15
$\begingroup$

I want to enolize a ketone, for instance acetone with a $\mathrm{p}K_\mathrm{a}$ value of about 20 (in $\ce{H2O}$).

I'd like to know if there exists a rule of thumb to predict how the $\mathrm{p}K_\mathrm{a}$ of the ketone will decrease if we add one of the following Lewis acids:

a) $\ce{(c-Hex)2BCl}$ (chlorine anion can be eliminated)

b) $\ce{Bu2BOTf}$ (triflate anion is a good leaving group)

c) $\ce{NaI}$ (sodium is bigger than lithium, and I expect the bond to oxygen is less strong meaning the decrease of the $\mathrm{p}K_\mathrm{a}$ will be less than in d))

d) $\ce{LiI}$ (iodine is bigger than lithium, therefore good hard-soft-mismatch; and oxygen is hard as well)

e) $\ce{HCl}$ (As @SYK suggested in his answer of my recent question [1], the proton is the strongest Lewis acid as possible and will lower the $\mathrm{p}K_\mathrm{a}$ as much as possible, that even a very weak base, may be of $\mathrm{p}K_\mathrm{a}~9$ as $\ce{NH4Cl}$ will (or won't it?) form the cis-enolate)

I'm especially interested in the lowering values for a), b) and c). My questions:

  • Is my qualitative lowering of $\mathrm{p}K_\mathrm{a}$ values a < b < c < d < e correct?
  • Do you have somes guesses for decreasing values for a, b and c ?
$\endgroup$
  • $\begingroup$ You think a,b will be worse than c,d? I don't think so. $\endgroup$ – Mithoron Jul 18 '15 at 22:00
  • $\begingroup$ I think $\ce{Na+}$ is harder and hence has a higher positive charge acting on the oxygen. Why do you prefer the other ones? $\endgroup$ – laminin Jul 18 '15 at 22:23
  • $\begingroup$ It coordinates weakly, for borium keton would act as third ligand - bound strongly. $\endgroup$ – Mithoron Jul 18 '15 at 23:01
  • $\begingroup$ @Mithoron Why ? $\endgroup$ – laminin Jul 20 '15 at 13:37
1
$\begingroup$

I used to work in a group that specialised on the total synthesis of polyketides. For obvious reasons, syntheses of polyketides rely on aldol additions a lot. Yet, I never heard of any simple rule of thumb for the $\mathrm{p}K_\mathrm{a}$ value differences so I suspect there isn’t one.

Both boron reagents enolise ketones practically by themselves, $\ce{NEt3}$ is typically added to capture any excess protons. On the other hand, I have never heard of lithium or sodium enolising a ketone by themselves.

Finally, $\ce{HCl}$ (or any strong proton source for that matter) will protonate the ketone but not to the enolate. Instead, the protonated ketone with $\ce{C=\overset{+}{O}-H}$ will be obtained.

$\endgroup$

Your Answer

By clicking “Post Your Answer”, you agree to our terms of service, privacy policy and cookie policy

Not the answer you're looking for? Browse other questions tagged or ask your own question.