Horva´th, and others have recently prepared a number of
fluorous aliphatic phosphonium salts with “ponytails” of the
formula CF3(CF2)n-1(CH2)m (abbreviated Rfn(CH2)m).5-7 Since
non-fluorous phosphonium salts are effective phase transfer
catalysts for anionic displacement reactions in organic
solvents,1 we thought that fluorous phosphonium salts might
catalyze analogous reactions in fluorous solvents. In this
Letter, we report that Finkelstein-type reactions8 of fluorous
aliphatic halides can be catalyzed by fluorous phosphonium
salts in fluorous solvents at moderate temperatures, and that
even non-fluorous phosphonium salts are effective under
related conditions. Additional types of fluorous phase transfer
catalysts have been developed for other applications, as
detailed below.9
other alkyl halides, which feature fewer methylene groups
or less polarizable halides, should be somewhat more
fluorophilic. None of the alkyl halides exhibit detectable
solubility in water.
In the first series of experiments, a 0.68 M solution of
Rf8(CH2)3I in CF3C6F11 and excess solid NaCl were stirred
at 76 °C. After 24 h, no reaction could be detected, as assayed
1
by H NMR (aliquot with added CDCl3; the CH2X signals
(t) for all of the fluorous alkyl halides are well-separated).
A similar experiment was conducted, but using a nearly
saturated 5.13 M aqueous solution of NaCl (88:12 NaCl/
Rf8(CH2)3I mol ratio). After 24 h, no reaction could be
detected.
Next, analogous liquid/liquid biphase experiments were
conducted, but in the presence of 10 mol % of the
phosphonium salts 1, 2, and 3. These are insoluble in water,
sparingly soluble in fluorous solvents at room temperature,
and highly soluble in fluorous solvents at elevated temper-
atures.5 The conditions are summarized in Scheme 1. Per
The fluorous phosphonium iodide and bromide salts
(Rf8(CH2)2)(Rf6(CH2)2)3P+ I- (1), (Rf8(CH2)2)4P+I - (2), and
(Rf8(CH2)2)(Rf6(CH2)2)3P+ Br- (3) shown in Scheme 1 were
1
entries 1-3 of Table 1, H NMR spectra showed 90-93%
Scheme 1. Phase Transfer Catalysis of Halide Substitution
Reactions in Fluorous Media
Table 1. Data for Halide Substitution Reactions Catalyzed by
Fluorous Phosphonium Salts under the Conditions of Scheme 1a
en-
tryb substrate M+ Y- X-
R4P+
temp time convn
product
(°C) (h)
(%)
1
2
3
4c
Rf8(CH2)3I
NaCl
NaCl
NaCl
NaCl
1
2
3
1
Rf8(CH2)3Cl
76
76
76
72
72
72
24
93
90
91
95
100
5
Rf8(CH2)3Cl KI
1
Rf8(CH2)3l
100
24
48
120
36
61
87
6
7
Rf8(CH2)2l
NaCl
1
1
Rf8(CH2)2Cl 100
Rf8(CH2)2Br 100
24
48
120
24
48
120
26
37
71
42
53
79
NaBr
8
Rf8(CH2)2Br KI
1
1
Rf8(CH2)2I
100
24
48
120
43
77
92
67
9d
NaCl
Rf8(CH2)2Cl 100 120
a Conditions: Rf8(CH2)mX (0.34 mmol), M+ Y- (2.56 mmol), fluorous
solvent (0.5 mL), water (0.5 mL), R4P+ X- (0.034 mmol). b The reactions
in entries 1-3 were conducted in CF3C6F11. All others were conducted in
perfluoromethyldecalin (CF3C10F17). c For the time profile of a duplicate
run, see Figure 2. d For the time profile, see Figure 1.
prepared as described previously.5 Two types of fluorous
alkyl halidessthe “three methylene spacer” substrates Rf8-
(CH2)3I and Rf8(CH2)3Cl and “two methylene spacer”
substrates Rf8(CH2)2I and Rf8(CH2)2Brswere obtained as
described in the Supporting Information. The CF3C6F11/
toluene partition coefficient of Rf8(CH2)3I is 50.7:49.3;10 the
conversions to the fluorous alkyl chloride Rf8(CH2)3Cl after
24 h at 76 °C. For entry 3, no further conversion was noted
after three weeks. These data are interpreted as phase transfer
catalysis of ionic displacement reactions in the fluorous
phase, as supported by additional results below.
Workup of entry 3 gave a 92% yield of a 93:7 Rf8(CH2)3-
Cl/Rf8(CH2)3I mixture, as assayed by NMR. When entries
1-3 were repeated in the absence of water, no reaction
occurred. The NaCl remained undissolved. Hence, solid/
(5) Emnet, C.; Weber, K. M.; Vidal, J. A.; Consorti, C. S.; Stuart, A.
M.; Gladysz, J. A. AdV. Synth. Catal. 2006, 348, 1625.
(6) (a) Vla´d, G.; Richter, F.; Horva´th, I. T. Org. Lett. 2004, 6, 4559. (b)
Vla´d, G.; Richter, F.; Horva´th, I. T. Tetrahedron Lett. 2005, 46, 8605.
(7) See also: Tindale, J. J.; Na, C.; Jennings, M. C.; Ragogna, P. J. Can.
J. Chem. 2007, 85, DOI 10.1139/v07-035.
(8) Smith, M. B.; March, J. AdVanced Organic Chemistry; Wiley: New
York, 2001; p 517.
(9) Shirakawa, S.; Tanaka, Y.; Maruoka, K. Org. Lett. 2004, 6, 1429.
(10) Rocaboy, C.; Rutherford, D.; Bennett, B. L.; Gladysz, J. A. J. Phys.
Org. Chem. 2000, 13, 596.
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Org. Lett., Vol. 9, No. 12, 2007