Synthesis of Pyrroles via Consecutive 6π-Electrocyclization/Ring-Contraction of Sulfilimines

We present a modular, synthetic entry to polysubstituted pyrroles employing readily available 2,5-dihydrothiophenes. Ring-opening of the heterocycle provides access to a panel of 1,3-dienes which undergo pyrrole formation in the presence of inexpensive chloramine-T trihydrate. The transformation is conducted in an open flask and proceeds at ambient temperatures (23 degrees C) in nondry solvents. A careful adjustment of the electronics and sterics of the 1,3-diene precursor allows for the isolation of key intermediates. DFT studies identified a reaction mechanism that features a 6 pi-electrocyclization of a sulfilimine intermediate followed by spontaneous ring-contraction to reveal the pyrrole skeleton.

Automated summary

This study presents a new synthetic approach to polysubstituted pyrroles using 2,5-dihydrothiophenes, with the ring-opening of the heterocycle providing access to a panel of 1,3-dienes that undergo pyrrole formation in the presence of inexpensive chloramine-T trihydrate. The reaction is conducted in an open flask at ambient temperatures and key intermediates can be isolated by carefully adjusting the electronics and sterics of the 1,3-diene precursor. DFT studies identified a reaction mechanism involving a 6 pi-electrocyclization of a sulfilimine intermediate followed by spontaneous ring-contraction to reveal the pyrrole skeleton.