Fluorous Compounds and Their Role in ... - ACS Publications

In the Classroom edited by

Products of Chemistry

George B. Kauffman California State University Fresno, CA 93740

Fluorous Compounds and Their Role in Separation Chemistry Maria Angeles Ubeda Departament de Quimica Inorganica, Universitat de Valencia, Valencia, Spain Roman Dembinski* Department of Chemistry, Oakland University, Rochester, MI 48309-4477; *[email protected]

Fluorous chemistry is the study of the structure, composition, properties, and reactions of highly fluorinated molecules, molecular fragments, materials, and media (1). Although it was known for many years that some combinations of fluorous and organic solvents form bilayers, the incipiency of fluorous chemistry began in an inconspicuous way in 1991 when M. Vogt, a graduate student with Keim at the University of Aachen defended his Ph.D. thesis describing the application of perfluorinated polyethers for the immobilization of homogeneous catalysts (2). In 1993, Zhu reported the use of perfluorocarbon reaction solvents for azeotropic separations (3). These works were generally overlooked until a 1994 widely publicized article by Horváth and Rábai (4, 5). This contribution described and named a general concept “fluorous biphase catalysis”, and established its application to an important process, rhodium-catalyzed hydroformylation, taking advantage of the temperature-dependent miscibility of organic and perfluorinated solvents. It also triggered vigorous research in the fluorous field, which is currently expanding throughout world laboratories, now reaching its 10th anniversary (6, 7). The main focus of fluorous chemistry targets resourceand time-consuming separation, in order to improve the material economy, and thus represents potentially environmentally friendly technology (green chemistry). To the authors’ knowledge, none of the current organic chemistry textbooks address the fluorous approach. It may broaden students intellectually if they are acquainted with the fluorous concept in organic chemistry (either in the classroom or laboratory), or in the environmental curriculum. Other modern separation techniques that are directed towards efficient workup in organic synthesis have recently been reviewed in detail (8).

Fluorous Phase The term fluorous phase was introduced, as an analogue to the aqueous phase, for highly fluorinated alkanes, ethers, and tertiary amines. Such compounds are usually colorless liquids of high density, inert, nontoxic, nonpolar, and, due to their very weak intermolecular forces, hydrophobic and lipophobic (amphiphobic). Many fluorous solvents, commonly the fluorinated alkanes, are commercially available; some of them are sold as mixtures of isomers (Table 1). They commonly form bilayers with organic solvents at room temperature, as illustrated by the left container in Figure 1.1 At the same time, many such solvent combinations become miscible at elevated temperatures. Temperature dependence of miscibility with organic solvents is shown for perfluoro(methylcyclohexane) in Table 2. Organic compounds normally have low affinities for fluorous solvents relative to organic solvents. However, compounds that consist mainly of perfluoroalkyl segments show high affinities. This reflects a “like dissolves like” (similia similibus solvuntur) effect. Accordingly, high fluorous affinities could be imparted to catalysts, reagents, and reactants by appending “fluorous tags (labels)” called also “ponytails” such as CF3(CF2)m-1(CH2)n, abbreviated in literature as Rfm(CH2)n, in sufficient numbers or lengths. These tags are usually stable under the reaction conditions and do not interfere with the chemical reactions. The (CH2)n segments of the fluorous tag can be used to fine-tune electronic properties (9). When sufficiently long, they insulate the active site from the electron-withdrawing fluorines. When short, catalysts and reagents have enhanced Lewis acidities. Thus, the fluorous molecules in general contain two domains: a fluorous domain that controls the fluorous solubility of the molecule

Table 1. Representative Fluorous Solvents Solvent

Formula

BPa/ºC

MPa/ºC

Common Name

Perfluorohexane

C6F14

057.1

0᎑87.1

FC-72b

Perfluoro(methylcyclohexane)

C6F11CF3

076.1

0᎑44.7

PFMC, PFMCH

Perfluorodecaline

C10F18

1420

00᎑10

–

Perfluorotributylamine

C12F27N

178–180

00᎑50

FC-43

Perfluoropolyether

CF3[(OCF(CF3)CF2)n(OCF2)m]OCF3c

070

50.1c

Carbon tetrachloride

rt

>26.7c

Benzene

rt

>84.9c

Ether

b

0

and an organic domain that directs the reactivity of the compound. The fluorous compounds are conveniently classified as “heavy fluorous” when they contain 60% or more fluorine by molecular weight and “light fluorous” with 40% or less fluorine by molecular weight, or no more than 21 fluorine atoms (7).

