Ligand (biochemistry)

Selectivity

Receptor

Organic chemistry

Steric effects

Combinatorial chemistry

Phosphine

Palladium

Catalysis

Chemistry

Ylide

Electronic effect

Coupling reaction

Phosphonium

Biochemistry

Accounts of Chemical Research

The development of homogeneous catalysts is strongly connected to the design of new, sophisticated ligands, which resolve limitations of a given reaction protocol by manipulating the electronic properties of the metal and its spatial environment. Phosphines are a privileged class of ligands that find applications in many catalytic transformations, ranging from hydrogenation reactions to hydroformylation and coupling chemistry. For many years, chemists have been trying to improve the efficiency, selectivity, and application of coupling reactions. The use of highly electron-rich and bulky phosphines was often associated with increased selectivity and efficiency and led to the development of a vast variety of electron-rich alkyl-substituted phosphines. However, this concept of increasing the ligand donor strength reaches its limits with the use of trialkyl-substituted phosphines with tri-tert-butylphosphine thus being one of the most active ligands for many years. In the course of our research efforts to use the special donor strength of ylides to stabilize electron-deficient, low-valent main group compounds, we realized that ylide-substituted phosphine (YPhos) ligands possess remarkably strong donor abilities. Moreover, the YPhos ligands are highly tunable by changing the nature of the groups on the phosphonium, phosphine, or central ylidic carbon atom. We thus obtained a ligand platform with donor capabilities ranging from PCy3 to even stronger donor abilities than N-heterocyclic carbenes, while being more sterically demanding than simple phosphines as well as many well-known biarylphosphine ligands.These properties led us to explore the applicability of the YPhos ligands in catalysis. In a series of recent reports, our group applied YPhos ligands in gold and palladium catalyzed reactions at catalytic loadings applicable for medium- to large-scale applications. The increased donor strength and unique architecture allowed for remarkable activities in a series of transformations at mild reactions conditions. For gold(I)-catalyzed reactions, we obtained turnover numbers (TONs) for the hydroamination of phenylacetylene with aniline of over 20 000. Also, more complex reactions were easily catalyzed with efficiencies greater than those of other known gold(I) catalysts. Similar efficacies were found in a series of palladium-catalyzed coupling reactions. In Buchwald-Hartwig aminations, unprecedented activities for the amination of aryl chlorides were reached at room temperature. The speed of formation of the catalytically active mono-YPhos palladium species allowed for some of the amination reactions to be completed in only a few minutes. Adjustment of the ligand design enabled the use of a large variety of different aryl and alkyl amines of different steric demands. Furthermore, the YPhos ligands in general showed high activities and selectivity in the coupling of a variety of carbon nucleophiles with aryl chlorides, bromides, and triflates. This enabled the development of efficient reaction protocols for the α-arylation of unhindered ketones and the coupling of Grignard and zinc reagents as well as the first efficient coupling of chloroarenes with alkyllithium compounds. This Account summarizes the recent development of YPhos ligands and their application in gold and palladium catalysis. We also hope to stimulate further use of this ligand platform in catalysis in the future.

Ylide-Substituted Phosphines: A Platform of Strong Donor Ligands for Gold Catalysis and Palladium-Catalyzed Coupling Reactions