Regioselective synthesis of 4-alkyl- and 4-aryl-6-(perfluoroalkyl)salicylic acid derivatives by formal [3+3] cyclocondensation of 1,3-bis(silyloxy)-1,3-butadienes with 3-silyloxy-1-(perfluoroalkyl)prop-2-en-1-ones

Article abstract of DOI:10.1016/j.tet.2008.06.009

4-Alkyl- and 4-aryl-6-(perfluoroalkyl)salicylic acid derivatives were regioselectively prepared by [3+3] cyclization of 1,3-bis(silyl enol ethers) with 3-silyloxy-1-(perfluoroalkyl)prop-2-en-1-ones.

Full text of DOI:10.1016/j.tet.2008.06.009

Tetrahedron 64 (2008) 7968–7976
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Regioselective synthesis of 4-alkyl- and 4-aryl-6-(perfluoroalkyl)salicylic
acid derivatives by formal [3þ3] cyclocondensation of 1,3-bis(silyloxy)-
1,3-butadienes with 3-silyloxy-1-(perfluoroalkyl)prop-2-en-1-ones
,b,
Stefan Bu¨ttner a, Mathias Lubbe a, Helmut Reinke a, Christine Fischer b, Peter Langer a
*
a Institut fu¨r Chemie, Universita¨t Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
b Leibniz-Institut fu¨r Katalyse e. V. an der Universita¨t Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 7 May 2008
Received in revised form 2 June 2008
Accepted 4 June 2008
4-Alkyl- and 4-aryl-6-(perfluoroalkyl)salicylic acid derivatives were regioselectively prepared by [3þ3]
cyclization of 1,3-bis(silyl enol ethers) with 3-silyloxy-1-(perfluoroalkyl)prop-2-en-1-ones.
Ó 2008 Elsevier Ltd. All rights reserved.
Available online 7 June 2008
1. Introduction
enones,8 the use of perfluoroketene dithioacetals and per-
fluorodithiocarboxylic acid derivatives as versatile tools for orga-
Perfluoroalkyl groups are of considerable importance in the field
of medicinal chemistry as they are chemically and biologically inert
and are, thus, not metabolized.1–3 The electronic properties of
perfluoroalkyl-substituted products differ greatly from the
alkyl-substituted analogues. This fact plays an important role in
drug–receptor interactions. In addition, the in vivo transport of
perfluoroalkyl-substituted molecules is improved, due to their in-
creased lipophilicity. Because of the high chemical and biological
stabilities of perfluoroalkyl groups, undesirable metabolic trans-
formations are often avoided. Noteworthy, perfluoroalkyl-
substituted molecules have received considerable attention also in
material sciences. For example, various perfluoroalkyl-substituted
compounds show amphiphilic properties and represent promis-
ing liquid crystals.4 Perfluoroalkyl-substituted compounds also
play an important role in catalytic reactions in fluorous biphase
systems.5
(Perfluoroalkyl)arenes have been prepared by reaction of
iodoarenes with (perfluoroalkyl)cuprates.6 However, these re-
actions may suffer from a number of side reactions; in addition, the
starting materialsdfunctionalized arenesdare often not readily
available. Fluorinated products are available also based on a build-
ing block strategy. For example, Portella and co-workers reported
the synthesis of fluorophenols by annulation reactions of 2,2-
difluoro-1,5 diketones, which were prepared from acylsilanes, tri-
fluoromethyltrimethylsilane and enones.7 They also studied the
synthesis of ortho-perfluoroalkyl phenones from hemifluorinated
nofluorine synthesis,9 the synthesis of new trifluoromethylated
furans, dihydrofurans and butenolides from g
-ketothioesters10 and
a new strategy for the synthesis of fluorinated compounds by re-
action of carboxylic acid dianions with perfluoroketene dithioace-
tals.11 Haufe and co-workers reported the synthesis of new
polyfluoroalkyl-containing pyrones, pyridones and pyrido[1,2-
a]benzazoles from fluorinated
b
-alkoxyenones12 and synthetic
applications of b-fluoro-alkylated enones as dienophiles in Diels–
Alder reactions.13 Hu and Guan developed a new approach to 4-
trifluoromethylpyridines and meta-trifluoromethylphenols based
on the reaction of active methylene compounds with
a-fluoroalkyl
ketones and esters.14
Chan and co-workers reported15 an elegant approach to salicy-
lates based on cyclization of 1,3-bis(silyloxy)-1,3-butadienes16
with 3-(silyloxy)alk-2-en-1-ones.17 Recently, we developed
a
convenient access to fluorinated trifluoromethyl-18 and per-
fluoroalkyl-substituted arenes19 by cyclocondensation of 1,3-bis-
(silyloxy)-1,3-butadienes with 3-ethoxy-2-en-1-ones. Herein, we
report the synthesis of
a variety of 4-alkyl- and 4-aryl-6-
(perfluoroalkyl)salicylic acid derivatives by, to the best of our
knowledge, the first [3þ3] cyclocondensations of 1,3-bis(silyloxy)-
1,3-butadienes with 3-silyloxy-1-(perfluoroalkyl)prop-2-en-1-ones.
These transformations provide a convenient and regioselective
approach to a variety of perfluoroalkyl-substituted arenes, which
are not readily available by other methods.
2. Results and discussion
Dicarbonyl compounds 3a–h,j,k,i were prepared by Claisen
condensation of ketones 1a–d with perfluoroalkyl-substituted
* Corresponding author. Fax: þ381 4986412.
E-mail address: peter.langer@uni-rostock.de (P. Langer).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.06.009

S. Bu¨ttner et al. / Tetrahedron 64 (2008) 7968–7976
7969
O
Me3SiO
R4
OSiMe3
R5
O
O
O
i
OH
O
R2
R2
RF
+
R3O
2a-d
RF
R4
R2
5a-d
R1
R1
3a-k
R5
i
+
1a-d
O
OSiMe3
RF
ii
RF
R1
6a-w
R2
O
OSiMe3
RF
R1
4a-k
R2
R1
4a-k
Scheme 3. Synthesis of 6a–w: (i) TiCl4, CH2Cl2, ꢀ78/20 ꢁC, 20 h.
Scheme 1. Synthesis of 3a–w: (i) NaOMe, O(C2H5)2, 0/20 ꢁC, 20 h; (ii) Me3SiOTf
(0.95 equiv), NEt3 (1.0 equiv), Et2O, 0 ꢁC, 30 min, 20 ꢁC, 3 days.
Table 2
Yields of 6a–w
esters 2a–d following a method reported by Moore and Levine.20
The silylation of 3a–k, following conditions reported by
Kra¨geloh and Simchen,21 afforded the novel 3-silyloxy-1-(per-
fluoroalkyl)prop-2-en-1-ones 4a–k (Scheme 1, Table 1).
The TiCl4 mediated cyclization of 4a–k with 1,3-bis(silyl enol
ethers) 5a–ddprepared from methyl acetoacetate, pentane-
2,4-dione, heptane-3,5-dione and methyl 3-oxohexanoate,
respectively15dafforded the novel 5-alkyl- and 5-aryl-3-(per-
fluoroalkyl)phenols 6a–w (Schemes 2 and 3, Table 2). All products
were formed with very good regioselectivity. The formation of the
products can be explained by TiCl4 mediated 1,4-addition of the
terminal carbon atom of the 1,3-bis(silyl enol ether) onto 4a–k and
subsequent cyclization by attack of the central carbon atom of the
bis(silyl enol ether) onto the carbonyl group (Scheme 2).
4
5
6
RF
R1
R2
R4
R5
6a (%)
a
a
a
b
b
b
c
a
b
c
a
d
b
a
b
c
a
d
b
c
a
c
a
a
a
b
c
c
a
c
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
C2F5
C2F5
C2F5
C2F5
C2F5
C2F5
C2F5
C2F5
C2F5
C3F7
C3F7
C3F7
C3F7
C3F7
C3F7
C3F7
C3F7
C6F13
C6F13
C7F15
C7F15
C7F15
C7F15
H
H
H
n-Pr
n-Pr
n-Pr
H
H
Me
H
Et
H
H
H
Me
H
Et
H
Me
H
Me
H
H
H
OMe
Me
Et
OMe
OMe
Me
OMe
Me
46
42
33
57
50
40
45
41
37
45
65
40
37
40
31
41
47
42
41
41
30
36
49
–(CH2)3–
–(CH2)3–
–(CH2)3–
H
H
H
H
H
H
H
H
H
Ph
Ph
Ph
Me
Me
Me
Me
n-Pr
n-Pr
c
c
Et
d
d
d
d
e
e
f
g
h
h
i
OMe
OMe
Me
Et
OMe
Et
OMe
OMe
OMe
Me
Et
Et
–(CH2)3–
H
H
H
Relatively good yields (50 and 65%) were obtained for products
6e and 6k, respectively, prepared from 1,3-bis(silyloxy)-1,3-buta-
diene 5d. The latter is derived from methyl 3-oxohexanoate, i.e., a b-
ketoester containing an ethyl group located at carbon atom C4. The
yields of products 6a,d,g,j,n,p–r,v, derived from the unsubstituted
Ph
Me
Me
n-Pr
s
t
u
v
w
H
H
Me
Me
H
j
k
k
–(CH2)3–
H
H
Ph
Ph
OMe
Et
Me
Table 1
Yields of 3a–k and 4a–k
a
Yields of isolated products.
1
2
3,4
RF
R1
R2
R3
3a (%)
4a (%)
b-ketoester-derived diene 5a, are in the range of 36–57%. The yields
decrease with the chain length of the perfluoroalkyl group. The
yields of 1,3-diketone derived products (6b,c,f,h,i,l,m,o,s,t,u,w) are
in most cases lower than those derived from ketoesters. This can be
explained by their lower reactivity. A systematic influence of sub-
stituents R1 and R2 on the yield could not be observed.
The structures of all products were established by spectroscopic
methods. The structures of 6c,g,j,l,q were independently confirmed
by X-ray crystal structural analysis (Figs. 1–5).22 For all products,
the carbonyl group is twisted out of the plane of the benzene
moiety. In contrast, the two benzene moieties of derivatives 6g and
6q are only slightly twisted out of plane. No intramolecular hy-
drogen bonds OꢀH/O were observed. For derivatives 6j,l,q,
a
b
c
d
a
b
c
d
a
b
c
a
a
a
b
b
b
b
c
a
b
c
d
e
f
g
h
i
C2F5
C2F5
C2F5
C3F7
C3F7
C3F7
C3F7
C6F13
C7F15
C7F15
C7F15
H
n-Pr
Et
Et
Et
Et
Et
Et
Et
Me
Me
Me
Me
59
57
60
47
80
68
80
70
70
69
62
92
88
90
82
80
84
87
92
94
95
85
–(CH2)3–
H
H
H
–(CH2)3–
H
H
H
Ph
Me
n-Pr
Ph
Me
n-Pr
d
d
d
j
k
–(CH2)3–
H
Ph
a
Yields of isolated products.
