Sulfobutyl Ether‐β‐Cyclodextrins: Promising Supramolecular Carriers for Aqueous Organometallic Catalysis

The potentialities of sulfobutyl ether‐β‐CDs derivatives as supramolecular carrier in a biphasic Tsuji–Trost reaction catalyzed by a water‐soluble palladium complex of trisulfonated triphenylphosphine have been investigated. The efficiency of these cyclodextrins (CDs) strongly depends on the average molar substitution degree of cyclodextrin and the highest rate enhancements were obtained with cyclodextrins containing about 7 sulfobutyl ether groups. This result was attributed to the absence of a strong interaction between this cyclodextrin and the trisulfonated triphenylphosphine used to dissolve the catalyst in the aqueous phase and to the presence of an extended hydrophobic cavity allowing a better molecular recognition between the substrate and the cyclodextrin. This constitutes the first example of a non‐interacting β‐cyclodextrin/phosphine couple with high catalytic activities.     

Efficient Synthesis of β,γ‐Alkynyl α‐Amino Acid Derivatives by Ag(I)‐Catalyzed Alkynylation of α‐Imino Esters

The first catalytic synthesis of β,γ‐alkynyl α‐amino acid derivatives was achieved by direct addition of terminal alkynes to α‐imino esters in the presence of an Ag(I) salt under mild reaction conditions.     

High‐Pressure 31P{1H} NMR Studies of RhH(CO)(TPPTS)3 in the Presence of Methylated Cyclodextrins: New Light on Rhodium‐Catalyzed Hydroformylation Reaction Assisted by Cyclodextrins

The effect of methylated cyclodextrins on the RhH(CO)(TPPTS)₃ complex in hydroformylation conditions [50 atm of CO/H₂ (1/1) and 80 °C] has been investigated by high‐pressure ³¹P{¹H} NMR spectroscopy. In the presence of methylated β‐cyclodextrin, the equilibria between the rhodium species lie in favor of phosphine low‐coordinated rhodium species. The formation of a stable inclusion complex between this cyclodextrin and the trisulfonated triphenylphosphine ligand (TPPTS) was found to be the key to understanding the displacement of the equilibria. Indeed, the methylated α‐cyclodextrin which does not interact with the TPPTS and the methylated γ‐cyclodextrin which can weakly bind to the TPPTS have no and a very low effect on the equilibria, respectively. These results explain for the first time why a decrease in the normal to branched aldehydes ratio is always observed when cyclodextrins are used as mass‐transfer agents in aqueous biphasic hydroformylation processes.     

Equalizing effect of β‐cyclodextrin on dyeing of polyamide 6,6 woven fabrics with acid dyes

Cyclodextrins (CD) are produced from starch by the action of cyclodextrin glycosyltransferase (CGTase) enzyme. Structurally, cyclodextrins consist of 6, 7, or 8 (α, β, and γ cyclodextrins, respectively) D‐glucopyranosyl units connected by α‐(1,4) glycosidic linkages. Having polar and hydrophilic outer sides and hydrophobic cavitation gives cyclodextrins a chance to form inclusion complexes with dyes in hydrophilic mediums. In this research, the equalizing effect of β‐cyclodextrins in dyeing of polyamide 6,6 woven fabrics with 6 different acid dyes were investigated. From the experimental results, it was determined that the β‐cyclodextrin shows a retarding and equalizing effect in dyeings carried out with the dyes that show interaction with β‐CD. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 2660–2668, 2007     

Heptakis(2,3‐di‐O‐methyl‐6‐O‐sulfopropyl)‐β‐cyclodextrin: A Genuine Supramolecular Carrier for Aqueous Organometallic Catalysis

The behavior of heptakis(2,3‐di‐O‐methyl‐6‐O‐sulfopropyl)‐β‐cyclodextrin as inverse phase transfer catalyst in biphasic Tsuji–Trost and hydroformylation reactions has been investigated. In terms of activity, this methylated sulfopropyl ether β‐cyclodextrin is much more efficient than the randomly methylated β‐cyclodextrin, which was the most active cyclodextrin known to date. From a selectivity point of view, the intrinsic properties of the catalytic system are fully preserved in the presence of this cyclodextrin as the chemo‐ or regioselectivity was found to be identical to that observed without a mass transfer promoter in the hydroformylation reaction. The efficiency of this cyclodextrin was attributed to its high surface activity and to the absence of interactions with the catalytically active species and the water‐soluble phosphane used to dissolve the organometallic catalyst in the aqueous phase.     

