1012
PAPER
Efficient Syntheses of Fluorous Primary Phosphines that Do Not Require PH3
Ef icentSynthes ofFluor usPrimaryPhosphinesthatDoNotRequirePH3 Emnet, J. A. Gladysz*
Charlotte
Institut für Organische Chemie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Henkestrasse 42, 91054 Erlangen, Germany
Fax +49(9131)8526865; E-mail: gladysz@organik.uni-erlangen.de
Received 12 November 2004
Key words: phosphines, phosphonates, Arbuzov reaction, fluorous, partition coefficients
Introduction
In the decade following the initial report of fluorous catalysis,1 a variety of processes have been developed.2,3 Many
have involved metal complexes of fluorous phosphines.4–6 However, there are also numerous reactions catalyzed by phosphines alone, which constitute part of the
growing field of ‘organocatalysis’.7 The applicability of
fluorous phosphines to such transformations has also been
demonstrated.8 These and other factors have spawned
great interest in their efficient synthesis. Both aliphatic
and aromatic systems, as well as diphosphines and mixed
bidentate donor ligands, have received attention.6,9
Many of the routes developed to fluorous aliphatic phosphines employ PH3. One subset involves free-radical
chain additions to fluorous terminal alkenes
Rfn(CH2)mCH = CH2 [Rfn = CF3(CF2)n–1],1,10 as exemplified in Scheme 1 (top). Such reactions are ideal from the
standpoint of atom economy. However, PH3 is a toxic gas,
difficult to handle, and expensive in small quantities.11 It
often contains traces of P2H4, which promotes spontaneous ignition in air.
Although we have had much success with such additions,10 we have also sought to develop alternative syntheses that might be more easily implemented in other
laboratories. Furthermore we required convenient routes
to fluorous primary phosphines Rfn(CH2)mPH2, which
cannot be prepared in high yields from PH3 and fluorous
alkenes due to rapid reactions of the remaining phosphorus-hydrogen bonds. These are versatile building blocks
for a variety of targets, such as unsymmetrically-substituted fluorous tertiary phosphines.10b In earlier work, we reported the procedure shown in Scheme 1 (bottom),10b
involving the condensation of LiPH2·DME with fluorous
primary alkyl iodides Rfn(CH2)mI. However, LiPH2·DME
must be synthesized from PH3, and therefore presents the
same disadvantages.
Thus, our attention was drawn to the Arbuzov reaction.12
With sufficiently electrophilic alkyl halides, this constitutes a reliable method for introducing phosphorus-carbon
bonds. The resulting phosphonate esters RP(O)(OR¢)2 are
easily reduced to primary phosphines.13 Although such sequences suffer from the standpoint of atom economy, they
are definitely safer, especially for researchers less familiar
with handling PH3. In this paper, we report the convenient
Initiator
>3
PH3
Rfn
85–90 °C
PH2
rapid
P
Rfn
Rfn
3
n = 6, 75%
n = 8, 70%
n = 10, 63%
Rfn = (CF2)n-1CF3
Rf8
n-BuLi
LiPH2⋅DME
PH3
THF, –45 °C
DME, –78 °C
91%
Scheme 1
I
m
Some previous syntheses of fluorous phosphines
SYNTHESIS 2005, No. 6, pp 1012–1018xx. 205
Advanced online publication: 14.02.2005
DOI: 10.1055/s-2005-861815; Art ID: Z21404SS
© Georg Thieme Verlag Stuttgart · New York
Rf8
PH2
m
m = 2, 48%, (6)
m = 3, 76%, (7)
m = 4, 75%
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Abstract: Arbuzov reactions of the fluorous primary iodides
Rfn(CH2)mI [Rfn = CF3(CF2)n–1; n/m = 6/2, 8/2, 8/3, 10/2] and
P(OEt)3 (excess, 160 °C) give the fluorous phosphonates
Rfn(CH2)mP(O)(OEt)2 (56–59%), which are reduced with LiAlH4 to
the title compounds Rfn(CH2)mPH2 (62–78%). Fluorophilicities
(CF3C6F11/toluene partition coefficients) increase with the length of
the Rfn moiety, decrease with the length of the (CH2)m moiety, and
decrease in the functional group sequence Rfn(CH2)mNH2 >
Rfn(CH2)mPH2 > Rfn(CH2)mP(O)(OEt)2.