Me3SiO
OMe
OSiMe3
O
OH
TiCl4
5a
CH2Cl2
OMe
+
_
Me3SiO
O
20 °C
20 h
78
nPr
C2F5
nPr
C2F5
4a
6a
TiCl4
Me3SiCl
H+, H2O
O
O
OH
Me3SiO
OMe
C2F5
OTiCl
OMe
Me3SiO
nPr
C2F5
OTiCl3
nPr
3 (Me3Si)2O
A
B
Scheme 2. Possible mechanism for the formation of 6a: (i) TiCl4, CH2Cl2, ꢀ78/20 ꢁC,
20 h.
Figure 1. Ortep plot of 6c (50% probability level).

7970
S. Bu¨ttner et al. / Tetrahedron 64 (2008) 7968–7976
Figure 2. Ortep plot of 6g (50% probability level).
Figure 5. Ortep plot of 6q (50% probability level).
bis(silyl enol ethers) with 3-silyloxy-1-(perfluoroalkyl)prop-2-en-
1-ones.
4. Experimental section
4.1. General comments
All solvents were dried by standard methods and all reactions
were carried out under an inert atmosphere. For 1H and 13C NMR
spectra, the deuterated solvents indicated were used. Tetrame-
thylsilane was used as the external standard. For 19F NMR spec-
troscopy, CFCl3 was used as the external standard. Mass
spectrometric data (MS) were obtained by electron ionization (EI,
70 eV), chemical ionization (CI, H2O) or electrospray ionization
(ESI). For preparative scale chromatography, silica gel (60–200
mesh) was used. Melting points are uncorrected.
Figure 3. Ortep plot of 6j (50% probability level).
4.2. General procedure for the synthesis of perfluoroalkyl-
diones 3a–k
containing a heptafluoropropyl group, an antiperiplanar confor-
mation is observed for the RCF2–CF2R0 moiety, due to steric reasons.
Only a very small alternation of the bond lengths within the ben-
zene moiety is observed.
To a stirred solution of methanol (1.3 equiv) in diethyl ether
(1 mL/1.0 mmol 1) was added sodium (1.1 equiv) at 0 ꢁC and stir-
ring was continued for 30 min. Perfluorinated acid ester
2
3. Conclusions
(1.0 equiv) was added, the reaction mixture was stirred for 30 min
and carbonyl compound 1 (1.0 equiv) was added. Then stirring was
continued for 16 h at 20 ꢁC. After addition of sulfuric acid (10%,
0.35 mL/mmol), the reaction mixture was extracted with diethyl
ether. The combined organic layers were dried (Na2SO4), filtered
and the filtrate was concentrated under reduced pressure. The
residue was purified by distillation.
In conclusion, a variety of novel 5-alkyl- and 5-aryl-3-(per-
fluoroalkyl)phenols were prepared by [3þ3] cyclization of 1,3-
4.2.1. 1,1,1,2,2-Pentafluoro-octane-3,5-dione (3a)
Starting with 2-pentanone 1a (2.524 g, 30 mmol) and 2,2,3,3,3-
pentafluoro-propionic acid ethyl ester 2a (5.763 g, 30 mmol), 3a
was isolated as a colourless liquid (4.127 g, 59%), bp¼70 ꢁC/30 mbar
(lit.20a 65.5 ꢁC/30 mbar). 1H NMR (250 MHz, CDCl3):
d
¼0.99 (t,
3J¼7.4 Hz, 3H, CH2CH2CH3), 1.62–1.78 (m, 2H, CH2CH2CH3), 2.42 (t,
3J¼7.5 Hz, 2H, CH2CH2CH3), 5.98 (s, 1H, CH); 19F NMR (235 MHz,
CDCl3):
d¼ꢀ124.2 (m, CF2), ꢀ82.8 (t, CF3).
4.2.2. 2-(2,2,3,3,3-Pentafluoro-propionyl)-cyclopentanone (3b)
Starting with cyclopentanone 1b (2.584 g, 30 mmol) and
2,2,3,3,3-pentafluoro-propionic acid ethyl ester 2a (5.763 g,
30 mmol), 3b was isolated as a colourless liquid (3.907 g, 57%),
bp¼72 ꢁC/15 mbar (lit.20a 82 ꢁC/30 mbar). 1H NMR (250 MHz,
Figure 4. Ortep plot of 6l (50% probability level).
CDCl3):
d
¼2.00 (t, 3J¼7.6 Hz, 2H, CH2CH2CH2), 2.52 (t, 3J¼7.9 Hz, 2H,

S. Bu¨ttner et al. / Tetrahedron 64 (2008) 7968–7976
7971
CH2CH2CH2), 2.74–2.84 (m, 2H, CH2CH2CH2), 13.46 (s, 1H, OH); 19F
NMR (235 MHz, CDCl3):
¼ꢀ121.9 (m, CF2), ꢀ83.3 (t, CF3).
ꢀ122.8 (m, CF2), ꢀ122.5 (m, CF2), ꢀ122.0 (m, CF2), ꢀ121.6 (m,
CF2), ꢀ121.0 (m, CF2), ꢀ80.8 (t, CF3); 13C NMR (75 MHz, CDCl3):
d
d
¼13.5 (CH3), 19.0 (CH2), 40.0 (CH2), 97.2 (CH), 178.0 (t, 2J¼26.4 Hz,
4.2.3. 4,4,5,5,5-Pentafluoro-1-phenyl-pentane-1,3-dione (3c)
Starting with 1-phenyl-ethanone 1c (1.056 g, 8.79 mmol) and
2,2,3,3,3-pentafluoro-propionic acid ethyl ester 2a (1.689 g,
8.79 mmol), 3c was isolated as a colourless liquid (1.002 g, 43%),
bp¼85 ꢁC/4 mbar (lit.20b 75.5–76.5 ꢁC/4 mbar). 1H NMR (250 MHz,
COCH2), 196.4 (CF2COH). MS (EI, 70 eV): m/z (%)¼482 (Mþ, 5), 454
(13), 439 (67), 113 (100); HRMS (ESI, 70 eV) calcd for C13H9F15O2
([MþH]þ): 483.04358, found: 483.04328. Anal. Calcd for
C13H9F15O2 (482.19): C, 32.38; H, 1.88. Found: C, 32.24; H, 1.73.
CDCl3):
d
¼6.65 (s, 1H, CH), 7.48–7.57 (m, 2H, PhH), 7.60–7.69 (m,1H,
4.2.10. 2-(2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-Pentadecafluoro-octanoyl)-
cyclopentanone (3j)
PhH), 7.92–8.01 (m, 2H, PhH), 15.32 (s, 1H, OH); 19F NMR (235 MHz,
CDCl3):
¼ꢀ123.9 (m, CF2), ꢀ82.6 (t, CF3).
d
Starting with cyclopentanone 1b (2.103 g, 25 mmol) and
2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-pentadecafluoro-octanoic acid methyl
ester 2d (5.137 g, 12 mmol), 3j was isolated as a colourless liquid
(3.979 g, 69%), bp¼72 ꢁC/0.5 mbar (lit.20f 75 ꢁC/0.8 mbar). 1H NMR
4.2.4. 5,5,6,6,7,7,7-Heptafluoro-heptane-2,4-dione (3d)
Starting with acetone 1d (1.952 g, 25 mmol) and 2,2,3,3,4,4,4-
heptafluoro-butyric acid ethyl ester 2b (6.052 g, 25 mmol), 3d was
isolated as a colourless liquid (3.014 g, 47%), bp¼48 ꢁC/20 mbar
(lit.20c 55.5–56.8 ꢁC/38–39 mbar). 1H NMR (250 MHz, CDCl3):
(250 MHz, CDCl3):
d
¼2.00 (t, 3J¼7.5 Hz, 2H, CH2CH2CH2), 2.53 (t,
3J¼7.9 Hz, 2H, CH2CH2CH2), 2.74–2.85 (m, 2H, CH2CH2CH2), 13.51 (s,
1H, OH);19FNMR(235 MHz,CDCl3):
CF2), ꢀ122.0 (m, CF2), ꢀ121.8 (m, CF2), ꢀ118.5 (m, CF2), ꢀ80.8 (t, CF3).
d¼ꢀ126.1 (m, CF2),ꢀ122.7(m, 4F,
d
¼2.23 (s, 3H, CH3), 5.97 (s, 1H, CH); 19F NMR (235 MHz, CDCl3):
¼ꢀ127.0 (m, CF2), ꢀ122.1 (m, CF2), ꢀ80.7 (t, CF3).
d
4.2.11. 4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-Pentadecafluoro-1-phenyl-
pentane-1,3-dione (3k)
4.2.5. 1,1,1,2,2,3,3-Heptafluoro-nonane-4,6-dione (3e)
Starting with 2-pentanone 1a (2.153 g, 25 mmol) and
2,2,3,3,4,4,4-heptafluoro-butyric acid ethyl ester 2b (6.052 g,
25 mmol), 3e was isolated as a colourless liquid (5.626 g, 80%),
Starting with 1-phenyl-ethanone 1c (1.081 g, 9.00 mmol) and
2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-pentadecafluoro-octanoic acid methyl
ester 2d (3.853 g, 9 mmol), 3k was isolated as a colourless liquid
(2.881 g, 62%), bp¼115 ꢁC/0.5 mbar. 1H NMR (250 MHz, CDCl3):
bp¼75 ꢁC/15 mmHg. 1H NMR (250 MHz, CDCl3):
d
¼0.99 (t,
3J¼7.4 Hz, 3H, CH2CH2CH3), 1.62–1.78 (m, 2H, CH2CH2CH3), 2.42 (t,
d
¼6.62 (s, 1H, CH), 7.47–7.57 (m, 2H, PhH), 7.60–7.68 (m, 1H, PhH),
3J¼7.5 Hz, 2H, CH2CH2CH3), 5.96 (s, 1H, CH); 19F NMR (235 MHz,
7.93–8.01 (m, 2H, PhH), 15.30 (s, 1H, OH); 19F NMR (235 MHz,
CDCl3):
CDCl3):
d
¼ꢀ127.0 (m, CF2), ꢀ122.0 (m, CF2), ꢀ80.7 (t, CF3).
d
¼ꢀ126.1 (m, CF2), ꢀ122.7 (m, CF2), ꢀ122.3 (m, CF2), ꢀ122.0
(m, CF2), ꢀ121.5 (m, CF2), ꢀ120.6 (m, CF2), ꢀ80.8 (t, CF3).
