Cyclodextrin phase-transfer catalysis

Oxymercuration/demercuration provides a milder alternative for the conventional acid-catalyzed hydration of alkenes. The reaction also provides the Markovnikov regiochemistry for unsymmetrical alkenes.33 Interestingly, an enantioselective/inverse phase-transfer catalysis (IPTC) reaction for the Markovnikov hydration of double bonds by an oxymercuration-demercuration reaction with cyclodextrins as catalysts was recently reported.34 Relative to the more common phase-transfer... 

Monflier and co-workers recently described a new approach based on the use of chemically modified /3-cyclodextrins to peform efficiently the functionalization of water-insoluble olefins in a two-phase system. These compounds behave as inverse phase transfer catalysis, i.e., they transfer olefins into the aqueous phase via the formation of inclusion complexes.322... 

Neutral cyclodextrins have been used as chiral phase-transfer catalysts for an interesting inverse phase-transfer catalysis reaction [50]. The Markovnikovhydration of the double bond by an oxymercuration-demercuration reaction has been demonstrated in the presence of cyclodextrins as chiral phase-transfer catalysts to obtain products in low to moderate enantioselectivity (Scheme 7.16). The mercuric salts are water-soluble, and remain in the aqueous phase, whereas the neutral alkenes prefer an organic phase. A neutral cyclodextrin helps to bring the alkenes into the aqueous phase in a biphasic reaction, and also provides the necessary asymmetric environment. 

Various allylic amines and protected allylic alcohols were tested using different cyclodextrins. Although only low to moderate enantioselectivity was obtained, the method demonstrated for the first time an enantioselective inverse phase-transfer catalysis hydration reaction via an oxymercuration-demercuration process. 

Several concepts have been suggested to increases the rates in aqueous-phase catalytic conversion of higher substrates such as addition of conventional surfactants [3, 5] (cf. Sections 4.5 and 6.1.5), counter (inverse)-phase transfer catalysis using /3-cyclodextrins [6] (cf. Section 4.6.1), addition of promoter ligands, e.g. PPh3 [7], or co-solvents (cf. Section 4.3). However, addition of foreign compounds militates against the facile catalyst separation and purification of the products and increase the costs as well. 

Finally, extraction of the important reactive species can be executed in the opposite direction, from organic phase to water. This is called inverse phase-transfer catalysis. Catalysts for such processes are mostly cyclodextrins or modified derivatives thereof. Relatively few applications of this type of PTC have been published. Whereas the present section is concerned only with the organic phase as the location of the proper chemical reaction, important contributions of inverse PTC toward organometallic catalysis are detailed in Section 4.6.2. 

Inverse-phase Transfer Catalysis (cf. Section 4.6.2) has been successfully applied to perform the quantitative and selective oxidation of 1-decene in an aqueous two-phase system [22]. The success of this oxidation is mainly due to the use of /3-cyclodextrin - a cyclic oligosaccharide composed of seven glucopyranose units - functionalized with hydrophilic or lipophilic groups. The best results have been obtained with a multicomponent catalytic system composed of PdS04, H9PV6Mo6O40, CuS04, and per(2,6-di-0-methyl)-/3-cyclodextrin (Eq. 7) [23]. 

Since the Reimer-Tiemann reaction always yields a mixture of ortho- and para-substituted phenols whenever the two positions are unsubstituted (and sometimes even when the positions are substituted, see carboxy-substituted phenols), it is not surprising that attempts have been made to increase the regioselectivity. Earlier attempts (for details, see reviews) emphasized the nature of the cation, the solvent, or used phase-transfer catalysis. Recent studies have concentrated on the use of cyclodextrins as base-stable host compounds, permitting exclusive para substitution. Attaching the cyclodextrins to a solid support has also been attempted, a natural step in view of the high cost of the cyclodextrins and the need for cheap product i.e. p-hydroxybenzaldehyde). p-Hydroxybenzaldehyde has been prepared in 59-65% yield using P-cyclodextrin that has been immobilized with epichlorohydrin. TTie catalyst is easily recovered and can be reused without appreciable loss of activity. 

The Haloform reaction is catalyzed by cyclodextrins in what the authors label as inverse phase transfer catalysis, 25 but the synthetic utility of this variation remains to be seen. An alternative to the use of halogen is a nitroarene catalyzed oxidation of acetophenone with sodium percarbonate or sodium perborate.26 However, the yields of substituted benzoic acids furnished by this method are mediocre (23-73%) in comparison to the conventional Haloform conditions. Likewise, the Haloform reaction of acetone with iodine in liquid ammonia is without synthetic merit (8-12%).27... 

Shimizu, S. Sasaki, Y. Hirai, C. (1990) Inverse phase-transfer catalysis by cyclodextrins. Palladium-catalyzed reduction of bromoanisoles with sodium formate. Bull Chem. Soc. // ., 63,176-8. 

