Polyfluorinated quaternary ammonium salts of polyoxometalate anions: Fluorous biphasic oxidation catalysis with and without fluorous solvents

Article abstract of DOI:10.1021/ol0348598

[Matrix presented] Polyfluorinated quaternary ammonium cations, [CF ₃(CF₂)₇(CH₂)₃] ₃CH₃N⁺ (R_FN⁺), were synthesized and used as countercations for the [WZnM₂(H ₂O)₂(ZnW₉O₃₄)₂] ^12- (M = Mn(II), Zn(II)) polyoxometalate. The (R_FN ⁺)₁₂[WZnM₂(H₂0)₂ (ZnW₉O₃₄)₂] compounds were fluorous biphasic catalysts for alcohol and alkenol oxidation, and alkene epoxidation with aqueous hydrogen peroxide. Reaction protocols with or without a fluorous solvent were tested. The catalytic activity and selectivity was affected by both the hydrophobicity of the solvent and the substrate.

Full text of DOI:10.1021/ol0348598

ORGANIC
LETTERS
2003
Vol. 5, No. 20
3547-3550
Polyfluorinated Quaternary Ammonium
Salts of Polyoxometalate Anions:
Fluorous Biphasic Oxidation Catalysis
with and without Fluorous Solvents
Galia Maayan, Richard H. Fish,† and Ronny Neumann*
Department of Organic Chemistry, Weizmann Institute of Science,
RehoVot, Israel 76100
ronny.neumann@weizmann.ac.il
Received May 18, 2003 (Revised Manuscript Received August 18, 2003 )
ABSTRACT
+
+
Polyfluorinated quaternary ammonium cations, [CF3(CF2)7(CH2)3]3CH3N (RFN ), were synthesized and used as countercations for the
-
+
[WZnM2(H2O)2(ZnW9O34)2]12 (M
) Mn(II), Zn(II)) polyoxometalate. The (RFN )12[WZnM2(H2O)2(ZnW9O34)2] compounds were fluorous biphasic
catalysts for alcohol and alkenol oxidation, and alkene epoxidation with aqueous hydrogen peroxide. Reaction protocols with or without a
fluorous solvent were tested. The catalytic activity and selectivity was affected by both the hydrophobicity of the solvent and the substrate.
An important area of homogeneous catalysis research remains
the quest for practical separation techniques of the intrinsi-
cally soluble catalyst from the remaining reaction compo-
nents. One method that has quite recently attracted significant
attention as a separation/recovery method is fluorous biphasic
catalysis.1 The concept espouses modification of known
catalytic entities with fluorous “ponytails” yielding catalysts
soluble in very hydrophobic perfluorohydrocarbon solvents.
Commonly, there are very temperature dependent organic
substrate/fluorous solvent liquid/liquid phase miscibilities that
allow single phase reactions at elevated reaction temperature
and biphasic separation of the organic product from the
fluorous solvent containing the catalyst at ambient or
subambient temperatures. In the context of catalytic oxida-
tion, fluorous biphasic catalysis has been realized by using
various appropriately modified organometallic complexes.2
Questions concerning the environmental impact and degrad-
ability of perfluorinated solvents, along with their relative
high cost, have also led to the concept of fluorous phase
catalysis without fluorous solvents.3 In such systems, poly-
fluorinated thermomorphic catalysts are soluble in normal
hydrocarbons at elevated temperatures but are immiscible
in the solvent at decreased temperatures, allowing the
separation by precipitation of the fluorous catalyst from the
product and solvent phase by cooling the reaction mixture.
† Permanent address: Lawrence Berkeley National Laboratory, 70-108B,
University of California, Berkeley, CA 94720.
Polyoxometalate anions have over recent years been
investigated as oxidation catalysts with use of a variety of
oxidants, including the more sustainable molecular oxygen
and hydrogen peroxide.4 Especially notable in the context
of this paper is the use of “sandwich”-type polyoxometalates,
[WZnM2(H2O)2(ZnW9O34)2]12- (M ) Mn(II), Zn(II)), for
catalytic oxidation of alkenes, alkenols, and alcohols with
(1) (a) Horva´th, I. T. Acc. Chem. Res. 1998, 31, 641-650. (b) Cavazzini,
M.; Montanari, F.; Pozzi, G.; Quici, S. J. Fluorine Chem. 1999, 94, 183-
193. (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, 247-255. (d) Fish,
R. H. Chem. Eur. J. 1999, 5, 1677-1680. (e) Barthel-Rosa, L. P.; Gladysz,
J. A. Coord. Chem. ReV. 1999, 190-192, 587-605. (f) Vincent, J.-M.;
Rabion, A.; Fish, R. H. ACS Symp. Ser. 2000, 767, 172-181.
