Cyclodextrins, as phase-transfer

Trifonov, A. Nikiforov, T. Cyclodextrins as phase-transfer catalysts in a nucleophilic clisplacenient reaction. J. Mol. Catal. 1984, 24. 15-18. 

Zahalka, H.A. Januszkiewicz, K. Alper, H. Olefin oxidation catalyzed by palladium chloride using cyclodextrins as phase-transfer agents. J. Mol. Catal. 1986. 35, 249-253. 

Pyridine-modified HPA-1 ha also been applied for the liquid-phase oxidation of benzene to phenol with 2.0 MPa of dioxygen at 1 lO C, in acetic acid. When using ascorbic as reducing reagent, phenol was obtained with 9% yield in 10 h. A 13% yield was observed in the presence of -cyclodextrin as phase transfer agent, under analogue conditions." ... 

Lanthanide ions (La3+, Ce3+) were found to promote the cobalt-catalyzed reaction in a two-phase system with p-cyclodextrin or PEG-400 (polyethylene glycol 400) as phase-transfer catalysts.134... 

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... 

The palladium leaching to the product phase was investigated via ICP-OES measurements. In all cases about 5% of the metal catalyst is lost. This palladium loss is in the same range as in the biphasic reaction in water with subsequent extraction with cyclohexane. Therefore, one can conclude that the use of cyclodextrins has almost no influence on the palladiiun leaching. For the reaction described in this work, this makes the use of cyclodextrins as PCT catalysts more attractive than the TMS systems to overcome mass transfer limitations. 

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. 

Chemically modified P-cyclodextrins were successfully used to accelerate the deprotection of various water insoluble allylic carbonates in genuine two-phase systems without organic cosolvents. The cyclodextrins act not only as reverse phase transfer agents but may increase the selectivity of the reactions through molecular recognition [59-60] (see also Chapter 10). 

One of the earliest use of cyclodextrins as inverse phase transfer agents was in the Wacker oxidation of higher olefins to methyl ketones [22] with [PdCU] + [CuCU] catalyst (Scheme 10.12). Already at that time it was discovered, that cyclodextrins not only transported the olefins into the aqueous phase but imposed a substrate-selectivity, too with Ckh olefins the yields decreased dramatically and 1-tetradecene was only slightly oxidized. 

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... 

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. 

In CE a successful method for enantiomer separation is the addition of a chiral selector to the mobile phase. This practice can be transferred to p-CEC by using a packing bed which consists of bare silica or ODS (octadecylsilica) and a mobile phase containing a chiral additive. At the first time, Lelievre et al. added hydroxypropyl-[5-cyclodextrin to the mobile phase using an ODS packed capillary. The enantiomer separation of chlorthalidone with a resolution Rs of 1.4 was feasible [41]. Deng et al. [59] used an ODS-packed column and (3-cyclodextrin as a mobile phase additive. A theoretical model for the enantiomer separation of salsolinol was developed and compared with the experimental data. For pressure supported CEC, very high pressure (about 100 bar) was applied to the inlet vial so that the mobile phase was mainly driven by the applied pressure. 

The use of thiazolium salts enables the benzoin condensation to proceed at room temperature. It can also be performed in dipolar aptotic solvents or under phase transfer conditions. Thiazolium salts such as vitamin Bi, thiazolium salts attached to y-cyclodextrin, macrobicyclic thiazolium salts, thiazolium carboxylate, ° naphtho[2,l-d]thiazolium and benzothiazolium salts catalyze the benzoin condensation and quaternary salts of 1-methylbenzimidazole and 4-(4-chlorophenyl)-4//-1,2,4-triazole are reported to have similar catalytic activity. Alkylation of 2-hydroxyethyl-4-methyl-l,3-thiazole with benzyl chloride, methyl iodide, ethyl bromide and 2-ethoxyethyl bromide yields useful salts for catalyzing 1,4-addition of aldehydes to activated double bonds. Insoluble polymer-supported thiazolium salts are catalysts for the benzoin condensation and for Michael addition of aldehydes. Electron rich al-kenes such as bis(l,3-dialkylimidazolidin-2-ylidenes) bearing primary alkyl substituents at the nitrogen atoms or bis(thiazolin-2-ylidene) bearing benzyl groups at the nitrogen atoms are examples of a new class of catalyst for the conversion of ArCHO into ArCHOHCOAr. 

Likewise, a thermoregulated phase transfer process within the aqueous/organic two-phase system has been reported by Jin and co-workers (cf. Section 3.1.1.1) [290]. A water-soluble supramolecular Rh catalyst based on functionalized /1-cyclodextrin was also described [291]. In a two-phase system this catalyst may function as a carrier for the transfer of both the starting material and the product between the different phases. As an alternative to polar media for biphasic hydroformylation, Chauvin et al., used ionic liquids based on imidazolium salts which are well known for dimerization reactions (cf. Sections 2.3.1.4 and 3.1.1.2.2) [270, 271, 292]. For introduction into technical processes the currently availability and price of ionic liquids could be a drawback, especially for bulk chemicals such as 0x0 products. 

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 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. 

Wacker oxidation of olefins to ketones catalyzed by palladium complexes is a well-known process which has been applied to numerous olefins [120]. However, selective oxidation of Cg-Cig a-olefins remains a challenge. Recently, Mortreux et al. have developed a new catalytic system for the quantitative and selective oxidation of higher a-olefins in an aqueous medium [121-123]. For example, 1-decene was oxidized to 2-decanone in 98% yield using PdS04/ H9PV6M06O40/CUSO4 as the catalyst in the presence of per(2,6-di-0-methyl)-j9-cyclodextrin, which probably played the role of a reverse phase transfer reagent [Eq. (22)]. 

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. 

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]. 

Hydridopentacyanocobaltate(II), [HCo(CN)5]3, is a catalyst of choice for selective hydrogenation of conjugated dienes and polyenes to monoenes unactivated alkenes are totally unreactive [12, 62, 63]. In general, hydrogenation proceeds with 1,4-addition of H2 (Eq. 28). Because of the insolubility of dienes in water, such reactions are carried out in aqueous/organic biphasic systems. The possibilities for modification of the catalyst by ligand alteration are very restricted but various additives, such as KCN, KOH, lanthanide salts, cyclodextrins, phase-transfer, and micellar agents, are known to influence the selectivity of [HCo(CN)r, 3 -catalyzed reactions. 

In benzene/water biphasic systems a variety of dienes were hydrogenated in the presence of /l-cyclodcxtrin (/i-CD) and La, Ce, and Yb salts [72]. 2,3-Dimethyl-l,3-butadiene gave 2,3-dimethyl-l-butene with 100% yield and 97% selectivity, representing a reduction with 1,2-addition of hydrogen (Eq. 29). In this /3-cyclodextrin acted as a reverse-phase transfer agent, assisting the diene to enter the aqueous phase equally selective reactions could be achieved by using poly (ethylene gly-col)s, such as PEG-400. 

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