Novel aromatic fluoroolefins via fluoro-Julia-Kocienski olefination

Article abstract of DOI:10.1055/s-0030-1258198

Fluoroolefins, which play an increasingly important role as peptide mimics in pharmaceuticals and as crop protection agents, are generated using a fluoro-Julia-Kocienski olefination. Their preparation can easily be accomplished using a Mitsunobu reaction and subsequent oxidation to generate the required benzothiazolyl sulfones. The key step of this process was the electrophilic -fluorination of the sulfone with N-fluorobenzenesulfonimide. The last stage of the successful synthesis of the fluoroolefins was the modified Julia-Kocienski olefination under basic conditions. Further functionalization was followed with the application of a Suzuki reaction. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0030-1258198

PAPER
3439
Novel Aromatic Fluoroolefins via Fluoro-Julia–Kocienski Olefination
N
ovel Aromatic Fl
a
uoroolefinsdine Allendörfer,a Mazen Es-Sayed,b Martin Nieger,c Stefan Bräse*a
a
Karlsruhe Institute of Technology (KIT), Institute of Organic Chemistry, Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany
E-mail: +49(721)6088581; E-mail: braese@kit.edu
b
c
Bayer CropScience SA Research, BCS-R-F-CFLYO, BP 99163/14 impasse Pierre Baizet, 69263 Lyon Cedex 09, France
Laboratory of Inorganic Chemistry, Department of Chemistry, P.O. Box 55, 00014 University of Helsinki, Finland
Received 1 May 2010; revised 22 June 2010
tween moderate to excellent yields (49–97%, Table 1).
Alcohol 1f was prepared from 2-chloronicotinic acid (4)
by simple reduction with BH3·THF.13,14
Abstract: Fluoroolefins, which play an increasingly important role
as peptide mimics in pharmaceuticals and as crop protection agents,
are generated using a fluoro-Julia–Kocienski olefination. Their
preparation can easily be accomplished using a Mitsunobu reaction
and subsequent oxidation to generate the required benzothiazolyl
sulfones. The key step of this process was the electrophilic a-fluo-
rination of the sulfone with N-fluorobenzenesulfonimide. The last
stage of the successful synthesis of the fluoroolefins was the modi-
fied Julia–Kocienski olefination under basic conditions. Further
functionalization was followed with the application of a Suzuki re-
action.
1) Ph3P, DIAD,
THF, r.t.
2) MCPBA,
CH2Cl2, r.t.
S
N
R
S
N
+
OH
SH
S
R
O
O
1
2
5
Scheme 1 Mitsunobu reaction of 1 and following oxidation
Key words: fluorine, olefination, sulfones, heterocycles, cross-
coupling
Table 1 Mitsunobu Reaction and Following Oxidation of Alcohols
1
Entry
1
3
Yield
(%)
5
Yield
(%)
The incorporation of fluorine atoms in organic com-
pounds results in the modifications of several fields of ac-
tion.1 Changes in biological activity are often observed
when fluorine is introduced into new compounds of me-
dicinal interest.2 These advantages of fluorine are illus-
trated by the prominence of organofluorine compounds
and the importance of new synthetic approaches for their
synthesis.3–7 Fluoroolefins have been successfully pre-
pared and used as precursors of medicines, agrochemi-
cals, and modified pheromones.8 In particular, among the
large variety of peptidomimetics, the monofluorinated
olefins described in this article are considered to be excel-
lent surrogates for amide bonds.9 One of the most efficient
strategies to install a C=C bond is the Julia olefination and
the method modified by Kocienski and co-workers.10,11
The combination of this well established olefination and
fluorine chemistry leads to useful building blocks for var-
ious research areas like drug discovery.
OH
1
2
1a
1b
3a
3b
97
75
5a
5b
94
78
Br
OH
OH
Cl
Cl
3
1c
3c
92
5c
82
Cl
OH
CF3
4
5
6
7
1d
1e
1f
3d
3e
3f
90
61
96
49a
5d
5e
5f
86
OH
quant
56
F3C
We herein present some modifications of a methodology
for the synthesis fluoroolefins, as previously developed by
Gosh and Zajc.12 In contrast to the reported syntheses we
started our route in a different way. Instead of a nucleo-
philic substitution of benzyl chlorides with 2-mercapto-
benzothiazole a Mitsunobu reaction of benzylic alcohols
1 as the first step for the synthesis was chosen (Scheme 1).
The use of a slight excess of 2-mercaptobenzothiazole (2),
triphenylphosphine, and diisopropyl azodicarboxylate
(DIAD) furnished the desired products 3 (not shown) be-
OH
N
Cl
S
0b
OH
1g
3g
5g
O
a See Figure 1.
b Decomposition of the starting material was observed.
A by-product 6 was isolated in the case of alcohol 1g,
which explains the modest yield of the main product 3g
(Figure 1). Under the previously mentioned Mitsunobu
conditions substitution of the nitrogen atom instead of the
sulfur atom of 2-mercaptobenzothiazole took place.15
SYNTHESIS 2010, No. 20, pp 3439–3448
x
x.
x
x
.
