[nirhananya]

Hello.
We all familiar with the Knoevenagel condensation, for example of malonate ester and aldehyde, to afford the corresponding α,β-unsaturated compound.
I had wondered - is it possible to make an aldol addition when you have only one acidic hydrogen?
For example, if you take dimethyl methylmalonate with an aldehyde, can you get the corresponding alcohol (because elimination can't happen)?
Thanks

[orgopete]

I would argue that generally this would not work. Although an addition may take place, if an alkoxide did form, the malonate or beta-ketoester would be the weaker base and would return the aldehyde and reform the malonate anion.

You can find reverse additions from beta keto esters without alpha hydrogens. Elimination isn't possible, so addition to the carbonyl creates the instance where the alkoxide intermediate can eliminate the weaker base to generate an ester and enolate of a ketone or ester.

I use this reasoning to explain when conjugate additions are preferred over addition to a carbonyl group. If the weakest base of the addition product is the weaker base, such as a malonate or keto ester, that reaction takes place. Conjugate additions can also reverse, but if protonation takes place, the aldehyde or ketone is a weaker acid and little or no enolate is formed to reverse the conjugate addition. The equilibrium favors the conjugate addition.

Using these examples, I would argue it would be difficult to carry out the reaction to just form an addition product. In this case, the additional hydrogen enables elimination and stops reversals from the tetrahedral intermediate.

[nirhananya]

Thank you for the explanation. I really couldn't find such examples, and now I can understand the reason.