December 12, 2019, 07:11:07 AM
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Topic: Selective Deprotonation  (Read 285 times)

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Offline AlphaScent

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Selective Deprotonation
« on: December 03, 2019, 12:14:55 PM »
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!!
If you're not part of the solution, then you're part of the precipitate

Offline AlphaScent

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Re: Selective Deprotonation
« Reply #1 on: December 03, 2019, 12:19:02 PM »
Realized I should show other product.

Cheers!
If you're not part of the solution, then you're part of the precipitate

Offline pgk

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Re: Selective Deprotonation
« Reply #2 on: December 03, 2019, 12:22:01 PM »
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?

Offline AlphaScent

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Re: Selective Deprotonation
« Reply #3 on: December 03, 2019, 12:41:30 PM »
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? 
If you're not part of the solution, then you're part of the precipitate

Offline pgk

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Re: Selective Deprotonation
« Reply #4 on: December 03, 2019, 12:47:01 PM »
Organic Chemistry is mainly experimental Science and thus, there is nothing unreasonable in advance, before being rejected by the experimental results.

Offline AlphaScent

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Re: Selective Deprotonation
« Reply #5 on: December 03, 2019, 12:49:26 PM »
Thank you for the laugh!!

Such a great response!!

Thanks pgk!!

Cheers!
If you're not part of the solution, then you're part of the precipitate

Offline pgk

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Re: Selective Deprotonation
« Reply #6 on: December 03, 2019, 12:59:34 PM »
You are welcome but this is the truth.

Offline AlphaScent

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Re: Selective Deprotonation
« Reply #7 on: December 03, 2019, 02:05:21 PM »
Oh I know...all too well.

Cheers!
If you're not part of the solution, then you're part of the precipitate

Offline rolnor

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Re: Selective Deprotonation
« Reply #8 on: December 03, 2019, 02:34:11 PM »
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.

Offline AlphaScent

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Re: Selective Deprotonation
« Reply #9 on: December 03, 2019, 03:29:39 PM »
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!
If you're not part of the solution, then you're part of the precipitate

Offline rolnor

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Offline AlphaScent

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Re: Selective Deprotonation
« Reply #11 on: December 03, 2019, 04:34:23 PM »
That material is a bit pricey.  But it would be worth a shot if LDA doesnt give good results.
If you're not part of the solution, then you're part of the precipitate

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