3-(Perfluoroalkyl)propanols: Valuable building blocks for fluorous chemistry

Article abstract of DOI:10.1055/s-2007-983779

2-Iodo-3-(perfluoroalkyl)propanols are obtained in excellent yields and several-hundred-gram quantities by the controlled radical addition of commercially available n-perfluoroalkyl and perfluoroisoalkyl iodides to allyl alcohol. Their consecutive reduction with hydrazine hydrate and Raney nickel catalyst in methanol afforded the corresponding 3-(perfluoroalkyl)propanols in high yields and purity. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-983779

PRACTICAL SYNTHETIC PROCEDURES
2581
3-(Perfluoroalkyl)propanols: Valuable Building Blocks for Fluorous
Chemistry
3
-(Perfluo
ó
roalkyl)prop
z
anols:
V
alu
s
a
ble Build
e
ing
B
locks
f
for Fluorous
C
R
hemistry ábai,* Csongor Szíjjártó, Peter Ivanko, Dénes Szabó
Department of Organic Chemistry, Institute of Chemistry, Eötvös Loránd University, P. O. Box 32,
1518 Budapest 112, Hungary
Fax +36(1)3722592; E-mail: rabai@elte.hu
Received 26 February 2007; revised 3 April 2007
PSP
Dedicated to Professor Neal O. Brace
No91
Abstract: 2-Iodo-3-(perfluoroalkyl)propanols are obtained in excellent yields and several-hundred-gram quantities by the controlled radi-
cal addition of commercially available n-perfluoroalkyl and perfluoroisoalkyl iodides to allyl alcohol. Their consecutive reduction with hy-
drazine hydrate and Raney nickel catalyst in methanol afforded the corresponding 3-(perfluoroalkyl)propanols in high yields and purity.
Key words: alkyl halides, alcohols, fluorine, reductive dehalogenation, transfer hydrogenation
Procedure 1
Procedure 2
I
a RF = n-C4F9
b RF = n-C6F13
c RF = (CF3)2CF(CF2)4
d RF = n-C8F17
e RF = (CF3)2CF(CF2)6
f RF = n-C10F21
Raney Ni, N2H4⋅H2O,
AIBN, aq K2S2O5,
80–90 °C, 2 h
MeOH, 0–10 °C, 2 h
OH
RF
OH
OH
RF
RF-I
+
83–98%
65–95%
2
1a–f
3a–f
4a–f
Scheme 1
Since the 1994 launching of the fluorous biphasic system
concept,1 and the consecutive elaboration of fluorous
Procedures
synthesis2 and fluorous mixture synthesis strategies,3 a va- The synthesis of F-propanols often involves the use of
riety of fluorous monofunctional organic precursors have fluorinated building blocks; perfluoroalkanecarboxylic
been prepared for the synthesis of more complex fluorous acids (RFCO2H), perfluoroalkanesulfonyl chlorides
molecules.4 Fluorous chemistry now spans across bipha- (RFSO2Cl), and perfluoroalkyl iodides (RFI). These pre-
sic catalysis to high-throughput synthesis of small mole- cursors are manufactured on an industrial scale and some
cules and the separation and immobilization of of them are accessible as bulk chemicals.