Because of their low solubilities in the aqueous phase, the hydroformylation of higher alkenes (>C2) is still a challenging problem. In addition to fluorous biphasic catalysis, possible solutions, which have been addressed, include the addition of surfactants240,241 or the use of amphiphilic ligands242-244 to enhance mutual solubility or mobility of the components across the phase boundary and thereby increase the rate of reaction. The use of polar solvents such as alcohols,245 p-cyclodextrin,246 cyclodextrin ligands,247 248 thermoregulated phase-transfer... 

Alkaline hydrolysis rates of a series of thiophenyl 4-X-benzoates (47 X = H, Me, N02) was significantly enhanced in the presence of cyclodextrins (CDs), and this was attributed to strong binding of the benzoyl moiety within the CD cavity and covalent catalysis by secondary hydroxy groups of the CDs (48).63 The effect of MeCN and MeOH on the alkaline hydrolysis of acetylsalicylic acid in aqueous micellar solutions was reported.64 Butylaminolysis of p-nitrophenyl acetate in chlorobenzene in the presence of different kinds of phase-transfer catalysts (crown ethers and gly-mes) supported the existence of a novel reaction pathway exhibiting a first-order dependence on the concentration of the phase-transfer catalyst and a second-order... 

Cyclodextrins can play the role of shuttles to transport an appropriate organic substrate. Harada has shown that they can act as counter phase-transfer agents, which function in the reverse manner of phase-transfer catalysts [34]. In fact, cyclodextrins, which are characterized by a high solubility in water but a poor solubility in a polar solvent, form inclusion complexes with a large variety of substrates, which leads to their transfer into the aqueous phase. Similarly, encapsulation of the product after catalysis allows it to be transferred into the organic phase according to the partition coefficients [35]. 

The solubility of olefins in aqueous phases can be increased by complex-ation with cyclodextrins (inverse or counterphase transfer catalysis). This was successfully employed for hydroformylation (156) of higher terminal olefins and for styrene derivatives (Scheme 17) under mild conditions (80°C, 5 MPa). The reaction took place with the neat substrates with no need for an organic solvent or cosolvent. Conversion of the olefins to aldehydes was in most cases close to quantitative, a very large increase compared to the 7-70% observed without the cyclodextrin. In all reactions, a decrease in the linear to branched aldehyde ratio was detected. Of the various cyclodextrin derivatives tested. 

The catalytic properties of the sulfonated diphosphine-stabilized RuNPs and sulfonated diphosphine/cyclodextrin-stabilized RuNPs were compared in the hydrogenation of unsaturated model substrates (styrene, acetophenone, and w-methylanisole) in biphasic liquid-hquid conditions (i.e., ruthenium aqueous colloidal solution and organic substrate no added solvent). Whilst all of these RuNPs displayed suitable performances in catalysis, different activities and selec-tivities were observed. This highhghted that supramolecular interactions on the metallic surface in the presence of a cyclodextrin control the catalytic reactivity of the nanocatalysts. Interestingly the CD acts as a phase-transfer promotor, which... 

Cyclodextrin is another type of mass-transfer promoter. Given that cyclodextrins are able to form inclusion complexes with hydrophobic substrates, it was proposed that they may carry the substrates into the aqueous phase, faciUtating catalysis with the water-soluble complexes. Monflier [38] first reported that, by using per(2,6-di-0-methyl)-P-cyclodextrin, the rate of hydroformylation of 1-decene increased up to 10 times than that observed without the cyclodextrin. 

In catalysis the excess of a phosphine ligand is often necessary because it preserves the active species in the medium [2a]. However, it retards to some extent the co-ordination of the alkene to the metal center. Recent studies, performed by Monflier and coworkers, have shown that the water-soluble TPPTS ligand could reduce the rate of the reaction by another effect. Indeed, TPPTS can be included partially in the cyclodextrin hydrophobic cavity [53,54] NMR measurements, observation by UV-visible spectroscopy and circular dichroism, as well as scanning tunneling microscopy are consistent with a 1 1 inclusion complex in which the phosphorus atom would be incorporated into the torus of the /S-CD. NMR investigations carried out on (m-sulfonatophenyl)diphenylphosphine have shown that a phenyl group is incorporated [55]. Thus, the phosphorus ligand could modify the association constant of the alkene with the cyclodextrin so that the mass transfer between the two phases could be decreased. 

Cyclodextrins are cyclic glucose oligomers consisting of six or more monomer units. The cyclodextrin structure is such that the hydrogens of C-H bonds are directed towards the inside of the cavity of the molecule and hydroxyl groups are directed towards the outside (Fig. 11-7). Therefore, the molecule has a hydrophobic cavity, which owing to its hydrophobicity can bind nonpolar molecules into host-guest complexes and transfer them into the polar phase. This property of cyclodextrins allows us to use them as components of catalytic systems in two-phase catalysis by metal complexes. [20-23, 182-196] this essentially increased the activity of these catalytic systems. 

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