2
0
1
0
Advanced online publication: 05.08.2010
DOI: 10.1055/s-0030-1258198; Art ID: T10010SS
© Georg Thieme Verlag Stuttgart · New York

3440
N. Allendörfer et al.
PAPER
1) base
S
2) NFSi
F
solvent
temperature
S
R
S
S
R
S
S
N
S
N
S
S
O
O
S
O
O
N
N
O
5
7
O
Scheme 2 Electrophilic fluorination of sulfones 5
3g (49%)
6 (31%)
Figure 1 Product 3g and by-product 6, isolated during the
Mitsunobu reaction of 1g
three hours and gave product 7a in 56% yield (Table 2,
entry 1). Next, attempts were made to increase the yield
by a longer reaction time, but the observed yield was low-
er than before (Table 2, entries 2, 3). No product could be
isolated by increasing the ratio of LDA to substrate
(Table 2, entry 4). Change of base to LiHMDS and sol-
vent to THF were not successful either (Table 2, entry 5).
As alternative reaction conditions, sodium hydride in ace-
tonitrile as solvent was tested at higher temperature and
led to an increased yield of fluorosulfone 7a (74%,
Table 2, entry 6). The fluorosulfones 7b, 7e, and 7f were
synthesized under similar reaction conditions (Table 2).
Sodium hydride and NFSi were used in small excesses of
1.22 and 1.23 equivalents. The fluorinated products could
be isolated in 33% to 58% yield. In case of sulfone 7d,
only the use of LDA and toluene led to acceptable 49%
yield (Table 2, entry 8). Pyridine derivative 7f could be
isolated in 56% yield.
Wicha et al. also observed this side reaction with an allylic
alcohol, so it was envisaged that the use of the Mitsunobu
reaction is limited to nonallylic alcohols.
Next, the oxidation reaction of sulfides 3 to the corre-
sponding sulfones 5 was explored. Gratifyingly, m-chlo-
roperbenzoic acid (MCPBA) led to good to excellent
yields of the sulfones (Scheme 1 and Table 1). Oxone was
less efficient. The reaction was carried out with 3 equiva-
lents of the oxidizing reagent. Use of smaller amounts of
MCPBA led to chiral sulfoxides as by-products, which
1
could be easily detected by H NMR spectroscopy. Fur-
thermore, in the case of the pyridine derivative 5f no pyri-
dine N-oxide was observed, although MCPBA can be
used for the preparation of such compounds.16
The general structure of sulfones was confirmed by con-
ducting an X-ray structural determination on 5a (Figure 2,
see experimental for details).
Table 2 Electrophilic Fluorination
Entry
5
Base
Solvent
Temp Time Prod- Yield
(°C)
–78
–78
–78
–78
–78
–30
–30
–78
–30
–30
(h)
uct 7 (%)
1
2
5a LDA
5a LDA
5a LDA
5a LDAa
toluene
toluene
toluene
toluene
3
7a
7a
7a
7a
7a
7a
7b
7d
7e
7f
56
28
12
0
15
48
24
3
3
4
5
5a LiHMDS THF
0
6
5a NaH
5b NaH
5d LDA
MeCN
24
24
3
74
58
49
33
56
7
MeCN
toluene
MeCN
MeCN
8
9
5e
5f
NaH
NaH
48
24
10
a Two equivalents.
Figure 2 X-ray crystal structure of 5a
The key step of our synthetic route was the introduction of
one fluorine atom to the BT-sulfone (BT = benzothia-
zolyl, Scheme 2). The deprotonation-fluorination reaction
was optimized in terms of base, solvent and temperature.
N-Fluorobenzenesulfonimide (NFSi) proved to be the
fluorinating agent of choice as already found earlier.12,17,18
During the electrophilic monofluorination of sulfone 5c
under the optimized conditions, traces of the monofluori-
nated sulfone 7c and the difluorinated sulfone 8c were iso-
lated. The crystal structure of 7c/8c (Figure 3) shows an
occupancy disorder between the (additionally position
disordered) monofluorinated sulfone 7c and the difluori-
nated sulfone 8c in the ratio of 3:1. The difluorinated com-
pound is probably formed due to the small excess of the
fluorination species.
Sulfone 5a was taken as a model system and different re-
action conditions were investigated. First attempt was car-
ried out with lithium diisopropylamide (LDA) as base and
toluene as solvent. The reaction was stirred at –78 °C for
Synthesis 2010, No. 20, 3439–3448 © Thieme Stuttgart · New York

PAPER
Novel Aromatic Fluoroolefins
Table 3 Olefination Reaction (Scheme 3)
3441
Entry Sulfone 7 Aldehyde
Product 10 E/Z
ratioa,b
Yield
(%)a
O
1
2
3
7a
7a
7a
9a
9bc
9c
10a
10b
10c
3.4:1.0
only E
4.5:1.0
61
CF3
O
57
51
N
Cl
O
Figure 3 Top: molecular structure of monofluorinated sulfone 7c;
bottom: molecular structure of difluorinated sulfone 8c
N
O
With the fluorosulfones in hand, the Julia–Kocienski ole-
fination was examined with a range of aldehydes under
‘Barbier-like’ conditions (the base is added to a mixture of
the aldehyde and sulfone). Reaction of the fluorosulfones
7 with a selection of functionalized (het)aryl aldehydes 9
gave the fluoro(hetero) stilbenes 10 in moderate to good
yields (Scheme 3, Table 3); E and/or Z-isomers were
formed depending on the substitution pattern.
