Syntheses of fluorous quaternary ammonium salts and their application as phase transfer catalysts for halide substitution reactions in extremely nonpolar fluorous solvents

Article abstract of DOI:10.1016/j.tet.2009.11.012

Perfluoromethyldecalin solutions of the fluorous alkyl halides R_f8(CH₂)_mX (m=2, 3; X=Cl, I) are inert toward aqueous NaCl, KI, KCN, and NaOAc. However, substitution occurs at 100 °C in the presence of 10 mol % of the fluorous ammonium salts (R_f8(CH₂)₂)(R_f8(CH₂)₅)₃N⁺ I^- (1) or (R_f8(CH₂)₃)₄N⁺ Br^- (2) (10 mol %), which are fully or partially soluble in perfluoromethyldecalin under these conditions. Stoichiometric reactions of (a) 1 and R_f8(CH₂)₃Br, and (b) 2 and R_f8(CH₂)₂I are conducted in perfluoromethyldecalin at 100 °C, and yield the same R_f8(CH₂)_mI/R_f8(CH₂)_mBr equilibrium ratio (60-65:40-35). This shows that ionic displacements can take place in extremely nonpolar fluorous phases, and suggests a classical phase transfer mechanism for the catalyzed reactions. Interestingly, the non-fluorous ammonium salt mixture CH₃(CH₃(CH₂)_m)₃N⁺ Cl^- (3, Aliquat 336; m=2:1 7/9) also catalyzes halide substitutions, but under triphasic conditions with 3 suspended between the lower fluorous and upper aqueous layers. NMR experiments establish very low solubilities in both phases, suggesting interfacial catalysis.

Full text of DOI:10.1016/j.tet.2009.11.012

Tetrahedron 66 (2010) 1070–1077
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Syntheses of fluorous quaternary ammonium salts and their application
as phase transfer catalysts for halide substitution reactions in extremely
nonpolar fluorous solvents
*
Debaprasad Mandal, John A. Gladysz
Department of Chemistry, Texas A&M University, PO Box 30012, College Station, TX 77842-3012, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 8 July 2009
Accepted 1 October 2009
Available online 6 November 2009
Perfluoromethyldecalin solutions of the fluorous alkyl halides Rf8(CH2)mX (m¼2, 3; X¼Cl, I) are inert toward
aqueous NaCl, KI, KCN, and NaOAc. However, substitution occurs at 100 ꢀC in the presence of 10 mol % of the
fluorous ammonium salts (Rf8(CH2)2)(Rf8(CH2)5)3Nþ Iꢁ (1) or (Rf8(CH2)3)4Nþ Brꢁ (2) (10 mol %), which are
fully or partially soluble in perfluoromethyldecalin under these conditions. Stoichiometric reactions of (a) 1
and Rf8(CH2)3Br, and (b) 2 and Rf8(CH2)2I are conducted in perfluoromethyldecalin at 100 ꢀC, and yield the
same Rf8(CH2)mI/Rf8(CH2)mBr equilibrium ratio (60–65:40–35). This shows that ionic displacements can take
place in extremely nonpolar fluorous phases, and suggests a classical phase transfer mechanism for the
catalyzed reactions. Interestingly, the non-fluorous ammonium salt mixture CH3(CH3(CH2)m)3Nþ Clꢁ (3,
AliquatÒ 336; m¼2:1 7/9) also catalyzes halide substitutions, but under triphasic conditions with 3 sus-
pended between the lower fluorous and upper aqueous layers. NMR experiments establish very low solu-
bilities in both phases, suggesting interfacial catalysis.
Keywords:
Fluorous
Ammonium salts
Phase transfer catalysis
Substitution
Finkelstein reaction
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
The related rhodium salt [Rh(dppe)2]þ B(4-C6H4Rf6)4ꢁ is insoluble
in FC-72 (<0.000006 M), but [Rh(dppe)2]þ B(3,5-C6H3(Rf6)2)4ꢁ (IIa),
Fluorous liquid phases such as perfluoroalkanes are, by a variety
of measures, the least polar known.1,2 They are rivaled only by the
noble gases, which are liquid over much narrower temperature
ranges. Hence, it is not surprising that common inorganic salts and
other ionic compounds are insoluble in such media. However, there
is a growing recognition that some fluorous salts can dissolve in
fluorous liquids, either at room temperature or upon heating,
which often dramatically enhances the solubilities of fluorous sol-
utes.3 Some examples are collected in Figure 1, in which Rfn denotes
a perfluoroalkyl group (CF2)nꢁ1CF3.
which features four additional perfluorohexyl groups in the anion,
partitions nearly equally between toluene and perfluoromethyl-
cyclohexane. Bu¨hlmann has reported that the analogous sodium
salt IIb is quite soluble in perfluorodecalin (0.0011 M), per-
fluoroperhydrophenanthrene (0.0014 M), and
a perfluoroether
(0.00091 M).5 Not unsurprisingly, distinctly higher solubilities are
realized when the cations are also fluorous, as in the rhodium salts
IIIb,c. In partitioning experiments, these showed much greater af-
finities for perfluoromethylcyclohexane than toluene.4a
In unpublished work from some time ago, we prepared the flu-
orous primary ammonium (anilinium) salt (3,5-C6H3((CH2)2-
Rf8)2)NHþ3 Clꢁ (IV, Fig.1) and noted a solubility of ca.10 g/L (0.01 M) in
perfluoromethylcyclohexane at room temperature.6 Pozzi and co-
workers have reported that the related fluorous anilinium triflates V
and VI, as well as the fluorous aliphatic secondary ammonium salt
VII, exhibit appreciable (and temperature dependent) solubilities in
perfluoro-1,3-dimethylcyclohexane.7
Neumann and Fish synthesized the fluorous quaternary ammo-
nium salt (CH3)(Rf8(CH2)3)3Nþ CH3SOꢁ3 , and used the cation to render
the dodecaanion in VIII ‘freely soluble in perfluorohydrocarbons’.8
Bu¨hlmann combined the same cation with a fluorous BArꢁf anion to
give IX, which exhibited solubilities of 0.010 M in FC-72 and per-
fluoroperhydrophenanthrene.5 Maruoka has utilized the chiral fluo-
rousammoniumsaltXasaphasetransfercatalystforenantioselective
Deelman and van Koten have synthesized a series of fluorous BArfꢁ
(‘Barf’) type anions, B(4-C6H4Rf6)ꢁ4 , B(4-C6H4Si(CH3)2(CH2)2Rf6)4ꢁ, and
B(3,5-C6H3(Rf6)2)ꢁ4 .4 These have been employed to solubilize several
cations. For example, the ammonium salt n-Bu4Nþ B(4-C6H4-
Si(CH3)2(CH2)2Rf6)ꢁ4 (I, Fig. 1) exhibits a solubility of 0.000052 M at
room temperature in FC-72,4b a medium that consists mainly of per-
fluorohexane. Note that due tothe high molecular weights commonly
associated with fluorous molecules, molar solubilities that appear
modest translate to mass-based solubilities that are more substantial
(0.113 g/L for I).
* Corresponding author.