PAPER
Efficient Syntheses of Fluorous Primary Phosphines that Do Not Require PH3
1013
O
P(OEt)3
Rfn
I
m
n/m
Rfn
–EtI
Rfn(CH2)mP(O)(OEt)2
LiAlH4
P(OEt)2
Et2O, r.t.
m
Rfn(CH2)mPH2
Rfn
PH2
m
overall yield
6/2
1, 57%
5, 78%
44%
8/2
2, 56%
6, 71%
40%
8/3
3, 57%
7, 66%
38%
10/2
4, 59%
8, 62%
37%
New route to fluorous primary phosphines
syntheses of fluorous primary phosphonates and phosphines depicted in Scheme 2. Alternative syntheses of
and/or patent literature pertaining to the phosphonates are
described in the discussion section.14–19
Results
The ‘two-methylene-spacer’ fluorous alkyl iodides in
Scheme 2 – Rf6(CH2)2I, Rf8(CH2)2I, and Rf10(CH2)2I –
were obtained from commercial sources. The ‘threemethylene-spacer’ iodide Rf8(CH2)3I was synthesized
from Rf8I and allyl alcohol via a simple published sequence.20 Each educt was treated with a five-fold excess
of P(OEt)3 without solvent at 160 °C. After 16 hours,
chromatographic workups gave the corresponding fluorous phosphonates Rfn(CH2)mP(O)(OEt)2 (n/m = 6/2, 1; 8/
2, 2; 8/3, 3; 10/2, 4) in 56–59% yields and analytically
pure form. The Rf6 and Rf8 compounds (1–3) were colorless oils, and the Rf10 compound (4) a waxy white solid. In
each case, the phosphonate resulting from an Arbuzov reaction of the liberated ethyl iodide, EtP(O)(OEt)2, also
formed. Reactions could be conducted on 25 g scales
without difficulty.
The fluorous phosphonates were characterized by NMR
(1H, 13C, 31P, 19F) spectroscopy, IR spectroscopy, and
mass spectrometry, as summarized in the experimental
section. The mass spectra displayed strong molecular
ions. The 13C NMR spectra showed characteristic doublets for the PCH2 signals (1JCP = 143–147 Hz), with
chemical shifts of the two-spacer compounds (1, 2, 4; 17.1
ppm) upfield of the three-spacer compound (3; 25.0 ppm).
The two-spacer compounds exhibited additional couplings to fluorine (3JCF = 4 Hz). The 31P{1H} NMR spectra showed singlets at 29.5–29.4 ppm (1, 2, 4) or 31.2 ppm
(3), and 19F NMR spectra exhibited the expected patterns.21 The phosphonates were soluble in a broad spectrum of non-fluorous solvents (hexane, toluene, Et2O,
CHCl3, THF, CF3C6H5), as well as CF3C6F11 [perfluoro(methylcyclohexane) or PFMC].
Next, phosphonates 1–4 were treated with LiAlH4 in Et2O
at room temperature. Workup and vacuum distillation
gave the target fluorous primary phosphines
Rfn(CH2)mPH2 (n/m = 6/2, 5; 8/2, 6; 8/3, 7; 10/2, 8) in 62–
78% yields in analytically pure form. The overall yields
(37–44%) could be increased somewhat by using crude
unchromatographed 1–4 as described in the experimental
section. Reactions could be conducted on 14 g scales
without difficulty. The Rf6 and Rf8 compounds (5–7) were
air-sensitive colorless liquids, and the Rf10 compound (8)
was a white solid (mp 58–59 °C) that could be kept in air
for several days.
The fluorous phosphines exhibited solubility profiles
comparable to those of the phosphonates, and were similarly characterized. The 1H NMR spectra showed PH2 signals at 2.76–2.67 ppm that were strongly coupled to
phosphorus (1JHP = 190–192 Hz). The 31P NMR spectra
exhibited signals at –138.1 ppm (5, 6, 8) or –141.2 ppm
(7) with analogous proton couplings. The 13C NMR spectra showed doublets for the PCH2 signals, but the 1JCP values (10–12 Hz) were much smaller than those of
phosphonates 1–4. The mass spectrum of 8 showed the
molecular ion for the corresponding phosphine oxide.
