Perfluoroalkylated-pyridine catalyzed Aldol condensations of aldehydes and ketones in a fluorous biphasic system without fluorous solvent

Aldol condensation of different ketones with various aromatic aldehydes proceeds efficiently in the presence of catalytic amount of perfluoroalkylated-pyridine in a fluorous biphasic system without fluorous solvent, which has prompted various concerns involving cost, solvent leaching, and environmental persistence. The catalyst can be recovered by simple cooling and precipitation and used again.     

Hf[N(SO2C8F17)2]4-catalyzed Friedel-Crafts acylation in a fluorous biphase system

In a fluorous biphase system, Hf[N(SO₂C₈F₁₇)₂]₄ complex (1 mol %) catalyzes Friedel-Crafts acylation of aromatic compounds such as anisole, toluene and chlorobenzene, and the corresponding aromatic ketones are obtained in satisfactory to high yields. The catalyst is selectively soluble in lower fluorous phase and can be easily recovered by simple phase separation. Furthermore, the catalyst can be reused without decrease of activity in most cases.     

Highly efficient asymmetric aldol reaction in brine using a fluorous sulfonamide organocatalyst

A fluorous organocatalyst promotes direct asymmetric aldol reactions of aromatic aldehydes with ketones in brine to afford the corresponding anti-aldol products in high yield with up to 96% ee. Fluorous organocatalyst can be readily recovered by solid phase extraction using fluorous silica gel and reused without purification.     

A novel fluorous palladium catalyst for Suzuki reaction in fluorous media

Palladium(II) perfluorooctanesulfonate [Pd(OSO₂R_f8)₂] catalyses the highly efficient Suzuki reaction in the presence of a catalytic amount of perfluoroalkylated-pyridine as a ligand in a fluorous biphase system (FBS). The fluorous phase containing the active palladium species is easily separated and can be reused several times without a significant loss of catalytic activity.     

Tin(IV) bis(perfluoroalkanesulfonyl)amide complex as a highly selective Lewis acid catalyst for Baeyer-Villiger oxidation using hydrogen peroxide in a fluorous recyclable phase

Sn[N(SO₂C₈F₁₇)₂]₄ catalyst was shown to give an excellent yield and selectivity in a fluorous biphasic catalytic system for Baeyer-Villiger oxidation of cyclic ketones by 35% aqueous hydrogen peroxide, a green, safe and cheap oxidant. Furthermore, the catalyst was completely recovered and reused in the fluorous immobilized phase without loss of activity.     

Mannich-type reaction of (1-methoxy-2-methylpropenyloxy)trimethylsilane with arylaldehydes and aromatic amines catalyzed by perfluorinated rare earth metal salts in fluorous phase

In this paper, we describe a useful Mannich-type reaction in fluorous phase. By use of perfluorodecalin (C₁₀F₁₈, cis- and trans-mixture) as a fluorous solvent and perfluorinated rare earth metal salts such as Sc(OSO₂C₈F₁₇)₃ or Yb(OSO₂C₈F₁₇)₃ (2.0 mol%) as a catalyst, the Mannich-type reaction of arylaldehydes with aromatic amines and (1-methoxy-2-methylpropenyloxy)trimethylsilane can be performed for many times without reloading the catalyst and the fluorous solvent.     

Immobilized baker's yeast reduction in fluorous media

The first example of immobilized bakers' yeast mediated reduction of ketones in fluorous media is described. The use of fluorous media permits simple work-up and reuse of the solvent without any purification.     

Novel fluorous prolinol as a pre-catalyst for catalytic asymmetric borane reduction of various ketones

Novel prolinol carrying two perfluorohexylethyl groups at the α-position was prepared from l-proline as a starting chiral substrate. Catalytic asymmetric reduction of various ketones, including mono-, di-, and trifluoromethylated acetophenones, using fluorous oxazaborolidines derived from fluorous prolinol afforded the corresponding alcohols in good to excellent yields and with high enantioselectivities (up to 93.2% ee). The fluorous prolinol was recovered without any fluorous solvents or silica gel by simply cooling the organic phase and filtration.     

Highly enantioselective aldol reactions catalyzed by a recyclable fluorous (S) pyrrolidine sulfonamide on water

Fluorous (S) pyrrolidine sulfonamide serves as an efficient promoter for highly enantioselective aldol reactions of ketones and aldehydes with aromatic aldehydes on water. A notable feature of the organocatalyst is that it can be recovered from the reaction mixtures by simple fluorous solid-phase extraction and subsequently reused (up to seven cycles) without a significant loss of catalytic activity and stereoselectivity.     