E-mail address: gladysz@mail.chem.tamu.edu (J.A. Gladysz).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.11.012

D. Mandal, J.A. Gladysz / Tetrahedron 66 (2010) 1070–1077
1071
alkylations in organic media, with subsequent recovery by extraction
with FC-72.9 Ammonium salts with fewer perfluoroalkyl groups per
nitrogen atom have also been described, but no data regarding solu-
bilities in fluorous solvents (which should be lower) are yet
available.10
The ammonium or imidazolium salt XI, which features a non-
fluorous cation and a fluorous BArꢁf anion, exhibits a solubility of
0.37 g/L (0.00018 M) in FC-72, and is a room temperature ionic
Rf6
Rf6
Si
Si
Si
Rf6
Rf6
Rf6
Rf6
n-Bu4N+
Rf6
M+
B
B
Rf6
Rf6
Rf6
Si
Rf6
Rf6
I4
II4,5
+
M+ = (a) Rh(dppe)2
(b) Na+
liquid.11 More recently, Kvıcalova has described a large family of
liquid salts with fluorous imidazolium cations (XII).12 These are
highly soluble in perfluoromethylcyclohexane, exceeding 50 g/L in
the best cases, and show much greater affinities for this solvent
than toluene. Other fluorous ionic liquids have been described, but
solubility data in fluorous solvents have not to our knowledge been
reported.13
´ˇ
´
(Rf6CH2CH2)x(CH3)3-xSi
P
P
Si(CH3)3-x(CH2CH2Rf6)
2
x 2
Rh
X–
X = (a) BF4 (x = 2, 3); (b) B(4-C6H4Rf6
III4
)4 (x = 2); (c) B(3,5-C6H3(Rf6)2)4 (x = 1)
–
NH3 CF3SO3
Rf8
Rf8
–
Rf8
NH2
CF3SO3
H3N
Cl–
´
¨
Yasuda, Sakakura, Stuart, Horvath, Buhlmann, and ourselves have
prepared a number of fluorous quaternary aliphatic phosphonium
halides and triflates (XIII-XVI).14–17 Those grouped in XIII have been
shown to be highly soluble in perfluoromethylcyclohexane at ele-
vated temperatures.15 With the triarylphosphonium salt XIV, solu-
bilities exceed 0.014 M in FC-72, perfluoromethylcyclohexane, and
perfluoroperhydrophenanthrene at room temperature. Presumably
many of XV-XVI would also exhibit significant solubilities. Phos-
phonium salts with a single perfluoroalkyl moiety have also been
reported.18 The manner in which the preceding salts are solvated in
fluorous mediaisanintriguing questionthatremains to beaddressed.
The growing portfolio of fluorous salts that are soluble in fluorous
liquid phases offers increased options for introducing polar ions that
may interact or react with fluorous solutes. One obvious application
would be phase transfer catalysis,19 whereby an ion of a salt that is
insoluble in a fluorous solvent is transported across a phase barrier
by a fluorous counter-ionwith an appreciable fluorous phase affinity.
Indeed, we recently established that fluorous quaternary aliphatic
phosphonium salts such as (Rf8(CH2)2)(Rf6(CH2)2)3Pþ Xꢁ (X¼I, Br)
and (Rf8(CH2)2)4Pþ Iꢁ catalyze Finkelstein-type20 substitution re-
actions of fluorous alkyl halides Rf8(CH2)mX (m¼2, 3; X¼Cl, Br, I) in
perfluoromethylcyclohexane (CF3C6F11) or perfluoromethyldecalin
(CF3C10F17) by aqueous NaCl, NaBr, KI, KCN, and NaOAc at 76–
100 ꢀC.21 These transformations are illustrated in Scheme 1. Other
creative approaches to interfacing fluorous chemistry with phase
transfer catalysis have also been described.9,22–24
2
Rf8
Rf8
IV6
V7
VI7
Rf8
Rf8
Rf6
Rf6
Rf6
Rf6
B
–
NH2
N–CH3
CF3SO3
Rf8
Rf8
Rf6
Rf6
Rf6
Rf6
VII7
IX5
Rf8
Rf8
Rf8
RFN+
RFN+
RFN+
RFN+
RFN+
Si
Si
Si
RFN+
RFN+
RFN+
Si
Si
Polyoxometalate
(POM)
Rf8
Rf8
Rf8
Rf8
N
RFN+
RFN+
RFN+
Br–
RFN+
Si
Si
Si
RFN+ = Rf8(CH2)3)3(CH3)N+
POM = [WZnM2(H2O)2(ZnW9O34)2]12–
M = Zn, Mn
Rf8
Rf8
VIII8
X9
Si
Si
Si
Rf6
Rf6
H3C
n-C4H9
N
N
XI11
B
Rf6
Rf6
Si
CF3CF2[CF2OCF(CF3)]2CH2
CH2Z
X–
XII12
N
N
Z = [(CF3)CFOCF2]2CF2CF3,
f6, CH2Rf6, CF3;
X = I, BF4, PF6, (CF3SO2)2N
R
76-100 °C
Rf6
Rf6
Rf8
Rf8
Rf8
X–
3
P X–
4
P
X = I, Br
XIII15
P
M+ X–
M+ Y–
3
I–
X = I, OTf
Aqueous
Phase
Rf8
Rf8
R4P+ X–
R4P+ Y–
Rf8
Fluorous
Phase
–
XIV17
P–CH3 CF3SO3
Rf8
Rf8(CH2)mY
Rf8(CH2)mX
Rf8
Rf8
M+ Y– = NaCl, NaBr, KI, KCN, NaOAc
Rfn
R4P+ X– = 10 mol%
(Rf8(CH2)2)(Rf6(CH2)2)3P+ I–,
(Rf8(CH2)2)4P+ I–,
Rfn
CN
CN
Rfn
Rfn
P
x
P
I–
4-x
4-x
x
P
I–
I–
Rfn
n/x = 4/1, 4/2, 4/3, 6/1, 6/2, 6/3, 8/1, 8/2, 8/3
(Rf8(CH2)2)(Rf6(CH2)2)3P+ Br–
n = 4, 6, 8
XV16
XVI16
X = Cl, Br, I; m = 2, 3
Figure 1. Fluorous salts that have documented solubilities in fluorous liquid phases
(I-XIV), and related species (XV-XVI) (Rfn¼(CF2)nꢁ1CF3).
Scheme 1. Phase transfer catalysis of halide substitution reactions in fluorous media
using fluorous phosphonium salts.

1072
D. Mandal, J.A. Gladysz / Tetrahedron 66 (2010) 1070–1077
Table 1
Quaternary ammonium salts are frequently employed as phase
Data for halide substitution reactions catalyzed by fluorous ammonium salts at
100 ꢀC under the conditions of Scheme 3 unless noteda
transfer catalysts for ionic displacement reactions in organic/
aqueous solvent systems.19 A variety of fluorous tertiary amines
have been reported,25–27 but to our knowledge, fluorous quaternary
ammonium salts have not been previously described, outside of
those depicted in VIII-X (Fig. 1). In this paper, we report (a) the first
fluorous quaternary ammonium salts in which the nitrogen atom
features four acyclic fluorous substituents, the iodide and bromide
salts (Rf8(CH2)2)(Rf8(CH2)5)3Nþ Iꢁ (1) and (Rf8(CH2)3)4Nþ Brꢁ (2), (b)
their application as phase transfer catalysts for Finkelstein-type
ionic displacement reactions of the general type in Scheme 1, and
(c) control experiments with the non-fluorous quaternary ammo-
nium salt CH3(CH3(CH2)m)3Nþ Clꢁ (3, AliquatÒ 336; m¼2:1 7/9). A
number of experiments pertaining to the scope, mechanism, and
phase where substitution takes place are also presented.