One‐Step Catalytic Enantioselective α‐Quaternary 5‐Hydroxyproline Synthesis: An Asymmetric Entry to Highly Functionalized α‐Quaternary Proline Derivatives

The highly enantioselective cascade reaction between N‐protected α‐cyanoglycine esters and α,β‐unsaturated aldehydes is disclosed. The reaction represents a one‐step entry to polysubstituted 5‐hydroxyproline derivatives having a quaternary α‐stereocenter generally in high yields with up to >95:5 dr and 99:1 er. It is also a direct catalytic two‐step entry to functionalized α‐quaternary proline derivatives.     

Palladium on Calcium Carbonate Combined to 2‐Hydroxypropyl‐α/β‐cyclodextrins: A Selective Catalytic System for Aqueous Heck Coupling and Hydroarylation

An efficient, selective and recoverable catalytic system for ligand‐free aqueous Heck reactions using hydroxypropylated cyclodextrins (HPCDs) and palladium on calcium carbonate (Pd/CaCO₃) is highlighted. Remarkably, stereo‐ and chemoselectivities could be tuned by the cavity size of cyclodextrins, exploiting the relevance of host‐guest interactions. UV‐Vis experiments have led to strong evidence concerning an interplay between Pd(II) and α‐HPCD, possibly ascribed to a reduction/stabilization effect of CDs. Unexpectedly, hydroarylation was the favored pathway with acrylonitrile which provided access to 3‐phenylpropionitrile derivatives without usual hydride donors. Finally, determination of soluble Pd(0/II) via AAS enabled the definition of a predominant homogeneous mechanism in which TONs over 5000 were observed.     

Cobalt catalyzed hydroformylation of higher olefins in the presence of chemically modified cyclodextrins

The cobalt catalyzed hydroformylation of higher olefins in the presence of chemically modified cyclodextrins was investigated in an aqueous biphasic system. The effect of various parameters, such as the nature of the cyclodextrin and olefin, the temperature, the CO/H₂ pressure, the concentration of the cyclodextrin and TPPTS was studied. The results demonstrate that the partially methylated β-cyclodextrin gives good conversion (>92%) and selectivity (>92%) for the hydroformylation of higher olefins without impeding the recovery of the catalytic system.     

Chemically modified β-cyclodextrins in biphasic catalysis: a fruitful contribution of the host–guest chemistry to the transition-metal catalyzed reactions

Biphasic hydroformylation, Wacker oxidation and hydrocarboxylation of water insoluble olefins have been investigated in the presence of chemically modified β-cyclodextrins. In all cases, cyclodextrins appear more efficient than common mass transfer promoters to increase the activity and the selectivity of reactions. Most of the results are interpreted from the molecular recognition between the host cavity of modified cyclodextrins and substrate. The stability of the chemically modified cyclodextrins is also reported.     

Enantioselective Phase‐Transfer Catalytic α‐Benzylation and α‐Allylation of α‐tert‐Butoxycarbonyllactones

A new enantioselective α‐benzylation and α‐allylation of α‐tert‐butoxycarbonyllactones was devloped. α‐Benzylation and α‐allylation of α‐tert‐butoxycarbonylbutyrolactone and α‐tert‐butoxycarbonylvalerolactone under phase‐transfer catalytic conditions (50% cesium hydroxide, toluene, −60 °C) in the presence of (S,S)‐3,4,5‐trifluorophenyl‐NAS bromide (1 mol%) afforded the corresponding α‐substituted α‐tert‐butoxycarbonyllactones in very high chemical yields (up to 99%) and optical yields (up to 99% ee). The synthetic potential of this method has been successfully demonstrated by the asymmetric synthesis of unnatural α‐quaternary homoserines, 3‐alkyl‐3‐carboxypyrrolidine and 3‐alkyl‐3‐carboxypiperidine.     

