[tak]

My substrate is not even remotely soluble in the traditional tBuOH/H2O system. It is somewhat soluble in THF and EtOAc, and good solubility in DMF. Not very soluble in EtOH and CH2Cl2. Do you guys know if I can expect good asymmetric Sharpless dihydroxylation in other solvent systems? Any suggestions? Thanks!

[OC pro]

In general, there is no need that substrates dissolve completely in solvens. Only small amounts are needed to be dissolved for the reaction to take place.
You should give the classical tBuOH/H2O system a chance before trying out other things.

[tak]

Thanks, OC Pro.
I have actually tried it in tBuOH/H2O a couple of times. And absolutely no rxn!! I concluded it must be the solubility issue because another substrate that is essentially the same except for having one less amine group protected by phthalate did undergo the dihydroxylation rxn fine. It appears that this extra NPhth group that messes with the solubility

[dunno260]

Sharpless has a Chem Reviews article from 94 I believe that I myself am slogging through right now to help troubleshoot some dihydroxylations I am running.  Its a rather lengthy and dense article though and I am not all the way through it, but from what I gather from reading the article and talking with my professor is that the dihydroxylation has been ridiculously optimized.  I don't know what effect changing the solvent would have, I would try it on a smaller scale and see.  I do know that the biphasic system is absolutely crucial for it to work.   I would give EtOAc a try and see on a small scale. 

http://pubs.acs.org/doi/abs/10.1021/cr00032a009  Thats the review article.