4.2.6. 2-(2,2,3,3,4,4,4-Heptafluoro-butyryl)-cyclopentanone (3f)
Starting with cyclopentanone 1b (2.103 g, 25 mmol) and
2,2,3,3,4,4,4-heptafluoro-butyric acid ethyl ester 2b (6.052 g,
25 mmol), 3f was isolated as a colourless liquid (4.771 g, 68%),
bp¼135 ꢁC/760 mbar (lit.20f 45 ꢁC/30 mbar). 1H NMR (250 MHz,
4.3. General procedure for the synthesis of 3-silyloxy-1-
(perfluoroalkyl)prop-2-en-1-ones 4a–k
To a stirred solution of perfluoralkyl-dione 3 (1.0 equiv) in
diethyl ether (2 mL/1.0 mmol 3), triethylamine (1.0 equiv) and
TMSOTf (0.95 equiv) were added at 0 ꢁC under an argon atmo-
sphere. The solution was stirred for 30 min at 0 ꢁC. The temperature
of the reaction mixture was allowed to rise to 20 ꢁC and stirring was
continued for 3 days. A liquid salt layer separated at the bottom of
the flask. The upper layer (ether solution containing the product)
was transferred to a dry flask by syringe under an argon atmo-
sphere. Diethyl ether (1.5 mL/mmol 3) was added to the liquid salt
layer, the mixture was stirred for 2 min and the layers were
allowed to separate within 2 h. The ether solutions were
combined and concentrated in vacuo. Due to their unstable nature,
silyl enol ethers 4a–k were directly used for the synthesis of phe-
nols 6a–w.
CDCl3):
d
¼2.00 (t, 3J¼7.6 Hz, 2H, CH2CH2CH2), 2.52 (t, 3J¼7.9 Hz, 2H,
CH2CH2CH2), 2.74–2.84 (m, 2H, CH2CH2CH2), 13.47 (s, 1H, OH); 19F
NMR (235 MHz, CDCl3):
(t, CF3).
d¼ꢀ127.2 (m, CF2), ꢀ119.5 (m, CF2), ꢀ80.7
4.2.7. 4,4,5,5,6,6,6-Heptafluoro-1-phenyl-hexane-1,3-dione (3g)
Starting with 1-phenyl-ethanone 1c (1.056 g, 8.79 mmol) and
2,2,3,3,4,4,4-heptafluoro-butyric acid ethyl ester 2b (6.052 g,
25 mmol), 3g was isolated as a colourless liquid (6.344 g, 80%),
bp¼65 ꢁC/1 mbar (lit.20g 70 ꢁC/0.1 mbar). 1H NMR (250 MHz,
CDCl3):
d
¼6.63 (s,1H, CH), 7.48–7.56 (m, 2H, PhH), 7.60–7.68 (m,1H,
PhH), 7.93–8.00 (m, 2H, PhH), 15.32 (s, 1H, OH); 19F NMR (235 MHz,
CDCl3):
¼ꢀ126.8 (m, CF2), ꢀ121.7 (m, CF2), ꢀ80.6 (t, CF3).
d
4.2.8. 5,5,6,6,7,7,8,8,9,9,10,10,10-Tridecafluoro-decane-2,4-dione (3h)
Starting with acetone 1d (1.405 g, 18 mmol) and
2,2,3,3,4,4,5,5,6,6,7,7,7-tridecafluoro-heptanoic acid methyl ester
2c (6.806 g, 18 mmol), 3h was isolated as a colourless liquid
(5.122 g, 70%), bp¼95 ꢁC/15 mbar. 1H NMR (250 MHz, CDCl3):
4.4. General procedure for the synthesis of
3-(perfluoroalkyl)phenols 6a–w
To a stirred dichloromethane solution (2 mL/1.0 mmol of 4) of
silyl enol ether 4 (1.0 equiv) and of 1,3-bis(silyl enol ether) 5
(1.1 equiv) was added TiCl4 (1.1 equiv) at ꢀ78 ꢁC under an argon
atmosphere. The temperature of the reaction mixture was allowed
to rise to 20 ꢁC in 16 h. To the solution was added hydrochloric acid
(10%, 3 mL/mmol) and the mixture was extracted with dichloro-
methane (3ꢂ15 mL). The combined organic layers were dried
(Na2SO4), filtered and the filtrate was concentrated under reduced
pressure. The residue was purified by column chromatography
(silica gel, heptanes/EtOAc/heptanes¼1:10).
d
d
¼2.23 (s, 3H, CH3), 5.97 (s, 1H, CH); 19F NMR (235 MHz, CDCl3):
¼ꢀ126.2 (m, CF2), ꢀ122.9 (m, CF2), ꢀ122.6 (m, CF2), ꢀ121.8 (m,
CF2), ꢀ121.1 (m, CF2), ꢀ80.9 (t, CF3).
4.2.9. 7,7,8,8,9,9,10,10,11,11,12,12,13,13,13-Pentadecafluoro-
tridecane-4,6-dione (3i)
Starting with 2-pentanone 1a (1.034 g, 12 mmol) and
2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-pentadecafluoro-octanoic acid methyl
ester 2d (5.137 g, 12 mmol), 3i was isolated as a colourless liquid
(4.040 g, 70%), bp¼110 ꢁC/3 mbar. 1H NMR (250 MHz, CDCl3):
4.4.1. 2-Hydroxy-6-pentafluoroethyl-4-propyl-benzoic acid
methyl ester (6a)
Starting with silyl enol ether 4a (0.620 g, 2.04 mmol), 1,3-bis-
silyl enol ether 5a (0.574 g, 2.20 mmol) and TiCl4 (0.24 mL,
d
¼0.99 (t, 3J¼7.4 Hz, 3H, CH2CH2CH3), 1.62–1.79 (m, 2H,
CH2CH2CH3), 2.42 (t, 3J¼7.5 Hz, 2H, CH2CH2CH3), 5.96 (s, 1H, CH),
14.60 (s, 1H, OH); 19F NMR (235 MHz, CDCl3):
d¼ꢀ126.1 (m, CF2),

7972
S. Bu¨ttner et al. / Tetrahedron 64 (2008) 7968–7976
2.20 mmol), 6a was isolated as a pale yellow solid (0.294 g, 46%),
empirical from equivalents. Max. and min. transmissions: 0.9885
and 0.9421. Refinement method: full-matrix least-squares on F2.
Data/restraints/parameters: 4597/0/206. Goodness-of-fit on F2:
mp¼43 ꢁC. 1H NMR (250 MHz, CDCl3):
d
¼0.95 (t, 3J¼7.3 Hz, 3H,
CH2CH3), 1.57–1.74 (m, 2H, CH2CH3), 2.61 (t, 3J¼7.6 Hz, 2H, ArCH2),
3.93 (s, 3H, OCH3), 7.02 (s, 2H, ArH), 9.48 (s, 1H, OH); 19F NMR
1.028. Final R indices [I>2
s
(I)]: R1¼0.0501, wR2¼0.1211. R indices
(235 MHz, CDCl3):
(75 MHz, CDCl3):
d
¼ꢀ103.0 (m, CF2), ꢀ80.9 (t, CF3); 13C NMR
(all data): R1¼0.0869, wR2¼0.1453. Largest diff. peak and hole:
d
¼13.6 (CH2CH3), 23.7 (CH2), 37.8 (CH2), 52.7
0.512 and ꢀ0.257 e/Å3.
(OCH3), 111.5 (t, 3J¼2.2 Hz, CCO2CH3), 121.0 (CHCOH), 121.3 (t,
3J¼8.9 Hz, CHCC2F5), 128.7 (t, 2J¼23.0 Hz, CC2F5), 148.9 (CC3H7),
4.4.4. 6-Hydroxy-4-pentafluoroethyl-indane-5-carboxylic acid
methyl ester (6d)
Starting with silyl enol ether 4b (0.607 g, 2.01 mmol), 1,3-bis-
silyl enol ether 5a (0.574 g, 2.20 mmol) and TiCl4 (0.24 mL,
2.20 mmol), 6d was isolated as a pale yellow solid (0.354 g, 57%),
159.7 (COH), 169.2 (CO); IR (ATR, cmꢀ1):
n
¼3286 (m), 2965 (w),
2940 (w), 2879 (w),1708 (s),1614 (m),1585 (w),1434 (m),1307 (m),
1277 (m), 1208 (s), 1174 (m), 1154 (m), 1135 (m), 1090 (m), 1038 (s),
990 (m); MS (EI, 70 eV): m/z (%)¼312 (Mþ, 32), 280 (96), 252 (100),
223 (40); HRMS (EI, 70 eV) calcd for C13H13F5O3 (Mþ): 312.07794,
found: 312.07795. Anal. Calcd for C13H13F5O3 (312.23): C, 50.01; H,
4.20. Found: C, 50.17; H, 4.21.
mp¼137 ꢁC; 1H NMR (250 MHz, CDCl3):
d
¼1.97–2.11 (m, 2H,
ArCH2CH2), 2.88 (t, 3J¼7.5 Hz, 2H, ArCH2), 3.00 (t, 3J¼7.3 Hz, 2H,
ArCH2), 3.90 (s, 3H, CH3), 7.02 (s, 1H, ArH), 8.20 (s, 1H, OH); 19F NMR
(235 MHz, CDCl3):
(75 MHz, CDCl3):
d
¼ꢀ102.1 (m, CF2), ꢀ79.1 (t, CF3); 13C NMR
4.4.2. 1-(2-Hydroxy-6-pentafluoroethyl-4-propyl-phenyl)-
ethanone (6b)
Starting with silyl enol ether 4a (0.573 g, 1.88 mmol), 1,3-bis-
silyl enol ether 5b (0.538 g, 2.20 mmol) and TiCl4 (0.24 mL,
2.20 mmol), 6b was isolated as a colourless solid (0.237 g, 42%),
d
¼25.4 (CH2), 32.7 (CH2), 32.9 (CH2), 52.7 (CH3),
114.2 (t, 3J¼3.9 Hz, CCC2F5), 116.8 (CHCOH), 124.2 (t, 2J¼23.5 Hz,
CC2F5), 137.0 (t, 3J¼4.1 Hz, CCC2F5), 151.6 (CCHCOH), 156.5 (COH),
169.5 (CO); IR (ATR, cmꢀ1):
n
¼3329 (m), 3004 (w), 2962 (w), 2853
(w), 1698 (m), 1606 (w), 1447 (m), 1437 (m), 1289 (m), 1191 (m),
1181 (m), 1165 (m), 1133 (m), 1117 (m), 1027 (m). MS (EI, 70 eV): m/z
(%)¼310 (Mþ, 13), 278 (100), 149 (32), 131 (15); HRMS (EI, 70 eV)
calcd for C13H11F5O3 (Mþ): 310.06229, found: 310.06187. Anal.
