A fluorous super br?nsted acid catalyst: Application to fluorous catalysis without fluorous solvents

Article abstract of DOI:10.1055/s-2002-32965

The preparation of a fluorous super Br?nsted acid catalyst, 4-(1H,1H-perfluorotetradecanoxy)-2,3,5,6-tetrafluorophenylbis (trifluoromethanesulfonyl)methane (3d), is described. The fluorous catalyst 3d can be recycled by using liquid/solid phase separation without fluorous solvents. A perfluorocarbon solvent is not essential for fluorous biphasic catalysis.

Full text of DOI:10.1055/s-2002-32965

LETTER
1299
A Fluorous Super Brønsted Acid Catalyst: Application to Fluorous Catalysis
without Fluorous Solvents
A
Fluorous Super
a
Brønsted A
z
cid Catalys
u
t
aki Ishihara, Aiko Hasegawa, Hisashi Yamamoto*
Graduate School of Engineering, Nagoya University, SORST, Japan Science and Technology Corporation (JST), Furo-cho, Chikusa,
Nagoya 464-8603, Japan
Fax +81(52)7893222; E-mail: yamamoto@cc.nagoya-u.ac.jp
Received 9 May 2002
Abstract: The preparation of a fluorous super Brønsted acid cata-
lyst, 4-(1H,1H-perfluorotetradecanoxy)-2,3,5,6-tetrafluorophenyl-
bis(trifluoromethanesulfonyl)methane (3d), is described. The
fluorous catalyst 3d can be recycled by using liquid/solid phase sep-
aration without fluorous solvents. A perfluorocarbon solvent is not
essential for fluorous biphasic catalysis.
Homogeneous
reaction
Product
Reactants
Heat
Cool
Organic
solvent
Organic
solvent
Key words: Brønsted acid, fluorous catalyst, ponytail, fluorous bi-
phasic catalysis, superacid
Rf-catalyst
Rf-catalyst
Recycle of Rf-catalyst (solid)
by decantation
(Rf: Perfluoroalkyl)
Figure 1 Fluorous catalysts recycling based upon liquid/solid phase
separation
Fluorous biphasic catalysis has recently become an envi-
ronmentally attractive alternative to traditional catalytic
methods.1 Fluorous techniques take advantage of the tem-
perature-dependent miscibility of organic and perfluoro-
carbon solvents to provide easier isolation of products and
the recovery of a fluorinated catalyst. The fluorous bipha-
sic technique involves dissolving a catalyst with long flu-
orinated alkyl chains (Rf) in a perfluorocarbon. The
reactants are added to an organic solvent that is immisci-
ble with the perfluorocarbon at room temperature, which
forms a second phase. On heating, the two phases mix and
the reaction occurs; on cooling, the fluorinated and organ-
ic layers separate. The organic phase can be removed and
the product isolated, while the fluorinated catalyst-solvent
phase can be reused. However, the large-scale use of per-
fluorocarbon solvents has some drawbacks: cost and con-
cern over environmental persistence.
sulfonyl)methane (1), and developed an organic-solvent-
swellable resin-bound super Brønsted acid, poly-
styrenebound
sulfonyl)methane (2), by using the para-substitution
reaction of 1 with alkyllithium as a key step (Scheme).4 In
this Letter, we describe a fluorous super Brønsted acid
catalyst which can be recycled by applying liquid/solid
phase separation without fluorous solvents.