biomolecules, including peptides, oligosaccharides, oli-
4,4,4-Trifluorobutan-1-ol (4, RF = CF3), the prototype of
all fluorous propanols, has been prepared by the lithium
gonucleotides, and glycopeptides.5
In this strategy ponytails with perfluoroalkyl segments aluminum hydride reduction of fluorinated aldehydes, ac-
[e.g., CnF2n+1(CH2)m, n = 4,6,8 and m ≥2] are appended to ids, and esters.10 Homologues with longer chains
target molecules, which then encode their fluorous char- (RF = C3F7, C6F13, C7F15) were also made by the reduction
acter, while the (CH2)m segments serve to insulate the ac- of fluorinated carboxylic acid derivatives, accessible by
tive site from the electron-withdrawing fluorines.6
multistep syntheses.11
3-(Perfluoroalkyl)propan-1-ols are receiving increasing Another strategy for the synthesis of the title alcohols in-
attention, since they constitute essential part of an emerg- volves the radical addition of perfluoroalkyl iodides 1 to
ing inventory of fluorous tools.7 Moreover, such alcohols allyl alcohol (2) or esters thereof, followed by dehaloge-
have been used for the synthesis of novel fluorous re- nation of the formed adducts 3. Thus, perfluoropropyl io-
agents, reactants, catalysts, chiral auxiliaries, scavengers, dide undergoes addition to allyl alcohol (2) using
protecting groups, and displaceable tags.8
ultraviolet activation, but several days of irradiation are
necessary for high conversions.12 Alternatively, a method
of using azonitrile initiators for the addition of RFI to al-
kenes has been disclosed by Brace,13 providing higher
conversion of RFI within hours.14 Thus, the reaction of
perfluorobutyl or perfluorohexyl iodide and allyl acetate
under similar conditions afforded 2-iodo-3-(perfluoro-
alkyl)propyl acetates, which were then reduced with lith-
Although some of them are commercially available, their
prices justifies the need to disclose optimized procedures
for the syntheses of these alcohols.9
SYNTHESIS 2007, No. 16, pp 2581–2584
x
x.
x
x
.
2
0
0
7
Advanced online publication: 12.07.2007
DOI: 10.1055/s-2007-983779; Art ID: T04007SS
© Georg Thieme Verlag Stuttgart · New York

2582
J. Rábai et al.
PRACTICAL SYNTHETIC PROCEDURES
ium aluminum hydride to afford the corresponding crude products, which then were easily separated from the
alcohols 4a and 4b.15
less volatile side products by vacuum distillation.
The synthesis of fluorous propanols has been improved by This method can be used in many laboratories since it
the substitution of allyl alcohol/triallyl borate for allyl needs only standard laboratory glassware and equipment,
acetate and tributyltin hydride for lithium aluminum hy- it is more atom-efficient than the tributyltin hydride pro-
dride in the reduction step.16 A great improvement in the tocol, and the hazards of using lithium aluminum hydride/
rate of addition of perfluoroalkyl iodides to allyl alcohol polyfluorinated substrate mixtures are eliminated.19
was achieved by the synergic action of sodium meta-
In summary, we have shown that a series of homologous
3-(perfluoroalkyl)propan-1-ols can be prepared from
bisulfite and 2,2¢-azobis(isobutyronitrile) as discussed by
Gambaretto.16d Although the latter alterations resulted in
readily available starting materials. In addition, the io-
higher isolated yields, the removal of minute traces of tox-
dohydrin intermediates obtained here are valuable precur-
ic organotin halide residues required additional purifica-
sors for the synthesis of other monofunctional fluorous
reagents, such as 3-(perfluoroalkyl)allyl alcohols
tions steps.17
(RFCH=CHCH2OH) and 3-(perfluoroalkyl)prop-1-enes
(RFCH2CH=CH2).20
Scope and Limitations
Et2O, MeOH, THF, and hydrazine hydrate (A.R. grades) were pur-
We thought that transfer hydrogenation with hydrazine
chased from Reanal. AIBN and Raney Ni (F-83440) were supplied
hydrate/Raney nickel would be the reagent of choice for
the reductive dehalogenation of 3, since many examples
are disclosed for this transformation in the patent litera-
ture using hydrogen and a catalyst at elevated pressures
and temperatures in the presence of an appropriate base.18
by Fluka. 1a (98%), 1b (99%), 1c (97%), 1d (98%), 1e (98%), and
1
1f (97%) were purchased from Fluorochem Ltd. H, 13C and 19F
NMR spectra (CDCl3 or acetone-d6, TMS) were recorded on Bruker
Avance 250 spectrometer. All reaction steps were monitored by GC
(Hewlett-Packard 5890 Series II, PONA: 50 m capillary, H2 carrier
gas, FID detection). Melting points: Boetius (uncorrected).
We noticed that the addition of perfluoroalkyl iodides to
allyl alcohol can further be improved if the introduction of
the radical initiator is continuous, instead of in one por-
tion. While Gambaretto controlled the exothermic reac-
tion by the addition rate of 2 to the stirred and preheated
mixture of 1, 2,2¢-azobis(isobutyronitrile), and aqueous
sodium metabisulfite, we used continuous addition of a
solution of the initiator 2,2¢-azobis(isobutyronitrile) in al-
lyl alcohol (2). This slight modification allowed the opti-
mal reaction temperature to be easily maintained and
resulted in higher isolated yields and GC purity of adducts
3.