Entry Solvent
Substrate
Mþ Yꢁ R4Nþ Xꢁ Product
Time Convn
(h)
(%)
1b
2
CF3C10F17
R
f8(CH2)3I NaCl
1
2
R
f8(CH2)3Cl
f8(CH2)3Cl
4
34
c
12 64
24 86
24 70
48 82
72 88
3.5 13
24 72
R
3
4
5
6
KCN
NaOAc
1
1
1
1
R
R
R
R
f8(CH2)3CN
f8(CH2)3OAc
f8(CH2)3I
4
6
24 12
24 22
72 48
24 25
48 37
120 65
24 15
48 26
120 41
24 31
60 72
Rf8(CH2)3Cl KI
CF3C10F17
Rf8(CH2)2I NaCl
f8(CH2)2Cl
2. Results
7
NaCl
2
Rf8(CH2)2Cl
2.1. Syntheses and characterization of fluorous quaternary
ammonium salts
d
8
9
CF3C6H5
R
f8(CH2)3I NaCl
f8(CH2)3I
2
2
R
f8(CH2)3Cl
f8(CH2)3Cl
d
CF3C6F5
R
R
5
12
As shown in Scheme 2, two symmetrically substituted fluorous
tertiary amines differing in the number of methylene spacers,
(Rf8(CH2)5)3N and (Rf8(CH2)3)3N,25 were selected. Reactions with the
fluorous alkyl halides Rf8(CH2)2I or Rf8(CH2)3Br, which also differ in
the number of methylene spacers, were carried out at 115 ꢀC in DMF.
After 24 h, workups gave the fluorous quaternary ammonium salts 1
and 2 in 78% and 86% yields as analytically pure light yellow or cream
white solids, respectively. They were characterized by NMR (1H, 13C)
and mass spectrometry, as summarized in Experimental section.
24 24
a
Conditions:
Rf8(CH2)mX
(0.10 mmol), Mþ Yꢁ (0.80 mmol), solvent (0.5 mL),
water (0.5 mL), R4Nþ Xꢁ (0.010 mmol, 10 mol %).
b
For the conversion profile, see Figure 2.
Perfluoromethyldecalin.
Hybrid or non-fluorous solvent.
c
d
10 mol%
R4N+ X–,
100 °C
Rf8(CH2)mY + M+ X–
M+ Y–
115 °C
+
Rf8(CH2)mX
(Rf8(CH2)m)3N
+
Rf8(CH2)m'
(excess)
X
(Rf8(CH2)m)3(Rf8(CH2)m')N+ X–
fluorous
phase
H2O/
24 h, DMF
(excess)
m = 2, 3
X = Cl, Br, I
M+ Y– =
m = 5,3
m/m'/X = 1, 5/2/I (78%)
2, 3/3/Br (86%)
Rfn = (CF2)n–1CF3
NaCl, KI, KCN,
NaOAc
Scheme 2. Syntheses of fluorous ammonium salts.
M+ X–
M+ Y–
Aqueous
Phase
Both ammonium salts melted at higher temperatures than re-
lated fluorous phosphonium salts. With 1, an apparent phase tran-
sition was visually noted prior to melting. DSC measurements
confirmed the presence of additional phases, presumably liquid
crystals as previously documented for a fluorous pyridinium salt.28
The salt 1 readily dissolved in the fluorous solvents perfluoro-
methylcyclohexane (CF3C6F11, bp 76 ꢀC) and perfluoromethyldecalin
(CF3C10F17, bp 160 ꢀC) at elevated temperatures, as well as the hybrid
(ambiphilic) solvent CF3C6H5 (bp 102 ꢀC).2,29 However, symmetri-
cally substituted 2 was only sparingly soluble in fluorous solvents
under similar conditions. Both 1 and 2 were insoluble in hexane,
toluene, diethyl ether, dichloromethane, and water. In contrast, they
exhibited appreciable solubilities in acetone at room temperature.
R4N+ X–
R4N+ Y–
Fluorous
Phase
(perfluoro-
methyl-
decalin)
Rf8(CH2)mY
Rf8(CH2)mX
R4N+ X– =
(Rf8(CH2)2)(Rf8(CH2)5)3N+ I– (1),
(Rf8(CH2)3)4N+ Br– (2)
Scheme 3. Phase transfer catalysis of halide substitution reactions in fluorous media.
illustrated earlier, the 1H NMR signals of the CH2X moieties (t) of all
fluorous substrates and products are well separated.21
2.2. Ionic displacement reactions
The salt 2 also catalyzed this transformation, but the rate was
slower, with 70% and 82% conversion after 24 and 48 h (entry 2,
Table 1). In contrast to the case with 1, the reaction mixture was not
homogeneous, as shown by the photograph in Figure 3. With 1,
samples often remained homogeneous upon cooling. Note that
after reaction, the leaving group and excess nucleophile can both
serve as counter-anions for the ammonium cation. No conversion
was observed in experiments without 1 or 2.
Additional nucleophiles were tested. An analogous reaction
with KCN (entry 3, Table 1) afforded the corresponding fluorous
cyanide Rf8(CH2)3CN.21 The conversion was 13% after 3.5 h and 72%
after 24 h. A similar reaction with NaOAc (entry 4) was much
slower, with only 12% conversion after 24 h. The same CNꢁ/OAcꢁ
The fluorous alkyl chlorides, bromides, and iodides summarized
in Table 1 were treated with NaCl, KI, KCN, and NaOAc under var-
ious conditions per the general Scheme 3.
First, a 0.10 M perfluoromethyldecalin solution of Rf8(CH2)3I was
prepared. It was treated with a nearly saturated 0.80 M aqueous so-
lution of NaCl to give a sample with a 1:8 Rf8(CH2)3I/NaCl mole ratio.
Then 10 mol % of 1 was added. The mixture was rapidly stirred at
100 ꢀC for 24 h. Aliquots were periodically taken and analyzed by 1H
NMR. As indicated in entry 1 of Table 1, 86% conversion to the fluorous
alkyl chloride Rf8(CH2)3Cl was realized. A rate or conversion profile,
representative of that made for all entries, is depicted in Figure 2. As

D. Mandal, J.A. Gladysz / Tetrahedron 66 (2010) 1070–1077
1073
Rf8(CH2)mX become less reactive toward nucleophiles as the length
of the methylene spacer decreases.30
2.3. Phase requirements
An obvious question associated with the preceding data is
whether aqueous solutions of nucleophiles are required. When en-
tries 1 or 2 of Table 1 were repeated with solid NaCl, no reaction or
apparent dissolution occurred. Thus, solid/liquid phase transfer ca-
talysis does not take place. Fluorous phosphonium salts behaved
similarly.21
The hybrid solvent CF3C6H5 commonly dissolves appreciable
quantities of both fluorous and non-fluorous solutes.29 The sym-
metrically substituted salt 2 exhibited higher solubility in this
medium than perfluoromethyldecalin. Thus, a CF3C6H5 solution of
Rf8(CH2)3I was combined with 2 and aqueous NaCl at 100 ꢀC in
a manner analogous to entry 2 of Table 1. Some 2 remained un-
dissolved, but the quantity was less than in Figure 3. Aliquots were
analyzed by 1H NMR, and showed a somewhat slower reaction than
in perfluoromethyldecalin, with 31% and 72% conversion after 24 h
and 60 h (entry 8, Table 1). A similar reaction in the perfluorinated
arene CF3C6F5 was comparably slow, with 24% conversion after 24 h
at 100 ꢀC (entry 9). The fluorous phosphonium salt catalysts also
gave diminished rates in these solvents.21
Figure 2. Conversion profile for the reaction of Rf8(CH2)3I and NaCl catalyzed by 1 in
water/perfluoromethyldecalin at 100 ꢀC (entry 1, Table 1).