Calcd for C13H11F5O3 (310.22): C, 50.33; H, 3.57. Found: C, 50.48; H,
3.38.
mp¼108 ꢁC. 1H NMR (250 MHz, CDCl3):
d
¼0.92 (t, 3J¼7.3 Hz, 3H,
CH2CH3), 1.51–1.69 (m, 2H, CH2CH3), 2.53 (t, 3J¼7.7 Hz, 2H, ArCH2),
2.53 (s, 3H, COCH3), 6.84 (s, 1H, ArH), 6.91 (s, 1H, ArH), 7.04 (s, 1H,
OH); 19F NMR (235 MHz, CDCl3):
d
¼ꢀ107.2 (m, CF2), ꢀ83.5 (t, CF3);
13C NMR (75 MHz, CDCl3):
d
¼13.5 (CH2CH3), 23.9 (CH2), 32.2
(COCH3), 37.5 (CH2), 119.8 (t, 3J¼7.2 Hz, CHCC2F5), 119.9 (CHCOH),
125.2 (t, 2J¼23.4 Hz, CC2F5), 126.2 (t, 3J¼2.7 Hz, CCOCH3), 146.0
4.4.5. 7-Ethyl-6-hydroxy-4-pentafluoroethyl-indan-5-carboxylic
acid methyl ester (6e)
Starting with silyl enol ether 4b (0.456 g, 1.51 mmol), 1,3-bis-
silyl enol ether 5d (0.480 g, 1.66 mmol) and TiCl4 (0.18 mL,
1.65 mmol), 6e was isolated as a yellow solid (0.234 g, 50%),
(CC3H7), 153.1 (COH), 205.8 (CO); IR (ATR, cmꢀ1):
n
¼3244 (m), 2971
(w), 2941 (w), 2865 (w), 1687 (m), 1614 (m), 1585 (w), 1433 (m),
1357 (m), 1321 (m), 1281 (m), 1200 (s), 1173 (m), 1145 (m), 1134 (s),
1047 (m), 987 (m). MS (EI, 70 eV): m/z (%)¼296 (Mþ, 11), 281 (100),
233 (10); HRMS (EI, 70 eV) calcd for C13H13F5O2 (Mþ): 296.08302,
found: 296.08316.
mp¼65 ꢁC. 1H NMR (250 MHz, CDCl3):
d
¼1.15 (t, 3J¼7.5 Hz, 3H,
CH2CH3), 1.97–2.11 (m, 2H, ArCH2CH2), 2.66 (q, 3J¼7.5 Hz, 2H,
CH2CH3), 2.88 (t, 3J¼7.5 Hz, 2H, ArCH2), 3.02 (t, 3J¼7.4 Hz, 2H,
ArCH2), 3.90 (s, 3H, CH3), 8.48 (s, 1H, OH); 19F NMR (235 MHz,
4.4.3. 1-(2-Hydroxy-3-methyl-6-pentafluoroethyl-4-propyl-
phenyl)-propan-1-one (6c)
Starting with silyl enol ether 4a (0.619 g, 2.04 mmol), 1,3-bis-
silyl enol ether 5c (0.600 g, 2.20 mmol) and TiCl4 (0.24 mL,
2.20 mmol), 6c was isolated as a yellow solid (0.216 g, 33%),
CDCl3):
CDCl3):
d
¼ꢀ101.0 (m, CF2), ꢀ78.8 (t, CF3); 13C NMR (75 MHz,
d¼12.8 (CH2CH3), 21.1 (CH2), 24.9 (CH2), 31.2 (CH2), 33.1
(CH2), 52.6 (CH3), 113.4 (t, 3J¼3.9 Hz, CCC2F5), 121.5 (t, 2J¼23.4 Hz,
CC2F5), 132.2 (CCH2CH3), 136.5 (t, 3J¼4.1 Hz, CCC2F5), 149.7
(CCCH2CH3), 154.6 (COH), 170.3 (CO); IR (ATR, cmꢀ1): v¼3235 (w),
3012 (w), 2963 (w), 2935 (w), 2874 (w), 1673 (m), 1593 (w), 1463
(w), 1444 (m), 1340 (m), 1292 (m), 1195 (s), 1162 (s), 1119 (m), 1096
(m), 1070 (m), 1050 (m), 1038 (m), 997 (m); MS (EI, 70 eV): m/z
(%)¼338 (Mþ, 23), 306 (100), 278 (27); HRMS (EI, 70 eV) calcd for
mp¼72 ꢁC. 1H NMR (250 MHz, CDCl3):
d
¼0.97 (t, 3J¼7.3 Hz, 3H,
CH2CH2CH3), 1.17 (t, 3J¼7.2 Hz, 3H, COCH2CH3), 1.50–1.66 (m, 2H,
CH2CH2CH3), 2.21 (s, 3H, ArCH3), 2.61 (t, 3J¼7.7 Hz, 2H, ArCH2), 2.79
(q, 3J¼7.2 Hz, 2H, COCH2), 6.11 (s,1H, OH), 6.95 (s,1H, ArH); 19F NMR
(235 MHz, CDCl3):
(75 MHz, CDCl3):
d
¼ꢀ107.0 (m, CF2), ꢀ83.4 (t, CF3); 13C NMR
C
15H15F5O3 (Mþ): 338.09359, found 338.09297.
d
¼7.9 (CH3), 11.5 (CH3), 13.8 (CH3), 23.2 (CH2), 35.8
(CH2), 38.1 (CH2), 120.8 (t, 3J¼7.3 Hz, CHCC2F5), 122.3 (t, 2J¼23.5 Hz,
CC2F5), 125.9 (t, 3J¼2.7 Hz, CCOCH2CH3), 128.0 (C), 143.8 (C), 151.0
(COH), 207.9 (CO); IR (ATR, cmꢀ1):
n¼3435 (m), 2977 (w), 2958 (w),
4.4.6. 1-(6-Hydroxy-4-pentafluoroethyl-indan-5-yl)-ethanone (6f)
Starting with silyl enol ether 4b (0.611 g, 2.02 mmol), 1,3-bis-
silyl enol ether 5b (0.538 g, 2.20 mmol) and TiCl4 (0.24 mL,
2.20 mmol), 6f was isolated as a colourless solid (0.240 g, 40%),
2943 (w), 2874 (w), 1699 (m), 1609 (w), 1573 (w), 1310 (m), 1194 (s),
1172 (s), 1134 (m), 1109 (m), 1096 (m), 1054 (m), 1025 (m). MS (EI,
70 eV): m/z (%)¼324 (Mþ, 5), 295 (100), 247 (12), 69 (15); HRMS (EI,
70 eV) calcd for C15H17F5O2 (Mþ): 324.11432, found: 324.11393.
Anal. Calcd for C15H17F5O2 (324.29): C, 55.56; H, 5.28. Found: C,
55.63; H, 5.24.
mp¼146 ꢁC. 1H NMR (250 MHz, CDCl3):
d
¼1.97–2.10 (m, 2H,
ArCH2CH2), 2.51 (s, 3H, CH3), 2.80 (t, 3J¼7.5 Hz, 2H, ArCH2), 2.97 (t,
3J¼7.3 Hz, 2H, ArCH2), 6.24 (s, 1H, OH), 6.83 (s, 1H, ArH); 19F NMR
Crystal data of 6c. Empirical formula: C15H17F5O2. Formula
weight: 324.29. Temperature: 173(2) K. Wavelength: 0.71073 Å.
Crystal system: monoclinic. Space group (H.-M.): P21/c. Space group
(235 MHz, CDCl3):
(63 MHz, CDCl3):
d
¼ꢀ107.2 (m, CF2), ꢀ83.0 (t, CF3); 13C NMR
d
¼25.4 (CH2), 32.1 (CH2), 32.3 (CH3), 32.5 (CH2),
116.3 (CHCOH), 120.7 (t, 2J¼23.4 Hz, CC2F5), 128.0 (t, 3J¼3.9 Hz,
(Hall): ꢀP2ybc. Unit cell dimensions: a¼5.97150(10) Å,
a
¼90ꢁ,
CCC2F5), 136.1 (t, 3J¼4.1 Hz, CCC2F5), 148.5 (CCHCOH), 151.1 (COH),
b¼22.7779(5) Å,
b
¼99.6550(10)ꢁ, c¼11.7411(3) Å,
g
¼90ꢁ. Volume:
205.5 (CO); IR (ATR, cmꢀ1):
n¼3254 (w), 2977 (w), 2946 (w), 2894
1574.38(6) Å3; Z¼4. Density (calculated): 1.368 Mg/m3. Absorption
(w), 2850 (w), 1694 (m), 1605 (w), 1445 (w), 1433 (w), 1304 (m),
1230 (m), 1219 (m), 1198 (m), 1179 (m), 1160 (m), 1130 (m), 1047
(m), 1024 (m); MS (EI, 70 eV): m/z (%)¼294 (Mþ, 21), 279 (100), 231
coefficient:
0.128 mmꢀ1
.
F(000)¼672.
Crystal
size:
0.47ꢂ0.30ꢂ0.09 mm3.
Q
Range for data collection: 2.51–29.99ꢁ.
Index ranges: ꢀ8ꢃhꢃ8, ꢀ28ꢃkꢃ32, ꢀ16ꢃlꢃ16. Reflections col-
(14), 133 (7); HRMS (EI, 70 eV) calcd for C
13H11F5O2 (Mþ):
lected: 21,080. Independent reflections: 4597 [R(int)¼0.0342].
294.06737, found 294.06718. Anal. Calcd for C13H11F5O2 (294.22): C,
53.07; H, 3.77. Found: C, 53.14; H, 3.64.
