International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

Monday, July 4, 2005
Opening
8:15
R. H. Fish, LBNL, Berkeley/USA
J.-M. Vincent, LCOO-CNRS, Talence/F
Chair: R. H. Fish
Plenary Lecture
8:30
Changing Designer Issues in Fluorous Chemistry
I. T. Horváth, Eötvös University, Budapest, Hungary
Invited Lecture
Enantiopure Fluorous Nitrogen Ligands: Synthesis and Applications in
9:30
Asymmetric Organometallic Catalysis
G. Pozzi, CNR-Istituto di Scienze e Tecnologie Molecolari, Milano, Italy
Oral Communication
Development of Industrial Reaction Processes Using Fluorous Lewis Acid
10:10
Catalysts
J. Nishikido, The Noguchi Institute, Tokyo, Japan
Noncovalent Attachment of Nucleotides by Fluorous-Fluorous Interactions
10:30
W. Bannwarth, University of Freiburg, Germany
10:50
Coffee break
Chair: G. Pozzi
Invited Lecture
11:10
Styling and Setting of Fluorous Ponytails for Engineered Separations
J. Rábai, Eötvös University, Budapest, Hungary
Oral Communication
Pernitrometalloporphyrins with Fluorous Ponytails as Catalysts in
11:50
Epoxydation of Alkenes
K. Pamin, Institute of Catalysis and Surface Chemistry, Kraków, Poland
Fluorous Catalysis With Metal Perfluorocarboxylates
12:10
A. Biffis, Dipartimento di Scienze Chimiche, Padova, Italy
12:30
Lunch
Chair: D. Bonnet-Delpon
Plenary Lecture
14:00
Advances in Highly Fluorinated Materials for Diagnosis and Therapy
J. Riess, University of California, San Diego, USA
Invited Lecture
Basic Principles and Recent Advances in Fluorinated Self-Assemblies and
15:00
Colloidal Systems
M.- P. Krafft, Institut Charles Sadron, Strasbourg, France.
Oral Communication
15:40
Gelation of Perfluorocarbons
J.-L. Pozzo, Unversité Bordeaux 1, Talence, France
16:00
Coffee break
Chair : M.-P. Krafft
Invited Lecture
16:20
Self-Assembly Mediated by the Fluorophobic Effect
V. Percec, University of Pennsylvania, Philadelphia, USA
Oral Communication
Spontaneous Resolution Phenomena In Perfluorocarbon-Hydrocarbon
17:00
Supramolecular Architectures
P. Metrangolo, Department of Chemistry Polytechnic of Milan, Italy
Poster Session (Wiley VCH prize committee: R. H. Fish, D. P. Curran, J. A.
17:20
Gladysz)
19:30
Reception City Hall of Bordeaux

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International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

Tuesday, July 5, 2005
Chair: D. P. Curran
Plenary Lecture
Fluorous Chemistry without Fluorous Solvents: New Catalyst Recovery
8:30
Protocols based upon Fluoropolymers
J. A. Gladysz, University Erlangen-Nürnberg, Germany
Invited Lecture
9:30
Fluoro-alcohols: Effective Solvents for Classical Organic Reactions
D. Bonnet-Delpon, Laboratoire BioCIS, Chatenay Malabry, France
Oral Communication
10:10
Fluorous-Derivatised Phase Transfer Catalysts
A. M. Stuart, University of Leicester, Leicester, UK
10:30
Coffee break
Chair: J. Otera
Invited Lecture
New Synthetic Methods for Natural Products Using Heavy Fluorous
11:00
Technics
T. Inazu, The Noguchi Institute, Tokyo, Japan
Oral Communication
11:40
Chemical Synthesis of Oligodeoxyribonucleotides on a Fluorous Dendron
T. Wada, The University of Tokyo, Japan
Synthesis of Monofunctional Perfluoropolyethers
12:00
G. Fontana, Solvay Solexis, Milan, Italy.
12:20
Lunch
Chair: A. M. Stuart
Plenary Lecture
14:00
Fluorous Organotin Chemistry
J. Otera, Okayama University of Science, Okayama, Japan
Oral Communication
Fluorous-Tagged Glycoside Primer for Saccharide Chain Elongation by
15:00
Cellular Enzyme
K. Hatanaka,The University of Tokyo, Japan
Solvation of oxygen, carbon dioxide, carbon monoxide and nitrous oxide
15:20
in fluorinated liquids
M. F. Costa Gomes, Université Blaise Pascal, France
15:40
St Emilion visit
20:00
Banquet at Chateaux La Couspaude

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International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

Wednesday, July 6, 2005
Chair: I. T. Horváth
Plenary Lecture
8:30

9:30
9:50
10:10
10:30

27

Fluorous Biphasic Catalysis: Oxidation of Alkanes, Alkenes, Alcohols, andAlkenols with Mn(II), Co(II), and Cu(I and II) Fluorous Soluble or
Thermomorphic Complexes in the Presence of TBHP/O2 or TEMPO/O2 or
H2O2.
R. H. Fish, University of California, Berkeley, USA
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Oral Communication
Design and Application of Highly Fluorous Catalysts
B.-J. Deelman, Utrecht University, The Netherlands
F-TEMPO Radicals: Efficient Mediators for the Oxidation of Alcohols
O. Holczknecht, CNR-Istituto di Scienze e Tecnologie Molecolari, Milano, Italy
Alternative Solid Supports for Fluorous Catalysis
E. G. Hope, University of Leicester, England
Coffee break

Chair: W. Bannwarth
Oral Communication
Perfluorinated Vinyl Sulfoxydes: Efficient Synthons for the Preparation of
10:50
Fluorinated Tetraazamacrocycles. Applications in Catalysis.
E. Magnier, Université de Versailles-Saint-Quentin, Versailles, France
Hydrogenation of Styrene and 1-octene catalyzed using Pd(II) complex
with monodentate perfluoropyridine in scCO2 and conventional organic
11:10
solvents
I. Kani, Anadolu University, Turkey
Fluorous Biphasic Catalysis Without Solvent: Novel Recycling Concept
11:30
P. Pollet, Georgia Institute of Technology, Atlanta, USA
Synthesis of Fluorous Phosphines
G. Vlád, J. Fraga-Dubreuil, N. Farkas, F. Richter, I. T. Horváth, Eötvös
11:50
University, Department of Chemical Technology and Environmental Chemistry,
Hungary
Lunch
12:10

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Chair: J. A. Gladysz
14:00

14:40

15:00

15:20

15:40

16:40
17:10

Invited Lecture
Application of Fluorous Technologies in Solution-Phase Synthesis
W. Zhang, Fluorous Technologies, Inc., Pittsburgh, USA
Oral Communication
An Expeditious Synthesis of Bistratamide H Using a New FluorousProtecting Group
S. Takeuchi, Niigata University of Pharmacy and Applied Life Sciences, Japan
Association of Fluorous ˝Phase-Vanishing˝ Method with Visible-light
Activation for Benzyl Bromination
J. Iskra, University of Ljubljana, Slovenia
Fluoroponytailed Carboxylate Complexes with Non-Fluorous Ligands as
Pre-Catalysts for the Oxidation of Alkenols and Alcohols Under Fluorous
Biphasic or Thermomorphic Modes
M. Contel, Universidad de Zaragoza-C.S.I.C., Spain
Plenary Lecture
Fluorous Mixture Synthesis of Murisolin and Passifloricin Stereoisomer
Libraries
D. P. Curran, University of Pittsburgh, USA
Future Perspectives Panel Discussion Panel: Fish (Chairman), Horváth,Curran, Yeske, Reiss, Krafft
Concluding Remarks / Announcement for next ISOFT

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International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

Poster Program
P1
AN INDICATOR-DISPLACEMENT ASSAY FOR HISTAMINE UNDER FLUOROUS
TRIPHASIC CONDITIONS
B. Fronton, R. Luguya, J.-M Vincent, University of Bordeaux 1, France
P2
HIGHLY FLUORINATED LC MATERIALS FOR SURFACE MODIFICATION
L. Caillier, E. Taffin de Givenchy, F. Guittard,* S. Geribaldi, Université de Nice-Sophia
Antipolis, France
P3
PREPARATION OF FLUOROALKYL PYRIDINE DERIVATIVES FROM 2-AZADIENES AND
DIENOPHILES
F. Palacios, C. Alonso, G. Rubiales, M. Villegas, E. Mtz. de Marigorta, M. Rodríguez,
Universidad del País Vasco, Spain
P4
FLUOROUS GOLD(I) CATALYZED HYDROSILYLATION
D. Lantos, M. Contel, S. Sanz, I. T Horváth, Eötvös University, Hungary
P5
H2O2/FLUORO-ALCOHOL SYSTEM FOR DIRECT AND SELECTIVE SYNTHESIS OF
ANTIMALARIAL 1,2,4,5-TETRAOXANES
K. Žmitek, S. Stavber, M. Zupan, D. Bonnet-Delpon, J. Iskra, University of Ljubljana Slovenia
P6
RECYCLBLE MOLECULAR THERMOMORPHIC CATALYSTS FOR ATOM TRANSFER
RADICAL ADDITIONS AND POLYMERIZATION
D. Lastécouères, G. Barré, D. Taton, J.-M Vincent, University of Bordeaux 1, France
P7
REVERSIBLE
HYDROCARBON/PERFLUOROCARBON
PHASE-SWITCHINGOF
PYRIDYL TAGGED MOLECULES
M. El Bakkari, J.-M Vincent, Université Bordeaux 1, France.
P8
APPLICATION OF THE "PHASE-VANISHING METHOD" TO CYCLOPROPANATION OF
ALKENESH. Matsubara, M Tsukida, M. T. Rahman, I. Ryu, Osaka Prefecture University, JapanP9SYNTHESIS OF OLIGOSACCHARIDE AND PEPTIDE, GLYCOPEPTIDE USINGFLUOROUS SUPPORT
M. MIzuno, K. Goto, T. Miura, T. Inazu, The Noguchi Institute, JAPANP10
REGIOSELECTIVE SYNTHESIS OF FLUORINATED α- AND β-AMINOPHOSPHORUS
DERIVATIVES FROM P-TOLYLSULFONYL OXIMESF.Palacios, A. M. Ochoa de Retana, J. M. Alonso, A. Vélez del Burgo, Universidad del País
Spain
P11
POLYFLUORINATED BAYTRON
V.Ya Popkova, S. Kirchmeyer, V. M. Bazhenov, V. A. Nikanorov, AO Bayer, Moskow, Russia
P12
FLUOROUS CHROMIUM REAGENTS FOR PREPARATION OF ORGANIC COMPOUNDS
S. Ghammamy, M. Rezaee, Azad Islamic University, IranP13
SYNTHESES AND X-RAY CRYSTAL STRUCTURES OF TWO MIXED ANIONICFLUOROUS COMPLEXES
S. Ghammamy, M. Rezaee, Azad Islamic University, Iran

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International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France
54
P14
FLUOROUS SYNTHESIS OF β,β-DIFLUORINATED CYCLIC QUATERNARY αAMINOACIDS
J. Sanz-Cervera, C. del Pozo, M. Sánchez-Roselló, V. Rodrigo, S. Fustero, Universidad de
Valencia, Spain
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P15
METHOD OF SYNTHESIS α,ω−DIPHENYLPERFLUORALKANES
T. Dovbysheva, A. Yasko. Belarusian Polytechnical Academy, Belarus
P16
56
THE SYNTHESIS OF PENTAFLUORIDE OF PHOSPHORUS BY FLUORINATION OFPENTAOXIDE PHOSPHORUS BY ELEMENTARY FLUORINE
T. Dovbysheva, Belarusian Polytechnical Academy, Belarus
P17
57
DEVELOPMENT OF OXYGEN SENSING SYSTEM BY STATIONARY QUENCHINGMETHOD USING ZnTFPP
T. Kamachi, K. Mochizuki, N. Asakura, I. Okura, Tokyo Institute of Technology, JapanP18
58
SYNTHESISAND
AIR-WATERINTERFACEOF
SULFOBETAINEFLUOROSURFACTANTS
P. Thebault, E. Taffin de Givenchy, F. Guittard, S. Geribaldi, Université de Nice-Sophia
Antipolis, France
P19
34
SYNTHESIS OF FLUOROUS PHOSPHINES
G. Vlád, J. Fraga-Dubreuil, N. Farkas, F. Richter, I. T. Horváth, Eötvös University, Departmentof Chemical Technology and Environmental Chemistry, Hungary
P20
59
DEVELOPMENT OF FLUOROUS LEWIS ACID-CATALYZED REACTIONS IN A
FLUOROUS BIPHASIC SYSTEM AND AN APPLICATION TO CONTINUOUS-FLOW
REACTION SYSTEM
A. Yoshida, X. Hao, J. Nishikido, The Noguchi Institute, Japan60
P21
DEVELOPMENT OF SYNTHETIC APPROACHES TO POLYFUNCTIONNAL COMPOUNDSWITH PENTAFLUOROSULFANYL (SF5) GROUPING
V. K. Brel, Russian Academy of Sciences, Chernogolovka, Russia

5International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

CHANGING DESIGNER ISSUES IN FLUOROUS CHEMISTRY
Horváth, I. T.
Department of Chemical Technology and Environmental Chemistry, Eötvös University,
Pázmány Péter sétány 1/A, Budapest, H-1117 Hungary
istvan.t.horvath@hit-team.net

Fluorous chemistry was invented to provide facile separation of the products
from reagents or catalysts.[1] Fluorous ponytails of various lengths and structures are
the key building components of fluorous reagents and catalysts, which are attachedto the reagents or catalysts in appropriate numbers to achieve effective separation.
Product phase
cA

cB

cA

cB

cP

A+B

L
ReagentorCatalyst

L

P

cP
L

L

L = Fluorous group

Fluorous phase

While a fluorous system is designed to remain inside a laboratory or a
production facility, low level leaching to products or accidental releases could resultin environmental issues. If such reagents or catalysts enter the environment, theoxidation of the hydrocarbon domains could lead to the formation of fluorous
carboxylic acids. Some of these acids have been shown to have negative health andenvironmental effects. The bioaccumulation could be limited by using shorter (C1-C4)
or longer (C10+) fluorous ponytails. The application of C10+ fluorous ponytails could
provide good separation, but significantly increases the molecular weight. The
combination of shorter (C1-C4) and longer (C10+) fluorous ponytails could lead tocommercially attractive reagents and catalysts. The incorporation of oxygen or
nitrogen atoms into the fluorous ponytails is another designer tool that could effectsimultaneously separation and environmental effects.
[1]

I.T. Horváth and J. Rábai, Science 1994, 266, 72-75 and I.T. Horváth, Acc.
Chem. Res. 1998, 31, 641-650.

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International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

ENANTIOPURE FLUOROUS NITROGEN LIGANDS: SYNTHESIS ANDAPPLICATIONS IN ORGANOMETALLIC CATALYSIS.
Pozzi, G.
CNR-Istituto di Scienze e Tecnologie Molecolari, via Golgi 19, 20133 Milano, Italy
gianluca.pozzi@istm.cnr.it

The use of novel reaction media in which homogeneous chiral catalysts caneffectively operate and then be easily recovered by simple phase separation iscurrently attracting considerable interest. Research in this field is also stimulated by
the unusual selectivities and increased activities, which are sometimes engenderedby the peculiar solvation environment. The molecular structure of the catalyst which,with the notable exception of ionic liquids, must be specifically tailored for use in oneof these reaction media, is also utterly important. The development of perfluoroalkylsubstituted (fluorous) chiral ligands to be used in liquid-liquid biphasic systems (orsupercritical CO2), [1] but also in common organic solvents or amphiphilic solvents(BTF) [2] nicely illustrates these points.
In this lecture the ongoing efforts to design and use fluorous chiral ligands forasymmetric organometallic catalysis will be summarised, with emphasis on the work
carried out in the author’s lab. [3] The synthesis of fluorous nitrogen ligands (Figure1) and the effect of the perfluoroalkyl chains and reaction media on the activity andselectivity of the corresponding metal complexes in representative enantioselective
transformation will be discussed. Recovery and recycling of catalysts based on chiralfluorous nitrogen ligands can be easily achieved, but after a limited number ofrecycles catalytic activity is usually lost. These are similar results to other supported
systems and have to be improved for fluorous catalysts to have wide applications.
Therefore, there are still many avenues to be researched in this fast expanding fieldin order to tailor fluorous ligands to the demanding requirements of recyclable
asymmetric catalysts.
H

R1

R2

H

H

NH HN
C8F17

C8F17
C8F17

C8F17

O

O

[2]
[3]

C8F17

O

O
N
But

R2

N

N

C8F17

N

H

OH HO
But

C8F17

C8F17

[1]

C8F17

R1

C8F17

But
NH

n C8F17

NH

C8F17
n

But

Sinou, D. in “Handbook of Fluorous Chemistry” (Gladysz, J. A.; Curran, D.;
Horváth; I. T. Eds.), Wiley-VCH, Weinheim, 2004, 306.
Takeuchi, S.; Nakamura, Y. in “Handbook of Fluorous Chemistry” (Gladysz, J.
A., Curran, D., Horváth, I. T. Eds.), Wiley-VCH, Weinheim, 2004, 316.
Pozzi, G.; Shepperson, I. Coord. Chem. Rev. 2003, 242, 115.

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International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

DEVELOPMENT OF INDUSTRIAL REACTION PROCESSES USINGFLUOROUS LEWIS ACID CATALYSTS
Yoshida A.,a Hao X.,a Yamazaki O.,b Nishikido J.ba

The Noguchi Institute, Itabashi-ku, Tokyo 173-0003, Japan
Asahi kasei Corporation, Fuji, Shizuoka 416-8501, Japanbnishikido.jb@om.asahi-kasei.co.jp
Aluminum chloride, boron trifluoride, etc. are known as Lewis acids, but they need to be used
stoichiometrically or in excess to achieved high yield and high selectivity. Furthermore, they are rarely
recovered and recycled. Thus, even though they are widely used industrially, these Lewis acids cause
the production of large amounts of wastes. Our procedure was, first, to develop highly active Lewis
acid catalysts, and then to meet the challenge of creating revolutionary organic reaction processes
using fluorous solvents, water and supercritical carbon dioxide as reaction media. The key
technological aim of the development was to achieve a catalyst recycling system using fluorous Lewis
acid catalysts.
We developed a number of fluorous biphasic reactions such as esterification, Diels-Alderreactions, Mukaiyama aldol reactions, Friedel-Crafts reactions,[1] Baeyer-Villiger oxidations withaqueous hydrogen peroxide,[2] transesterifications and direct esterifications[3] catalyzed by
M[N(SO2Rf)2]n and M[C(SO2Rf)3]n (M = Yb, Sc, Sn, Hf, Ga, Bi, etc.; Rf = n-C8F17, C10HF20O3).