Another obvious question concerns the loci of the reactions in
Scheme 3. The preceding results are consistent with substitution
occurring in the fluorous phase via a classical phase transfer catalysis
mechanism. However, interfacial phenomena might alsoplaya role.31
Hence, we sought to confirm that stoichiometric analogs of the pre-
ceding reactions could be carried out solely in a fluorous phase.
As depicted in Scheme 4, two reactions (A, B) were conducted
with equimolar amounts of fluorous alkyl halides and ammonium
salts in perfluoromethyldecalin at 100 ꢀC. The fluorous alkyl
Figure 3. Photograph of the reaction of Rf8(CH2)3I with NaCl in the presence of 2 at
100 ꢀC (entry 2, Table 1) showing undissolved 2 at the water/perfluoromethyldecalin
interface.
nucleophilicity order was found using fluorous phosphonium salt
catalysts (Scheme 1).21
The reverse of the reaction in entry 1 was investigated. As
shown in entry 5, a perfluoromethyldecalin solution of Rf8(CH2)3Cl,
excess aqueous KI (1:8 mol ratio), and 1 were similarly combined at
100 ꢀC. Substitution occurred, but at a much slower rate (conver-
sion after 24 h, 22%; 72 h, 48%). Data with fluorous phosphonium
salt catalysts established the nucleophilicity order Iꢁ>Clꢁ.21 Thus,
the poorer leaving group ability of chloride (or equivalently, the
diminished electrophilicity of the alkyl halide) likely plays a key
role. However, other factors may also contribute.
Reactions analogous to those in entries 1 and 2 were conducted
with the fluorous alkyl iodide Rf8(CH2)2I, which has two methylene
spacers instead of three. As shown in entries 6 and 7, substitutions
were much slower, with 25–15% conversions to Rf8(CH2)2Cl after
24 h and 65–41% after 120 h. Parallel trends were observed with the
fluorous phosphonium salt catalysts.21 All fluorous electrophiles
Scheme 4. Reactions of fluorous alkyl halides with equimolar amounts of fluorous
quaternary ammonium salts, and conversion data.

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D. Mandal, J.A. Gladysz / Tetrahedron 66 (2010) 1070–1077
bromide Rf8(CH2)3Br, which features three methylene spacers, and
the ammonium iodide 1 reacted under homogeneous conditions to
give the fluorous alkyl iodide Rf8(CH2)3I. In less than 1 h, 60% con-
version was realized, but no further product formed after a total of
24 h. A transformation approximating the reverse reaction was
conducted with the fluorous alkyl iodide Rf8(CH2)2I, which features
two methylene spacers, and the ammonium bromide 2. In this case,
the catalyst was only partially soluble in perfluoromethyldecalin
under the conditions employed. As shown by the rate profile in
Scheme 4B, 35% conversion was reached over the course of 7 h. This
level, which was replicated in a second experiment, remained
constant after a total of 24 h. Hence, despite the differences in the
reactants and homogeneities, similar equilibrium constants are
reached in both directions.
10 mol%
R4N+ X–,
100 °C
+
Rf8(CH2)3X
M+ Y–
Rf8(CH2)3Y + M+ X–
H2O/fluorous
phase
(excess)
X = Cl, I
M+ Y– =
NaCl, KI, KCN,
NaOAc
M+ X–
Aqueous
Phase
M+ Y–
R4N+ X–
Catalyst
Phase
R4N+ Y–
Fluorous
Phase
R
f8(CH2)m
Y
Rf8(CH2)m
X
R4N+ X– =
Cl–
+
CH3(CH3(CH )
2 m N
2.4. Catalyst requirements: non-fluorous ammonium salts
(3; Aliquat 336 (m 2:1 7/9))
=
(triphasic)
or
n-Bu4N F ·3H2O, n-Bu4N Br
For obvious reasons, we sought to test a comparable non-fluorous
quaternary ammonium salt for catalytic activity. AliquatÒ 336 (3),
a commercially available room temperature ionic liquid that is a 2:1
mixture of the octyl- and decyl-substituted species CH3(CH3(CH2)7)3Nþ
Clꢁ and CH3(CH3(CH2)9)3Nþ Clꢁ, was selected.32 This cocktail sees ex-
tensive use for organic/aqueous phase transfer catalysis.19a,24
+
–
+
–
(biphasic)
Scheme 5. Phase transfer catalysis of halide substitution reactions using non-fluorous
ammonium salts under triphasic conditions.
illustrated in Figure 4. There was also a significant acceleration with
NaOAc, but much less difference with NaCl.
Entry 1 of Table 1, corresponding to the protocol in Scheme 3,
was repeated using the salt 3. As shown in entry 1 of Table 2, the
fluorous alkyl iodide Rf8(CH2)3I was 85% converted to the chloride
Rf8(CH2)3Cl after 24 h. However, the conditions were now triphasic,
with 3 layered between the fluorous and aqueous phases to give
a liquid/liquid/liquid system as shown in Scheme 5. As summarized
in entries 2 and 3 of Table 2, 3 similarly catalyzed reactions of
Rf8(CH2)3I with KCN and NaOAc. In both cases, some fluorous alkyl
chloride Rf8(CH2)3Cl builds up, derived from the anion of 3. In this
context, entry 4 shows that Rf8(CH2)3Cl is distinctly less reactive
toward nucleophiles than Rf8(CH2)3I. As compared to the fluorous
catalyst 1, there was a marked rate enhancement with KCN, as
NMR experiments involving internal standards (Experimental
section) established that 3 has no detectable solubility in per-
fluoromethyldecalin at room temperature (<0.0006 M) and only
a very low solubility at 100 ꢀC (ca. 0.0016 M or 0.001 g/mL). The
solubility of 3 in water was low at room temperature (ca. 0.0030 M
or 1.3 g in 1000 g), but increased slightly at 100 ꢀC (ca. 0.0039 M or
1.7 g in 1000 g). However, 3 was highly soluble at 100 ꢀC in the neat
fluorous alkyl iodide Rf8(CH2)2I, which liquefies at 54–58 ꢀC (>191 g
in 1000 g, or >25 mol %). Note that the iodide functionality renders
this substance more polar than saturated perfluorocarbons.
Table 2
Data for halide substitution reactions catalyzed by non-fluorous ammonium salts at 100 ꢀC under the conditions of Scheme 5 unless noteda
Entry
1
Substrate
Mþ Yꢁ
Product
Catalyst
Time (h)
Product
convn (%)
Rf8(CH2)3Cl
convn (%)b
R
f8(CH2)3I
NaCl
R
f8(CH2)3Cl
Aliquat 336 (3)c
3.5
12
24
32
71
85
2
3
KCN
R
R
f8(CH2)3CN
1
2
78
91
7
7
NaOAc
f8(CH2)3OAc
1
3
24
18
26
54
11
5
7
4
R
R
f8(CH2)3Cl
f8(CH2)3I
KI
R
R
f8(CH2)3I
1
24
5
20
5d
NaCl
f8(CH2)3Cl
3
4
24
43
93
6d
7d
KCN
R
R
f8(CH2)3CN
2
98
2
NaOAc
f8(CH2)3OAc
2
3
73
82
6
5
8e
R
R
f8(CH2)3I
f8(CH2)3I
NaCl
R
f8(CH2)3Cl
n-Bu4Nþ Fꢁ$3H2O
n-Bu4Nþ Brꢁ
24
48
72
26
39
50
9e
NaCl
R
f8(CH2)3Cl
24
5
a
Conditions: Rf8(CH2)3I (0.20 mmol), Mþ Yꢁ (1.60 mmol), perfluoromethyldecalin (0.5 mL), water (0.5 mL), 4 (0.020 mmol).