Data for 6 and 7 agreed well with that reported previously.10b
We sought to quantify the fluorous-phase affinities of the
compounds in Scheme 2. Thus, the CF3C6F11/toluene partition coefficients were measured by 1H NMR as described in the experimental section. Results are
summarized in Table 1, together with some previously reported values for reference compounds. These data are interpreted below.
Discussion
The sequence in Scheme 2 exploits the unique status of
P(OEt)3 as an inexpensive and readily available monofunctionalizable building block for the synthesis of organophosphorus compounds. Many literature syntheses of
fluorous and non-fluorous phosphines involve reactions
of PAr3–xClx or PR3–xClx species with organozinc, organolithium, or Grignard reagents.22 However, in the case of
PCl3, good yields of monosubstituted derivatives ArPCl2
or RPCl2 can only be obtained with very bulky groups.23
Although this problem is often avoided with (Et2N)2PCl,
longer sequences are then required.24 Furthermore, fluo-
Synthesis 2005, No. 6, 1012–1018
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Scheme 2
160 °C
Table 1
Entry
PAPER
C. Emnet, J. A. Gladysz
and P(OEt)3 are mentioned in a recent patent,14 but the
phosphonates 1 and 2 were directly used for further chemistry without characterization.15 Methyl and isopropyl analogs of the ethyl ester 2 have also been noted.16
Phosphonates 1, 2, and 4 were also claimed in a patent describing free radical additions of phosphonic acid diesters
HP(O)(OR)2 to fluorous alkenes.17 However, only syntheses of methyl and isobutyl esters were described, with no
characterization.
Summary of Partition Coefficients
Analyte
CF3C6F11/Toluene
1
EtP(O)(OEt)2
<1:>99a,b
2
Rf6(CH2)2P(O)(OEt)2 (1)
22:78c
3
Rf8(CH2)2P(O)(OEt)2 (2)
38:62d
4
Rf8(CH2)3P(O)(OEt)2 (3)
24:76c
5
Rf10(CH2)2P(O)(OEt)2 (4)
50:50a
The syntheses in Scheme 3 have been detailed in the open,
peer-reviewed literature. Scheme 3a shows an alternative
approach to two-spacer systems such as 1.18 This nickelcatalyzed conjugate addition utilizes a commercially
available vinyl phosphonate. Scheme 3b depicts an alternative approach to three-spacer systems such as 3.19 This
addition/deiodination sequence utilizes a commercially
available allyl phosphonate. A similar strategy is used to
access the starting iodide Rf8(CH2)3I in Scheme 2. Hence,
the two methods have about the same number of steps,
and overall yields are comparable.
a
6
Rf6(CH2)2PH2 (5)
53:47
7
Rf8(CH2)2PH2 (6)
64:36e
8
Rf8(CH2)3PH2 (7)
60:40a
9
Rf10(CH2)2PH2 (8)
74:26e
10
Rf8(CH2)3NH2
70.0:30.0f
11
[Rf6(CH2)2]3P
98.8:1.2e,10a
12
[Rf8(CH2)2]3P
>99.7:<0.3e,10a
13
[Rf8(CH2)3]3P
98.8:1.2e,10a
14
[Rf10(CH2)2]3P
>99.7:<0.3e,10a
a
Data at 25 °C.
EtP(O)(OEt)2 and CF3C6F11 are immiscible at r.t.
c
Data at 23 °C.
d
Data at 22 °C.
e
Data at 27 °C.
f
Data at 24 °C.27
b
rous Grignard or lithium reagents are frequently difficult
to generate and can show poor stability.25
As noted in the introduction, there is existing literature for
some of the fluorous phosphonates, or closely related
compounds. Arbuzov reactions of Rfn(CH2)2I (n = 6, 8)
O
a)
Rf6Cl +
P(OEt)2
The partition coefficients in Table 1 show several now-familiar patterns.26 First, fluorophilicities increase as the
lengths of the Rfn segments are increased (entries 2, 3, 5
and 6, 7, 9). Second, fluorophilicities decrease as the
lengths of the methylene spacers are increased (entries 3,
4 and 7, 8). Third, monofunctional organic compounds
with a single Rf6, Rf8, or Rf10 segment are not very fluorophilic.26 Thus, the phosphonates preferentially partition
into the toluene phase, except for the Rf10 compound 4.
When they are reduced to phosphines 5–8, two non-fluorous ethoxy groups (and an oxygen atom) are jettisoned.
