Particle size effect in the mechanically assisted synthesis of ß-cyclodextrin mesitylene sulfonate.

The mechanically assisted synthesis of organic compounds has recently focused considerable attention as it may be unique in features to selectively direct the reaction pathway. In the continuation of our work on the synthesis of modified cyclodextrins (CDs) via mechanochemical activation, we sought to discriminate the contribution of supramolecular effects and grinding during the course of a reaction in the solid state. As such, we recently investigated the influence of the particle size of ß-CD in the synthesis of ß-CD mesitylene sulfonate (ß-CDMts) in the solid state using a vibrating ball-mill. We were particularly interested in the role of the particle size on the kinetics of the reaction. In this study, we show that grinding ß-CD reduces the particles size over time down to a limit of 167 nm. The granulometric composition remains rather invariant for grinding times over 1 h. Each type of ß-CD particles reacted with mesitylenesulfonyl chloride (MtsCl) to produce ß-CDMts. Contrary to what could be intuitively anticipated, smaller particles did not lead to the highest conversions. The impact of grinding on the conversion was limited. Interestingly, the proportion of ß-CDMts mono-substituted on the primary face significantly increased over time when the reaction was carried out in the presence of KOH as a base. The data series were confronted with kinetics models to get insight in the way the reactions proceeded. The diversity of possible models suggests that multiple mechanochemical processes can account for the formation of ß-CDMts in the solid state. Throughout the study, we found that the reactivity depended more upon diffusion phenomena in the crystalline parts of the material than on the increase in the surface area of the CD particles resulting from grinding.

Hydroformylation of Alkenes in a Planetary Ball Mill: From Additive-Controlled Reactivity to Supramolecular Control of Regioselectivity.

The Rh-catalyzed hydroformylation of aromatic-substituted alkenes is performed in a planetary ball mill under CO/H2 pressure. The dispersion of the substrate molecules and the Rh-catalyst into the grinding jar is ensured by saccharides: methyl-α-d-glucopyranoside, acyclic dextrins, or cyclodextrins (CDs, cyclic oligosaccharides). The reaction affords the exclusive formation of aldehydes whatever the saccharide. Acyclic saccharides disperse the components within the solid mixture leading to high conversions of alkenes. However, they showed typical selectivity for α-aldehyde products. If CDs are the dispersing additive, the steric hindrance exerted by the CDs on the primary coordination sphere of the metal modifies the selectivity so that the ß-aldehydes were also formed in non-negligible proportions. Such through-space control via hydrophobic effects over reactivity and regioselectivity reveals the potential of such solventless process for catalysis in solid state.

Selective Secondary Face Modification of Cyclodextrins by Mechanosynthesis.

α-, ß-, and γ-cyclodextrins (CDs) were modified on their secondary face by mechanosynthesis at room temperature using a laboratory-scale ball-mill. Mono-2-tosylated α-, ß-, and γ-CDs were obtained in good yield from mixtures of native α-, ß-, and γ-CDs, respectively, N-tosylimidazole, and an inorganic base, with each of them being in the solid state. The yields appeared to be dependent upon the nature of the base and the reaction time. A kinetic monitoring by (1)H NMR spectroscopy demonstrated that the highest yields in mono-2-tosyl-CDs were measured using KOH as a base in very short reaction times (up to 65% in 80 s). Mono-(2,3-manno-epoxide) α-, ß-, and γ-CDs were subsequently synthesized by ball-milling a mixture of monotosylated α-, ß-, and γ-CDs, respectively, and KOH. The characterization of the modified CDs was carried out by X-ray diffraction, mass spectrometry, solid-state NMR, and diffuse reflectance UV-vis (DR UV-vis) spectroscopies. Clues to the supramolecular arrangement of the molecules in the solid state provide information on the reaction mechanism.

Catalytic decarbonylation of biosourced substrates.

Linear α-olefins (LAO) are one of the main targets in the field of surfactants, lubricants, and polymers. With the depletion of petroleum resources, the production of LAO from renewable feedstocks has gained increasing interest in recent years. In the present study, we demonstrated that Ir catalysts were suitable to decarbonylate a wide range of biosourced substrates under rather mild conditions (160 °C, 5 h reaction time) in the presence of potassium iodide and acetic anhydride. The resulting LAO were obtained with good conversion and selectivity provided that the purity of the substrate, the nature of the ligand, and the amounts of the additives were controlled accurately. The catalytic system could be recovered efficiently by using a Kugelrohr distillation apparatus and recycled.

Cyclodextrin-grafted polymers functionalized with phosphanes: a new tool for aqueous organometallic catalysis.

New cyclodextrin (CD)-grafted polymers functionalized with water-soluble phosphanes were synthesized in three steps starting from polyNAS. Once characterized by NMR spectroscopy and size-exclusion chromatography, they were used as additives in Rh-catalyzed hydroformylation of 1-hexadecene. The combined supramolecular and coordinating properties of these polymers allowed increasing the catalytic activity of the reaction without affecting the selectivities.

Hydroformylation in aqueous biphasic media assisted by molecular receptors.

The role of molecular receptors in aqueous biphasic hydroformylation of higher olefins is highlighted through a detailed analysis of their molecular recognition properties. The behavior of cyclodextrins and calixarenes as molecular receptors is especially emphasized and discussed. Their supramolecular interactions with the substrates and the water-soluble ligands proved to be an essential parameter guiding the reaction performances. The hydroformylation activity and chemo- and regio-selectivities can thus be accurately controlled by a suitable match between the receptor and the reaction components. Development outlooks are also presented.