This arises from the chloride counter anion of 3.
b
c
CH3(CH3(CH2)m)3Nþ Clꢁ, 2:1 m¼7/9.
d
e
As in a but without fluorous solvent; the substrate constitutes the fluorous phase, in which 3 is soluble (biphasic conditions).
The catalyst is a water soluble n-Bu4Nþ salt (biphasic conditions).

D. Mandal, J.A. Gladysz / Tetrahedron 66 (2010) 1070–1077
1075
established with the phosphonium salts,21 an aqueous/fluorous
liquid/liquid interface is not necessary. Therefore, interfacial
mechanisms are not required for phase transfer catalysis as in
Schemes 1 and 3. However, it should be noted that when simple
alkali metal halides are employed, the presence of an aqueous
phase is essential. Phase transfer across such fluorous liquid/solid
interfaces does not occur at detectable rates.
At the outset of this study, we did not anticipate that related
non-fluorous quaternary ammonium or phosphonium salts would
be effective phase transfer catalysts for reactions in fluorous media.
However, salts in which the heteroatom features at least three long
alkyl substituents are active under the triphasic conditions in
Scheme 5, in which the molten salt localizes between the lower
fluorous and upper aqueous layers. In this study, we have further
shown that less lipophilic onium cations, such as n-Bu4Nþ, afford
poor catalysts (entries 8 and 9, Table 2). Given the very low solu-
bility of 3 in perfluoromethyldecalin, we presume that the domi-
nant mode of catalysis involves an interfacial mechanism.
Interfacial phenomena can play substantial roles in organic/aque-
ous phase transfer catalysis, as elegantly summarized in a review.31
Although this unexpected observation is most deserving of further
study, it is beyond the scope of the present investigation.
Why is chemistry that can be carried out in fluorous solvents of
interest? Increasing attention is being given to remediation tech-
nologies that would involve sequestering toxic or hazardous com-
pounds in fluorous phases. A secondary objective then becomes the
processingof such substances into benign materials, and toward this
end the development of a wider vocabulary of reactions that can be
applied in very nonpolar fluorous phases is desirable. Note that
phase transfer catalysis allows a reactive species to access a new
phase, but does not irreversibly introduce new solutes in the usual
manner of a reagent. Thus, one avoids increasing the complexity of
what is often a ‘soup’ of hazardous and non-hazardous substances.
Finally, there are several additional ways in which fluorous
chemistrycan be exploited inphase transfer catalysis, as summarized
in a recent review.24 These include (1) the use of fluorous ammonium
salt X (Fig. 1) as a recoverable catalyst for organic/aqueous phase
transfer processes,9 (2) the use of fluorous aza/oxa crown ethers to
catalyze the reaction of n-C8H17Br and KI under liquid/solid biphase
conditions using the hybrid solvent CF3C6H5,22 and (3) the use of
fluorous oxa crown ethers to catalyze the same reaction in both
CF3C6H5 and chlorobenzene.23 The last study also described trans-
formations involving perfluoromethylcyclohexane as the host phase
for the crown ether catalyst (middle layer), n-C8H17Br or n-
C8H17OSO2CH3 as a second organic phase (neat reactant; upperlayer),
and KI or KCN as solid phases (lower layer). Effective recovery pro-
tocols were established for all of the fluorous crown ether systems.
In summary, this study, together with our previous full paper,21b
has opened up unanticipated new vistas for both phase transfer
catalysis and fluorous chemistry. Ionic displacement reactions are
easily conducted in extremely nonpolar fluorous media at 76–
100 ꢀC with either stoichiometric or catalytic quantities of fluorous
quaternary onium salts. Related non-fluorous onium salts are even
better catalysts, but appear to function interfacially. Future efforts
will be directed at expanding the scope of fluorous salts that exhibit
significant solubilities in fluorous media (Fig. 1), and other types of
applications for such substances.35
Figure 4. Conversion profiles for the reactions of Rf8(CH2)3I and KCN catalyzed by 3 (C;
entry 2, Table 2) and 1 (-; entry 3, Table 1) in perfluoromethyldecalin/water at 100 ꢀC.
Interestingly, when the fluorous solvent was omitted from the
reactions with 3 (entries 5–7, Table 2), conversions were even
faster. The alkyl halide now served as its own fluorous liquid phase,
and due to the high solubility of 3, only two phases were present.
The reaction with NaCl gave 93% conversion over 24 h, and that
with KCN showed complete consumption of the fluorous alkyl io-
dide within 2 h, with 98% conversion to the fluorous alkyl cyanide.
Even in the case of NaOAc, 82% conversion to the fluorous acetate
was evident after 3 h, when the experiment was terminated.
To better define the requirements for non-fluorous ammonium
salt catalysts, analogous experiments were carried out with shorter-
chained tetralkylammonium salts. Thus, entry 1 of Table 2 was re-
peated using 10 mol % of n-Bu4NþFꢁ$3H2O or n-Bu4Nþ Brꢁ in place of
3 (entries 8 and 9). Unlike 3, these are very water soluble (ꢂ600 g/L at
20 ꢀC from vendor data sheets), so the reactions were biphasic.
However, muchslowerconversionswereobserved(26–5%over24 h).
3. Discussion
Non-fluorous quaternary ammonium and phosphonium salts
can be regarded as the prototype organic/aqueous phase transfer
catalysts, dating back to the seminal studies of Starks.33 In some
cases, ammonium salts have been found to be slightly more active
catalysts than phosphonium salts,34 but they are also less stable in
reactions conducted at higher temperatures (except when hy-
droxide is the anion).19a,33 Similarly, we have now established that
fluorous quaternary ammonium and phosphonium salts are ex-
cellent aqueous/fluorous phase transfer catalysts for ionic dis-
placements in highly nonpolar fluorous solvents. We have
furthermore shown that the phosphonium salts can be recycled,
either by precipitation or adsorption onto TeflonÒ tape.21 Similar
protocols can likely be developed with 1 and 2, which exhibit the
necessary highly temperature dependent solubilities.
TheslowerreactionsinTable 1 provideunambiguouscomparisons
withpreviouslyreporteddata. Forexample, thatofRf8(CH2)3IandKCN
is faster when catalyzed by 1 (entry 3, Table 1) than the fluorous
phosphonium salt (Rf8(CH2)2)(Rf8(CH2)3)3Pþ Iꢁ (72% vs 17% conver-
sion after 24 h).21 However, that of Rf8(CH2)3I and NaOAc is slower
whencatalyzedby1(entry4,Table 1)thanthephosphoniumsalt(12%
vs 56% conversion after 24 h).21 Thus, the relative nucleophilicities of
the cyanide and acetate anions appear to invert in the two systems.
