Fluorous Reverse Phase Silica Research Articles

Continuous Flow Asymmetric Hydrogenation with Supported Ionic Liquid Phase Catalysts Using Modified CO2as the Mobile Phase: from Model Substrate to an Active Pharmaceutical Ingredient

The continuous flow asymmetric hydrogenation of (hetero)aromatic enamides has been realized using a Rh-Quinaphos catalyst immobilized in a supported ionic liquid phase (SILP) and employing supercritical CO2 modified with toluene (modCO2) as the mobile phase. This approach allows expansion of the scope of the original SILP/scCO2 system to nonvolatile substrates with poor solubility in pure CO2. The potential of a SILP catalyst in combination with modCO2 was demonstrated for an industrial case study using the continuous flow hydrogenation for the synthesis of a key intermediate of an active pharmaceutical ingredient (API) from AstraZeneca’s portfolio. Toluene was selected as the most promising modifier, and the influence of the ratio of modifier to CO2 was evaluated in detail. The catalyst support was found to play a major role for maintaining constant performance and the use of hydrophobic fluorous reverse-phase silica (FRP-SiO2) instead of dehydroxylated silica strongly enhanced the long-term stability un...

ChemInform Abstract: Preparation of a Fluorous Chiral BINOL Derivative and Application to an Asymmetric Protonation Reaction.

Fluorous Chiral Proton Source (R,S)-FDHPEB resulted in a higher enantioselectivity (95% ee) than that of the original nonfluorous (R,S)-DHPEB (87% ee) in an enantioselective protonation of a samarium enolate. (R,S)-FDHPEB was easily recovered by a simple filtration through a fluorous reverse phase silica gel and was recyclable.

Fluorous dimethylthiocarbamate ( FDMTC) protecting groups for alcohols

N, N-Bis(perfluoroalkyl)thiocarbamoyl chlorides ( FDMTC-Cls) were synthesized as reagent for the protection of alcohols. Using the crystalline FDMTC-Cls, the FDMTC groups were introduced into the alcohol molecules in excellent yields in the presence of sodium hydride in THF at room temperature. The products were separated from the excess alcohols by solid-phase extraction with a fluorous reverse-phase silica gel column (Fluorous Solid Phase Extraction; FSPE). The FDMTC groups were readily removed by oxidation with m-chloroperbenzoic acid ( m-CPBA) and subsequent hydrolysis with KHCO 3.

A microfluidic fluorous solid-phase extraction chip for purification of amino acids

An electrokinetically-driven microfluidic chip was developed to realize beads-based solid-phase extraction (SPE) of amino acids. This chip uses a two-level (deep/shallow) poly(dimethylsiloxane) (PDMS) microchannel network to confine the fluorous reversed-phase silica beads within the SPE chamber. The mixture of fluorous tagged and non-tagged amino acids was carried into the fluorous solid-phase extraction (F-SPE) chamber by electrokinetic pumping and was successfully separated and extracted. By adding a reference material to the sample, the extraction efficiency of the eluted fluorous-tagged amino acid was calculated using the detection results from mass spectrometry (MS). The F-SPE microchips showed good reproducibility and efficiency, yielding an average extraction efficiency of 55% with a RSD of 10.6% under the typical experimental conditions.

Fluorous‐Silica‐Supported Perfluoro‐Tagged Palladium Complexes Catalyze Suzuki Couplings in Water.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Recycling of a perfluoroalkylated BINOL ligand using fluorous solid-phase extraction

After the asymmetric addition of allyltri-n-butyltin to benzaldehyde, a perfluoroalkylated BINOL-Sn complex was separated from the organic product using fluorous reverse phase silica gel. The lightly fluorinated ligand was then recovered by hydrolysis of the Rf6-BINOL-Sn complex with dilute hydrochloric acid and was reused three times without loss of activity or enantioselectivity.

New Fluorous Reversed Phase Silica Gels for HPLC Separations of Perfluorinated Compounds

Two new perfluoroalkyl-modified stationary phases were prepared and compared with two commercially available perfluorinated stationary phases (Fluophase RP and Fluophase Pentafluorophenyl) and a C18-RP column with respect to retention times of an array of perfluoroalkyl-tagged and untagged molecules. A few highly lipophilic compounds were also included in the study. They showed high retention times on C18-RP columns, but not on perfluorinated support materials. Perfluoroalkyl-tagged compounds revealed a weak interaction with the pentafluorophenyl-modified support. The interaction between perfluoroalkyl-tagged compounds and perfluoroalkyl-modified stationary phases was strong, and dependent on the chain length of the perfluoro tags. Surprisingly, there was only a small difference between the retention times of perfluorinated compounds on C18-RP and C6F13-modified support. Fluorous-fluorous interactions became prevalent only with C8F17-tagged compounds on C8F17 functionalized silica gel. Compounds with two perfluoro tags showed a drastic increase in retention time, which might be due to a cooperative effect. These results demonstrate the uniqueness of fluorous-fluorous interactions based on linear perfluoroalkyl chains and open up possibilities for the design of new perfluoro tags for purifications and noncovalent attachments of catalysts or biomolecules on perfluorinated solid supports.

Fluorous Reverse‐Phase Silica Gel Supported Lewis Acids as Recyclable Catalysts in Water

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Fluorous reverse-phase silica gel-supported Lewis acids as recyclable catalysts in water

Fluorous reverse-phase silica gel (FRPSG)-supported Lewis acids which have fluorous ligands acted as effective catalysts of Baeyer–Villiger and Diels–Alder reactions in water. Direct esterification of carboxylic acid with alcohol in organic media was also catalyzed. The FRPSG-supported Lewis acids could be recycled by simple filtration after the reaction.