tetrafluorophenylbis(trifluoromethane-
F
F
F
F
Tf
Tf
F
H
H
Tf
Tf
F
F
F
F
1
2
Recently, our group2 and Gladysz’s group3 independently
demonstrated that a perfluorocarbon solvent is not essen-
tial for fluorous biphasic catalysis: the perfluorocarbon
solvent can be omitted by designing fluorinated catalysts
that themselves show temperature-dependent phase mis-
cibility, i.e., solubility, in ordinary organic solvents
(Figure 1). We previously reported that 3,5-bis(perfluoro-
decyl)phenylboronic acid is a good amide condensation
catalyst which is insoluble in organic solvents at room
temperature but becomes soluble under reflux in o-xylene
(reaction conditions).2 Gladysz et al. also reported the
temperature-dependent solubility of the solid phosphine
catalyst P[(CH2)2(CF2)7CF3]3 in octane.3
–
F
F
F
F
F
F
Tf
Tf
1. RLi
Li+
F
R
H
2. H3O+
Tf
Tf
F
F
Scheme
Pentafluorophenylbis(trifluoromethanesulfonyl)methane
1 (47 wt% F) is soluble in most organic and fluorous sol-
vents. If the nucleophilic para-substitution reaction of 1
can be adapted to not only alkyl anions but also alkoxy
anions, it may be possible to achieve high fluorous-phase
affinity for 4-alkoxy-2,3,5,6-tetrafluorophenyl-bis(triflu-
oromethanesulfonyl)methane (3) by appending several
‘ponytails’ OCH2(CF2)nCF3 groups to 1. In preliminary
experiments, the preparation of 4-hexanoxy- and 4-
trifluroroethanoxy-2,3,5,6-tetrafluorophenylbis(trifluoro-
methanesulfonyl)methanes, 3a and 3b, was examined by
reacting a lithium salt of 1 with the corresponding sodium
Recently, we successfully synthesized a new super
Brønsted acid, pentafluorophenylbis(trifluoromethane-
Synlett 2002, No. 8, Print: 30 07 2002.
Art Id.1437-2096,E;2002,0,08,1299,1301,ftx,en;G12702ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

1300
K. Ishihara et al.
LETTER
alkoxides in pyridine at room temperature (Equation 1).5 sides this acetalization, 3d was also effective as a fluorous
As expected, 3a and 3b were obtained in respective yields catalyst for the acylation of L-menthol with benzoic anhy-
of 83% and 93%.
dride (Equation 4) and esterification of 3-phenylpropionic
acid in methanol (Equation 5).7
F
F
1. C6F5CTf2Li (1 equiv)
rt, 1 day
Tf
NaH (3 equiv)
ROH
3c or 3d (1 mol%)
O
RO
H
PhCHO
HO
OH
pyridine
(3 equiv)
2. 4 M HCl
Tf
cyclohexane
azeotropic reflux, 3 h
Ph
O
(1.2 equiv)
0 °C to rt, 2 h
F
F
3
The use of 3c: Acetal: 74% yield; recovery of 3c: failed
The use of 3d: Acetal: 86% yield; recovery of 3d: 96%
3a (R: n-C6H13): 83% yield
3b (R: CF3CH2): 93% yield, 47% wt% F
3c (R: CF3(CF2)8CH2): 97% yield, 59 wt% F
Equation 3
Equation 1
3d (3 mol%)
Their pKa values in glacial acetic acid were measured by
the 1H NMR method of Schantl et al. (Table).4,6 The Brøn-
sted acidity of 3a was less than that of concd H2SO4, while
3b was a superacid like 1.
Bz2O
toluene
OBz
OH
(1.5 equiv)
70 °C, 14 h
i-Pr
i-Pr
>99% yield; recovery of 3d: 70%
Table Brønsted Acidities of Arylbis(trifluoromethanesulfon-
yl)methanes
Equation 4
3d (1 mol%)
3a
Concd
H2SO4
3b
1
CO2H
CO2Me
Ph
Ph
MeOH
70 °C, 7 h
1H NMR (ppm)a
6.19
11
–
6.23
6.6
6.21b
1.5b
>99% yield; recovery of 3d: 68%
pKa in AcOH
7.5b (7.0)c
Equation 5
a 1H NMR chemical shift observed for an acidic proton of ArCHTf2 in
CDCl3 is indicated.
