Cyclodextrin ketones

Cyclodextrin ketones have been used as powerful catalysts of amine oxidation in the presence of hydrogen peroxide as the stoichiometric oxidant. This oxidation follows Michaelis-Menten kinetics and depending on the substrate the oxidation rate is increased up to 1100-fold. It has been proposed that hydrogen peroxide reacts with the ketone to form a hydroperoxide adduct and this adduct is responsible for oxidizing the amine, bound in the cavity, to the hydroxylamine.189... 

Several cyclodextrin ketones with a ketone attached to the secondary face of the cyclodextrin in the form of a 2,3-0-( 1,3-acetone) group (79), and some selected cyclodextrin ketones having the ketone at the primary face, were investigated for their catalysis of epoxidation of stilbenes and styrene by oxone in 1 1 acetonitrile/H20. It was found that secondary face ketones were better catalysts giving a cat uncat over 10, and more stereoselective giving up to 76% ee in (5)-styrene oxide. ... 

The strategy of manipulation of the macro-environment can be utilized for biotransformations. Thus, Zelinski and Kula (1997) have enzymatically reduced lipophillic ketones like 2-acetylnaphthalene using dimethylether of P-cyclodextrin in the organic phase. The use of cyclodextrin increases the solubility of the ketone by a factor of 147 resulting in high yields with excellent enantioseiectivity. 

The use of chiral ruthenium catalysts can hydrogenate ketones asymmetrically in water. The introduction of surfactants into a water-soluble Ru(II)-catalyzed asymmetric transfer hydrogenation of ketones led to an increase of the catalytic activity and reusability compared to the catalytic systems without surfactants.8 Water-soluble chiral ruthenium complexes with a (i-cyclodextrin unit can catalyze the reduction of aliphatic ketones with high enantiomeric excess and in good-to-excellent yields in the presence of sodium formate (Eq. 8.3).9 The high level of enantioselectivity observed was attributed to the preorganization of the substrates in the hydrophobic cavity of (t-cyclodextrin. 

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. 

PdS04/H9PV6Mo604o/CuS04 in the presence of chemically modified P-cyclodextrins were also used as CPTC systems in the Wacker-type oxidation of higher a-olefins (Cg-Cje) to the corresponding 2-ketones (Equation 18) with high yields (90-98%) in an aqueous/organic two phase system.545,571... 

Harada, A., Hu. Y. and Takahashi. S. (1986) Cyclodextrin-paJJadium chloride. New catalytic system for selective oxidation of olefins to ketones. Chem. Lett., 2083-2084. 

The progress of the reaction can be monitored by TLC by working up a sample of the reaction mixture filter through Celite, cool to 0°C, and acidify to pH 1 with 10% aqueous HCI. The solid that precipitates is isolated by filtration and dissolved in dimethylformamide (DMF) for TLC analysis on Merck precoated-silica gel 60 plates with methyl ethyl ketone-methanol-water (4 1 1) as eluent, developed by dipping in 5% sulfuric acid-ethanol and heated to 450°C (e.g., with a Bunsen burner). Rf values are 0.25 for fl-cyclodextrin, 0.5 for monotosylate and 0.65 for a second product, probably ditosylate. 

In new studies heteropoly acids as cocatalysts were found to be very effective in combination with oxygen in the oxidation of ethylene.1311 Addition of phosphomo-lybdic acid to a chloride ion-free Pd(II)-Cu(II) catalyst system results in a great increase in catalytic activity and selectivity.1312 Aerobic oxidation of terminal alkenes to methy ketones can be performed with Pd(OAc)21313 or soluble palladium complexes. Modified cyclodextrins accelerates reaction rates and enhance selectivities in two-phase systems under mild conditions.1315 1316... 

The pathways followed by radical pairs, 42 (disproportionation or coupling with rearrangement) resulting from the type I cleavage of 2-phenylcycloalkanones (41) are influenced by cyclodextrin complexation [164], The product ratio depends both on the size of the cyclic ketone and on... 

Solid inclusion complexes of photoreactive ketones with cyclodextrins as hosts (Figure 6) provide interesting examples of how a fairly stiff, somewhat heterogeneous (in terms of polarity, size, and guest orientation) reaction... 