Iodohydrins 3; General Procedure
To a 1-L, 3-necked flask, fitted with thermometer, dropping funnel,
magnetic stirrer bar, and condenser with an argon bypass, was add-
ed the perfluoroalkyl iodide 1 (1.00 mol) and K2S2O5 (70 g, 315
mmol) dissolved in H2O (200 mL). It was flushed with argon, then
the mixture was heated to 65–70 °C and a soln of AIBN (5.0 g, 30
mmol) dissolved in allyl alcohol (2, 87 g, 105 mL, 1.5 mol) was
added with stirring at a rate to keep the temperature at 75–80 °C
thus controlling the slightly exothermic reaction; this addition usu-
ally takes 2.5–3 h. To complete the conversion of 1 (GC monitor-
ing), it was stirred at 80 °C for 1 h, then at 100 °C for 10 min. The
mixture was poured into H2O, and then worked up. The solid prod-
ucts were isolated by filtration, washed with H2O and dried in air;
while the liquid ones were extracted with Et2O (3 × 150 mL) and
purified by fractional distillation in vacuum. Analytical samples of
the solid iodohydrins (GC ≥98%) can be obtained by recrystalliza-
tion (boiling benzene, 1.3 mL g–1).
The addition of liquid perfluoroalkyl iodides 1a–e afford-
ed iodohydrins 3a–e in 83–98% yields as shown in
Scheme 1 and detailed in the general procedure. Since the
optimal temperature of 2,2¢-azobis(isobutyronitrile) initi-
ation is about 80 °C, perfluoroalkyl iodides with lower
boiling point (CF3I, –22.5 °C; C2F5I, 12–13 °C; n-C3F7I,
41 °C) are not suitable for Procedure 1, unless a pressure
reactor is used.
2-Iodo-3-(perfluorobutyl)propan-1-ol (3a)
The reaction was performed according to the general procedure us-
ing 1a (185 g, 92 mL, 535 mmol) and K2S2O5 (37.5 g, 168 mmol)
in H2O (107 mL) with 2 (56.3 mL, 804 mmol) and AIBN (2.68 g,
16 mmol). Pale-yellow oil; yield: 180 g (83%); GC: 97.5%; bp 105–
110 °C/21 mbar (Lit.15a 57–58 °C/1 mbar).
1H NMR (CDCl3): d = 4.44 (m, 1 H, CHI), 3.83 (m, 2 H, CH2OH),
2.90 (m, 2 H, CH2CHI), 2.46 (br s, 1 H, CH2OH).
13C NMR (CDCl3): d = 21.9 (C2), 37.7 (t, C3), 68.3 (C1).
19F NMR (CDCl3): d = –81.7 (m, 3 F), –114.3 (q, 2 F), –125.1 (m,
2 F), –126.6 (m, 2 F).
Another limiting case for using Procedure 1 could be the
higher melting point of the adduct 3 than the optimal
working temperature of the radical initiator, as it was
found for 3f; 64% conversion of 1f was observed and
longer heating and additional initiator and allyl alcohol
were necessary to reach 99% conversion of 1f.
All of the fluorous iodohydrins 3a–d, but 3f, were readily
soluble in methanol and reacted with hydrazine hydrate
and Raney nickel catalyst under optimized conditions to
furnish the title alcohols in 65–95% yields (Scheme 1,
2-Iodo-3-(perfluorohexyl)propan-1-ol (3b)
The reaction was performed according to the general procedure us-
ing 1b (1500 g, 735 mL, 3.36 mol) and K2S2O5 (90 g, 405 mmol) in
Procedure 2). For the less soluble 3f, the methanol– H2O (300 mL) with 2 (255 mL, 3.75 mol) and AIBN (9.0 g, 55
mmol). Yield: 1592 g (94%), GC: 96.4%. Recrystallization (ben-
tetrahydrofuran solvent system and a longer reaction time
zene) gave white crystals, mp 46–48 °C (Lit.21 44 °C). The spectro-
scopic data were in agreement with those reported by Gambaretto et
were applied. We observed that using lower temperatures
for the reductions resulted in the formation of more pure
al.16d
Synthesis 2007, No. 16, 2581–2584 © Thieme Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
Building Blocks for Fluorous Chemistry
2583
2-Iodo-3-(perfluoro-5-methylhexyl)propan-1-ol (3c)
The reaction was performed according to the general procedure us-
ing 1c (10 g, 4.90 mL, 20 mmol) and K2S2O5 (1.4 g, 6.3 mmol) in
H2O (10 mL) with 2 (2.1 mL, 31 mmol) and AIBN (0.10 g, 0.6
mmol). Colorless oil solidifies on cooling;22 yield: 9.81 g (88%),
GC: 96%; mp 16–20 °C.