Fluorous solid catalyst 3d was also used in the Mukaiya-
ma aldol reaction (Equation 6) and Sakurai–Hosomi allyl-
ation reaction (Equation 7). These reactions were
performed at –78 °C and r.t., respectively, under heteroge-
neous conditions. Postreaction, 3d was recovered in high
yield by decanting the liquids at room temperature.
b Ref.4a
c Ref.6
Based on the above results, 3c (59 wt% F) was prepared
in 97% yield from a lithium salt of 1 and sodium 1H,1H-
perfluorodecanoxide in the similar manner (Equation 1).
To obtain higher fluroinated Brønsted acid, 3d (62 wt% F)
was prepared in 84% yield by heating a lithium salt of 1
and sodium 1H,1H-perfluorotetradecanoxide in a 2:1
mixed solvent of pyridine and perfluorotributylamine at
70 °C (Equation 2). Perfluorotributylamine was added to
partially dissolve sodium 1H,1H-perfluorotetradecanox-
ide.
1. 3d (3 mol%), toluene
–78 °C, 3 h
OSiMe3
OH
O
PhCHO
Ph
Ph
Ph
2. 1 M HCl-THF (1:1)
(1.2 equiv)
82% yield
Recovery of 3d: 92%
Equation 6
1. 3d (1 mol%), CH2Cl2, rt, 0.5 h
2. Addition of PhCHO (1 equiv)
at rt over 30 min
1. C6F5CTf2Li (1 equiv),
70 °C, 1 day
NaH (3 equiv)
OH
3d
CF3(CF2)12CH2OH
(3 equiv)
SiMe3
pyridine:(C4F9)3N
=2:1
rt to 70 °C, 1 h
2. 4 M HCl
Ph
84% yield
62 wt %F
3. Stirred at rt, 1 h
4. 1 M HCl-THF (1:1)
(1.5 equiv)
84% yield
Recovery of 3d: 97%
Equation 2
Equation 7
The acetalization of benzaldehyde with 1,3-propanediol
was examined in the presence of 1 mol% of a fluorous su-
per Brønsted acid, 3c or 3d, at azeotropic reflux in cyclo-
hexane with the removal of water for 3 h (Equation 3).
Both solid acids were soluble in cyclohexane under reflux
conditions, and promoted the reaction well to give the de-
sired acetal in good yields. Postreaction, 3d was recovered
in 96% yield by precipitation at room temperature. How-
ever, 3c could not be recovered in the same manner. Be-
We believe that one-solvent protocols of the type de-
scribed above may be applicable to a wide variety of
fluorous catalysts. In this Letter, we demonstrate that 1 of-
fers a great advantage over other analogous super Brøn-
sted acids such as tris(trifluoromethanesulfonyl)methane,
bis(trifluoromethanesulfonyl)imide, and trifluorome-
thanesulfonic acid from the perspective of synthetic mod-
ification. Barrett’s group8 and Mikami’s group9 have
Synlett 2002, No. 8, 1299–1301 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
A Fluorous Super Brønsted Acid Catalyst and its Application
1301
–64.00) –153.7 (dd, J = 6.2, 21.4 Hz, 1 F), –152.7 (dd, J = 9.2,
21.3 Hz, 1 F), –141.3 (br, 1 F), –128.7 (dt, J = 9.0, 21.4 Hz, 1 F),
–127.1 (s, 2 F), –124.0 (s, 2 F), –123.7 (s, 2 F), –122.8 (s, 8 F),
–121.5 (s, 2 F), –81.9 (t, J = 18.3 Hz, 3 F), –75.3 (s, 6 F). Anal.
