Synthesis and stability of 2-(1,1-difluoroalkyl) thiophenes and related 1,1-difluoroalkyl benzenes: Fluorinated building blocks for liquid crystal synthesis

Article abstract of DOI:10.1016/S0040-4020(01)00519-1

The synthesis of a series of 2-(1,1-difluoroalkyl) thiophenes, including some biphenylthienyl liquid crystalline materials, was examined using a variety of fluorination approaches. For comparison purposes, a series of 1,1-difluoroalkyl benzene analogs were also prepared. The direct fluorodeoxygenation of alkyl thienyl ketones and alkyl phenyl ketones using various aminofluorosulfuranes proceeded in only moderate to poor yields. In contrast, fluorodesulfurization of the corresponding 1,3-dithiolanes using NOBF₄/PPHF cleanly afforded the desired 2-(1,1-difluoroalkyl) thiophenes (and analogous 1,1-difluoroalkyl benzenes) in high yields. Fluorodesulfurization of 2-alkyl-2-thienyl-1,3-dithiolanes using NBS (or DBH)/PPHF was complicated by competing ring and/or side chain bromination pathways. These problems were avoided when using NIS/PPHF. Although the various 1,1-difluoroalkyl arene products were sensitive to hydrolytic decomposition on prolonged exposure to silica, the purified products proved quite stable and were well suited for use as building blocks for liquid crystal synthesis.

Full text of DOI:10.1016/S0040-4020(01)00519-1

TETRAHEDRON
Pergamon
Tetrahedron 57 &2001) 5757±5767
Synthesis and stability of 2-ꢀ1,1-di¯uoroalkyl) thiophenes and
related 1,1-di¯uoroalkyl benzenes: ¯uorinated building blocks
for liquid crystal synthesis
Andre A. Kiryanov, Alexander J. Seed and Paul Sampsonp
Department of Chemistry, Kent State University, Kent, OH 44242, USA
Received 3 January 2001; accepted 9 May 2001
AbstractÐThe synthesis of a series of 2-&1,1-di¯uoroalkyl) thiophenes, including some biphenylthienyl liquid crystalline materials, was
examined using a variety of ¯uorination approaches. For comparison purposes, a series of 1,1-di¯uoroalkyl benzene analogs were also
prepared. The direct ¯uorodeoxygenation of alkyl thienyl ketones and alkyl phenyl ketones using various amino¯uorosulfuranes proceeded
in only moderate to poor yields. In contrast, ¯uorodesulfurization of the corresponding 1,3-dithiolanes using NOBF4/PPHF cleanly afforded
the desired 2-&1,1-di¯uoroalkyl) thiophenes &and analogous 1,1-di¯uoroalkyl benzenes) in high yields. Fluorodesulfurization of 2-alkyl-2-
thienyl-1,3-dithiolanes using NBS &or DBH)/PPHF was complicated by competing ring and/or side chain bromination pathways. These
problems were avoided when using NIS/PPHF. Although the various 1,1-di¯uoroalkyl arene products were sensitive to hydrolytic
decomposition on prolonged exposure to silica, the puri®ed products proved quite stable and were well suited for use as building blocks
for liquid crystal synthesis. q 2001 Elsevier Science Ltd. All rights reserved.
1.Introduction
The relatively small size of ¯uorine and the high dipole
moment of the C±F bond have resulted in the increasingly
widespread application of ¯uorine substituents in liquid
crystalline materials.1 As part of a program aimed at the
development of novel liquid crystals, we were interested
in examining the impact of incorporating a 1,1-di¯uoroalkyl
terminal chain adjacent to a thiophene or a benzene ring as
in general structures 1 and 2.
The high transverse molecular dipole imparted by the
di¯uoromethylene unit was expected to afford a high dielec-
tric biaxiality which is necessary for dielectric contrast
enhancement of chevron-based surface-stabilized ferro-
electric displays,2 while the relatively small size of the
di¯uoromethylene moiety3 was anticipated to maintain
tilted phase behavior4 and relatively low material vis-
cosities.5 Therefore, our attention was directed toward the
synthesis of appropriate 1,1-di¯uoroalkyl arene building
blocks 3 and 4, which we anticipated would prove useful
as intermediates in the synthesis of ¯uorinated mesogens 1
and 2.
A limited number of methods have been reported previously
for the synthesis of simple 1,1-di¯uoroalkyl benzenes;
essentially all of this chemistry was directed at the prepa-
ration of compounds bearing very short &#C3) 1,1-di¯uoro-
alkyl chains.6 The direct ¯uorodeoxygenation of a limited
number of substituted phenyl alkyl ketones has been
achieved using [bis&2-methoxyethyl)amino]sulfur tri-
¯uoride &DeoxoFluorw)7 or diethylaminosulfur tri¯uoride
&DAST).8,9 Other approaches have involved ¯uorination of
an intermediate hydrazone or oxime derivative.10,11 The
¯uorodesulfurization of 2-alkyl-2-phenyl-1,3-dithiolanes
Keywords: ¯uorine and compounds; thiophenes; liquid crystals; halogen-
ation.
Corresponding author. Tel.: 11-330-672-0034; fax: 11-330-672-3816;
e-mail: psampson@kent.edu
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020&01)00519-1

5758
A. A. Kiryanov et al. /Tetrahedron 57 $2001) 5757±5767
Table 1. Fluorodeoxygenation of alkyl aryl ketones 5 and 6 using DAST
Entry
Substrate
DAST &equiv.)
T &8C)
Solvent
Vessel
Time
Conversion &%)a
1
2
3
4
5
6
7
8
5
5
5
5
5
5
6
6
6
6
6
6
6
6
2
1
1
0.74
2
2.2
1
40
85
60
80
55
55
40
85
40
60
80
55
55
55
CH2Cl2
Glyme
Neat
Neat
Neat
Glass
Glass
Glass
Glass
Plastic
Plastic
Glass
Glass
Glass
Glass
Glass
Plastic
Plastic
Plastic
50 h
23 h
50 h
24 h
102 h
6 d
45 h
24 h
23 h
17 h
24 h
27 h
6 d
0
0
4
5
30
32
,1
3
18
30
22
35
67
73
Neat
CH2Cl2
Glyme
Neat
Neat
Neat
Neat
Neat
Neat
1
5
9
10
11
12
13
14
1.1
1.1
1.1
2.0
1.6
14 d
a
% Conversion was determined by GC and was in agreement with NMR ratios of product to starting material.
has previously been reported but with mixed success. Thus,
¯uorodesulfurization using Bu4NH2F3/N-iodosuccinimide
&NIS) proceeded in good yields in the presence of activated
phenyl rings, but complex mixtures of products were formed
in the presence of deactivated &nitro-, carbonyl-, or halogen-
substituted) phenyl rings.12 Fluorodesulfurization has also
been carried out in low yields using hexa¯uoropropene-
diethylamine in the presence of either 1,3-dibromo-5,5-
dimethylhydantoin &DBH) or NIS/water.13 The use of
DBH led to large amounts of dehydro¯uorination. Finally,
clean ¯uorodesulfurization of a limited range of ring
substituted 2-methyl-2-phenyl-1,3-dithiolanes was reported
using NOBF4/PPHF;14 however, this method was not
applied with other 2-alkyl-2-aryl-1,3-dithiolanes. Interest-
ingly, no applications of this chemistry have appeared
since its original communication &see below).
$where alkyl±methyl). For comparative purposes we also
report the synthesis of the analogous 1,1-di¯uoroalkyl
benzenes 4 which are, in themselves, useful intermediates
en route to the corresponding terphenyl mesogens 2.18 The
work outlined herein provides the ®rst comparative study of
a broad range of potential ¯uorinating approaches to 2-&1,1-
di¯uoroalkyl) thiophene and 1,1-di¯uoroalkyl benzene
targets and clearly reveals the preferred synthetic methods
for the preparation of such targets.19
2.Results and discussion
2.1. Synthesis of 1,1-di¯uoroalkyl aromatic compounds
using ¯uorodeoxygenation approaches
Our initial studies involved the ¯uorodeoxygenation of alkyl
aryl ketones using DAST. Model substrates chosen for
initial optimization of the reaction conditions were 2-buta-
noyl thiophene &5) and butanoyl benzene &6) &see Table 1).
In the presence of solvent, no signi®cant reaction took place
even at extended reaction times &entries 1, 2, 7 and 8).
Virtually no attention has been paid in the literature to the
synthesis of 1,1-di¯uoroalkyl thiophenes. There are no
examples reported in the literature for the synthesis of
1,1-di¯uoroalkyl thiophenes that proceed via ¯uorination
of a thiophene-containing ketone precursor or a derivative
thereof. Indeed, there is only one literature synthesis of any
2-&1,1-di¯uoroalkyl) thiophene &where alkyl±methyl).15
This chemistry involved de novo construction of the thio-
phene ring from an acyclic b,b,g,g-tetra¯uoro ester &rather
than ¯uorination of an a-oxo thiophene or a derivative
thereof) and it was restricted to the synthesis of 5-&1,1-
di¯uoroalkyl)-3-hydroxythiophene-2-carboxylates.16,17 As
such, it was not useful for the synthesis of the liquid crystal-
line compounds targeted in the present study.