O

1

+

H2O2 aq.
(35%)

:

1

O

Cat. (1 mol%)O

ClCH2CH2Cl 3 mL
CF3-c-C6F11 3 mLrt, 2 h

Cat.

cycle

yield(%) selec.(%)

Sn[N(SO2-n-C8F17)2]4

1
4

93
93

99
99

Sc[N(SO2-n-C8F17)2]3
Sc(OTf)3

1
1

53
31

69
66

We applied the batch fluorous biphasic reactions to the industrial continuous-flow system.[4]The acetylation of cyclohexanol and Baeyer-Villiger oxidation of 2-adamantanone with 35% aqueous
solution of hydrogen peroxide in organic-fluorous biphase were examined to give the corresponding
products with high TON using our original continuous-flow system.
productsin organic solvent
emulsion.. ...
.. . ..
.. ...
.. . ..
.. ...
.
.
.. ...
.
.

organic phasefluorous phasedecantersubstrates
reactorin organic solvent

Continuous-flow reaction model

Bench-Scale continuous-flow system

The fluorous reverse-phase silica gel-supported Lewis acids which have our fluorous ligands
acted as effective catalysts of Baeyer-Villiger oxidation and Diels-Alder reactions in water. Direct
esterification of carboxylic acid with alcohol in organic media was also catalyzed. Our fluorous solid
catalysts could be recycled by simple filtration after reaction.[5]
[1]
[2]
[3]
[4]
[5]

Nishikido, J., et al.,Synlett, 1998, 1347; 1999, 1990; Hao, X.; Yoshida, A.; Nishikido, J.
Tetrahedron Lett. 2005, 46, 2697.
Hao, X.; Yamazaki, O.; Yoshida, A.; Nishikido, J. Tetrahedron Lett. 2003, 44, 4977.
Hao, X.; Yoshida, A.; Nishikido, J. Tetrahedron Lett. 2004, 45, 781.
Yoshida, A.; Hao, X.; Nishikido, J. Green Chem. 2003, 5, 554.
Yamazaki, O.; Hao, X.; Yoshida, A.; Nishikido, J. Tetrahedron Lett. 2003, 44, 8791.

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International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

NONCOVALENT ATTACHMENT OF NUCLEOTIDES BY FLUOROUSFLUOROUS INTERACTIONS
Beller, C.; Bannwarth, W.
Institute of Organic Chemistry and Biochemistry, University of Freiburg,
Albertstr. 21, D-79104 Freiburg
willi.bannwarth@organik.chemie.uni-freiburg.de

In aqueous phase, interactions of perfluoro-tags can become very intense.[1]. We
have used these interactions to immobilize DNA-fragments noncovalently on fluorous
silica gel (FSG) as a basis to develop a simple purification system for synthetic
oligonucleotides.[2,3] The procedure is compatible with standard solid-phase
synthesis of oligonucleotides. It can be performed on small cartridges in parallel
fashion avoiding purifications by polyacrylamide gel electrophoresis (PAGE) or
HPLC. Currently, the approach is being extended to the immobilization of RNA andproteins.

[1]
[2]
[3]

Kobos, R.K.; Eveleigh, J.W.; Arentzen, R.; Trends in Biotechnology 1989, 101105.
Andrushko, V.; Schwinn, D.; Tzschucke, C.C.; Michalek, F.; Horn, J.; Mössner,
C.; Bannwarth, W.; Helv. Chim. Acta 2005, 88, 936-949.
Beller, C.; Bannwarth W; Helv. Chim. Acta 2005, 88, 171-179.

9International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

STYLING AND SETTING OF FLUOROUS PONYTAILS FORENGINEERED SEPARATIONS
Rábai, J.
Department of Organic Chemistry, Eötvös Loránd University, Pázmány Péter sétány 1A, Budapest, H1117, Hungary
rabai@elte.hu

Ideal purification processes rely on the transfer of the target compounds and othercomponents to different phases involving e.g. fluorous liquid-organic liquid, fluorous
solid-organic liquid, and homogeneous vapour - two immiscible liquid pairs. Here only
simple operations are used including extraction (L-L, SPE), filtration (S-L) or
distillation to furnish pure products. Since the molecular structure of the compounds
determines their bulk properties, the understanding of this correlation is a key fordesigning molecules with tuned phase characters. To make compounds fluorous the
temporary or permanent attachment of longer perfluoroalkyl (Rfn = CF3(CF2)n-1)
chains to organic molecules became a general practice of today. The purposefulincorporation of these domains in target molecules is the base for the invention ofseveral techniques, such as fluorous biphasic catalysis, fluorous synthesis andfluorous mixture synthesis. All unique properties of fluorous compounds and phases
are governed by complex thermodynamic principles. The state-of-matter (solid, liquid,gas) of compounds are defined by their molecular structure, while some othermacroscopic properties including solubility (e.g. thermomorphism) and miscibility canvary very steeply by temperature. Most of the fluorous properties can be learnt by
experimental observations, while the specific fluorophilicity can also be predicted withreliable accuracy to the empirical values by using estimated molar volumes andcalculated Hildebrand parameters. Structure-fluorophilicity studies revealed that thetrifluoromethyl (CF3-) group have the highest impact on fluorousness, it makes thesteepest relative increase of fluorophilicities referred to fluorines used per ponytails.
Another important parameter is molar volume, which allows dramatic increasing of
the fluorous partition coefficient, while the fluorine content and polarity of compoundare kept unchanged. This inspired us to design and synthesize novel fluorous modelcompounds rich in CF3-groups and initiated a systematic study of the effect of“styling” and “setting” of ponytails on selected properties, including melting point,solubility, fluorophilicty and volatility. Since the state-of-matter of compounds can bea determining factor of engineered separations, it is necessary to have a control on
this property at the design stage of these processes. It will be demonstrated, thatmelting points can be tuned at two levels: first with the styling of ponytails by using
linear or branching chains, by the presence of hetero atoms in the tails providing
conformational flexibility, and second with their numbers and setting patterns which
ultimately define the degree of symmetry of the final molecules. Syntheses of somenovel generation F-compounds with defined state-of-matter will also be discussed [1].

[1]

Szabó, D.; Bonto, A.-M.; Kövesdi, I.; Gömöry, Á.; Rábai, J. J. Fluorine Chem.
2005, 126, 641-652; and references cited therein.

10International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

PERNITROMETALLOPORPHYRINS WITH FLUOROUS PONYTAILSAS CATALYSTS IN EPOXYDATION OF ALKENES
Połtowicz J., Pamin K., Tabor E., Haber J. aaInstitute of Catalysis and Surface Chemistry, Polish Academy of Sciences
Niezapominajek 8, 30-239 Kraków, Poland
nchaber@cyf-kr.edu.pl

Oxidation of hydrocarbons catalyzed by metalloporphyrins with molecularoxygen is one of the most attractive transformations in organic synthesis [1]. The
major drawback which prevents progress in practical application of themetalloporphyrin catalysts for large scale oxidation is their recycling and re-use. Oneof the methods to circumvent this problem is the catalysis in fluorous solvents, inparticular in a relatively new fluorous biphase system (FBS) that is designed tofacilitate the separation of catalysts from reaction mixtures [2]. Thus, we havesynthesized the pernitrated metalloporphyrins with ponytails and we have appliedthese compounds in epoxydation of alkenes with molecular oxygen.
In this work we prepared for the first time pernitrometalloporphyrins with ponytails:
FeTPFP(NO2)4(C6F13)4P,
MnTPFP(NO2)4(C6F13)4P,
CoTPFP(NO2)4(C6F13)4P,
CoTPFP(NO2)4(C8F17)4P, CoTPFP(NO2)4(C10F21)4P, and characterized them by
UV-Vis, EPR and FTIR spectroscopy. These metallocomplexes are soluble in someperfluorosolvents
likeperfluoro(methylcyclohexane),
perfluorohexaneorperfluorodecalin and were applied as catalysts in epoxidation of alkenes inperfluorohexane/CH3CN biphase system with molecular oxygen and sacrificial
aldehyde as the reducing agent [2]. Reactions were carried out at room temperature
under O2 at atmospheric pressure. All synthesized metalloporphyrins were active in
the investigated epoxidation reaction. We examined the epoxidation of cyclic andlinear olefins. The main product was epoxide. No epoxydation products have been
observed in blank experiment without catalyst showing that catalytic activity is
associated with metalloporphyrin component. The conversion of substrates andepoxide yields were high, about 90-100% for cyclooctene and cyclohexene.
However, these pernitrometalloporphyrins were less active in epoxidation of
dodecene and propene which are rather inert linear olefins. The conversions ofpropene were between 9-15% and of dodecene reached 39-45% wheras epoxideyields were rather high (85-90%). The perfluorohexane phase containing cobalt
complex CoTPFP(NO2)4(C6F13)4P was recycled and re-used twice in epoxidation of
cyclooctene without decrease of conversion of substrate or yield of epoxide,
indicating that the metalloporphyrin does not lose catalytic activity during oxidation
process.
Summarizing, we stress that physicochemical and catalytic properties of
pernitrometalloporphyrins with ponytails are mainly governed by the strong electronwithdrawing effect of the nitro- and fluoro- substituents.
[1] Połtowicz, J; Haber. J. J. Mol. Catal. 2004, 220, 43.
[2] Pozzi, G; Montanari, F, Quici, S. Chem. Comm. 1997, 69

11International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

FLUOROUS CATALYSIS WITH METALPERFLUOROCARBOXYLATESBiffis, A.
Dipartimento di Scienze Chimiche, Via Marzolo 1, I-35131 Padova, Italy
andrea.biffis@unipd.it

Fluorous strategies for the recovery and recycling of homogeneous catalysts
have proven to be extremely effective for a variety of catalytic species and reactions.
However, the cost of perfluorinated solvents as well as the doubts on theirecocompatibility have recently pushed research towards the development of fluorous
separation strategies which minize or even eliminate the need for fluorous solvents.
We have an ongoing program aimed at the application of fluorous recovery andrecycling strategies to metal perfluorocarboxylates, which are highly useful catalysts
for a number of technologically relevant application.[1-3] In particular, we havedeveloped for such compounds diverse strategies which imply minimal use offluorous solvents.[2,3]In this contribution, we would like to illustrate some of our most recent
achievements in this field, including 1) a novel approach to fluorous catalysts
heterogenization on solid supports, indipendently introduced by our group[2] as well
as by others,[4] which we have termed “Bonded Fluorous Phase Catalysis” (BFPC);
2) strategies for the recovery and recycling of fluorous chiral dirhodium(II)carboxylates,[3] which are active and selective catalysts in intermolecular asymmetric
cyclopropanation and C-H bond activation reactions; 3) a novel, general protocol forthe preparation of heterogenized metal perfluorocarboxylates, making use of fluorous
solid ion exchangers.

[1]
[2]

[3]
[4]

Biffis, A.; Castello, E.; Zecca, M.; Basato, M. Tetrahedron 2001, 57, 10391.
a) Biffis, A.; Zecca, M.; Basato, M. poster communication at the
Symposium“Green Solvents for Catalysis”, Bruchsal (Germany) 13-16 October
2002; b) Biffis, A.; Zecca, M.; Basato, M. Green Chem. 2003, 5, 170; b) Biffis,
A.; Braga, M.; Basato, M. Adv. Synth. Catal. 2004, 346, 451;
Biffis, A.; Braga, M.; Cadamuro, S.; Tubaro, C.; Basato, M. Org. Lett., ASAPa) Tzschucke, C.C.; Markert, C.; Glatz, H.; Bannwarth, W. Angew. Chem. Int.
Ed. 2002, 41, 4501; b) Ablan, C.D.; Hallet, J.P.; West, K.N.; Jones, R.S.;
Eckert, C.A.; Liotta, C.L.; Jessop, P.G. Chem. Commun. 2003, 2972; c)Jenkins, P.M.; Steele, A.M.; Tsang, S.C. Catal. Commun. 2003, 4, 45; d)Yamazaki, O.; Hao, X.; Yoshida, A.; Nishikido, J. Tetrahedron Lett. 2003, 44,
8791.

12

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

ADVANCES IN HIGHLY FLUORINATED MATERIALS FORDIAGNOSIS AND THERAPY
Riess J. G.
University of California at San Diego and Alliance Pharmaceutical Corp.
jriess@allp.com

The basic properties of perfluorocarbons (PFCs) relevant to their use in
medicine will be reminded. Exceptionally strong intramolecular binding and weakintermolecular cohesiveness of liquid PFCs result in a unique combination of high O2and CO2-dissolving capacities, extreme hydrophobicity and lipophobicity as well, andhigh chemical and biological inertness. Injected PFCs are not metabolized and are
excreted with the exhaled air.
Poor water solubility of PFC gases allowed the development of stable injectablemicron-size gas bubbles that serve as contrast agents for ultrasound diagnosis. The
PFC gas compensates for Laplace pressure and arterial pressure, thus opposing
dissolution of the microbubbles in the blood. Several such PFC-based microbubble
contrast agents have been approved by the EMEA or FDA in the recent years.
Where PFC emulsions for in vivo oxygen delivery are concerned, the challenge wasto identify a PFC that had a relatively low vapor pressure, yet was readily excreted,capable of producing stable emulsions and easy to manufacture. Perfluorooctyl
bromide, a slightly lipophilic PFC, obeys these conditions. Intravascular use
supposes the preparation of a stable, sterile, ready-for-use submicron-size PFC-inwater emulsion. Phospholipids are privileged as emulsifiers as they effectively reduce
the PFC/water interfacial tension and have a long history of use in pharmaceuticals.
Particle growth in such emulsions (which is driven by molecular diffusion) is slowed
down by addition of a higher molecular weight PFC such as perfluorodecyl bromide.
Heat sterilized PFC emulsions ca. 0.15 µm in size were prepared that are stable forover 2 years. Other emulsion stabilization principles rely on the use of fluorocarbonhydrocarbon diblocks that modify the interfacial film. In vivo oxygen delivery has been
established through preclinical experimentation and human clinical trials.
Targeted microbubbles and emulsions are now being investigated that allow
molecular imaging of disease using ultrasound or magnetic resonance, as well as
drug delivery.
[1]
[2]
[3]

Riess, J.G. Chem. Rev. 2001, 101, 2797-2919.
Riess J.G. Tetrahedron 2002, 58, 4113-4131.
Schutt E.G., Klein D.H., Mattrey R.M., Riess J.G., Angew. Chem. Int. Ed. 2003, 42,
3218.

13

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

BASIC PRINCIPLES AND RECENT ADVANCES IN FLUORINATED
SELF-ASSEMBLIES AND COLLOIDAL SYSTEMS
Krafft M. P.
Colloïdes et Interfaces. Institut Charles Sadron (CNRS).
6 rue Boussingault, 67083 Strasbourg Cedex, France.
krafft@ics.u-strasbg.fr

A clear understanding of the basic properties of fluorinated self-assembled
systems and interfaces should be valuable to chemists using fluorous phases forsynthesis, as these properties determine phase separations, the development oflarge size interfaces and the possible constitution of micro- or nanoreactors andtemplates. Many reagents, catalysts and substrates, once fitted withperfluoroalkylated chains for use in fluorous chemistry, are likely to become
amphiphilic or to experience enhanced amphiphilic character. Hence, they become
susceptible to adsorption at interfaces and to self-association into colloidal systems,
including spherical and worm-like micelles, vesicles and fibers, emulsions,microemulsions or other more or less complex colloidal systems. In addition,
fluorinated compounds, due to their combined hydro- and lipophobia, andconsequent tendency to phase separate from both aqueous and hydrocarbon media,
can generate compartmentalization in molecular systems. Interface-driven
parameters, which depend largely on the length of the fluorinated moiety, cancomplicate otherwise simple chemistry.
After a brief reminder of the basic physicochemical properties of fluorocarbons
and fluorinated surfactants, we will focus on recent advances on self-assemblies andcolloidal systems, e.g. micelles, vesicles, tubules, monolayers and emulsions thatcomprise fluorinated components. Their present and potential applications, primarily
in materials sciences will also be presented.

[1]
[2]
[3]
[4]
[5]

Special issue of Curr. Opin. Colloid Interface Sci. on Fluorinated Colloids andInterfaces (M.P. Krafft, ed), 2003, 8, 213-314.
M.P. Krafft, in Handbook of Fluorous Chemistry (J.A. Gladysz, I. Horváth, D.P.
Curran, eds); Wiley-VCH: Weinheim, pp. 478-490, 2004.
J. G. Riess, ibid, pp. 521-573.
P. Fontaine, M. Goldmann, P. Muller, M.-C. Faure, O. Konovalov, M.P. Krafft,
J. Am. Chem. Soc. 2005; 127, 512-513.
F. Gerber, M.P. Krafft, T.F. Vandamme, M. Goldmann, P. Fontaine, Angew.
Chem. Int. Ed. 2005, 44, 2749-2752.