New Approaches in Radical Carbonylation Chemistry: Fluorous Applications and Designed Tandem Processes by Species Hybridization with Anions and Transition Metal Species

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Multistep Parallel Synthesis of Quinazoline‐2,4‐diones by a Fluorous Biphasic Concept Without Perfluorinated Solvents.

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Multistep Parallel Synthesis of Quinazoline‐2,4‐diones by a Fluorous Biphasic Concept without Perfluorinated Solvents

AbstractBased on perfluoro‐tagged benzyl alcohol adsorbed via fluorous–fluorous interactions on fluorous reversed‐phase silica gel (FRPSG), we have performed a multistep synthesis leading finally to a small library of quinazoline‐2,4‐diones. The whole reaction sequence runs without isolation of intermediates and most importantly, without the need of perfluorinated solvents.

New approaches in radical carbonylation chemistry: fluorous applications and designed tandem processes by species-hybridization with anions and transition metal species.

New approaches in radical carbonylation chemistry are described. We have successfully integrated tin mediated radical carbonylation chemistry into modern fluorous applications and separation techniques. We revealed that radical carbonylation reactions can be performed using fluorous tin mediators, such as fluorous tin hydride and fluorous allyltin reagents. Fine tuning of the reaction conditions resulted in a good efficiency equivalent to conventional tin mediators. The tedious procedure of removing organotin byproducts can be circumvented through the use of fluorous/organic liquid-liquid extraction or fluorous liquid-solid phase extraction with fluorous reverse phase silica (FRPS). Also described are newly developed tandem carbonylation reactions that are based on species hybridization approaches. Using a radical/anionic hybrid system based on zinc-induced one-electron reduction, we achieved a three-component coupling reaction consisting of 4-alkenyl iodides, carbon monoxide, and electron-deficient alkenes. We observed two types of annulations processes, namely [4 + 1](radical)/[3 + 2](anionic) and [5 + 1](radical)/[3 + 2](anionic), which lead to the production of bicyclo[3.3.0]octanols and bicyclo[3.2.1]octanols, respectively. We found a radical/palladium hybrid system to be useful in the construction of new cyclic systems that incorporate two or three molecules of carbon monoxide.

Parallel fluorous biphasic synthesis of 3H-quinazolin-4-ones by an Aza-Wittig reaction employing perfluoroalkyl-tagged triphenylphosphine

A perfluoroalkyl-tagged triphenylphosphine was applied in a fluorous biphasic system for the efficient parallel synthesis of 3H-quinazolin-4-ones via an Aza-Wittig reaction. The products were isolated by solid-phase extraction on fluorous reversed-phase silica gel. A new solid-phase bound phosphine derivative was used for comparison and yielded similar results.

ChemInform Abstract: Fluorous Reverse Phase Silica Gel. A New Tool for Preparative Separations in Synthetic Organic and Organofluorine Chemistry

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Enantioselective addition of diethylzinc to aldehydes catalyzed by fluorous β-aminoalcohols

A fluorous aminoalcohol prepared from ephedrine has been used as a catalyst for the enantioselective addition of diethylzinc to aldehydes to afford the corresponding alcohols in up to 84% ee. The fluorous amino alcohol was easily recovered by a simple filtration through a fluorous reverse phase silica gel and was reusable without purification.

Synthesis of perfluorinated allylic compounds by radical allylation and their purification over fluorous reverse-phase silica

A simple free-radical method for the preparation of a variety of perfluorinated allylic compounds has been developed starting from perfluoroalkyl iodides and allyltins. Allyltributyltin, methallyltributyltin and crotyltributyltin all proved to be useful for the transformation. The desired perfluorinated allylic compound was conveniently isolated from the crude mixture by solid-phase extraction with fluorous reverse-phase silica (FRPS).

Fluorous Reverse Phase Silia Gel. A New Tool for Preparative Separations in Synthetic Organic and Organofluorine Chemistry

Fluorous reverse phase silica gel, or silica gel with a fluorocarbon bonded phase, can be readily prepared by standard techniques, but shows unusual separation features. This silica gel separates primarily by fluorine content. Uses of fluorous reverse phase silica gel in both synthetic organic chemistry and organofluorine chemistry are introduced. Solid phase extraction can be used to separate fluorous or fluorous-tagged compounds from organic compounds. Fluorous chromatography can be used to purify mixtures of compounds with differing fluorine content as well as for "demixing" in the new technique of fluorous mixture synthesis.

Separation of "light fluorous" reagents and catalysts by fluorous solid-phase extraction: synthesis and study of a family of triarylphosphines bearing linear and branched fluorous tags.

Practical syntheses of new triarylphosphines bearing both linear and branched fluorous tags (Rf) are reported. The phosphines have one, two, or all three aryl rings bearing fluorous tags: (Ph)(3)(-)(n)()P(C(6)H(4)(CH(2))(m)()Rf)(n)(). Fluorous-organic partition coefficients have been measured and the retention properties of both the phosphines and the derived phosphine oxides on fluorous reverse phase silica have been studied. While applications relying on liquid-liquid extractive separations of these phosphines may be limited to those bearing three fluorous chains, the technique of solid phase extraction should be broadly applicable to phosphines, phosphine oxides, and derived metal complexes. A parallel platinum-catalyzed allylation of aldehydes with fluorous allyl stannanes illustrates the usefulness of the new fluorous ligands in small-scale synthesis.

Preparation of a Fluorous Chiral BINOL Derivative and Application to an Asymmetric Protonation Reaction

Fluorous Chiral Proton Source ( R, S)-FDHPEB resulted in a higher enantioselectivity (95% ee) than that of the original nonfluorous ( R, S)-DHPEB (87% ee) in an enantioselective protonation of a samarium enolate. ( R, S)-FDHPEB was easily recovered by a simple filtration through a fluorous reverse phase silica gel and was recyclable.