[quantumnumber]

Hi again guys,

I was wondering if there is a strong theoretical explanation for the regioselectivity of deprotonated pyrrole in its reaction with an electrophile (SEAr). I know why it is preferred the substitution in position 2 above 3, but... why not directly on the nitrogen atom? I thought, in theory, the most favorable resonance structure is the one that places the negative charge above nitrogen atom, so...

In particular, I was studying the reaction attached: treatment of pyrrole with EtMgI, and then with IMe, to get 2-methylpyrrole as the major product.

What do you think?

[quantumnumber]

I've looked for computational calculations of pyrrole anion electron density distribution, but I didn't found anything useful.
I think this regioselectivity is determined by HSAB, and only hard acids would react at nitrogen atom (low energy HOMO), with a great ionic affinity.

[orgopete]

This is one of those really excellent questions that unless asked, can be easily overlooked, or at least I did.

If you look at the curved arrows, they should be wrong. There is no resonance. The electrons on the nitrogen are orthogonal to the pi electrons. Alkylation should have occurred on the nitrogen just as it does with pyridine. However, deprotonation must alter the aromaticity in some way for alkylation to take place. The intermediate in non-aromatic. This still doesn't answer the question. However, I believe the products are exactly the same as electrophilic substitution reactions. Here the curved arrow would apply.