4
5
6
7
7b
7d
7e
7f
9a
9d
9e
9d
10d
10e
10f
10g
0.4:1.0
only Z
6.2:1.0
2.4:1.0
65
20
85
60
CF3
O
Br
O
O
N
F
Ar
9
O
F
LiHMDS
THF, 0 °C
R
S
R
S
Ar
O
N
O
F
Br
7
10
a Isomers are separable in some cases. Combined yields are given.
b Geometry ascertained using NMR spectroscopy.12,19,20
c Aldehyde 9b was obtained by oxidation of alcohol 1f using DMP as
oxidizing species.21,22
Scheme 3 Olefination of fluorosulfones 7 with aldehydes 9
We next turned our attention to the preparation of fluoro-
stilbenes bearing one substituted aromatic ring and one
heterocyclic unit. Therefore, the reaction was carried out
with a small excess of fluorosulfones 7 (1.20 equiv) and
an excess of LiHMDS (2.40 equiv). The appropriate sol-
vent was THF and the optimal temperature was 0 °C as
Gosh and Zajc had reported earlier.12
coupling, the E/Z-ratio was determined to be 1.0 to 1.6.
Double bond isomerizations are described in radical or
photochemical processes.26 But it is also known that the
isomerization can be induced under palladium(II) cataly-
sis,27 which presumably appears during the Suzuki cou-
pling of 10b. Indeed, the biaryl 11e could be prepared
under the same condition in 86% yield, but the isomeriza-
tion of the double bond did still occur. Due to this fact, the
reaction conditions were changed and the reaction of 10a
and 4-chlorophenylboronic acid was carried out using
Pd(PPh3)4 as catalyst, saturated aqueous Na2CO3 as base,
and a mixture of dimethoxyethane and ethanol as sol-
vent.25 The desired product 11a could be obtained in 75%
yield and no isomerization of the double bound was ob-
served.
The fluoroolefins 10a–c (Table 3, entries 1–3) and 10f,g
(Table 3, entries 6, 7) were mostly obtained as the E-iso-
mers. If a mixture was obtained, the E/Z ratio varied be-
tween 6.2:1 and 2.4:1. Only the vinyl fluorides 10d and
10e (Table 3, entries 5, 7) were predominantly isolated as
the Z-isomers.
A Suzuki reaction was used to achieve further functional-
ization of the brominated fluoro(hetero)stilbenes.23–25 The
reactions provided the biaryl systems 11a,b and e in mod-
erate to excellent yields (25–86%, Figure 4). Biaryl 11b
could be isolated in 25% yield. As catalyst palladium ac-
etate and triphenylphosphine were employed, the reaction
was carried out in DMF and potassium carbonate was
used as base.24 As mentioned before, the fluoroolefin 10b
was isolated only as the E-isomer. After the Suzuki cross-
In conclusion, we have presented here the application of a
fluoro-Julia–Kocienski method for the generation of (het-
ero)arylfluorostilbenes and synthetic alternatives of the
procedure developed by Gosh and Zajc. We successfully
applied several aromatics with various functional groups
Synthesis 2010, No. 20, 3439–3448 © Thieme Stuttgart · New York

3442
N. Allendörfer et al.
PAPER
ing yellow residue was purified by column chromatography on sil-
ica gel (cHex–EtOAc) to afford the title compounds 3 (Table 1).
2-(2-Bromobenzylthio)benzo[d]thiazole (3a)
Yield: 0.874 g (2.59 mmol, 97%); yellow oil; Rf = 0.62 (cHex–
EtOAc, 5:1).
F
F
CF3
N
Cl
IR (KBr): 3441, 3061, 1640, 1460, 1427, 1309, 1239, 1026, 994
cm–1.
Cl
Cl
11a (75%)
E/Z = 1.7:1.0
11b (25%)
E/Z = 1.0:1.6
1H NMR (400 MHz, CDCl3): d = 4.75 (s, 2 H, CH2), 7.14 (dt, J =
1.7, 7.7 Hz, 1 H, ArH-5¢), 7.25 (dt, J = 1.3, 7.5 Hz, 1 H, ArH-4¢),
7.28–7.32 (m, 1 H, ArH-3¢), 7.43 (ddd, J = 1.2, 7.3, 8.3 Hz, 1 H,
ArH-6¢), 7.60 (ddd, J = 1.4, 8.2, 11.3 Hz, 2 H, ArH-5,6), 7.76 (dd,
J = 0.5, 1.1 Hz, 1 H, ArH-4), 7.92 (ddd, J = 0.5, 0.9, 8.1 Hz, 1 H,
ArH-7).
F
CF3
13C NMR (100 MHz, CDCl3): d = 37.9, 121.0, 121.6, 124.3, 124.8,
126.0, 127.6, 129.4, 131.3, 133.0, 135.5, 136.1, 153.1, 166.0.