Completeness to
Q
¼29.99ꢁ: 99.9%. Absorption correction: semi-

S. Bu¨ttner et al. / Tetrahedron 64 (2008) 7968–7976
7973
4.4.7. 3-Hydroxy-5-pentafluoroethyl-biphenyl-4-carboxylic acid
methyl ester (6g)
10), 329 (100), 281 (18), 183 (7); HRMS (EI, 70 eV) calcd for
C
C
18H15F5O2 (Mþ): 358.09867, found 358.09878. Anal. Calcd for
18H15F5O2 (358.30): C, 60.34; H, 4.22. Found: C, 59.99; H, 4.13.
Starting with silyl enol ether 4c (0.677 g, 2.00 mmol), 1,3-bis-
silyl enol ether 5a (0.573 g, 2.20 mmol) and TiCl4 (0.24 mL,
2.20 mmol), 6g was isolated as a colourless solid (0.309 g, 45%),
4.4.10. 2-Heptafluoropropyl-6-hydroxy-4-methyl-benzoic acid
methyl ester (6j)
mp¼142 ꢁC. 1H NMR (250 MHz, CDCl3):
¼3.98 (s, 3H, OCH3), 7.40–
d
7.64 (m, 7H, ArH), 9.55 (s, 1H, OH); 19F NMR (235 MHz, CDCl3):
Starting with silyl enol ether 4d (0.619 g, 1.90 mmol), 1,3-bis-
silyl enol ether 5a (0.574 g, 2.20 mmol) and TiCl4 (0.24 mL,
2.20 mmol), 6j was isolated as a colourless solid (0.286 g, 45%),
d
¼ꢀ103.1 (m, CF2), ꢀ80.8 (t, CF3); 13C NMR (63 MHz, CDCl3):
¼52.9
d
(OCH3), 112.7 (CCO2CH3), 119.5 (CHCOH), 119.6 (t, 3J¼9.2 Hz,
CHCC2F5), 127.2 (Ph), 129.0 (Ph), 129.1 (Ph), 129.5 (t, 2J¼23.2 Hz,
CC2F5), 138.3 (C), 146.2 (C), 159.9 (COH), 169.1 (CO); IR (ATR, cmꢀ1):
mp¼85 ꢁC. 1H NMR (250 MHz, CDCl3):
¼2.40 (s, 3H, ArCH3), 3.91
d
(s, 3H, OCH3), 7.00 (s, 1H, Ar), 7.03 (s, 1H, Ar), 9.78 (s, 1H, OH); 19F
n
¼3389 (m), 3040 (w), 3010 (w), 2956 (w), 1722 (s), 1614 (m), 1573
NMR (235 MHz, CDCl3):
d
¼ꢀ121.1 (m, CF2), ꢀ99.7 (m, CF2), ꢀ80.7 (t,
(m), 1412 (m), 1299 (m), 1217 (s), 1193 (s), 1154 (s), 1042 (s); MS (EI,
70 eV): m/z (%)¼346 (Mþ, 41), 314 (100), 286 (24), 217 (34),188 (15),
108 (14); HRMS (EI, 70 eV) calcd for C16H11F5O3 (Mþ): 346.06229,
found 346.06246. Anal. Calcd for C16H11F5O3 (346.25): C, 55.50; H,
3.20. Found: C, 55.72; H, 2.94.
Crystal data of 6g. Empirical formula: C16H11F5O3. Formula
weight: 346.25. Temperature: 173(2) K. Wavelength: 0.71073 Å.
Crystal system: monoclinic. Space group (H.-M.): P21/c. Space group
CF3); 13C NMR (75 MHz, CDCl3):
d¼21.6 (ArCH3), 52.6 (OCH3), 111.1
(t, 3J¼2.5 Hz, CCO2CH3), 121.8 (t, 3J¼9.6 Hz, CHCC3F7), 121.9
(CHCOH), 129.1 (t, 2J¼23.6 Hz, CC3F7), 144.4 (CCH3), 160.2 (COH),
169.3 (CO); IR (ATR, cmꢀ1):
n
¼3300 (m), 1705 (s), 1615 (m), 1344 (s),
1300 (s), 1222 (s), 1198 (s), 1130 (m), 1111 (s); MS (EI, 70 eV): m/z
(%)¼334 (Mþ, 25), 302 (100), 255 (9), 155 (59); HRMS (EI, 70 eV)
calcd for C12H9F7O3 (Mþ): 334.04344, found 334.04406. Anal. Calcd
for C12H9F7O3 (334.19): C, 43.13; H, 2.71. Found: C, 43.13; H, 2.77.
Crystal data of 6j. Empirical formula: C12H9F7O3. Formula
weight: 334.19. Temperature: 173(2) K. Wavelength: 0.71073 Å.
Crystal system: monoclinic. Space group (H.-M.): P21/c. Space group
(Hall): ꢀP2ybc. Unit cell dimensions: a¼9.6140(3) Å,
a
¼90ꢁ,
b¼15.1090(5) Å,
b
¼91.042(2)ꢁ, c¼10.3975(3) Å,
g
¼90ꢁ. Volume:
1510.07(8) Å3; Z¼4. Density (calculated) 1.523 Mg/m3. Absorption
coefficient:
0.145 mmꢀ1
.
F(000)¼704
.
Crystal
size:
(Hall): ꢀP2ybc. Unit cell dimensions: a¼11.6397(4) Å,
a
¼90ꢁ,
0.56ꢂ0.44ꢂ0.18 mm3.
Q
Range for data collection: 2.51–30.00ꢁ.
b¼10.1363(3) Å,
b
¼100.016(2)ꢁ, c¼11.2196(4) Å,
g
¼90ꢁ. Volume:
Index ranges: ꢀ13ꢃhꢃ13, ꢀ18ꢃkꢃ21, ꢀ14ꢃlꢃ13. Reflections col-
lected: 19,091. Independent reflections: 4409 [R(int)¼0.0225].
1303.55(8) Å3; Z¼4. Density (calculated): 1.703 Mg/m3. Absorption
coefficient:
0.185 mmꢀ1
.
F(000)¼672.
Crystal
size:
Completeness to
Q
¼30.00ꢁ: 99.9%. Absorption correction: semi-
0.48ꢂ0.38ꢂ0.11 mm3.
Q
Range for data collection: 2.68–30.00ꢁ.
empirical from equivalents. Max. and min. transmissions: 0.9744
and 0.9234. Refinement method: full-matrix least-squares on F2.
Data/restraints/parameters 4409/0/223. Goodness-of-fit on F2:
Index ranges: ꢀ16ꢃhꢃ16, ꢀ14ꢃkꢃ14, ꢀ15ꢃlꢃ15. Reflections col-
lected: 19,441. Independent reflections: 3799 [R(int)¼0.0315].
Completeness to
Q
¼30.00ꢁ: 99.7%. Absorption correction: semi-
1.034. Final R indices [I>2
s
(I)]: R1¼0.0365, wR2¼0.0973. R indices
empirical from equivalents. Max. and min. transmissions: 0.9800
and 0.9166. Refinement method: full-matrix least-squares on F2.
Data/restraints/parameters: 3799/0/205. Goodness-of-fit on F2:
(all data): R1¼0.0445, wR2¼0.1057. Extinction coefficient:
0.0127(16). Largest diff. peak and hole: 0.397 and ꢀ0.275 e/Å3.
1.029. Final R indices [I>2
s
(I)]: R1¼0.0415, wR2¼0.1061. R indices
4.4.8. 1-(3-Hydroxy-5-pentafluoroethyl-biphenyl-4-yl)-
ethanone (6h)
(all data): R1¼0.0543, wR2¼0.1170. Largest diff. peak and hole:
0.563 and ꢀ0.423 e/ Å3.
Starting with silyl enol ether 4c (0.626 g, 2.06 mmol), 1,3-bis-
silyl enol ether 5b (0.538 g, 2.20 mmol) and TiCl4 (0.24 mL,
2.20 mmol), 6h was isolated as a colourless solid (0.279 g, 41%),
4.4.11. 3-Ethyl-6-heptafluoropropyl-2-hydroxy-4-methyl-benzoic
acid methyl ester (6k)
Starting with silyl enol ether 4d (0.436 g, 1.34 mmol), 1,3-bis-
silyl enol ether 5d (0.476 g, 1.65 mmol) and TiCl4 (0.18 mL,
1.65 mmol), 6k was isolated as a yellow liquid (0.314 g, 65%). 1H
mp¼141 ꢁC. 1H NMR (250 MHz, CDCl3):
d
¼2.60 (s, 3H, CH3), 6.76 (s,
1H, OH), 7.27 (s, 1H, ArH), 7.34 (s, 1H, ArH), 7.41–7.56 (m, 5H, PhH);
19F NMR (235 MHz, CDCl3):
NMR (125 MHz, CDCl3):
d
¼ꢀ106.9 (m, CF2), ꢀ83.2 (t, CF3); 13C
d
¼32.2 (CH3), 118.5 (CHCOH), 118.7 (t,
NMR (250 MHz, CDCl3):
d
¼1.14 (t, 3J¼7.5 Hz, 3H, CH2CH3), 2.38 (s,
3J¼6.5 Hz, CHCC2F5), 126.1 (t, 2J¼23.5 Hz, CC2F5), 127.0 (C), 127.2
3H, ArCH3), 2.74 (q, 3J¼7.5 Hz, 2H, CH2CH3), 3.91 (s, 3H, OCH3), 6.98
(Ph), 128.6 (Ph), 129.0 (Ph), 138.5 (C), 144.1 (C), 153.5 (COH), 204.8
(s, 1H, Ar), 10.06 (s, 1H, OH); 19F NMR (235 MHz, CDCl3):
d¼ꢀ121.1
(CO); IR (ATR, cmꢀ1):
n¼3381 (w), 3066 (w), 3033 (w), 2927 (w),
(m, CF2), ꢀ99.4 (m, CF2), ꢀ80.8 (t, CF3); 13C NMR (75 MHz, CDCl3):
1700 (m),1612 (m),1409 (m), 1319 (m),1197 (s), 1142 (m),1045 (m);
MS (EI, 70 eV): m/z (%)¼330 (Mþ, 39), 315 (100), 267 (23); HRMS (EI,
70 eV) calcd for C16H11F5O2 (Mþ): 330.06737, found 330.06706.
d
¼12.6 (CH2CH3), 19.7 (ArCH3), 19.9 (CH2CH3), 52.6 (OCH3), 110.6 (t,
3J¼2.3 Hz, CCO2CH3), 122.3 (t, 3J¼9.6 Hz, CHCC3F7), 125.9 (t,
2J¼23.6 Hz, CC3F7), 135.5 (CCH2CH3), 141.8 (CCH3), 158.2 (COH),
170.0 (CO); IR (ATR, cmꢀ1):
n
¼2961 (w), 2879 (w), 1677 (m), 1607
4.4.9. 1-(3-Hydroxy-2-methyl-5-pentafluoroethyl-biphenyl-4-yl)-
propan-1-one (6i)
(m), 1440 (m), 1348 (m), 1285 (m), 1223 (s), 1201 (s), 1181 (s), 1151
(m), 1106 (s), 952 (s); MS (EI, 70 eV): m/z (%)¼362 (Mþ, 38), 330
(100), 310 (26), 302 (20); HRMS (EI, 70 eV) calcd for C14H13F7O3
(Mþ): 362.07474, found 362.07409.
