Heck couplings solvent

Dioxane is an equally suitable solvent for these Heck couplings (and is the solvent used in the published procedures) however, due to the lower cost and the lower toxicity of toluene, it was chosen as the solvent for these reactions. 

General procedure for Heck coupling. A mixture of POPd (16.0 mg, 6 mol%), quinoline derivative (0.56 mmol), tert-butyl acrylate (356 mg, 2.8 mmol), and base (0.61 mmol) was stirred in 5 mL of anhydrous DMF at 135 °C for 24 h. The reaction mixture was allowed to cool to room temperature, quenched with water, and extracted with Et20. The combined organic layers were washed with water, dried over MgS04, and the solvents were removed under vacuum. The crude products were purified by flash chromatography on silica gel. 

A very recent addition to the already powerful spectrum of microwave Heck chemistry has been the development of a general procedure for carrying out oxidative Heck couplings, that is, the palladium)11)-catalyzed carbon-carbon coupling of arylboronic acids with alkenes using copper(II) acetate as a reoxidant [25], In a 2003 publication (Scheme 6.6), Larhed and coworkers utilized lithium acetate as a base and the polar and aprotic N,N-dimethylformamide as solvent. The coupling... 

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]. 

As mentioned in the previous section, there are good reasons to search for new reaction conditions for Heck and related reactions, which permit catalyst recovery, the use of less toxic solvents, and simpler product recovery. The use of liquid or supercritical (SC) CO2 addresses all of these issues [171]. Until recently, however, the use of supercritical COj had been limited to organometallic Pd complexes functionalized with perfluorinated ligands [172-174], due to the limited solubility of metal colloids in CO2, and often required the use of water as a co-solvent [175]. The work described here shows that dendrimers can be used to solubilize Pd nanoclusters in liquid and SC CO2. This new finding opens the door to the combined benefits of a catalyst that promotes Heck couplings, but without the need for toxic ligands or solvents. 

Heck coupling of phenyl iodide with alkenes Pd(OCOCH3)2/ P(C6H5)3 B[(CH3CH2C6F13)n (n = 1,2) Solvent replacement Carroll and Holmes (1998)... 

Heck coupling of phenyl iodide with acrylates Pd(02CCF3), Pd[CF3C(0)CHC(0)CF3]2 Solvent replacement Shezad et al. (1999)... 

Scheme 6.8 Effect of solvent on the regioselectivity of the Heck coupling between butyl vinylether and 1-bromonaphthalene...

As with all solvent alternatives discussed in this book, palladium catalysed C-C bond-forming reactions in RTILs have been studied at length. Because of the low volatility of ionic liquids and their rapid dielectric heating upon microwave irradiation, reaction times for Heck couplings have been significantly reduced by combining the two technologies. ... 

Blaser and Spencer used aroyl halides in place of aryl halides, with aroyl chlorides being of specific interest as ubiquitous, relatively cheap compounds ( Blaser reaction ) [24], This latter reaction is normally conducted in aromatic solvents phosphines are not used here as catalyst ligands since they fully inhibit the reaction. In the same way, benzoic acid anhydrides can be used as the aryl source in combination with PdCl2 and catalytic amounts of NaBr [79]. In this reaction, one of the arenes is used in the coupling reaction by elimination of CO, whereas the other benzoate serves as the base. The benzoic acid thus formed can easily be recycled into the anhydride. The use of aryl and vinyl triflates according to Cacchi [25] and Stille [26] extends the scope of the Heck coupling to carbonyl compounds phenol derivatives act via triflate functionalization as synthetic equivalents of the aryl halides. The arylation of cyclic alkenes [27], electron-rich vinyl ethers [28], and allylic alcohols [29] is accessible through Heck reactions. Allylic alcohols yield C-C-saturated carbonyl compounds (aldehydes) for mechanistic reasons (y9-H elimination), as exemplified in eq. (6). 

A main question - not yet really considered - concerns the inertness of ionic liquids. Not only are the anions potential ligands, especially for neutral and cationic metal complexes one has also to take into consideration what is known for cations like (imid)azolium formation of carbene complexes via deprotonation is a rather facile process especially if ligands of sufficient basicity are present, e. g., -OR, -NR2. Therefore, several of the impressive catalytic results [113] deserve mechanistic investigation to find out whether they are really limited to the ionic liquid effects. For example, solvent and complexation effects are likely to enhance one another in the Heck coupling reactions that were run in the presence of Structure 18, Scheme 11 [115]. 

