Conformational Dynamics in Asymmetric Catalysis: Is Catalyst Flexibility a Design Element?

Abstract

Traditionally, highly selective low molecular weight catalysts have been designed to contain rigidifying structural elements. As a result, many proposed stereochemical models rely on steric repulsion for explaining the observed selectivity. Recently, as is the case for enzymatic systems, it has become apparent that some flexibility can be beneficial for imparting selectivity. Dynamic catalysts can reorganize to maximize attractive non-covalent interactions that stabilize the favored diastereomeric transition state, while minimizing repulsive non-covalent interactions for enhanced selectivity. This short review discusses catalyst conformational dynamics and how these effects have proven beneficial for a variety of catalyst classes, including tropos ligands, cinchona alkaloids, hydrogen-bond donating catalysts, and peptides.1 Introduction2 Tropos Ligands3 Cinchona Alkaloids4 Hydrogen-Bond Donating Catalysts5 Peptide Catalysts6 Conclusion

Disulfonimides versus Phosphoric Acids in Brønsted Acid Catalysis: The Effect of Weak Hydrogen Bonds and Multiple Acceptors on Complex Structures and Reactivity

“…In DSI complexes, the conformational and structural dynamics may also stabilize noncovalent interactions or minimize steric repulsion to achieve high selectivities, as proposed previously. 37…”

JoyaPhos: An Atropisomeric Teraryl Monophosphine Ligand

“…The rigidity of the ligand and the consequential repulsive interactions with bulky substrates such as 18 might hinder structural reorganizations that favor attractive non‐covalent interactions. The ligand flexibility, which minimizes repulsive and maximizes attractive interactions for an optimal enantio‐induction, is therefore strongly impacted in the case of atroposelective C−N cross‐coupling reactions, which require a high degree of substitution for sufficient configurational stability of the products.…”

A Comprehensive Discovery Platform for Organophosphorus Ligands for Catalysis

“…The LKB-P consists of computed properties of 366 monodentate organophosphorus ligands in typical coordination environments. 23 Recently, the profound impact of ligand dynamics on catalytic reactions has been recognized more frequently, 24,25 however, the systematic quantification of ligand flexibility is still underdeveloped. Thus, inspired by the previous approaches to the mapping of ligand space, we aimed at developing a workflow that encompasses a wide range of steric and electronic properties of catalytically relevant ligands including descriptors for their flexibility to enhance the capabilities of data-driven catalyst design.…”