Ytterbium perfluorooctanesulfonates catalyzed synthesis of benzimidazole derivatives in fluorous solvents

Catalytic condensation of o-phenylenediamine and aldehydes was accomplished using rare earth(III)perfluorooctane sulfonates (RE(OPf)₃), RE = Sc, Y, La ∼ Lu) as catalysts in fluorous solvents. Ytterbium perfluorooctanesulfonates (Yb(OPf)₃) catalyzes the high-efficient synthesis of benzimidazole derivatives in fluorous solvents. By simple separation, fluorous phase containing only catalyst can be reused several times.     

Efficient one-pot conversion of carbonyl compounds to their alpha,beta-unsaturated derivatives using a recoverable, minimally fluorous organoselenium reagent

A protocol for the preparation of a fluorous arylselenenyl chloride is described. This selenenyl chloride may be used for the direct alpha-selenation of ketones and, following oxidation and syn-elimination, formation of alpha,beta-unsaturated carbonyl compounds. Treatment of the crude reaction mixtures with sodium metabisulfite reduces the various selenium species to the diaryl diselenide, which is then recovered in high yield by continuous fluorous extraction.     

Porous alumina-based fluorous liquid membranes: Dependence of transport on fluorous solvent

We report here the properties of supported fluorous liquid membranes based on porous alumina. The alumina is first rendered compatible with fluorous solvents by surface modification with an oligomeric perfluoropropylene oxide-based carboxylic acid, Krytox 157FSH. After modification, simply dipping the porous alumina membrane into a perfluorinated solvent results in a supported liquid membrane with high selectivity for fluorous compounds. Two homologous series of compounds differing in the number of -CF₂- groups were investigated, namely esters of cinnamyl alcohol and the analogous naphthyl derivative with 2H,2H,3H,3H-perfluoroalkanoic acids (HOOC-(CH₂)₂-(CF₂)_m−1CF₃, m = 2, 4, 6 and 8). Four perfluorinated membrane solvents (FC-77, PF-5080, FC-3283 and FC-43) were investigated. In FC-3283, the permeabilities, which are the products of a diffusion coefficient and a partition coefficient in the solution-diffusion model, of cinnamyl alcohol derivatives are 3.62 ± 0.36 times greater than those of the analogous naphthyl compounds for the solutes containing the same perfluorinated chain. Permeability, P, increases as the perfluorinated chain length increases in all of the perfluorinated solvents. Values of log(P) vs m are linear with a slope of 0.147 ± 0.002 but with different intercepts for the various solvents. Independent measurements of the partition coefficients of the solutes between the source/receiving phase solvent, ethanol, and the fluorous solvents reveal that the selectivity behavior is dominated by partitioning rather than diffusion. The free energy of transfer of a -CF₂- group (ethanol to perfluorinated solvents) is −1.1 kJ/mol. Despite the fact that the solvents are mixtures, not pure liquids, the partition coefficients are well correlated with values calculated based on group contributions with ‘mobile order and disorder’ theory. The diffusion coefficients of four solutes in four membrane solvents were also determined based on the solution-diffusion model. The Stoke-Einstein equation shows satisfactory estimation of experimental results.     

Recoverable fluorous CBS methodology for asymmetric reduction of ketones

[reaction: see text]. An operationally simple and recoverable fluorous CBS methodology was developed. The in situ-generated fluorous oxazaborolidine efficiently catalyzed the reduction of ketones with high enantioselectivity and reactivity. The subsequent recycling of the fluorous prolinol precatalyst was achieved by fluorous solid-phase extraction.     

Catalytic enantioselective cyclopropanation of allylic alcohols using recyclable fluorous disulfonamide ligand

Cyclopropanation of allylic alcohols with Et₂Zn and CH₂I₂ in the presence of a catalytic amount of fluorous disulfonamide 3 afforded the corresponding cyclopropylmethanols in 69-96% yield with 49-83% ee. The fluorous ligand 3 was readily recovered from the reaction mixture by the fluorous solid-phase extraction (FSPE) and could be reused without a significant loss of the catalytic activity and enantioselectivity.     

Electrophilic aromatic nitration using perfluorinated rare earth metal salts in fluorous phase

In this paper, we describe a practical, useful electrophilic aromatic nitration process in fluorous phase by using perfluorodecalin (C10F18, cis- and trans-mixture) as a fluorous solvent and perfluorinated rare earth metal salt [Yb(OSO2C8F17)3] as a catalyst for the electrophilic aromatic nitration.     

