Among thioester and ester which has more electrophilic carbonyl carbon?

In few reactions I’ve seen that nucleophiles preferably attack **thioester’s carbonyl carbon** instead of **ester’s carbonyl carbon**


[![enter image description here](https://i.stack.imgur.com/YdgSA.jpg)](https://i.stack.imgur.com/YdgSA.jpg)


According to me, the initiation of reaction is decided by the electrophilicity of the carbonyl compound, in esters O being more electronegative makes c=o more electrophilic, thus attack should have been at ester, but many reactions suggest that attack first occurs at thioester.


What makes thioester’s carbonyl carbon more electrophilic?




[Reactivity of thioesters with respect to nucleophilic attack](https://chemistry.stackexchange.com/q/27132/16683)


[Why is the thioester bond weaker than a regular ester bond?](https://chemistry.stackexchange.com/q/42848/16683)


Let's consider a reaction mechanism like this:


[![reaction mechanism](https://i.stack.imgur.com/ydBSh.png)](https://i.stack.imgur.com/ydBSh.png)


A steady-state analysis will show that the rate of formation of product is


$$r = \frac{k\_1k\_2[\text{ester}][\text{Nu}]}{k\_{-1} + k\_2}$$


* $k\_1$ for the thioester is larger, because the sulfur 3p lone pair overlaps poorly with the C=O π\* orbital (which is formed from 2p orbitals). Recall that esters are less electrophilic than ketones *because* there is an ester oxygen which has a lone pair capable of overlapping with the C=O π\*. In this case, since this overlap is diminished, it turns out that thioesters are typically roughly as reactive towards nucleophilic attack as ketones.
* $k\_2$ for the thioester is also larger because thiolates are better leaving groups than alkoxides.


Depending on the relative rates of $k\_2$ and $k\_{-1}$, though, the second point may or may not be relevant. For example if $k\_2 \gg k\_{-1}$, then the rate equation simplifies to $r \approx k\_1[\text{ester}][\text{Nu}]$, in which case the comparison of $k\_2$ is no longer useful.


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