Applications of Biphenol-Based Phosphine Ligands in Asymmetric Reactions

Abstract

Catalytic asymmetric synthesis plays a crucial role in organic synthesis as it provides a means in which one or more chiral centers can be produced in complex compounds. Within the last 5 decades, significant new developments in asymmetric catalysis have been reported. One of particular interest was the introduction of the chiral monodentate phosphine. Chiral ligands, such as chiral phosphines, are useful for their abilities to produce complex compounds bearing chiral centers. Bidentate ligands have been frequently employed in asymmetric synthesis. Though several bidentate ligands have been prepared, the synthesis of these ligands is difficult. As such a lot of focus has been given to the preparation of monodentate phosphorous ligands and their application in asymmetric synthesis. In 2003, the Ojima group has developed a series of chiral biphenol-based monophosphoramidite (MPN) ligands which have performed nicely in various asymmetric reactions. Futhermore, in 2010, a series of chiral biphenol-based diphosphonite (BOP) ligands was developed that showed to be successful in the asymmetric allylic amination reaction. To further demonstrate the applicability of the ligands, they were employed in the asymmetric rhodium-catalyzed 1,4-conjugate addition and palladium-catalyzed intermolecular Heck reaction. The BOP ligand was employed for the synthesis of a versatile key intermediate of the indoline derivative which can be used towards the total synthesis of Strychnos indole alkaloids. The synthesis of this key intermediate entails an intermolecular asymmetric allylic amination catalyzed by BOP-Pd complex and an intramolecular Heck reaction of the resulting allylic amination product. The intramolecular Heck reaction and subsequent reactions is demonstrated.