10.1021/ol0348598 CCC: $25.00
© 2003 American Chemical Society
Published on Web 09/06/2003

aqueous hydrogen peroxide.5 Also in the area of polyoxo-
metalate oxidation catalysis various techniques for separation/
recovery of the polyoxometalate from the other reaction
components have been considered. These methods include
supported catalysts,6 aqueous biphasic media,7 solvent an-
chored catalysts,8 and others.9 In this paper we report on our
adaptation of the concept of biphasic fluorous phase catalysis
into the realm of oxidation catalysis by polyoxometalates.
We have found that thermomorphic fluorous polyoxometa-
lates may be prepared and used in fluorous biphasic catalysis
despite the polyanionic nature of the polyoxometalates by
use of perfluorinated quaternary ammonium cations, [CF3-
(CF2)7(CH2)3]3CH3N+ or (RFN+), as countercations. Conse-
quently, effective catalytic oxidation reactions of alkenes,
alkenols, and alcohols can be carried out using “sandwich”-
type polyoxometalates, (RFN+)12[WZnM2(H2O)2(ZnW9O34)2],
Figure 1, with aqueous hydrogen peroxide as oxidant with
or without fluorous solvents.
Figure 1. Representation of the [WZnM2(H2O)2(ZnW9O34)2]12-
polyoxometalate with two (out of twelve) (RFN+) countercations.
polyoxometalates, (RFN+)12[WZnM2(H2O)2(ZnW9O34)2], were
The fluorous quaternary ammonium salt {[CF3(CF2)7-
(CH2)3]3CH3N+}CH3OSO3- was prepared by quaternization
of the known fluorous tertiary aliphatic amine,10 by dimethyl
sulfate (see Supporting Information for details). The fluorous
then prepared by mixing 12 equiv of {[CF3(CF2)7(CH2)3]3-
-
CH3N+}CH3OSO3 with 1 equiv of Na12[WZnM2(H2O)2-
(ZnW9O34)2] polyoxometalate.11 The fluorine content by
weight of (RFN+)12[WZnM2(H2O)2(ZnW9O34)2] is 51.5%.
Thus, despite the polyanionic character of the polyoxo-
metalate, (RFN+)12[WZnM2(H2O)2(ZnW9O34)2] is freely soluble
in perfluorohydrocarbons at room temperature. In other
common solvents such as ethyl acetate and toluene (RFN+)12-
[WZnM2(H2O)2(ZnW9O34)2] is insoluble at room tempera-
ture, but dissolves upon heating to 60-80 °C. This property
leads to two different reaction protocols for the fluorous
biphasic catalysis, Figure 2: (a) with a perfluorohydrocarbon
(perfluorodecalin) solvent and (b) without a fluorous solvent,
e.g. EtOAc. Results with the two catalytic reaction protocols
for the oxidation of alcohols, alkenols, and alkenes are
presented in Tables 1-3, respectively.
(2) (a) Vincent, J.-M.; Rabion, A.; Yachandra, V. K.; Fish, R. H. Angew.
Chem., Int. Ed. Engl. 1997, 36, 2346-2349. (b) Vincent, J.-M.; Rabion,
A.; Yachandra, V. K.; Fish, R. H. Can. J. Chem. 2001, 79, 888-895. (c)
Ragagnin, G.; Betzemeier, B.; Quici, S.; Knochel, P. Tetrahedron 2002,
58, 3985-3991. (d) Klement, I.; Knochel, P. Synlett 1995, 1113-1114.
(e) Klement, I.; Lutjens, H.; Knochel, P. Angew. Chem., Int. Ed. Engl. 1997,
36, 1454-1456. (f) Betzemeier, B.; Lhermitte, F.; Knochel, P. Tetrahedron
Lett. 1998, 39, 6667-6670. (g) Betzemeier, B.; Knochel, P. Synlett 1999,
489-491. (h) Betzemeier, B.; Cavazzini, M.; Quici, S.; Knochel, P.