14

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

GELATION OF PERFLUOROCARBONS
Pozzo, J.-L.;a Gan J. ;a Belin, C. ;b Vincent, J.-M.aab

LCOO, 351 crs de la libération, 33405 Talence Cedex, France
LPCM, 351 crs de la libération, 33405 Talence cedex, France
jl.pozzo@lcoo.u-bordeaux1.fr

Perfluorocarbons (PFCs) are hydrophobic and lipophobic gas-like liquids thathave been extensively studied and used for the preparation of micron- and submicron-size fluorous colloidal phases (F-colloids).[1] F-colloids have found major
applications in medicine including, in vivo oxygen delivery (PFC-in-water emulsions),
controlled drug delivery (micelles, vesicles, tubules), pulmonary drug delivery (waterin-PFC or HC-in-PFC emulsions) or ultrasound contrast agent (PFC gas emulsion inwater). The PFC gels are another class of F-colloids that have received special
attention (with their potential use as topical delivery barrier cream).[2] To date, mostof these PFC gels were obtained using fluorous surfactants in the presence of ~1–
20% water.[3] Only a few examples of compounds were shown to gelate “purePFCs” and, moreover, for each of these compounds gelation is restricted to only one
PFC.[4] Now we report on the gelling ability of the charged fluorinated surfactant 1Na for a range of PFCs along with AFM observations of unprecedented selforganization of fluorous vesicles into giant three-dimensional periodic structures.

H

CF3 -(CF2)7 -CH2 -CH2 -CH2N
CF3 -(CF2)7 -CH2 -CH2 -CH2

[1]
[2]
[3]
[4]

O
(CH2)10OOR

R = H 1-H
R = Na 1-Na

Riess, J.G. Tetrahedron. 2002, 58, 4113-4131.
Krafft, M.P. Fluorocarbon Gels. 2001, 66, Chap. 10, 195-219.
Krafft, M.-P.; Riess, J.G. Angew. Chem. Int. Ed. 2002, 58, 4113-4131.
a) perfluorodecaline gel: Höpken, J.; Pugh, C.; Richtering, W.; Möller, M.
Makromol. Chem. 1988, 189, 911-925; b) perfluorooctane gel: George, M.;
Snyder, S.L.; Terech, P.; Glinka, C.J.; Weiss, R.G.J. Am. Chem. Soc. 2003,
125, 10275-10283. c) perfluorotributylamine gel: Loiseau, J.; Lescanne, M.;
Colin, A.; Fages, F.; Verlhac, J.-B.; Vincent, J.-.M. Tetrahedron 2002, 58,
4049-4052.

15

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

SELF-ASSEMBLY MEDIATED BY THE FLUOROPHOBIC EFFECT
Percec V.
Roy & Diana Vagelos Laboratories, Department of Chemistry,
University of Pennsylvania, Philadelhia, PA 19104-6323, USA
percec@sas.upenn.edu

This lecture will discuss selected examples from our laboratory in which the fluorophobic
effect has been exploited as an extraordinarily efficient tool to both generate and amplify
nonbonding intramolecular and intermolecular interactions in order to mediate
unprecedented self-assembly processes. Most examples will discuss the design ofsupramolecular structure and through the supramolecular structure the engineering of thesupramolecular order and function. [1, 2, 3, 4]

[1]
[2]
[3]
[4]

Percec, V., Glodde, M., Bera, T.K., Miura, Y., Shiyanovskaya, I., Singer, K.D.,
Balagurusamy, V.S.K., Heiney, P.A., Schnell, I., Rapp, A., Spiess, H.-W., Hudson,
S.D., Huan, H. Nature 2002, 419, 384.
Percec, V., Glodde, M., Johansson, G., Balagurusamy, V.S.K., Heiney, P.A.
Angew. Chem. Int. Ed. 2003, 42, 4338.
Percec, V., Imam, M.R., Bera, T.K., Balagurusamy, V.S.K., Peterca, M., Heiney,
P.A. Angew. Chem. Int. Ed. 2005, in press.
Percec, V., Johansson, G., Ungar, G., Zhou, J. J. Am. Chem. Soc. 1996, 118,
9855.

16

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

SPONTANEOUS RESOLUTION PHENOMENAIN PERFLUOROCARBON-HYDROCARBON
SUPRAMOLECULAR ARCHITECTURES
Metrangolo, P. ;a Meyer, F. ;a Pilati, T. ;b Resnati, G. ;a Ursini, M.aaLaboratory of Nanostructured Fluorinated Materials (NFMLab)
Department of Chemistry, Materials, and Chemical Engineering “G. Natta”, Polytechnic of Milan
Via L. Mancinelli 7, 20131 Milan, Italyb
ISTM - C.N.R, University of Milan, Via C. Golgi 19, 20133 Milan, Italy
pierangelo.metrangolo@polimi.it
Web-site: http://nfmlab.chem.polimi.it

The term halogen bonding (XB) describes any non-covalent interaction involving
halogens as electron density acceptors [1]. Bromo- and iodo-substituted
perfluorocarbons (PFCs) are nicely tailored to XB-based supramolecular chemistry,
and thus behave as particularly robust tectons [2]. The XB-mediated self-assembly of
PFCs and hydrocarbons (HCs) revealed to be an efficient strategy in affording new
and structurally different hybrid PFC-HC supramolecular architectures [3]. The
particular ability of XB in controlling spontaneous resolution phenomena in hybrid
PFC-HC supramolecules has been only recently discovered [4]. To date we observed
spontaneous resolutions occurring in five crystals of PFC-HC systems affording chiral
PFC-HC supramolecular architectures starting from achiral modules. Three of them
involved long-chain iodo-PFCs (C8-C10) with either QUATS or N,N,N’,N’-tetramethylp-phenylendiamine as Lewis bases. Their different features with regard to thesegregation behaviour and the conformation of the PFC chains will be outlined.
Through this approach, for the first time a long chain haloperfluoroalkane has beenobtained in the chiral and enantiopure form in the solid state.

Single crystal X-ray structure of the chiral halogen bonded supramolecule TBA-I/I-(CF2)10-I.

[1]
[2]
[3]
[4]

Metrangolo, P.; Neukirch, H.; Pilati, T.; Resnati, G. Acc. Chem. Res. 2005, 38,
386.
Metrangolo, P.; Resnati, G. in Halogen Bonding, Encyclopedia ofSupramolecular
Chemistry, Marcel Dekker Inc., New York, 2004, p. 628.
Metrangolo, P.; Pilati, T.; Resnati, G.; Stevenazzi, A. Curr. Opin. Colloid
Interface Sci. 2003, 8, 215.
Neukirch, H.; Guido, E.; Liantonio, R.; Metrangolo, P.; Pilati, T.; Resnati G.
Chem. Commun. 2005, 1534.
17

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

FLUOROUS CHEMISTRY WITHOUT FLUOROUS SOLVENTS: NEW
CATALYST RECOVERY PROTOCOLS BASED UPONFLUOROPOLYMERSGladysz, J. A.
Institut für Organische Chemie, Universität Erlangen-Nürnberg, Henkestraße 42, 91054
Erlangen, Germany
gladysz@organik.uni-erlangen.de

Conventional fluorous catalysis exploits the temperature-dependent miscibilitiesof fluorous and organic solvents. Reactions are often conducted at the hightemperature, one phase limit, with product/catalyst separation at the lowtemperature, two-phase limit. This talk will focus on recent efforts to eliminate thefluorous solvent requirement. We have found that many fluorous compounds
exhibit highly temperature dependent solubilities in organic solvents. Such"thermomorphic" behavior allows fluorous catalysts to be utilized under one
phase conditions at elevated temperatures in ordinary organic solvents, andrecovered by a simple liquid/solid phase separation at low temperature.[1] It isadvantageous to conduct these reactions in the presence of a fluorous support,
especially when catalyst quantities are small. This talk will highlight recent
refinements involve fluoropolymers such as Teflon.[2] Rhodium-catalyzedhydrosilylations and ruthenium-catalyzed alkene metatheses will be emphasized.

[1]
[2]

Wende, M.; Gladysz, J. A. J. Am. Chem. Soc. 2003, 125, 5861.
Dinh, L. V.; Gladysz, J. A. Angew. Chem., Int. Ed. 2005, 44, in press.

18

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

FLUORO-ALCOHOLS: EFFECTIVE SOLVENTS FOR CLASSICALORGANIC REACTIONSBonnet-Delpon D.
BIOCIS-CNRS , Faculté de Pharmacie, rue J. B. Clément, 92296 Châtenay-Malabry, France
daniele.bonnet-delpon@cep.u-psud.fr

Fluorinated alcohols such as hexafluoroisopropanol (HFIP) and trifluoroethanol (TFE)[1] are not considered stricto sensu as fluorous media. However, the presence of one
or more fluoroalkyl groups brings them specific properties compared to non
fluorinated alcohols, what could provoke changes in reaction courses if they are usedas solvents. Their properties, with a combination of high hydrogen bonding donor
ability, low nucleophilicity, high ionizing power (Table) [2] allowed carrying onreactions which usually require the use of additive reagents or metal catalysts.
Table :

Properties of fluorinated alcohols compared to ethanol
EtOH

TFE

HFIP

b.p. (°C)

78

73.8

58.6

m.p. (°C)

-

-43.5

-5

Density (d)

0.79

1.383

1.605

pKa

15.9

12.4

9.3

Nucleophilicity (N)

0

-2.78

-4.23

Dielectric constant ( )

24.5

26.7

16.7

Ionizing power (Y)

-1.75

1.8

3.82

Hydrogen bond donor ( )

0.83

1.51

1.96

Hydrogen bond acceptor ( ) 0.77

00Auto association constant
0.89(dm3.mol-1)

0.65

0.13

Providing they are used as solvents, HFIP and, in a less extent, TFE, are able tofacilitate O-O bond and C-O bond cleavages or to facilitate C-C bond formation withno need of metal or acid catalysis.
Examples will be given in oxidation and epoxidation reactions, reactions of oxiranering opening, cycloaddition reactions and three component reactions.
The procedures offer several advantages like mild and neutral reaction conditions,operational simplicity and ease of isolation of products, good yields of products. In
most cases there are no effluents after reaction, and the fluorinated alcohols can berecovered and reused for other reactions [3,4].
[1]
[2]
[3]
[4]

HFIP is purchased by Central Glass Co, Ltd (Japan)
Mortimer, J. K.; Abboud, J. L. M.; Abraham, M. H.; Taft, R. W. J. Org. Chem. 1983, 48,2877; Schadt, F. L.; Bentley, T. W.; Schleyer P. v. R. J. Am. Chem. Soc. 1976, 98, 766.
Bégué, J.P. ; Bonnet-Delpon, D. ; Crousse, B. Synlett, 2004, 1, 18-29.
V. Kesavan, K.S. Ravikumar, B. Crousse, D. Bonnet-Delpon, J.P. Bégué Organic
Synthesis , 2003, 80, 184-189.

19

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

FLUOROUS-DERIVATISED PHASE TRANSFER CATALYSTS
Stuart, A. M. ; Vidal, J.; Weber, K. M.
Department of Chemistry, University of Leicester, Leicester, UK, LE1 7RH.
amc17@le.ac.uk

Phase transfer catalysis finds wide industrial applications, but the drive towards
cleaner technologies requires the ability to recover, recycle and reuse the phasetransfer catalysts.[1] Curran has elegantly shown that product/reagent separation
can be readily achieved using fluorous-tagging procedures and fluorous solid-phaseextraction on fluorous reverse phase silica gel.[2] We have recently extended thisapproach to catalyst/product separation [3] and here, we describe the extension ofthis methodology to phase transfer catalysts.

O
R

+
P

X-

C6F13

Rf(CH2)nO

N

N(CH2)nRf

3

(1)

O

O

(2)

A series of novel aryl phosphonium salts (1) and 4,13-diaza-18-crown-6 ethers(2) containing fluorous ponytails have been synthesised.
All of theseperfluroalkylated phase transfer catalysts extract picrate from the aqueous phase intoa partially-fluorinated phase, benzotrifluoride. An evaluation of their catalytic
applications under liquid-liquid and solid-liquid conditions will be reported, as well as
the separation, recovery and recycling results.
[1]
[2]
[3]

Starks, C. M.; Liotta, C. L.; Halpern, M.; Phase Transfer Catalysis;
Fundamentals, Applications and Industrial Perspectives, 1994, Chapman & Hall,New York.
Curran, D. P. Synlett. 2001, 9, 1488.
Croxtall, B. C.; Hope, E. G.; Stuart, A. M. Chem. Commun. 2004, 2430.

20

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

NEW SYNTHETIC METHOD FOR NATURAL PRODUCTS USINGHEAVY FLUOROUS TECHNIQUE
Inazu T.
Department of Applied Chemistry, School of Engineering, and Institute of Glycotechnology,
Tokai University, Kitakaname 1117, Hiratsuka, Kanagawa 259-1292 Japan
inz@kayaki.cc.u-tokai.ac.jp

Since Horváth and Rábai introduced the concept of the fluorous biphasic
system in 1994, fluorous chemistry has been developed for use in several fields suchas combinatorial chemistry, parallel synthesis, and catalytic chemistry. Curran andco-workers elaborated the fluorous synthesis (fluorous-tag method) as a strategic
alternative to solid-phase synthesis. The fluorous protecting groups are essential forthe fluorous synthesis performance.
Recently, we reported a method for the fluorous oligosaccharide synthesis
involving the novel fluorous acyl protective group, the Bfp (bisfluorous chain typepropanoyl) group and the Hfb (hexafluorous chain type butanoyl) group. [1-3] The
use of these groups made it possible to rapidly synthesize the several
oligosaccharides by minimal column chromatography purification. Each synthetic
intermediate was able to be easily purified only by simple fluorous-organic solvent
extraction, and monitored by TLC, NMR, and MS.
We also reported the new fluorous support based on Hfb group. Bioactive
peptides were synthesized on these fluorous supports by an Fmoc strategy.[4,5]

OH
C8F17
C8F17

N
O

Bfp-OH

[1]
[2]
[3]
[4]
[5]

O

OH
(CH2)3
O
O O
F17C8
N
N
C8F17
N N N
H
F17C8
N
C8F17
N
O H
O
C8F17
F17C8
O
O
Hfb-OHO

Miura, T. ; Hirose, Y. ; Ohmae, M. ; and Inazu, T. ; Org. Lett., 2001, 3, 39473950.
Miura, T. ; Goto, K. ; Hosaka, D. ; and Inazu, T. ; Angew. Chem., Int. Ed., 2003,
42, 2047.
Miura, T. ; Goto, K. ; Waragai, H. ; Matsumoto, H. ; Hirose, Y. ; Ohmae, M. ;Ishida, H.-K. ; Satoh, A. ; and Inazu, T. ; J. Org. Chem., 2004, 69, 5348.
Mizuno, M. ; Miura, T. ; Goto, K. ; Hosaka, D. ; and Inazu, T. ; Chem. Commun.,
2003, 972.
Mizuno, M. ; Goto, K. ; Miura, T. ; Matsuura, T. ; and Inazu, T. ; Tetrahedron
Lett., 2004, 45, 3425.

21

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

CHEMICAL SYNTHESIS OF OLIGODEOXYRIBONUCLEOTIDES ON A
FLUOROUS DENDRON
Wada T.,a Narita R.,a Kato Y.,a Saigo, K.aaDepartment of Medical Genome Sciences, Graduate School of Frontier Sciences,
The University of Tokyo
Bioscience Building 702, 5-1-5 Kashiwanoha, Kashiwa 277-8562, Japanwada@k.u-tokyo.ac.jp

In recent years, a great deal of attention has been focused on small DNA and RNA
molecules as therapeutic agents for selective inhibition of gene expression.[1]Oligonucleotide therapeutic agents such as antisense DNAs, ribozymes, and siRNAs
act on the target mRNAs and arrest the protein synthesis. In order to meet theglowing demands for these relatively short oligonucleotides, a completely new
approach for the large-scale production of DNA and RNA should be developed.
Under these circumstances, we have focused on the fluorous chemistry [2] and its
application to the solution-phase (fluorous-phase) synthesis of nucleic acids. In the
fluorous-phase synthesis of organic compounds involving a fluorous tag, theintermediates can be purified by a simple extraction with a fluorous solvent without
using chromatography. In this paper, we wish to describe a novel H-phosphonate
method [3] for the synthesis of oligonucleotides using a highly-fluorinated dendricmolecule 1 (fluorous dendron) as a fluorous support and fluorous protecting groups
for nucleobase protection.

[1]
[2]
[3]

Therapeutic Oligonucleotides; Cho-Chung, Y. S.; Gewirtz, A. M.; Stein, C. A.,
Eds; New York Academy of Sciences: New York, 2004.
Handbook of Fluorous Chemistry; Gladysz, J. A.; Curran, D. P.; Horváth, I. T.,
Eds; Wiley-VCH: Weinheim, 2004.
Wada, T.; Sato, Y.; Honda, F.; Kawahara, S.; Sekine, M.; J. Am. Chem. Soc.
1997, 119, 12710-12721.

22International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

SYNTHESIS OF MONOFUNCTIONAL PERFLUOROPOLYETHERS
Fontana G., Navarrini W.
Solvay Solexis S.p.A., R&D Center, Viale Lombardia 20, 20021 Bollate, Milan, Italy.
giovanni.fontana@solvay.com

Perfluoropolyethers (PFPEs) are a well-known class of fluids for many industrial applications
which can be obtained by reaction of tetrafluoroethylene (TFE) with oxygen in an inert
solvent at low temperature using UV irradiation [1]. The reductive cleavage of the peroxidebonds of the peroxidic perfluoropolyether precursor (1) with hydrogen over a suitable catalyst
yields essentially bifunctional acylfluorides (2) which can be converted by specific end group
modifications to give valuable functionalized PFPEs such as  hydroperfluoropolyethers [2]and PFPE derivatives [3]In this work, new monoacylfluoride PFPEs (3) with different molecular weights have beensynthesized by direct fluorination of the PFPE diacylfluorides (2) in the presence of catalysts
metal fluorides having formula MeFy.zHF (es. CsF, KF) [4]. The fluorination of (2) catalyzed
by metal fluorides gives PFPEs with terminal groups hypofluorites –OCF2CF2OF which by insitu thermal decomposition lead to the formation of the corresponding neutral end groups –OCF3 [5].
The conversion of initial acylfluoride terminal groups to give end units –OCF3 is quantitative.
Yield and selectivity to monoacylfluorides (3) with respect to neutral PFPE products (4)depend on the conversion of initial –CF2C(O)F end groups, on temperature as well as on the
catalyst. After hydrolysis and purification of the reaction mixtures by fractional distillation,
pure products as well as fractions with more than 90% molar content of PFPE
monocarboxylic acids (5) with a number average molecular weight from 350 to 1500 havebeen isolated in very good yields:
CF3O(CF2CF2O)m(CF2O)nCF2COOH(5)These new monofunctional perfluoropolyethers are useful intermediates for the preparationof valuable additives and fluorinated materials for many high technological and industrial
sectors.
[1]
[2]
[3]
[4]
[5]

Sianesi, D.; Marchionni, G.; De Pasquale, R.J. in R.E. Banks (Ed.), “Organofluorine
Chemistry Principles and Commercial Applications”, Plenum Press, New York, 1994,
pp. 431-461.
Fontana, G.; Spataro, G.; Marchionni, G. Fluid Phase Equilibria 2000, 174, 41-50.
Tonelli, C.; Gavezzotti, P.; Strepparola, E. J. Fluorine Chem. 1999, 95, 51-70.
Fontana, G.; Navarrini, W., U.S. Patent 2004, No. 0147780 ( to Solvay Solexis).
Fontana, G.; Navarrini, W., U.S. Patent 2004, No. 0147778 ( to Solvay Solexis).