The role of metals and ligands in organic hydroformylation.

In this chapter the effect of transition metals and of ancillary stabilizing ligands on the activity, regioselectivity, and chemoselectivity in hydroformylation reactions applied to organic synthesis will be reviewed, highlighting recent cases of particular interest, including examples of both homogeneous and heterogeneous catalytic reactions.

Impact of cyclodextrins on the behavior of amphiphilic ligands in aqueous organometallic catalysis.

In this study, we showed that the addition of randomly modified ß-cyclodextrin (RAME-ß-CD) in aqueous medium could have a beneficial impact on the catalytic performances of phosphane-based aggregates in the Pd-catalyzed cleavage of allyl carbonates (Tsuji-Trost reaction). The RAME-ß-CD/phosphane supramolecular interactions helped explain the catalytic results. The presence of RAME-ß-CD in the aqueous compartment improved the phosphane-based aggregate dynamics. The exchanges between the hydrophobic substrate-containing aggregate core and the catalyst-containing aqueous phase were then greatly favored, resulting in an increase in the catalytic performances.

Unusual inversion phenomenon of ß-cyclodextrin dimers in water.

A conformational analysis of three triazole-containing bridged bis-ß- cyclodextrins (CD) has been carried out to evaluate their recognition ability. NMR spectroscopy and ITC measurements clearly demonstrate that one of the CD glucopyranose units undergoes a 360° rotation in water so that the spacer linking the two CDs is deeply included into one of the CD cavities. The amplitude of this inversion phenomenon depends on the nature of the spacer and results in a limited accessibility to the CD cavities in line with previous catalytic results.

Using click chemistry to access mono- and ditopic ß-cyclodextrin hosts substituted by chiral amino acids.

A wide range of chiral mono- and ditopic cyclodextrin-based receptors have been synthesized by CuI-catalyzed azide-alkyne cycloaddition starting from mono-6-azido-ß-cyclodextrin and chiral amino acids. Of interest, microwaves proved very efficient to access a wide range of ditopic ß-cyclodextrin receptors with quantitative yields.

Amphiphilic photo-isomerisable phosphanes for aqueous organometallic catalysis.

Water-soluble phosphanes were tagged with a light-responding diazo group. Upon UV exposure, the diazo-isomerisation led to phosphane morphology change, resulting in an increase in the reaction rate of an aqueous palladium-catalysed cleavage reaction.

A property-matched water-soluble analogue of the benchmark ligand PPh3.

A series of sulfonated biphenylphosphanes were readily prepared from commercially available, inexpensive, and air-stable organic compounds. Of these, the trisulfonated trisbiphenylphosphane can be considered as a true water-soluble analogue of PPh(3) as the cone angle and basicity of both phosphanes are very close and result in a similar coordination mode on palladium and rhodium complexes. The catalytic performance of the trisulfonated trisbiphenylphosphane was evaluated in the aqueous hydroformylation of 1-decene and the Tsuji-Trost reaction.

Unexpected multifunctional effects of methylated cyclodextrins in a palladium charcoal-catalyzed Suzuki-Miyaura reaction.

[reaction: see text] Native and modified cyclodextrins (CDs) have shown polyvalent properties in a biphasic Pd/C-catalyzed Suzuki-Miyaura reaction. In addition to their mass transfer ability, the CDs favored the dispersion of the catalyst in water. With the randomly methylated CDs (RaMe-beta-CD), the gains of initial activities were multiplied by factors between 3.8 and 343 depending on the nature of the substrates. The reusability of the system was also demonstrated.

How cyclodextrins can mask their toxic effect on the blood-brain barrier.

The toxicity of monosubstituted n-alkyldimethylammonium-beta-cyclodextrins (DMA-C(n)-CD with n=2, 4 and 12) towards endothelial cells of an in vitro model of the blood-brain barrier (BBB) was evaluated and compared to that of the native beta-CD. DMA-C(12)-CD was found to be non-toxic below 10mM due to the self-inclusion of the alkyl chain in the CD cavity. A high percentage of passage (30%) of DMA-C(12)-CD through the endothelial cells has been measured.

Adamantoylated monosaccharides: new compounds for modification of the properties of cyclodextrin-containing materials.

Adamantoyl glycosides were obtained in good yields by coupling adamantanecarboxylic acid with monosaccharides. They form very stable inclusion complexes with beta-cyclodextrin, as shown by (1)H NMR measurements.

Evidence of a self-inclusion phenomenon for a new class of mono-substituted alkylammonium-beta-cyclodextrins.

A new class of mono-substituted N-alkyl-N,N-dimethylammonium-beta-cyclodextrins has been synthesized in a three step procedure from the native beta-cyclodextrin. The structural analysis of these compounds undertaken by combined use of 1D and 2D NMR spectra indicate that the two methyl groups bound on the nitrogen are magnetically inequivalent due to a self-inclusion phenomenon of the alkyl chain inside the CD cavity. A variable-temperature 1H NMR study showed that these mono-substituted CD derivatives formed temperature-independent intramolecular complexes with their own alkylammonium substituent. The strength of the interaction between the alkyl moiety and the cyclodextrin cavity has been evaluated by a competitive method using an adamantane derivative. Finally, surface tension measurements demonstrated the surface active character of these compounds and confirmed their self-inclusion ability.