cool

reactant

fluorous solvent

F-catalyst

product

F-catalyst

biphase

monophase

biphase

reactant

product

F-catalyst

rt

a Volume ratio 1:1. Data from ref 6j. bExperimental observation—not a consolute temperature. cConsolute temperature: The temperature above which phase separation does not occur irrespective of composition of the liquid mixture. rt: room temperature.

warm

organic solvent

recycle F-catalyst

Figure 1. Fluorous biphase catalysis: liquid–liquid extraction.

condensed fluorous catalyst P condensed product

amphiphilic solvent monophase

F

reactant F-catalyst product

recycle F-catalyst

Fluorous Separation Techniques

recycle F-catalyst remove solvent

Fluorous chemistry offers the advantage of easy separation based on different affinities of organic and fluorous molecules. Representative fluorous approaches exploit phase separation and are summarized below.

Separation by Liquid–Liquid Extraction: Fluorous Biphase System A catalytic or stoichiometric reaction can be carried out in the fluorous biphase system. When the temperature is increased, the organic and fluorous solvents become miscible, and the reaction, using a fluorous catalyst or reagent, is effected under homogeneous conditions in the higher temperature monophasic limit (Figure 1, middle container).2 When the temperature is decreased to biphasic limit, two phases appear again. The organic products are separated from the fluorous catalyst or transformed reagents by liquid–liquid extraction (Figure 1, right container). In the fluorous biphase catalysis, the catalyst can be recycled with the fluorous phase for a new reaction. Heavy-fluorous compounds are preferred for this technique to facilitate good separation; the number of perfluoroalkyl groups is also an important factor controlling the partition coefficient, as appropriate shielding of the hydrocarbon domain leads to higher fluorous solubility and higher partitioning. Separation by Filtration after Reaction in an Amphiphilic Solvent Amphiphilic solvents, frequently less expensive than fluorous solvents, may provide an appropriate solubility for both the fluorous catalyst (or reagent) and organic reactants. Thus, the reaction can be carried out under homogeneous conditions with the use of one solvent (Figure 2). An additional manipulation is required to effect the separation. After removal of the solvent, a fluorous catalyst (or reagent) can

www.JCE.DivCHED.org

•

extract w. organic solvent

extract w. fluorous solvent

F-catalyst P P

product

isolate

P

P

isolate

F F

F

Figure 2. Fluorous reaction in amphiphilic solvent.

be precipitated from an organic solvent, or organic products can be precipitated from the fluorous solvent. Separation is usually attained by filtration. This system as well as the former one can be applied for fluorous reactants or products with the use of an organic catalyst or reagent. Alternatively, after reaction in an amphipilic solvent a solid–liquid extraction (see below) can be applied.

Separation by Solid–Liquid Extraction A large number of fluorines in a molecule reduces its solubility in organic solvents. This fact, although desired during the separation, can be a serious impediment during the reaction stage. Lowering the fluorine content without compromising the separation effectiveness is possible by replacing the liquid–liquid extraction by solid–liquid extraction over a fluorous reverse-phase silica gel (10). Silica gel can be modified, analogously to alkyl reverse phase, by fluorous means; by reaction of regular silica gel with

Vol. 83 No. 1 January 2006

•

Journal of Chemical Education

85

In the Classroom

a perfluoroalkyl silane reagent (Scheme I). The resulting fluorous reverse-phase silica gel contains perfluoroalkyl chains that can retain the fluorous molecules and may be used as a chromatography support for separation and purification. Fluorous silica gel is charged with a mixture of fluorous and organic compounds (Figure 3, left column). Compounds without any fluorous groups are eluted first using the “fluorophobic solvent” in which the fluorous compounds have little solubility; then “fluorophilic solvent” is used to elute the fluorous compounds (Figure 3, middle and right column). Whereas effective partitioning into a fluorous liquid phase generally requires two or three perfluoroalkyl groups to be attached, the fluorous reverse-phase silica gel technique re-

CH3 silica OH

+

Cl Si CH2CH2(CF2)7CF3

CH3 silica gel

fluorous chlorosilane

base

CH3 silica O Si CH2CH2(CF2)7CF3

CH3 fluorous reverse-phase silica gel

Scheme I. Synthesis of fluorous reverse-phase silica gel.

fluorophobic solvent

fluorophilic solvent

O F O F O F F F F

O

F

quires much lower fluorine content for separation to be effective and can be applied to light-fluorous compounds. This process called solid-phase extraction finds application in light-fluorous synthesis allowing efficient separation in a short period of time. Fluorous reverse-phase silica gel can also be used for separation of mixtures of compounds with differing fluorine content (11) or for immobilization of fluorous catalysts (12). The effort required for preparation of fluorous silica gel results in a higher price for this chromatography medium.