23

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

FLUOROUS ORGANOTIN CATALYSTS
Otera, J.
Department of Applied Chemistry, Okayama University of Science,
Ridai-cho, Okayama 700-0005, Japanotera@high.ous.ac.jp

A variety of fluoroalkyltin compounds as shown below are synthesized. These
compounds exhibit unusual solubility in organic and fluorous solvents. Their use forhighly efficient (trans)esterfication and acetylation will also be the subject of thislecture.

[1]

Otera, J. Acc. Chem. Res. 2004, 37, 288.

24

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

FLUOROUS-TAGGED GLYCOSIDE PRIMER FOR SACCHARIDECHAIN ELONGATION BY CELLULAR ENZYME
Hatanaka, K. ;a Kasuya, M.C.Z. ;a Ito, A.aaInstitute of Industrial Science, The University of Tokyo
4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japanhatanaka@iis.u-tokyo.ac.jp

Facile synthesis of oligosaccharides could be accomplished by combining
chemical synthetic methods with cellular biosynthetic processes. This strategy
involves the preparation of saccharide primers (amphiphilic glycoside derivatives) by
simple synthetic means, and subsequent incorporation of these primers into cells thatserve as substrates for glycosylation by cellular enzymes. The cellular uptake ofprimers and release of glycosylation products to the culture medium by cells depend
not only on the saccharide moiety and number of hydrophilic groups, but also on thehydrophobic aglycon unit.
Fluorinated compounds can also act as viable building blocks for oligosaccharide
synthesis by cellular enzymes. In this research, the incorporation of fluorine to thelipophilic aglycon unit of the lactoside primer was carried out to further establish therole of the aglycon unit in priming oligosaccharide synthesis. Moreover, theincorporation of a fluorous tag is perceived to facilitate the extraction of theglycosylated product from the culture medium by using a fluorous solvent.
Lactoside (Lac), galactoside (Gal) and glucoside (Glu) primers with different
fluorous-tags, perfluorohexylhexyl (F6) or perfluorodecylethyl (F10), were prepared
and were examined in mouse B16 melanoma cells for their feasibility as substrate foroligosaccharide biosynthesis. The synthesis of the fluorous-tagged lactoside primers
was accomplished by glycosylation of lactose peracetate with perfluorohexylhexanol,
or with perfluorodecylethanol, followed by deacetylation. Synthesis of the fluoroustagged galactoside and fluorous-tagged glucoside primers was carried out in asimilar manner.
After 48-h incubation of cells with the primer, the lipids were extracted from thecell homogenates and the culture media and analyzed by HPTLC. New bands wereextracted from the HPTLC plate and analyzed by MALDI TOF mass spectrometry.
Results showed that incorporation of the lactoside primers (Lac-F6 or Lac-F10) gave
monosialylated products. Treatment of the glycosylated products with α-(2→3)
neuraminidase from Arthrobacter ureafaciens in phosphate buffer (pH 7.3) for 16 h at
37 oC confirmed that the product is α-(2→3) sialylated lactoside which is the sameoligosaccharide as GM3 – the glycosphingolipid predominantly expressed on the cellsurface of B16 melanoma cells, and effective on several important bioactivities.
Treatment of B16 cells with the galactoside primer (Gal-F6) likewise gave amonosialylated product. On the other hand, Gal-F10 primer and the glucosideprimers (Glu-F6 and Glu-F10) were not glycosylated.
This research demonstrates for the first time that fluorous-tagged compounds
could be taken-up by the cell and take part in the biosynthetic machinery to afford thesialylated oligosaccharides without the need for a series of protection anddeprotection steps usually required for chemical synthesis. The efficient extraction of
the sialylated products with fluorous solvents is in progress.
25

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

SOLVATION OF OXYGEN, CARBON DIOXIDE, CARBON MONOXIDEAND NITROUS OXIDE IN FLUORINATED LIQUIDS
Costa Gomes, M.F. ;a Padua, A.A.H.; a Deschamps, J.; a Menz, D.-H. baLaboratoire de Thermodynamique des Solutions et des Polymères, UMR 6003 CNRS/Université
Blaise Pascal, Clermont-Ferrand, 24 avenue des Landais, 63177 Aubière Cedex, Franceb
Pharmpur GmbH, Holzweg 27, 86156 Augsburg, Germany
rmargarida.c.gomes@univ-bpclermont.fr

The solvation of four gases ⎯ oxygen, carbon dioxide, carbon monoxide or nitrous
oxide ⎯ in fluorinated organic liquids, with potential for bio-medical applications(perfluorohexylethane, C6F13C2H5, perfluorooctane, C8F18 and perfluorobromooctane,
C8F17Br), were studied in terms of molecular interactions, solution structure andthermodynamics.
An original experimental study of the gas solubility as a function of temperature, atpressures close to atmospheric, is reported. These measurements allow thecalculation of thermodynamic quantities related to the solution process, such as freeenergies, that provide macroscopic information about the energetic and structural(entropic) contributions [1]. It is observed that the solubility of the three solutes
decrease with temperature (corresponding to an exothermic solvation) and that
nitrous oxide is the more soluble gas, followed by carbon dioxide. Carbon monoxide
is the less soluble species in all the fluorinated liquids studied.
At the atomic scale, the same systems were investigated using molecular simulation
techniques. These tools give access to the structural aspects of solvation through thesolute-solvent radial distribution functions. The free energy routes of statisticalmechanics provide values for the solutes’ chemical potentials, which can becompared to the experimental results to validate the force-field models used in thesimulations [2,3].
Apart from their applications in pharmacology and bio-medicine, the gaseous solutes
chosen present different molecular characteristics: for example, carbon monoxide isslightly dipolar, carbon dioxide is purely quadrupolar, and nitrous oxide is both. The
nature of the solute-solvent interactions in solution can be elucidated, in terms of thestrength of the interactions and also of the role of structural effects (cavity formationin the solvents, organisation of the solvation shell). The solvation of these gases canthen be understood in molecular terms and the behaviour of the fluorous solutions
more accurately predicted.

[1]
[2]
[3]

Costa Gomes, M.F.; Deschamps, J.; Menz, D.-H. J. Fluorine Chemistry 2004,
125, 1325.
Deschamps, J. ; Costa Gomes, M.F. ; Padua, A.A.H. J. Fluorine Chemistry
2004, 125, 409.
Costa Gomes, M.F.; Padua, A.A.H. Pure Appl. Chem. 2005, 77, 653.

26

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

FLUOROUS BIPHASIC CATALYSIS: OXIDATION OF ALKANES,
ALKENES, ALCOHOLS, AND ALKENOLS WITH Mn(II), Co(II), AND
Cu(I AND II) FLUOROUS SOLUBLE OR THERMOMORPHICCOMPLEXES IN THE PRESENCE OF TBHP/O2 ORTEMPO/O2 OR H2O2
Fish R. H.
Lawrence Berkeley National Laboratory, University of California, Berkeley, CA 94720
rhfish@lbl.gov

One of the main problems that persists in homogeneous catalysis is the separation of
the precatalyst from the resulting products. More than a decade ago, Horváth and Rábai
published a seminal paper that described a new and novel biphasic catalysis technique thatelegantly separates the precatalyst from the products of catalysis; they named it Fluorous
Biphasic Catalysis (FBC).[1] The FBC technique has now been adapted for almost everyclassic organic reaction, including homogeneous oxidation chemistry.[2] I will focus on the
FBC oxidation studies that have been conducted at LBNL, and in collaboration withcolleagues at Bordeaux, Zaragoza, and Rehovot.
I will present several FBC scenarios that encompasses the use of fluoroponytailed
ligands with sparingly soluble fluoroponytailed metal carboxylates to form fluorocarbon
soluble complexes of Mn(II), Co(II), Cu(II), and Cu(I). Moreover, the reverse situation, where
the fluorocarbon soluble metal carboxylate phase switches the non-fluoroponytailed ligandfrom the hydrocarbon layer to the fluorocarbon layer by the insitu formation of afluoroponytailed metal carboxylate-ligand complex, where M= Cu(II). The focus of these
FBC oxidation studies was alkanes, alkenes, alcohols, and alkenols; a typical FBC oxidation
scenario is shown in the Scheme. I will also discuss the thermomorphic properties of severalof the Mn(II) and Cu(II) complexes, which entails the solubilization of a solid fluoroponytailed
metal carboxylate-ligand complex in a non-fluorous solvent at higher temperatures, while at
RT, the solid precipitates. Finally, I will introduce a novel concept for an FBC gas to liquid
scenario for methanol synthesis from CO/H2 in collaboration with SUNY Stony Brook andZaragoza colleagues.
O

OH
+

O2
t-BuO2H

Rf

N

N

Rf

N

[Mn2+(Rf(CH2)2CO2)2]

Rf = C8F17

Rf
Perfluoroheptane
O2 (1 atm)
298 K

[1]
[2]

Horváth, I.T.; Rábai, J. Science 1994, 266, 72 and refs. therein.
(a)Vincent, J.-M.; Rabion, A.; Yachandra, V.K.; Fish, R.H. Angew. Chem., Int. Ed.
Engl., 1997, 36, 2346. (b)Vincent, J.-M.; Rabion, A.; Yachandra, V.K.; Fish, R.H. Can.J.
Chem. 2001, 79, 888. (c)Contel, M.; Izuel, C.; Laguna, M.; Villuendas,P. R.; Alonso,
P. J.; Fish, R. H.. Chem. Eur. J., 2003, 9, 4168. (d)Maayan, G., Fish, R. H.; Neumann,
R. Org. Lett. 2003, 5, 3547 (e) Fish, R. Chem. Eur. J. 1999, 5, 167.

27

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

DESIGN AND APPLICATION OF HIGHLY FLUOROUS CATALYSTS
de Pater, J.J.M..,a De Wolf, A.C.A.,a Deelman, B.-J,b Elsevier, C.J.,c van Koten, G.aaUtrecht University, Department of Organic Chemistry and Catalysis, Padulaan 8, NL-3584 CH,
Utrecht, The Netherlandsb
ARKEMA Vlissingen B.V., P.O. Box 70, NL-4380 AB Vlissingen, The NetherlandscVan ‘t Hoff Institute for Molecular Sciences, Molecular Inorganic Chemistry, University of Amsterdam,
Nieuwe Achtergracht 166, NL-1018 WV, Amsterdam
berth-jan.deelman@arkemagroup.com

Highly fluorous homogeneous catalysts have been developed that can be recycled
efficiently using flourous biphasic separation techniques. For fluorous separation
techniques to compete effectively with aqueous biphasic separation, catalyst
recycling efficiencies have to be > 99.9%.
This talk focuses on some specific applications and discusses recently developed
theoretical tools to direct the synthesis and design of catalysts with improved fluorous
phase affinity.

28

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

F-TEMPO RADICALS: EFFICIENT MEDIATORS FOR THE
OXIDATION OF ALCOHOLS
Holczknecht, O. ;a Pozzi, G.a, Quici, S.aa

CNR-Istituto di Scienze e Tecnologie Molecolari, via Golgi 19, 20133 Milano, Italy
horsika@hotmail.com

Selective oxidation of primary alcohols to aldehydes or secondary alcohols to ketones can be carriedout conveniently with cheap and safe primary oxidants in the presence of nitroxyl radicals, in particular
2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO).[1] Nitroxyl radicals are relatively expensive and,
although used in small amounts (1-10 mol%), their separation from the products often requires lengthy
workup procedures. This means efficient recovery and recycling are important issues. Several groups
have addressed these problems by designing heterogeneous variants of TEMPO, e.g. via anchoring
TEMPO to inorganic supports, [2] or by using soluble polymer-supported TEMPO.[3]Recyclable TEMPO radicals can be designed without recourse to polymeric supports with all theirdrawbacks: in this contribution, the preparation of TEMPO derivatives bearing perfluoroalkyl
substituents (F-TEMPOs, Figure 1) and their activity as catalysts in the oxidation of alcohols aredescribed. The influence of the linkage between the TEMPO moiety and the fluorous domain on theselectivity of the catalytic system, the use of various primary oxidants, including molecular oxygen,and the recoverability of the different catalysts are also discussed.
F-TEMPOs obtained from easily available precursors have found to be efficient mediators for theoxidation of a variety of alcohols, affording results very similar to those obtained with TEMPO.
Reactions were performed in conventional organic solvents under mild, homogeneous or liquid-liquidaqueous-organic conditions. Fluorous separation techniques were then applied to isolate the fluoroustagged radicals from the organic products. Promising results were obtained using popular primaryoxidants such as aqueous NaOCl and [bis(acetoxy)iodo]benzene (BAIB). With the latter, the heavy
fluorous radical 6 could be reused up to six times in the oxidation of 1-octanol showing only minor lossof catalytic activity.[4]F-TEMPOs thus share the advantages usually associated with the use of polymer-supported TEMPO
derivatives (simplified workup procedures, quick recovery, recyclability) without some of their common
limitations (lack of versatility, mass transfer limitations, poor accessibility to the active site). Results
obtained provide further guidelines for the rational design of other fluorous nitroxyl radicals and open
new vistas for a possible development of “all-fluorous” catalytic systems involving F-TEMPOs. In thiscontext, the combination of F-TEMPOs with a recyclable fluorous version of BAIB [5] and the use ofmolecular oxygen as the primary oxidant are worth investigating.
O
X

C8F17
RF

C8F17

N

C8F17

C8F17

N

C8F17
N

N

O

O

1 X = O, R = n-C7F15

[3]
[4]
[5]

N

N
N

C8F17

O
6

5

2 X = O, R = n-C8F17CH2CH2
3 X = NH, R = n-C7F15
4 X = NH, R = n-C8F17CH2CH2

[1]
[2]

N

N
O

Sheldon, R. A.; Arends, I. W. C. E. Adv. Synth.Catal. 2004, 346, 1051.
Ciriminna, R.; Bolm, C.; Fey, T.; Pagliaro, M. Adv. Synth. Catal. 2002, 344, 159 and references
therein.
Pozzi, G.; Cavazzini, M.; Quici, S.; Benaglia, M.; Dell’Anna, G. Org. Lett. 2004, 6, 441.
Holczknecht, O.; Cavazzini, M.; Quici, S.; Shepperson, I.; Pozzi, G. Adv. Synth. Catal. 2005, inpress
Rocaboy,C.; Gladysz, J. A. Chem.-Eur. J. 2003, 9, 88.

29

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

ALTERNATIVE SOLID SUPPORTS FOR FLUOROUS CATALYSIS
Audic, N. A. ;a Bennett, J. A ;a Dyer, P. W. ;b Hope, E. G.;a Stuart, A. M. ;a Suhard, S.aa

Department of Chemistry, University of Leicester, Leicester, LE1 7RH, England
Department of Chemistry, University of Durham, Durham, DH1 3LE, Englandb

egh1@le.ac.uk

Fluorous silica gel has been used as a solid support for heterogenisinghomogeneous catalysts [1] and for fluorous solid phase extraction.[2] However, thesilica framework contains free hydroxyl groups, which can bind destructively to manyeffective homogeneous transition metal catalysts, compromising either catalytic
activity or catalyst recycle.[3] Here, we are evaluating two, alternative, inert solid
supports (fluorous zirconium phosphonates, perfluoroalkylated polystyrenes) for
catalysis/solid phase extraction.
In this presentation, the synthesis of amorphous perfluoroalkylated zirconium
phosphonates and perfluoroalkylated polystyrene beads will be described, along withinitial results from a test catalytic reaction; cyclopropanation of styrene using
dirhodium perfluorobutyrate as catalyst. The work will compare the activity of thecatalyst under homogeneous conditions with those from the catalyst supported on
both fluorous and non-fluorous solid supports, along with recovery, recycle andrhodium leaching levels. In addition, the efficacy of these materials as supports forcatalyst recovery and recycle using solid-phase extraction will be presented.

CO2Et

O
+

[1]
[2]
[3]

N2

0.1 mol% supported [Rh2(O2C4F7)4]O

110 oC, N2, 4 hours

Gladysz, J. A.; Correa da Costa, R.; Handbook of Fluorous Chemistry, Ed.
Gladysz, J. A.; Curran, D. P.; Horváth, I. T.; Wiley-VCH Verlag GmbH & Co.,
Weinheim, Germany, 2004, 35.
Curran, D. P.; Handbook of Fluorous Chemistry, Ed. Gladysz, J. A.; Curran, D.
P.; Horváth, I. T.; Wiley-VCH Verlag GmbH & Co., Weinheim, Germany, 2004,
101.
Zhang, Q.; Luo, Z.; Curran, D. P.; J. Org. Chem., 2000, 65, 8866; Hope, E. G.;
Stuart, A. M.; West, A. J.; Green Chem., 2004, 6, 345.

