Alternative Biarylphosphinesfor Use in the Palladium-Catalyzed Amination of Aryl Halides

Abstract

Two families of biarylphosphine ligands were prepared for use in the Pd-catalyzed amination reaction. The first series investigated was derived from N-phenylpyrroles, and the second, was derived from N-phenylpyrazoles. While the pyrrole ligands were not as general in substrate scope, one of the readily prepared pyrazole ligands (R = t-Bu) was found to have a fairly broad substrate scope.

Palladium‐Catalyzed CN and CO Coupling–A Practical Guide from an Industrial Vantage Point†

“…Heterocyclic subtypes of Buchwalds biphenyl-based ligand systems were reported by Singer [35] in 2003. These pyrrole-and pyrazole-based systems are characterized by the synthetic ease of their formation while their use still requires the combination with the strong base tBuONa.…”

“…[16] Other additives reported by Buchwald are alcohols, especially the low nucleophilic tert-butyl alcohol to increase conversion. [35,52,68] Mixed solvent systems can have a great impact mostly on the degree of conversion in certain amination reactions, often owing to the solubilities of the components. Sometimes it is beneficial to premix the catalyst and the ligand in a suitable solvent such as THF to allow time for the formation of the catalytically active complex before adding this to the actual reaction mixture.…”

“…[66, 16,42,33] As derivatives of this ligand system, heterocyclic biphenyl ligands first introduced by Singer [35] and further elaborated by Beller [36] show wide scope in the amination of aryl chlorides, with no obvious advantage in reactivity over the biphenyl ligands, however.…”

Dialkylphosphinoimidazoles as New Ligands for Palladium‐Catalyzed Coupling Reactions of Aryl Chlorides

“…Notable recent catalyst developments for the use of aryl chlorides [6] have been reported by Bedford, [7] Buchwald, [8] Fu, [9] Herrmann, [10] Nolan, [11] us, [12] and others. [13] In addition, our group has reported the use of di-(1-adamantyl)-n-butylphosphine [12c,14] and N-aryl-2-(dialkylphosphino)pyrrole/indole as highly active ligands for the coupling of a wide range of aryl chlorides with phenylboronic acid [12a] and amines, [15] respectively. Nevertheless, there is a continuous interest in efficient but more practical new ligands.…”

An Improved Synthesis of Imidazo[4,5‐b]pyridines and Imidazo[4,5‐b]pyrazines by Palladium Catalyzed Amidation using Xantphos in a 1,4‐Dioxane:tert‐Amyl Alcohol Solvent System

“…asc.wiley-vch.de choice of additive was determined based on previous literature precedents demonstrating the effectiveness of binary solvent systems. [31,33,34] The Fu group has also demonstrated the advantage of mixed protic and aprotic solvent systems. [35][36][37] First, mixtures of toluene and t-AmOH were examined.…”