When using neat DAST a slow conversion of the ketone into
the di¯uorinated product was observed &entries 3±6, 9±14).
The reaction temperature was found to be an important
factor. The use of higher temperatures &808C) afforded
only low conversions to the desired product &entries 4 and
11), perhaps due to DAST decomposition and/or possible
hydrolysis of the ¯uorinated product back to the parent
ketone &see later). In contrast, lower temperatures &408C)
led to a very sluggish reaction &entry 9). Optimal conditions
employed extended reaction times in the presence of an
excess of DAST at 50±608C &entries 5, 6, 13 and 14). Gener-
ally, higher yields were obtained when using plastic rather
than glass vessels.
In a preliminary communication8d we reported the synthesis
of 1,1-di¯uoropentyl thiophene 3 in low yield via direct
DAST-mediated ¯uorodeoxygenation of the corresponding
2-pentanoyl thiophene. We now report full details of our
exploratory studies aimed at uncovering ¯uorination
methods suitable for the ef®cient synthesis of 1,1-di¯uoro-
alkyl thiophenes 1 and 3. This work constitutes the ®rst
practical synthetic entry to 1,1-di¯uoroalkyl thiophenes
On a preparative scale, application of these optimized
conditions to the ¯uorodeoxygenation of bromothienyl
ketone 7 afforded the corresponding 1,1-di¯uoropentyl

A. A. Kiryanov et al. /Tetrahedron 57 $2001) 5757±5767
5759
Table 2. Fluorodeoxygenation of thienyl ketone 7 using neat amino¯uor-
osulfuranes
Instead, the parent ketones were recovered quantitatively in
each case after 3±5 days of heating at 558C in the presence
of 5.7 equiv. DAST. This reaction was performed using
either neat DAST or using a minimal amount of solvent
&CDCl3) to at least partially dissolve the starting ketone.
The low solubility of these ketones in DAST may be prob-
lematic here, while our earlier studies demonstrated that
the presence of solvent can be deleterious to ¯uorodeoxy-
genation &see Table 1).
Entry
R2NSF3
DAST
DAST
# equiv.
T &8C)
Time
Yield &%)a
1
2
3
4
5
6
7
3.9
3.8
2.8
4.1
4.3
4.3
4.3
55
55
75
65
65
65
80
60 h
70 h
60 h
128 h
70 h
6 d
27 &24)
30 &28)
31
MorphDAST
MorphDAST
DeoxoFluor
DeoxoFluor
DeoxoFluor
36
43
50
25
2.2. Synthesis of 1,1-di¯uoroalkyl aromatic compounds
using ¯uorodesulfurization approaches
18 hb
a
1
The next stage of our investigation focused on the synthesis
of 2-&1,1-di¯uoroalkyl) thiophenes &and the analogous
1,1-di¯uoroalkyl benzenes) via the ¯uorodesulfurization
of 1,3-dithiolane derivatives of the corresponding alkyl
aryl ketones. In preliminary studies, ¯uorodesulfurization
of 2-phenyl-2-propyl-1,3-dithiolane using NBS/PPHF
using a protocol analogous to that described by Katzenel-
lenbogen21 afforded a complex mixture of products from
which the desired 1,1-di¯uorobutyl benzene was isolated
by column chromatography in only 17% yield. Attempts
to achieve similar ¯uorodesulfurization of 2-&5-bromo-
thienyl)-2-butyl-1,3-dithiolane &10) using DBH/PPHF21
gave a complex mixture of inseparable products containing
the desired 2-bromo-5-&1,1-di¯uoropentyl)thiophene &3) in
low &10±20%) yield. The low yield in each of these reac-
tions could be attributed to product decomposition observed
during the highly exothermic ®ltration through a basic
alumina plug on workup, along with the instability of the
products toward silica gel chromatography. The relatively
electron-rich thiophene ring also appeared prone to ring
bromination under the reaction and/or workup conditions.
These problems could largely be circumvented by dilution
of the reaction mixture with petroleum ether±CH2Cl2 &7:1)
followed by separation of the HF±pyridine layer prior to
®ltration. Application of this modi®ed workup procedure
to the ¯uorodesulfurization of 2-&2-thienyl)-1,3-dithiolane
GC yields, which were in agreement with H NMR ratios of product to
starting material; isolated yields in parentheses.
No signi®cant change occurred after 18 h.
b
thiophene 3 in a modest 24±28% isolated yield &Table 2,
entries 1 and 2).
Attempts were made to evaluate the utility of other amino-
¯uorosulfuranes for the preparation of 3. Morph-DAST20 was
employed with no substantial improvement &entries 3 and 4).
DeoxoFluorw,7 led to a somewhat better conversion but only
after prolonged reaction times &entries 5 and 6). The use of
higher reaction temperatures proved deleterious &entry 7).
Interestingly, employment of DAST with related higher
molecular weight thienyl ketones 8 and 9 did not lead to
the formation of any ¯uorinated organic products &Eq. 1).
ꢀ1†
Table 3. Fluorodesulfurization of dithiolane 10 using Hal1/PPHF
Entry
Hal1 source
Time &min)
Yields &%)a
Unidenti®ed products &%)
Combined isolated yield &%)
3
11
12
13
14
1
2
3
DBH
DBH
NBS
NBS
NBS
NIS
15
45
15
45
15
15
58
39
58
80
54
80
7
15
5
,1
,0.2
±
4
2
2
1
1
3
,1
1
-
,1
1
±
±
±
3
2
7
3
7
,2
74
60
75
84
63
80
4
1
5b
6
,0.5
±
±
a
Yields of each component were determined based on combined isolated yield and GC ratios, which were in accord with ratios obtained by 1H and 19F NM R
spectroscopy.
A cooled &2708C) petroleum ether±CH2Cl2 mixture was used during workup.
b

5760
A. A. Kiryanov et al. /Tetrahedron 57 $2001) 5757±5767
Figure 1. Formation of brominated byproducts during ¯uorodesulfurization of 10.
10 with NBS/PPHF or DBH/PPHF allowed us to obtain the
desired di¯uorinated product 3 in moderate to good yield
as a mixture with smaller amounts of various ring and/or
side chain brominated byproducts &see Table 3). The ratios
of products depended on the Hal1 source and the reaction
time. When using DBH, competitive ring bromination was
observed even at low reaction temperatures and traces of
side-chain brominated byproducts were also obtained &entry
1). Longer reaction times proved deleterious to both the
yield and purity of the desired product 3 &entry 2). In
contrast, when using NBS, longer reaction times led to a
better yield of 3 and a more favorable product distribution
&compare entries 3 and 4). One explanation for this obser-
vation may be that residual unreacted NBS present after a
short reaction time can effect bromination during workup
&entry 3). In contrast, longer reaction times lead to the
complete consumption of NBS prior to workup, when
such side reactions are precluded &entry 4). In any event,
these side reactions could be largely &though not com-
pletely) suppressed by using precooled &2708C) petroleum
ether±CH2Cl2 during workup &entry 5). The somewhat
surprising formation of minor byproduct 13a in all these
reactions can be explained by the presence of small amounts
of adventitious Br2 in DBH and NBS &Fig. 1). Reaction of
Br2 with some nucleophilic species in solution would
provide a source of bromide ion, which can intercept a
carbocation such as 15a. Subsequent elimination chemistry
would then afford 13a. Formation of 12a can be envisaged
to proceed via electrophilic bromination of the initially
formed ¯uoroalkene 16 with subsequent attack of ¯uoride
ion on the resulting bromonium ion intermediate 17.
Compound 14a would be formed via an analogous pathway.
Table 4. Fluorodesulfurization of alkyl aryl dithiolanes using NOBF4/PPHF
Entry
1
Substrate
Ar
Alk
Time &min)
60
Scale &mmol)
1.00
Product
Isolated yield &%)
29
10
±C4H9
3
2
3
4
5
6
7
8
10
10
10
10
10
18
19
±C4H9
±C4H9
±C4H9
±C4H9
±C4H9
±C4H9
±C7H15
180
45
6
1.95
1.97
2.17
4.68
6.25
4.52
4.52
3
3
0
38
87
81
75
72
81
3
6
3
6
3
6
4a
4b
6
9
20
21
±C4H9
±C4H9
6
6
0.50
3.00
1a
1b
78
47
10

A. A. Kiryanov et al. /Tetrahedron 57 $2001) 5757±5767
5761
All of the byproducts formed in these reactions are close in
polarity to the desired product 3 and hence separation was
problematic.
puri®cation &see below). The above results constitute the
®rst application of NOBF4/PPHF-mediated ¯uorodesulfur-
ization of 1,3-dithiolanes beyond the original literature
communication14 and, under the modi®ed conditions
developed herein, provide the ®rst convenient synthetic
entry to 2-&1,1-di¯uoroalkyl) thiophenes &alkyl±methyl).
