Suzuki cross-coupling in aqueous media

Abstract

We report a simple and efficient procedure for the ligand-free as well as ligand-assisted Suzuki reaction in both pure water and aqueous media. The cross-coupling reactions proceed successfully using phenylboronic acid or potassium phenyltrifluoroborate as a nucleophilic coupling partner. The method can be effectively applied to both activated and deactivated aryl halides yielding quantitative conversions. The catalytic activity of couplings performed in pure water increases when utilizing supramolecular additives, but decreases under standard phase-transfer conditions. Finally, the palladium loading is reducible from 3.0 mol% to 0.4 mol% without any loss of conversion.

Green chemical synthesis of Pd nanoparticles for use as efficient catalyst in Suzuki‐Miyaura cross‐coupling reaction

“…However, 62% (Table , entry 1) of yield was isolated after a span of 12 hr. The low yield of the product led us to check the effect of co‐solvent on the reaction because; it has been reported that the addition of co‐solvent to an aqueous system assist in the complete dissolution of the organic substrates, and thereby increase the efficiency of the reaction . Thereby, in the next assessment we checked the effectiveness of different alcoholic co‐solvents like ethanol, isopropanol, methanol, etc.…”

“…For these reasons, the focus is to make the experimental conditions more environmentally benign and to develop ligand‐free palladium catalysts. Consequently, many studies have been engaged in recent times to search for the effective solvents in the context of green chemistry . Water is commonly considered as a benign solvent in view of its non‐toxicity and abundant natural occurrence.…”

“…Around 80% of the chemical waste from a reaction mixture corresponds to the solvent. Therefore, the use and release of clean water instead of organic solvents is the significant concern with respect to environmentally friendly organic synthesis . Recently, many reports have been published on the successful use of Pd NPs synthesized by plant extract as catalysts in cross‐coupling reactions in water and/or a water‐alcohol mixture .…”

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

“…This observation could be presumably due to the steric effects between the amino group and the adjacent bromine atom (Entry 9, Table 8). 69 The current protocol was not as effective for the Suzuki couplings of 4-bromobenzylamine (an aliphatic amine substrate), 2- 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 16 amino-5-bromopyridine and 4-amino-2-bromopyridine (Entries 10-12, Table 8). Only a 13% yield was achieved with 4-bromobenzylamine while the yields associated with 2-amino-5-bromopyridine and 4-amino-2-bromopyridine were 37% and 29%, respectively.…”

“…[57][58][59][60][61][62][63][64][65][66][67][68][69] In addition, a clear answer has not been provided on whether the current ligand-free/aqueous protocols are effective for the Suzuki couplings of 6 unprotected basic nitrogen containing substrates at scales greater than a few milliliters. Herein, we report 100-mL scale palladium-catalyzed Suzuki reactions with no added ligand in neat water involving four model substrates, three of which contain basic nitrogen centers.…”