Hence, fluorophilicities increase by 24–36%, and all
phosphines preferentially partition into the CF3C6F11
phase.
However, as illustrated by entries 11–14 of Table 1, additional pony tails must be introduced to achieve high fluo-
Zn (1.5 equiv)
NiCl2 (10 mol%)
PPh3 (40 mol%)
DMF, 100 °C, N2
O
P(OEt)2
Rf6
1, 71%
I
O
b)
RfnI
+
P(OEt)2
Na2S2O4
Rfn
O
P(OEt)2
CH2Cl2/H2O, 40 °C
n = 6, 8
n = 6, 98%; 8, 89%
Zn/EtOH
110 °C
O
Rfn
P(OEt)2
n = 6, 75%; 8 (3), 75%
Scheme 3
Alternative syntheses of fluorous phosphonates
Synthesis 2005, No. 6, 1012–1018
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1014
Efficient Syntheses of Fluorous Primary Phosphines that Do Not Require PH3
rous phase affinities. A number of fluorous primary,
secondary, and tertiary amines have been synthesized, and
show similar trends.27 One, Rf8(CH2)3NH2, can be directly
compared with 7 (entry 10 vs. 8). As expected, the smaller
and less polarizable amino group confers a higher fluorophilicity.26 The NMR method employed in this study is
not considered as accurate as the GC assay used in entries
10–14. Hence, the new partition coefficients have fewer
significant digits.
In summary, a simple and convenient synthesis of fluorous primary phosphines has been developed that avoids
PH3 or PH3-derived reagents. It therefore constitutes a less
hazardous and more student-friendly protocol than existing methods.10b Given the broad generality of the Arbuzov
reaction with respect to primary halides,12 it can be expected that numerous other fluorous phosphonates and
phosphines can be similarly synthesized. Our data furthermore establish that fluorophilicities decrease in the functional group sequence Rfn(CH2)mNH2 > Rfn(CH2)mPH2 >
Rfn(CH2)mP(O)(OEt)2. Some applications of the primary
fluorous phosphines 6 and 7 in syntheses of fluorous tertiary phosphines have been reported,10b and new applications in the synthesis of fluorous secondary phosphines
will be described in the near future.28
1015
1
H NMR (CDCl3): d = 4.13–4.00 (m, 4 H, CH2CH3), 2.40–2.20 (m,
2 H, CH2CF2), 1.96–1.84 (m, 2 H, PCH2), 1.26 (t, 3JHH = 7 Hz, 6 H,
CH2CH3).
13
C{1H} NMR (CDCl3): d = 62.1 (d, 2JCP = 6 Hz, CH2CH3), 25.1 (t,
JCF = 24 Hz, CH2CF2), 17.1 (dt, 1JCP = 147 Hz, 3JCF = 4 Hz, PCH2),
16.2 (d, 3JCP = 6 Hz, CH2CH3).
2
31
P{1H} NMR (CDCl3): d = 29.4 (s).
19
F NMR (CDCl3): d = –77.3 (t, 3JFF = 10 Hz, 3 F, CF3), –111.9
(pseudo quint., JFF = 15 Hz, 2 F), –118.5 (m, 2 F), –119.4 (m, 2 F),
–119.9 (m, 2 F), –122.7 (m, 2 F).
MS (positive FAB, 3-NBA): m/z (%) = 485 ([M + H]+, 100), 429
(79).
Anal. Calcd for C12H14F13O3P: C, 29.77; H, 2.91. Found: C, 29.28;
H, 3.14.
Rf8(CH2)2P(O)(OEt)2 (2)
P(OEt)3 (37.4 mL, 36.2 g, 218 mmol) and Rf8(CH2)2I (25.000 g,
43.554 mmol) were combined in a procedure analogous to that for
1. An identical workup (SiO2 column: 674 g, ∅ 9.7 cm)30 gave 2 as
a colorless oil (14.215 g, 24.341 mmol, 56%).
Bp 98 °C, 0.020 Torr.
IR (oil film): 2991 (w), 1235 (s), 1200 (s), 1146 (s), 1023 (s), 961
(m) cm–1.
1
H NMR (CDCl3): d = 4.15–4.02 (m, 4 H, CH2CH3), 2.42–2.20 (m,
2 H, CH2CF2), 1.98–1.86 (m, 2 H, PCH2), 1.29 (t, 3JHH = 7 Hz, 6 H,
CH2CH3).
