[birwin91]

I've started working with substituted 3-bromo-2-methylthiophenes. Using n-BuLi in dry THF or ether at -78 degrees under a nitrogen atmosphere, I'm trying to lithiate the thiophene moiety and then further react it with octafluorocyclopentene (injected directly into the system with a gas-tight syringe) and create a carbon-carbon bond between the two with loss of LiF. This reaction is well studied in the literature, however i can't get the reaction to completion, and I simply crash out starting material upon work-up. There is no obvious colour change upon addition of the n-Buli (which is from a brand new bottle). The starting material is fairly soluble in the solvent, but not at all in hexane, which is how the n-BuLi usually comes, i was wondering if this could be an issue? Does anyone have any experience working with these compounds in particular that knows what I could be doing wrong, or some glaringly obvious mistakes that may happen when working with n-BuLi that I just don't know about? I would greatly appreciate any help, I'm starting to lose sanity now at this stage

[discodermolide]

Why not use a different base in a different solvent. For example LDA in THF or KHMDS in toluene.

[clarkstill]

Hi Birwin,

So you're trying to do lithium-halogen exchange on the aryl bromide right? Are you using at least 2 eq. of BuLi for the reaction? You need to, since butyl bromide is produced stoichiometrically. Also, although the BuLi is new, did you titrate it? You can do this in any number of (googleable) ways, my preference is with a heavyish dry alcohol in THF with 1,10-phenanthroline as an indicator. Since you need 2 eq. of BuLi any error in the concentration will be compounded... Have you tried trapping with any other electrophiles to ensure the Li-Br exchange is occurring? Even just throwing in a source of H+?

Hope this helps