Suzuki reactions water

The Suzuki reaction has been successfully used to introduce new C - C bonds into 2-pyridones [75,83,84]. The use of microwave irradiation in transition-metal-catalyzed transformations is reported to decrease reaction times [52]. Still, there is, to our knowledge, only one example where a microwave-assisted Suzuki reaction has been performed on a quinolin-2(lH)-one or any other 2-pyridone containing heterocycle. Glasnov et al. described a Suzuki reaction of 4-chloro-quinolin-2(lff)-one with phenylboronic acid in presence of a palladium-catalyst under microwave irradiation (Scheme 13) [53]. After screening different conditions to improve the conversion and isolated yield of the desired aryl substituted quinolin-2( lff)-one 47, they found that a combination of palladium acetate and triphenylphosphine as catalyst (0.5 mol %), a 3 1 mixture of 1,2-dimethoxyethane (DME) and water as solvent, triethyl-amine as base, and irradiation for 30 min at 150 °C gave the best result. Crucial for the reaction was the temperature and the amount of water in the... 

Recently, Suzuki-type reactions in air and water have also been studied, first by Li and co-workers.117 They found that the Suzuki reaction proceeded smoothly in water under an atmosphere of air with either Pd(OAc)2 or Pd/C as catalyst (Eq. 6.36). Interestingly, the presence of phosphine ligands prevented the reaction. Subsequently, Suzuki-type reactions in air and water have been investigated under a variety of systems. These include the use of oxime-derived palladacycles118 and tuned catalysts (TunaCat).119 A preformed oxime-carbapalladacycle complex covalently anchored onto mercaptopropyl-modified silica is highly active (>99%) for the Suzuki reaction of p-chloroacetophenone and phenylboronic acid in water no leaching occurs and the same catalyst sample can be reused eight times without decreased activity.120... 

For the solution-phase preparation of functionalized tropanylidenes, the authors simply dispensed solutions of the bromo N-H precursor in 1,2-dichloroethane (DCE) into a set of microwave vials, added the aldehydes (3 equivalents) and a solution of sodium triacetoxy borohydride in dimethylformamide (2 equivalents), and subjected the mixtures to microwave irradiation for 6 min at 120 °C. Quenching the reductive amination with water and subsequent concentration allowed a microwave-assisted Suzuki reaction (Section 6.1.2) to be performed directly on the crude products [295]. 

A number of Suzuki reactions (see Scheme 10.9) have been conducted in ionic liquids using Pd(PPh3)4 as the catalyst at 30 °C [10], Although the catalyst is neutral, the ionic liquid-catalyst solution can be used repeatedly without a decrease in activity. In fact, the catalyst shows a significant increase in activity compared to when it is used in conventional organic solvents. Another attractive feature of the system is that NaHC03 and Na[XB(OH)2] (X = halide) by-products can be removed from the ionic liquid-catalyst phase by washing with water. 

The palladium-catalyzed coupling of boronic acids with aryl and alkenyl halides, the Suzuki reaction, is one of the most efficient C-C cross-coupling processes used in reactions on polymeric supports. These coupling reactions requires only gentle heating to 60-80 °C and the boronic acids used are nontoxic and stable towards air and water. The mild reaction conditions have made this reaction a powerful and widely used tool in the organic synthesis. When the Suzuki reaction is transferred to a solid support, the boronic add can be immobilized or used as a liquid reactant Carboni and Carreaux recently reported the preparation of the macroporous support that can be employed to efficiently immobilize and transform functionalized arylboronic adds (Scheme 3.12) [107, 246, 247]. 

In a modified version of the Suzuki reaction arylboronates or boranes are utilized instead of arylboronic acid. Under the action of phosphine-free palladium catalysts NaBPh4 and tra(l-naphtyl)borane were found suitable phenyl-sources for arylation of haloaromatics in fully or partially aqueous solutions at 20-80 °C with good to excellent yields (Scheme 6.12) [32-34]. Aryl halides can be replaced by water-soluble diaryliodonium salts, At2IX (X = HSO4, BF4, CF3COO) in the presence of a base both Ar groups take part in the coupling [35]. 

Boronic acids can be reversibly esterified with resin-bound diols (Figure 3.15). The resulting boronic esters are stable under the standard conditions of amide bond formation, but can be cleaved by treatment with water under acidic or neutral conditions to yield boronic acids. Treatment of the resin-bound boronic esters with alcohols yields the corresponding boronic esters [197]. Resin-bound boronic esters are suitable intermediates for the Suzuki reaction [198], Treatment with H202 leads to the formation of alcohols (Entry 8, Table 3.36), while treatment of resin-bound aryl boronates with silver ammonium nitrate leads to the conversion of the C-B bond into a C-H bond (Entry 14, Table 3.46). 

Scheme 2.10 Ligand free Suzuki reaction in water.

Leadbeater and Marco also undertook to optimise the reaction conditions for ligand-free Suzuki reactions in water using both aryl bromides and chlorides. Comparisons between reactions performed under microwave irradiation and oil-bath heating led to the conclusion that the yields were identical or better with oil baths when aryl bromides were used as aryl precursors. However, comparisons between microwave and oil-bath heating with aryl chlorides as starting material clearly favoured the microwave technique38. 

Leadbeater, N.E. and Marco, M., Ligand-free palladium catalysis of the Suzuki reaction in water using microwave heating, Org. Lett., 2002,4, 2973-2976. 

Superfund sites 160, 277, 407-8, 552 surface charges 47-52 surface waters see lakes rivers and streams Suzuki reaction 25... 

Salen-like ligands have also been used to complex, and hence immobilize, a number of metals onto polystyrene and silica for use in a variety of cross-coupling reactions. The salen-palladium complex 32 was used in Suzuki reactions (Figure 4.7). The column containing the immobilized catalyst was heated to 1000 C in a water bath and the reagents were recirculated continuously at a flow rate of 6 pi/min for 5 h, resulting in conversions in the range of 65-75% [154],... 

Like the Heck reaction, the Suzuki coupling can use water as the solvent. Water-based Suzuki reactions are attractive both for industrial processes and for labs that want to minimize the purchase and disposal of toxic solvents. The following examples show the variety of combinations that can be coupled using Suzuki reactions. 

Some of the most widely studied organic reactions at this time are palladium catalysed carbon-carbon cross coupling reactions, which have been extensively investigated in water. For example, palladium catalysed Suzuki reactions can be performed in water in the presence of poly (ethylene glycol) (PEG). It should be noted that the PEG may be playing the role of a surfactant (PTC) and/or a support for the metal catalyst in water. Interestingly, in this example, no phosphine is needed and the products are easily separated and the catalyst phase reused. Unfortunately, diethyl ether was used to extract the product and as this solvent is hazardous (low flash point and potential peroxide formation), the overall process would be greener if an alternative solvent could be used. 

The Suzuki reaction has already found a first industrial application [24], after the catalyst Pd(TPPTS)a n HaO became available [25], In a two-phase procedure, the water-soluble catalyst effects the C-C coupling of arylboronic acis with aryl chlorides to form pharmaceutical intermediates. The Suzuki C-C cross-coupling is on the way to industrial perfection. Since the basic mechanistic features are clear by now, it is desirable that the catalysts are easy to prepare, easy to handle, and cheap, and that they bear cr-donor type ligands of which at least one does not dissociate from the metal throughout the catalytic cycle. Thus the Suzuki coupling will be seen in the syntheses of a growing number of fine chemicals and pharmaceuticals in due course. 

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