Fluorous primary phosphines were synthesized under N2 atmospheres. Et2O, toluene, and THF were distilled from Na/benzophenone unless being used for chromatography (simple distillation).
Other materials were treated as follows: CF3C6F11 (ABCR, 90%)
and CH2Cl2, distilled from CaH2; CF3C6H5 (ABCR, 99%), distilled
and degassed; water, degassed; CDCl3 (Deutero GmbH, 99.8%),
THF-d8 (Acros, 99.5%), C6F6 (Aldrich, 99.5+%), P(OEt)3 (Fluka,
95%), Rf6(CH2)2I, Rf8(CH2)2I, Rf10(CH2)2I (3 × Lancaster, 97%),
LiAlH4 (Acros, 95%), used as received; Rf8(CH2)3I, synthesized as
described previously.20
C{1H} NMR (CDCl3): d = 62.1 (d, 2JCP = 6 Hz, CH2CH3), 25.2 (t,
JCF = 24 Hz, CH2CF2), 17.1 (dt, 1JCP = 147 Hz, 3JCF = 4 Hz, PCH2),
16.3 (d, 3JCP = 6 Hz, CH2CH3).
NMR spectra were recorded on a Bruker Avance 300 MHz spectrometer at 27.0 °C in CDCl3 or THF-d8 and referenced as follows:
1
H, residual internal CHCl3 (d = 7.24 ppm) or THF-d7 (d = 3.58
ppm); 13C, internal CDCl3 (d = 77.0 ppm) or THF-d8 (d = 25.5
ppm); 31P, external H3PO4 (d = 0.00 ppm); 19F, internal C6F6 (d =
–162.0 ppm). The highly coupled 13C signals of the fluorinated carbons are not listed below. IR and mass spectra were recorded on
ASI React-IR 1000 and Micromass Zabspec instruments, respectively. DSC and TGA data were recorded with a Mettler-Toledo
DSC821 apparatus and treated by standard methods.29 Elemental
analyses were conducted on a Carlo Erba EA1110 instrument.
Anal. Calcd for C14H14F17O3P: C, 28.78; H, 2.42. Found: C, 28.50;
H, 2.53.
Rf6(CH2)2P(O)(OEt)2 (1)
A round-bottom flask was charged with P(OEt)3 (20.0 mL, 19.4 g,
117 mmol) and Rf6(CH2)2I (10.934 g, 23.068 mmol), and fitted with
a distillation head. The mixture was stirred at 160 °C for 16 h, during which time most of the EtI distilled off. The mixture was cooled
somewhat, and a vacuum applied. The excess P(OEt)3 (bp 80 °C, 23
Torr) was removed, followed by the byproduct EtP(O)(OEt)2 (bp
106–110 °C, 23 Torr). The remaining light yellow oil was chromatographed on SiO2 (14.0 g, ∅ 2.5 cm) with toluene and then toluene–Et2O (1:1, v/v).30 Solvent was removed from the productcontaining fractions by rotary evaporation to give 1 as a colorless oil
(6.356 g, 13.13 mmol, 57%).
13
2
31
P{1H} NMR (CDCl3): d = 29.5 (s).
19
F NMR (CDCl3): d = –77.6 (t, 3JFF = 10 Hz, 3 F, CF3), –112.0
(pseudo quint., JFF = 15 Hz, 2 F), –118.5 (m, 6 F), –119.4 (m, 2 F),
–120.0 (m, 2 F), –122.9 (m, 2 F).
MS (positive FAB, 3-NBA): m/z (%) = 586 ([M + 2H]+, 100), 530
(73).
Rf8(CH2)3P(O)(OEt)2 (3)
P(OEt)3 (5.2 mL, 5.0 g, 30 mmol) and Rf8(CH2)3I (3.560 g, 6.056
mmol) were combined in a procedure analogous to that for 1. An
identical workup (SiO2 column: 8.3 g, ∅ 2.5 cm)30 gave 3 as a colorless oil (2.064 g, 3.452 mmol, 57%). An analytical sample was
distilled.
Bp 115 °C, 0.020 Torr.
IR (oil film): 2989 (w), 1237 (s), 1200 (s), 1146 (s), 1028 (s), 961
(m) cm–1.