In sharp contrast to the results obtained with NBS and DBH,
the use of NIS/PPHF provided 3 in 80% yield after 15 min,
with no byproduct formation &Table 3, entry 6). Thus, this
protocol was the best of the Hal1/PPHF-based ¯uoro-
desulfurization approaches to 2-&1,1-di¯uoropentyl)-
thiophene 3.
2.3. Stability of 1,1-di¯uoroalkyl arene products
A priori, we had some concerns as to the likely hydrolytic
and thermal stability of the 1,1-di¯uoroalkyl thiophene and
analogous 1,1-di¯uoroalkyl benzene compounds targeted in
this study. Interestingly, however, to our knowledge, the
only examples reported in the literature for the hydrolysis
of a 1,1-di¯uoroalkyl arene into the corresponding aryl
ketone have involved per¯uoroalkyl arene substrates.22
We found that higher molecular weight &teraryl) 1,1-
di¯uoroalkyl arenes &e.g. 1 or 223) underwent partial or
complete decomposition to the corresponding ketones on
prolonged exposure to silica during ¯ash column chroma-
tography or TLC. Therefore, very rapid ®ltration through a
silica plug was required for ef®cient puri®cation of these
substances. Although small amounts of decomposition still
occurred, the resulting ketone byproduct was retained by the
silica column. Generally, laterally ¯uorinated teraryls &e.g.
biphenylthiophene 1a) have higher solubility when
compared to their non-laterally ¯uorinated analogs. As a
result, the biphenylthiophene 1b lacking lateral ¯uorine
substitution suffered longer exposure times to silica during
®ltration and therefore higher levels of decomposition were
observed. Such problems were not evident in the case of the
lower molecular weight 1,1-di¯uoroalkyl arenes 3, 4a and
4b, which proved relatively stable to rapid silica gel
chromatography. Recrystallization of compounds 1 and 2
from alcohols or any wet solvents also led to a partial
decomposition to the corresponding ketone. Pure 1,1-
di¯uoroalkyl thiophene 3 decomposed after 1±5 days in
CDCl3 solution in an NMR tube, while the corresponding
benzene analogs 4a and 4b had somewhat longer lifetimes
&1±2 weeks). In each case, the decomposed dark mixtures
contained primarily the corresponding ketones. The glass of
the NMR tubes was etched after decomposition, suggesting
HF formation. Compounds 3, 4a and 4b each had suf®cient
thermal stability to be reproducibly analyzed by GC &injec-
tion port at 2908C). In the puri®ed form, all higher molecu-
lar weight &teraryl) di¯uoroalkyl derivatives &e.g. 1 or 2)
proved to be stable solids &no decomposition over a two-
year period), and only high-melting compounds showed
decomposition when in the isotropic phase or when
approaching the isotropic phase &.1808C).18 The corre-
sponding liquid 1,1-di¯uoroalkyl thiophene 3 and 1,1-
di¯uoroalkyl benzenes 4a and 4b can be stored for several
months in the open air in pyrex glass or plastic vessels
without noticeable decomposition. In contrast, some
samples decomposed within a few days when stored in boro-
silicate glass vials. These compounds can also be stored in
the presence of Et3N.
Next we investigated the use of the NOBF4/PPHF-mediated
¯uorodesulfurization protocol originally developed by Olah
and Prakash.14 It was reported that the HF-containing layer
in these reactions could be separated from the reaction
mixture during workup after dilution with CH2Cl2. The
separated product-containing layer could then be ®ltered
through an alumina plug without an exothermic reaction;
however, in our hands, separation of the HF-containing
layer in these reactions was not observed, which precluded
isolation of the reaction product. Therefore, the workup
procedure was modi®ed by adding petroleum ether to dilute
the reaction mixture, which allowed us to ef®ciently sepa-
rate the HF-containing layer. Moreover, the low polarity of
this solvent system allowed for a better separation of the
product from the various impurities during the ®ltration
process than was possible with a more polar solvent. We
found that the reaction time dramatically in¯uenced the
outcome of these reactions &see Table 4). In their original
work,14 Olah and Prakash reported the use of 60 min reac-
tion times for the ¯uorodesulfurization of a range of dithio-
lanes; however, ¯uorodesulfurization of our thienyl
dithiolane 10 under these conditions gave the desired
di¯uorinated product 3 in only low yield &29%, entry 1).
Longer reaction times did not lead to improved yields
and, if the reaction was continued for 3 h, no desired product
was isolated &entry 2). Apparently, the thiophene-containing
product 3 slowly decomposes and/or polymerizes under the
reaction conditions. However, the use of a somewhat shorter
reaction time &45 min) slightly improved the reaction yield
&38%, entry 3), while a very short reaction time &ca.6 min)
provided a very good yield of the desired di¯uorinated
product &87%, entry 4). Scaling up the procedure to 4±
7 mmol led to a small decrease in yields &75±81%)
&compare entries 4±6). No side reactions were observed in
any of these experiments.
Several other substrates were then subjected to these
optimized conditions. Analogous phenyl-containing dithio-
lanes 18 and 19 were employed and high yields of the
corresponding 1,1-di¯uoroalkyl benzenes 4a and 4b were
obtained &entries 7 and 8). In contrast to the results observed
during the DAST-mediated ¯uorodeoxygenation of the
corresponding teraryl ketones 8 and 9 &Eq. &1)), even the
higher molecular weight biphenylthienyl dithiolanes 20 and
21 could be effectively converted into the corresponding
di¯uorinated liquid crystal derivatives 1a and 1b using
this procedure, since these substrates have good solubility
in CH2Cl2 at 08C. Thus, 20 was ¯uorinated successfully on a
0.50 mmol scale in 78% yield &entry 9). Larger scale
&3.0 mmol) ¯uorination for 21 led to a more modest 47%
yield of the desired product &entry 10). This lower yield is
attributed to solubility problems during chromatographic
2.4. Application of 1,1-di¯uoropentyl arene building
blocks 3 and 4 in liquid crystal synthesis
The stable 2-&1,1-di¯uoropentyl)thiophene 3 and its ben-
zene analog 4a could be prepared on a multigram scale

5762
A. A. Kiryanov et al. /Tetrahedron 57 $2001) 5757±5767
and proved useful as building blocks in the construction of a
series of teraryl liquid crystalline targets bearing the 1,1-
di¯uoropentyl terminal chain. For example, Suzuki cross-
coupling of 2-bromo-5-&1,1-di¯uoropentyl)thiophene &3)
with dodecyloxy-substituted biphenylboronic acid 22
&0.1 MPdCl 2, 2 Maq Na 2CO3, acetone) afforded mesogenic
target 1b in 72% yield &Eq. 2). In line with other 1,1-
di¯uoropentyl-substituted teraryl mesogenic targets that
we have prepared,8d,18 this compound has a high melting
temperature &155.98C) and supports a disordered smectic
A phase below the clearing point &172.48C); however, in
contrast to other related 1,1-di¯uoropentyl-bearing teraryl
mesogens, this particular material also supported a more
low lying disordered tilted smectic F phase &160.48C). In
addition, smectic mesophases such as the orthogonal hexatic
smectic B phase have been detected in other 1,1-di¯uoro-
alkyl-containing teraryl mesogens. A full paper detailing the
mesomorphic phase behavior of a series of 1,1-di¯uoro-
alkyl-substituted teraryl liquid crystals, as well as various
functional group derivatives thereof, will appear sepa-
rately.18
tyl benzene analog 4a were well suited for use as building
blocks in the synthesis of liquid crystalline materials via
application of Suzuki cross-coupling methodology. The
application of this chemistry in the synthesis of a range of
1,1-di¯uoroalkyl-containing liquid crystalline materials
&and variously functionalized analogs thereof), along with
full details of their mesomorphic phase behavior, will be
reported elsewhere.18
4.Experimental
4.1. General
Unless otherwise stated, NMR spectra were recorded in
CDCl3 as follows: 1H NMR &300 MHz), 13C NM R
&75 MHz) and 19F NMR &470 MHz). Chemical shifts are
reported in ppm down®eld from TMS &1H and 13C NMR)
or CFCl3 &19F NMR). Unless otherwise noted, coupling
1
constants refer to H±1H coupling &JH±H). In some samples
containing mixtures of components, overlapping signals
precluded the observation of all NMR signals. In these
cases, only those selected signals which were readily
discernible are reported for each component. Low resolution
mass spectra &MS) were recorded using a Hewlett Packard
&HP) 5890 Series II GC hooked to an HP 5972 Mass
Selective DetectorÐonly selected ions are presented.