Separation by Filtration with the Use of a Thermomorphic Catalyst (Liquid–Solid Separation) The larger scale use of perfluorocarbon solvents has the drawback of higher costs and a growing concern over their environmental fate. Although the compounds typically used in fluorous techniques are not known to be toxic and are believed to have no significant contribution to ozone depletion, the issue of persistence and potential bioaccumulation remains. Recent work has shown that the fluorous solvent normally required for catalyst or reagents recovery can be eliminated. Fluorous biphasic catalysis has been demonstrated without the use of fluorous solvents (13, 14). In this modified version the reaction is carried out in the absence of a fluorous solvent, by taking advantage of the temperature-dependent solubility of perfluorinated compounds in organic solvents. As shown in Figure 4, a system containing a solid, thermomorphic3 fluorous catalyst and an organic solvent is warmed to achieve monophasic reaction conditions. After a homogenous catalytic transformation, the system is cooled to precipitate the catalyst, which can then be isolated by simple filtration. Triphasic Reactions The dimensions of fluorous chemistry have been extended to triphase reactions. Different approaches are possible. The most obvious system includes fluorous, organic, and water phases. Other procedures, such as phase vanishing–fluorous phase screen reactions, were also developed (15, 16).

organic solvent

warm reactant

reactant

cool product

F-catalyst F F

O

organic compound

F

fluorous compound fluorous reverse phase silica gel

O

product

biphase (insoluble catalyst)

F

monophase (soluble catalyst)

F

F

biphase (insoluble catalyst)

recycle F-catalyst O

F

F

Figure 3. Solid phase extraction over the fluorous reverse-phase silica gel.

86

F F


•

thermomorphic F-catalyst as precipitate

Figure 4. Strategy with the use of a fluorous thermomorphic catalyst.


•

www.JCE.DivCHED.org

Fluorous Synthesis The general factors that determine preferential fluorous solubility apply to metal-based catalysts, inorganic, organic, or organometallic reagents. Thus, the fluorous concept can be adapted to either catalytic or stoichiometric organic reactions. The fluorous tags can be implemented into different reaction components: catalysts, reagents, and reactants (8b).

Fluorous Catalysts When a fluorous catalyst is used in an organic reaction, the organic product usually remains in the organic solution phase, the catalyst being present in the other phase. Products and the catalyst can be separated by fluorous techniques and the catalyst can be recovered and recycled for further use (Figure 6). This situation complements the separation approaches illustrated in Figures 1, 2, and 4. This approach is described for the amide synthesis. The condensation catalyst, 3,5-bis(perfluorodecyl)phenylboronic acid (1), is used under reflux conditions and is effectively recovered after precipitation at room temperature (13). In a test reaction of the condensation of cyclohexanecarboxylic acid and benzylamine, a 99% conversion is achieved in each of ten consecutive cycles (Scheme II). The electron-withdrawing properties of a perfluoroalkyl chain are used as an advantage in developing 1 as a condensation catalyst. The lack of methylene spacers allow for the transfer of the inductive effect over the phenyl ring, decreasing the electron density on the boron atom and increasing Lewis acidity. Another example of a fluorous thermotropic reaction includes the phosphine-catalyzed addition of alcohols to propiolates (Scheme III) (14). Comparable yields are reported for experiments involving the fluorous solvent and also when carried out in its absence. In the latter case, the higher yielding recovery of the catalyst phosphines P[(CH2)2(CF2)7CF3]3 and P[(CH2)3(CF2)7CF3]3 (2) allow for retention of ca. 90% of catalytic activity for all subsequent cycles. Since the catalysts are usually used for reactions in a fraction of a molar percent compared to the reactants, the amount of the catalyst handled in common laboratory experiments is small. The increase of mass and volume of the filtered precipitation was achieved by addition of Teflon shavings to the reaction mixture. Although the attraction between saturated fluorocarbons is weak, it was sufficient enough for the catalyst residues, such that they become firmer and easier to manipulate, allowing for less catalyst leaching. www.JCE.DivCHED.org

