[Undergrad992]

Hey all,

I'm on campus doing research over the summer and I've been banging my head against the wall trying to get a Grignard Reagent to Form.

I've been trying to perform a Grignard Reaction with TBDMS protected 2-Bromoethanol, and after trying 7 different times to form the actual Grignard Reagent i'm running out of ideas. So far, to activate the Mg I've tried: mortar and pestle pulverization, dry stir, sonication, sonication + heat, addition of iodide crystals, and addition of methyl iodide and nothing seems to be working. Like I said, I'm running out of ideas so any input would be extremely helpful.

I know beggars can't be choosers but I'm avoiding using metallic potassium or mercury, mainly because I enjoy having all my fingers and not slowly going insane. Call me old fashioned...

Thanks to anyone who even took the time to read all this, and thanks a whole ton to anyone who offers their two cents.

[Doc Oc]

What transformation are you trying to achieve?  There may be an alternative (unless you are hellbent on learning the Grignard chemistry).

[Undergrad992]

I need to turn it into the Grignard Reagent to try and add it to a really hindered ketone (camphor-like structure with a few more substituents). I've tried Wittig and HWE to add to the same ketone but neither can break through the steric hindrance to add on to it.

[408]

Add lithium chloride.

And give up the phobia of potassium.  It is not going to hurt you unless you lick it.
Hg on the other hand...yeah, that is nasty.

[dunno260]

Use magnesium powder that has been dry stirred under an inert atmosphere for at least 48 hours and react it with the chloride (not bromide) to reduce the amount of self coupling that you are probably getting.  This is assuming that your problem isn't magnesium activation but that after you make a molecule of grignard reagent it is reacting with another molecule of starting material to produce the homocoupled product.  Cooling the reaction to 0C and switching to the chloro will reduce the likelihood of this.

I haven't heard of the lithium chloride additive before.  What does it do?

[408]

Your grignard can stick to the surface of the metal.  LiCl forms a more-soluble complex , exposing fresh Mg for reaction.  

I attempt to represent below in ASCII

LiX2MgR

..Cl..
./..\.
..Li....Mg-R
.\../.
..Cl...

or

Li+  X2MgR-


....Cl..
..\.
Li+.(-)Mg-R
../.
....Cl...

Two representations of the same thing.

[Undergrad992]

Thanks for all the help guys....i'll try the LiCl technique in my next trials. How much LiCl do I use? Excess amounts same as the Mg or equivalent to the Bromoethanol protected stuff?

[408]

As much as the n of grignard you expect to form, plus a little.

[ardbeg]

is your magnesium fresh?  because if it has enough of an oxidised surface layer then it will be a struggle to get it to do anything.

[Agathiyar]

My suggestion is that analyzing what you are getting, is it starting material remains, or the self coupled product, or TBDMS cleaves off. Based on what you are getting,  you can make your rxn to success.

Various scenario,  i) Cooling to 0 C, more dilution and taking chloride instead of bromide avoid self coupling
ii) Other protecting groups like benzyl might help if there is deprotection of TBDMS
iii) Follow others suggestion for successful initiation and propagation

Good luck