1H NMR (CDCl3): d = 4.4 (m, 1 H, CHI), 3.8 (m, 2 H, CH2OH), 2.9
(m, 2 H, CH2CHI), 2.2 (br s, 1 H, CH2OH).
13C NMR (CDCl3): d = 22.0 (C2), 37.8 (t, C3), 68.3 (C1).
workup finished. The fluorous layer was taken up in some Et2O,
washed with H2O (3 × 50 mL), and dried (Na2SO4). After filtration,
the solvent was evaporated and the crude oil was purified by vacu-
um distillation to give the product as a colorless oil; yield: 311 g
(82%); GC: 99.0%; bp 84–86 °C/26.7 mbar (as reported, Lit.23).
The spectroscopic data were in agreement with a sample prepared
previously in this laboratory.16c
3-(Perfluorobutyl)propan-1-ol (4a)
The reaction was performed according to the typical procedure us-
ing 3a (50 g, 124 mmol). Yield: 28.2 g (82%), collected under argon
as colorless oil, GC: 98%; bp 64 °C/26.7 mbar (as reported, Lit.23).
19F NMR (CDCl3): d = –72.4 (m, 6 F), –114.0 (td, 2 F), –115.7 (m,
2 F), –121.2 (m, 2 F), –123.6 (m, 2 F), –186.7 (m, 1 F).
1H NMR (CDCl3): d = 1.80–1.91 (m, 2 H, 2 H2), 2.09–2.31 (m, 2
H, 2 H3), 2.51 (br s, OH), 3.72 (t, 3JHH = 6.2 Hz, 2 H, 2 H1).
2-Iodo-3-(perfluorooctyl)propan-1-ol (3d)
The reaction was performed according to the general procedure us-
ing 1d (545 g, 267 mL, 1 mol). Pale-yellow solid; yield: 592 g
(98%), GC: 94.2%; mp 91–92 °C. Recrystallization (benzene) gave
white crystals, GC: 98%, mp 93–94 °C (Lit.16b 93–94 °C). The
spectroscopic data were in agreement with those reported by Gam-
baretto et al.16d
13C NMR (CDCl3): d = 23.5 (C2), 27.7 (t, C3), 61.5 (C1).
19F NMR (CDCl3): d = –81.9 (m, 3 F), –115.4 (m, 2 F), –125.2 (m,
2 F), –126.9 (m, 2 F).
3-(Perfluoro-5-methylhexyl)propan-1-ol (4c)
The reaction was performed according to the typical procedure us-
ing 3c (8.46 g, 15.3 mmol) to give the product as a colorless oil;
yield: 4.25 g (65%); GC: 96.5%. Short-path distilled at 26.7 mbar/
145–150 °C (bath temperature).
2-Iodo-3-(perfluoro-7-methyloctyl)propan-1-ol (3e)
The reaction was performed according to the general procedure us-
ing 1e (50 g, 83.9 mmol) and K2S2O5 (5.8 g, 26 mmol) in H2O (35
mL) with 2 (7.3 g, 8.8 mL, 126 mmol) and AIBN (0.42 g, 0.25
mmol). Yield: 53.6 g (98%); GC: 96.2%. Recrystallization (ben-
zene) gave white crystals (43.2 g, 84%); GC: 99%; mp 69–70 °C.
1H NMR (CDCl3): d = 4.4 (m, 1 H, CHI), 3.8 (m, 2 H, CH2OH), 2.9
(m, 2 H, CH2CHI), 2.3 (br s, 1 H, CH2OH).