The stoichiometric transformations in Scheme 4 indicate that
fluorous quaternary ammonium halides can effect ionic displace-
4. Experimental section
4.1. General
Reactions were conducted under air unless noted. Chemicals were
treated as follows: hexanes, diethyl ether, and CF3C6H5 (ABCR, 99%),
simple distillation; CF3C6F5 (ABCR, 98%), passed through neutral
alumina and stored over molecular sieves; DMF, distilled from CaH2
ments wholly within
a fluorous liquid phase. As similarly

1076
D. Mandal, J.A. Gladysz / Tetrahedron 66 (2010) 1070–1077
and freeze/pump/thaw degassed; perfluoromethyldecalin (ABCR,
88%), Rf8(CH2)2I (ABCR, 97%), NaCl (Acros, 99.5%), KCN (Acros, 97%), KI
(Acros, 99%), n-Bu4Nþ Fꢁ$3H2O (Aldrich, 97%), n-Bu4Nþ Brꢁ (Acros,
þ99%), AliquatÒ 336 (Aldrich, CH3(CH3(CH2)m)3Nþ Clꢁ, m¼2:1 7/9
(3)), and resorcinol (Acros, 98%), used as received. For substitution
reactions, educts and authentic product samples were purchased
(above) or prepared by literature procedures (Rf8(CH2)3I,36
Rf8(CH2)3I (0.059 g, 0.100 mmol), 1 (0.021 g, 0.010 mmol), per-
fluoromethyldecalin (0.50 mL), NaCl (0.047 g, 0.80 mmol), and
water (0.50 mL). The vial was tightly sealed and the mixture vig-
orously stirred at 100 ꢀC for 24 h. Aliquots were taken from the
fluorous phase hourly and diluted with CDCl3, and 1H NMR spectra
were recorded. Data: Figure 2.
Rf8(CH2)3Br,37
Rf8(CH2)2Br,15
Rf8(CH2)3Cl,21b
Rf8(CH2)3CN,21b
4.1.4. Phase requirements. A (reaction without fluorous solvent;
Table 2, entry 1). A 4 mL vial was charged with Rf8(CH2)3I (0.059 g,
0.100 mmol), 1 (0.019 g, 0.010 mmol), NaCl (0.047 g, 0.80 mmol),
and water (0.50 mL). The vial was tightly sealed and the homoge-
neous mixture vigorously stirred at 100 ꢀC for 24 h. The sample was
cooled and CDCl3 was added. A 1H NMR spectrum of the CDCl3 layer
showed 90% conversion to Rf8(CH2)3Cl.
Rf8(CH2)3OAc21b).
NMR spectra were recorded on Bruker 300 or 400 MHz spec-
trometers at ambient probe temperatures, and referenced as fol-
lows: 1H, residual internal CHCl3, acetone-d5, or C6D5H (
d
7.24, 2.04,
or 7.16 ppm); 13C, internal CDCl3 or acetone-d6 (
d 77.0 or 29.8 ppm).
The highly coupled 13C signals of the fluorinated carbons are not
listed. Mass spectra were recorded on a Micromass Zabspec in-
strument. Elemental analyses were conducted on a Carlo Erba
EA1110 instrument. Melting points were determined using a SRS
MPA100 OptiMelt automated melting point system. DSC and TGA
data were recorded with a Mettler-Toledo DSC821 instrument and
treated by standard methods.38
B (reaction with hybrid solvent; Table 1, entry 8). A 4 mL vial was
charged with Rf8(CH2)3I (0.059 g, 0.100 mmol),
2 (0.019 g,
0.010 mmol), CF3C6H5 (0.50 mL), NaCl (0.047 g, 0.80 mmol), and
water (0.50 mL). The vial was tightly sealed and the heterogeneous
mixture vigorously stirred at 100 ꢀC. Aliquots were periodically
taken from the CF3C6H5 phase and diluted with CDCl3, and 1H NMR
spectra were recorded. Data: Table 1.
4.1.1. (Rf8(CH2)2)(Rf8(CH2)5)3Nþ Iꢁ (1). A Schlenk flask was charged
with (Rf8(CH2)5)3N (0.815 g, 0.550 mmol),25 Rf8(CH2)2I (0.471 g,
0.821 mmol), and DMF (2 mL). The mixture was stirred at 115 ꢀC for
24 h. The volatiles were removed at 100 ꢀC and 2ꢃ10ꢁ3 mbar. The
residue was washed with diethyl ether (2ꢃ4 mL) and dried by oil
pump vacuum to give 1 as a light yellow solid (0.882 g, 0.43 mmol,
78%). Capillary thermolysis data (OptiMelt monitoring): 110.5 ꢀC
(turns red; apparent phase change with some liquefaction),
139.0 ꢀC (clear point). DSC: stronger endotherm with Ti/Te/Tp/Tc/Tf
81.9/106.1/113.5/116.5/125.0 ꢀC; weaker endotherm with Ti/Te/Tp/
Tc/Tf 138.8/147.2/152.1/158.0/159.7 ꢀC. TGA: onset of 97% mass loss
(Ti), 157.9 ꢀC. Anal. Calcd for C49H34F68IN: C, 28.63; H, 1.67; N, 0.68.
Found: C, 28.97; H, 1.73; N, 0.87.
C (one phase stoichiometric reaction; Scheme 4). A 4 mL vial
was charged with Rf8(CH2)3Br (0.054 g, 0.10 mmol), 1 (0.205 g,
0.10 mmol), and perfluoromethyldecalin (0.25 mL). The vial was
tightly sealed and the homogeneous sample vigorously stirred at
100 ꢀC. Aliquots were removed hourly and diluted with CDCl3, and
1H NMR spectra were recorded. Data: Scheme 4. As noted in the
text, the corresponding reaction of Rf8(CH2)2I and
2 is not
homogeneous.
4.1.5. Representative substitution reactions with non-fluorous cata-
lysts. A (Table 2, entry 1). A 4 mL vial was charged with Rf8(CH2)3I
(0.118 g, 0.201 mmol), 3 (0.010 g, 0.023 mmol), perfluoromethyl-
decalin (0.50 mL), NaCl (0.095 g, 1.60 mmol), and water (0.50 mL).
The vial was tightly sealed and the mixture vigorously stirred at
100 ꢀC for 24 h. Aliquots were periodically taken from the CF3C6H5
phase and diluted with CDCl3, and 1H NMR spectra were recorded.
Data: Table 2.
B (Table 2, entry 6). A 4 mL vial was charged with Rf8(CH2)3I
(0.118 g, 0.201 mmol), 3 (0.010 g, 0.023 mmol), KCN (0.110 g,
1.69 mmol), and water (0.50 mL). The vial was tightly sealed and
the mixture vigorously stirred at 100 ꢀC for 4 h. A 1H NMR spectrum
(CDCl3) of an aliquot from the Rf8(CH2)3I phase showed a 98:2
NMR (d
): 1H (acetone-d6) 3.20 (br s, 6H), 2.33–2.18 (m, 8H), 2.03
(overlapped with acetone-d5, m, 8H), 1.89–1.87 (m, 2H), 1.73–1.66
(m, 6H), 1.60–1.54 (m, 6H), 1H (CF3C6F5/CDCl3) 3.08 (t, 6H), 2.15–
2.04 (m, 8H), 1.94 (br m, 6H), 1.72–1.67 (m, 8H), 1.52 (m, 6H);
2
13C{1H} (acetone-d6) 52.7 (CH2N), 47.0 (CH2N), 35.0 (t, JCF¼20 Hz
CH2CF2), 30.9, 30.4, 26.6, 23.5, 20.3. MS (3-NBA, FABþ) m/z: 1927
([(Rf8(CH2)2)(Rf8(CH2)5)3N]þ, 100%).