Phase‐vanishing methods based on fluorous phase screen: A simple way for efficient execution of organic synthesis

The phase‐vanishing (PV) method is based on spontaneous reaction controlled by diffusion of reagents into fluorous media, such as perfluorohexanes (FC‐72) and polyperfluoroethers. Thus, the original PV reaction utilizes a triphasic test tube method composed of a bottom reagent phase, a middle fluorous phase, and a top substrate phase. In such a triphasic system, the fluorous phase acts as a liquid membrane to transport the bottom reagents to the top organic phase containing substrates. In the end, the bottom layer disappears and two phases remain. Since the first demonstration of the PV method by bromination of alkenes with molecular bromine, a number of applications have been developed thus far. These include halogenation of alcohols with SOBr₂ and PBr₃, demethylation of methoxyarenes with BBr₃, cyclopropanation of alkenes by CH₂I₂‐AlEt₃, and Friedel–Crafts acylation of aromatic compounds with SnCl₄. A fluorous triphasic U‐tube method is effective for chlorination of alcohols based on lighter (less dense) reagents such as SOCl₂ and PCl₃. A system using a solution containing reagents as a bottom phase is useful for oxidation with m‐CPBA, which may be defined as a new category for the “extractive PV” method. Recent advances include a “quadraphasic” PV method, in which an aqueous “scavenger” phase is added to the original triphasic PV method to remove acidic by‐products. © 2008 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 8: 351–363; 2008: Published online in Wiley InterScience ( www.interscience.wiley.com ) DOI 10.1002/tcr.20161     

Rare earth(III) perfluorooctanesulfonates catalyzed Friedel-Crafts alkylation in fluorous biphase system

The catalyst of rare earth(III) perfluorooctanesulfonates (RE(OSO₂C₈F₁₇)₃, RE = Sc, Y, La-Lu) were prepared from either rare earth chlorides(III) or oxides and perfluorooctanesulfonic acid. The perflates thus obtained act as novel catalysts for Friedel-Crafts alkylation in fluorous biphasic system. Perfluorohexane (C₆F₁₄), perfluoromethylcyclohexane (C₇F₁₄), perfluorotoluene (C₇F₈), perfluorooctane (C₈F₁₈), perfluorooctyl bromide (C₈F₁₇Br) and perfluorodecalin (C₁₀F₁₈, cis- and trans-mixture) can be used as fluorous solvents for this reaction. By simple separation of the fluorous phase containing only catalyst, alkylation can be repeated many times.     

Total synthesis of cucurbitoside A using a novel fluorous protecting group

The first total synthesis of cucurbitoside A was achieved using a new fluorous N-phenylcarbamoyl (^FCar) protecting group. The ^FCar group was introduced into carbohydrates in high yield and was selectively removed with Bu₄NNO₂ without damaging other acyl protecting groups. The synthetic intermediates were easily isolated by fluorous solid-phase extraction.     

Preparation, properties and synthetic potentials of fluorous boronates

A fluorous approach to the chemistry of boronic acids and its application in fluorous-phase techniques are described. Treatment of fluorous bromosilane 2 with allyl Grignard reagent followed by dihydroxylation provided fluorous diol 1. A series of boronic acids were attached to 1 by esterification. The formed fluorous boronates 4 were moisture sensitive and thus their synthetic potentials were limited. Thus a fluorous pinacol, 5, was designed and synthesized by treatment of fluorous bromosilane 2 with excess 2,3-dimethyl-2-butyenylmagnesium bromide 9 to afford fluorous tetramethyl ethene 8, and was dihydroxylated. Compound 5 was successfully used to prepare fluorous boronates in a one-pot process from organic bromides. We have demonstrated that olefin cross-metathesis can be carried out in a fluorous version. It is noteworthy that all of the fluorinated compounds reported in this paper were purified by simple liquid extraction.     

A fluorous tag-bound fluorescence derivatization reagent, F-trap pyrene, for reagent peak-free HPLC analysis of aliphatic amines

We have developed a novel pre-column fluorescence derivatization reagent for amines, F-trap pyrene. This reagent comprises a fluorescent pyrene moiety, an amine-reactive Marshall linker, and a fluorophilic perfluoroalkyl group known as fluorous tag. When the reagent reacts with aliphatic amines and amino acids to give fluorescent derivatives, the fluorous tag in the reagent is eliminated simultaneously. Therefore, excess unreacted reagents in the derivatization reaction solution still have the fluorous tag and could be removed by fluorous solid-phase extraction selectively before high-performance liquid chromatography (HPLC) analysis. By using this reagent, 13 kinds of aliphatic amine (C₂–C₁₆) derivatives can be separated within 40 min by reversed-phase HPLC with gradient elution. In this chromatogram, unreacted reagents peak at around 28 min, greatly decrease after fluorous solid-phase extraction, and do not interfere with the quantification of each amine. The detection limits (S/N = 3) for examined aliphatic amines are 3.6–25 fmol per 20 μL injection. We have also applied this reagent successfully to the amino acid analysis.