High resolution mass spectra &HRMS) were recorded in
electron impact mode at the Ohio State University
Chemistry Mass Spectrometry Facility. Combustion
analyses were performed using a LECO Model CHNS-932
elemental analyzer. Transition temperatures for mesogen 1b
were measured upon cooling at a rate of 58C per minute
using a Mettler FP82HT hot-stage and FP90 control unit
in conjunction with a Leica Laborlux 12PolS polarizing
microscope. The progress of reactions was monitored
using either silica TLC or GC using a Shimadzu GC-14A
gas chromatograph ®tted with a 30 m capillary column.
Unless otherwise stated, all chemicals were used as received
without additional puri®cation. Anhydrous CH2Cl2 was
obtained by stirring and distillation from CaH2. Anhydrous
ether and THF were obtained by distillation from benzo-
phenone ketyl. All chromatographic separations were
performed using ¯ash column chromatography on silica
gel &200±425 mesh) or alumina &activated, basic, 50±
200 mm, Acros Organics). The synthesis of ketone 8 will
be reported elsewhere.18 The synthesis of ketone 9 was
achieved by deprotection of dithiolane 21 using
Hg&ClO4)2´3H2O.24
ꢀ2†
3.Conclusion
We have described a survey of various methods for the
synthesis of 2-&1,1-di¯uoroalkyl) thiophenes &and related
1,1-di¯uoroalkyl benzenes). A thorough exploration of
various amino¯uorosulfurane-mediated ¯uorodeoxygenation
approaches was performed; however, only moderate to low
yields of the desired 1,1-di¯uoroalkyl arene targets could be
obtained. A variety of approaches involving ¯uorodesulfuri-
zation of 2-alkyl-2-aryl-1,3-dithiolanes were also explored.
The most successful approach to 2-&1,1-di¯uoropentyl) thio-
phenes involved use of NOBF4/PPHF employing very short
reaction times and a modi®ed workup protocol. Although
use of NBS &or DBH)/PPHF also gave reasonable yields of
the desired products, competing ring and/or side chain
bromination pathways made this approach less attractive.
These problems were avoided when using NIS/PPHF. The
NOBF4/PPHF ¯uorodesulfurization conditions also proved
useful in the synthesis of analogous 1,1-di¯uoroalkyl
benzenes 4a and 4b bearing longer alkyl chains &pentyl
and octyl), which had not been previously reported,6 as
well as higher molecular weight biphenylthienyl-based
liquid crystalline materials 1a and 1b. Although the various
1,1-di¯uoroalkyl arene products were susceptible to hydro-
lytic decomposition on prolonged exposure to silica, the
puri®ed products proved quite stable. Both 2-bromo-5-
&1,1-di¯uoropentyl) thiophene &3) and the 1,1-di¯uoropen-
4.2. Synthesis of ketone precursors
4.2.1. 2-Bromo-5-pentanoylthiophene ꢀ7). FeCl3 &9.95 g,
0.0613 mol) was added in one portion to a stirred mixture of
2-bromothiophene &50.0 g, 0.307 mol) and valeric anhy-
dride &65.7 g, 0.353 mol) under nitrogen at rt &a temperature
rise to 1008C was noted). The reaction mixture was stirred at
rt for a further 2 h &TLC and GC analyses con®rmed a
complete reaction) and was then poured into water
&300 mL). The organic layer was separated and the aqueous
layer was washed with ether &2£50 mL). The combined
organic extracts were washed with 2 Maq Na 2CO3
&2£200 mL). The organic layer was dried &MgSO4) and

A. A. Kiryanov et al. /Tetrahedron 57 $2001) 5757±5767
5763
concentrated in vacuo to give a black liquid. The crude
product was distilled in vacuo to give the title compound
7 as a colorless liquid &bp 128±1338C/0.5 mmHg) &62.36 g,
benzene &9.64 g, 40.0 mmol), ethane-1,2-dithiol &7.37 mL,
88.0 mmol) and BF3´2HOAc &6.13 mL, 44.0 mmol). The
crude dried organic extract was passed through a short silica
plug &5 cm long, 4 cm in diameter). The plug was washed
with petroleum ether &200 mL). Concentration in vacuo
afforded the title compound 18 as a colorless liquid
&9.80 g, 77%) which was suf®ciently pure for use in the
1
82%). H NM Rd 0.94 &t, Jˆ7.2 Hz, 3H), 1.39 &sextet,
Jˆ7.5 Hz, 2H), 1.70 &quint, Jˆ7.5 Hz, 2H), 2.82 &t, Jˆ
7.2 Hz, 2H), 7.09 &d, Jˆ3.9 Hz, 1H), 7.44 &d, Jˆ3.9 Hz,
1H); 13C NM Rd 13.8, 22.6, 26.6, 38.3, 122.2, 130.5,
132.8, 145.9, 192.3. Anal. Calcd for C9H11BrOS: C,
43.74; H, 4.49; S, 12.97. Found: C, 43.91; H, 4.51; S, 13.06.
1
next step without further puri®cation. H NM Rd 0.84 &t,
Jˆ6.8 Hz, 3H), 1.15±1.30 &m, 4H), 2.32 &t, Jˆ7.9 Hz, 2H),
3.14±3.41 &m, 4H), 7.42 &d, Jˆ8.7 Hz, 2H), 7.59 &d, Jˆ
8.7 Hz, 2H). 13C NM Rd 14.1, 22.9, 30.2, 39.3, 45.6, 74.0,
121.0, 129.3, 131.1, 144.8. Anal. Calcd for C13H15BrS2: C,
49.21; H, 5.40; S, 20.21; Found: C, 48.89; H, 5.41; S, 20.60.
4.2.2. 1-Bromo-4-pentanoylbenzene.25 Valeryl chloride
&20.6 g, 0.171 mol) was added dropwise to a stirred, cooled
&08C) mixture of bromobenzene &29.1 g, 0.185 mol) and
AlCl3 &49.8 g, 0.373 mol) under argon. The reaction mixture
was maintained under these conditions for a further 1 h and
was then heated at 70±808C for 2 h &GC analysis indicated a
complete reaction). The cooled mixture was poured into aq
HCl &18%, 200 mL). The product was extracted into CH2Cl2
&2£100 mL), washed with water &2£100 mL) and dried
&MgSO4). Concentration in vacuo followed by vacuum
distillation afforded the title compound as a colorless semi-
4.3.3. 2-ꢀ4-Bromophenyl)-2-heptyl-1,3-dithiolane ꢀ19).
This compound was prepared following the procedure
described for compound 10 using 1-bromo-4-octanoyl-
benzene &5.66 g, 20.0 mmol), ethane-1,2-dithiol &3.7 mL,
44.0 mmol) and BF3´2HOAc &3.1 mL, 22.0 mmol). The
crude dried organic extract was passed through a short silica
plug &5 cm long, 4 cm in diameter). The plug was washed
with petroleum ether &200 mL). Concentration in vacuo
afforded the title compound 19 as a colorless liquid
&7.22 g, 100%) which was suf®ciently pure for use in the
1
solid &bp 85±878C/1.1 mmHg) &35.7 g, 85%). H NM Rd
0.94 &t, Jˆ7.4 Hz, 3H), 1.39 &sextet, Jˆ7.4 Hz, 2H), 1.70
&quint, Jˆ7.5 Hz, 2H), 2.92 &t, Jˆ7.4 Hz, 2H), 7.59 &d,
Jˆ8.7 Hz, 2H), 7.81 &d, Jˆ8.7 Hz, 2H).
1
next step without further puri®cation. H NM Rd 0.85 &t,
Jˆ6.8 Hz, 3H), 1.00±1.40 &m, 10H), 2.30 &t, Jˆ6.6 Hz, 2H),
3.12±3.40 &m, 4H), 7.41 &d, Jˆ8.7 Hz, 2H), 7.58 &d,
Jˆ8.7 Hz, 2H). 13C NM Rd 13.9, 22.4, 27.7, 28.8, 29.4,
31.5, 39.0, 45.5, 73.6, 120.6, 128.9, 130.7, 144.4. Anal.
Calcd for C16H17BrS2: C, 53.47; H, 6.45; S, 17.84; Found:
C, 53.82; H, 6.50; S, 18.22.
4.2.3. 1-Bromo-4-octanoylbenzene.26 This compound was
prepared following the above procedure using octanoyl
chloride &35.00 g, 0.2152 mol), bromobenzene &40.00 g,
0.2548 mol) and AlCl3 &57.34 g, 0.4300 mol) under argon.
The crude product was distilled in vacuo to give the title
compound as a colorless solid &50.61 g, 83%), mp 65±668C.
1H NM Rd 0.88 &t, Jˆ6.9 Hz, 3H), 1.23±1.42 &m, 8H), 1.72
&quint, Jˆ7.4 Hz, 2H), 2.92 &t, Jˆ7.4 Hz, 2H), 7.59 &d,
Jˆ8.5 Hz, 2H), 7.81 &d, Jˆ8.5 Hz, 2H); 13C NM Rd 14.2,
22.7, 24.4, 29.2, 29.4, 31.8, 38.7, 128.1, 129.7, 132.0, 136.0,
199.5.
