I've spent several hours searching the WWW with entries like "stereoselective enolate formation" and similar ones, but I find almost only entries for Li-amide bases (LDA, LMTP) and no other bases like t-BuO, NMe3, NaH, n-BuLi concerning the stereoselectivity.

I'd like to know if the addition of these four bases to 3-pentanone all results with preference in the cis or trans enolate (and if possible with an explanation why).

Related: Stereoselective enolate formation with different bases: Does the addition of a base NR3 to a ketone affords the cis or the trans enolate?

  • $\begingroup$ How is this different from the previous question, other than being a specific case? I recommend you edit this into the previous questions rather than posting a new one. $\endgroup$
    – bon
    Jul 17, 2015 at 18:56
  • $\begingroup$ I thought the old question is more a detailed question on the effect of the three different alkyl chains, here I'd like to discuss some general ideas (e.g. attack of the least motion, allylic A1,2 and A1,3 interaction, stereoelectronic effects and so on). $\endgroup$
    – laminin
    Jul 17, 2015 at 19:18
  • $\begingroup$ @laminin If you know all of the factors to consider (e.g. attack of the least motion, allylic A1,2 and A1,3 interaction, stereoelectronic effects and so on), please provide your analysis for those factors. $\endgroup$
    – jerepierre
    Jul 17, 2015 at 20:40
  • $\begingroup$ @jerepierre It was just a guess. May be the trans-enolate is disfavoured from stereoelectronic view, because Me could donate electron density into the sigma*(C-O) (I mean the C-O bond with negative charge seems for me more like a donor than an acceptor). To get the trans-enolate you can do it with LDA because of the isopropyle group. I expect the diaxial interaction of Me with i-Pr around 4.5 kcal/mol. How much costs a A1,2 interaction of two Me groups? (it's less than the Me//i-Pr interaction) $\endgroup$
    – laminin
    Jul 17, 2015 at 21:38
  • $\begingroup$ Now I was looking if I find some reactions of ketones with NEt3: books.google.ch/… I think to say if we obtain here the cis or trans enolate we have first to decide if the carbonyl oxygen is less bulky than the CH2Me moiety (which I treat here almost as Me). $\endgroup$
    – laminin
    Jul 17, 2015 at 21:43

1 Answer 1


As a prenote: My answer is somehow speculative because I have no experimental data or reference values of similar reactions used. In other words: The argumentation pathway below might be wrong.

Addition of LDA mostly gives the trans-enolate if a primary alkyl substituent next to the carbonyl group has been used.

Carbonyl(O) is smaller than the methyl group [ref.], therefore the allylic A13 interaction of Me//Me or even Me//i-Pr is bigger than the allylic A12 interaction.

An allylic A13 Me//Me interaction is about 3,7 kcal/mol, an allylic A12 Me//Me is may be around 3,2 kcal/mol (this is just a guess).

If HMPA is added Li might coordinate to four HMPA molecules forming a cluster and inhibiting the cyclic transition state of LDA and hence no longer providing the trans-enolate, meaning an open transition state must be lower in activation energy for the cis-enolate formation.

enter image description here

So I tried to draw the conformations of 3-pentanone and then treated the base as "point bulk", meaning the base is like a sphere with different sizes.

Hard bases have a bigger repulsion to the carbonyl oxygen.

I have used arbitrarily numbers for the stereoselectivity.

Here is my answer which base gives more cis-enolate than the other:

enter image description here


Your Answer

By clicking “Post Your Answer”, you agree to our terms of service and acknowledge you have read our privacy policy.

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