Studies on selectivity in the Pauson-Khand reaction and synthesis of an intermediate of isocarbacyclin

Abstract

The Pauson-Khand reaction is a highly convergent process that is an efficient way to make substituted cyclopentenones. Some substrates undergo cyclization with high diastereoselectivity while others do not. It was thought that an efficient construction of the bicyclo[3.3.0]octenone core of isocarbacylin could be achieved using the thermal catalytic Pauson-Khand reaction developed in the Livinghouse laboratories in combination with known trends in the diastereoselective features of this reaction. Efforts toward this end are described using two different routes, involving cyclization of a dienyne and a hydroxymethyl enyne respectively. Additionally, work on the diastereoselective and enantioselective aspects of the Pauson-Khand reaction are presented. While some substrate based selectivities are presented, the focus is on ligand based strategies, and the preparation of the ligands is shown. Additionally, studies on cobaltcarbonyl-ligand complexes are presented, and related to their activity in the Pauson-Khand reaction. Modest enantioselectivities were realized using a monodentate phosphoramidite based ligand for the catalytic asymmetric Pauson-Khand reaction.