Starting with silyl enol ether 4c (0.668 g, 1.97 mmol), 1,3-bis-
silyl enol ether 5c (0.600 g, 2.20 mmol) and TiCl4 (0.24 mL,
2.20 mmol), 6i was isolated as a yellow solid (0.262 g, 37%),
mp¼126 ꢁC. 1H NMR (250 MHz, CDCl3):
d
¼1.22 (t, 3J¼7.3 Hz, 3H,
4.4.12. 1-(2-Heptafluoropropyl-6-hydroxy-4-methyl-phenyl)-
ethanone (6l)
CH2CH3), 2.21 (s, 3H, ArCH3), 2.85 (q, 3J¼7.3 Hz, 2H, CH2CH3), 5.84
(s, 1H, OH), 7.09 (s, 1H, ArH), 7.23–7.50 (m, 5H, PhH); 19F NMR
Starting with silyl enol ether 4d (0.414 g, 1.27 mmol), 1,3-bis-
silyl enol ether 5b (0.403 g, 1.65 mmol) and TiCl4 (0.18 mL,
1.65 mmol), 6l was isolated as a colourless solid (0.163 g, 40%),
(235 MHz, CDCl3):
(75 MHz, CDCl3):
d
¼ꢀ107.3 (m, CF2), ꢀ83.4 (t, CF3); 13C NMR
d
¼7.8 (CH3), 13.4 (CH3), 38.1 (CH2), 122.0 (t,
3J¼7.4 Hz, CHCC7F15), 122.8 (t, 2J¼23.9 Hz, CC7F15), 127.5 (C), 127.7
mp¼109 ꢁC. 1H NMR (250 MHz, CDCl3):
¼2.30 (s, 3H, CH3), 2.51 (s,
d
(C), 127.9 (Ph), 128.4 (Ph), 129.0 (Ph), 139.6 (C), 144.3 (C), 151.0
3H, CH3), 6.80 (s, 1H, Ar), 6.89 (s, 1H, Ar), 6.98 (s, 1H, OH); 19F NMR
(COH), 206.9 (CO); IR (ATR, cmꢀ1):
n
¼3412 (w), 3055 (w), 2986 (w),
(235 MHz, CDCl3):
d
¼ꢀ124.4 (m, CF2), ꢀ104.7 (m, CF2), ꢀ80.1 (t,
2944 (w), 2906 (w), 2884 (w), 1704 (m), 1599 (w), 1564 (w), 1204
CF3); 13C NMR (75 MHz, CDCl3):
d¼21.1 (ArCH3), 32.2 (COCH3),120.7
(s), 1142 (s), 1128 (s), 1099 (m); MS (EI, 70 eV): m/z (%)¼358 (Mþ,
(CHCOH), 120.8 (t, 3J¼7.3 Hz, CHCC3F7), 125.4 (t, 2J¼23.4 Hz, CC3F7),

7974
S. Bu¨ttner et al. / Tetrahedron 64 (2008) 7968–7976
126.3 (t, 3J¼2.8 Hz, CCOCH3), 141.1 (CCH3), 152.9 (COH), 205.1 (CO);
CH2CH2CH3), 1.16 (t, 3J¼7.2 Hz, 3H, COCH2CH3), 1.49–1.66 (m, 2H,
CH2CH2CH3), 2.21 (s, 3H, ArCH3), 2.61 (t, 3J¼7.7 Hz, 2H, ArCH2), 2.77
(q, 3J¼7.2 Hz, 2H, COCH2), 6.03 (s, 1H, OH), 6.94 (s, 1H, ArH); 19F
IR (ATR, cmꢀ1):
n
¼3330 (m), 1694 (m), 1614 (m), 1342 (s), 1219 (s),
1198 (s), 1109 (s); MS (EI, 70 eV): m/z (%)¼318 (Mþ, 16), 303 (100),
255 (23), 155 (5); HRMS (EI, 70 eV) calcd for C12H9F7O2 (Mþ):
318.04853, found 318.04879.
NMR (235 MHz, CDCl3):
d¼ꢀ124.4 (m, CF2), ꢀ104.7 (m, CF2), ꢀ80.1
(t, CF3); 13C NMR (75 MHz, CDCl3):
d
¼7.9 (CH3), 11.5 (CH3), 13.8
Crystallographic data of 6l. Empirical formula: C12H9F7O2. For-
mula weight: 318.19. Temperature: 173(2) K. Wavelength:
0.71073 Å. Crystal system: monoclinic. Space group (H.-M.): P21/c.
Space group (Hall): ꢀP2ybc. Unit cell dimensions: a¼11.3509(4) Å,
(CH3), 23.2 (CH2), 35.7 (CH2), 38.1 (CH2), 121.2 (t, 3J¼7.2 Hz,
CHCC3F7), 122.2 (t, 2J¼23.5 Hz, CC3F7), 126.5 (t, 3J¼2.8 Hz,
CCOCH2CH3), 128.2 (C), 143.6 (C), 150.8 (COH), 207.8 (CO); IR (ATR,
cmꢀ1):
n
¼3379 (m), 2963 (w), 2936 (w), 2876 (w), 1702 (m), 1608
a
¼90ꢁ, b¼10.9404(3) Å,
b
¼99.845(2)ꢁ, c¼10.2349(3) Å,
g
¼90ꢁ.
(w), 1572 (w), 1353 (m), 1223 (s), 1199 (s), 1109 (s); MS (EI, 70 eV):
m/z (%)¼374 (Mþ, 10), 345 (100), 297 (13), 227 (4); HRMS (EI, 70 eV)
calcd for C16H17F7O2 (Mþ): 374.11113, found 374.11086.
Volume: 1252.29(7) Å; Z¼4. Density (calculated): 1.688 Mg/m3.
Absorption coefficient: 0.182 mmꢀ1
.
F(000)¼640. Crystal size:
0.35ꢂ0.31ꢂ0.17 mm3.
Q
Range for data collection: 2.60ꢂ30.00ꢁ.
Index ranges: ꢀ14ꢃhꢃ15, ꢀ15ꢃkꢃ14, ꢀ14ꢃlꢃ13. Reflections col-
lected: 13,542. Independent reflections: 3646 [R(int)¼0.0253].
4.4.16. 4-Heptafluoropropyl-6-hydroxy-indane-5-carboxylic acid
methyl ester (6p)
Completeness to
Q
¼30.00ꢁ: 99.9%. Absorption correction: semi-
Starting with silyl enol ether 4f (0.705 g, 2.00 mmol), 1,3-bis-
silyl enol ether 5a (0.573 g, 2.20 mmol) and TiCl4 (0.24 mL,
2.20 mmol), 6p was isolated as a colourless solid (0.294 g, 41%),
empirical from equivalents. Max. and min. transmissions: 0.9698
and 0.9391. Refinement method: full-matrix least-squares on F2.
Data/restraints/parameters 3646/0/196. Goodness-of-fit on F2:
mp¼90 ꢁC. 1H NMR (250 MHz, CDCl3):
d
¼1.98–2.11 (m, 2H,
1.039. Final R indices [I>2
s
(I)]: R1¼0.0379, wR2¼0.1006. R indices
ArCH2CH2), 2.89 (t, 3J¼7.5 Hz, 2H, ArCH2), 3.02 (t, 3J¼7.4 Hz, 2H,
(all data): R1¼0.0482, wR2¼0.1089. Largest diff. peak and hole:
ArCH2), 3.88 (s, 3H, CH3), 7.04 (s, 1H, ArH), 8.37 (s, 1H, OH); 19F NMR
0.402 and ꢀ0.273 e/ Å3
(235 MHz, CDCl3):
d
¼ꢀ120.1 (m, CF2), ꢀ99.5 (m, CF2), ꢀ80.8 (t, CF3);
13C NMR (75 MHz, CDCl3):
d
¼25.4 (CH2), 32.8 (CH2), 32.9 (CH2), 52.7
4.4.13. 1-(6-Heptafluoropropyl-2-hydroxy-3,4-dimethyl-phenyl)-
propan-1-one (6m)
Starting with silyl enol ether 4d (0.414 g, 1.27 mmol), 1,3-bis-
silyl enol ether 5c (0.450 g, 1.65 mmol) and TiCl4 (0.18 mL,
1.65 mmol), 6m was isolated as a pale yellow solid (0.163 g, 37%),
(CH3), 114.2 (t, 3J¼4.2 Hz, CCC3F7), 117.1 (CHCOH), 124.2 (t,
2J¼23.5 Hz, CC3F7), 137.2 (t, 3J¼4.3 Hz, CCC3F7), 151.7 (CCHCOH),
156.8 (COH), 169.6 (CO); IR (ATR, cmꢀ1):
n
¼3359 (m), 2966 (w),
2956 (w), 2873 (w), 1712 (s), 1608 (m), 1441 (m), 1342 (m), 1284 (s),
1239 (s), 1215 (s), 1195 (s), 1167 (s), 1106 (s), 962 (s), 950 (s), 732 (s);
MS (EI, 70 eV): m/z (%)¼360 (Mþ, 16), 328 (100), 209 (8), 181 (24);
HRMS (EI, 70 eV) calcd for C14H11F7O3 (Mþ): 360.05909, found
360.05893. Anal. Calcd for C14H11F7O3 (360.22): C, 46.68; H, 3.08.
Found: C, 46.79; H, 2.94.
mp¼76 ꢁC. 1H NMR (250 MHz, CDCl3):
d
¼1.16 (t, 3J¼7.2 Hz, 3H,
CH2CH3), 2.18 (s, 3H, CH3), 2.31 (s, 3H, CH3), 2.76 (q, 3J¼7.2 Hz, 2H,
CH2CH3), 6.05 (s, 1H, OH), 6.95 (s, 1H, Ar); 19F NMR (235 MHz,
CDCl3):
(75 MHz, CDCl3):
d
¼ꢀ124.3 (m, CF2), ꢀ104.5 (m, CF2), ꢀ80.1 (t, CF3); 13C NMR
d
¼7.8 (CH2CH3), 11.9 (ArCH3), 20.3 (ArCH3), 38.1
(CH2CH3), 121.5–121.8 (m, CHCC3F7), 122.1 (t, 2J¼23.9 Hz, CC3F7),
4.4.17. 5-Heptafluoropropyl-3-hydroxy-biphenyl-4-carboxylic acid
methyl ester (6q)
126.8 (t, 3J¼2.9 Hz, CCO2CH2CH3), 128.8 (CCH3), 139.3 (CCH3), 150.6
(COH), 207.9 (CO); IR (ATR, cmꢀ1):
n
¼3365 (m), 2980 (w), 2945 (w),
Starting with silyl enol ether 4g (1.165 g, 3.00 mmol), 1,3-bis-
silyl enol ether 5a (0.860 g, 3.30 mmol) and TiCl4 (0.36 mL,
3.30 mmol), 6q was isolated as a colourless solid (0.560 g, 47%),
1698 (s), 1610 (m), 1350 (m), 1200 (s), 1100 (s); MS (EI, 70 eV): m/z
(%)¼346 (Mþ, 11), 317 (100), 277 (9), 269 (29); HRMS (EI, 70 eV)
calcd for C14H13F7O2 (Mþ): 346.07983, found 346.08060. Anal.