Cl
MS (70 eV, EI): m/z (%) = 337/335 (48/45, [M+]), 256 (100,
11e (86%)
E/Z = 2.6:1.0
[C14H10NS2 ]), 223 (43), 171/169 (56/59, [C7H6Br+]), 90 (34).
+
Figure 4 Synthesized biaryls 11a, b, and e
HR-EIMS: m/z calcd for C14H10BrNS2: 334.9438; found: 334.9432.
Anal. Calcd for C14H10BrNS2: C, 50.00; H, 3.00; N, 4.17; S, 19.07.
Found: C, 50.07; H, 3.06; N, 4.36; S, 18.97.
and heterocyclic compounds like pyridine derivatives.
Furthermore, we succeeded in the Suzuki cross-coupling
of brominated fluoroolefins with 4-chlorophenylboronic
acid leading to functionalized biaryls, which provides a
higher diversity of products.
2-(4-Chlorobenzylthio)benzo[d]thiazole (3b)
Yield: 0.275 g (0.938 mmol, 75%); white solid; Rf = 0.46 (cHex–
EtOAc, 10:1).
IR (KBr): 3083 (w), 3063 (w), 2926 (w), 1950 (vw), 1912 (w), 1794
(w), 1595 (w), 1558 (w), 1492 (m), 1456 (m), 1426 (m), 1405 (w),
1309 (w), 1274 (w), 1239 (w), 1192 (w), 1123 (w), 1094 (m), 1078
(w), 1017 (m), 1003 (m), 973 (w) cm–1.
1H NMR (400 MHz, CDCl3): d = 4.56 (s, 2 H, CH2), 7.27–7.33 (m,
3 H, ArH-6,2¢,6¢), 7.28–7.45 (m, 2 H, ArH-3¢,5¢), 7.43 (m, 1 H,
ArH-5), 7.75 (d, J = 7.8 Hz, 1 H, ArH-4), 7.90 (d, J = 8.1 Hz, 1 H,
ArH-7).
13C NMR (100 MHz, CDCl3): d = 36.8, 121.0, 121.6, 124.4, 126.1,
128.8, 130.5, 133.6, 134.9, 135.3, 153.0, 165.8.
MS (70 eV, EI): m/z (%) = 293/292/291 (40/15/94, [M+]), 260/259/
258 (11/5/32, [M – S+]), 173 (25), 171 (26), 127/126/125 (30/6/100,
[C7H6Cl+]).
All reagents, except 1f and 9b, were purchased from ABCR, Apollo
Scientific, Merck, Sigma-Aldrich and Thermo Fisher Scientific and
used without further purification. The starting materials 1f13 and
9b22 were prepared according to literature. Solvents were dried and
purified by standard methods. For TLC, aluminum foils layered
with silica gel (silica gel 60 F254) produced by Merck were used.
Column chromatography was performed employing Merck silica
gel 60 under flash conditions (EtOAc, cHex = cyclohexane). Unless
1
otherwise indicated, all solvent ratios are given as v/v. H, 13C and
19F NMR spectra were measured with a Bruker Avance 400 (400
MHz, 100 MHz, and 376 MHz, respectively) spectrometer. CDCl3
was used as solvent and residual CHCl3/CDCl3 as shift reference: d
(CHCl3) = 7.26 ppm, d (CDCl3) = 77.0 ppm. 19F NMR spectra were
recorded with an external standard. IR spectra were recorded with
Bruker FTIR device IFS 88. EI-MS, FAB-MS, FAB-HRMS, and
HR-EIMS spectra were recorded on a Finnigan MAT 95 instru-
ment; elemental analyses were performed using an Elementar Vario
Micro device.
HR-EIMS: m/z calcd for C14H10ClNS2: 290.9943; found: 290.9945.
Anal. Calcd for C14H10ClNS2: C, 57.62; H, 3.45; N, 4.80; S, 21.98.
Found: C, 57.45; H, 3.41; N, 4.76; S, 21.85.
2-(3,4-Dichlorobenzylthio)benzo[d]thiazole (3c)
Yield: 0.443 g (1.15 mmol, 92%); yellow oil; Rf = 0.36 (cHex–
EtOAc, 19:1).
(2-Chloropyridin-3-yl)methanol (1f)13
Colorless solid. Yield: 0.417 g (2.89 mmol, 83%).
IR (KBr): 3856, 3772, 3448, 3061, 3029, 2926, 2850, 2290, 1901,
1781, 1711, 1592, 1561, 1469, 1427, 1309, 1275, 1239, 1204, 1133,
1076, 1032, 1018, 998 cm–1.
1H NMR (400 MHz, CDCl3): d = 4.53 (s, 2 H, CH2), 7.32 (dt, J =
4.5, 10.7 Hz, 2 H, ArH-5,6), 7.38 (d, J = 8.3 Hz, 1 H, ArH-5¢), 7.44
(m, 1 H, ArH-6¢), 7.58 (d, J = 2.0 Hz, 1 H, ArH-3¢), 7.75 (d, J = 8.0
Hz, 1 H, ArH-4), 7.90 (d, J = 8.1 Hz, 1 H, ArH-7).