1
H NMR (CDCl3): d = 4.14–4.00 (m, 4 H, CH2CH3), 2.25–2.08 (m,
2 H, CH2CF2), 1.97–1.72 (m, 4 H, PCH2CH2), 1.28 (t, 3JHH = 7 Hz,
6 H, CH2CH3).
13
C{1H} NMR (CDCl3): d = 61.7 (d, 2JCP = 6 Hz, CH2CH3), 31.1
(dt, 3JCP = 15 Hz, 2JCF = 22 Hz, CH2CF2), 25.0 (d, 1JCP = 143 Hz,
PCH2), 16.2 (d, 3JCP = 6 Hz, CH2CH3), 14.0 (pseudo q,
2
JCP = 3JCF = 5 Hz, PCH2CH2).
31
P{1H} NMR (CDCl3): d = 31.2 (s).
19
Bp 60 °C, 0.21 Torr.
F NMR (CDCl3): d = –77.5 (t, 3JFF = 10 Hz, 3 F, CF3), –111.2
(pseudo quint., JFF = 15 Hz, 2 F), –118.4 (m, 6 F), –119.4 (m, 2 F),
–120.2 (m, 2 F), –122.8 (m, 2 F).
IR (oil film): 2991 (w), 1235 (s), 1193 (s), 1143 (s), 1023 (s), 965
(s) cm–1.
MS (positive FAB, 3-NBA): m/z (%) = 599 ([M + H]+, 100), 543
(63).
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PAPER
1016
PAPER
C. Emnet, J. A. Gladysz
Anal. Calcd for C15H16F17O3P: C, 30.12; H, 2.70. Found: C, 29.90;
H, 2.77.
13
C{1H} NMR (THF-d8): d = 35.4 (t, 2JCF = 22 Hz, CH2CF2), 5.6
(dt, 1JCP = 12 Hz, 3JCF = 4 Hz, PCH2).
31
P NMR (THF-d8): d = –138.1 (t of pseudo quint., 1JPH = 192 Hz,
JPH = 4 Hz).
2
19
F (THF-d8): d = –77.2 (t, 3JFF = 10 Hz, 3 F, CF3), –110.9 (pseudo
quint., 2 F), –117.8 (m, 6 F), –118.7 (m, 2 F), –119.4 (m, 2 F),
–122.2 (m, 2 F).
Bp 121 °C, 0.029 Torr; mp 48.0 (DSC, Te); TGA: onset of a 98%
mass loss 120.2 °C.
Anal. Calcd for C10H6F17P: C, 25.02; H, 1.26. Found: C, 24.98; H,
1.25.
IR (powder film): 2988 (w), 1204 (s), 1150 (s), 1023 (s), 965 (m)
cm–1.
Rf8(CH2)3PH2 (7)
LiAlH4 (0.143 g, 3.76 mmol), Et2O (40.0 mL), and 3 (1.649 g, 2.758
mmol)30 in Et2O (5.0 mL) were combined in a procedure analogous
to that for 5. A similar workup (Et2O extraction 3 × 20 mL; distillation) gave 7 as a colorless liquid (0.903 g, 1.83 mmol, 66%).
1
H NMR (CDCl3): d = 4.17–4.04 (m, 4 H, CH2CH3), 2.44–2.24 (m,
2 H, CH2CF2), 2.01–1.89 (m, 2 H, PCH2), 1.31 (t, 3JHH = 7 Hz, 6 H,
CH2CH3).
13
C{1H} NMR (CDCl3): d = 62.1 (d, 2JCP = 6 Hz, CH2CH3), 25.2 (t,
JCF = 24 Hz, CH2CF2), 17.1 (dt, 1JCP = 147 Hz, 3JCF = 4 Hz, PCH2),
16.2 (d, 3JCP = 6 Hz, CH2CH3).
2
31
P{1H} NMR (CDCl3): d = 29.5 (s).
Bp 122 °C, 57 Torr.
1
H NMR (THF-d8): d = 2.67 (dm, 1JHP = 190 Hz, 2 H, PH2), 2.32–
2.16 (m, 2 H, CH2CF2), 1.89–1.73 and 1.65–1.53 (2 m, 2 × 2 H,
PCH2CH2).
19
F NMR (CDCl3): d = –77.4 (t, 3JFF = 10 Hz, 3 F, CF3), –111.9
(pseudo quint., JFF = 15 Hz, 2 F), –118.3 (m, 10 F), –119.3 (m, 2 F),
–119.9 (m, 2 F), –122.7 (m, 2 F).