Enzymatic Synthesis of α‐Glucosides of Resveratrol with Surfactant Activity

We report the synthesis of a series of α‐glucosyl derivatives of resveratrol (3,5,4′‐trihydroxystilbene) by a transglycosylation reaction catalyzed by the enzyme cyclodextrin glucanotransferase (CGTase) using starch as glucosyl donor. Several reaction parameters (temperature, solvent composition, enzyme concentration and starch/resveratrol ratio) were optimized. The yield of α‐glucosylated products reached 50% in 24 h. The structures of the derivatives were determined by a combination of amyloglucosidase‐hydrolysis tests, MS and 2D‐NMR. Three families of products were obtained: glucosylated at 3‐OH, at 4′‐OH and at both 3‐OH and 4′‐OH. The bonds between glucoses were basically α(1→4). Interestingly, the water solubilities of the α‐glucosylated derivatives were at least 65‐ and 5‐fold higher than those of resveratrol and the natural β‐glucosylated derivative (piceid), respectively. In contrast with piceid, the synthesized α‐glucosylated compounds exhibited surfactant activity, with critical micelle concentration (CMC) values in the range 0.5–3.6 mM. Although the incorporation of a glucosyl moiety caused a loss of antioxidant activity (more pronounced in the position 3‐OH compared with 4′‐OH), the fact that the glycosides need to be converted into the aglycones before they are absorbed minimizes such an effect. In contrast, the modification of physicochemical properties such as solubility and partition coefficient by glycosylation could exert a positive influence on the bioavailability of resveratrol.     

Catalytic Asymmetric Hydrogenation of α‐Arylcyclohexanones and Total Synthesis of (−)‐α‐Lycorane

An efficient catalytic asymmetric hydrogenation of racemic α‐arylcyclohexanones with an ethylene ketal group at the 5‐position of the cyclohexane ring via dynamic kinetic resolution has been developed, giving chiral α‐arylcyclohexanols with two contiguous stereocenters with up to 99% ee and >99:1 cis/trans‐selectivity. Using this highly efficient asymmetric hydrogenation reaction as a key step, (−)‐α‐lycorane was synthesized in 19.6% overall yield over 13 steps from commercially available starting material.     

Chiral N,N′‐Dioxide–Yttrium Triflate Complexes‐Catalyzed Asymmetric Aldol Cyclization of α‐Keto Esters with α‐Isothiocyanato Imide

A highly effective aldol cyclization of α‐isothiocyanato imide to both β,γ‐unsaturated α‐keto esters and aryl‐substituted α‐keto esters has been developed. A chiral N,N′‐dioxide–yttrium triflate complex was used as the catalyst. A series of cyclic thiocarbamates bearing chiral quaternary stereocenters was synthesized in good to high yields, excellent diastereo‐ (up to 25:1 dr) and enantioselectivities (up to 99 % ee). In addition, the reaction could be carried out on a gram‐scale, and other functionalized derivatives are also conveniently transformed. Interestingly, a discrepancy of diastereoselection was observed between the reactions of β,γ‐unsaturated α‐keto esters and aryl‐substituted α‐keto esters. Moreover, a substrate dependency of non‐linear effects was observed in this reaction. On the basis of the experimental results and the absolute configuration of the products, possible catalytic models have been proposed to explain the origin of the asymmetric process.

     

Chemo‐ and Enantioselective Brønsted Acid‐Catalyzed Reduction of α‐Imino Esters with Catecholborane

The chemo‐ and enantioselective reduction of α‐imino esters with catecholborane has been developed employing 10 mol% of an enantiopure BINOL‐based phosphoric acid as organocatalyst. Various differently substituted aromatic α‐amino acid derivatives can be achieved in almost quantitative yields and very good to excellent enantioselectivities of up to 96% ee under mild reaction conditions.     

Biphasic Aqueous Organometallic Catalysis Promoted by Cyclodextrins: How to Design the Water‐Soluble Phenylphosphane to Avoid Interaction with Cyclodextrin

The ability of cyclodextrin to interact with meta‐trisulfonated triphenylphosphane derivatives bearing one or two methyl (or methoxy) groups on the aromatic ring has been investigated by NMR and UV‐vis spectroscopy. In the case of native β‐cyclodextrin (β‐CD), the presence of one methyl or methoxy group in the ortho‐position on each aromatic ring is necessary to hamper the formation of an inclusion complex between the β‐CD and meta‐trisulfonated triphenylphosphane derivatives. In the case of methylated β‐CD, the formation of an inclusion complex is only observed when the meta‐trisulfonated triphenylphosphane contains a methyl group in the para‐position. The poor affinity of methylated β‐CD towards modified trisulfonated triphenylphosphanes was attributed to the steric hindrance generated by the methyl groups on the CD secondary face. The absence or presence of an interaction between phosphanes and methylated β‐CD was also confirmed by catalytic experiments. Thus, the phosphanes that do not interact with the methylated CD were the most efficient mass‐transfer promoters in an aqueous biphasic palladium‐catalyzed Tsuji–Trost reaction.     