4.3.4. 2-Butyl-2-[5-ꢀ40-dodecyloxy-2-¯uorobiphenyl-4-yl)-
thien-2-yl]-1,3-dithiolane ꢀ20). To a stirred biphasic
mixture of compound 10 &0.485 g, 1.50 mmol), &Ph3P)4Pd
&0.085 g, 0.075 mmol) and 2 Maq Na 2CO3 &1.5 mL,
3.0 mmol) in benzene &3.0 mL), was added 40-dodecyloxy-
2-¯uorobiphenyl-4-ylboronic acid28 &0.752 g, 1.88 mmol) in
ethanol &1.5 mL). The reaction mixture was heated under
re¯ux for 3 h. The cooled mixture was diluted with water
&20 mL) and extracted with CH2Cl2 &4£20 mL). The
combined organic extracts were washed with water
&3£30 mL), brine &2£30 mL) and dried &Na2SO4). Concen-
tration in vacuo gave a dark yellow oil which was puri®ed
by gradient column chromatography on silica gel &petro-
leum ether±CHCl3, 10:1±1:1). The resulting yellow solid
was dried in vacuo &P2O5, paraf®n wax, 1.1 mmHg) to afford
the title compound 20 as a yellow solid &0.840 g, 94%). 1H
NMR d 0.89 &t, Jˆ6.9 Hz, 3H), 0.91 &t, Jˆ7.2 Hz, 3H),
1.24±1.51 &m, 22H), 1.81 &quint, Jˆ7.1 Hz, 2H), 2.41 &m,
2H), 3.43 &s, 4H), 4.00 &t, Jˆ6.6 Hz, 2H), 6.97 &d, Jˆ8.8 Hz,
2H), 7.07 &d, Jˆ3.8 Hz, 1H), 7.15 &d, Jˆ3.8 Hz, 1H), 7.29±
7.43 &m, 3H), 7.50 &dd, Jˆ8.7 Hz, JH±Fˆ1.5 Hz, 2H); 19F
NMR d 2118.4 &br dd, JF±Hˆ7.5, 4.4 Hz). Anal. Calcd for
C35H47FOS3: C, 70.19; H, 7.91; S, 16.06; Found: C, 69.79;
H, 7.97; S, 16.20.
4.3. General procedure for synthesis of 1,3-dithiolane
precursors27
4.3.1. 2-ꢀ5-Bromothien-2-yl)-2-butyl-1,3-dithiolane ꢀ10).
BF3´2HOAc &6.25 mL, 44.9 mmol) was added over a period
of 5 min to a mixture of 2-bromo-5-pentanoylthiophene &7)
&10.04 g, 40.65 mmol) and ethane-1,2-dithiol &7.50 mL,
89.6 mmol) under nitrogen. The resulting solution was
stirred vigorously for 20 min. The mixture was diluted
with hexanes &100 mL) and washed sequentially with sat.
aq NaHCO3, 15% aq NaOH, and brine &3£80 mL in each
case). The organic layer was dried &Na2SO4) and concen-
trated in vacuo to afford the title compound 10 as a slightly
yellow liquid &12.85 g, 98%) which was suf®ciently pure for
use in the next step without further puri®cation. 1H NM Rd
0.88 &t, Jˆ7.1 Hz, 3H), 1.23±1.47 &m, 4H), 2.32 &t, Jˆ
8.0 Hz, 2H), 3.38 &m, 4H), 6.83 &d, Jˆ3.9 Hz, 1H), 6.86
&d, Jˆ3.9 Hz, 1H); 13C NM Rd 13.8, 22.6, 30.0, 39.5,
44.7, 69.7, 111.3, 125.3, 129.7, 154.6. Anal. Calcd for
C11H15BrS3: C, 40.86; H, 4.68; S, 29.75; Found: C, 40.77;
H, 4.74; S, 30.11.
4.3.5. 2-Butyl-2-[5-ꢀ40-dodecyloxybiphenyl-4-yl)thien-2-
yl]-1,3-dithiolane ꢀ21). To a stirred, cooled &08C) solution
of PdCl2&dppf) &0.200 g, 0.273 mmol) and dithiolane 10
&7.80 g, 24.1 mmol) in anhydrous THF &20 mL) under
argon, was added dropwise, over a period of 30 min, a
solution of 40-dodecyloxybiphenyl-4-yl magnesium bromide
4.3.2. 2-ꢀ4-Bromophenyl)-2-butyl-1,3-dithiolane ꢀ18).
This compound was prepared following the procedure
described for compound 10 using 1-bromo-4-pentanoyl-

5764
A. A. Kiryanov et al. /Tetrahedron 57 $2001) 5757±5767
&prepared from magnesium &0.660 g, 0.267 mol) and
4-bromo-40-dodecyloxybiphenyl28 &10.43 g, 0.0250 mol) in
anhydrous THF &30 mL)). The reaction mixture was
allowed to warm to rt and was stirred until completion of
the reaction &ca. 1 day, as established by TLC analysis).
Methanol &1.0 mL) was added and the reaction mixture
was diluted with CH2Cl2 &300 mL). The mixture was ®ltered
through a short silica plug and the solvent was evaporated in
vacuo. The residue was puri®ed by column chromatography
on silica gel &CH2Cl2) and dried in vacuo to afford the title
&1,1-di¯uoropentyl)thiophene &3) as a clear colorless liquid
1
&0.865 g, 80%). The H-, 13C- and 19F NMR spectra of this
product were identical to those reported above for this
compound.
4.5.2. ꢀ2) DBH/PPHF-Mediated ¯uorodesulfurization of
2-ꢀ5-bromothien-2-yl)-2-butyl-1,3-dithiolane ꢀ10). 2-&5-
Bromothien-2-yl)-2-butyl-1,3-dithiolane &10) was subjected
to ¯uorodesulfurization following the general procedure
described above except that DBH &1.11 g, 4.00 mmol) was
employed as the Hal1 source and the reaction was allowed
to proceed for 45 min. The ®ltrate was concentrated in
vacuo to afford a mixture of several products &0.705 g,
60%). NMR, GC and GC±MS analysis revealed the
following components:
1
compound 21 &5.00 g, 36%) as a yellow solid. H NM Rd
0.88 &t, Jˆ6.9 Hz, 3H), 0.90 &t, Jˆ7.2 Hz, 3H), 1.24±1.52
&m, 22H), 1.80 &quint, Jˆ7.2 Hz, 2H), 2.41 &m, 2H), 3.43 &s,
4H), 3.99 &t, Jˆ6.5 Hz, 2H), 6.96 &d, Jˆ8.7 Hz, 2H), 7.05
&d, Jˆ3.6 Hz, 1H), 7.13 &d, Jˆ3.6 Hz, 1H), 7.52 &d, Jˆ
8.7 Hz, 2H), 7.53 &d, Jˆ8.4 Hz, 2H), 7.60 &d, Jˆ8.4 Hz,
2H). 13C NM Rd 13.8, 14.0, 22.6, 22.7, 25.9, 29.2 &2),
29.3, 29.5, 30.1, 31.8, 39.6, 45.1, 68.0, 70.0, 114.7, 122.3,
125.7, 126.2, 126.8, 127.7, 132.6, 139.6, 143.1, 152.1,
158.7. Anal. Calcd for C35H48OS3: C, 72.36; H, 8.33;
Found: C, 72.34; H, 8.20.
2-Bromo-5-ꢀ1,1-di¯uoropentyl)thiophene ꢀ3) &39%): the
1H-, 13C- and 19F NMR spectra of this product were
identical to those reported above for this compound; MS
m/z 270 &20, M1), 268 &20, M1), 213 &100, M12C4H9),
211 &98, M12C4H9), 189 &37, M12Br), 133 &20, M12
Br±C4H8), 132 &19, M12Br±C4H9), 57 &8, C4H9).
4.4. General procedure for DAST-mediated ¯uoro-
deoxygenation of thienyl ketones
2,3-Dibromo-5-ꢀ1,1-di¯uoropentyl)thiophene ꢀ11a) &15%):
²
1H NM R &selected signals) d 7.02 &t, JH±Fˆ1.5 Hz, 0.4H).
