Heterocyclic alpha-alkylidene cyclopentenones obtained via a Pauson-Khand reaction of amino acid derived allenynes. A scope and limitation study directed toward the preparation of a tricyclic pyrrole library.
The synthesis of a novel class of tricyclic pyrroles has been accomplished by using a Pauson-Khand/Stetter/Paal-Knorr reaction sequence. Full details of the Pauson-Khand reaction of amino acid tethered allenynes 4a-e and 9a-d are disclosed. The study of this reaction led to the discovery of an unprecedented substituent effect on the diastereoselectivity of the Mo(CO)6 mediated allenic Pauson-Khand reaction. It was found that amino acid tethered allenynes with aromatic side chains afford alpha-alkylidene cyclopentenones with the opposite diastereoselectivity compared to those with aliphatic side chains. This effect has been attributed to complexation of the metal mediator to the aromatic ring in the substrate. Furthermore, an isomerization of one of the diastereomers of the alpha-alkylidene cyclopentenones was encountered, leading to eventual decomposition. The stable diastereomers were found to react well in the Stetter reaction leading to 1,4-diketones that were converted to pyrroles. The observation that the first generation of 2-alkyl-substituted pyrroles was unstable led to a second generation of 2-carboxamide pyrroles with sufficient stability for biological tests which are in progress.
Brummond
Kay M
KM
University of Pittsburgh, Department of Chemistry, Pittsburgh, Pennsylvania 15260, USA. kbrummon@pitt.edu
Curran
Dennis P
DP
Mitasev
Branko
B
Fischer
Stefan
S
D000480:Alkynes / Q000138:chemical synthesis / Q000737:chemistry*; D000596:Amino Acids / Q000737:chemistry*; D003517:Cyclopentanes / Q000138:chemical synthesis*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis*; D008968:Molecular Conformation; D011758:Pyrroles / Q000138:chemical synthesis*
D000480:Alkynes; D000596:Amino Acids; D003517:Cyclopentanes; D006571:Heterocyclic Compounds; D011758:Pyrroles