Chiral phosphoric acid-catalyzed Friedel-Crafts reaction of 2,5-disubstituted and 2-monosubstituted pyrroles with isoindolinone-derived ketimines

The enantioselective reaction between 2,5-disubstituted pyrroles and diaryl-ketimines, generated in situ from isoindolinone-derived alcohols, is described. Pyrrole derivatives possessing a congested tetrasubstituted stereogenic center at the beta-(C3) position are generally obtained in high yields and enantioselectivities. The transformation can be extended to 2-monosubstituted pyrroles, generating chiral alpha-(C5) functionalized pyrrole products. Control experiments were conducted in order to elucidate the origin of the low enantioselectivities observed in some of the products.

Automated summary

This paper describes the enantioselective reaction between 2,5-disubstituted pyrroles and diaryl-ketimines generated from isoindolinone-derived alcohols. Pyrrole derivatives with a congested tetrasubstituted stereogenic center at the beta-(C3) position are obtained in high yields and enantioselectivities. The reaction can also be extended to 2-monosubstituted pyrroles, producing chiral alpha-(C5) functionalized pyrrole products. Control experiments were conducted to explain the origin of low enantioselectivities in some products.