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DOI: 10.1055/s-0028-1083609
Synthesis of 4-Hydroxy-1H-pyrrole-2,3-dicarboxylic Acids
Contributor(s):Victor Snieckus, Timothy HurstTarbiat Modares University, Tehran, Iran
Synthesis of 4-Hydroxy-1H-pyrrole-2,3-dicarboxylic Acid Derivatives: Unusual Coupling of Acetylenic Esters and α-Amino Acids in the Presence of Cyclohexyl Isocyanide or N,N′-Dicyclohexylcarbodiimide
Synthesis 2008, 2462-2466
Publication History
Publication Date:
20 November 2008 (online)
Key words
pyrroles - α-amino acids - acetylenes
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.
Comment
Pyrroles are one of the most important classes of π-excessive heterocycles as they are crucial building blocks in porphyrin chemistry and have many applications in medicine and agriculture (see Book below). Synthetic approaches to pyrrole derivatives are often multistep and low-yielding. The current method constitutes a mild, operationally simple and high-yielding one-pot method for the formation of highly substituted pyrroles from simple and inexpensive starting materials.
Book: D. StC. Black, In Science of Synthesis, Vol. 9; G. Maas, Ed.; Georg Thieme Verlag: Stuttgart, New York, 2001, 441-552.