30

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

PERFLUORINATED VINYL SULFOXYDES: EFFICIENT SYNTHONSFOR THE PREPARATION OF FLUORINATEDTETRAAZAMACROCYCLES. APPLICATIONS IN CATALYSIS
Magnier, E.a ; de Castries, A.a; Larpent, C.aa

SIRCOB CNRS UMR 8086, Université de Versailles-Saint-Quentin, Bâtiment Lavoisier
45 avenue des Etats-Unis, 78000 Versailles
magnier@chimie.uvsq.fr

We have recently described the straightforward preparation of perfluoroalkyl
sulfoxides and sulfones, on multi-gram scale.[1] These molecules possess multiple
reactivity: dienophiles in Diels-Alder reactions,[2] but also good acceptors for theMichael reaction. This chemical behaviour makes these compounds efficientsynthons for the introduction of long perfluorinated chains and the synthesis ofperfluorinated ligands.
Tetraazacyclotetradecane (cyclam) and its derivatives are well known andefficient ligands of transition metal cations. The properties (solubility, metal bonding)of the macrocycle could be modified by the functionnalization of the nitrogen atoms.
One of the easiest way to achieve this chemical modification is the Michael
addition.[3]The goal of this study is to take profit of the high reactivity of perfluoroalkyl
vinyl sulfoxide to synthesize new perfluorinated azamacrocycles in order to develop
catalytic fluorous chemistry, after complexation with a transition metal (scheme).
O
NH HN
NH HN

1)

SOC6F13

iPrOH, 78%

F13C6
F13C6

2) CuX2

S

O
N

S

N
Cu2+

S
O

N

N

S
2X

C6 F13C6 F13- O

The preparation of different perfluorinated macrocycles and our first results ofoxidation reaction in fluorous biphasic catalysis will be presented.

[1]
[2]
[3]

Magnier, E.; Tordeux, M.; Goumont, R.; Magder, K.; Wakselman, C. J. Fluorine
Chem. 2003, 124, 55.
Moïse, J.; Goumont, R.; Magnier, E.; Wakselman C. Synthesis 2004, 14, 2297.
Fensterbank, H.; Zhu, J.; Riou, D.; Larpent, C. J. Chem. Soc., Perkin Trans. 1,
1999, 811–815

31

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

HYDROGENATION OF STYRENE AND 1-OCTENE CATALYZEDUSING Pd(II) COMPLEX WITH MONODENTATEPERFLUOROPYRIDINE IN ScCO2 AND CONVENTIONAL ORGANICSOLVENTS
Kani, I.;a Yilmaz, F.aaChemistry Department, Science Faculty, Anadolu University,
26470, Eskisehir, Turkey
ibrahimkani@anadolu.edu.tr

The fluorous pyridine [1,2], NC5H4COOCH2(CF2)7CF3, is prepared in two stepfrom nicotinic acid and then reacted with Pd(OAc)2 to gave soluble and active
catalyst in supercritical carbon dioxide (scCO2) [3]. We evaluated its hydrogenation
activity using styrene and 1-octene as model reactions. Nitrogen donor Pd(II)compound examined for both supercritical carbon dioxide and organic solvents(toluene, acetone and methanol). Different substrate/catalyst molar ratios werestudied for the hydrogenation of olefins at 80 oC and 102 bar in scCO2. Also theeffect of temperature at 102 bar, and the effect of pressure at 80 oC were analyzed
for the same reactions. The product of 1-octene was mostly n-octane together withisomerization products. Styrene converted to single product ethyl benzene. The
synthesis of the catalyst is reproducible, as shown by reaction activity studies on
different batches of catalyst. scCO2 is a more effective, green reaction medium forstyrene and 1-octene compared with conventional organic solvents.

[1]
[2]
[3]

Nishimura T.; Maeda,Y.; Uemura, S. , J. Chem. Soc. Perkin Trans. 1 2000,
4301.
Rocaboy C.; Hampel F.; Gladysz J. A., J. Org. Chem. 2002, 67, 6863.
Kani I, Omary M .A. ; Rawashdeh-Omary M. A.; Lopez-Castillo Z. K.; Flores R.;
Akgerman A.; Fackler J. P., Tetrahedron 2002, 58, (20), 3923

32

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

FLUOROUS BIPHASIC CATALYSIS WITHOUT SOLVENT: NOVELRECYCLING CONCEPT
Pollet P.,a Hallett J.,a Thomas C.,a Jones R.S., a Eckert C.A., a Liotta, C.L. a
Jessop P.G.baGeorgia Institute of Technology, Atlanta, GA, 30332-0100b
Queens University, Kingston, Canada
pamela.pollet@chemistry.gatech.edu

The regulations and needs for maintaining the ecologic equilibrium of our planet havemade the scientific community facing new challenges. Efficiently synthesizing chemicalcommodities or high added value products is not satisfactory anymore; the synthetic
processes must minimize the impact on the environment and/or society and remain
economically competitive.
Homogeneous catalysis is technically superior to the heterogeneous catalysis but isreluctantly use in industry due to often strenuous separations and contaminations of the
product. Numbers of concept have been devised in order to achieve homogenous catalysis
while ease the separation—ideally mimic the heterogeneous separation. Fluorous Biphasic
Catalysis is a wonderful tool which allows the reaction to proceed in homogeneousconditions while the separation deals with a biphasic system.[1] Unfortunately, fluorous
solvents are environmentally persistent, they are expensive and do possess small solubility
in organic which lead to leaching phenomena.
Our concept relies on using a minimum amount of fluorous phase which will be
immobilized—minimize leaching—and will be recycled as normal fluorous phase—to limit theactual amount of fluorous compound. The inter-disciplinary approach of the problem
combined the Gas Expanded Liquid (GXLs) technology and the fluorous chemistry.
“Fluorous silica” in which fluorous tails have been chemically bond to the silica core provides
a fluorophile surface in place of fluorous phase. The critical ‘switch’ which will turn on/off theimmobilization of the fluorinated-tagged catalyst onto thefluorous silica surface is CO2. Gas expanded liquids are
unique, extremely tunable, and possess hybrid properties
from both gases and liquids. CO2 expanded organic
solvents are fluorophilic and can induced miscibility oforganic and fluorous phases under moderate CO2
pressure (Figure 1). CO2 is the trigger that allows the
Figure 1. Biphasic system FC75fluoro-tagged catalyst to be reversibly immobilized andtoluene 0b of CO2, in the middle
recycled, while permitting the reaction to process under
32b, and in the right monophasic
homogeneous conditions.
Hydrogenation is a powerful reaction that has been used to highlight the potential ofthis novel concept. Eliminating the fluorous solvent phase, reducing the need for organic
phase from the CO2 benefit and recycling the costly and/or toxic catalyst combined with theeasy separation constitute a step-toward sustainable and “green” technology.
[1]

Horváth, I.T. and J. Rábai, Facile Catalyst Separation Without Water: Fluorous Biphase
Hydroformylation of Olefins. Science, 1994. 266: p. 72

33

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

SYNTHESIS OF FLUOROUS PHOSPHINES
Vlád G., a Fraga-Dubreuil J.,a Farkas N.,a Richter F.,b
Horváth I. T.aa

Eötvös University, Department of Chemical Technology and Environmental Chemistry, Pázmány Péters. 1/A, Budapest, Hungary.
b
Bayer MaterialScience AG, Leverkusen, Germany
gabor.vlad@yahoo.com

Fluorous catalysts could offer facile product separation for many homogeneous
catalytic reactions. One of the most effective ways to make an organometallic
catalyst soluble in the fluorous phase is the incorporation of perfluoroalkyl-group(s)into the ligands of the catalyst.1 Since phosphines are frequently used as ligands, wehave been developing novel and efficient synthetic protocols for the preparation offluorous soluble phosphines.
We have already reported the stepwise incorporation of individual perfluoroalkylalkyl groups, which provided an opportunity to fine-tune the electron-density on thephosphorus center by varying the length of the alkyl-spacer between the phosphorus
atom and the perfluoroalkyl-group.2 We have used another approach involving theradical addition of two perfluoroalkyl-olefines to phenylphosphine followed by analkylation of the resulted bis(perfluoroalkyl-alkyl)phenylphosphine with theappropriate fluorous iodoalkane. The phenyl-group of this phosphonium-salt can beselectively removed leading to a fluorous phosphine oxide, the reduction of whichyields the target phosphine.
1.
PH2

2.

x

RFy

RFwRHvI

x+2

P

RFy
x+2

v

RFy

3. NaOH

x+2

O

I

RFw

P

RFy
x+2

v

RFy

RFw

4. HSiCl3

x+2

P

RFy
x+2

v

RFy

RFw

x: 0, 1, 2; y: 4, 6, 8, 10; v: 3, 4; w: 8

BINAPHOS and BINAS are among the most efficient diphosphine ligands forrhodium-catalyzed asymmetric hydroformylation in homogeneous or biphasic
conditions, respectively.3 In order to combine the efficiency of the BINAPHOS ligand
with the advantages of facile fluorous biphasic separation, we have developed asynthesis for the corresponding fluorous BINAPHOS ligand.
RF8

RF8

RF8

P
P

RF8
RF8

RF8

[1]
[2]

[3]

I.T. Horváth and J. Rábai, Science 1994, 266, 72-75 and I.T. Horváth, Acc. Chem.
Res. 1998, 31, 641-650.
G. Vlád, F. Richter, I. T. Horváth, Org. Lett. 2004, 6, 4559-4561.
R.W. Eckl, T. Priermeier, W.A. Herrmann, J. Organomet. Chem. 1997, 532, 243-249.

34

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

APPLICATION OF FLUOROUS TECHNOLOGIES INSOLUTION-PHASE SYNTHESIS
Zhang W.
Fluorous Technologies, Inc. 970 William Pitt Way, Pittsburgh, PA 15238 USA
w.zhang@fluorous.com

Fluorous synthesis has been recently introduced as a “beadless” combinatorial technology.
It employs perfluoroalkyl chains instead of resins as “phase tags” to facilitate the separation
process. The separation is performed by strong and selective interactions between fluorous
molecules with fluorous sorbents in solid-phase extraction or chromatography formats.
Traditional solution-phase reaction conditions and facile phase-tag separations are
successfully integrated into fluorous synthesis. Major advantages of fluorous synthesis
include: fast homogeneous reaction kinetics; easy purification by fluorous separations aswell as conventional methods such as chromatography; no large excess of fluorous
reagents required for the completion of the reaction; and recoverable of fluorous species.
This presentation describes the recent effort at FTI on the development of fluorouscompounds including reagents (e.g. F-DEAD and F-phosphine for Mitsunobu reactions),
scavengers (e.g. F-thiol for electrophiles, F-iscyanate and F-isatoic anhydride fornucleophiles), protecting groups (e.g. F-Boc, F-Cbz, F-Fmoc, and F-silanes), tags (e.g. FFluoMar and F-sulfonyl fluoride), building blocks (e.g. F-benzaldehydes and F-amino acids),
and their applications in parallel and mixture synthesis of drug-like small molecule andnatural product libraries including hydantoins, dihydropteridinones, and mappcines.
Combination of fluorous synthesis with microwave heating, Pd-catalyzed coupling reactions,multi-component reactions, and comparison of fluorous synthesis with conventional solutionphase and solid-phase synthesis are also highlighted.

Rf

O

Cl

O

O
N N

O

Rf

R4 S

N

N

O
Rf

Rf

O

O

O
N

O

R3

N
N
N

functionalized
hydantoinsY

HNF-Boc-ON

F-isatoic anhydride
R1
O H

R3

O
R3

CN

N
Ph

F-dichlorotriazine

R2
N

O

O

Cl

F-DEAD

R1

N

O

Rf

O

N

R3 N
R2

R2

NH

O H

N

CO2R

O
N

R3

R4

N
HO

R2

functionalized
dihydropteridinones

biaryl-substituted
proline analogs

R1

mappcineanalogs

Rf = perfluoroalkyl group[1](a) Zhang, W. Chem. Rev. 2004, 104, 2531. (b) Zhang, W. Curr. Opin. Drug Disc. Dev. 2004,
7, 784. (c) Nagashima, T.; Zhang W. J. Comb. Chem. 2004, 6, 942. (d) Zhang, W. in
Handbook of Fluorous Chemistry; Gladysz, J. A.; Curran, D. P.; Horvath, I. T. Eds. Wiley-VCH,
2004, pp222-236. (e) Lu. Y.; Zhang, W. QSAR Comb. Sci. 2004, 23, 827. (f) Zhang, W.; Chen,
C. H-T.; Lu, Y.; Nagashima, T. Org. Lett. 2004, 6, 1473. (g) Zhang, W. Tetrahedron, 2003, 59,4475. (h) Zhang, W.; Lu, Y. Org. Lett. 2003, 5, 2555. (i) Zhang, W.; Luo, Z.; Chen, C.; Curran,D. P. J. Am. Chem. Soc. 2002, 124, 10443. (j) Curran, D. P. Synlett 2001, 1488.

35

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

AN EXPEDITIOUS SYNTHESIS OF BISTRATAMIDE H USING A NEW
FLUOROUS PROTECTING GROUP
Takeuchi S., Nakamura Y., Okumura K.
Niigata University of Pharmacy and Applied Life Sciences, 265-1 Higashijima, Niigata 956-8603,
Japan
takeuchi@niigata-pharm.ac.jp

Bistratamides are cyclic tri- or tetra-peptides of amino acids that include
heterocycles such as thiazole and oxazole. They were isolated from ascidian
Lissolinum bistratum and shown to have bioactivities such as anti-tumor and anticancer effects. Shin's and Kelly's groups have recently synthesized some ofbistratamides in a normal way of peptide synthesis [1]. Here we would like to reportan examination of an expeditious synthesis of bistratamide H by using a novel
fluorous protecting
group, 2-(tris(perfluorodecyl)silyl)ethoxycarbonyl (FTeoc), a
fluorous version of 2-(trimethyl)ethoxycarbonyl group as follows.
TBAF

F

TeocHNF

CO2H

N

TeocHN

1
F

N

H2N

4 steps

2

3

CO2Et

S

LiOHaq. F
O

Teoc = (C8F17CH2CH2)3Si

CO2Et

S

N

TeocHN

CO2H

S

4
O

3 + 4

1) PyBOP
2) LiOH aq.

TeocHN

PyBOP

CO2H

S

F

H
N

N

N
S

N

H2N

O

CO2Me

O
6

5

O
O
S

F

TeocHN

H
N

N

N
H

N
S

O

1) LiOH aq.
2) TBAF

O
N
CO2Me

O

N

3) PyBOP
DMAP

S

N
H

N
HN

NH
O

O

N
S

7

Bistratamide H

In this method, most of the fluorous intermediates including the precursor wereisolated by fluorous liquid-liquid extraction. Optimization of the reactions was carriedout by monitoring the reactions with TLC. In addition, the optical purity of the fluorous
intermediate was checked by HPLC with a chiral column to avoid racemization of theintermediate products.
[1] a) Shin, C.; Abe, C.; Yonezawa, Y. Chem. Lett. 2004, 33, 664. b) You, S-L.;
Kelly, J. W. Chem. Eur. J. 2004, 10, 71.
36

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

ASSOCIATION OF FLUOROUS ˝PHASE-VANISHING˝ METHOD WITH
VISIBLE-LIGHT ACTIVATION FOR BENZYL BROMINATION
Podgoršek, A.; Stavber, S.; Zupan, M.; Iskra, J.
Laboratory of Organic and Bioorganic Chemistry, "Jožef Stefan" Institute and Faculty of Chemistry andChemical Technology of University of Ljubljana, Jamova 39, Ljubljana, Slovenia;
jernej.iskra@ijs.si

Benzyl bromination is one of the synthetic methodologies widely used for thefunctionalization of alkyl aromatics through the nucleophilic substitution of benzyl
bromine. A classical direct method is radical bromination utilizing NBS with the use ofradical initiators and CCl4 as a solvent. Due to a heavy environmental burden createdby the Wohl-Ziegler bromination there is a lot of interest in providing moreenvironmentally benign method.[1,2,3]
Molecular bromine has some advantages and would offers a better alternative to theuse of NBS. Furthermore, activation of radical bromination requires only visible light.
In order to achieve a selective radical reaction over an electrophilic one, theconcentration of bromine needs to be low and thus the amount of solvent used forthe reaction is high. The approach taken by Curran et al. offers a unique possibility touse fluorous solvent as a bulk membrane for the slow diffusion of the molecularbromine into the reaction mixture.[4] So-called ˝phase-vanishing˝ reaction was
already used in many cases and is useful for very reactive reagents and exothermic
reactions. [5]To achieve benzyl bromination in highly concentrated solutions, we combined slow
addition of bromine to the reaction phase by “phase-vanishing” method with its
concomitant activation for radical reaction by visible-light. Interesting results wereobtained that reveal the role of phase transfer in the reaction process. Benzyl
bromination was observed in various solvents including methanol and acetonitrile.
The substituent on the aromatic ring effects the course of bromination and threedifferent processes were observed: benzyl bromination, bromination at the aromaticring and bromination on the side chain of the substituent.

Ar

hν

Ar

CH2Br

CH3
HBr

C8F18
Br2

[1]
[2]
[3]
[4]
[5]

Amijs, C. H. M.; Klink, G. P. M.; van Koten, G. Green Chem. 2003, 5, 470.
Togo, H.; Hirai, T. Synlett, 2003, 702.
Mestres, R.; Palenzuela, J. Green Chem. 2002, 4, 314.
Ryu, I.; Matsubara, H.; Yasuda, S.; Nakamura, H.; Curran, D. P. J. Am. Chem.
Soc. 2002, 124, 12946.
Curran, D.P.; Werner, S. Org. Lett. 2004, 6, 1021 and references cited therein.

