Synthesis of 2-oxazoline ferrocenes: Towards high-efficient chiral ligands and catalysts

Abstract

Ferrocene, discovered in 1951, has been widely applied in the field of chemistry, mainly because of its unique properties such as chemical and thermodynamic stability, redox properties, and easy derivatization. Chiral ligands with ferrocene backbones have gained considerable attention from chemists in the field of asymmetric catalytic methodology. Since the breakthrough of ferrocene ligands in the 1970s, numerous chiral ligands and catalysts with excellent activities have been designed by combining various coordination groups on the Cp ring. Notably, as a crucial factor for obtaining highly stereoselective optically active products, planar chirality is provided by the layered sandwich structure of ferrocene. Research on chiral ferrocenyl ligands has expanded from academic and laboratory studies to industrial-scale manufacturing. In several typical large-scale synthetic processes for stereoselective intermediates, transition metal complexes derived from ferrocene ligands have been certified as the preferred enantioselective catalysts.Among chiral ferrocene compounds, oxazolinyl ferrocene ligands and catalysts are of great interest to researchers. Since 1995, hundreds of novel chiral frameworks with oxazolinyl ferrocene cores have been synthesized. Correspondingly, using oxazolinyl ferrocenes, numerous valuable optically active compounds can be generated with high chemical conversion and stereoselectivity using concise transition-metal-catalyzed transformations. More recently, with bimetallic synergistic catalytic strategy introduced in the 2010s, the use of chiral oxazolinyl ferrocene ligands has entered a new application era.Although approaches to the synthesis of oxazolinyl ferrocene derivatives have been developed, the requirements for advanced efficiency systems and sustainable progress have prompted researchers to discover the application of chiral catalysts in an economical and environmentally benign manner. In this short review, we describe previously published chiral oxazolinyl ferrocene ligands in terms of their chelation forms. Subsequently, as a fundamental platform for chiral ligands, practical synthetic methods for 2-oxazolinyl ferrocene derivatives are presented in detail. Significant processes applied to the synthesis of oxazolinyl ferrocenes with diverse patterns are discussed in this section. Moreover, combined with the research trends in asymmetric synthesis, we discuss the potential challenges and applications of oxazolinyl ferrocene derivatives in the future.