Calcd for C19H3O5F29S2: C, 24.64; H, 0.33. Found: C, 24.61; H,
0.36.
independently reported metal tris(perfluoroalkanesulfo-
nyl)methides as fluorous Lewis acids. Similarly, it may be
possible to design pentafluorophenylbis(perfluoroalkane-
sulfonyl)methanes. However, it is synthetically more con-
cise and practical to append 1H,1H-perfluoroalkoxy
groups to 1 by a para-substitution reaction. In addition,
solid acids 2 and 3d are more active catalysts than perflu-
oresinsulfonic acids such as Nafion®.4
Experimental Procedure for the Acetalization of Benzaldehyde
with 1,3-Propanediol: To a solution of 3d (33.8 mg, 0.03 mmol) in
cyclohexane (6 mL) were added benzaldehyde (0.30 mL, 3.0 mmol)
and 1,3-propanediol (0.24 mL, 3.3 mmol), and the resulting mixture
was heated at azeotropic reflux with the removal of water using a
Dean-Stark apparatus. While monitoring the disappearance of the
starting materials by TLC (for 3 h), the reaction mixture was cooled
to ambient temperature to precipitate 3d, which was filtered and
washed with cyclohexane (2 mL) to recover 3d (32.4 mg, 0.029
mmol, 96% yield). The filtrate was concentrated under reduced
Experimental Procedure for Preparing 3d: To a mixture of NaH
(60% dispersion in mineral oil, 30 mg, 0.75 mmol) and 1H,1H-per-
fluorotetradecanol (0.53 g, 0.75 mmol) were added pyridine (4 mL)
and perfluorotributylamine (2 mL) at room temperature. The result-
ing mixture was heated to 70 °C and stirred at the same temperature
for 1 h. Lithium pentafluorophenylbis(trifluoromethanesulfon-
yl)methide4a (0.11 g, 0.25 mmol) was then added at 70 °C, and the
resulting mixture was stirred for an additional 1 day at the same
temperature. After cooling to 0 °C, the reaction was quenched with
4 M aqueous HCl (40 mL) at 0 °C. The resultant acidified mixture
was extracted with diethyl ether (40 mL 2). The organic layers
were dried over MgSO4, filtered and concentrated under reduced
pressure to give a brown solid. Furthermore excess 1H,1H-perfluo-
rotetradecanol which was contained in the solid was removed by
vacuum sublimation (120 °C, 0.06 torr). The residual dark-brown
solid was dissolved in diethyl ether (20 mL) or perfluoromethylcy-
clohexane (20 mL), and some insoluble impurities were then re-
moved by filtration. The filtrate was concentrated under reduced
pressure to give 3d (0.238 g, 0.21 mmol, 84% yield) as a white sol-
id. Mp. 95~96 °C; IR (KBr) 1503, 1406, 1397, 1213, 1154, 1111,
984, 646, 625, 550, 527 cm–1; 1H NMR (toluene-d8 + perfluorotol-
uene, 80 °C, 300 MHz) 4.06 (t, J = 12.5 Hz, 2 H), 6.21 (s, 1 H).
Anal. Calcd for C23H3O5F37S2: C, 24.53; H, 0.27. Found: C, 24.51;
H, 0.31.
1
pressure. The purity of the recovered catalyst was checked by H
and 19F NMR analyses. The crude oil was purified by column chro-
matography on silica gel (eluent:hexane-EtOAc = 20:1 to 5:1) to af-
ford the corresponding acetal (0.425 g, 2.6 mmol, 86% yield).
References
(1) (a) Horváth, I. T. Acc. Chem. Res. 1998, 31, 641.
(b) Cavazzini, M.; Montanari, F.; Pozzi, G.; Quici, S. J.
Fluorine Chem. 1999, 94, 183. (c) Bhattacharyya, P.;
Croxtall, B.; Fawcett, J.; Fawcett, J.; Gudmunsen, D.; Hope,
E. G.; Kemmitt, R. D. W.; Paige, D. R.; Russell, D. R.;
Stuart, A. M.; Wood, D. R. W. J. Fluorine Chem. 2000, 101,
247.
(2) Ishihara, K.; Kondo, S.; Yamamoto, H. Synlett 2001, 1371.