13C NMR &selected signals) d 24.6, 38.5 &t, JC±Fˆ26.3 Hz),
4.4.1. 2-Bromo-5-ꢀ1,1-di¯uoropentyl)thiophene ꢀ3). 2-
Bromo-5-pentanoylthiophene &7) &1.00 g, 4.02 mol) was
added dropwise to stirred DAST &2.40 g, 14.9 mol) under
argon at rt in a 7 mL plastic vial. The reaction mixture was
heated at 558C for 4 days. The cooled reaction mixture was
diluted with petroleum ether &40 mL, bp 35±608C) and washed
with saturated aq NaHCO3 until free of acid. The organic layer
was ®ltered through a short silica column &petroleum ether)
and the solvent was removed in vacuo to give the title
113.9, 120.4 &t, JC±Fˆ241.5 Hz), 128.8 &t, JC±Fˆ6.0 Hz),
³
140.8 &t, JC±Fˆ32.2 Hz); 19F NM R &282 MHz) d 286.6
&t, JF±Hˆ16.0 Hz, 0.4F); MS m/z 350 &14, M1), 348 &28,
M1), 346 &14, M1), 293 &52, M12C4H9), 291 &100,
M12C4H9), 289 &50, M12C4H9), 269 &22, M12Br), 267
&17, M12Br), 245 &7, M12CF2C4H8), 244 &8, M12
CF2C4H9), 243 &14, M12CF2C4H8), 242 &15, M12
CF2C4H9), 241 &8, M12CF2C4H8), 240 &8, M12
CF2C4H9), 162 &19, M12CF2C4H9±Br), 160 &14, M12
CF2C4H9±Br), 131 &32, M122Br±C4H9), 57 &8, C4H9).
1
compound 3 as a colorless liquid &0.302 g, 28%); H NM R
d 0.91 &t, Jˆ6.9 Hz, 3H), 1.33±1.52 &m, 4H), 2.17 &m, 2H),
6.95 &dt, Jˆ3.6 Hz, JH±Fˆ1.5 Hz, 1H), 6.99 &dt, Jˆ3.6 Hz,
JH±Fˆ0.9 Hz, 1H); 13C NM Rd 13.9, 22.4, 24.7, 38.6 &t,
JC±Fˆ26.6 Hz), 114.4, 120.8 &t, JC±Fˆ240.3 Hz), 126.4 &t,
JC±Fˆ6.0 Hz), 129.8, 141.1 &t, JC±Fˆ32.2 Hz); 19F NM R
&282 MHz) d 285.3 &t, JF±Hˆ16.0 Hz). HRMS found m/z
267.9733 &M1, 79Br isotope), C9H11BrF2S requires 267.9733.
2-Bromo-5-ꢀ2-bromo-1,1-di¯uoropentyl)thiophene ꢀ12a)
1
²
&2%): H NM R &selected signals) d 4.22 &app. ddt, Jˆ2.8,
10.5 Hz, JH±Fˆ10.7 Hz, 0.05H), 7.03 &dt, Jˆ3.9 Hz, JH±F
ˆ
1.5 Hz, 0.05H); 7.07 &dt, Jˆ3.9 Hz, JH±Fˆ1.1 Hz, 0.05H).
13C NMR &selected signals) d 54.7 &t, JCFˆ 26.6 Hz), 128.4
³
&t, JC±Fˆ6.0 Hz). 19F NM R &282 MHz) d 289.6 &d, JF±H
ˆ
11.0 Hz, 0.05F); MS m/z 350 &3, M1), 348 &6, M1), 346 &3,
M1), 269 &2, M12Br), 267 &2, M12Br), 213 &100, M12
C4H8Br), 211 &100, M12C4H8Br), 132 &14, M12C4H8Br±
Br), 105 &21, CF2C4H7).
4.5. Fluorodesulfurization of 1,3-dithiolanes using Hal1/
PPHF
4.5.1. ꢀ1) NIS/PPHF-Mediated ¯uorodesulfurization
of 2-ꢀ5-bromothien-2-yl)-2-butyl-1,3-dithiolane ꢀ10)
ꢀGeneral procedure). 2-&5-Bromothien-2-yl)-2-butyl-1,3-
dithiolane &10) &1.29 g, 4.00 mmol) was added dropwise to
a stirred, cooled &2788C) solution of NIS &1.80 g,
8.00 mmol) in CH2Cl2 &12 mL) under argon in a 25 mL
plastic bottle. After stirring at this temperature for 15 min,
the red reaction mixture was poured into a plastic graduated
cylinder containing petroleum ether &70 mL). The upper
orange organic layer was removed and the bottom dark
layer was extracted with petroleum ether±CH2Cl2 &7:1,
2£35 mL). The combined organic layers were diluted with
petroleum ether &50 mL) and CH2Cl2 &5 mL) and passed
through a short silica plug followed by short basic alumina
plug29 &7 cm long, 4 cm in diameter). Petroleum ether±
CH2Cl2 &7:1, 150 mL) was used to wash the plug. The
®ltrate was concentrated in vacuo to afford 2-bromo-5-
2-Bromo-5-ꢀ1-bromopent-1-enyl)thiophene ꢀ13a) &1%):
²
1H NM R &selected signals for major geometrical isomer)
d 6.20 &t, Jˆ7.1 Hz, 0.02H); 7.37 &d, Jˆ3.9 Hz, 0.02H),
7.57 &d, Jˆ3.9 Hz, 0.02H); MS m/z 312 &30, M1), 310
&57, M1), 308 &30, M1), 270 &7, M12C3H6), 268 &13,
M12C3H6), 266 &7, M12C3H6), 231 &42, M12Br), 229
&41, M12Br), 202 &77, M12Br-CH2CH3), 200 &77, M12
Br±CH2CH3), 189 &35, M12Br±C3H6), 187 &34, M12Br±
C3H6), 150 &100, M122Br).
2,3-Dibromo-5-ꢀ2-bromo-1,1-di¯uoropentyl)thiophene
ˆ
³
ꢀ14a) &1%): 19F NM R &282 MHz) d 290.5 &d, JF±H
²
These 1H NMR integrals are relative to 1H/H for the protons in 3.
³
These 19F NMR integrals are relative to 1F/F for the ¯uorine atoms in 3.

A. A. Kiryanov et al. /Tetrahedron 57 $2001) 5757±5767
5765
11.0 Hz, 0.02F); MS m/z 430 &2, M1), 428 &6, M1), 426 &6,
and
&1.43 g, 4.52 mmol) in anhydrous CH2Cl2 &9 mL). The
2-&4-bromophenyl)-2-heptyl-1,3-dithiolane
&19)
M1), 424 &2, M1), 349 &0.5, M12Br), 347 &1.1, M12Br),
345 &0.6, M12Br), 293 &51, M12C4H8Br), 291 &100, M12
C4H8Br), 289 &52, M12C4H8Br), 212 &5, M12C4H8Br±
Br), 210 &5, M12C4H8Br±Br), 162 &8, M12CF2C4H8Br±
Br), 160 &8, M12CF2C4H8Br±Br), 105 &31, CF2C4H7).
title compound 4b was obtained as a colorless liquid
1
&1.12 g, 81%). H NM Rd 0.87 &t, Jˆ6.8 Hz, 3H), 1.19±
1.32 &m, 8H), 1.38 &m, 2H), 2.08 &m, 2H), 7.33 &d, Jˆ8.6 Hz,
2H), 7.54 &d, Jˆ8.7 Hz, 2H); 13C NM Rd 13.9, 22.3, 22.5,
28.9, 29.0, 31.5, 38.9 &t, JC±Fˆ27.3 Hz), 122.7 &t, JC±F
ˆ
4.5.5. ꢀ3) NBS/PPHF-Mediated ¯uorodesulfurization of
2-ꢀ5-bromothien-2-yl)-2-butyl-1,3-dithiolane ꢀ10). 2-&5-
Bromothien-2-yl)-2-butyl-1,3-dithiolane &10) was subjected
to ¯uorodesulfurization following the general procedure
described above except that NBS &1.42 g, 8.00 mmol) was
employed as the Hal1 source and the reaction was allowed
to proceed for 45 min. The ®ltrate was concentrated in
vacuo. NMR, GC and GC±MS analysis revealed a mixture
of the following components &based on a comparison with
the spectral data for each component listed above): 3 &80%),
11a &,1%), 12a &1%), 13a &,1%).
242.3 Hz), 123.8, 126.6 &t, JC±Fˆ6.1 Hz), 131.5, 136.5 &t,
JC±Fˆ27.4 Hz); 19F NM Rd 296.0 &t, JF±Hˆ15.7 Hz).
HRMS found m/z 304.0640 &M1, 81Br isotope),
C14H19BrF2 requires 304.0638.
4.6.4. 2-ꢀ40-Dodecyloxy-2-¯uorobiphenyl-4-yl)-5-ꢀ1,1-di-
¯uoropentyl)thiophene ꢀ1a). Compound 1a was prepared
following the above general procedure using NOBF4
&0.156 g, 1.33 mmol) and PPHF &0.5 mL, 70% HF content)
in anhydrous CH2Cl2 &4 mL) and 2-butyl-2-[5-&40-dodecyl-
oxy-2-¯uorobiphenyl-4-yl)thien-2-yl]-1,3-dithiolane &20)
&1.43 g, 4.52 mmol) in anhydrous CH2Cl2 &2.5 mL).
