I've used a small-molecule analogue (O-methylbenzaldoxime) under nearly identical conditions (excepting concentration), and it's worked in most cases (except, if I recall correctly, not working well in water).

Water isn't completely necessary, though I'd like to be able to do it in aqueous solution.

[kriggy]

Doesnt NaBH₄ decompose in water?

[Archer]

Doesnt NaBH₄ decompose in water?

Only to a certain point when it then buffers itself with NaOH. The concentration of commercial NaBH₄ solution is about 12%.

[Oxime]

Another part of the issue with the borohydride reducing agents is that acid is necessary for the reduction of the oxime. The key first step is actually protonation of the oxime nitrogen in order to activate the carbonyl carbon for attack by the hydride. I think that the presence of the acid is leading to quenching of the reducing agent before it can react with the oxime under the low concentration conditions.