Tetrahedron Lett. 2000, 41, 4343-4346. (i) Pozzi, G.; Cavzzini, M.; Quici,
S.; Maillard, D.; Sinou, D. J. Mol. Catal. A Chem. 2002, 182-183, 455-
461. (j) Cavazzini, M.; Manfredi, A.; Montanari, F.; Quici, S.; Pozzi, G.
Eur. J. Org. Chem. 2001, 4639-4649. (k) Pozzi, G.; Banfi, S.; Manfredi,
A.; Montanari, F.; Quici, S. Tetrahedron 1996, 52, 11879-11888. (l) Pozzi,
G.; Montanari, F.; Quici, S. Chem. Commun. 1997, 69-70. (m) Pozzi, G.;
Colombani, I.; Miglioli, M.; Montanari, F.; Quici, S. Tetrahedron 1997,
53, 6145-6162. (n) Pozzi, G.; Cavazzini, M.; Quici, S.; Fontana, S.
Tetrahedron Lett. 1997, 38, 7605-7608. (o) Quici, S.; Cavazzini, M.;
Ceragioli, S.; Montanari, F.; Pozzi, G. Tetrahedron Lett. 1999, 40, 3647-
3650. (p) Cavazzini, M.; Manfredi, A.; Montanari, F.; Quici, S.; Pozzi, G.
Chem. Commun. 2000, 2171-2172. (q) Collonna, S.; Gaggero, N.;
Montanari, F.; Pozzi, G.; Quici, S. Eur. J. Org. Chem. 2001, 181-186. (r)
ten Brink, G.-J.; Vis, J. M.; Arends, I. W. C. E.; Sheldon, R. A. Tetrahedron
2002, 58, 3977-3983.
(3) (a) Wende, M.; Meier, R.; Gladysz J. A. J. Am. Chem. Soc. 2001,
123, 11490-11491. (b) Wende, M.; Gladysz, J. A. J. Am. Chem. Soc. 2003,
125, 5861-5872.
(4) (a) Kozhevnikov, I. V. Catalysis by Polyoxometalates; Wiley:
Chichester, England, 2002. (b) Hill, C. L.; Prosser-McCartha, C. M. Coord.
Chem. ReV, 1995, 143, 407-455. (c) Mizuno, N.; Misono, M. Chem. ReV.
1998, 98, 199-218. (d) Neumann, R. Prog. Inorg. Chem. 1998, 47, 317-
370.
(5) (a) Neumann, R.; Gara, M. J. Am. Chem. Soc. 1994, 116, 5509-
5510. (b) Neumann, R.; Gara, M. J. Am. Chem. Soc. 1995, 117, 5066-
5074. (c) Neumann, R.; Juwiler, D. Tetrahedron 1996, 47, 8781-8788.
(d) Adam, W.; Alsters, P. L.; Neumann, R.; Saha-Mo¨ller, C. R.; Sloboda-
Rozner, D.; Zhang, R. Synlett 2002, 2011-2014. (e) Adam, W.; Alsters,
P. L.; Neumann, R.; Saha-Mo¨ller, C. R.; Sloboda-Rozner, D.; Zhang, R. J.
Org. Chem. 2003, 68, 1721-1728.
Table 1. Oxidation of Aliphatic Alcohols with 30% Aqueous
H2O2 Catalyzed by (RFN+)12[WZn3(H2O)2(ZnW9O34)2]a
conversion, mol %
substrate
fluorous solvent
nonfluorous solvent
2-butanol
2-pentanol
2-hexanol
2-heptanol
2-octanol
3
32
44
46
67
43
50b
8
36
55
48
28
82
19c
cyclohexanol
1-octanol
a Reaction conditions: 1 mmol of alcohol, 2 mmol of 30% aq.H2O2, 1
mL of perfluorodecalin or EtOAc, 5 µmol of (RFN+)12[WZn3(H2O)2-
(ZnW9O34)2], 80 °C, 8 h. Analysis by GC; ketones were the only observed
product. b 4% octanal, 76% octanoic acid, 20% octyloctanoate. c 15%
octanal, 36% octanoic acid, 39% octyloctanoate.
(6) (a) Neumann, R.; Levin, M. J. Org. Chem. 1991, 56, 5707-5710.
(b) Yamaguchi, K.; Mizuno, N. New J. Chem. 2002, 26, 972-974. (c) Okun,
N. M.; Anderson, T. M.; Hill, C. L. J. Am. Chem. Soc. 2003, 125, 3194-
3195. (d) Khenkin, A. M.; Neumann, R.; Sorokin, A. B.; Tuel, A. Catal.