1H NMR (400 MHz, CDCl3): d = 4.67 (d, J = 5.4 Hz, 2 H, CH2),
7.17 (m, 1 H, ArH-5), 7.79 (m, 1 H, ArH-4), 8.18 (dd, J = 1.7, 4.7
Hz, 1 H, ArH-6).
2-Chloropyridin-3-carbaldehyde (9b)22
Light yellow solid. Yield: 0.245 g (1.72 mmol, 54%).
1H NMR (400 MHz, CDCl3): d = 7.43 (ddd, J = 0.6, 4.8, 7.6 Hz, 1
H, ArH-5), 8.24 (dd, J = 2.1, 7.7 Hz, 1 H, ArH-4), 8.62 (dd, J = 2.1,
4.7 Hz, 1 H, ArH-6), 10.45 (d, J = 0.6 Hz, 1 H, CHO).
13C NMR (100 MHz, CDCl3): d = 36.1, 121.0, 121.6, 124.5, 126.1,
128.4, 130.5, 131.1, 131.7, 132.5, 135.3, 136.9, 152.9, 165.2.
MS (70 eV, EI): m/z (%) = 329/327/325 (5/20/28, [M+]), 292 (9, [M
+
– S+]), 163/161/159 (2/16/25, [C7H5Cl2 ]), 43 (100).
Benzothiazole Sulfides 3; General Procedure
HR-EIMS: m/z calcd for C14H9Cl2NS2: 324.9553; found: 324.9554.
To a solution of 2-mercaptobenzothiazole (2; 1.10 equiv), Ph3P
(1.10 equiv), and the corresponding alcohol 1 (0.279–2.84 mmol,
1.00 equiv) in anhyd THF (14.5 mL/mmol 1) was added DIAD
(1.10 equiv) dropwise. The reaction mixture was stirred for 15 h at
r.t. The solvent was removed under reduced pressure and the result-
Anal. Calcd for C14H9Cl2NS2: C, 51.54; H, 2.78; N, 4.29; S, 19.66.
Found: C, 51.87; H, 2.90; N, 4.35; S, 19.42.
Synthesis 2010, No. 20, 3439–3448 © Thieme Stuttgart · New York

PAPER
Novel Aromatic Fluoroolefins
3443
2-[2-(Trifluoromethyl)benzylthio]benzo[d]thiazole (3d)
Yield: 0.832 g (2.56 mmol, 90%); colorless oil; Rf = 0.59 (cHex–
EtOAc, 10:1).
IR (KBr): 3064, 2923, 2881, 1718, 1639, 1491, 1466, 1428, 1371,
1313, 1240, 1143, 1078, 1005 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.89 (s, 3 H, CH3), 2.90 (m, 2 H,
SCH2), 4.10 (s, 2 H, CH2), 4.16 (m, 2 H, OCH2), 7.20 (m, 1 H, ArH-
5), 7.32 (m, 1 H, ArH-6), 7.66 (dd, J = 0.8, 7.7 Hz, 1 H, ArH-4),
7.78 (dd, J = 0.8, 8.0 Hz, 1 H, ArH-7).
IR (KBr): 3065, 1943, 1607, 1584, 1497, 1459, 1428, 1316, 1240,
1179 cm–1.
1H NMR (400 MHz, CDCl3): d = 4.84 (s, 2 H, CH2), 7.32 (ddd, J =
1.2, 7.4, 8.3 Hz, 1 H, ArH-4¢), 7.37 (t, J = 7.7 Hz, 1 H, ArH-6), 7.44
(ddd, J = 1.2, 7.4, 8.3 Hz, 1 H, ArH-3¢), 7.49 (t, J = 7.6 Hz, 1 H,
ArH-5), 7.68 (d, J = 7.8 Hz, 1 H, ArH-4), 7.75 (d, J = 2.9 Hz, 1 H,
ArH-7), 7.74–7.78 (m, 1 H, ArH-5¢), 7.92 (m, 1 H, ArH-6¢).
13C NMR (100 MHz, CDCl3): d = 33.7, 121.1, 121.6, 122.9, 124.4,
126.1, 126.2, 127.8, 128.6, 128.9, 131.8, 132.3, 135.4, 153.0, 166.0.
13C NMR (100 MHz, CDCl3): d = 18.1, 25.9, 37.3, 65.6, 95.3,
120.9, 121.4, 124.2, 125.9, 135.2, 146.7, 152.9, 166.4.
MS (70 eV, EI): m/z (%) = 295 (7, [M+]), 262 (21, [M+ – SH], 208
(39), 167 (100, [C7H5NS2 ]), 129 (65, [C6H9OS+]), 103 (64).
+
3-[(2-Methyl-5,6-dihydro-1,4-oxathiin-3-yl)methyl]ben-
zo[d]thiazole-2(3H)-thione (6)
Isolated as the by-product together with 3g. Yield: 0.156 g (0.527
mmol, 31%); yellow oil; Rf = 0.47 (cHex–EtOAc, 5:1).
