Sequential Modification of Pyrrole Ring with up to Three Different Nucleophiles

An umpolung strategy was used for the preparation of
highly functionalized
3-pyrrolin-2-ones. This approach involves dearomative double chlorination
of 1H-pyrroles to form highly reactive dichloro-substituted
2H-pyrroles. The resulting intermediate reacts selectively
with wet alcohols to form the corresponding alkoxy-substituted 3-pyrrolin-2-ones
via double nucleophilic substitution in up to 99% yield. The subsequent
reaction with different N-, O-,
and S-nucleophiles opens access to highly functionalized
pyrrolinones bearing additional functionality. The overall outcome
of the reported sequence is step-by-step nucleophilic modification
of pyrroles with three different nucleophiles. All steps were found
to be highly efficient and 100% regioselective. This transformation
proceeds under mild conditions and does not require any catalyst to
give final products in very high yields. The obtained experimental
results are in perfect agreement with the data obtained by theoretical
investigation of these reactions.