Hexanes±CH2Cl2 &3:1) was used as the solvent system for
workup and ®ltration. The resulting solid was dried in vacuo
&P2O5, paraf®n wax, 1.1 mmHg) to afford the title compound
4.6. General procedure for ¯uorodesulfurization of 1,3-
dithiolanes using NOBF4/PPHF
1
1a as a white solid &0.213 g, 78%). H NM Rd 0.89 &t,
4.6.1. 2-Bromo-5-ꢀ1,1-di¯uoropentyl)thiophene ꢀ3). To a
pre-dried 50 mL plastic bottle charged with a magnetic
stirrer was added nitrosonium tetra¯uoroborate &NOBF4)
&0.543 g, 4.64 mmol) under argon. Anhydrous CH2Cl2
&10 mL) and pyridinium poly&hydrogen ¯uoride) &PPHF)
&2 mL, 70% HF content) were injected into the bottle and
the reaction mixture was cooled to 08C. A solution of
2&5-bromothien-2-yl)-2-butyl-1,3-dithiolane &10) &0.700 g,
2.17 mmol) in anhydrous CH2Cl2 &4 mL) was then added
dropwise over a period of 3±5 min. The ice bath was
removed and the reaction mixture was stirred for a further
2 min before dilution with petroleum ether &80 mL) in a
plastic cylinder. The upper organic layer was removed and
the dark bottom layer was extracted with a petroleum ether±
CH2Cl2 mixture &3:1, 40 mL). The organic layers were
combined and passed through a short silica plug &5 cm).
The colorless ®ltrate was concentrated in vacuo to afford
the title compound 3 as a colorless liquid &0.508 g, 87%).
Jˆ6.9 Hz, 3H), 0.94 &t, Jˆ7.2 Hz, 3H), 1.24±1.55 &m,
22H), 1.82 &quint, Jˆ7.0 Hz, 2H), 2.25 &m, 2H), 4.01 &t,
Jˆ6.6 Hz, 2H), 6.98 &d, Jˆ8.8 Hz, 2H), 7.18 &dt, Jˆ3.8,
1.3 Hz, 1H), 7.23 &dt, Jˆ3.8, 1.2 Hz, 1H), 7.34±7.47 &m,
3H), 7.50 &d, Jˆ8.7 Hz, 1H), 7.51 &d, Jˆ8.7 Hz, 1H). 13C
NMR d 14.0, 14.3, 22.5, 22.9, 24.9, 26.2, 29.4, 29.5, 29.6,
29.8, 32.1, 38.8 &t, JC±Fˆ26.7 Hz), 68.3, 113.6 &d, JC±F
24.8 Hz), 114.7, 121.3 &t, JC±Fˆ239.7 Hz), 122.0 &d, JC±F
2.8 Hz), 123.3, 127.1 &t, JC±Fˆ5.7 Hz), 127.4, 128.5 &d, JC±F
ˆ
ˆ
ˆ
13.4 Hz), 130.1 &d, JC±Fˆ3.2 Hz), 131.0 &d, JC±Fˆ3.8 Hz),
134.1 &d, JC±Fˆ8.3 Hz), 139.2 &t, JC±Fˆ31.8 Hz), 158.2,
159.9 &d, JC±Fˆ247.3 Hz). 19F NM Rd 285.0 &t, JF±H
ˆ
16.0 Hz, 2F), 2117.9 &dd, JF±Hˆ11.0, 7.0 Hz, 1F). Anal.
Calcd for C33H43F3OS: C, 72.76; H, 7.96; S, 5.89; found
C, 72.94; H, 7.70; S, 6.26.
4.6.5.
2-ꢀ40-Dodecyloxybiphenyl-4-yl)-5-ꢀ1,1-di¯uoro-
1
The H-, 13C- and 19F NMR spectra of this product were
pentyl)thiophene ꢀ1b). Compound 1b was prepared follow-
ing the above general procedure using NOBF4 &0.907 g,
7.75 mmol) and PPHF &3.0 mL, 70% HF content) in anhy-
drous CH2Cl2 &15 mL) and 2-butyl-2-[5-&40-dodecyloxy-
identical to those reported above for this compound.
4.6.2. 1-Bromo-4-ꢀ1,1-di¯uoropentyl)benzene ꢀ4a). Com-
pound 4a was prepared following the above general pro-
cedure using NOBF4 &1.27 g, 10.9 mmol) and PPHF
&4.5 mL, 70% HF content) in anhydrous CH2Cl2 &22 mL),
and 2-&4-bromophenyl)-2-butyl-1,3-dithiolane &18) &1.43 g,
4.51 mmol) in anhydrous CH2Cl2 &9 mL). The title
compound 4a was obtained as a colorless liquid &0.860 g,
biphenyl-4-yl)thien-2-yl]-1,3-dithiolane
&21)
&1.74 g,
3.00 mmol) in anhydrous CH2Cl2 &9.0 mL). The combined
organic extracts were ®ltered through a short &7 cm long,
4 cm in diameter) silica plug &hexanes±dichloromethane,
4:1) to obtain pure 1b after drying in vacuo &P2O5, paraf®n
wax, 1.1 mmHg) &0.472 g, 30%). Product decomposition
was observed during ®ltration &the corresponding ketone
produced a bright blue band under UV light as decompo-
sition occurred). The plug was washed with CH2Cl2 and the
®ltrate concentrated in vacuo to afford a mixture of title
1
72%). H NM Rd 0.88 &t, Jˆ7.1 Hz, 3H), 1.25±1.42 &m,
4H), 2.09 &m, 2H), 7.33 &d, Jˆ8.7 Hz, 2H), 7.55 &d, Jˆ
8.6 Hz, 2H); 13C NM Rd 13.7, 22.2, 24.4 &t, JC±F
ˆ
3.5 Hz), 38.6 &t, JC±Fˆ28.0 Hz), 122.7 &t, JC±Fˆ242.5 Hz),
1
compound 1b &0.270 g, 17%: based on H NMR ratio;
total yield 47%) together with the corresponding 2-&40-
dodecyloxybiphenyl-4-yl)-5-pentanoylthiophene &9) &0.203
126.7 &t, JC±Fˆ6.2 Hz), 123.8, 131.5, 136.5 &t, JC±F
ˆ
27.3 Hz); 19F NM Rd 296.0 &t, JF±Hˆ16.0 Hz). HRMS
found m/z 264.0166 &M1, 81Br isotope), C11H13BrF2 requires
264.0148.
1
1
g, 13%: based on H NMR ratio). 1b: H NM Rd 0.88 &t,
Jˆ6.9 Hz, 3H), 0.93 &t, Jˆ7.2 Hz, 3H), 1.27±1.56 &m, 22H),
1.81 &quint, Jˆ6.6 Hz, 2H), 2.25 &m, 2H), 4.00 &t, Jˆ6.6 Hz,
4.6.3. 1-Bromo-4-ꢀ1,1-di¯uorooctyl)benzene ꢀ4b). Com-
pound 4b was prepared following the above general pro-
cedure using NOBF4 &1.270 g, 10.86 mmol) and PPHF
&4.5 mL, 70% HF content) in anhydrous CH2Cl2 &22 mL),
2H), 6.98 &d, Jˆ9.0 Hz, 2H), 7.17 &dt, Jˆ3.9 Hz, JH±F
ˆ
1.5 Hz, 1H), 7.22 &dt, Jˆ3.6 Hz, JH±Fˆ1.2 Hz, 1H), 7.54
&d, Jˆ8.7 Hz, 2H), 7.57 &d, Jˆ9.0 Hz, 2H), 7.63 &d,

5766
A. A. Kiryanov et al. /Tetrahedron 57 $2001) 5757±5767
Jˆ8.7 Hz, 2H); 13C NM Rd 13.7, 14.0, 22.2, 22.6, 24.6,
26.0, 29.2, 29.3 &2), 29.5, 31.8, 38.6 &t, JC±Fˆ26.5 Hz),
68.0, 114.8, 121.2 &t, JC±Fˆ237.5 Hz), 122.3, 126.2, 126.7
31.2 Hz), 140.5, 145.6, 158.9; 19F NM Rd 285.1&t, JF±H
16.2 Hz). Anal. Calcd for C33H44F2OS: C, 75.24; H, 8.42; S,
Challenges and Biomedicinal Targets; Soloshonok, V. A.,
Ed.; Wiley: Chichester, 1999; pp 535±556. &d) Hiyama, T.;
Kusumoto, T.; Matsutani, H. In Asymmetric Fluoroorganic
ChemistryÐSynthesis, Applications and Future Directions;
Ramachandran, P. V., Ed.; ACS Symposium Series 746,
ACS: Washington, DC, 2000; pp 226±238.
&t, JC±Fˆ4.8 Hz), 127.0, 127.8, 131.8, 132.4, 138.2 &t, JC±F
ˆ
ˆ
2. &a) Jones, J. C.; Raynes, E. P.; Towler, M. J.; Sambles, J. R.
