Copper-catalyzed condensation of imines and alpha-diazo-beta-dicarbonyl compounds: modular and regiocontrolled synthesis of multisubstituted pyrroles

In the presence of a copper(II) catalyst, enolizable imines bearing various N-substituents and alpha-diazo-beta-ketoesters undergo denitrogenative and dehydrative condensation to afford highly substituted pyrroles in moderate to good yields with exclusive regioselectivity. The reaction likely involves nucleophilic addition of the imine nitrogen to a copper carbenoid, tautomerization of the resulting azomethine ylide to an alpha-enaminoketone, and a subsequent enamine-ketone cyclocondensation. With Yb(OTf)(3) as a unique cocatalyst, alpha-diazo-beta-diketones also participate in the same condensation reaction. The present reaction is applicable to acyclic, exocyclic, and endocyclic imines with tolerance of a broad range of functional groups and heterocyclic moieties, thus opening a new convenient route for the synthesis of the lamellarin family of natural products.