Calcd for C14H13F7O2 (346.24): C, 48.56; H, 3.78. Found: C, 48.79; H,
3.73.
mp¼84 ꢁC. 1H NMR (250 MHz, CDCl3):
¼3.96 (s, 3H, OCH3), 7.40–
d
7.64 (m, 7H, ArH), 9.85 (s, 1H, OH); 19F NMR (235 MHz, CDCl3):
d
¼ꢀ121.1 (m, CF2), ꢀ99.8 (m, CF2), ꢀ80.7 (q, CF3); 13C NMR
(75 MHz, CDCl3):
d
¼52.8 (OCH3), 112.3 (t, 3J¼2.2 Hz, CCO2CH3),
4.4.14. 2-Heptafluoropropyl-6-hydroxy-4-propyl-benzoic acid
methyl ester (6n)
Starting with silyl enol ether 4e (0.709 g, 2.00 mmol), 1,3-bis-
silyl enol ether 5a (0.574 g, 2.20 mmol) and TiCl4 (0.24 mL,
2.20 mmol), 6n was isolated as a pale yellow solid (0.286 g, 40%),
119.7 (t, 3J¼9.6 Hz, CHCC3F7), 119.7 (CHCOH), 127.2 (Ph), 129.0 (Ph),
129.1 (Ph), 129.8 (t, 2J¼23.5 Hz, CC3F7), 138.2 (C), 146.3 (C), 160.4
(COH), 169.2 (CO); IR (ATR, cmꢀ1):
n
¼3290 (m), 3090 (w), 3062 (w),
3042 (w), 1699 (s), 1615 (m), 1574 (m), 1437 (m), 1414 (m), 1349 (s),
1311 (s), 1284 (s), 1223 (s), 1187 (s), 1149 (m), 1110 (s), 984 (m); MS
(EI, 70 eV): m/z (%)¼396 (Mþ, 38), 364 (100), 336 (13), 217 (43), 188
(12), 109 (12); HRMS (EI, 70 eV) calcd for C17H11F7O3 (Mþ):
396.05909, found 396.05970. Anal. Calcd for C17H11F7O3 (396.26):
C, 51.53; H, 2.80. Found: C, 51.68; H, 2.87.
mp¼56 ꢁC. 1H NMR (250 MHz, CDCl3):
d
¼0.95 (t, 3J¼7.3 Hz, 3H,
CH2CH3), 1.57–1.74 (m, 2H, CH2CH3), 2.62 (t, 3J¼7.6 Hz, 2H, ArCH2),
3.91 (s, 3H, OCH3), 7.01 (s, 1H, Ar), 7.03 (s, 1H, Ar), 9.75 (s, 1H, OH);
19F NMR (235 MHz, CDCl3):
d
¼ꢀ121.2 (m, CF2), ꢀ99.8 (m, CF2),
ꢀ80.7 (t, CF3); 13C NMR (75 MHz, CDCl3):
d
¼13.6 (CH2CH3), 23.7
Crystallographic data of 6l. Empirical formula: C17H11F7O. For-
mula weight: 396.26. Temperature: 173(2) K. Wavelength:
0.71073 Å. Crystal system: monoclinic. Space group (H.-M.): P21/c.
Space group (Hall): ꢀP2ybc. Unit cell dimensions: a¼14.2740(3) Å,
(CH2), 37.8 (CH2), 52.6 (OCH3), 111.3 (t, 3J¼2.2 Hz, CCO2CH3), 121.2
(CHCOH), 121.3 (t, 3J¼9.8 Hz, CHCC3F7), 129.0 (t, 2J¼23.3 Hz, CC3F7),
149.1 (CCH2CH2CH3), 160.2 (COH), 169.3 (CO); IR (ATR, cmꢀ1):
n
¼3288 (m), 2963 (w), 2938 (w), 2878 (w), 1706 (s), 1615 (m), 1434
a
¼90ꢁ, b¼8.9786(2) Å,
b
¼92.3180(10)ꢁ, c¼13.1741(3) Å,
g
¼90ꢁ.
(m), 1342 (m), 1220 (s), 1201 (s), 1115 (s); MS (EI, 70 eV): m/z
(%)¼362 (Mþ, 26), 330 (100), 302 (88), 273 (35); HRMS (EI, 70 eV)
calcd for C14H13F7O3 (Mþ): 362.07474, found 362.07454.
Volume: 1687.02(6) Å3; Z¼4. Density (calculated): 1.560 Mg/m3.
Absorption coefficient: 0.157 mmꢀ1
.
F(000)¼800. Crystal size:
0.42ꢂ0.35ꢂ0.23 mm3.
Q
Range for data collection: 2.68–30.00ꢁ.
Index ranges: ꢀ20ꢃhꢃ19, ꢀ12ꢃkꢃ12, ꢀ18ꢃlꢃ18. Reflections col-
4.4.15. 1-(6-Heptafluoropropyl-2-hydroxy-3-methyl-4-propyl-
phenyl)-propan-1-one (6o)
lected: 38,562. Independent reflections: 4903 [R(int)¼0.0226].
Completeness to
Q
¼30.00ꢁ: 99.3%. Absorption correction: semi-
Starting with silyl enol ether 4e (0.709 g, 2.00 mmol), 1,3-bis-
silyl enol ether 5c (0.600 g, 2.20 mmol) and TiCl4 (0.24 mL,
2.20 mmol), 6o was isolated as a pale yellow solid (0.229 g, 31%),
empirical from equivalents. Max. and min. transmissions: 0.9649
and 0.9372. Refinement method: full-matrix least-squares on F2.
Data/restraints/parameters: 4903/0/249. Goodness-of-fit on F2:
mp¼63 ꢁC. 1H NMR (250 MHz, CDCl3):
d
¼0.97 (t, 3J¼7.3 Hz, 3H,
1.033. Final R indices [I>2
s
(I)]: R1¼0.0408, wR2¼0.1044. R indices

S. Bu¨ttner et al. / Tetrahedron 64 (2008) 7968–7976
7975
(all data): R1¼0.0522, wR2¼0.1146. Largest diff. peak and hole:
0.453 and ꢀ0.306 e/Å3.
(m, 2H, ArCH2CH2), 2.26 (s, 3H, ArCH3), 2.77 (q, 3J¼7.2 Hz, 2H,
CH2CH3), 2.88 (t, 3J¼7.4 Hz, 2H, ArCH2), 3.02 (t, 3J¼7.4 Hz, 2H,
ArCH2), 7.95 (s, 1H, OH); 19F NMR (235 MHz, CDCl3):
d¼ꢀ125.8 (m,
4.4.18. 2-Hydroxy-4-methyl-6-tridecafluorohexyl-benzoic acid
methyl ester (6r)
CF2), ꢀ122.3 (m, CF2), ꢀ121.5 (m, CF2), ꢀ121.3 (m, CF2), ꢀ118.4 (m,
CF2), ꢀ102.5 (m, CF2), ꢀ80.8 (t, CF3); 13C NMR (75 MHz, CDCl3):
Starting with silyl enol ether 4h (0.703 g, 1.48 mmol), 1,3-bis-
silyl enol ether 5a (0.430 g, 1.65 mmol) and TiCl4 (0.18 mL,
1.65 mmol), 6r was isolated as a colourless solid (0.297 g, 42%),
d
¼7.9 (CH3), 13.2 (CH3), 25.7 (CH2), 32.2 (CH2), 33.8 (CH2), 38.2
(CH2), 118.4 (t, 2J¼23.7 Hz, CC7F15), 127.6 (C), 131.4 (t, 3J¼4.4 Hz,
CCC7F15), 136.4 (t, 3J¼4.1 Hz, CCC7F15), 147.7 (C), 151.1 (COH), 204.9
mp¼106 ꢁC. 1H NMR (250 MHz, CDCl3):
d
¼2.39 (s, 3H, ArCH3), 3.91
(CO); IR (ATR, cmꢀ1):
n
¼3333 (w), 2984 (w), 2943 (w), 2881 (w),
(s, 3H, OCH3), 7.01 (s, 1H, Ar), 7.03 (s, 1H, Ar), 9.71 (s, 1H, OH); 19F
1698 (m), 1583 (w), 1367 (w), 1288 (w), 1238 (m), 1198 (s), 1142 (s),
1127 (m),1097 (m); MS (EI, 70 eV): m/z (%)¼572 (Mþ,18), 543 (100),
503 (13), 495 (25); HRMS (EI, 70 eV) calcd for C20H15F15O2 (Mþ):
572.08270, found 572.08315.