37

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

FLUOROPONYTAILED COPPER(II) CARBOXYLATE COMPLEXESWITH NON-FLUOROUS LIGANDS AS PRE-CATALYSTS FOR THE
OXIDATION OF ALKENOLS AND ALCOHOLS UNDER FLUOROUS
BIPHASIC OR THERMOMORPHIC MODES
Contel, M.,a Villuendas, P.R.,a Fernández-Gallardo J.,a Alonso, P.J.,b
Vincent, J.-M,c and Fish, R.H.da

Departamento de Química Inorgánica, bDepartamento de Física de la Materia Condensada.
Instituto de Ciencia de Materiales de Aragón, Facultad de Ciencias, Universidad de ZaragozaC.S.I.C. 50009 Zaragoza, Spain. cLaboratoire de Chimie Organique et Organométallique (UMR-CNRS5802), Université Bordeaux 1, 351 cours de la Libération, 33405 Talence Cedex, France. dLawrence
Berkeley National Laboratory, University of California, Berkeley, CA 94720, USA.

a,bmcontel@unizar.es

In this fluorous biphasic catalysis (FBC) contribution, we will present the synthesis andcharacterization of new fluoroponytailed copper (II) complexes that also contain non-fluorous
ligands, and define their role, as precatalysts, in the oxidation of alkenols and alcohols under
FBC conditions, or as thermomorphic solids (soluble at higher temperatures in organic
solvent). The dimeric complex, [Cu({C8F17(CH2)3}CHCO2)2], 1, was found to be soluble inperfluorocarbons.[1] The catalytic activity of 1 under FBC conditions[2] for the oxidation ofalkenols and alcohols to aldehydes was demonstrated, and will be presented. Furthermore,
addition of non-fluorous nitrogen ligands, such as N-1,4,7-trimethyl-TACN or N,N,N’,N’,N”pentamethyldiethylenetriamine to trifluoromethylbenzene solutions of 1 afforded novel
fluorous soluble derivatives, 2 and 3, respectively, whose tentative structures were
elucidated by EPR and IR spectroscopic analysis.

R
O

O
O
R

Cu

Me

O

Cu

O
O

O
R

R
O

Me

R C

N
O
O

N

Cu

Me
N
O

Me

C R

Me N
Me
R C

O

2

O
O

N

Cu

N
O

Me
Me
C R

O

3

1

-

R = -CH{(CH2CH2CH2)C8F17}2

While 2 and 3 can catalyze the FBC oxidation of 4-nitrobenzyl alcohol to the 4nitrobenzaldehyde, their thermomorphic properties were more interesting to study. Thus,
solid 3 was soluble in a mixture of chlorobenzene and toluene (1:3) at 80 oC, while insolubleat room temperature, in these same solvents. This thermomorphic property of 3 was used toperform the oxidation of 4-nitrobenzyl alcohol, with TEMPO and O2, at 90 oC in
chlorobenzene/toluene, with recovery of precatalyst 3, by cooling to room temperature.[3] Themechanisms of these FBC/thermomorphic oxidations will also be discussed.
[1]
[2]
[3]

El Bakkari, M. ; McClenaghan, N. ; Vincent, J.M. J. Am. Chem. Soc., 2002, 124, 12942.
Contel, M. ; Izuel, C. ; Laguna, M. ; Villuendas, P.R., Alonso, P.J. ; Fish, R.H. Chem. Eur. J.
2003, 9, 4168.
Wende, M.; Gladysz, J.A. J. Am. Chem. Soc., 2003, 125, 5861 and refs. therein.

38

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

FLUOROUS MIXTURE SYNTHESIS OF MURISOLIN AND
PASSIFLORICIN STEREOISOMER LIBRARIES
Curran D. P.
Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania, 15260 USA
curran+@pitt.edu

Because it separates primarily by fluorine content, fluorous reverse phasesilica gel can be used in a chromatographic mode to separate fluorous moleculesfrom each other. This separation forms the basis of new mixture synthesis
techniques in which members of a series of substrates are tagged with different
fluorous tags, mixed, carried through a series of reactions, and then separated
based on the tag prior to detagging. Recent fluorous mixture syntheses ofstereoisomer libraries of murisolins and passifloricins will be highlighted.
OH
OH
O

C12H25OOH

OH

C14H29OH

OH

O

O
passifloricins

murisolins

39OInternational Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

POSTER PROGRAM

40

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

AN INDICATOR-DISPLACEMENT ASSAY FOR HISTAMINE UNDERFLUOROUS TRIPHASIC CONDITIONS
Fronton, B.; Luguya, R. ; Vincent, J.-M.
LCOO, 351, crs de la libération, 33405 Talence Cedex, France
r.luguya@lcoo.u-bordeaux1.fr

A synthetic receptor, which is bound through noncovalent interactions to anindicator, can function as a chemosensor.[1] Using a “classical” one-phasemethodology the fundamental requirement is that the displacement of the indicator byan analyte results in a change of its optical properties. In such an IndicatorDisplacement Assay (IDA) the indicator is attached to the binding site of the hostthrough non-covalent interactions such as electrostatic interactions, hydrogenbonding or coordination bonds. While IDAs have been used to detect various
analytes their applicability in highly polar solvents such as water is limited due tocompetition with the indicator for host binding. There is thus a great challenge insearching for new methodologies allowing the use of water with these systems.
We previously reported a reversible phase-switching methodology betweenhydrocarbon and perfluorocarbon phases based on the reversible coordination ofpyridyl tags on a highly fluorous copper(II)-carboxylate complex.[2] We wish now to
describe the application of such a highly sensitive reversible phase-switching process
for the detection of histamine under triphasic H2O/CH2Cl2/C6F14 conditions. We will
demonstrate that the fluorous phase can act as an effective barrier against water
enabling detection and titration of histamine in water solution.

[1]
[2]

Wiskur, S. L.; Aït-Haddou, H.; Lavigne, J. J.; Anslyn, E. V. Acc. Chem. Res.
2001, 34, 963.
(a) El Bakkari, M.; McClenaghan, N.; Vincent, J.-M. J. Am. Chem. Soc. 2002,
124, 12942. (b) El Bakkari, M.; Vincent, J.-M. Org. Lett. 2004, 6, 2765.

41

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

HIGHLY FLUORINATED LC MATERIALS FOR SURFACE
MODIFICATION
Cailler L., Taffin de Givenchy E., Guittard F.,* Geribaldi S.
Lab. Chimie des Matériaux Organiques et Métalliques (C.M.O.M.), Faculté des Sciences, Universitéde Nice-Sophia Antipolis, Parc Valrose, 06108 Nice Cedex 2, France.
guittard@unice.fr

The development of highly fluorinated compounds is of great interest in academic
and industrial fields. In fact, the wide use of these materials is due to their unique
physico-chemical properties. This type of compounds is well known for coating
surface, i.e., for marine protection. In this kind of application, the surface properties ofmaterials is important but also the ability of surface reconstruction. In order to find out
the influence of F-alkylated moiety on the microorganized systems like LC, we have
prepared and charaterized new series containing the following main segments :-an hydrophobic and oleophobic part (the fluorinated tail) with different lengths-a spacer oligomethylenic-a connector (linked to the mesogenic core) which can improve the LC properties
All these compounds are well defined and can be easily obtained from commercial
raw materials such as 2-(F-alkyl)ethyl iodide or 2-(F-alkyl)iodide with a purity higher
than 98 %. In this work, we report the preparation, characterization and evaluation ofphysical properties of these new materials. The relation structure - surface
modification of the bulk will be illustred.

42

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

PREPARATION OF FLUOROALKYL PYRIDINE DERIVATIVES FROM
2-AZADIENES AND DIENOPHILES
Palacios, F., Alonso, C., Rubiales, G., Villegas, M., Mtz. de Marigorta, E.,
Rodríguez M.
Departamento de Química Orgánica I, Facultad de Farmacia, Universidad del País Vasco, Spain
qoppagaf@vc.ehu.es

Functionalized 2-azadienes systems are efficient synthons in Organic Synthesis forthe preparation of nitrogen heterocyclic compounds [1] through cycloaddition
reactions and special interest has been focused on the incorporation of a fluorinecontaining group into organic molecules [2] for the preparation of fluorinated building
blocks with biological activity and commercial applications.
In this communication, we report the preparation of fluoroalkyl pyridine derivatives
through a [4+2] cycloaddition strategy involving fluoroalkyl substituted 2-azadienes[3] 1 with dienophiles 2 and 5. Reaction of 3-fluoroalkyl-2-azadienes 1 withenamines 2a (R4 R5=(CH2)4) or 2b (R4=H; R5=iPr) gave pyridine derivatives 3 or/and
also dehydrofluorinated compounds 4, whereas catalyzed reaction with dienophile 5
gave bicyclic pyridine derivatives 6.
R4

R3
N
F2C
RF

N

2

1

4

R5

2

R

R3

RF = F, CF3, C6F13

R (R )N
F2C
RF

R5(R4)
2

R

O
N
N

O

N

5

Yb(OTf)3

F2C
RF

R4(R5)NF

R5(R4)
RF

3

2

R

4

R3

N Ph

R3

5

O
N
N

N Ph
O

R2
6

Acknowledgements:
The present work has been supported by the Dirección General de Investigación delMinisterio de Ciencia y Tecnología (MCYT, Madrid, DGI, PPQ2003-00910) and by
the Universidad del País Vasco (UPV-GC/2002).
References:
[1]
[2]
[3]

Jayakumar, S.; Ishar, M. P. S.; Mahajan, M. P. Tetrahedron 2002, 58, 379-471.
P. Kirsh, Modern Fluoroorganic Chemistry: Synthesis, Reactions andApplications Wiley: New York, 2004.
Palacios, F.; Alonso, C.; Rubiales, G; Villegas, M. Tetrahedron Lett. 2004, 45,4031-4034.

43International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

FLUOROUS GOLD(I) CATALYZED HYDROSILYLATION
Lantos D.,a Contel M.,b Sanz S.,b Horváth I. T.aa

Department of Chemical Technology and Environmental Chemistry, Eötvös University, Pázmány
Péter sétány 1/A, Budapest, H-1117 HungarybDepartamento de Química Inorgánica – Instituto de Ciencia de Materiales de Aragón, Universidad
de Zaragoza – C.S.I.C., Zaragoza, E-50009 Spain
diana.lantos@hit-team.net

The application of gold compounds in catalysis has been rapidly growing, asgold could be a green replacement of toxic heavy metals. In order to provide facile
product separation and catalyst recycling, we have developed a fluorous [1] gold
catalyst.
Several fluorous-soluble phosphine-modified gold(I) compounds have beensynthesized, characterized, and used for the catalytic hydrosilylation of various
aldehydes. The facile separation of the fluorous gold(I) catalyst was demonstrated byrecycling the fluorous phase. Hydrosilylations with the fluorous gold(I) catalyst in theabsence of fluorous solvents were also studied. The catalyst recycling was based on
the temperature dependent solubility of the fluorous gold(I) catalyst [2, 3].
In situ IR and NMR studies suggest a novel mechanism for the catalytichydrosilylation of aldehydes in the presence of gold compounds:

Ph

PR3
C

O

H
R3 P
Ph
H

C

O
Au(PR3)x

Cl

Ph
H

H
Ph
H

[1]
[2]
[3]

H SiR3

R3P
C

O

Cl
Au(PR3)x

SiR3
C

O

Horváth, I.T.; Rábai, J. Science, 1994, 266, 72
Wende, M.; Gladysz, J.A. J. Am. Chem. Soc., 2003, 123, 11491.
Ishihara, K. ; Kondo, S. ; Yamamoto, H. Synlett 2001, 1371.

44

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

H2O2/FLUORO-ALCOHOL SYSTEM FOR DIRECT AND SELECTIVESYNTHESIS OF ANTIMALARIAL 1,2,4,5-TETRAOXANESŽmitek, K.;a Stavber, S.;a Zupan, M.;a Bonnet-Delpon, D.;b Iskra, J.aaLaboratory of Organic and Bioorganic Chemistry, "Jožef Stefan" Institute and Faculty of Chemistry
and Chemical Technology of University of Ljubljana, Jamova 39, Ljubljana, Slovenia;b
BIOCIS UPRES-A 8079, Faculté de Pharmacie, Université Paris-Sud, Chatenay-Malabry, France;
jernej.iskra@ijs.si

Malaria causes or contributes to millions of deaths per year worldwide. Resistance ofparasites to conventional drugs like chloroquine is a severe problem in dealing withmalaria. Artemisinin and its semi-synthetic derivatives with endoperoxide functionalgroup represent a new class of antimalarials, active against a chloroquine-resistantseves of parasite Plasmodium falciparum.[1] This boosted the research into cyclic
peroxides as a group of potential anti-malarial agents and 1,2,4,5-tetraoxanes among
them. Synthesis of tetraoxanes by acid-catalyzed oxidative cyclization is potentially auseful method due to its simplicity. Yet, during the synthesis of dispiro-1,2,4,5tetraoxanes (TO) hexaoxonane (HO) is also formed.[2] Consequently, a different
method had to be applied - mainly ozonolysis of O-methyloximes.[3]We took fluoro-alcohols (1,1,1-trifluoroethanol - TFE and 1,1,1,3,3,3-hexafluoro-2propanol - HFIP) as solvents that activate hydrogen peroxide and in these conditions
tetraoxanes were selectively formed directly from ketone, 30% H2O2 and acid as acatalyst.[4] Besides cyclic ketones also dialkyl ketones were used as the starting
compounds and 3,3,6,6-tetraalkyl-1,2,4,5-tetraoxanes were isolated as the only
products.
R

R
O O
O
O

O O
R

R

O
O

O O
( TO )( HO )R

By using fluoroalcohols as solvents, non-symmetric TOs were also synthesised
directly in a one-pot procedure by the in-situ formation of gem-dihydroperoxide fromcarbonyl compound and H2O2 followed by acid-catalyzed cyclization step withanother ketone. The only compound formed was non-symmetric TO in high yield.
[1]
[2]

[3]

Rosenthal, P. J., ed. ˝Antimalarial Chemotherapy˝, Humana press, Totowa, New
Jersey, 2001.
Wiesner, J.; Ortmann, R.; Jomaa, H.; Schlitzer, M. Angew. Chem. Ind. Ed. 2003,
42, 5274-5293. Kim, H.-S.; Begum, K.; Ogura, N.; Wataya, Y.; Nonami, Y.; Ito,T.; Masuyama, A.; Nojima, M.; McCullough, K. J. Med. Chem. 2003, 46, 19571961.
Dong, Y.; Vennerstrom, J. L. J. Org. Chem. 1998, 63, 8582-8585.

45

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

RECYCLBLE MOLECULAR THERMOMORPHIC CATALYSTS FORATOM TRANSFER RADICAL ADDITIONS AND POLYMERIZATION
Lastécouères, D. ;a Barré, G. ;a Taton, D. ;b Vincent, J.-M.aa

LCOO, 351 crs de la libération, 33405 Talence Cedex, Franceb
LCPO, 16 av Pey-Berland, 33607 Talence cedex, Franced.lastecoueres@lcoo.u-bordeaux1.fr

The search for “ideal recoverable catalysts” is a major concern of modern
chemistry.[1] We have been interested in developing molecular recyclable catalysts
for Atom Transfer Radical Additions and Polymerizations (ATRA, ATRP). We
previously reported the first example of a molecular recyclable catalyst for ATRA thatwas based on the thermomorphic behaviour of a Fluorous Biphasic System (FBS).[2]The fluorous polyamine ligands 1 and 2 were prepared and their CuCl complexes
used as catalysts for the preparation of lactones. Efficient recycling of the catalyst
was achieved by simple hydrocarbon/perfluorocarbon extraction, leading to low
copper contamination of the final products. This FBS also proved to be effective forcatalyst recovery in ATRP.[3]We recently developed a simple non-fluorous recyclable catalyst for ATRP using thetetramine ligand 3.[4] Compound 3 exhibits an exceptionally large temperaturedependent solubility in 1,4-dioxane, its solubility increasing ca. ~104-fold between 23
and 50°C. The CuBr/3 complex was shown to catalyze the ATRP of methyl
methacrylate with excellent controls of the molar masses and polydispersities. Due tothe thermoresponsive character of CuBr/3 polymerizations were carried out inhomogeneous conditions while catalyst recovery (> 95 %) was achieved by a simple
filtration after lowering the temperature to 10°C. Very low residual copper
contamination (~200 ppm) was measured in the final polymer. The catalyst has also
been recycled two times without significant loss of activity.

(CH2)3C8F17 (CH2)3C8F17
NN
C8F17(H2C)3
N(CH2)3C8F17(CH2)3C8F17

1

[1]
[2]
[3]
[4]

C8F17(H2C)3
N (CH ) C F
2 3 8 17N
C8F17(H2C)3
N

2

C8F17(H2C)3

N(CH2)3C8F17

C18H37
NC H
18 37
N

C18H37

C8F17(H2C)3

C18H37

3

N

C18H37N

C18H37

Gladysz, J. A. Pure Appl. Chem. 2001, 73, 1319.
De Campo, F.; Lastécouères, D.; Vincent, J.-M.; Verlhac, J.-B. J. Org. Chem.
1999, 64, 4969.
Haddleton, D. M.; Jakson, S. G.; Bon, S. A. F. J. Am. Chem. Soc. 2000, 122,
1542.
Barré, G.; Taton, D.; Lastécouères, D.; Vincent, J.-M. J. Am. Chem. Soc. 2004,
126, 7764.

46

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

REVERSIBLE HYDROCARBON/PERFLUOROCARBON PHASESWITCHING OF PYRIDYL TAGGED MOLECULESEl Bakkari M., Vincent J.-M.
Laboratoire de Chimie Organique et Organométallique UMR-CNRS 5802, Université Bordeaux 1,
Talence, France.
mounir_is@yahoo.fr

The search for rapid and efficient protocols for the purification of organic compounds
is a major concern of modern chemistry.[1] This research area has received special
attention during the past decade with the advent of combinatorial synthesis andautomated organic synthesis that require straightforward separation protocols. In
addition to the heterogeneous and homogeneous macromolecular systems,
homogeneous molecular approaches have been developed in which the phaseseparation is driven by a small functional group called a phase tag.[2]We discovered that pyridyl groups may be used as masked phase tags for thehydrocarbon/perfluorocarbon phase-switching of fluorine-free pyridyl-tagged
molecules.[3] We showed that rather large and polar molecules such as meso-pyridyl
substituted porphyrins are very effectively extracted into perfluorocarbons by pyridine
coordination to a fluorous dicopper(II)-carboxylate complex. Due to the high lability of
the coordination bonds, release of the tagged molecules into the hydrocarbon phaseis achieved by simply adding THF in excess to the biphasic system, the THF acting
as a competitive ligand.
Recently, as a case study for application of this novel phase-switching technique, abis-monopyridyl benzyl alcohol tag was synthesized and used to prepare an
analytically pure hydantoin.[4] After each step, the product was recovered in highyield and purity using the straightforward liquid-liquid extraction/recovery procedure.