Lett. 1999, 63, 189-192. (e) Neumann, R.; Miller, H. J. Chem. Soc., Chem.
Commun. 1995, 2277-2778.
(7) Sloboda-Rozner, D.; Alsters, P. L.; Neumann, R. J. Am. Chem. Soc.
2003, 125, 5280-5281.
(8) (a) Neumann, R.; Cohen, M. Angew. Chem., Int. Ed. Engl. 1997, 36,
1738-1740. (b) Cohen, M.; Neumann, R. J. Mol. Catal. A 1999, 146, 293-
300.
One may observe that secondary aliphatic alcohols were
rather effectively oxidized to the expected ketones without
(10) Rocaboy, C.; Bauer, W.; Gladysz, J. A. Eur. J. Chem. 2000, 2621-
2628.
(11) Zonnevijlle, F.; Tourne´, C. M.; Tourne´, G. F. J. Chem. Soc., Dalton
Trans. 1991, 143-155.
(9) Haimov, A.; Neumann, R. Chem. Commun. 2002, 876-877.
3548
Org. Lett., Vol. 5, No. 20, 2003

Figure 2. Reaction protocols for oxidation with aqueous hydrogen peroxide catalyzed by (RFN+)12[WZnM2(H2O)2(ZnW9O34)2].
formation of byproducts. For a representative primary
alcohol, 1-octanol, one observes low selectivity, with forma-
tion first of octanal. Octanal may be further oxidized to
octanoic acid or a reaction between octanal and 1-octanol
leads to formation of a hemiacetal that is oxidized to the
octyloctanoate ester. It is also interesting to note that there
appear to be interesting trends of reactivity as a function
of the length of the aliphatic chain. Fairly water soluble
2-butanol hardly reacts due to its limited solubility in EtOAc
and perfluorodecalin in the presence of aqueous H2O2. For
the shorter chain alcohols, e.g. 2-pentanol, 2-hexanol, and
also cyclohexanol, probably better solubility in EtOAc versus
perfluorodecalin leads to higher conversion in the nonfluo-
rous solvent. As the aliphatic chain is lengthened, the relative
activity EtOAc/perfluorodecalin is inverted. 2-Octanol is
more reactive in the fluorous phase.
phobicity of the substrate. One general observation was that
allylic alkenols were more reactive (reactions at ambient
temperature) than nonallylic alkenols (reactions at 60 °C).
Furthermore, a general selectivity trend was observed: for
alkenols with primary alcohol moieties, epoxidation is the
predominant reaction, whereas for alkenols with secondary
alcohol moieties, alcohol oxidation is the predominant
reaction. Selectivity to epoxidation was highest in 3-methyl-
2-buten-1-ol due to the higher nucleophilicity of the alkene.
For the acyclic allylic primary alcohols tested, E-2-hexen-
1-ol, Z-2-hexen-1-ol, and 3-methyl-2-buten-1-ol, the men-
tioned chemoselectivity for epoxidation versus alcohol
oxidation was retained. However, activity and selectivity was
strongly dependent on the carbon chain length (hydrophobic-
ity) and the nature of the solvent. 3-Methyl-2-buten-1-ol was
more reactive in EtOAc compared to perfluorodecalin
because it is relatively more hydrophilic. For 2-hexen-1-ol
the opposite was observed, presumably because of improved
solubility in perfluorodecalin. Importantly, the alcohol moiety
was less reactive for 2-hexen-1-ol in perfluorodecalin than
in EtOAc leading to improved chemoselectivity due to the
limited miscibility of the OH group in the fluorous phase.