19F NMR (376 MHz, CDCl3): d = –59.3.
MS (70 eV, EI): m/z (%) = 325 (96, [M+]), 159 (100, [C8H6F3 ]),
+
109 (36).
IR (KBr): 3422, 3063, 2966, 2927, 2876, 1737, 1642, 1458, 1429,
1367, 1223, 1137 cm–1.
HR-EIMS: m/z calcd for C15H10F3NS2: 325.0206; found: 325.0209.
1H NMR (500 MHz, CDCl3): d = 2.10 (s, 3 H, CH3), 2.88 (m, 2 H,
SCH2), 4.20 (m, 2 H, OCH2), 5.26 (s, 2 H, NCH2), 7.30 (t, J = 8.1
Hz, 1 H, ArH-6), 7.34 (d, J = 7.5 Hz, 1 H, ArH-7), 7.37 (t, J = 7.4
Hz, 1 H, ArH-5), 7.47 (d, J = 8.2 Hz, 1 H, ArH-4).
13C NMR (125 MHz, CDCl3): d = 18.7, 25.5, 47.5, 65.3, 96.1,
112.8, 121.2, 124.7, 126.7, 127.2, 136.1, 154.5, 190.2.
Anal. Calcd for C15H10F3NS2: C, 55.37; H, 3.10; N, 4.30; S, 19.71.
Found: C, 55.43; H, 3.23; N, 4.45; S, 19.31.
2-[4-(Trifluoromethyl)benzylthio]benzo[d]thiazole (3e)
Yield: 0.248 g (0.763 mmol, 61%); white solid; mp 183 °C; Rf =
0.35 (cHex–EtOAc, 19:1).
IR (KBr): 3071, 2925, 2307, 1958, 1921, 1799, 1615, 1589, 1559,
1458, 1427, 1412, 1332, 1310, 1237, 1172, 1155, 1122, 1097, 1070,
1019, 1004, 979 cm–1.
MS (70 eV, EI): m/z (%) = 295 (47, [M+]), 262 (25, [M – SH+]), 166
+
(28, [C7H4NS2 ]), 129 (100, [C6H9OS+]), 43 (86, [C2H3O+]).
HR-EIMS: m/z calcd for C13H13NOS3: 295.0159; found: 295.0160.
1H NMR (400 MHz, CDCl3): d = 4.64 (s, 2 H, CH2), 7.29–7.34 (m,
1 H, ArH-6), 7.44 (ddd, J = 1.2, 7.4, 8.3 Hz, 1 H, ArH-5), 7.58 (s, 4
H, ArH-2¢,3¢,5¢,6¢), 7.76 (d, J = 8.0 Hz, 1 H, ArH-4), 7.91 (d, J =
8.1 Hz, 1 H, ArH-7).
13C NMR (100 MHz, CDCl3): d = 36.8, 121.1, 121.6, 124.0, 124.5,
125.6, 126.1, 129.4, 129.9, 135.4, 140.7, 153.0, 165.4.
Benzothiazole Sulfones 5; General Procedure
A solution of benzothiazole sulfide 3 (0.455–8.02 mmol, 1.00
equiv) in CH2Cl2 (20 mL/mmol 3) was cooled to 0 °C and MCPBA
(3.00 equiv) was added portion by portion. The reaction mixture
was stirred for additional 10 min at 0 °C and allowed to warm to r.t.
and stirred for 5 h. The mixture was quenched with sat. aq NaHCO3
(10 mL/mmol 3) and the layers were separated. The aqueous layer
was extracted with CH2Cl2 (3 × 30 mL/mmol 3), and the combined
organic layers were washed with H2O (10 mL/mmol 3) and brine
(10 mL/mmol 3), dried (Na2SO4), and the solvent removed under re-
duced pressure. Purification of the crude product by column chro-
matography on silica gel (cHex–EtOAc) gave the pure products 5
(Table 1).
19F NMR (376 MHz, CDCl3): d = –62.5.
MS (70 eV, EI): m/z (%) = 325 (100, [M+]), 292 (44, [M – S+]), 159
+
(50, [C8H6F3 ]).
HR-EIMS: m/z calcd for C15H10F3NS2: 325.0206; found: 325.0209.
Anal. Calcd for C15H10F3NS2: C, 55.37; H, 3.10; N, 4.30; S, 19.71.
Found: C, 55.36; H, 3.12; N, 4.16; S, 20.05.
2-[(2-Chloropyridin-3-yl)methylthio]benzo[d]thiazole (3f)
Yield: 0.786 g (0.268 mmol, 96%); yellow oil; Rf = 0.38 (cHex–
EtOAc, 5:1).
2-(2-Bromobenzylsulfonyl)benzo[d]thiazole (5a)
Yield: 2.76 g (7.54 mmol, 94%); brown solid; Rf = 0.26 (cHex–
EtOAc, 5:1).
IR (KBr): 3068, 2993, 2951, 2913, 2736, 2621, 1919, 1793, 1562,
1458, 1427, 1408, 1259, 1239 cm–1.
IR (KBr): 3064, 2995, 2941, 1959, 1921, 1795, 1701, 1569, 1467
cm–1.