4.1.2. (Rf8(CH2)3)4Nþ Brꢁ (2). A Schlenk flask was charged with
(Rf8(CH2)3)3N (1.482 g,1.06 mmol),25 Rf8(CH2)3Br (0.866 g, 1.60 mmol),
and DMF (2 mL) under an inert atmosphere. The mixture was stirred
at 115 ꢀC for 24 h. The volatiles were removed at 100 ꢀC and
2ꢃ10ꢁ3 mbar. The residue was washed with hexane (5ꢃ4 mL) and
diethyl ether (2ꢃ4 mL) and dried by oil pump vacuum to give 2 as
a cream white solid (1.762 g, 0.909 mmol, 86%). Capillary thermolysis
data (OptiMelt monitoring): 115.8 ꢀC (darkening), 138.0 ꢀC (dec; for-
mation of black liquid). DSC: strong endotherm with Ti/Te/Tp/Tc/Tf
33.9/39.1/42.7/45.8/50.1 ꢀC; medium endotherm with Ti/Te/Tp/Tc/Tf
116.4/121.1/131.5/134.8/136.0 ꢀC; weak endotherm with Ti/Te/Tp/Tc/Tf
136.7/137.2/141.7/146.6/148.4 ꢀC. TGA: onset of 99% mass loss (Ti),
149.7 ꢀC. Anal. Calcd for C44H24BrF68N: C, 27.26; H, 1.25; N, 0.72.
Found: C, 27.20; H, 1.35; N, 0.76.
Rf8(CH2)3CN/Rf8(CH2)3Cl ratio (d 2.49/3.65 ppm, t, CH2X) and es-
sentially no Rf8(CH2)3I ( 3.23 ppm).
d
C (Table 2, entry 8). A 4 mL vial was charged with Rf8(CH2)3I
(0.118 g, 0.201 mmol), n-Bu4Nþ BrL (0.006 g, 0.02 mmol), per-
fluoromethyldecalin (0.50 mL), NaCl (0.094 g, 1.60 mmol), and
water (0.50 mL). The vial was tightly sealed and the mixture vig-
orously stirred at 100 ꢀC for 24 h. Aliquots were periodically taken
from the fluorous phase and diluted with CDCl3, and 1H NMR
spectra were recorded. Data: Table 2.
4.1.6. Solubility data. A. A flask was charged with 3 (0.030 g,
0.069 mmol), resorcinol standard (0.013 g, 0.118 mmol), and D2O
(1.0 mL). The sample was vigorously stirred at 24 ꢀC for 15 min.
Stirring was halted, and an aliquot of the supernatant was removed
and diluted with acetone-d6. The sample was stirred at 100 ꢀC. An
aliquot of the supernatant was similarly removed, and diluted with
acetone-d6. The 1H NMR spectra of both aliquots were recorded,
NMR (
d
): 1H (CF3C6F5þCDCl3 (capillary)): 2.71 (br s, 8H, NCH2),
2.24–2.11 (br m, 8H, CH2Rf8), 1.87 (br m, 8H, CH2CH2Rf8); 1H
(CF3C6F5þthree drops acetone-d6; external lock CDCl3 (capillary)):
2.83 (br t, 8H, 3JHH¼7 Hz, NCH2), 2.32 (br m, 8H, CH2Rf8), 1.99 (br m,
8H, CH2CH2Rf8); 13C{1H} (same solvent) 52.0 (s, CH2N), 28.2 (t,
2JCF¼22 Hz, CH2CF2), 20.7 (s, CH2CH2CF2). MS (3-NBA, FABþ) m/z:
1858 ([(Rf8(CH2)3)4N]þ, 60%), 1398 ([(Rf8(CH2)3)3NH]þ, 100%).
and the N-methyl signal of 3 (d 3.35 ppm, s, 3H) was integrated
versus the 2-CH signal of resorcinol (
text.
d 7.16 ppm, t, 1H). Data: see
B. A flask was charged with 3 (0.0384 g, 0.089 mmol), CF3C6H5
standard (0.0145 g, 0.101 mmol), and perfluoromethyldecalin
(0.50 mL). The sample was vigorously stirred at 24 ꢀC. Stirring was
4.1.3. Representative substitution reaction with fluorous catalysts
(Scheme 2; Table 1, entry 1). A 4 mL vial was charged with

D. Mandal, J.A. Gladysz / Tetrahedron 66 (2010) 1070–1077
1077
11. van den Broeke, J.; Winter, F.; Deelman, B.-J.; van Koten, G. Org. Lett. 2002, 4,
halted, and after the layer of 3 had separated, an aliquot from the
lower layer of perfluoromethyldecalin was removed and diluted
with C6D6. The sample was stirred at 100 ꢀC. An aliquot of the per-
fluoromethyldecalin layer was similarly removed, and diluted with
C6D6. The 1H NMR spectra of the aliquots were recorded, and the N-
methyl signal of 3 (see A) was integrated versus the CH signals of
CF3C6H5 (7.47–7.64 ppm, 5H). No signal was detected for 3 at 24 ꢀC,
so a solubility limit was assigned using a noise peak. Data: see text.
C. A flask was charged with 3 (0.0436 g, 0.101 mmol), CF3C6H5
standard (0.0145 g, 0.101 mmol), and Rf8(CH2)2I (0.2013 g,
0.351 mmol). The sample was stirred at 100 ꢀC, giving a single
phase. An aliquot was removed and diluted with CDCl3. The N-
methyl signal of 3 (see A) was integrated versus the CH signals of
CF3C6H5 (7.47–7.64 ppm, 5H), showing 0.089 mmol of 3 to be
present. Data: see text.
3851–3854.
ˇ
´
´
´ˇ
´
ˇ
´ˇ
12. Kysilka, O.; Ryba´ckova, M.; Skalicky, M.; Kvıcalova, M.; Cvacka, J.; Kvıcala, J. J.
Fluorine Chem. 2009, 130, 629–639.
13. (a) Merrigan, T. L.; Bates, E. D.; Dorman, S. C.; Davis, J. H., Jr. Chem. Commun.
2000, 2051–2052; (b) Heitzman, H.; Young, B. A.; Rausch, D. J.; Rickert, P.;
Stepinski, D. C.; Dietz, M. L. Talanta 2006, 69, 527–531; (c) Liu, C.; VanDerver, D.;
DesMarteau, D. D. Org. Lett. 2008, 10, 5565–5568 and references therein; (d)
Bara, J. E.; Gabriel, C. J.; Carlisle, T. K.; Camper, D. E.; Finotello, A.; Gin, D. L.;
Noble, R. D. Chem. Eng. J. 2009, 147, 43–50.
14. He, L.-N.; Yasuda, H.; Sakakura, T. Green Chem. 2003, 5, 92–94.
15. Emnet, C.; Weber, K. M.; Vidal, J. A.; Consorti, C. S.; Stuart, A. M.; Gladysz, J. A.
Adv. Synth. Catal. 2006, 348, 1625–1634.
´
´
´
16. (a) Vlad, G.; Richter, F.; Horvath, I. T. Org. Lett. 2004, 6, 4559–4561; (b) Vlad, G.;
Richter, F.; Horva´th, I. T. Tetrahedron Lett. 2005, 46, 8605–8608.
17. Boswell, P. G.; Anfang, A. C.; Bu¨hlmann, P. J. Fluorine Chem. 2008, 129, 961–967.
18. (a) Tindale, J. J.; Na, C.; Jennings, M. C.; Ragogna, P. J. Can. J. Chem. 2007, 85, 660–
667; (b) Tindale, J. J.; Ragogna, P. J. Chem. Commun. 2009, 1831–1833.
