Water, palladium -catalysed reactions

Another palladium catalysed reaction that has been successfully performed in water is the direct coupling of acid chlorides with alkynes.Copper is used as a CO catalyst and the choice and use of a surfactant are essential to the success of the reaction (Figure 3.10). 

The standard Heck conditions shown in the example above " ° illustrate a common cause of confusion in understanding palladium-catalysed reactions, for while Pd(0) is actually involved in the catalytic cycle, palladium(II) acetate is generally used as an ingredient. This is just, a matter of convenience because palladium acetate is stable and easily stored it is reduced to Pd(0) by the phosphine (with a trace of water) or triethylamine in situ in a preliminary, initiating step. 

Butadiene reacts with primary or secondary amines (/.e., R R NH) in the presence of [Pd(acac)2]+PPh3 to give 94% CH2=CH(CH2)3CH=CHCH2-NR R. Similar palladium-catalysed reactions of isoprene with diethyl-amine and isoprene with 3,3-dimethyldiaziridine, Me2CN(H)NH, have been reported. In the presence of traces of water, Pd(OAc)2+3.5 PPh3 catalyses reaction (22) the catalyst also isomerizes (23) to (22). ... 

Heck-, Suzuki- and Stille-type Couplings - The Heck reaction, palladium-catalysed coupling of aryl or vinyl halides with alkenes or alkynes, is an extremely useful synthetic method. Only recently have Heck reactions been performed in aqueous media, probably due to the perception that water must be carefully... 

Reductive coupling of iodonium salts catalysed by a palladium-zinc system also produced biaryls in good yield [38]. Also very effective was the palladium-catalysed cross-coupling of iodonium salts with sodium tetraphenylborate in water [39]. The reaction of 3-indolyl phenyliodonium trifluoroacetate with several alkyl and aryl lithium reagents gave 3-substituted indoles [40] ... 

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. 

A further evidence on the acceleration enjoyed by a typical Pd-catalysed reaction, the Heck reaction, in an ionic phase ( V-mcthyl-Y.Y. V.-trioctylammonium chloride or Aliquat 336) is found in a triphasic protocol developed by Tundo and coworkers. 7b.The arylation of electron poor olefins is catalysed by palladium supported on charcoal (Pd/C) and is carried out in the heterogeneous isooctane/Aliquat 336/water system (Figure 27). Under this multiphasic condition, Aliquat 336 forms a third liquid phase between the organic and the aqueous phase that traps the catalyst. The use of phosphines is not necessary. As a matter of fact, Aliquat 336 incorporates the solid-supported catalyst and ensures an efficient mass transfer between the bulk phases resulting in an increase of the reaction rate of an order of magnitude compared to the reaction in the absence of the ionic liquid. A determing role is played by the base while I LN drives the reaction towards the formation of ethyl cinnamate, reaction carried out in the presence of KOH lead to formation of Ullmann dimerisation products. 

The heteroaryl derivatives of boron, silicon, and tin, which show related patterns of reactivity, have found considerable application in synthesis. Unlike lithium compounds, they are generally fairly stable to air and water but will undergo a range of selective reactions under relatively mild conditions. Heteroaryl boronic acids and stannanes are particularly useful as the organometallic component in palladium-catalysed coupling reactions (section 2.7.2.2) heteroaromatic silanes such as 2-... 

Much research has been carried out on the Ugand-free palladium-catalysed Suzuki reaction. Already in 1989, Beletskaya reported a Ugand-free Suzuki reaction in water, between iodobenzoates and phenylboronic acid using Pd(OAc)2 as catalyst [81]. Later, Novak took up the quest to develop a highly active catalyst for the Suzuki reaction and since he noted that this reaction suffers from phosphine inhibition he decided to test three Ugand-free palladium catalyst precursors Pd(OAc)2, [(Ti -CsHsjPd PdCl]2, and Pd2(dba)3.QH6 [82]. All three catalysts performed well in the Suzuki reaction between 4-nitro-iodobenzene and phenylboronic acid. In the reaction with 4-nitro-bromobenzene the first and last catalyst were clearly superior with yields of 96-98% (Scheme 10.7). Novak suggests that... 

The three basic steps in the palladium-catalysed Suzuki-Miyaura reaction involve oxidative addition, transmetalation, and reductive elimination. A systematic study of the transmetalation step has found that the major process involves the reaction of a palladium hydroxo complex with boronic acid, path B in Scheme 3, rather than the reaction of a palladium halide complex with trihydroxyborate, path A. A kinetic study using electrochemical techniques of Suzuki—Miyaura reactions in DMF has also emphasized the important function of hydroxide ions. These ions favour reaction by forming the reactive palladium hydroxo complex and also by promoting reductive elimination. However, their role is a compromise as they disfavour reaction by forming of unreactive anionic trihydroxyborate. A method for coupling arylboronic acids with aryl sulfonates or halides has been developed using a nickel-naphthyl complex as a pre-catalyst. It works at room temperature in toluene solvent in the presence of water and potassium carbonate. ... 

Neutral ionic liquids are excellent solvents for the palladium catalysed coupling of alkyl halides with alkenes (Heck reaction). The special advantage of using neutral ionic liquids is that many palladium complexes are soluble in ionic liquids and that the products or product of the reaction can be extracted with water or alkane solvents. So the expensive catalyst can be recycled compared to the routine Heck reaction in which the catalyst is lost at the end of the reaction (see Section 12.11). A typical Heck reaction is given (Scheme 7). 

The direct catalytic synthesis of azo or azoxy compounds from nitro compounds is not a common reaction. Apart from Fe(CO)5, Ru3(CO)i2 has been reported to catalyse reaction 17 [113], but mononitro compounds failed to give appreciable amounts of azo compounds with this catalyst. Very recently, however, it has been reported that good selectivities (up to 72.5 %) in azoxybenzene can be obtained by using Pd(Phen)(OTf)2 as catalyst in the presence of an excess (best 12.5 1 with respect to palladium) of sodium benzoate [114]. Conditions were 60 bar and 135 °C in methanol as solvent (note that no water was added). The principal by-product was methyl phenylurethane, with minor amounts of aniline and diphenylurea being also formed. The study was principally aimed at evidencing the effect of benzoate anion on the synthesis of carbamates, so no attempt has apparently been made to optimise the experimental conditions for the synthesis of azoxybenzene and better yields can be probably obtained under different conditions. 

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