13
MS (positive FAB, 3-NBA): m/z (%) = 685 ([M + H]+, 100), 629
(43).
31
Anal. Calcd for C16H14F21O3P: C, 28.09; H, 2.06. Found: C, 27.47;
H, 2.30.
19
F NMR (THF-d8): d = –77.2 (t, 3JFF = 10 Hz, 3 F, CF3), –110.2
(pseudo quint., JFF = 14 Hz, 2 F), –117.8 (m, 6 F), –118.7 (m, 2 F),
–119.4 (m, 2 F), –122.2 (m, 2 F).
Rf6(CH2)2PH2 (5)
A Schlenk flask was charged with LiAlH4 (0.619 g, 16.3 mmol) and
Et2O (100 mL), and cooled to 0 °C. A solution of 1 (4.564 g, 9.429
mmol)30 in Et2O (3.0 mL) was added dropwise with stirring. The
mixture was stirred at r.t. for 16 h, and cooled again to 0 °C. Water
was slowly added with stirring until a white precipitate had formed.
The ethereal layer was separated, and the precipitate was extracted
with Et2O (3 × 30 mL). The combined ethereal layers were dried
(MgSO4), and the solvent was removed under partial membrane
pump vacuum. The light yellow residue was distilled to give 5 as a
colorless liquid (2.785 g, 7.329 mmol, 78%).
Bp 79 °C, 59 Torr.
1
H NMR (THF-d8): d = 2.76 (dm, 1JHP = 192 Hz, 2 H, PH2), 2.50–
2.27 (m, 2 H, CH2CF2), 1.79–1.67 (m, 2 H, PCH2).
13
C{1H} NMR (THF-d8): d = 35.4 (t, 2JCF = 22 Hz, CH2CF2), 5.6
(dt, 1JCP = 12 Hz, 3JCF = 4 Hz, PCH2).
31
P NMR (THF-d8): d = –138.1 (t of pseudo quint., 1JPH = 192 Hz,
2
JPH = 4 Hz).
19
F NMR (THF-d8): d = –77.3 (t, 3JFF = 10 Hz, 3 F, CF3), –111.0
(pseudo quint., 2 F), –117.9 (m, 2 F), –118.9 (m, 2 F), –119.5 (m, 2
F), –122.3 (m, 2 F).
Anal. Calcd for C8H6F13P: C, 25.28; H, 1.59. Found: C, 24.90; H,
1.75.
Rf8(CH2)2PH2 (6)
LiAlH4 (1.224 g, 32.24 mmol), Et2O (200 mL), and 2 (13.806 g,
23.640 mmol)30 in Et2O (5.0 mL) were combined in a procedure
analogous to that for 5. A similar workup (Et2O extraction 3 × 50
mL; distillation) gave 6 as a colorless liquid (8.084 g, 16.84 mmol,
71%).
Bp 99 °C, 35 Torr.
1
H NMR (THF-d8): d = 2.76 (dm, 1JHP = 192 Hz, 2 H, PH2), 2.49–
2.30 (m, 2 H, CH2CF2), 1.79–1.67 (m, 2 H, PCH2).
Synthesis 2005, No. 6, 1012–1018
© Thieme Stuttgart · New York
C{1H} NMR (THF-d8): d = 32.4 (dt, 3JCP = 5 Hz, 2JCF = 22 Hz,
CH2CF2), 25.1 (pseudo q, 2JCP = 3JCF = 4 Hz, PCH2CH2), 14.2 (d,
1
JCP = 10 Hz, PCH2).
P NMR (THF-d8): d = –141.2 (t of pseudo quint., 1JPH = 190 Hz,
JPH = 5 Hz).
2
Anal. Calcd for C11H8F17P: C, 26.74; H, 1.63. Found: C, 26.88; H,
1.87.
Rf10(CH2)2PH2 (8)
LiAlH4 (0.355 g, 9.34 mmol), Et2O (60.0 mL), and 4 (4.685 g, 6.849
mmol)30 in Et2O (10.0 mL) were combined in a procedure analogous to that for 5. A similar workup (Et2O extraction 3 × 70 mL;
‘distillation’ at 127 °C, 33 Torr, with heating as necessary to liquify
any solid accumulating in the head) gave 8 as a white solid (2.474
g, 4.265 mmol, 62%).