NMR (235 MHz, CDCl3):
d
¼ꢀ126.1 (m, CF2), ꢀ122.7 (m, CF2), ꢀ122.2
(m, CF2), ꢀ117.1 (m, CF2), ꢀ99.4 (m, CF2), ꢀ80.8 (t, CF3); 13C NMR
(75 MHz, CDCl3):
d
¼21.6 (ArCH3), 52.6 (OCH3), 111.2 (t, 3J¼2.2 Hz,
CCO2CH3), 121.9 (CHCOH), 122.1 (t, 3J¼9.5 Hz, CHCC6F13), 129.2 (t,
2J¼23.3 Hz, CC6F13), 144.4 (CCH3), 160.1 (COH), 169.3 (CO); IR (ATR,
4.4.22. 3-Hydroxy-5-pentadecafluoroheptyl-biphenyl-4-carboxylic
acid methyl ester (6v)
cmꢀ1):
n
¼3306 (w), 2924 (w), 2855 (w), 1706 (m), 1615 (w), 1438
(w), 1362 (w), 1302 (m), 1283 (m), 1234 (m), 1194 (s), 1176 (s), 1145
(s), 1134 (s), 1093 (m), 1067 (m); MS (EI, 70 eV): m/z (%)¼484 (Mþ,
14), 452 (100), 433 (7), 405 (5), 155 (62); HRMS (EI, 70 eV) calcd for
Starting with silyl enol ether 4k (1.177 g, 2.00 mmol), 1,3-bis-
silyl enol ether 5a (0.573 g, 2.20 mmol) and TiCl4 (0.24 mL,
2.20 mmol), 6v was isolated as a colourless solid (0.424 g, 36%),
C
15H9F13O3 (Mþ): 484.03386, found 484.03389.
mp¼113 ꢁC. 1H NMR (250 MHz, CDCl3):
¼3.96 (s, 3H, OCH3), 7.37–
d
7.66 (m, 7H, ArH), 9.75 (s, 1H, OH); 19F NMR (235 MHz, CDCl3):
4.4.19. 1-(2-Hydroxy-4-methyl-6-tridecafluorohexyl-phenyl)-
ethanone (6s)
d
¼ꢀ126.1 (m, CF2), ꢀ122.7 (m, CF2), ꢀ121.9 (m, 4F, CF2), ꢀ117.0 (m,
CF2), ꢀ99.4 (m, CF2), ꢀ80.8 (t, CF3); 13C NMR (75 MHz, CDCl3):
Starting with silyl enol ether 4h (0.708 g, 1.49 mmol), 1,3-bis-
silyl enol ether 5b (0.403 g, 1.65 mmol) and TiCl4 (0.18 mL,
1.65 mmol), 6s was isolated as a pale red solid (0.288 g, 41%),
d
¼52.8 (OCH3), 112.7 (t, 3J¼2.2 Hz, CCO2CH3), 119.7 (CHCOH), 119.8
(t, 3J¼9.8 Hz, CHCC7F15), 127.2 (Ph), 129.0 (Ph), 129.1 (Ph), 129.8 (t,
2J¼23.4 Hz, CC7F15), 138.3 (C), 146.2 (C), 160.2 (COH), 169.1 (CO); IR
mp¼122 ꢁC. 1H NMR (250 MHz, CDCl3):
d
¼2.35 (s, 3H, CH3), 2.52 (s,
(ATR, cmꢀ1):
n
¼3400 (w), 3085 (w), 3061 (w), 3040 (w), 3011 (w),
3H, CH3), 6.31 (s, 1H, OH), 6.86 (s, 1H, Ar), 6.95 (s, 1H, Ar); 19F NMR
2959 (w), 1711 (m), 1614 (m), 1410 (m), 1307 (m), 1277 (m), 1240
(m),1191 (s), 1140 (s), 1126 (s), 1098 (m),1062 (m),1026 (m); MS (EI,
70 eV): m/z (%)¼596 (Mþ, 22), 564 (100), 536 (13), 217 (82), 188
(13); HRMS (EI, 70 eV) calcd for C21H11F15O3 (Mþ): 596.04632,
found 596.04696.
(235 MHz, CDCl3):
d
¼ꢀ126.1 (m, CF2), ꢀ122.8 (m, CF2), ꢀ121.6 (m,
CF2), ꢀ119.6 (m, CF2), ꢀ103.5 (m, CF2), ꢀ80.8 (t, CF3); 13C NMR
(75 MHz, CDCl3):
d
¼21.1 (ArCH3), 32.2 (COCH3), 120.5 (t, 3J¼7.6 Hz,
CHCC6F13), 121.1 (CHCOH), 125.7 (t, 2J¼23.3 Hz, CC6F13), 128.8 (t,
3J¼3.3 Hz, CCOCH3), 141.5 (CCH3), 154.8 (COH), 201.4 (CO); IR (ATR,
cmꢀ1):
n
¼3287 (w), 2963 (w), 2932 (w), 1694 (m), 1615 (w), 1361
4.4.23. 1-(3-Hydroxy-2-methyl-5-pentadecafluoroheptyl-biphenyl-
4-yl)-propan-1-one (6w)
(w), 1322 (m), 1282 (w), 1231 (m), 1190 (m), 1178 (m), 1136 (m),
1067 (m); MS (EI, 70 eV): m/z (%)¼468 (Mþ,12), 453 (100), 405 (10);
HRMS (EI, 70 eV): calcd for C15H9F13O2 (Mþ): 468.03895, found
468.03843. Anal. Calcd for C15H9F13O2 (468.21): C, 38.48; H, 1.94.
Found: C, 38.31; H, 1.92.
Starting with silyl enol ether 4k (1.177 g, 2.00 mmol), 1,3-bis-
silyl enol ether 5c (0.600 g, 2.20 mmol) and TiCl4 (0.24 mL,
2.20 mmol), 6w was isolated as a pale red solid (0.600 g, 49%),
mp¼126 ꢁC. 1H NMR (250 MHz, CDCl3):
d
¼1.22 (t, 3J¼7.3 Hz, 3H,
CH2CH3), 2.21 (s, 3H, ArCH3), 2.85 (q, 3J¼7.3 Hz, 2H, CH2CH3), 5.84
4.4.20. 1-(2-Hydroxy-3-methyl-6-pentadecafluoroheptyl-4-propyl-
phenyl)-propan-1-one (6t)
(s, 1H, OH), 7.09 (s, 1H, ArH), 7.23–7.50 (m, 5H, PhH); 19F NMR
(235 MHz, CDCl3):
d
¼ꢀ126.1 (m, CF2), ꢀ122.7 (m, CF2), ꢀ122.0 (m,
Starting with silyl enol ether 4i (0.930 g,1.68 mmol),1,3-bis-silyl
enol ether 5c (0.600 g, 2.20 mmol) and TiCl4 (0.24 mL, 2.20 mmol),
6t was isolated as a yellow solid (0.398 g, 41%), mp¼83 ꢁC. 1H NMR
CF2), ꢀ121.4 (m, CF2), ꢀ119.7 (m, CF2), ꢀ104.1 (m, CF2), ꢀ80.8 (t,
CF3); 13C NMR (75 MHz, CDCl3):
d¼7.8 (CH3), 13.4 (CH3), 38.1 (CH2),
122.0 (t, 3J¼7.4 Hz, CHCC7F15), 122.8 (t, 2J¼23.9 Hz, CC7F15), 127.5
(250 MHz, CDCl3):
d
¼0.97 (t, 3J¼7.3 Hz, 3H, CH2CH2CH3), 1.17 (t,
(C), 127.7 (C), 127.9 (Ph), 128.4 (Ph), 129.0 (Ph), 139.6 (C), 144.3 (C),
3J¼7.2 Hz, 3H, COCH2CH3), 1.50–1.67 (m, 2H, CH2CH2CH3), 2.22 (s,
3H, ArCH3), 2.62 (t, 3J¼7.7 Hz, 2H, ArCH2), 2.79 (q, 3J¼7.2 Hz, 2H,
COCH2), 5.87 (s, 1H, OH), 6.95 (s, 1H, ArH); 19F NMR (235 MHz,
151.0 (COH), 206.9 (CO); IR (ATR, cmꢀ1):
n
¼3412 (w), 3055 (w),
2986 (w), 2944 (w), 2906 (w), 2884 (w), 1704 (m), 1599 (w), 1564
(w), 1204 (s), 1142 (s), 1128 (s), 1099 (m); MS (EI, 70 eV): m/z
(%)¼608 (Mþ, 30), 579 (100), 531 (56), 262 (24); HRMS (EI, 70 eV)
calcd for C23H15F15O2 (Mþ): 608.08270, found 608.08305.
CDCl3):
d
¼ꢀ126.1 (m, CF2), ꢀ122.7 (m, CF2), ꢀ122.0 (m, CF2), ꢀ121.4
(m, CF2), ꢀ119.8 (m, CF2), ꢀ103.9 (m, CF2), ꢀ80.8 (t, CF3); 13C NMR
(75 MHz, CDCl3):
d
¼7.9 (CH3), 11.5 (CH3), 13.8 (CH3), 23.2 (CH2), 35.8
(CH2), 38.1 (CH2), 121.3 (t, 3J¼7.53 Hz, CHCC7F15), 122.4 (t,
Acknowledgements
2J¼23.4 Hz, CC7F15), 126.5 (t, 3J¼2.7 Hz, CCOCH2CH3), 128.1 (C),
143.6 (C),150.8 (COH), 207.7 (CO); IR (ATR, cmꢀ1):
n
¼3265 (w), 2967
Financial support by the State of Mecklenburg-Vorpommern
(Exzellenzfo¨rderprogramm UR 07 068) is gratefully acknowledged.
(w), 2944 (w), 2879 (w), 1693 (m), 1606 (w), 1571 (w), 1316 (w),
1233 (m), 1194 (s), 1139 (m), 1129 (s), 1113 (m), 1101 (m), 1014 (m);
MS (EI, 70 eV): m/z (%)¼574 (Mþ, 5), 545 (100), 497 (12); HRMS (EI,
70 eV): calcd for C20H17F15O2 (Mþ): 574.09843, found 574.09733.
References and notes
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4.4.21. 1-(6-Hydroxy-7-methyl-4-pentadecafluoroheptyl-indan-5-
yl)-propan-1-one (6u)
Starting with silyl enol ether 4j (0.730 g, 1.32 mmol),1,3-bis-silyl
enol ether 5c (0.450 g, 1.65 mmol) and TiCl4 (0.18 mL, 1.65 mmol),
6u was isolated as a yellow solid (0.227 g, 30%), mp¼167 ꢁC. 1H
2. (a) Ryckmans, T.; Balancon, L.; Berton, O.; Genicot, C.; Lamberty, Y.; Lallemand,
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NMR (250 MHz, CDCl3):
d
¼1.09 (t, 3J¼7.2 Hz, 3H, CH2CH3), 1.99–2.14

7976
S. Bu¨ttner et al. / Tetrahedron 64 (2008) 7968–7976
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´
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22. CCDC 689114–689118 contain the supplementary crystallographic data for this
paper. These data can be obtained free of charge from The Cambridge Crys-
tallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.