(3) Wende, M.; Meier, R.; Gladysz, J. A. J. Am. Chem. Soc.
2001, 123, 11490.
(4) (a) Ishihara, K.; Hasegawa, A.; Yamamoto, H. Angew.
Chem. Int. Ed. 2001, 40, 4077. (b) Ishihara, K.; Hasegawa,
A.; Yamamoto, H. Synlett 2002, 1296.
Spectral and analytical data of 3a–c are indicated as follows:
3a: Liquid; IR (film) 2959, 2090, 1651, 1505, 1406, 1215, 1119,
1017, 980, 627, 577, 513 cm–1; 1H NMR (CDCl3, 300 MHz) 0.91
(t, J = 7.1 Hz, 3 H), 1.32–1.37 (m, 4 H), 1.43–1.51 (m, 2 H), 1.83
(quintet, J = 6.8 Hz, 2 H); 4.44 (t, J = 6.8 Hz, 2 H), 6.19 (s, 1 H);
19F NMR (CDCl3, 282 MHz, CF3Ph –64.00) –75.35 (s, 6 F),
–130.64 (dt, J = 9.9, 21.2 Hz, 1 F), –143.16 (br, 1 F), –154.07 (d,
J = 21.2 Hz, 1 F), –155.31 (d, J = 21.2 Hz, 1 F). Anal. Calcd for
C15H14O5F10S2: C, 38.47; H, 3.01. Found: C, 38.54; H, 2.98.
(5) (a) Byron, D. J.; Matharu, A. S.; Wilson, R. C. Liquid
Crystals 1995, 19, 39. (b) Pyridine was more effective as a
solvent in the para-substitution reaction of a lithium salt of
1 with sodium alkoxides. In contrast, this reaction did not
occur smoothly in diethyl ether, which was effective in the
para-substitution reaction with alkyllithiums.4
(6) Rode, B. M.; Engelbrecht, A.; Schantl, J. Z. J. Prakt. Chem.
1973, 253, 17.
(7) In the case of the esterification, the resultant solution was
concentrated under reduced pressure, and the crude
compounds were diluted in hexane to precipitate 3d. Thus,
3d was recovered by filtration.
(8) Barrett, A. G. M.; Braddock, D. C.; Catterick, D.; Chadwick,
D.; Henschke, J. P.; McKinnell, R. M. Synlett 2000, 847.
(9) Mikami, K.; Mikami, Y.; Matsumoto, Y.; Nishikido, J.;
Yamamoto, F.; Nakajima, H. Tetrahedron Lett. 2001, 42,
289.
3b: Mp. 81–82 °C; IR (KBr) 1653, 1505, 1401, 1347, 1200, 1119,
995, 656, 610, 515, 494 cm–1; 1H NMR (CDCl3, 300 MHz) 4.71
(q, J = 7.8 Hz, 2 H), 6.23 (s, 1 H); 19F NMR (CDCl3, 282 MHz,
CF3Ph –64.00) –153.8 (dd, J = 7.6, 22.8 Hz, 1 F), –152.8 (dd, J
= 8.3, 21.4 Hz, 1 F), –141.3 (br, 1 F), –128.8 (dt, J = 9.9, 21.2 Hz,
1 F), –76.1 (t, JFH = 7.6 Hz, 3 F), –75.3 (s, 6 F). Anal. Calcd for
C11H3O5F13S2: C, 25.11; H, 0.57. Found: C, 25.12; H, 0.55.
3c: Mp. 74–75 °C; IR (KBr) 1653, 1502, 1406, 1393, 1220, 1159,
1117, 1057, 984, 623 cm–1; 1H NMR (CDCl3, 300 MHz) 4.84 (t, J
= 12.5 Hz, 2 H), 6.20 (s, 1 H); 19F NMR (CDCl3, 282 MHz, CF3Ph
Synlett 2002, No. 8, 1299–1301 ISSN 0936-5214 © Thieme Stuttgart · New York