Mol. Cryst. Liq. Cryst. Lett. 1990, 7, 91±99. &b) Jones, J. C.;
Towler, M. J.; Hughes, J. R. Displays 1993, 14, 86±93.
6.09; Found: C, 75.54; H, 8.62; S, 5.97. 9: identi®ed by
comparison of its H NMR spectrum with an authentic
1
sample prepared by the deprotection of thienyl dithiolane
21 using Hg&ClO4)2´3H2O:24 d 0.88 &t, Jˆ6.8 Hz, 3H), 0.97
&t, Jˆ7.4 Hz, 3H), 1.24±1.51 &m, 22H), 1.78 &quint, Jˆ
7.5 Hz, 2H), 2.90 &t, Jˆ7.5 Hz, 2H), 4.01 &t, Jˆ6.6 Hz,
2H), 6.98 &d, Jˆ8.7 Hz, 2H), 7.34 &d, Jˆ3.6 Hz, 1H), 7.55
&d, Jˆ8.7 Hz, 2H), 7.60 &d, Jˆ8.1 Hz, 2H), 7.69 &d, Jˆ
3.6 Hz, 1H), 7.00 &d, Jˆ8.4 Hz, 2H).
Â
&c) Markscheffel, S.; Jakli, A.; Saupe, A. Ferroelectrics
1996, 180, 59±70. &d) Lagerwall, S. T. Ferroelectric and Anti-
ferroelectric Liquid Crystals; Wiley±VCH: Weinheim, 1999.
&e) Lagerwall, S. T. In Handbook of Liquid Crystals: Low
Molecular Weight Liquid Crystals II; Gray, G. W., Spiess,
H.-W., Vill, V., Eds.; Wiley±VCH: Weinheim, 1998; pp
515±664.
4.7. Synthesis of 2-ꢀ40-dodecyloxybiphenyl-4-yl)-5-ꢀ1,1-
di¯uoropentyl)thiophene ꢀ1b) via Suzuki cross-coupling
approach
3. &a) Kitazume, T.; Yamazaki, T. Experimental Methods in
Organic Fluorine Chemistry; Gordon and Breach: Tokyo,
1998; pp 9±10. &b) Smart, B. E. In Organo¯uorine Chemistry:
Principles and Commercial Applications; Banks, R. E., Smart,
B. E., Tatlow, J. C., Eds.; Plenum: New York, 1994; pp 80±
81.
Palladium&II) chloride &0.1 Msolution in water, 0.2 mL,
0.02 mmol) was added in one portion to a stirred mixture
of 40-dodecyloxybiphenyl-4-ylboronic acid &22)18 &0.500 g,
1.30 mmol), 2-bromo-5-&1,1-di¯uoropentyl)thiophene &3)
&0.210 g, 0.78 mmol) and sodium carbonate &2.0 M,
1.68 mL, 3.36 mmol) in acetone &10 mL) under dry argon.
The reaction mixture was heated under re¯ux for 40 h and
the cooled reaction mixture was then diluted with aq hydro-
chloric acid &10%, 10 mL) and extracted with CH2Cl2
&3£20 mL). The combined organic extracts were washed
with water &100 mL) and dried &Na2SO4). The drying
agent was ®ltered off and the extract was ®ltered through
a column of silica gel &petroleum ether±dichloromethane,
3:1) before the solvent was removed in vacuo. The crude
product was crystallized from ethyl acetate followed by
petroleum ether &bp 35±608C) to afford the title compound
1b as a white solid, which was dried in vacuo &P2O5, paraf®n
wax, 24 h) &0.280 g, 72%). The 1H, 13C and 19F NM R
spectra of this product were identical to those reported
above for this compound. Liquid crystal transitions &8C):
Cryst 155.9 SF 160.4 SA 172.4 I.
4. &a) Goodby, J. W. Mol. Cryst. Liq. Cryst. 1997, 292, 245±263.
&b) Wulf, A. Phys. Rev. A 1975, 11, 365±375.
5. Goodby, J. W. In Properties and Structures of Ferroelectric
Liquid Crystals; Taylor, G. W., Ed.; Gordon and Breach:
Philadelphia, 1991; pp 99±241.
6. After the completion of our studies described herein, Goodby
and coworkers brie¯y communicated the ¯uorodesulfurization
of 2-alkyl-2-&2,3-di¯uorophenyl)-1,3-dithiolanes bearing
longer alkyl chains using HF/pyridine. Unfortunately, no
yields were cited and no experimental detail was provided:
Goodby, J. W.; Hird, M.; Jones, J. C.; Lewis, R. A.; Sage,
I. C.; Toyne, K. J. Ferroelectrics 2000, 243, 19±26.
7. Lal, G. S.; Pez, G. P.; Pesaresi, R. J.; Prozonic, F. M.; Cheng,
H. J. Org. Chem. 1999, 64, 7048±7054.
8. &a) Middleton, W. J. J. Org. Chem. 1975, 40, 574±578.
&b) Hudlicky, M. Org. React. 1988, 35, 513±637. &c) Bart-
mann, E. Ber. Bunsenges. Phys. Chem. 1993, 97, 1349±
1355. &d) Kiryanov, A. A.; Sampson, P.; Seed, A. J. Mol.
Cryst. Liq. Cryst. 1999, 328, 237±244.
9. &a) SeF4 has also been used for the ArC&O) to ArCF2 transfor-
mation: Olah, G. A.; Nojima, M.; Kerekes, I. J. Am. Chem.
Soc. 1974, 96, 925±927. &b) CF2Br2/Zn has also been used for
the ArC&O) to ArCF2 transformation: Hu, C.-M.; Qing, F.-L.;
Shen, C.-X. J. Chem. Soc., Perkin Trans. 1 1993, 335±338.
10. &a) Prakash, G. K. S.; Reddy, V. P.; Li, X.-Y.; Olah, G. A.
Synlett 1990, 594±596. &b) Rozen, S.; Zamir, D. J. Org. Chem.
1991, 56, 4695±4700. &c) Patrick, T. B.; Flory, P. A.
J. Fluorine Chem. 1984, 25, 157±164. &d) York, C.; Prakash,
G. K. S.; Wang, Q.; Olah, G. A. Synlett 1994, 425±426.
&e) Rozen, S.; Mishani, E.; Bar-Haim, A. J. Org. Chem.
1994, 59, 2918.
Acknowledgements
We thank Kent State University for ®nancial support of this
work. One of us &A. A. K.) acknowledges Kent State
University for a University Fellowship. The assistance
with some NMR experiments provided by Dr Mahinda
Gangoda is greatly appreciated. Dr James D. Dudones
&Case Western Reserve University) is thanked for his
assistance in obtaining GC±MS data.
11. Other reported approaches to the synthesis of 1,1-di¯uoroalkyl
benzenes include the ¯uorination of phenylacetylene using HF
&Matsuda, K.; Sedlak, J. A.; Noland, J. S.; Gleckler, G. C.
J. Org. Chem. 1962, 27, 4015±4020) or 6HF±Et3N &Hara,
S.; Kameoka, M.; Yoneda, N. Synlett 1996, 529±530), and
anodic and/or chemical oxidation of a-phenylthio-a-aryl
esters in Et3N±3HF followed by ¯uorodesulfurization of the
resulting a-¯uoro thioether using DBH±HF±Et3N &Laurent,
E.; Marquet, B.; Roze, C.; Ventalon, F. J. Fluorine Chem.
1998, 87, 215±220).
References
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286. &c) Kusumoto, T.; Hiyama, T. In Enantiocontrolled
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16. Three syntheses of 2-di¯uoromethyl thiophenes &i.e. 2-&1,1-
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debromination of 2,5-bis-dibromomethyl-3,4-dibromothio-
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22. See, for example: &a) Zhou, Q.-L.; Huang, Y.-Z. J. Fluorine
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data was not provided.
26. The synthesis and 1H NMR spectrum of 1-bromo-4-octanoyl-
benzene have previously been reported: Liu, M. S.; Liu, Y.;
Urian, R. C.; Ma, H.; Jen, A. K-Y. J. Mater. Chem. 1999, 9,
2201±2204.
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27. The synthesis of dithiolanes followed the protocol reported by
Katzenellenbogen &Ref. 21).
28. The synthesis of this compound will be reported separately
&see Ref. 18).
29. The grade of basic alumina employed had a profound impact
on the outcome of this ®ltration step. Use of activated basic
alumina &50±200 mm) from Acros Organics as the support for
this ®ltration step worked well; however, when Brockman
activity I-grade basic alumina from Fisher Scienti®c was
employed, a substantial amount of HF elimination was
observed. Mono¯uoroalkenyl- and alkynylthiophene products
were obtained in varying ratios along with little or none of the
desired 1,1-di¯uoropentylthiophene 3.
18. The synthesis of a series of ¯uorinated teraryl mesogenic
targets using this chemistry will be published elsewhere:
Kiryanov, A. A.; Sampson, P.; Seed, A. J. J. Mater. Chem.
Submitted for publication.