Aqueous solvents Heck reactions

In the Heck reactions discussed above it was essential to use polar aprotic solvents such as acetonitrile or DMF if high regioselectivity was to be achieved. In other Heck couplings the use of water as a solvent has recently gained attention. The advantages of water compared with standard organic solvents are many - it is, for example, cheap and nontoxic - but its usefulness extends only over a number of well-defined applications, partly because of problems with the solubility of the reactants and catalysts. The development of aqueous catalytic systems is, consequently, an important field [21]. 

Initially, only dipolar aprotic solvents such as W,A -dimethylformamide (DMF), N-methylpyrrolidinone (NMP), dimethyl sulfoxide (DMSO), and acetonitrile (MeCN) were common (Table 3-2). However, the presence of water has been found to accelerate certain Heck reactions [17], and consequently the development has gone to water-soluble tiiarylphosphane ligands (e.g triphenylphosphane w-trisulfonate sodium salt (TPPTS) [18a], with which many alkene arylations succeed superbly in aqueous solvent mixtures [19]. 

Heck reactions are compatible with water (see Chapter 3.2.4) [35], which increases the speed of reaction in the presence of quaternary ammonium salts [36 a]. It is not surprising, then, that aqueous solvents (e. g. CH3CN/H2O) and water-soluble catalysts such as Pd(TPPTS)3 where TPPTS = P(C6H4-m-S03Na)3 [35, 67] can be employed successfully (eq. (10)). However, only aryl and vinyl iodides and aromatic diazonium salts (generated in situ from arylamines in aqueous media) are, up to the present, accessible to this method [36 b-h]. 

Erdelyi, M., Gogoll, A. Rapid Microwave Promoted Sonogashira Coupling Reactions on Solid Phase. J. Org. Chem. 2003, 68, 6431-6434. Najera, C., Gil-Molto, J., Karlstroem, S., Falvello, L. R. Di-2-pyridylmethylamine-Based Palladium Complexes as New Catalysts for Heck, Suzuki, and Sonogashira Reactions in Organic and Aqueous Solvents. Org. Lett. 2003, 5,1451-1454. 

The PTC technique has been advantageously applied to alkylationand Pd-catalyzed arylation of alkynes. For the Heck reaction, the proper selection of Pd, base, and PTC allows a reaction in water, aqueous/organic solvent mixture, or strictly anhydrous... 

Nair and co-workers [8] have coupled of semi-continuous NF with the Heck reaction. The objective was the synthesis of trans-stilbene from styrene and iodobenzene using Pd(OAc)2(PPh3)2 as catalyst and Pjo-tolyljj as stabilizing agent. They used solvent-resistant membranes and different aqueous/solvent systems (ethyl acetate and acetone/H20 methyl tert-butyl ether and acetone/H20 tetra-hydrofuran/H20). The best conversion was obtained with the first-mentioned solvent mixture. A selectivity of 100% of trans-stilbene with a cumulative turnover number of 1200 was reported, where the rejection of the catalyst turned out to be as high as 97%. Therefore, the authors concluded that NF was a convenient technique to run catalytic reactions with catalyst recycling, since this method saves the catalyst, prevents the metal contamination of the products, and increases reactor productivity. 

The products were surprisingly similar to those found in typical organic solvents, although the isolated yields were lower (17-54% based on conversion of the iodoben-zene). A group at Clemson University have also reported aqueous Heck reactions at 260 °C and in supercritical water at 400 °C. ... 

Hence, the majority of Mizoroki-Heck reactions show a clear preference for polar media, which lends assistance to both deligation of halide and support of the palladium catalyst (1) highly Lewis basic organic solvents such as DMF, DMA, iV-methylpyrrolidone (NMP) and dimethylsulfoxide (DMSO) (2) aqueous solvents (3) ionic liquids. 

In the last decade, a lot of attention has been paid to environmental aspects. As to the Mizoroki-Heck reaction, environmentally benign media currently involved in the design of catalytic systems encompass supercritical carbon dioxide (scCOa), fluorous systems, water and aqueous systems, solvent-free systems [66]. In this context, it should be noted that the so-called solvent-free reactions are actually not literally such, but are performed in media composed of substrates and often liquid amine. This was described as early as in 1972 by Heck himself [2, 8] (microwave heated version [53]). Amines are good coordinating solvents during the reaction, the amine is transformed into amine salt, which, being a major constituent or reaction mixture in the absence of a true solvent, adds to the net media polarity. 

Ndjera, C., Gil-Molt6, J., Karlstrom, S. and Falvello, L.R. (2003) Di-2-pyridylmethylamine-based palladium complexes as new catalysts for Heck, Suzuki, and Sonogashira reactions in organic and aqueous solvents. Org. Lett., 5, 1451-4. 

BoteUa, L. and Najera, C. (2004) Synthesis of methylated resveratrol and analogues by Heck reactions in organic and aqueous solvents. Tetrahedron, 60, 5563-70. 

Gron, L.U. and Tinsley, A.S. (1999) Tailoring aqueous solvents for organic reactions Heck coupling reactions in high temperature water. Tetrahedron Lett., 40, 227-30. 

Polar aprotic solvents (Section 9.3D) such as N, N-dimethylformamide (DMF), acetonitrile, and dimethyl sulfoxide (DMSO) are commonly used. It is also possible to cany out some Heck reactions in aqueous methanol. The polar solvents are needed to dissolve the Pd(OAc)2 at the beginning of the reaction. 

It has been found that the Heck reaction can be accomplished under PTC conditions with inorganic carbonates as bases under mild conditions at room temperature. Such conditions can be used in case of substrates, like methyl vinyl ketone, which do not survive the usual conditions of Heck arylation (action of base at high temperature). Subsequently, it has been shown that the Heck reaction can be carried out in water and aqueous organic solvents, catalysed by simple palladium salts in presence of inorganic bases like K2CO3, Na2C03, NaHC03, KOH etc. ... 

The Heck reaction can be accomplished under phase-transfer conditions with inorganic carbonates as bases under very mild conditions even at room temperature. The reactions were carried out in a liquid-liquid system composed of aqueous solution of base and organic reagents without organic solvent. Later, this method was developed into a common-purpose Jeffery-Larock protocol. It has been shown that, depending on substrates and base, the phase-transfer Heck reaction can be accomplished in either an aqueous liquid-liquid or a nonaqueous solid-liquid system,t THi i though (he actual choice between these two techniques is often a matter of taste. 

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