Mp 58–59 °C (capillary), 54.8 °C (DSC, Te); TGA: onset of a 98%
mass loss 82.3 °C.
IR (powder film): 2297 (w), 1204 (s), 1150 (s) cm–1.
1
H NMR (THF-d8): d = 2.76 (dm, 1JHP = 192 Hz, 2 H, PH2), 2.49–
2.27 (m, 2 H, CH2CF2), 1.79–1.67 (m, 2 H, PCH2).
13
C{1H} NMR (THF-d8): d = 35.4 (t, 2JCF = 22 Hz, CH2CF2), 5.6
(dt, 1JCP = 12 Hz, 3JCF = 4 Hz, PCH2).
31
P NMR (THF-d8): d = –138.1 (t of pseudo quint., 1JPH = 192 Hz,
JPH = 4 Hz).
2
19
F NMR (THF-d8): d = –77.2 (t, 3JFF = 10 Hz, 3 F, CF3), –111.0 (m,
2 F), –117.7 (m, 10 F), –118.7 (m, 2 F), –119.4 (m, 2 F), –122.2 (m,
2 F).
MS (positive FAB, 3-NBA): m/z (%) = 597 ([M + H + O]+, 100%
vs. peaks with m/z > 400).
Anal. Calcd for C12H6F21P: C, 24.85; H, 1.04. Found: C, 25.01; H,
1.25.
Partition Coefficients
A
The following is representative of entries 2–5 of Table 1. A 4 mL
vial was charged with 4 (0.0140 g, 0.0205 mmol), CF3C6F11 (2.00
mL), toluene (2.00 mL), and a stir bar. It was tightly sealed, vigorously shaken (5 min), and vigorously stirred (1 h). After 12–24 h
(25 °C), aliquots (0.35 mL) were taken from both phases. Then ali-
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Rf10(CH2)2P(O)(OEt)2 (4)
P(OEt)3 (10.4 mL, 10.1 g, 60.8 mmol) and Rf10(CH2)2I (8.029 g,
11.91 mmol) were combined in a procedure analogous to that for 1.
An identical workup (SiO2 column: 63.0 g, ∅ 3.5 cm)30 gave 4 as a
white waxy solid (4.806 g, 7.026 mmol, 59%).
Efficient Syntheses of Fluorous Primary Phosphines that Do Not Require PH3
quots of a solution of THF (0.0273 g, 0.379 mmol; internal standard) in CDCl3 (6.0270 g) were added gravimetrically (CF3C6F11
phase: 0.2641 g solution, 0.01653 mmol THF; toluene phase:
0.2659 g solution, 0.01665 mmol THF). Some CF3C6H5 (0.15 mL)
was added to the CF3C6F11/CDCl3 mixture to achieve homogeneity.
The samples were analyzed by 1H NMR, integrating the OCH2 signal of 4 (d 4.15–4.02) vs. the OCH2 signal of THF (d 3.75). The procedure was repeated and the result averaged.
B
The following is representative of entries 6–9 of Table 1. A 4 mL
vial was charged with 8 (0.0424 g, 0.0731 mmol), CF3C6F11 (2.00
mL), toluene (2.00 mL), and a stir bar. It was tightly sealed, vigorously shaken (5 min), and vigorously stirred (1 h). After 12–24 h
(27 °C), aliquots (0.40 mL) were taken from both phases. Then
THF-d8 (0.15 mL) was added volumetrically, and aliquots of a solution of CH2Cl2 (0.0181 g, 0.213 mmol; internal standard) in THF
(5.0123 g) were added gravimetrically (CF3C6F11 phase: 0.1848 g
solution, 0.007825 mmol CH2Cl2; toluene phase: 0.1753 g solution,
0.007423 mmol CH2Cl2). Some CF3C6H5 (0.5 mL) was added to the
CF3C6F11/THF mixture to achieve homogeneity. The samples were
analyzed by 1H NMR, integrating the PH2 signal of 8 (d 3.08) vs. the
CH2 signal of CH2Cl2 (d 5.30). The procedure was repeated and the
result averaged.
Acknowledgment
We thank the Deutsche Forschungsgemeinschaft (DFG, GL 300/31) for support.
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Synthesis 2005, No. 6, 1012–1018
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PAPER
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C. Emnet, J. A. Gladysz
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