•

P

organic solvent

Pph as e

I

Sph as e

R

organic solvent

Pph as e

Sph as e

I S-F

Pph as e

One possible procedure exploits two organic phases separated by a fluorous phase by means of a U-tube (Figure 5) (17). The fluorous phase (F-phase) acts as a barrier (phase screen) between the organic phases, only molecules that can cross the F-phase can move between the two organic phases. The fluorous reactant or substrate that contains impurities is added to an organic phase (S-phase), and the organic reagents to the other organic phase. The fluorous compound migrates from the S- to F-phase and in the interface with the P-phase the reaction and the detagging process takes place. The product accumulates in the organic P-phase. This triphasic system allows for removal of the fluorous tag combined with separation of fluorous tagged compounds from other organic products or impurities. This method can be used with light-fluorous compounds.

Sph as e

In the Classroom

P

organic solvent

I

R

R S-F

F S-F F

S-F F

F

S-F

S-F F-phase

F-phase

F-phase

S-F fluorous reactant F

residual fluorous tag

I

impurities

R

reagent

P detagged product

Figure 5. An example of strategy for triphase systems reaction.

reactant

ⴙ

reagent

F

catalyst

product

ⴙ

catalyst

F

separation by fluorous techniques

product

catalyst

F

Figure 6. Strategy with the use of a fluorous-tagged catalyst. O OH

+

H2N

(CF2)9CF3 (HO)2B (CF2)9CF3 1 (5% mol)

O N H

Scheme II. Synthesis of an amide catalyzed by fluorous phenylboronic acid, 1.


•


87

In the Classroom

Fluorous Reagents When fluorous reagents are used in an organic reaction the “fluorous tags” remain in the reagent excess and byproducts (Figure 7). The organic products can be easily separated by fluorous techniques. For instance, chlorodimethoxy-1,3,5-triazine (CDMT), a well-known condensation agent that is remarkably useful for formation of a C(O)–N bond, can be replaced by a derived fluorous reagent (F-CDMT, 3, Scheme IV). The addition of two perfluorooctyl “ponytails” ensures a fluorine content of 63.8% that exceeds the requirements for good fluorous partitioning and provides appropriate shielding. This reagent has been successfully applied for the synthesis of peptide bonds (18).

Similarly, difficulties in the separation of byproducts in the Mitsunobu reaction (19) prompted the synthesis of fluorous analogs of the commonly used Mitsunobu reagent, diethyl azodicarboxylate (DEAD). The fluorinated azodicarboxylate (F-DEAD, 4, Scheme V), which can be combined with fluorous phosphine (5), renders separation of the fluorous byproduct and subsequent recovery of the fluorous reagent (20). O Cbz

H C

N

C

OH

H2N

+

COOMe

CH

CH2OH

Cl

R

OH

N

N

OCH3

+

CF3(CF2)7CH2O

4-methylmorpholine

OCH2(CF2) 7 CF3

N 3

O

Cbz = C6H5CH2OCO

P[(CH2)x (CF2)7CF3] 3 2

R = H or Me

Cbz

O

H C

N

C

H N

H C

COOMe

CH2OH

(10% mol, x = 2, 3)

Cbz-Pro-Ser-OMe

O

R

OCH3

Scheme IV. Synthesis of a dipeptide with the use of fluorous-modified triazine reagent, 3.

O COOH

Scheme III. Fluorous alkyl phospine-catalyzed addition of alcohols to methyl propiolate.

reactant

ⴙ

+

COOEt OH

O2N

NO2

F

reagent

CF3(CF2)5(CH2)2O

P

O N N O

ⴙ

product

reagent

ⴙ

F

byproduct

F

(CH2)2(CF2)7CF3

CF3(CF2)5(CH2)2O 4

5


COO product

COOEt

F

reagent ⴙ

F

byproduct

Figure 7. Strategy with the use of a fluorous-tagged reagent.

88


•

O2N

NO2

Scheme V. Mitsunobu reactions with the use of fluorous-modified reagents: azodicarboxylate, 4, and phosphine, 5.


•

www.JCE.DivCHED.org

In the Classroom

Phosphines, which can also serve as ligands for catalysts, were the first organic fluorous compounds reported; numerous articles and reviews cover this area (6e, 7).

