Small peptides as ligands for catalytic asymmetric alkylations of olefins. Rational design of catalysts or of searches that lead to them?

Amino acid-based chiral ligands have been developed for use in Cu-catalyzed enantioselective allylic alkylations and conjugate additions that allow access to optically enriched compounds that are otherwise difficult to prepare. These chiral ligands are easily modified and have been identified through mechanism-based library screening. The data presented point to the significance of the availability of a collection of catalysts, since subtle variations in substrate or nucleophile structure often call for a different optimal chiral ligand. Can a catalyst be truly "rationally designed" or do we design our search pathway that eventually leads us to such a catalyst? What is meant by a "general catalyst"? Do we need a class of effective catalysts instead? These and related questions are addressed in the context of the above studies.