Inverse phase-transfer catalysts

Alternatively, the Sn2 nucleophilic substitution reaction between alcohols (phenols) and organic halides under basic conditions is the classical Williamson ether synthesis. Recently, it was found that water-soluble calix[n]arenes (n = 4, 6, 8) containing trimethylammonium groups on the upper rim (e.g., calix[4]arene 5.2) were inverse phase-transfer catalysts for alkylation of alcohols and phenols with alkyl halides in aqueous NaOH solution to give the corresponding alkylated products in good-to-high yields.56... 

The water-soluble calix[n]arenes 6.3 (n = 4, 6 and 8) containing trimethylammonium groups act as efficient inverse phase-transfer catalysts in the nucleophilic substitution reaction of alkyl and arylalkyl halides with nucleophiles in water (Eq. 6.19).40 In the presence of various surfactants (cationic, zwitterionic and anionic), the reactions of different halides and ketones show that the amount of ketone alkylation is much higher and that the reactions are faster in the presence than in the absence of surfactant aggregates.41 The hydrolysis of the halide is minimized in the presence of cationic or zwitterionic surfactants. 

Reduction of carbonyl compounds can be carried out in an aqueous medium by various reducing reagents. Among these reagents, sodium borohydride is the most frequently used. The reduction of carbonyl compounds by sodium borohydride can also use phase-transfer catalysts (Eq. 8.4),10 inverse phase-transfer catalysts,11 or polyvinylpyridines12... 

Compared with esters, acid halides and anhydrides are more reactive and are hydrolyzed more readily. It is interesting to note that there is a substantial lifetime for these acid derivatives in aqueous media. Acid halides dissolved in PhCl or in PhBr shaken at a constant rate with water shows that hydrolysis occurs at the boundary between the two liquid phases.35 The reaction of benzoyl chloride (PhCOCl) and benzoate ion with pyridine A-oxide (PNO) as the inverse phase-transfer catalyst yields both the substitution product (benzoic anhydride) and the... 

Cyclodextrins are often used as inverse phase transfer catalysts [11-14]. They are able to intercalate hydrophobic substances and to transport them into a polar phase like water, where the reaction takes place. To study the influence of cyclodextrins on the isomerizing hydroformylation of frans-4-octene in the biphasic solvent system propylene carbonate/dodecane, the concentration of methylated /3-cyclodextrin was varied from 0.2 up to 2.0 mol.-% relative to the substrate frans-4-octene [24]. The results are given in Table 7. 

Higher (and supramolecular) ligands based on sugar, porphyrin, dendrimers, cyclodextrins, calix[4]arenes, etc., have also been tested for water-soluble conversions, the hydroformylation of water-insoluble olefins included [219]. In some cases the water-soluble, macromolecular cpds. act as inverse phase-transfer catalysts, e. g., when crown ethers are involved [269]. 

Monflier, E. Versatile inverse phase transfer catalysts for the functionalization of substrates in aqueous-organic two-phase systems the chemically modified 3-cyclodextrins. Rec. Res. Dev. Org. Chem. 1998, 2, 623-635. 

Monflier et al. reported very high conversion (up to 100%) and regioselec-tivity (<95%) in the hydroformylation of various water-insoluble terminal olefins such as 1-decene with Rh/tppts catalyst system in water in the presence of per(2,6-di-0-methyl)- -cyclodextrin (or Me-p-CD) [Eq. 7] [65, 66]. These high activities and selectivities were attributed to the formation of an alkene/cyclodextrin inclusion complex and to the solubility of the cyclodextrin in both the aqueous and organic layers the cyclodextrin probably plays the role of an inverse phase transfer catalyst. 

In addition to calixarenes which have been made water-soluble as new inverse phase-transfer catalysts [85], novel ligands have been designed, based on a cydo-propene moiety bearing pyridyl substituents and called [hexakis(2- or 3-pyridyl) 3 -radialene] 37. A metallosupramolecular chemistry is envisioned by the authors and the solubility in water and their stability offer innovative perspectives [86]. 

The best results in terms of activity have been obtained with cationic surfactants such as octadecyltrimethylammonium bromide. The normal to branched (njiso) aldehydes ratio was found to be very dependent on the nature of the surfactant. For example, methyl 9-decenoate hydroformylation gave methyl 11-formylunde-canoate with an n/iso aldehydes ratio of 6.1 1, 4.0 1, 2.3 1 and with anionic, amphophilic, and cationic surfactants, respectively. Interestingly, hydroformylation of this substrate has also been achieved successfully with inverse-phase transfer catalysts such as chemically modified /l-cyclodcxtrins. In this approach, the cyclodextrin forms an inclusion complex with methyl 9-decenoate and transfers the alkene into the aqueous phase. Under optimal conditions, the aldehydes are obtained in a 100% yield and in an n/iso aldehydes ratio of 2.3 1 [10]. 