There are a few efficient methods for the stereoselective synthesis of vinyl halides, and this transformation remains a synthetic challenge. Research by S. Roy showed that the Hunsdiecker reaction can be made metal free and catalytic catalytic Hunsdiecker reaction) and can be used to prepare ( )-vinyl halides from aromatic a,p-unsaturated carboxylic acids. The unsaturated aromatic acids were mixed with catalytic amounts of TBATFA and the A/-halo-succinimide was added in portions over time at ambient temperature. The yields are good to excellent even for activated aromatic rings which do not undergo the classical Hunsdiecker reaction. The fastest halodecarboxylation occurs with NBS, but NCS and NIS are considerably slower. The nature of the applied solvents is absolutely critical, and DCE proved to be the best. This strategy was extended and applied in the form of a one-pot tandem Hunsdiecker reaction-Heck coupling to prepare aryl substituted (2 ,4 )-dienoic acids, esters, and amides. 

Heck reaction. Solvent-free conditions with microwave irradiation have been developed for the Heck reaction. Phosphites are excellent ligands such that even electron-deficient aryl chlorides can be used to couple with different alkenes. Isoquinolines are formed by using the more conventional procedure note the same 3-(o-iodobenzylamino)acrylic esters give dihydroisoindole derivatives when they are exposed to Bu,SnH-AIBN. A combination of BUjP and dppp together with /-Pr NEt constitutes support for Pd(OAc)2 in an intramolecular coupling which leads to benzophenanthridines. ... 

A special type of Heck coupling was demonstrated vstith 1,2-allenyl carboxylic acids, which led to butenolides. Ma et al. [146] demonstrated a dramatic dependence of the reaction on the base and solvent used. In acetonitrile, intramolecular addition of the carboxylic acid to the adjacent allenic group proceeded without a subsequent Heck reaction. In toluene as solvent, especially in the presence of Bu4NBr, the desired butenohde was obtained. 

A co-solvent that is poorly miscible with ionic liquids but highly miscible with the products can be added in the separation step (after the reaction) to facilitate the product separation. The Pd-mediated Heck coupling of aryl halides or benzoic anhydride with alkenes, for example, can be performed in [BMIM][PF(l], the products being extracted with cyclohexane. In this case, water can also be used as an extrachon solvent, to remove the salt by-products formed in the reaction [18]. From a practical point of view, the addition of a co-solvent can result in cross-contamination, and it has to be separated from the products in a supplementary step (distillation). More interestingly, unreacted organic reactants themselves (if they have nonpolar character) can be recycled to the separation step and can be used as the extractant co-solvent. 

Zhang and Daves reported that water-containing solvents (H20/EtOH, 1 1) are more effective than conventionally used solvents (DMF, acetronitrile) in certain Heck couplings of iodoheterocycles and glycals or other cyclic enol ethers in the... 

The IMI OMC production process involves two main chemical transformations (Scheme 3) [24]-bromination of commercial anisole produces p-bromoanisole (p-BA) with para-regioselectivity > 97 %. Heterogeneous Heck coupling between the p-BA and commercially available octyl acrylate (OA), in the presence of a Pd/C catalyst, with Na2C03 as HBr sponge, and A-methylpyrrolidone (NMP) as the polar, non-protic solvent, furnishes OMC. 

Table 4 Variation of the solvent Heck coupling of p-bromoacetophenone with...

Figure 2 investigation of activity and Pd leaching as a function of time Heck coupling of bromobenzene with styrene reaction conditions bromobenzene (200 mmol), styrene (300 mmol), sodium acetate (240 mmol), 1.0 mol% Pd, catalyst 3W, DM Ac (200 mL) T = 140 °C styrene was added last after catalyst, solvent, and bromo benzene had reached 140 °C. 

The palladium catalyzed Heck coupling reaction induced by MW irradiation under solvent-free liquid-liquid PTC conditions, in the presence of potassium carbonate and a small amount of [Pd(PPh3)2Cl2]-TBAB as catalyst, has recently been reported [112]. The arylation of alkenes with aryl iodides proceeded smoothly to afford exclusively trans products in high yields (86-93%) (Eq. 78). 

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