Fluorous Reactants or Protecting Groups Fluorous tagging of reagents may prove costly and impractical in multistep syntheses that require different reagents for each transformation stage. Another possible approach would be tagging the reaction substrates for one or a series of reactions with regular reagents, followed by isolation of the tagged product, and subsequent detagging. The most popular and widely used tagging protocol, utilizing polymeric tags, is the solid-phase synthesis, which does not offer the advantage of a solution method. The fluorous synthesis can be carried out in solution, in an analogous way to solid-phase synthesis (21, 22). In the first stage of this protocol, a fluorous tag is attached to an organic substrate. The size and fluorine content of the tag should ensure facile isolation of the tagged intermediates and products in fluorous media. After one or a sequence of chemical transformations, the excess reagents and byproducts are separated by appropriate techniques; the desired product is obtained after detachment of the fluorous tag at the final stage (Figure 8). This methodology is illustrated for a well-known transformation such as the Mitsunobu reaction. A typical reagent, benzoic acid, is replaced by its tagged (gallic acid) derivative

(6, Scheme VI) and reaction is carried out in the presence of regular reagents, diisopropyl azodicarboxylate (DIAD) and triphenylphosphine (23). As a result, separation of the fluorous ester from reagent-derived byproducts is achieved in excellent yield by simple precipitation after exchange of the solvent, thus avoiding a chromatographic separation. The fluorous tag can be introduced temporarily as a protecting group or to render separation. For example, a fluorous benzyloxycarbonyl reagent (7) can be introduced into a peptide at the final stage of the solid-phase peptide synthesis (Scheme VII) (24) to facilitate purification by fluorous chromatography (25). Many applications of the synthetic approaches discussed above have been developed over the last few years. Almost every well-known “named” organic reaction has been converted into a fluorous protocol. In addition to the already mentioned Mitsunobu protocol, Wittig (26), Appel (27), or asymmetric aldol (28) reaction, Friedel–Crafts acylation (29), Swern (30) or Baeyer–Villiger (31) oxidation, Ugi (21) or Biginelli (21, 22) condensation, and Heck (32), Negishi (33), Sonogashira (12, 34), Stille (35), or Suzuki (36) coupling have been carried out in fluorous conditions. Alternative Solvents Low solubility of polar substrates in a nonpolar fluorous medium could have been a serious limitation of the scope of

HO

ⴙ

F

reactant

reagent CF3(CF2)7(CH2)4O CF3(CF2)7(CH2)4O

COOH

DIAD PPh3

CF3(CF2)7(CH2)4O 6

product

ⴙ

F

reagent

ⴙ

byproduct

CF3(CF2)7(CH2)4O


CF3(CF2)7(CH2)4O

COO

CF3(CF2)7(CH2)4O

product

F

reagent KOH

ⴙ detagging

byproduct

product HO

Figure 8. Strategy with the use of fluorous-tagged reactants.

www.JCE.DivCHED.org

•

Scheme VI. The Mitsunobu reaction with fluorous acid, 6.


•


89

In the Classroom

reactions that could be carried out in biphase systems. Since not all organic–fluorous combinations are miscible, even at elevated temperatures, a need emerged for a solvent that would dissolve both the typical organic (and often polar) compounds, as well as the fluorinated reagents (amphiphilic solvent). A lightly fluorinated solvent, C6H5CF3 (α,α,αtrifluorotoluene or benzotrifluoride, BTF), can be used for such homogenous reactions. Separation is achieved by the appropriate solvent exchange and extraction of the fluorous compounds into a fluorous phase (or organic compounds into organic phase) similarily as discussed earlier, see Figure 2 (37). The use of supercritical CO2 (scCO2) as the reaction medium for processes involving fluorous reagents or catalysts represents a possible alternative, as the nonpolar fluorous part of the molecules notably increases its solubility in nonpolar scCO2 (38). Fluorous compounds may also serve as surfactants to dissolve organic materials in scCO2 (39). Dissolving CO2 (at 25 bar or higher) into a fluorophobic solvent makes the solvent become fluorophilic. This can be used to extract a fluorous catalyst from the surface of fluorous silica gel to allow homogeneous catalysis. After the catalysis is completed the CO2 pressure can be released, causing the catalyst to be readsorbed by the silica gel (40).