1H NMR (CDCl3): d = 1.80–1.95 (m, 2 H, 2 H2), 2.08 (s, OH), 2.09–
2.32 (m, 2 H, 2 H3), 3.73 (t, 3JHH = 5.7Hz, 2 H, 2 H1).
13C NMR (CDCl3): d = 23.7 (C2), 27.9 (t, C3), 61.7 (C1).
19F NMR (CDCl3): d = –72.6 (m, 6 F), –115.0 (td, 2 F), –115.7 (m,
2 F), –121.3 (m, 2 F), –123.7 (m, 2 F), –186.7 (m, 1 F).
13C NMR (CDCl3): d = 22.1 (C2), 37.8 (t, C3), 68.2 (C1).
19F NMR (CDCl3): d = –72.5 (m, 6 F), –114.0 (td, 2 F), –115.7 (m,
2 F), –121.3 (m, 2 F), –122.2 (m, 4 F), –124.1 (m, 2 F), –186.7 (m,
1 F).
3-(Perfluorooctyl)propan-1-ol (4d)
The reaction was performed according to the typical procedure us-
ing 3d (500 g, 828 mmol) giving the product as a colorless melt or
white solid; yield: 310 g (78%); GC: 99.1%; bp 82–83 °C/0.13
mbar; mp 42 °C (as reported, Lit.23). The spectroscopic data were in
agreement with a sample prepared previously in this laboratory.16c
2-Iodo-(3-perfluorodecyl)propan-1-ol (3f)
The reaction was started according to the general procedure using
1f (32.3 g, 50 mmol) and K2S2O5 (3.5 g, 16 mmol) in H2O (10 mL)
with 2 (5.2 mL, 75 mmol) and AIBN (0.25 g, 1.5 mmol). When the
addition of 2 was completed the mixture became a solid mass (GC:
1f ~36%). After 3 h stirring at 80 °C more AIBN (0.25 g) was added
and kept at 80 °C for 2 h (GC: 1f ~20%). More AIBN (0.25 g) dis-
solved in 2 (2.6 mL, 38 mmol) was added and kept at 80 °C for 3 h
(GC: 1f ~2%). Finally, it was heated to 100 °C and stirred for 15
min (GC: 1f £1%); then worked up. Yield: 33.1 g (94%), GC: 96%;
mp 123–125 °C (isooctane).
3-(Perfluoro-7-methyloctyl)propan-1-ol (4e)
The reaction was performed according to the typical procedure us-
ing 3d (42 g, 64 mmol) giving the product as a white solid; yield: 32
g (95%); GC: 97.4%; mp 42–43 °C.
1H NMR (CDCl3): d = 1.80–1.92 (m, 2 H, 2 H2), 2.09–2.32 (m, 2
H, 2 H3), 3.74 (t, 3JHH = 6.2 Hz, 2 H, 2 H1).
13C NMR (CDCl3): d = 23.5 (C2), 27.7 (t, C3), 61.5 (C1).
19F NMR (CDCl3): d = –72.6 (m, 6 F), –115.0 (td, 2 F), –115.7 (m,
2 F), –121.4 (m, 2 F), –122.2 (m, 4 F), –124.1 (m, 2 F), –186.7 (m,
1 F).
1H NMR (acetone-d6): d = 4.77 (br s, OH, 1 H), 2.85 (2 m, 2 H, RF-
CH2), 3.85 (d m, 2 H, CH2OH), 4.35 (m, 1 H, CHI).
13C NMR (acetone-d6): d = 19.9 (C2), 37.5 (t, C3), 68.6 (C1).
19F NMR (acetone-d6): d = 93.5 (m, 3 F), 61.1 (q, 2 F), 52.9 (m, 10
3-(Perfluorodecyl)propan-1-ol (4f)
F), 51.9 (m, 2 F), 51.0 (m, 2 F), 48.4 (m, 2 F).