A similar chiral environment is given by inclusion to cyclodextrins (CDs), cyclic oligosaccharides (3). The outside of the host molecule is hydrophilic and the inside hydrophobic. The diameters of the cavities are approximately 6 (a), 7-8 (j3), and 9-10 A (7), respectively. Reduction of some prochiral ketone-j3-CD complexes with sodium boro-hydride in water gives the alcoholic products in modest ee (Scheme 2) (4). On the other hand, uncomplexed ketones are reduced with a crystalline CD complex of borane-pyridine complex dispersed in water to form the secondary alcohols in up to 90% ee, but in moderate chemical yields. Fair to excellent enantioselection has been achieved in gaseous hydrohalogenation or halogenation of a- or /3-CD complexes of crotonic or methacrylic acid. These reactions may seem attractive but currently require the use of stoichiometric amounts of the host CD molecules. 

A remarkably high diastereoselective excess was obtained in the addition of the anion of (S)-(-)-methyl 1-naphthyl sulfoxide to n-alkyl phenyl ketones. The sulfoxide was prepared in optically pure form by oxidation of the complex of methyl 1-naphthyl sulfide and 13-cyclodextrin with peracetic acid followed by crystallization. Desulfurization of the adducts provided enantiomerically pure tertiary alcohols (393]. 

The milder metal hydride reagents are also used in stereoselective reductions Inclusion complexes of amine-borane reagent with cyclodextrins reduce ketones to optically active alcohols, sometimes in modest enantiomeric excess [59] (equation 48). Diisobutylaluminum hydride modified by zmc broniidc-iV./V.A V -tetra-methylethylenediamine (TMEDA) reduces a,a-difluoro-(3-hydroxy ketones to give predominantly erythro-2,2-difluoro-l,3-diols [60] (equation 49). The threo isomers arc formed on reduction with aluminum isopropoxide... 

Another type of inclusion compd is the channel or canal compound. Here the straight chain compds, such as hydrocarbons, acids,esters , alcohols, aldehydes, ketones, etc are enclosed in the channels formed by compds, such as urea, thiourea, choleic acids, cyclodextrins, etc. As examples of channel compds may be cited, the urea-decone compd, [CO(NH2)2] g.C, 2H26, and various zeolites. (See also Ref 10, pp431 ... 

The observed differences in the reactivity of these crystals are rationalized in terms of crystal packing. Though cyclodextrins have been extensively studied, very few photochemical reactions involving molecules complexed to cyclodextrins have been examined. In this connection, the utility of cyclodextrins in bringing about selectivity in photochemical reactions through the study of excited state behavior of olefins and aryl alkyl ketones has been demonstrated in our laboratory. 

Table II. Product Distribution Upon and in Cyclodextrins Irradiation of Aryl Alkyl Ketones in Organic Solvents ...

Figure 7. Schematics of Type I and II reactions of Aryl alkyl ketones in Cyclodextrins.

Diels-Alder catalysis. Water can accelerate the Diels-Alder reaction of cyclopentad iene with methyl vinyl ketone or acrylonitrile by a hydrophobic interaction. / -Cyclodextrin can increase this effect, possibly because the components can fit into the hydrophobic cavity.1... 

Small peptides - simple di- and tri-peptides with a primary amine at the N-terminus -catalyse the aqueous aldol between unmodified ketones and aldehydes with up to 86% ee.121 This is dramatically different from the corresponding amino acid-catalysed reaction, suggesting that peptide formation may have been significant in the evolution of asymmetric synthesis. Addition of a-cyclodextrin raised the ee further through the hydrophobic effect. 

By using water-soluble organic solvents, usually referred to as precipitants, the reaction can be directed to produce only one cyclodextrin. In the presence of toluene, the enzyme from B. macerans produces only (3-cyclodextrin and linear starch chains. Beta-cyclodextrin can be separated from the soluble starch chains and recovered as a precipitated toluene complex. In the presence of decanol, a-cyclodextrin is the only cyclodextrin produced using the enzyme from B. macerans.21,22 Precipitants such as large cyclic compounds similar to musk oil23 or a-naphthol and methyl ethyl ketone (butanone)24 can be used to produce 8-cyclodextrin. 

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