Dialkylbiaryl Phosphine Ligands

Dialkylbiaryl phosphine ligands were first described by Stephen L. Buchwald in 1998 for their use in palladium-catalyzed coupling reactions to form carbon-nitrogen and carbon-carbon bonds. Until this point, previously reported ligands such as P(o-Tol)₃ required harsh conditions to catalyze a limited scope of C-N bond forming reactions. Since this initial report, extensive work has been done by both Buchwald and other laboratories to develop ligands of this type which can catalyze a wide range of reactions including Buchwald-Hartwig amination, etherification, arylation, Negishi cross-coupling, and Suzuki-Miyaura cross-coupling. Today, these ligands are widely used in both academia and industry.

All of the Buchwald ligands are air-stable crystalline solids. Many can be bought commercially or synthesized in only a few steps from inexpensive starting materials. One pot protocols have been developed for the synthesis of these ligands and have been employed on >10 kg scales

Both the steric bulk and electron-rich nature of these ligands have been attributed to their enhanced catalytic activity over other ligands in Palladium-catalyzed coupling reactions. Extensive experimentation by the Buchwald group has shown that minor changes to the structure of these ligands can dramatically alter their catalytic activity in cross coupling reactions with different substrates. This has led to the evolution of multiple ligands that are tailored for specific trasformations.

DavePhos is the first reported dialkylbiaryl phosphine ligand and was initially used in mild Pd-catalyzed Suzuki-Miyaura cross-coupling reactions as well as Buckwald-Hartwig aminations. This ligand has additionally been used to catalyze a wide array of reactions, including the -arylation of ketones and esters, borylation of aryl chlorides, and the arylation of indoles.

Many additional modified versions of DavePhos have been synthesized. tBuDavePhos has been shown to be an even more reactive variant of DavePhos in the room temperature Suzuki-Miyaura coupling of aryl bromides and chlorides. The biphenyl equivalent (PhDavePhos) is also available as an alternative catalyst in Suzuki-Miyaura couplings.

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