Comparison of the reactivity of remaining substrates also
reveals that the more hydrophobic substrates were more
Analysis of the results of the oxidation of alkenols needs
to take into account at least five factors: (i) allylic versus
nonallylic alcohols, (ii) secondary versus primary alcohols,
(iii) secondary versus primary alkenes, (iv) fluorous versus
nonfluorous solvents, and (v) the hydrophilicity or hydro-
Table 2. Oxidation of Alkenols with 30% Aqueous H2O2
a
Catalyzed by (RFN+)12[WZn3(H2O)2(ZnW9O34)2
conversion (selectivity),b mol %
substrate
fluorous solvent
nonfluorous solvent
Table 3. Epoxidation of Alkenes with 30% Aqueous H2O2
E-2-hexen-1-ol
Z-2-hexen-1-ol
3-Me-2-buten-1-ol
Z-3-hexen-1-ol
5-hexen-1-ol
1-octen-3-ol
1-cyclohexen-3-ol
(-)-isopulegolc
95 (94, 6)
95 (98, 2)
43 (100, 0)
71 (82, 18)
58 (97, 3)
66 (0, 100)
82 (0, 100)
87 (0, 100)
53 (72, 28)
66 (65, 35)
100 (100, 0)
94 (90, 10)
56 (96. 4)
35 (0, 100)
89 (0, 100)
40 (0, 100)
Catalyzed by (RFN+)12[WZnMn2(H2O)2(ZnW9O34)2
substrate
conversion, mol %
1-octene
E-2-octene
0
3
cyclooctene
52
2-methyl-2-heptene
cyclohexene
4-methylcyclohexene
1-methylcyclohexene
64
100
97
a Reaction conditions: 1 mmol of alcohol, 2 mmol of 30% aq H2O2, 1
mL of perfluorodecalin or EtOAc, 5 µmol of (RFN+)12[WZn3(H2O)2-
(ZnW9O34)2], 22 °C (allylic alcohols), 60 °C (other alkenols), 8 h. Analysis
by GC, GC-MS. b Selectivity is given as mol % product/all products (%
epoxide, % ketone or aldehdye). c (1R,2S,5R)-2-Isopropenyl-5-methyl-
cyclohexanol.
100
a Reaction conditions: 1 mmol of alkene, 2 mmol of 30% aq H2O2, 1
mL of toluene, 20 µmol of (RFN+)12[WZnMn2(H2O)2(ZnW9O34)2], 60 °C,
13 h. Analysis by GC, GC-MS. Only epoxides were formed.
Org. Lett., Vol. 5, No. 20, 2003
3549

reactive in perfluorodecalin compared to EtOAc and vice
versa.
precipitated catalyst was collected by filtration and reused.
Three repetitions showed no significant loss of reactivity;
81, 80, and 78 mol % of cyclohexanone were formed in each
cycle. 19F NMR of the organic product phases showed no
measurable (by NMR) presence of the catalyst in the product
phase.
Polyfluorinated quaternary ammonium salts of polyoxo-
metalate anions can be used in fluorous biphasic oxidation
catalysis with and without fluorous solvents for oxidation
of alkenes, alkenols, and alcohols with hydrogen peroxide.
The solvent (fluorous or “normal”) has an effect on reactivity
and selectivity.
The reactivity of weakly nucleophilic alkenes (1-octene,
2-octene) was very low with use of the fluorous polyoxo-
metalate catalyst; however, the more reactive cyclohexene
derivatives reacted very nicely with this catalyst with no
evidence of acid-catalyzed epoxide ring opening and diol
formation, which is unusual for such acid-sensitive epoxides
in the absence of a buffer. Alkenes of moderate nucleophi-
licity such as 2-methyl-2-heptene showed intermediate
reactivity.
Importantly, one can demonstrate the catalyst recovery
protocols described in Figure 2. Thus, in a fluorous solvent
1-cyclohexen-3-ol was used as a model substrate (1 mmol
of 1-cyclohexen-3-ol, 2 mmol of H2O2, 5 µmol of (RFN+)12-
[WZn3(H2O)2(ZnW9O34)2], in 1 mL of perfluorodecalin at
22 °C). After 8 h of reaction the fluorous phase was separated
and used as is for another reaction cycle. This process was
repeated; no loss of reactivity was noted as conversions to
1-cyclohexen-3-one for each cycle were 80, 83, and 79 mol
%, respectively. Similarly, with EtOAc as solvent, cyclo-
hexanol was reacted (1 mmol of cyclohexanol, 2 mmol of
H2O2, 5 µmol of (RFN+)12[WZn3(H2O)2(ZnW9O34)2] in 1 mL
of EtOAc at 80 °C). After 8 h of reaction and cooling the
Acknowledgment. This research was supported by the
Israel Science Foundation, the Israel Ministry of Science,
and the Helen and Martin Kimmel Center for Molecular
Design. R.H.F. thanks the Weston Foundation for funding a
Visiting Professorship. R.N. is the Rebecca and Israel Sieff
Professor of Organic Chemistry.
Supporting Information Available: Experimental de-
tails. This material is available free of charge via the Internet
at http://pubs.acs.org.
OL0348598
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Org. Lett., Vol. 5, No. 20, 2003