[1]
[2]
[3]
[4]

Review: Curran, D. P. Angew. Chem., Int. Ed. 1998, 37, 1174.
Yoshida, J.-I.; Itami, K. Chem. Rev. 2002, 102, 3693.
El Bakkari, M.; McClenaghan, N.; Vincent, J.-M. J. Am. Chem. Soc. 2002, 124,
12942.
El Bakkari, M.; Vincent, J.-M. Org. Lett. 2004, 6, 2765.

47

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

APPLICATION OF THE "PHASE-VANISHING METHOD" TOCYCLOPROPANATION OF ALKENES
Matsubara H. , Tsukida M., Rahman M. T., Ryu I.
Department of Chemistry, Graduate School of Science, Osaka Prefecture University,
Sakai, Osaka 599-8531, Japanmatsu@c.s.osakafu-u.ac.jp

The “phase-vanishing (PV) method” utilize unique properties of the fluorous
phase, which can divide otherwise miscible two phases. The PV method, which
capitalizes on the diffusion of reagents through the fluorous phase, does not need
any dropping funnels, heating/cooling baths, and even thermometers. Using the PV
method, we carried out various organic reactions including bromination of olefins with
Br2, demethylation of aryl methyl ethers with BBr3, bromination and chlorination of
alcohols with PBr3 or SOBr3 and PCl3 or SOCl2 respectively, and the Friedel-Crafts
acylation of aromatic compounds with SnCl4. [1] Recent work demonstrates that the
PV method has been modified to use gases [2] or a reagent reservoir with greater
density than the fluorous phase, such as 1,2-dibromoethane. [3]Here we will show an application of the PV method to cyclopropanation of
olefins. While PV cyclopropanation of olefins using CH2I2 / Et2Zn gave poor results,
CH2I2 / Et3Al systems afforded the cycloprapane derivatives in good yields. We also
discuss about alternative fluorous media other than FC-72 available for the PV
method.

[1]

[2]
[3]

Ryu, I. ; Matsubara, H. ; Yasuda, S. ; Nakamura, H. ; Curran, D. P. J. Am.
Chem. Soc. 2002, 124, 12946 ; Nakamura, H. ; Usui, T. ; Kuroda, H. ; Ryu, I. ;Matsubara, H. ; Yasuda, S. ; Curran, D. P. Org. Lett. 2003, 5, 1167 ; Matsubara,
H. ; Yasuda, S. ; Ryu, I. Synlett 2003, 247.
Iskra, J. ; Stavber, S. ; Zupan, M. Chem. Commun. 2003, 2496.
Jana, N. K. ; Verkade, J. G. Org. Lett. 2003, 5, 3787 ; Curran, D. P. ; Werner, S.
Org. Lett. 2004, 6, 1021.

48

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

SYNTHESIS OF OLIGOSACCHARIDE AND PEPTIDE,GLYCOPEPTIDE USING FLUOROUS SUPPORTMIzuno, M. ;a Goto, K. ;a Miura, T. ;a Inazu, T.a, baLaboratory of Glycoorganic Chemistry, The Nnoguchi Institute, 1-8-1, Kaga, Itabashi-ku,Tokyo,
173-0003 JAPANb
Department of Applied Chemistry, School of Engineering, and Institute of Glycotechnology, Tokai
University, Kitakaname 1117, Hiratsuka, Kanagawa 259-1292 JAPANmmizuno@noguchi.or.jp

Novel acyl-type fluorous protecting group (Bfp) [1] and fluorous support [2, 3] as aheavy fluorous tag were prepared, and these fluorous tags made it possible tosynthesize oligosaccharide with minimal column chromatography purification.

Bfp-O
Bfp-O

Glycosylation&
TBDPSOOH
deprotection
AcO
O
OBn
AcO
O-Bfp

O

O
AcO
OAc
AcO

O

C8F17

N

O

OAc
AcO

O
AcO
OAc
AcO

O

O
BfpO
OAc
BfpO

O

OBn
OBfp

9 steps, 29%, with1 chromatography

O
C8F17

O
AcO

Bfp-OHOH
O

Syntheis of oligosaccharide using fluorous chemistry

Furthermore, rapid synthesis of peptides and glycopeptides were achieved on a
fluorous support with suitable linker corresponding to the C-terminal form.
C-terminal COOH peptide
HO

H-Tyr-Gly-Gly-Phe-Leu O

F

O
O
TFA

F

O
O

H-Tyr-Gly-Gly-Phe-Leu-OH

F

Fluorous support

Glycopeptide
Fmoc strategy

Fmoc-Leu O

F

O
O

[1]
[2]
[3]
[4]
[5]

HO
HO

OH
O
AcHN
H-Ile-Asn-Ala-Thr-Leu-OH

Miura, T.; Goto, K.; Waragai, H.; Matsumoto, H.; Hirose, Y.; Ohmae, M.; Ishida, H-k.;
Satoh, A.; Inazu, T. J. Org. Chem. 2004, 69, 5348.
Miura. T.; Goto, K.; Hosaka, D.; Inazu, T. Angew. Chem., Int. Ed. 2003, 42, 2047.
Goto, K.; Miura, T.; Mizuno, M.; Takaki, H.; Imai, N.; Murakami, Y.; Inazu, T. Synlett
2004, 2221.
Mizuno, M.; Goto, K.; Miura, T.; Hosaka, D.; Inazu, T. Chem. Commun. 2003, 972.
Mizuno, M.; Goto, K.; Miura, T. Chem. Lett. 2005, 34, 426.

49

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

REGIOSELECTIVE SYNTHESIS OF FLUORINATED Α- AND ΒAMINOPHOSPHORUS DERIVATIVES FROM
p-TOLYLSULFONYL OXIMESPalacios, F.; Ochoa de Retana, A. M.; Alonso, J. M.; Vélez del Burgo, A.
Dpto. Química Orgánica I, Fac. Farmacia, Universidad del País Vasco UPV/EHU
Apdo. 450, 01080 Vitoria-Gasteiz, Spain
qoppagaf@vc.ehu.es

The chemistry of 2H-azirines has been extensively explored because of the highreactivity of this ring towards nucleophilic and electrophilic reagents as well as fortheir photochemical and thermal behaviour [1]. In this way, we disclosed the first
asymmetric synthesis of 2H-azirines derived from phosphine oxides andphosphonates by alkaloid- and solid-supported amines-mediated Neber reaction of
tosyloximes [2].
Following our studies on the synthetic applications of this heterocycles, here we
disclose the synthesis of functionalized aziridines 3 through addition of Grignard
reagents to 2H-azirines 2, generated in situ from fluorine containing p-tolylsulfonyl
oximes derived from diphenylphosphine oxide 1 (R= Ph) and diethyl phosphonate 1(R= OEt). We also explore the use of these aziridinyl derivatives 3 as versatile key
intermediates for the regioselective synthesis of fluorinated α- and βaminophosphorus derivatives 4 and 5 [3] (Figure 1).
NH2
R1
TsO

R1-MgBrNRF

P(O)R2

1 R= Ph, OEt

R1-MgBrNRF

P(O)R2

R1

H
N

RF

2

H

P(O)R2
RF

H2

4
or

P(O)R2NH2

3P(O)R2

1

RRF

5

Figure 1
Acknowledgements:
The present work has been supported by the Dirección General de Investigación delMinisterio de Ciencia y Tecnología (MCYT, Madrid, DGI, PPQ2003-00910) and by
the Universidad del País Vasco (UPV-GC/2002).
[1]
[2]
[3]

Palacios, F.; Ochoa de Retana, A. M.; Martínez de Marigorta, E.; De los Santos,
J. M., Org. Prep. Proc. Int., 2002, 34, 219-269.
Palacios, F.; Aparicio, D.; Ochoa de Retana, A. M.; De los Santos, J. M.; Gil, J.
I.; Alonso, J. M., J. Org. Chem., 2002, 67, 7283-7288.
Palacios, F.; Alonso, C.; De los Santos, J. M., Chem. Rev., 2005, 105, 899-931.

50

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

POLYFLUORINATED BAYTRON
Popkova, V.Ya.;a Kirchmeyer, S. ;b Bazhenov, V. M. ;c Nikanorov, V. A. ca

R&D department, AO Bayer (Moscow), Bolshoi Tryokhgornyi per. 1, 123022 Moscow, Russia,
Central R&D Division, H.C. Starck GmbH, c/o Bayer AG, B 202, 52368 Leverkusen, Germany,c
A.N.Nesmeyanov Institute of Organoelement compounds, RAS, Vavilov str. 28, 119991 Moscow,
Russiab

vera.popkova.vp@bayer-ag.de

Baytron® M (3,4-Ethylenedioxythiophene (EDT, EDOT,) (1) is a monomer for thesynthesis of the latest generation of conductive polymers, which is used incapacitors, antistatic coatings for plastics and glass, organic light-emitting diodes(OLEDS).[1-4] It is available in ton scale from H.C. Starck GmbH, a subsidiary of theBayerMaterialScience Group. Fluorinated analogues of Baytron® M were unknown
up to now. However the introduction of fluorine atoms in the ethylene chain of 1 is ofgreat interest and could radically change the electronic properties of polymer material
by the introduction of the strong electron-withdrawing group and might havesignificant impact on the transparency, conductivity, and thermal stability of theresulting polymer. The known method of the synthesis of 1, which involves thereaction of the corresponding derivatives of dihydroxythiophene with 1,2dibromoethane [5] cannot be transferred automatically to the synthesis of 3,4tetrafluoroethylenedioxythiophene. In the case of 1,2-dibromoperfluoroethane themixture of inseparable products is the result of the reaction.
We have found a way for the preparationof 3,4-polyfluoroalkylenedioxythiopheneson the example of a new 3,4trifluoroethylene analogue (2).
The later was obtained by the reaction of dimethyl 3,4-dihydroxy-2,5thiophenecarboxylate, as a starting material with trifluorochloroethylene as areactant, in DMSO as a solvent, in the presence of NaOH as a base Æ the following
water-alkaline hydrolysis of methyl ester of the bicycle obtained in the first step withthe formation of the corresponding free carboxylic acid at the thiophene ring Æ andthe decarboxylation of the carboxylic group at the thiophene ring of the productformed in the second step using Cu-powder in quinoline as a promoter. The details of
the different approaches to the synthesis of 3,4-polyfluoroethylenedioxythiophene,
the reaction's conditions and the properties of 2, as well as its electrochemical
properties, will be discussed.
[1]
[2]
[3]
[4]
[5]

Jonas, F.; Heywang, G.; Schmidtberg, W.; Heinze, J.; Dietrich, M. 1988, DE 38
135 89; 1988, DE 38 434 12; 1989 EP 339 340 A2, A3, B1 ; b) Kiebooms, R.;
Aleshin, A.; Hutchison, K.; Wudl, F.; Heeger, A. 1999, Synthetic Metals, 101, 436.
a) Jonas, F.; Meier, H.; Pielartzik, H.; Freitag, D. 1995, Kunststoffe-Plast Europe,86(8),1079; b) Cutler, C.; Bouguettaya, M.; Reynolds, J. 2002, Adv. Mater.,
14(9), 684.
a) Jonas, F.; Krafft, W.; 1991 EP 440 957 A2, A3, B1 ; b) Krafft, W.; Jonas, F.;
Muys, B.; Quintens, D. 1993 EP 564911 A2, A3.
Heuer, H.; Wehrmann, R.; Kirchmeyer, S. 2002, Adv. Funct. Mater., 12 (2), 89.
Guha, P.; Iyer, B. 1938, J. Ind. Inst.Sc., A21,115.

51

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

FLUOROUS CHROMIUM REAGENTS FOR PREPARATION OF
ORGANIC COMPOUNDS
Ghammamy S.,a Rezaee M.ba

Department of Chemistry, Azad Islamic University, Saveh Campus, Saveh, Iranb
Iran Teaching and Growthing Ministry, Qazvin Organization, Qazvin, Iranshghamami@yahoo.com

Development of oxidizing agents based upon higher-valent transition metal oxo
derivatives has been the objective of many research laboratories and a host of suchreagents derived from ruthenium, osmium, iron, manganese, molybdenum, vanadiumand chromium have all proven to be capable of oxidation. In particular, there iscontinued interest in the development of new chromium(VI) reagents for the effective
and selective oxidation of organic substrates under mild conditions. In recent years,
significant improvements were achieved by the use of new oxidizing agents, such as
pyridinium fluorochromate,[1] caffeinilium chlorochromate,[2] isoquinolinium
fluorochromate,[3] and tetramethylammonium fluorochromate.[4] We have now
investigated the synthetic potential of trialkylammonium fluorochromates,
R3NH[CrO3F], (TriAAFC) and we have found that these reagents have certain
advantages over similar oxidizing agents in terms of amounts of oxidant and solvent
required, easier working up and high yields. The results obtained withtrialkylammonium fluorochromates are very satisfactory and show the new reagentsas valuable additions to the existing oxidizing agents. Trialkylammonium
fluorochromates have also been used for oxidations of carbohydrates such as
1,2:5,6-Di-O-isopropylidine-α-D-Glucofuranose to its relative ketosugar like by use of
the equimolar ratio of the reagent.

[1]
[2]
[3]
[4]

Bhattacharjee, M. N.; Chauduri, M. K.; Dasgupta, H. S. Synthsesis 1982, 588.
Shirini, F.; Mohammadpoor-Baltork, I.; Hejazi, Z.; Heravi, P. Bull. Korean Chem.
Soc 2003, 2 4 , 517.
Srinivasan, R.; Stanley P.; Balasubramanian, K. Synthetic Communications
1997, 2 7 , 2057.
Mahjoub, A. R.; Ghammami, S.; Kassaee, M. Z. Tetrahedron Lett. 2003,44,
4555.

52

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

SYNTHESES AND X-RAY CRYSTAL STRUCTURES OF TWO MIXEDANIONIC FLUOROUS COMPLEXES
Ghammamy S.,a,b Rezaee M.cab

Department of Chemistry, Azad Islamic University, Saveh Campus, Saveh, Iran
Department of Chemistry, Imam Khomeini International University, Qazvin, Iranb
Iran Teaching and Growthing Ministry, Qazvin Organization, Qazvin, Iranshghamami@yahoo.com

In recent years, many compounds found that have not configurations predicted by
VSEPR model. These systems named as “Non-VSEPR” compounds. On the base ofligands similarity this compounds classified as “Homoleptic” and “Heteroleptic”
systems. These terms mean that systems have one kind of ligands named
Homoleptic and systems that have different kinds of ligands named Heteroleptic.
Because of the simplicity of homoleptic systems, these systems have been studied
more than heteroleptic systems.[1,2] We report here the synthesis and structures of
two heteroleptic mixed-anionic systems of molybdenum and tungsten compounds.
The structures of these two systems were determined by X-ray crystallography. The
coordination geometries are similar in two complexes. In these crystals there are two
crystallographically distinct anions, both have cis geometry. Experimental data
showed the Non-VSEPR structures that have good agreement with sd5 hybridation
rather than sp3d2.

[1]
[2]

Kaupp, M., Angew. Chem. Int. Ed. 2001, 1 1 1 , 3534.
Kaupp, M., Angew. Chem. Int. Ed. 1999, 3 8 , 1687.

53

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

FLUOROUS SYNTHESIS OF β,β-DIFLUORINATED CYCLICQUATERNARY α-AMINOACIDS.
Sanz-Cervera, J. ; del Pozo, C. ; Sánchez-Roselló, M.; Rodrigo, V. ; Fustero, S.
Departamento de Química Orgánica.Universidad de Valencia. E-46100 Burjassot, Spain.
Juan.F.Sanz@uv.es

We wish to report the fluorous synthesis of β,β-difluorinated cyclic quaternary aminoacids using as a key step a ring closing metathesis reaction (RCM). The
introduction of the fluorous tag was performed in imidoyl chloride 1 by means ofalcoxycarbonilation of the corresponding iodide following the method developed by
Uneyama,[1] in the presence of the prefluorinated alcohol. Fluorous imino ester 2
was treated then with the corresponding organozinc derivative and the resulting
dienes were heated in refluxing toluene in the presence of second generation Grubbs
catalyst affording α-amino acids 3 in high yield. The cleavage of the fluorous tag was
accomplished by using a transesterification method mediated by CHTD
(ClBu2SnOSnBu2OH),[2] giving rise to the protected amino acids 4 and theprefluorinated alcohol used as a fluorous tag.
In all the reactions carried out that contain the fluorinated tag, the purification wasmade by fluorous solid phase extraction (FSPE), affording the desired products withhigh purity and yield, which demonstrate the efficiency of SPE in the purification of
the final products. In addition, the technique allows the easy recover of theperfluorinated alcohol used as a fluorinated tag.
N
F
F

PMP
N
Cl

F
F

1. NaI

Rf

R

O

Rf

OH

ZnBr

1.

