Synthesis of new, optically active 1-(substituted aryl)pyrrole derivatives via atropisomerism directed diastereoselective metalation

Abstract

Axial chirality directed highly diastereoselective formation of a new stereogenic center in the benzylic position of racemic and optically active 1-[2-(carboxymethyl)-6-ethylphenyl]-1H-pyrrole-2-carboxylic acid (4) is reported as the very first example of efficient intramolecular asymmetric induction effect of the atropisomeric 1-phenylpyrrole skeleton containing dicarboxylic acid on the metalation, alkylation reaction sequence. Configuration of a product ((R a ,S)-7a) was determined by single crystal X-ray diffraction measurements. In addition, stereochemical stability of the new, two chirality elements containing compounds was demonstrated by selective, stepwise transformation of the carboxylic groups into ester and amide functions, respectively.