Study of a New Rate Increasing “Base Effect” in the Palladium-Catalyzed Amination of Aryl Iodides

Abstract

Evidence for an interphase deprotonation of Pd(II)-amine complexes with weak carbonate base has been gained for the first time. When a rate-limiting deprotonation step is involved in the catalytic cycle, controlling the structure (shape and size of the particles) and/or molar excess of the carbonate base used can significantly increase the reaction rate of Buchwald-Hartwig aminations. By taking such a "base effect" into account a general protocol for the intermolecular amination of aryl iodides with all types of amines has been developed based on a standard Pd-BINAP catalyst, using cesium carbonate as the base.

Dialkylbiaryl phosphines in Pd-catalyzed amination: a user's guide

“…In non-polar solvents such as toluene, in which these inorganic bases have very low solubility, the deprotonation of the Pd-bound amine is thought to occur at the solid-liquid boundary. 149 In this situation, the particle size and shape of the inorganic base can be important in determining the rate and ultimate success of a cross-coupling reaction. 150, 151 This topic has seen the most detailed discussion by Maes in the use of Cs 2 CO 3 in Pd-catalyzed amination with BINAP as ligand, 149 although the findings are almost certainly applicable to biaryl phosphine ligands.…”

“…149 In this situation, the particle size and shape of the inorganic base can be important in determining the rate and ultimate success of a cross-coupling reaction. 150, 151 This topic has seen the most detailed discussion by Maes in the use of Cs 2 CO 3 in Pd-catalyzed amination with BINAP as ligand, 149 although the findings are almost certainly applicable to biaryl phosphine ligands. Cs 2 CO 3 from different suppliers exhibited varying reactivity and SEM imaging of the base showed a correlation between the particle properties and the activity of the base.…”

Synthesis of (R)‐(–)‐2‐Fluoronorapomorphine — A Precursor for the Synthesis of (R)‐(–)‐2‐Fluoro‐N‐[11C]propylnorapomorphine for Evaluation as a Dopamine D2 Agonist Ligand for PET Investigations

“…This feature may be attributed to the "base effect" hypothesis which suggests that liquid-solid interphase deprotonation of the palladium(ii)-amine complex is the rate-determining step. [32] It was found that using 1.2 equiv. benzophenone imine, 0.04 equiv.…”

Plant coumarins: VII. Amination of oreoselone trifluoromethanesulfonate

“…Replacement of DMF by acetonitrile and lowering the temperature (85°C, 10 h) did not result in increased yield of IIIb. The amination of I using a different catalytic system, Pd(OAc) 2 /BINAP (2/8 mol %), and cesium carbonate as base (solvent toluene) [17] was characterized by considerably lower yield of the target product. Thus the most efficient were Pd(OAc) 2 /BINAP as catalytic system and triethylamine as base.…”