The Combinatorial Approach to Asymmetric Hydrogenation: Phosphoramidite Libraries, Ruthenacycles, and Artificial Enzymes

Abstract

For a more general implementation of asymmetric catalysis in the production of fine chemicals, the screening for new catalysts and ligands must be dramatically accelerated. This is possible with a high-throughput experimentation (HTE) approach. However, implementation of this technology requires the rapid preparation of libraries of ligands/catalysts and consequently dictates the use of simple ligands that can be readily synthesised in a robot. In this concept article, we describe how the development of new ligands based on monodentate phosphoramidites enabled the development of an integral HTE protocol for asymmetric hydrogenation. This "instant ligand library" protocol makes it possible to synthesise 96 ligands in one day and screen them the next day. Further diversity is possible by using mixtures of monodentate ligands. This concept has already led to an industrial application. Other concepts, still under development, are based on chiral ruthenacycles as new transfer hydrogenation catalysts and the use of enzymes as ligands for transition-metal complexes.