The reaction was performed according to the typical procedure un-
der an argon flow; using a mixture of iodohydrin 3f (200 g, 284
mmol), THF (430 mL), and Raney Ni (14 g, 0.24 g-atom) in MeOH
(85 mL), and hydrazine hydrate (34 g, 685 mmol) in MeOH (85 mL)
at 10 °C for 2 h and at 20 °C for 18 h. 12 M HCl (68 mL), H2O (500
mL) and Et2O (250 mL) were added consecutively to the stirred
mixture over 30 min. Then it was filtered on Celite and the clear fil-
trate was separated to organic and aqueous layers. The aqueous
phase was extracted with Et2O (2 × 200 mL) and added to the or-
ganic layer. The combined extracts were washed with H2O (3 × 500
mL) and dried (Na2SO4). After filtration, the solvent was evaporat-
ed and the crude melt was purified by vacuum distillation to give a
colorless melt or white solid; yield: 131 g (80%); GC: 98.1%; bp
110 °C/0.13 mbar; mp 86–89 °C (as reported, Lit.23). The spectro-
scopic data were in agreement with a sample prepared previously in
this laboratory.16c
3-(Perfluorohexyl)propan-1-ol (4b); Typical Procedure
To a 4-L, 3-necked flask, fitted with stirrer, reflux condenser, pres-
sure-equalizing dropping funnel, thermometer and argon bypass,
was added MeOH (750 mL), in a flow of argon a suspension of
Raney Ni (48 g) in MeOH (200 mL), 3b (504 g, 1.00 mol), and
MeOH (450 mL). The mixture was cooled with an ice-water bath to
keep the internal temperature below 10 °C during the addition (3 h)
of a soln of hydrazine hydrate (121 g, 2.41 mol) in MeOH (300 mL).
The mixture was stirred at r.t. for 1.5 h for complete conversion of
3b (GC monitoring). Next, the mixture was filtered through a Celite
pad under an argon flow, the used Raney Ni catalyst quenched with
H2O, while the filtrate was diluted with ice-water (6 L). The crude
product was completely settled out standing overnight as a lower
oily phase from the clear upper aqueous layer. They were separated,
and the H2O phase was saved for Et2O extraction if needed, until
Synthesis 2007, No. 16, 2581–2584 © Thieme Stuttgart · New York

2584
J. Rábai et al.
PRACTICAL SYNTHETIC PROCEDURES
Loncrini, D. F. J. Am. Chem. Soc. 1955, 77, 3637. From
CF3CO2Et and CH3CO2Et, see: (d) Raiter, M.; Pereyere,
M.; Davies, A. G.; Sutcliffe, R. J. Chem. Soc., Perkin Trans.
2 1984, 1907. From CF3CH2OTf and malonic ester, see:
(e) Tsushima, T.; Kawada, K.; Ishihara, S.; Uchida, N.;
Shiratori, O.; Higaki, J.; Hirata, M. Tetrahedron 1988, 44,
5375.
Acknowledgment
We thank the Hungarian Scientific Research Foundation (OTKA
K62191, T043738) and the European Contract of Research Training
Network (‘Fluorous Phase’ HPRN-CT-2000-00002) for support.
References
(11) From C3F7CO2Me and CH3OAc, see: (a) Ahlbrecht, A. H.;
Smith, S. GB 904,263, 1962; Chem. Abstr. 1963, 58, 4426 .
From C6F13I and ethyl acrylate (hn), see: (b) Buchanan, G.
W.; Smits, R.; Munteanu, E. J. Fluorine Chem. 2003, 123,
255. From C7F15I and ICH=CHI, see: (c) Coe, P. L.;
Millner, N. E.; Smith, J. A. J. Chem. Soc., Perkin Trans. 1
1975, 654.
(1) (a) Horváth, I. T.; Rábai, J. Science 1994, 266, 72.
(b) Horváth, I. T.; Rábai, J. US 5,463,082, 1995; Chem.
Abstr. 1995, 123, 87349.
(2) Studer, A.; Hadida, S.; Ferritto, R.; Kim, S.-Y.; Jeger, P.;
Wipf, P.; Curran, D. P. Science 1997, 275, 823.
(3) Oderaotoshi, Y.; Zhang, Q.; Luo, Z.; Curran, D. P. Science
2001, 291, 1766.
(4) Rábai, J. In Handbook of Fluorous Chemistry; Gladysz, J.
A.; Curran, D. P.; Horváth, I. T., Eds.; Wiley-VCH:
Weinheim, 2004, Chap. 9.
