Rh-Catalyzed Synthesis of N-Aryl Trisubstituted Pyrroles

Significance

A new Rh-catalyzed route to 1,2-diaryl-substituted pyrroles in a three-component assembly reaction is reported. The combination of rhodium(II) salt with excess of diazoacetonitrile leads to the formation of a metallocarbenoid species which, in the presence of an imine, leads to the generation of an azomethine ylide. The reactive ylide intermediate is trapped by an activated acetylene diester in a [3+2] cycloaddition to form the 1,2-diaryl pyrroles in moderate to good yields. Notable is that only 1 mol% catalyst is needed for this transformation.

Comment

1,2-Diaryl-substituted pyrroles are common structural motifs in biologically active natural products, whereas 1,3-diaryl-substituted analogues are less common (F. Bellina, R. Rossi Tetrahedron 2006, 62, 7213-7256). The reported method affords 1,2-diaryl-3,4-diester substituted pyrroles in a one-step, single-pot reaction, an advantage compared to previous reported methods. Boyd has described the synthesis of 1,2-diaryl-substituted pyrroles via [3+2] cycloaddition reaction of mesoionic oxazolium-5-oxide perchlorates with dimethyl acetylene dicarboxylate (G. Boyd, P. Wright J. Chem. Soc ., Perkin Trans. 1 1972, 909-913) and Katritzky has reported a synthesis of pyrroles with the same substitution pattern from a thermal reaction of 2-benzotriazolylaziridines with acetylenedicarboxylate (A. Katritzky, J. Yao, W. Bao, M. Qi, P. Steel J. Org. Chem. 1999, 64, 346-350). Both methods afford products in good comparable yields but require high temperatures and prolonged reaction time.