H2N

Conclusions Processes featuring easy isolation procedures are of great interest in the development of environmentally friendly technologies. Many applications of fluorous methods that combine the advantages of solution-phase reactions with effective separation have been developed over the last few years. Although environmental concerns may be reflected in legislation that phases out hydrofluorocarbons, further development of fluorous chemistry has a great potential as a green method for chemical synthesis. To match the increasing importance of fluorous chemistry, the inexpensive and instructive spectacular demonstrations or undergraduate laboratory experiments that are included in “Fun and Games with Fluorous Chemistry“ chapter of ref 7 can be discussed or demonstrated in any chemistry curriculum. Sets of slides or animations and other valuable materials are available (can be downloaded at no charge) from Fluorous Technologies, Inc. (41). Notes 1. Perfluorinated aromatic solvents are usually miscible with organic solvents. Some can serve as amphiphilic solvents; they con-

protected peptide

resin

O O

CF3(CF2)7

Cl

7

O O

CF3(CF2)7

protected peptide (target)

+

resin

nontagged byproduct immobilized peptides

clevage, selective deprotection

O

protected peptide (target)

O

CF3(CF2)7

+

nontagged byproduct peptides

tag-specific purification, deprotection

peptide (target)

Scheme VII. Application of fluorous benzyloxycarbonyl tagging reagent, 7, for purification in peptide synthesis.

90


•


•

www.JCE.DivCHED.org

In the Classroom tain a few fluorine atoms and can dissolve organic and fluorous reagents (see also Alternative Solvents). 2. Sometimes the reactions can proceed below the mixing temperature of the solvent, in the inner phase of both solvents, and it is not necessary to achieve homogeneous conditions. 3. A catalyst or reagent with a highly temperature-dependent property, such as solubility.

Acknowledgments We thank Oakland University, the Research Excellence Program in Biotechnology, and the Ministerio de Ciencia y Tecnologia (Project MAT2002-0442-1-C02-02) for funding. We also thank M. Dembinska for technical assistance. RD is grateful to J. A. Gladysz for introducing him to fluorous chemistry and invaluable support. Literature Cited 1. Gladysz, J. A.; Curran, D. P. Tetrahedron 2002, 58, 3823– 3825. 2. Vogt, M. Ph.D. Thesis, Rheinisch-Westfälischen Technischen Hochschule, Aachen, Germany, 1991. 3. Zhu, D.-W. Synthesis 1993, 953–954. 4. Horváth, I. T.; Rábai, J. Science 1994, 266, 72–75. 5. Horváth, I. T.; Rábai, J. Fluorous Multiphase Systems. US Patent 5,463,082, Oct 1995. 6. Reviews: (a) Zhang, W. Chem. Rev. 2004, 104, 2531–2556. (b) Zhang, W. Arkivoc 2004, i, 101–109. (c) Tavener, S. J.; Clark, J. H. J. Fluorine Chem. 2003, 123, 31–36. (d) Zhang, W. Tetrahedron 2003, 59, 4475–4489. (e) Pozzi, G.; Shepperson, I. Coord. Chem. Rev. 2003, 242, 115–124. (f ) Dobbs, A. P.; Kimberley, M. R. J. Fluorine Chem. 2002, 118, 3–17. (g) Curran, D. P. Pure Appl. Chem. 2000, 72, 1649–1653. (h) Curran, D. P. In Stimulating Concepts in Chemistry; Stoddard, F., Reinhoudt, D., Shibasaki, M., Eds.; Wiley-VCH: New York, 2000; pp 25–37. (i) de Wolf, E.; van Koten, G.; Deelman, B.J. Chem. Soc. Rev. 1999, 28, 37–41. (j) Barthel-Rosa, L. P.; Gladysz, J. A. Coord. Chem. Rev. 1999, 190–192, 587–605. (k) Betzemeier, B.; Knochel P. Top. Curr. Chem. 1999, 206, 61–78. (l) Fish, R. H. Chem. Eur. J. 1999, 5, 1677–1680. (m) Cavazzini, M.; Montanari, F.; Pozzi, G.; Quici, S. J. Fluorine Chem. 1999, 94, 183–193. (n) Curran, D. P. Angew. Chem., Int. Ed. Engl. 1998, 37, 1174–1196. (o) Horváth, I. T. Acc. Chem. Res. 1998, 31, 641–650. (p) Cornils, B. Angew. Chem., Int. Ed. Engl. 1997, 36, 2057–2059. (r) A collection of articles can be found in the special issue: Fluorous Chemistry. In Tetrahedron; Gladysz, J. A., Curran, D. P., Eds.; 2002, 58, 3823–4131. 7. Handbook of Fluorous Chemistry; Gladysz, J. A., Curran, D. P., Horváth, I. T., Eds.; Wiley-VCH: Weinheim, Germany, 2004; pp 1–595. 8. (a) Tzschucke, C. C.; Markert, C.; Bannwarth, W.; Roller, S.; Hebel, A.; Haag, R. Angew. Chem., Int. Ed. Engl. 2002, 41, 3964–4000. (b) Yoshida, J.; Itami, K. Chem. Rev. 2002, 102, 3693–3716. 9. Jiao, H.; Le Stang, S.; Soos, T.; Meier, R.; Kowski, K.; Rademacher, P.; Jafarpour, L.; Hamard, J.-B.; Nolan, S. P.; Gladysz, J. A. J. Am. Chem. Soc. 2002, 124, 1516–1523. 10. (a) Cavazzini, M.; Quici, S.; Pozzi, G. Tetrahedron 2002, 58, 3943–3949. (b) Curran, D. P. Synlett 2001, 1488–1496. (c) Curran, D. P.; Luo, Z. J. Am. Chem. Soc. 1999, 121, 9069– 9072. (d) Kainz, S.; Luo, Z.; Curran, D. P.; Leitner, W. Synthesis 1998, 1425–1427.

