Unraveling the Science of Asymmetric Hydrogenation: A Deep Dive into Rhodium and Ruthenium Catalysts

Asymmetric hydrogenation is a pivotal method in synthetic chemistry, particularly in the production of chiral molecules. Initial research efforts led by Ikariya's group in Tokyo, alongside contributions from the Takasago Company, set the stage for significant advancements. Notably, the work of Noyori's laboratory etched the process of ruthenium-BINAP hydrogenations into the annals of scientific achievement. While early experiments focused primarily on alkene reductions, it was the asymmetric hydrogenation of ketones that would later become a cornerstone of synthetic methodologies.

The distinction between rhodium and ruthenium catalysts is integral to understanding their applications. Rhodium asymmetric hydrogenation is characterized by its mildness and specificity, particularly effective with dehydroamino acids and a limited array of alkenes, such as itaconates. In contrast, ruthenium asymmetric hydrogenation exhibits a broader substrate scope, allowing for greater versatility in synthetic applications. The dominance of BINAP and its derivatives in ruthenium catalysis has become a defining feature.

Recent developments in this field have shifted towards more focused applications in synthesis, particularly in refining reaction media. Noteworthy advancements include the introduction of "third generation" ligands in rhodium chemistry, which have significantly enhanced substrate applicability and enantiomeric selectivity. The Dupont ligands—DU-PHOS and BPE—developed by Burk's group, exemplify this trend, demonstrating consistent success in various reactions.

The exploration of reaction mechanisms is vital for a deeper understanding of asymmetric hydrogenation. Initial studies, particularly those involving Wilkinson's catalyst in alkene hydrogenation, revealed critical insights into dihydrogen activation steps. These investigations uncovered complexities that reshaped the understanding of catalyst behavior, establishing the bisphosphine complexes as key players in catalytic turnover, while also emphasizing the role of 31P-NMR techniques in delineating reaction pathways.

As the field of asymmetric catalysis continues to grow, the vast literature necessitates a selective approach in reviewing recent advances and mechanisms. With significant contributions from researchers, including comprehensive overviews in Noyori's Baker lectures, the ongoing evolution of ligand design and synthetic methodologies promises exciting developments in the world of asymmetric hydrogenation.