The decrease in the activity with 2-ethylhexyl acrylate is more familiar and can be attributed to low mass transfer between aqueous and organic phases due to the very poor solubility of this acrylate in water. As a matter of fact, it must be noticed that the hydroformylation of this substrate can be achieved by using an aqueous-phase supported rhodium catalyst [20] or inverse-phase transfer catalysts such as... 

Nevertheless, it must be pointed out that the formation of such transient species has never been spectroscopically observed. Native CDs are effective inverse phase-transfer catalysts for the deoxygenation of allylic alcohols, epoxydation,or oxidation " of olefins, reduction of a,/ -unsaturated acids,a-keto ester,conjugated dienes,or aryl alkyl ketones.Interestingly, chemically modified CDs like the partially 0-methylated CDs show a better catalytic activity than native CDs in numerous reactions such as the Wacker oxidation,hydrogenation of aldehydes,Suzuki cross-coupling reaction, hydroformylation, " or hydrocarboxylation of olefins. Methylated /3-CDs were also used successfully to perform substrate-selective reactions in a two-phase system. 

Enhanced catalytic activity has also been observed for the hydroformylation of oct-l-ene and dec-l-ene with water-soluble phosphine-caltK[4]arene—rhodium complexes (Figure 32). " These organometallic compounds behave, not only as homogeneous metal catalysts but also as inverse phase-transfer catalysts, that is, they perform a dual functional catalysis. The olefin is believed to be included in the hydrophobic cavity and to simultaneously interact with a catalytic transition metal center coordinated to the phosphine moieties. 

Solubilization of water-insoluble substrate in the aqueous phase containing the organometalhc catalyst can be achieved by using catalytic amounts of water-soluble receptors such as cyclodextrins [1] or calixarenes [2], The beneficial effect of these water-soluble host compounds on the mass transfer is ascribed to their complexing properties and it is postulated that these compounds operate like inverse phase-transfer catalysts according to Figure 1. 

Shimizu. S. Shirakawa. S. Suzuki, T. Sasaki, Y. Water-soluble calixarenes as new inverse phase-transfer catalysts. Their application to aldol-type condensation and Michael addition reaction in water. Tetrahedron 2001. 57, 6169-6173. 

Baur. M. Frank, M. Schatz. J. Schildbach, F. Water-soluble calix[ j]arenes as receptor molecules for non-polar substrates and inverse phase transfer catalysts. Tetrahedron 2001. 57. 6985-6991. 

Inverse phase-transfer catalysis (IPTC) can be applied to synthesize synmietric and antisymmetric acid anhydride in organic synthesis." Pyridine 1-oxide (PNO), 4-dimethylarninopyridine (DMAP), 4-pyrrolidinopyridine (PPY) and l-methyl-2(lH)-pyridothione are usually used as the inverse phase-transfer catalysts... 

Water-soluble calix[n]arenes (n = 4, 6, and 8) with ammonium groups were used as high-performance inverse phase-transfer catalysts in the nucleophilic substitution reaction in water, (Scheme 4.6) [52]. The efficiency of the calix[n] arenes as catalysts varied with the size and/or shape of the substrate molecules. 

Shimizu S, Kito K, Sasaki Y, Hirai C. Water-soluble calixarenes as new inverse phase-transfer catalysts nucleophilic substitution of alkyl and arylalkyl halides in aqueous media. Chem Commun 1997 17 1629-30. 

The reduction of carbonyl compounds in aqueous media has been carried out by a number of reagents under mild conditions. The most frequently used reagent is sodium borohydride, which can also be used using phase-transfer catalysts or inverse phase transfer catalyst in a two phase medium in the presence of surfactants. 

Water-soluble calix[n]arenes are powerful receptors for non-polar substrates in aqueous solution. These compounds are promising candidates as carrier molecules for the transport of non-polar substrates through bulk water as well as inverse phase-transfer catalysts, as proven for the Suzuki coupling of iodobenzene with phenyl boronic acid [91]. 1.5-bis(4,4 -bis(perfluorooctyl)penta-l,4-dien-3-one (39) stabilizes palladium 0) nanoparticles (transmission electron microscopy) formed in the reduction of palladium dichloride with methanol. These palladium colloids are soluble in perfluorinated solvents, and they are efficient recoverable catalysts for Suzuki crosscoupling under fluorous biphasic conditions (Equation 69) [92]. 

In an outstanding study, calix[6]arene sulfonic acids (Calix[6]arene 3a-3d) were employed as efficient surfactant-type acid catalysts for Michael reactions of indoles with a,p-unsaturated ketones in water [24]. It was pointed out that calix[6] arene sulfonic acids were efficient inverse phase-transfer catalysts, and performed a significant catalytic activity in water (see Fig. 27.10). This remarkable activity in... 

Monflier, E. Fremy, G. Castanet, Y. Mortreux, A. (1995) A further breakthrough in biphasic, rhodium-catalyzed hydroformylation - the use of per(2,6-di-0-methyl)-p-cyclo-dextrin as inverse phase-transfer catalyst. Tetrahedron Lett., 36,9481. ... 

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