www.JCE.DivCHED.org

•

11. Luo, Z.; Zhang, Q.; Oderaotoshi, Y.; Curran, D. P. Science 2001, 291, 1766–1769. 12. Tzschucke, C. C.; Markert, C.; Glatz, H.; Bannwarth, W. Angew. Chem. Int. Ed. Engl. 2002, 41, 4500–4503. 13. Isihara, K.; Kondo, S.; Yamamoto, H. Synlett 2001, 1371– 1374. 14. (a) Wende, M.; Gladysz, J. A. J. Am. Chem. Soc. 2003, 125, 5861–5872. (b) Wende, M.; Meier, R.; Gladysz, J. A. J. Am. Chem. Soc. 2001, 123, 11490–11491. 15. (a) Curran, D. P.; Werner, S. Org. Lett. 2004, 6, 1021–1024. (b) Jana, N. M.; Verkade, J. G. Org. Lett. 2003, 5, 3787–3790. (c) Iskra, J.; Stavber, S.; Zupan, M. Chem. Commun. 2003, 2496–2497. (c) Nakamura, H.; Usui, T.; Kuroda, H.; Ryu, I.; Matsubara, H.; Yasuda, S.; Curran, D. P. Org. Lett. 2003, 5, 1167–1169. (d) Ryu, I.; Matsubara, H.; Yasuda, S.; Nakamura, H.; Curran, D. P. J. Am. Chem. Soc. 2002, 124, 12946–12947. 16. Luo, Z.; Swaleh, S. M.; Theil, F.; Curran, D. P. Org. Lett. 2002, 4, 2585–2587. 17. Nakamura, H.; Linclau, B.; Curran, D. P. J. Am. Chem. Soc. 2001, 123, 10119–10120. 18. Markowicz, M. W.; Dembinski, R. Synthesis 2004, 80–86. 19. (a) Dembinski, R. Eur. J. Org. Chem. 2004, 2763–2772. (b) Dandapani, S.; Curran, D. P. Chem. Eur. J. 2004, 10, 3130– 3138. 20. (a) Dandapani, S.; Curran, D. P. Tetrahedron 2002, 58, 3855– 3864. (b) Dobbs, A. P.; McGregor-Johnson, C. Tetrahedron Lett. 2002, 43, 2807–2810. 21. Studer, A.; Jeger, P.; Wipf, P.; Curran, D. P. J. Org. Chem. 1997, 62, 2917–2924. 22. Studer, A.; Hadida, S.; Ferrito, R.; Kim, S. Y.; Jeger, P.; Wipf, P.; Curran, D. P. Science 1997, 275, 823–826. 23. Markowicz, M. W.; Dembinski, R. Org. Lett. 2002, 4, 3785– 3787. 24. Filippov, D. V.; van Zoelen, D. J.; Oldfield, S. P.; van der Marel, G. A.; Overkleeft, H. S.; Drijfhout, J. W.; van Boom, J. H. Tetrahedron Lett. 2002, 43, 7809–7812. 25. Curran, D. P.; Dandapani, S.; Werner, S.; Matsugi, M. Synlett 2004, 1545–1548. 26. (a) Galante, A.; Lhoste, P.; Sinou, D. Tetrahedron Lett. 2001, 42, 5425–5427. (b) For Aza–Wittig reaction see: Barthélémy, S.; Schneider, S.; Bannwarth, W. Tetrahedron Lett. 2002, 43, 807–810. 27. Desmaris, L.; Percina, N.; Cottier, L.; Sinou, D. Tetrahedron Lett. 2003, 44, 7589–7591. 28. Hultin, P. G.; Hein, J. E. Synlett 2003, 635–638. 29. Barrett, A. G. M.; Braddock, D. C.; Catterick, D.; Chadwick, D.; Henschke, J. P.; McKinnell, R. M. Synlett 2000, 847–849. 30. Crich, D.; Neelamkavil, S. J. Am. Chem. Soc. 2001, 123, 7449–7450. 31. Hao, X.; Yamazaki, O.; Yoshida, A.; Nishikido, J. Tetrahedron Lett. 2003, 44, 4977–4980. 32. (a) Curran, D. P.; Fischer, K.; Moura-Letts, G. Synlett 2004, 1379–1382. (b) Vallin, K. S. A.; Zhang, Q.; Larhed, M.; Curran, D. P.; Hallberg, A. J. Org. Chem. 2003, 68, 6639– 6645. (c) Moineau, J.; Pozzi, G.; Quici, S.; Sinou, D. Tetrahedron Lett. 1999, 40, 7683–7686. 33. Betzemeier, B.; Knochel, P. Angew. Chem., Int. Ed. Engl. 1997, 36, 2623–2624. 34. Markert, C.; Bannwarth, W. Helv. Chim. Acta 2002, 85, 1877– 1882.