Hydrophobically modified poly[(divinyl ether)‐co‐(maleic anhydride)]: interactions with cyclodextrin derivatives and hydrogel formation

Hydrolyzed cyclocopolymer prepared from divinyl ether and maleic anhydride, poly[(divinyl ether)‐ co ‐(maleic anhydride)] (DIVEMA), was functionalized with aminoadamantane and subsequently compared with the hydrolyzed DIVEMA with respect to physicochemical properties. The complexation behavior of adamantyl modified DIVEMA with cyclodextrin derivatives was examined by dynamic light scattering, nuclear magnetic resonance spectroscopy and zeta potential. The scattering studies indicated the formation of well‐defined aggregated structures with an average diameter of 120 nm. These aggregated structures collapsed on addition of randomly methylated β‐cyclodextrin to give 4.2 nm in hydrodynamic diameter. Interactions with crosslinked β‐cyclodextrins indicated gel formation which was analyzed by means of rheology and temperature‐dependent viscosity showing disaggregation of the host‐guest system at 42 °C. This novel physical hydrogel is very interesting for medical applications as a drug delivery system with included anti‐tumor activity. Copyright © 2012 Society of Chemical Industry     

Chiral Amino Diol Derivatives as New Modular Organocatalysts for the Enantioselective α‐Chlorination of Cyclic β‐Keto Esters

Highly modular chiral amino diol derivatives have been used as organocatalysts in the enantioselective α‐chlorination of cyclic β‐keto esters. Optimization of the catalyst structure and the reaction conditions has allowed the synthesis of optically active α‐chlorinated products with high enantioselectivities (up to 96% ee) using inexpensive commercially available N‐chlorosuccinimide (NCS) as the chlorine source under mild conditions.     

Highly Enantioselective Allylation of Aromatic α‐Keto Phosphonates Catalyzed by Chiral N,N′‐Dioxide‐Indium(III) Complexes

The ramipril derivative N,N′‐dioxide 3g ‐indium(III) complex was found to be an efficient catalyst for the allylation of the aromatic α‐keto phosphonates. The corresponding α‐hydroxy phosphonates were obtained with high yields (up to 98 %) and high enantioselectivities (up to 91 % ee). A bifunctional catalyst system was described with an N‐oxide as Lewis base activating tetraallyltin and indium as Lewis acid activating aromatic α‐keto phosphonates. A possible catalytic cycle has been proposed to explain the mechanism of the reaction.     

Organocatalytic Asymmetric Mannich Reactions of 5H‐Oxazol‐4‐ones: Highly Enantio‐ and Diastereoselective Synthesis of Chiral α‐Alkylisoserine Derivatives

The first organocatalytic Mannich reaction of 5H‐oxazol‐4‐ones with various readily prepared aryl‐ and alkylsulfonimides has been developed. Two commercially available pseudoenantiomeric Cinchona alkaloids‐derived tertiary amine/ureas have been demonstrated as the most efficient catalysts to access the opposite enantiomers of the Mannich products with equally excellent enantio‐ and diastereoselectivities. From the Mannich adducts, important α‐methyl‐α‐hydroxy‐β‐amino acid derivatives, such as the α‐methylated C‐13 side chain of taxol and taxotere, can be conveniently prepared.     

Dual Amine‐ and Brønsted Acid‐Catalyzed α‐Allylic Alkylation of Aldehydes

A very simple method was developed for the direct, palladium‐free catalytic α‐allylic alkylation of aldehydes. The direct organocatalytic intermolecular α‐allylic alkylation reaction was mediated by a simple combination of Brønsted acid and enamine catalysis which furnished α‐allylic alkylated aldehydes and cyclohexanone in high yields and chemoselectivities. The reaction conditions are mild and environmental friendly, the process is conducted under an atmosphere of air without the need for dried solvents, and water is the only side product of the allylic alkylation reaction.