Heterocyclic α-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 α-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
α-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.