Ligand Design for Asymmetric Catalysis: Combining Mechanistic and Chemoinformatics Approaches

A core element to the successful development of asymmetric catalytic reactions is finding a suitable chiral catalyst or ligand. The discovery and optimization of chiral catalysts can be enormously challenging. Traditionally, chemists have approached this endeavour by screening existing ligands. The most promising structures are then modified based on mechanistic knowledge, chemical intuition and the results of screening experiments, with the aim of optimizing selectivity and yield. However, this empirical approach has begun to change: new methods to accelerate the experimental screening process have emerged together with computational and physical-organic approaches that provide a systematic, and hopefully faster, route to new catalysts. Practical and theoretical understanding of highthroughput screening and multi-parameter optimization are now requirements at the cutting edge of the field, in addition to synthetic and mechanistic expertise. In this chapter, we summarize the recent examples of combinatorial approaches taken to discover and develop asymmetric catalytic transformations. In particular, we highlight the use of quantitative models to predict reaction outcomes. A series of guidelines are presented to aid chemists in adopting these approaches, followed by illustrated examples of recent work in this area.