(5) (a) Horváth, I. T. Acc. Chem. Res. 1998, 31, 641. (b) Rábai,
J.; Szlávik, Z.; Horváth, I. T. In Handbook of Green
Chemistry and Technology; Clark, J.; MacQuarrie, D., Eds.;
Blackwell Science: Oxford, 2002, Chap. 21, 502–523.
(c) Special issue on Fluorous Chemistry: Tetrahedron 2002,
58, 3823–4131. (d) Handbook of Fluorous Chemistry;
Gladysz, J. A.; Curran, D. P.; Horváth, I. T., Eds.; Wiley-
VCH: Weinheim, 2004. (e) Andrushko, V.; Schwinn, D.;
Tzschucke, C. C.; Michalek, F.; Horn, J.; Mössner, C.;
Bannwarth, W. Helv. Chim. Acta 2005, 88, 936.
(12) Moore, L. D. J. Chem. Eng. Data 1964, 9, 251; and
references cited therein.
(13) (a) Brace, N. O. J. Org. Chem. 1962, 27, 3033. (b) Brace,
N. O. US 3,145,222, 1964; Chem. Abstr. 1964, 61, 10589.
(14) Brace, N. O. J. Fluorine Chem. 1999, 93, 1.
(15) (a) Brace, N. O. J. Fluorine Chem. 1982, 20, 313. For the
addition of (CF3)2CFI to allyl acetate, see: (b) Boggs, J.;
Brandstadter, S. M.; Chien, J.; Cohn, M.; Edwards, B. E.;
Hedrick, V.; Jackson, A.; Leman, G.; Ameduri, B.; Kostov,
G. K. WO 2005,074,637, 2005; Chem. Abstr. 2005, 143,
213355.
(16) (a) Metzger, J. O.; Mahler, R.; Schmidt, A. Liebigs Ann.
Org. Bioorg. Chem. 1996, 5, 693. (b) Vincent, J.-M.;
Rabion, A.; Yachandra, V. K.; Fish, R. H. Angew. Chem.,
Int. Ed. Engl. 1997, 36, 2346; Angew. Chem. 1997, 109,
2438. (c) Szlávik, Z.; Tárkányi, G.; Tarczay, Gy.; Gömöry,
Á.; Rábai, J. J. Fluorine Chem. 1999, 98, 83.
(f) Pearson, W. H.; Berry, D. A.; Stoy, P.; Jung, K.-Y.;
Sercel, A. D. J. Org. Chem. 2005, 70, 7114. (g) Special
issue on Fluorous Chemistry: QSAR Comb. Sci. 2006, 25,
679–806.
(d) Gambaretto, G.; Conte, L.; Fornasieri, G.; Zarantonello,
C.; Tonei, D.; Sassi, A.; Bertani, R. J. Fluorine Chem. 2003,
121, 57.
(6) (a) Horváth, I. T.; Kiss, G.; Cook, R. A.; Bond, J. E.;
Stevens, P. A.; Rábai, J.; Mozeleski, E. J. J. Am. Chem. Soc.
1998, 120, 3133. (b) Szlávik, Z.; Tárkányi, G.; Gömöry, Á.;
Tarczay, G.; Rábai, J. J. Fluorine Chem. 2001, 108, 7.
(c) Gladysz, J. A. Ponytails: Structural and Electronic
Considerations, In Handbook of Fluorous Chemistry;
Gladysz, J. A.; Curran, D. P.; Horváth, I. T., Eds.; Wiley-
VCH: Weinheim, 2004, Chap. 5.
(17) For replacement of toxic organotin hydrides and/or removal
of residual tin compounds from end products, see:
(a) Baguley, P. A.; Walton, J. C. Angew. Chem. Int. Ed.
1998, 37, 3072; Angew. Chem. 1998, 110, 3272. (b) Studer,
A.; Amrein, S. Synthesis 2002, 835. For an improved
preparation of 3d and 4d using 1d (100 g) with the triallyl
borate/Bu3SnH protocol, see: (c) Rábai, J.; Kövesi, I.;
Bonto, A.-M. In Handbook of Fluorous Chemistry; Gladysz,
J. A.; Curran, D. P.; Horváth, I. T., Eds.; Wiley-VCH:
Weinheim, 2004, 419–420.