1H NMR (400 MHz, CDCl3): d = 4.70 (s, 2 H, CH2), 7.18 (dd, J =
7.6, 4.8 Hz, 1 H, ArH-5¢), 7.31 (t, J = 7.6 Hz, 1 H, ArH-6), 7.43
(ddd, J = 1.2, 7.4, 8.3 Hz, 1 H, ArH-5), 7.75 (d, J = 8.5 Hz, 1 H,
ArH-4), 7.90 (d, J = 8.1 Hz, 1 H, ArH-4¢), 8.00 (dd, J = 1.9, 7.6 Hz,
1 H, ArH-7), 8.30 (dd, J = 1.9, 4.8 Hz, 1 H, ArH-6¢).
13C NMR (100 MHz, CDCl3): d = 34.3, 121.1, 121.6, 122.6, 124.5,
126.2, 131.7, 135.5, 139.7, 148.7, 151.3, 152.9, 165.2.
1H NMR (400 MHz, CDCl3): d = 5.00 (s, 2 H, CH2), 7.21 (dt, J =
1.7, 7.6 Hz, 1 H, ArH-4¢), 7.29 (dt, J = 1.3, 7.5 Hz, 1 H, ArH-5¢),
7.45 (dd, J = 1.7, 7.7 Hz, 1 H, ArH-3¢), 7.53 (dd, J = 1.3, 8.0 Hz, 1
H, ArH-6¢), 7.57–7.68 (m, 2 H, ArH-5,6), 7.94 (dd, J = 0.6, 8.0 Hz,
1 H, ArH-7), 8.25 (dd, J = 0.6, 8.2 Hz, 1 H, ArH-4).
13C NMR (100 MHz, CDCl3): d = 60.5, 122.3, 125.6, 126.1, 126.9,
127.7, 127.9, 128.1, 130.9, 133.1, 133.4, 137.3, 152.7, 164.8.
MS (70 eV, EI): m/z (%) = 292.1/294.1 (66/27, [M+]), 257.1 (100,
MS (70 eV, EI): m/z (%) = 367/369 (0.12/0.13, [M+]), 288 (100,
+
[C13H9N2S2 ]), 224 (27), 126/128 (59/17, [C6H5ClN+]).
[C14H10NO2S2 ]), 170/169 (70/68, [C7H6Br+]), 90 (33, [C7H6 ]).
+
+
HR-EIMS: m/z calcd for 291.9895; found 291.9897.
HR-EIMS: m/z calcd for C14H10BrNO2S2: 366.9336; found:
366.9336.
Anal. Calcd for C13H9ClN2S2: C, 53.32; H, 3.10; N, 9.57; S, 21.90.
Found: C, 53.74; H, 3.06; N, 9.94; S, 21.81.
Anal. Calcd for C14H10BrNO2S2: C, 45.66; H, 2.74; N, 3.80; S,
17.41. Found: C, 45.49; H, 2.87; N, 3.63; S, 16.59.
2-[(2-Methyl-5,6-dihydro-1,4-oxathiin-3-yl)methylthio]ben-
zo[d]thiazole (3g)
Yield: 0.248 g (0.833 mmol, 49%); yellow solid; Rf = 0.59 (cHex–
EtOAc, 5:1).
Synthesis 2010, No. 20, 3439–3448 © Thieme Stuttgart · New York

3444
N. Allendörfer et al.
PAPER
2-(4-Chlorobenzylsulfonyl)benzo[d]thiazole (5b)
Yield: 0.237 g (0.728 mmol, 78%); white solid; Rf = 0.42 (cHex–
EtOAc, 4:1).
IR (KBr): 3435, 3007, 2955, 2473, 2297, 1962, 1936, 1890, 1799,
1701, 1619, 1552, 1470, 1420, 1334, 1266, 1239, 1152, 1128, 1070,
1021, 960, 945, 854 cm–1.
IR (KBr): 3070, 3031, 2990, 2941, 1918, 1793, 1594, 1554, 1491,
1475, 1455, 1406, 1332, 1316, 1279, 1234, 1146, 1127, 1088, 1015,
946 cm–1.
1H NMR (400 MHz, CDCl3): d = 4.73 (s, 2 H, CH2), 7.22–7.30 (m,
4 H, Ar-H-2¢,3¢,5¢,6¢), 7.60 (m, 1 H, ArH-6), 7.66 (m, 1 H, ArH-5),
7.97 (d, J = 7.9 Hz, 1 H, ArH-7), 8.26 (d, J = 8.0 Hz, 1 H, ArH-4).
1H NMR (400 MHz, CDCl3): d = 4.82 (s, 2 H, CH2), 7.43 (d, J = 8.1
Hz, 2 H, ArH-2¢,6¢), 7.56 (d, J = 8.1 Hz, 2 H, ArH-3¢,5¢), 7.61 (ddd,
J = 1.3, 7.3, 8.3 Hz, 1 H, ArH-6), 7.67 (ddd, J = 1.3, 7.2, 8.4 Hz, 1
H, ArH-5), 7.97 (dd, J = 0.9, 7.6 Hz, 1 H, ArH-4), 8.26 (dd, J = 0.7,
7.8 Hz, 1 H, ArH-7).
13C NMR (100 MHz, CDCl3): d = 60.3, 122.4, 123.7, 125.5, 125.8,
127.9, 128.3, 130.4, 131.1, 131.6, 136.9, 152.5, 164.7.