O

2. Pd2(dba)3·CHCl3,CO
1

PMP

2. (IMes)(PCy3)Cl2Ru=CHPh

2
Rf = (CF2)7CF3

PMP
F
F

NH CO2PMP

Rf
ClBu2SnOSnBu2OHRFFNH CO2Bn
+ HO

BnOH

3

Rf

4

[1]

Amii, H.; Kishikawa, Y.; Kageyama, K.; Uneyama, K. J. Org. Chem. 2000, 65,
3404-3408.
[2] (a) Suzuki, A.; Mae, M.; Amii, H.; Uneyama, K. J. Org. Chem. 2004, 69, 51325134. (b) Otera, J.; Yano, T.; Okawa, R. Chem. Lett. 1985, 901-. (c) Otera, J.;
Yano, T.; Okawa, R. Organometallics 1986, 5, 1167-1170. (d) Otera, J.; Dan-oh,
N.; Nozaki, H. J. Org. Chem. 1991, 56, 5307-5311.
54International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

METHOD OF SYNTHESIS α,ω DIPHENYLPERFLUORALKANES
Dovbysheva T., Yasko A.
Belarusian Polytechnical Academy, Str .Gudro, 23-20, Minsk 220121, Belarus
tdovbysheva@bntu.by

The hydrocarbons containing two aromatic cycles connected by bridges fromdifluoromethylene groups - diarylperfluoralkanes are investigated a little. It is known
some diphenyl perfluor alkanes.
It is described two methods of production ofdiphenylperfluoralkanes. One of them is based on replacement of chlorine indiphenylchloralkanes on fluorine by action of fluorinating agents, for example
trifluoride antimony.However this way has production only diphenyl perfluor alkanes
with one or to two difluoromethylene groups between phenylic radicals. As the atomsof chlorine which are taking place in α-position to a benzene ring routinely easily
come into exchange reaction.
The second method of synthesis diphenyl perfluor alkanes are driven in tocompounds with two and three difluoromethylene groups is based on replacementof carbonyl atoms of oxygen in aromatic tri- and diketene on fluorine under action ofsniphur tetrafluoride.
The dibenzoylperfluoralkanes with various number difluoromethylene groups
can be easily obtained at interaction corresponding aliphatic perfluordicaboxylic
acids with phenyl magnesium bromide.
In this paper is described fluorination of the aromatic diketenes by sniphur
tetrafluoride. These two reactions have resulted in the development of general
methods for the synthesis of diphenylperfluoralkanes with a number ofdifluoromethylene groups higher than 3. Interaction diketenes with sulfur tetrafluoride
was executed according to the scheme:
C6H5CO(CF2)COC6H5 + SF4
C6H5(CF2)x + 2 C6H5 + SOF2→

C6H5(CF2)x+1 COC6H5 +SOF2 + SF4→

X = 2, 3, 4.

Conclusions
1. The general method of synthesis α,ω− diphenylperfluoralkanes by action ofsniphur tetrafluoride on α,ω− diphenylperfluoralkanes easily received{obtained} ofperfluordicarboxylic
acids is developed. By such way are synthesized 1,4diphenylperfluorbutane ; 1,5-diphenylperfluorpentane; 1,6- diphenylperfluorhexane.
2. The conditions of synthesis 1,2-diphenylperfluoethane from benzyl and sniphur
tetrafluoride are specified.
3. The replacement of atoms of oxygen in diketenes on the fluorine occurs seriallyand at reduction of duration of reaction with sniphur tetrafluoride, in a case forexample dibenzoylperfluorpropane alongside with 1,5-diphenylperfluorpentane isformed mainly 1-phenyl-4-benzoylperfluorbutane.

55

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

THE SYNTHESIS OF PENTAFLUORIDE OF PHOSPHORUS
BY FLUORINATION OF PENTAOXIDE PHOSPHORUS BY
ELEMENTARY FLUORINE
Dovbysheva T.
Belarusian Polytechnical Academy, Str .Gudro, 23-20, Minsk 220121, Belarus
tdovbysheva@bntu.by

The problem of making of soft fluorinating agents for fluororganic synthesis towhich it is necessary to relate and phosphorus pentafluoride is actual.
In laboratory practice for reception РР5 routinely use an exchange reaction between
pentachloride phosphorus and such fluorides as АsF3НF, С6Н5СОF and 5FР5, useof the last provides rather high yield of a finished product.
The purpose of research were improvement of a technique of synthesis and making
clean phosphorus pentafluoride. The pentafluoride phosphorus was received using
interaction Р205 with elementary fluorine. This synthesis highly was complicatedowing to reaction of formation of the fluorine phosphoryl going in parallel of the basic
reaction.
The starting reagents - fluorine and Р205 carefully has been refined from fluorine
hydride and a moisture accordingly. The purification of fluorine from fluorine hydride(НF) has been made by freeze-out at the temperature a minus 95°С (with use of solidacetone and the subsequent adsorption on fluorine sodiums. The reaction ofinteraction of phosphorus pentoxide with elementary fluorine was carried out innickeliferous equipment at the temperature 300-400°С and 15 % excess of fluorine.
The formed reactionary gas was missed through the heated column of after-burning
filled by the fluorinated nickeliferous grid at the temperature 250-300 °С.
Further gas entered in system of the condensation. This system has incorporated ofthree tandem quartz traps working at freezing temperatures of ethyl acetate (87,4°С), acetone (-94,6°С) and ethanol (-112°С). Traps were cooled by liquid
nitrogen. The finite product was pentafluoride phosphorus condensed in two lastcondensers. And the basic quantity pentafluoride phosphorus collected in thecondenser having temperature-112°С. Gas analyzed a mass - spectrometric method.
The impurity level in synthesized pentafluoride phosphorus was slight and did notexceed 0,5 - 1 %. The yield pentafluoride phosphorus has made 75 % fromtheoretical
The analysis of the formed condensates in the first two the condensers having
temperature - 87,4°С and - 94,6°С accordingly, has specified content in them mainly
fluorine hydride.
At fluorination of phosphorus pentoxide by elementary fluorine significant
temperature effect for speed of interaction has been noticed.

56

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

DEVELOPMENT OF OXYGEN SENSING SYSTEM BY STATIONARYQUENCHING METHOD USING ZnTFPP
Kamachi T., Mochizuki K., Asakura N., Okura I.
4259 Nagatsuta,Yokohama, 226-8501, Japan, Tokyo Institute of Technology
tkamachi@bio.titech.ac.jp

Determination of oxygen concentration is of importance in various fields of chemical,
clinical analysis and environmental monitoring. Several oxygen detection systems
using luminescence quenching by oxygen have been developed. Many sensing dyesfor these systems are luminescent organic dyes, such as polycyclic aromatichydrocarbons and transition metal complexes. As the most organic dyes, however,
do not show the luminescence at room temperature, the novel oxygen sensor basedon T-T absorption quenching using pulse laser has been developed.
The
conventional laser flash photolysis system is adopted for oxygen sensing and nonluminescent dyes can be used in this system. As the triplet lifetime of the dye
decreases with oxygen concentration, oxygen concentration is given by themeasurement of triplet lifetime of the dye. This system, however, is inconvenient
because of the large scale apparatus like a pulse laser. In this study, a new oxygen
sensing system by T-T absorption at steady state quenching using CW laser isdeveloped.
Figure shows the outline of the
Oxygen sensing device
oxygen sensing system using CW
Nd-YAG lase as an excitation light.
(450〜480 nm)
A xenon arc lamp was used as amonitoring light. Oxygen pressure ina gas stream was controlled by theflow rates of oxygen and nitrogen Xe lamp
gases.
The intensity of thetransmittance of the ZnTFPP-PS film
was measured by using digital
storageoscilloscopethroughmonochromator.
CW laser
T-T absorption spectrum of ZnTFPPMonochromator(532 nm)
PS film observed with CW laser
system was almost same as that ofconventional transient absorption spectrum, attributed to the T1-Tn absorption. As the
maximum T-T absorption was observed at 470 nm, oxygen sensitivity is measured at
470 nm in the following experiments. Effect of the oxygen concentration on the T-T
absorption intensity of ZnTFPP-PS film was measured. The intensity of T-T
absorption at 470 nm was about 0.8 under nitrogen and decreased with the oxygen
concentration, indicating that the excited triplet state of ZnTFPP-PS film wasquenched by the oxygen and the steady state T-T absorption reached the new
equilibrium state.

57

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

SYNTHESIS AND AIR-WATER INTERFACE OF SULFOBETAINEFLUOROSURFACTANTS
Thebault P., Taffin de Givenchy E., Guittard F.,* Geribaldi S.
Lab. Chimie des Matériaux Organiques et Métalliques (C.M.O.M.), Faculté des Sciences, Universitéde Nice-Sophia Antipolis, Parc Valrose, 06108 Nice Cedex 2, France.
guittard@unice.fr

The development of highly fluorinated compounds mainly of surfactant type are ofgreat interest in numerous fields like surface modifications (i.e. AFFF). We present inthis work the synthesis and characterization of new compounds of sulfobetaine typein fluorinated series. As structural point of view, these amphiphilic compounds havethe main chemical segments:-a highly fluorinated chain-an hydrocarbon spacer-a polar sulfobetaine head
The overall compounds are synthetized in three steps from raw materials, ie, 2-Falkylethyliodide or directly from F-alkyliodide. These compounds are monodisperse.
The air-water interface properties have been investigated from tensiometric method.
We present also the critical micellar concentrations and adsorption kinetic for eachsurfactant. A correlation between the length of the hydrocarbon spacer and thecorresponding surface properties will be discussed. The results are described andcompared to hydrocarbon or fluorocarbon homologues.

58

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

DEVELOPMENT OF FLUOROUS LEWIS ACID-CATALYZEDREACTIONS IN A FLUOROUS BIPHASIC SYSTEM AND AN
APPLICATION TO CONTINUOUS-FLOW REACTION SYSTEM
Yoshida A.,a Hao X.,a Nishikido J.ba

The Noguchi Institute, Itabashi-ku, Tokyo 173-0003, Japan
Asahi Kasei Corporation, Fuji, Shizuoka 416-8501, Japanbayoshida@noguchi.or.jp

We have already found that lanthanide(III), tin(IV), and hafnium(IV)bis(perfluoroalkanesulfonyl)amides would be highly active catalysts of Lewis acidpromoted reactions such as (direct) esterification, transesterification, Diels−Alderreactions, Friedel−Crafts reactions, and Baeyer−Villiger reactions with aqueoushydrogen peroxide in a fluorous biphasic system.[1-3]In a fluorous biphasic batch system, a fluorous phase containing fluorous Lewis
acid catalyst described above was readily recovered and reused by phase separation
without loss of catalytic activity after the reactions (Figure 1). We applied this batch
system to a continuous-flow reaction system. Our continuous-flow system is asfollows (Figure 2).[4] At first, fluorous solvent is poured into the reactor followed byadding the catalyst such as ytterbium(III) bis(perfluorooctanesulfonyl)amide, which isimmobilized in the fluorous solution because of its insolubility in general organic
solvent. Next, organic solution containing organic substrates and reagents as themobile organic phase is continuously flowing into the stationary fluorous phase in thereactor with vigorous stirring. The reaction proceeds in the resultant emulsion. Afterthe reaction, the emulsion mixture is automatically introduced to the decanter whereorganic/fluorous phases are separated.
Then, the upper organic phase isoverflowing and lower fluorous phase is recycled. Thus, the substrates can beconverted to the products through this continuous-flow system. We performed
acetylation of cyclohexanol in toluene and GALDEN® SV135 (Solvay Solexis K.K.)
catalyzed by ytterbium(III) bis(perfluorooctanesulfonyl)amide to give cyclohexyl
acetate with high TON (≈ 22,000).
Figure 2

Figure 1

productsin organic solvent

product

substrate
emulsion

catalyst

catalyst(vigorous stirring)emulsionorganic phase(standing)fluorous phasedecanterrecyclable catalyst in fluorous phase: organic phase: fluorous phase containing Lewis acid such as Yb[N(SO2-n-C8F17)2]3

[1]
[2]
[3]
[4]

substrates
reagents
in organic solvent

reactorHao, X.; Yoshida, A.; Nishikido, J. Tetrahedron Lett. 2004, 45, 781.
Hao, X.; Yamazaki, O.; Yoshida, A.; Nishikido, J. Tetrahedron Lett. 2003, 44,4977.
Hao, X.; Yoshida, A.; Nishikido, J. Tetrahedron Lett. 2005, 46, 2697.
Yoshida, A.; Hao, X.; Nishikido, J. Green Chem. 2003, 5, 554.

59

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

DEVELOPMENT OF SYNTHETIC APPROACHES TOPOLYFUNCTIONAL COMPOUNDS WITHPENTAFLUOROSULFANYL (SF5) GROUPING.
Brel, V. K.
aInstitute of physiologically active compounds, Russian Academy of Sciences, 142432
Chernogolovka, Moscow region, Russia
brel@ipac.ac.ru

As part of a program concerned with the synthesis and characterization of new
pentafluorosulfur derivatives, we became interested in the development of synthetic
approaches to various unsaturated compounds with pentafluoro-λ6-sulfanyl terminalgroupings. Organic compounds in which pentafluoro-λ6-sulfanyl group is present are of
special interest because they often possess the advantageous properties of the parent
compound, SF6, among which are a high group electronegativity, large steric bulk, anonfunctional hexacoordinate stereochemistry, and high thermal and hydrolytic stability. The
synthesis and chemistry of these compounds are the subjects of ongoing studies.[1-3]
Cl
F5S

F5S

F5S

O

OH
Cl
F5S

Cl
F5S

SF5Cl

( )n

n=1

n = 1, 2

F5S

F5S

( )n

F5S

( )n

O N
Ar

F5S

OH
( )n

O
( )n

SF5
COOH

COOH
SF5
COOH

Sulfur chloride pentafluoride (F5SCl) has been utilized in reactions with variety ofunsaturated compounds. We have investigated the development of some novel reaction
systems with (F5SCl). Using the reaction between the sulfur chloride pentafluoride (F5SCl)and unsaturated alcohols or 1,4-, 1,5-alkadienes (in gas phase) under irradiation of ultraviolet light leads to products of addition of F5SCl to the double bounds in good yields. These
adducts were used as useful precursors for preparation of new unsaturated, cyclyc andheterocyclic compounds with pentafluorothio groups. The structure of synthesized newcompounds, were characterized by 1H, 13C, and 31P NMR data and in some cases by single
crystal X-ray crystallography. The details of the synthesis, spectroscopic properties and Xray data will be discussed.
[1]

[2]
[3]

(a) Gard, G. L.; Woolf, C. W. US Pat. 3 448 121, 1969; (b) Gard, G. L.; Bach, J.; Woolf,
C. W. Br. Pat. 1 167 112, 1969; (c) Gilbert, E. E.; Gard, G. L. US Pat. 3 475 453,
1969; (d) Banks, R. E.; Haszeldine, R. N. Br. Pat. 1 145 263, 1969; (e) Shepard, W. A.
US Pat. 3 219 690, 1965.
(a) Witucki, E. F.; Frankel, M.B. J. Chem. Eng. Data 1979, 24, 382; (b) Sitzmann, M. E.;
Gilligan, W. H.; Ornellas, D. L.; Thrasher, J. S. J. Energ. Mater. 1990, 8, 352-374.
Sitzmann, M. E. J. Fluorine Chem. 1995, 70, 31-38.

60

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

Author Index

A
AlonsoAlonsoAlonsoAsakura
Audic

C.
J. M.
P. J.
N.
N. A.

43
50
38
57
30

W.
G.
V. M.
C.
C.
J. A.
A.
D.
V. K.

9
46
51
15
9
30
12
19, 45
60

L.
A.
M.
M. F.
D. P.

42
31
38, 44
26
39

B.-J.
J.
T.
P. W.

28
26
55, 56
30

C. A.
M.
C. J.

11
47
28

N.
J.
G.
R. H.
J.
B.
S.

34
38
23
27, 38
34
41
54

J.
S.
S.
J. A.
K.
F.

15
41, 5852, 5318
49
42, 58

J.
J.
X.
K.
O.
E. G.
I. T.

11
33
8, 59
25
29
30
6, 34, 44

B
Bannwarth
BarréBazhenov
Belin
BellerBennett
BiffisBonnet-Delpon
BrelC
Caillerde CastrieContel
Costa Gomes
CurranD
DeelmanDeschamps
Dovbysheva
Dyer

E
EckertEl Bakkari
ElsevierF
FarkasFernandez-Gallardo
FontanaFish
Fraga-Dubreuil
FrontonFusteroG
Gan
Geribaldi
Ghammamy
Gladysz
Goto
Guittard

H
Haber
HalletHao
Hatanaka
Holczknecht
Hope
Horváth61

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

I
Inazu
Iskra
Ito

T.
J.
A.

21, 4937, 45
25

P. G.
R. S.

33
33

T.
I.
Y.
M. C. Z.
S.
G.
M.-P.

57
32
22
25
51
28
14

D.
C.
D.
C. L.
R.

44
31
46
33
41

E.
H.
D.-H.
P.
F.
T.
M.
K.
E.

31
48
26
17
17
49
49
57
43

Y.
R.
W.
V. A.
J.

36
22
23
51
8, 59

A. M.
K.
I.
J.
K.
A. A. H.
F.

50
36
57
24
33
26
43, 50
11
28
16
17
37
33
11
51
7, 29
54
15

J
Jessop
Jones

K
Kamachi
Kani
Kato
KasuyaKirchmeyer
van Koten
KrafftL
Lantos
Larpent
Lastécouères
LiottaLuguyaM
Magnier
Matsubara
Menz
Metrangolo
Meyer
Miura
MizunoMochizuki
Mtz de Marigorta

N
Nakamura
NaritaNavarrini
NikanorovNishikidoO
Ochoa de Retana
Okumura
Okura
Otera

P
Padua
Palacios
Pamin
de Pater
PercecPilati
Podgoršek
PolletPoltowicz
Popkova
Pozzi
Del Pozo
Pozzo

J. J. M.
V.
T.
A.
P
J.
V. Y.
G
C.
J.-L.

62

International Symposium On Fluorous Technologies, 3-6 July 2005, Bordeaux/Talence, France

Q
Quici

S.

29

J.
M. T.
G.
M.
F.
J. G.
V.
M.
G.
I.

10
48
17
52, 53
34
13
54
43
43
48

K.
M.
S.
J.
S.
A. M.
S.

22
54
44
54
37, 4520, 30
30

E.
E.
D.
S.
P.
C.
M.

11
42, 58
46
36
58
33
48

M.

17

A.
J.
M.
P. R.
J.-M.
G.

50
20
43
38
15,38,41,46,47
34

T.
K. M.
A. C. A.

22
20
28

O.
A.
F.
A.

8
55
32
8, 59

W.
K.
M.

35
45
37, 45R
Rábai
RahmanResnatiRezaeeRichter
Riess
RodrigoRodriguez
Rubiales
Ryu

S
Saigo
Sanchez-Rosello
Sanz
Sanz-Cervera
Stavber
StuartSuhardT
TaborTaffin de Givenchy
Taton
TakeuchiThebault
ThomasTsukidaU
UrsiniV
Vélez del Burgo
Vidal
Villegas
Villuendas
Vincent
Vlád

W
Wada
Weber
De WolfXY
Yamasaki
Yasko
Yilmaz
YoshidaZ
ZhangŽmitekZupan

63