Systematic Variation of Bidentate Ligands Used in Aryl Halide Amination. Unexpected Effects of Steric, Electronic, and Geometric Perturbations

Abstract

This paper presents effects of varying bidentate phosphine steric properties, electronic properties, and bite angle on product ratios in the amination of aryl bromides. Comparisons of the ratios of amine products to dehydrohalogenation products showed that catalysts containing electron rich, modestly hindered phosphines with small bite angles (∼90°) gave the best selectivities. Surprisingly, the arene side product formed from reaction of alkylamines deuterated in the N-H position or deuterated in the position R to the nitrogen showed low levels of deuterium incorporation in many examples. Steric properties and ligand bite angle had the greatest impact on the selectivity for monoarylation versus diarylation of primary amines; ligands with small bite angles gave higher monoarylation-to-diarylation ratios, as did ligands with increased steric bulk. Electron poor or sterically hindered bidentate phosphines reduced the amount of product resulting from aryl exchange of electron rich palladium-bound arenes with those of aryl groups on the phosphine ligands.

Pd‐Catalyzed Aryl Amination Mediated by Well Defined, N‐Heterocyclic Carbene (NHC)–Pd Precatalysts, PEPPSI

“…[5] In recent years, substantial progress has been achieved in optimizing the phosphine ligands' structure to achieve high yields with a diverse array of substrates ( Figure 1). [8][9][10][11][12][13][14][15] Presently, Buchwalds biaryl phosphine 6 is shown to have the broadest applicability in Pd-catalyzed amination. [13] Recently, the use of N-heterocyclic carbenes (NHCs) as ligands in Pd-catalyzed aminations have shown much promise.…”

Pyrazole-based P,N-ligand for palladium catalyst: applications in Suzuki coupling and amination reactions

“…Recently, significant developments in Suzuki coupling reaction 1 and amination of aryl halide or triflate have been reported by Buchwald 2 and Hartwig 3 . That stereoelectronic effects and the bite angle 4 of the employed ligands are significant factors for efficient coupling reactions, have been illustrated by a recent set of electron-rich and functionalized phosphine ligands displayed in Fig-1. For example, Buchwald has shown that 2-dicyclohexylphosphanyl-2′-dimethylaminobiphenyl, ii, is an excellent ligand 2e,2f for coupling of aryl bromides and chlorides with boronic acids at room temperature.…”

Palladium‐Catalyzed Three‐Component Diaryl Sulfone Synthesis Exploiting the Sulfur Dioxide Surrogate DABSO

“…As expected, a more electron-rich phosphine gave more arylphenyl transfer product (entry 6). [21] Electron-poor phosphines, which have been reported to suppress transfer for the arylation of ureas, [20] gave similar or a small increase in selectivity as hoped, but for the more selective reaction, the conversion was poor (entries 8-10). However, by switching to the aryl bromide substrate in place of the iodide substrate, and increasing the temperature of the reaction, full conversion was achieved with high selectivity when using the 3,5-bis(CF 3 )-substituted XantPhos 5 f (entry 13).…”

“…Such exchange processes are known in arylation of electronpoor nucleophiles and in Suzuki couplings. [19][20][21][22] Conditions for the palladium coupling step were fully explored, with the choice of base, additive, solvent, palladium source, and temperature being investigated. However, no improvement in selectivity whilst maintaining good conversion of starting material was observed.…”