•


91

In the Classroom 35. (a) Hoshino, M.; Degenkolb, P.; Curran, D. P. J. Org. Chem. 1997, 62, 8341–8349. (b) Curran, D. P.; Hoshino, M. J. Org. Chem. 1996, 61, 6480–6481. (c) Schneider, S.; Bannwarth, W. Angew. Chem. Int. Ed. Engl. 2000, 39, 4142–4145. 36. (a) Schneider, S.; Bannwarth, W. Helv. Chim. Acta 2001, 84, 735–742. (b) Chen, D.; Qing, F.; Huang, Y. Org. Lett. 2002, 4, 1003–1005. 37. (a) Review: Maul, J. J.; Ostrowski, P. J.; Ublacker, G. A.; Linclau, B.; Curran, D. P. Top. Curr. Chem. 1999, 206, 80– 105. (b) Curran, D. P.; Hadida, S.; Kim, S.-Y.; Luo, Z. J. Am. Chem. Soc. 1999, 121, 6607–6615. (c) Ogawa, A.; Curran, D. P. J. Org. Chem. 1997, 62, 450–451. (d) Curran, D. P.; Hadida, S. J. Am. Chem. Soc. 1996, 118, 2531–2532. 38. (a) West, K. N.; Hallett, J. P.; Jones, R. S.; Bush, D.; Liotta, C. L.; Eckert, C. A. Ind. Eng. Chem. Res. 2004, 43, 4827–4832. (b) Blaser, H. U.; Studer, M. Green Chem. 2003, 5, 112–117. (c)

92


•

Ablan, C. D.; Hallett, J. P.; West, K. N.; Jones, R. S.; Eckert, C. A.; Liotta, C. L.; Jessop, P. G. Chem. Commun. 2003, 2972–2973. (d) Kho, Y. W.; Conrad, D. C.; Shick, R. A.; Knutson, B. L. Ind. Eng. Chem. Res. 2003, 42, 6511–6517. (e) Leitner, W. Acc. Chem. Res. 2002, 35, 746–756. (f) Zhu, J.; Robertson, A.; Tsang, S. C. Chem. Commun. 2002, 2044–2045. (g) Chen, W.; Xu, L.; Hu, Y.; Banet Osuna, A. M.; Xiao, J. Tetrahedron 2002, 58, 3889– 3899. (h) Wells, S. L.; DeSimone, J. Angew. Chem., Int. Ed. Engl. 2001, 40, 518–527. (i) Bonafoux, D.; Hua, Z. H.; Wang, B. H.; Ojima, I. J. Fluorine Chem. 2001, 112, 101–108. 39. Komoto, I.; Kobayashi, S. J. Org. Chem. 2004, 69, 680–688. 40. Ablan, C. D.; Hallett, J. P.; West, K. N.; Jones, R. S.; Eckert, C. A.; Liotta, C. L.; Jessop, P. G. Chem. Commun. 2003, 2992– 2973. 41. Advanced Separation Chemistry for Life Sciences. http:// www.fluorous.com (accessed Sep 2005).


•

www.JCE.DivCHED.org

Fluorous Compounds and Their Role in ... - ACS Publications

Recommend Documents