19. (a) Phase-Transfer Catalysis; Starks, C. M., Liotta, C. L., Halpern, M., Eds.; Chap-
man & Hall: New York, NY, 1994; (b) Makoszka, M. Pure Appl. Chem. 1975, 43,
439; (c) Yadav, G. D. Top. Catal. 2004, 29, 145–161.
20. Smith, M. B.; March, J. Advanced Organic Chemistry, 6th ed.; John Wiley & Sons:
New York, NY, 2007; p 574.
Acknowledgements
21. (a) Consorti, C. S.; Jurisch, M.; Gladysz, J. A. Org. Lett. 2007, 9, 2309–2312; (b)
Mandal, D.; Jurisch, M.; Consorti, C. S.; Gladysz, J. A. Chem. Asian J. 2008, 3,
1772–1782.
22. Stuart, A. M.; Vidal, J. A. J. Org. Chem. 2007, 72, 3735–3740.
23. (a) Pozzi, G.; Quici, S.; Fish, R. H. Adv. Synth. Catal. 2008, 350, 2425–2436; (b)
Pozzi, G.; Mihali, V.; Foschi, F.; Penso, M.; Quici, S.; Fish, R. H. Adv. Synth. Cat., in
press.
We thank the Welch Foundation (A-1656) and the Humboldt
Foundation (Fellowship to D.M.) for support. Some preliminary
experiments were conducted at the Universita¨t Erlangen-Nu¨rnberg.
References and notes
24. Review: Pozzi, G.; Quici, S.; Fish, R. H. J. Fluorine Chem. 2008, 129, 920–929.
25. Rocaboy, C.; Bauer, W.; Gladysz, J. A. Eur. J. Org. Chem. 2000, 2621–2628.
1. Freed, B. K.; Biesecker, J.; Middleton, W. J. J. Fluorine Chem. 1990, 48, 63–75.
2. Gladysz, J. A.; Emnet, C. Fluorous solvents and related media. In Handbook of
´
¨
´
26. (a) Kiss, L. E.; Rabai, J.; Varga, L.; Kovesdi, I. Synlett 1998, 1243–1245; (b) Szlavik,
´
Z.; Ta´rka´nyi, G.; Go¨mo¨ry, A.; Tarczay, G.; Ra´bai, J. J. Fluorine Chem. 2001, 108, 7–
´
Fluorous Chemistry; Gladysz, J. A., Curran, D. P., Horvath, I. T., Eds.; Wiley/VCH:
14; (c) Szabo´ , D.; Nemes, A.; Ko¨vesdi, I.; Farkas, V.; Hollo´ si, M.; Ra´bai, J. J.
Weinheim, 2004; pp 11–23.
´
´
Fluorine Chem. 2006, 127, 1405–1414; (d) Szabo, D.; Mohl, J.; Balint, A.-M.;
Bodor, A.; Ra´bai, J. J. Fluorine Chem. 2006, 127, 1496–1504.
3. (a) Temperature controlled catalyst recycling: new protocols based upon tem-
perature-dependent solubilities of fluorous compounds and solid–liquid phase
separations. Gladysz, J. A.; Tesevic, V. Top. Organomet. Chem. 2008, 23, 67–89;
(b) Gladysz, J. A. Catalysis involving fluorous phases: fundamentals and di-
rections for greener methodologies. In Handbook of Green Chemistry; Anastas, P.,
Crabtree, R. H., Eds.; Homogeneous Catalysis; Wiley/VCH: Weinheim, 2009; Vol.
1, pp 17–38.
4. (a) van den Broeke, J.; de Wolf, E.; Deelman, B.-J.; van Koten, G. Adv. Synth. Catal.
2003, 345, 625–635; (b) van den Broeke, J.; Lutz, M.; Kooijman, H.; Spek, A. L.;
Deelman, B.-J.; van Koten, G. Organometallics 2001, 20, 2114–2117.
5. (a) Boswell, P. G.; Bu¨hlmann, P. J. Am. Chem. Soc. 2005, 127, 8958–8959; (b)
Boswell, P. G.; Lugert, E. C.; Ra´bai, J.; Amin, E. A.; Bu¨hlmann, P. J. Am. Chem. Soc.
2005, 127, 16976–16984.
27. (a) Felling, K. W.; Lagow, R. J. J. Fluorine Chem. 2003, 123, 233–236; (b) Mol-
davskii, D. D.; Bispen, T. A.; Kaurova, G. I.; Furin, G. G. J. Fluorine Chem. 1999, 94,
157–167; (c) Meinert, H.; Fackler, R.; Mader, J.; Reuter, P.; Ro¨hlke, W. J. Fluorine
ˇ´
´
´
Chem. 1992, 59, 351–365; (d) Kapla´nek, R.; Brıza, T.; Havlık, M.; Martasek, P.;
Kra´l, V. J. Fluorine Chem. 2007, 128, 179–183.
28. Rocaboy, C.; Hampel, F.; Gladysz, J. A. J. Org. Chem. 2002, 67, 6863–6870.
29. Maul, J. J.; Ostrowski, P. J.; Ublacker, G. A.; Linclau, B.; Curran, D. P. Top. Curr.
Chem. 1999, 206, 79–105.
30. Gladysz, J. A. Ponytails: structural and electronic considerations. In Handbook of
Fluorous Chemistry; Gladysz, J. A., Curran, D. P., Horva´th, I. T., Eds.; Wiley/VCH:
Weinheim, 2004; pp 41–55.
31. Yang, H.-M.; Wu, H.-S. Catal. Rev. Sci. Eng. 2003, 45, 463–540.
32. Mikkola, J.-P.; Virtanen, P.; Sjo¨holm, R. Green Chem. 2006, 8, 250–255.
33. Starks, C. M. J. Am. Chem. Soc. 1971, 93, 195–199.
34. Landini, D.; Maia, A.; Montanari, F. J. Am. Chem. Soc. 1978, 100, 2796–2801.
35. Mandal, D. work in progress.
36. Vincent, J.-M.; Rabion, A.; Yachandra, V. K.; Fish, R. H. Can. J. Chem. 2001, 79,
888–895.
37. Sugiyama, K.; Nemoto, T.; Koide, G.; Hirao, A. Macromol. Symp. 2002, 181, 135–
153.
38. Cammenga, H. K.; Epple, M. Angew. Chem., Int. Ed. Engl. 1995, 34, 1171–1187;
Angew. Chem. 1995, 107, 1284–1301.
6. Rutherford, D. unpublished results, University of Utah (final research report,
March 1999).
7. Mercs, L.; Pozzi, G.; Quici, S. Tetrahedron Lett. 2007, 48, 3053–3056.
8. Maayan, G.; Fish, R. H.; Neumann, R. Org. Lett. 2003, 5, 3547–3550.
9. (a) Shirakawa, S.; Tanaka, Y.; Maruoka, K. Org. Lett. 2004, 6, 1429–1431; (b)
Shirakawa, S.; Ueda, M.; Tanaka, Y.; Hashimoto, T.; Maruoka, K. Chem. Asian J.
2007, 2, 1276–1281; (c) Hashimoto, T.; Sakata, K.; Maruoka, K. Angew. Chem., Int.
Ed. 2009, 48, 5014–5017; Angew. Chem. 2009, 121, 5114–5117.
10. (a) Shen, W.; Wang, L.-M.; Tian, H. J. Fluorine Chem. 2008, 129, 267–273; (b) See
also: Qiu, W. US Patent 6054615 (Filed May 27, 1997); Chem. Abstr. 2000, 132,
264882.