Tetraphosphine/palladium‐catalyzed Suzuki–Miyaura coupling of heteroaryl halides with 3‐pyridine‐ and 3‐thiopheneboronic acid: an efficient catalyst for the formation of biheteroaryls

Abstract

An easily prepared tetraphosphine N,N,N′,N′‐tetra(diphenylphosphinomethyl)‐1,2‐ethylenediamine (L1) associated with [Pd(η3‐C3H5)Cl]2 affords an efficient catalyst for Suzuki–Miyaura coupling of 3‐pyridineboronic acid with heteroaryl bromides. Reaction could be performed with as little as 0.02 mol% catalyst and a high turnover number of 2500 is obtained. A wide range of substrates is investigated with satisfactory yields, and good compatibility with aminogroup‐substituted pyridines and unprotected indole is exhibited. This protocol can also be applied successfully to the reaction of heteroaryl bromides with 3‐thiopheneboronic acid. This Pd‐tetraphosphine catalyst efficiently restrains the poisoning effect from heteroaryls, and shows good stability and longevity. Copyright © 2013 John Wiley & Sons, Ltd.

Palladium-Catalyzed Suzuki Reactions in Water with No Added Ligand: Effects of Reaction Scale, Temperature, pH of Aqueous Phase, and Substrate Structure

“…The active Pd(0) particles play an important role in the mechanism of Suzuki couplings in water without added ligand. As early studies indicated, − the coupling process can be retarded by the competitive interactions between the basic nitrogen centers and Pd catalyst; meanwhile, the resulting complexes can also efficiently protect the Pd(0) from deactivation by aggregation (or amalgamation in the mercury test) and stabilize the soluble catalytic species, enabling homogeneous catalysis. The advantage of the latter effect probably overcame the negative influence of the former one under our ligand-free/water conditions.…”

“…Melting points were measured on a Mel-Temp capillary melting point apparatus. 1 H (400 MHz) and 13 C (100 MHz) NMR Spectra were recorded on a Varian Mercury Vx 400 spectrometer. Chemical shifts (δ) are reported in ppm relative to TMS and coupling constants (J) are in Hz.…”

“…Ligand complexity can vary greatly as a function of the application and reaction system requirement. For example, Suzuki reactions with substrates that contain basic nitrogen centers, such as aromatic amines and pyridines, suffer from the limitations of slow rates and low yields − due to the competitive interaction between the basic nitrogen center and the palladium catalyst. − However, the development of customized ligands that strategically incorporate bulky and electron-rich groups enable high yields with reasonable rates. ,, …”

The effects of CO2pressure and pH on the Suzuki coupling of basic nitrogen containing substrates

“…It has been reported that reaction partners containing basic nitrogen centers often react very slowly and/or produce desired coupled products in low yields. [9][10][11][12][13] In these cases, the basic nitrogen centers are postulated to coordinate with the Pd catalyst, reducing or poisoning its catalytic activity. 9,[14][15][16] As a consequence, the use of additional protection/deprotection steps or the use of expensive designer ligands is often necessary to achieve reasonable reaction rates and high yields.…”

Suzuki–Miyaura Reactions of (4-bromophenyl)-4,6-dichloropyrimidine through Commercially Available Palladium Catalyst: Synthesis, Optimization and Their Structural Aspects Identification through Computational Studies

“…On the other side, poor yields were obtained with electron-withdrawing substituents, namely boronic acids. Due to the deficiency of electrons on aryl boronic acids, the transmetalation step is slowed [50]. Moreover, the most probable side reaction which lowers the yield is protodeboronation which was reported by Kuivila for the first time in both acidic and basic media and also in the presence of metal ions which leads to the formation of Ar-H linking of aryl boronic acid instead of Ar-Ar/R bond formation with substrates [51][52][53].…”