(18) For the use of PtO2/NH4OAc, see: (a) Otsuka, T.;
Yamamoto, S. JP 2003,146,921, 2003; Chem. Abstr. 2003,
138, 385058. For the use of Pd-C/Et3N, see: (b) Rock,
M.-H.; Marhold, A. DE 19,748,775, 1999; Chem. Abstr.
1999, 130, 268838. For the use of Raney Ni/KOAc, see:
(c) Ukihashi, K.; Hayashi, T. JP 7,022,523, 1970; Chem.
Abstr. 1970, 73, 98363. For the use of Raney Ni, NaOH,
see: (d) Ahlbrecht, A. H. US 3,285,975, 1966; Chem. Abstr.
1967, 66, 46093.
(7) http://www.fluorous.com.
(8) (a) Miura, T.; Hirose, Y.; Ohmae, M.; Inazu, T. Org. Lett.
2001, 3, 3947. (b) Mizuno, M.; Goto, K.; Miura, T.;
Matsuura, T.; Inazu, T. Tetrahedron Lett. 2004, 45, 3425.
(c) Goto, K.; Miura, T.; Mizuno, M. Tetrahedron Lett. 2005,
46, 8293. (d) Miura, T.; Satoh, A.; Goto, K.; Murakami, Y.;
Imai, N.; Inazu, T. Tetrahedron: Asymmetry 2005, 16, 3.
(e) Vlád, G.; Richter, F. U.; Horváth, I. T. Tetrahedron Lett.
2005, 46, 8605. (f) Emnet, C.; Gladysz, J. A. Synthesis
2005, 1012. (g) Fustero, S.; Sancho, A. G.; Chiva, G.; Sanz-
Cervera, J. F.; del Pozo, C.; Acena, J. L. J. Org. Chem. 2006,
71, 3299. (h) Zhang, W.; Curran, D. P. Tetrahedron 2006,
62, 11837; and references therein. (i) Mizuno, M.;
Matsumoto, H.; Goto, K.; Hamasaki, K. Tetrahedron Lett.
2006, 47, 8831. (j) Kojima, M.; Nakamura, Y.; Ishikawa, T.;
Takeuchi, S. Tetrahedron Lett. 2006, 47, 6309.
(19) For hazards with the use of LiAlH4/RF-amides, see: Marks,
B. S.; Schweiker, G. C. J. Am. Chem. Soc. 1958, 80, 5789.
(20) Ivanko, P.; Takács, F. T.; Rábai, J. Abstracts of Papers, 14th
European Symposium on Fluorine Chemistry, Poznan,
Poland, 2004; Abstract 84.
(21) Lahiouhel, D.; Ameduri, B.; Boutevin, B. J. Fluorine Chem.
2001, 107, 81.
(k) Bayardon, J.; Holczknecht, O.; Pozzi, G.; Sinou, D.
Tetrahedron: Asymmetry 2006, 17, 1568. (l) Zhang, W.;
Williams, J. P.; Lu, Y.; Nagashima, T.; Chu, Q. Tetrahedron
Lett. 2007, 48, 563.
(9) FTI Catalogue (2006) lists RFn(CH2)3OH at $32, $35, $100,
and $35 for 2 g each of n = 4, 6, 7, and 8, respectively.
(10) From CF3CH2CH2MgCl and (EtO)3CH, see: (a) McBee, E.
T.; Kelley, A. C.; Rapkin, E. J. Am. Chem. Soc. 1950, 72,
5071. From CF3CH2CH2MgCl and CO2, see: (b) Gavlin,
G.; Maguire, R. G. J. Org. Chem. 1956, 21, 1342. From
CF3CH2CH2CO2Et, see: (c) Walborsky, H. M.; Baum, M.;
(22) For an analogous synthesis of 3c with bp 88–90 °C/1.7–2.0
mbar using only 1c, 2, and AIBN at 70–80 °C, see: Daikin
Ind. Ltd., GB 1,101,049, 1968; Chem. Abstr. 1968, 68,
60504.
(23) Bálint, A.-M.; Bodor, A.; Gömöry, Á.; Vékey, K.; Szabó,
D.; Rábai, J. J. Fluorine Chem. 2005, 126, 1524.
Synthesis 2007, No. 16, 2581–2584 © Thieme Stuttgart · New York