[AlphaScent]

Hello All,

The attached scheme shows a possible product for the reaction.  Do you any of you think under the conditions that it would be the major product?  Is the kinetic proton the one most likely to be deprotonated even though the thermodynamic proton would give conjugation?  Is the pivlate and the TBS groups large enough to deprotonate the kinetic proton even though the other proton may be more reactive (more acidic?)

Please rip me apart.

Kind regards!!

[AlphaScent]

Realized I should show other product.

Cheers!

[pgk]

Although conjugation plays an important role, remember that you are working at very low temperature that usually favors the kinetic contol.
But what about the influence of the substituents steric hindrance?

[AlphaScent]

pgk,

Yeah I would assume that kinetic control would predominate in theory.  That seems to be the only logic to follow but I have seen that there can be other factors at play that one (I) may not predict until the experiment is done.

So my initial thought on sterics was to protect the tertiary alcohol with something like TBDPS or TIPS, which are larger than TBS, but it may prove difficult.  Tertiary alcohols are the hardest to protect but using TBSOTf, 2,6-lutadine, DMAP in DCM should work fine based on the literature.  There is also the possibility of using a PMB group, which is a go-to for tertiary alcohols, but may not have the steric bulk I am looking for.  The LDA (or HMDS) is also very bulky and should allow for deprotonation specifically under the kinetic conditions. 

Do you think with all the factors that it is not unreasonable to think it is possible? 

[pgk]

Organic Chemistry is mainly experimental Science and thus, there is nothing unreasonable in advance, before being rejected by the experimental results.

[AlphaScent]

Thank you for the laugh!!

Such a great response!!

Thanks pgk!!

Cheers!

[pgk]

You are welcome but this is the truth.

[AlphaScent]

Oh I know...all too well.

Cheers!

[rolnor]

If you make computer modeling or make a physical model you will see that there is very crowded around the non-wanted protonation site so its probably OK, you will get the deprotonation were you want it.

[AlphaScent]

rolnor,

Yeah that is what I am leaning towards.  When I make a 3D model in ChemBio Draw it really is quite sterically hindered.  Then with the kinetic conditions I think it should work well.

Cheers!

[rolnor]

There is a even more bulky base; lithiumdicyclohexylamide.

https://www.sigmaaldrich.com/catalog/search?term=Lithium+dicyclohexylamide&interface=All&N=0&mode=match%20partialmax&lang=en&region=SE&focus=product

[AlphaScent]

That material is a bit pricey.  But it would be worth a shot if LDA doesnt give good results.