Synthesis of 4-Hydroxy-1H-pyrrole-2,3-dicarboxylic Acids

Significance

A facile synthesis of 4-hydroxy-1H-pyrrole-2,3-dicarboxylic acid derivatives 3 via ring annulation of acetylenic esters 2 and α-amino ­acids 1 is reported. Several amino acids including phenylalanine, valine, isoleucine and tryptophan were examined in the reaction with dimethyl and diethyl acetylenedicarboxylate to give the desired tetrasubstituted pyrroles 3 in good to excellent yield. In all cases, the coupling agent DCC was found to give superior yields to the more expensive cyclohexyl isocyanide. A reasonable mechanism involving intermediates 4 and 5 was proposed, in analogy to similar systems previously reported by the authors.