13C NMR (100 MHz, CDCl3): d = 60.2, 122.3, 124.9, 125.5, 127.7,
128.1, 129.2, 132.4, 135.6, 137.0, 152.5, 164.8.
19F NMR (376 MHz, CDCl3): d = –62.9.
MS (70 eV, EI): m/z (%) = 325/324/323 (8/3/21, [M+]), 260/259/
MS (70 eV, EI): m/z (%) = 359/358/357 (2/4/28, [M+]), 294/293/
292 (9/36/100, [M – SO2 ]), 159 (70, [C8H6F3 ]).
258 (14/12/36, [M – SO2 ]), 127/126/125 (32/7/100, [C6H7Cl+]).
+
+
+
HR-EIMS: m/z calcd for C14H10ClNO2S2: 322.9841; found:
HR-EIMS: m/z calcd for C15H10N2O4S2: 357.0105; found:
322.9844.
357.0108.
Anal. Calcd for C14H10ClNO2S2: C, 54.71; H, 3.28; N, 4.56; S,
20.86. Found: C, 54.71; H, 3.23; N, 4.60; S, 20.87.
2-(2-Chloropyridin-3-yl)methylsulfonylbenzo[d]thiazole (5f)
Yield: 0.285 g (0.879 mmol, 56%); beige solid; Rf = 0.10 (cHex–
EtOAc, 5:1).
2-(3,4-Dichlorobenzylsulfonyl)benzo[d]thiazole (5c)
Yield: 0.275 g (0.768 mmol, 82%); white solid; Rf = 0.28 (cHex–
EtOAc, 5:1).
IR (KBr): 3930, 3819, 3073, 2949, 2908, 2789, 2494, 2445, 2273,
1954, 1925, 1584, 1562, 1470, 1417, 1203 cm–1.
IR (KBr): 3071, 2993, 2936, 2445, 2324, 1965, 1934, 1802, 1679,
1554, 1469, 1419, 1395, 1327, 1274, 1244, 1200, 1150, 1087 (m),
1030 (m), 984 (w) cm–1.
1H NMR (400 MHz, CDCl3): d = 4.71 (s, 2 H, CH2), 7.12 (dd, J =
2.1, 8.3 Hz, 1 H, ArH-5¢), 7.36 (d, J = 8.3 Hz, 1 H, ArH-6¢), 7.41 (d,
J = 2.1 Hz, 1 H, ArH-3¢), 7.61 (ddd, J = 1.3, 7.3, 8.3 Hz, 1 H, ArH-
6), 7.67 (ddd, J = 1.3, 7.3, 8.3 Hz, 1 H, ArH-5), 7.98 (dd, J = 0.7,
7.4 Hz, 1 H, ArH-7), 8.25 (dd, J = 0.7, 7.7 Hz, 1 H, ArH-4).
1H NMR (400 MHz, CDCl3): d = 4.95 (s, 2 H, CH2), 7.30 (dd, J =
4.8, 7.7 Hz, 1 H, ArH-5¢), 7.59–7.68 (m, 2 H, ArH-5,6), 7.90 (dd,
J = 1.9, 7.7 Hz, 1 H, ArH-4¢), 7.99 (d, J = 8.2 Hz, 1 H, ArH-7), 8.23
(d, J = 7.8, 1 H, ArH-4), 8.40 (dd, J = 1.9, 4.8 Hz, 1 H, ArH-6¢).
13C NMR (100 MHz, CDCl3): d = 57.7, 122.3, 122.5, 122.9, 125.7,
127.9, 128.4, 137.2, 141.7, 150.4, 152.4, 152.6, 164.1.
MS (70 eV, EI): m/z (%) = 324/326 (0.06/0.03, [M+]), 289 (100,
+
[C13H9N2S2O2 ]), 259 (21), 225 (45), 126 (70, [C6H5ClN+]).
13C NMR (100 MHz, CDCl3): d = 59.6, 122.4, 125.5, 126.4, 127.8,
128.3, 130.2, 130.8, 132.9, 133.1, 133.9, 136.9, 152.4, 164.7.
HR-EIMS: m/z calcd for C13H9ClN2O2S2: 323.9794; found:
323.9797.
MS (70 eV, EI): m/z (%) = 361/359/357 (4/16/21, [M+]), 294/293/
Anal. Calcd for C13H9ClN2O2S2: C, 48.07; H, 2.79; N, 8.62; S,
19.74. Found: C, 48.07; H, 2.93; N, 8.68; S, 19.44.
+
+
292 (32/22/43, [M – SO2 ]), 161/159 (63/100, [C7H5Cl2 ]).
HR-EIMS: m/z calcd for C14H9Cl2NO2S2: 356.9451; found:
356.9449.
Electrophilic Fluorination; 2-[(2-Bromophenyl)fluoromethyl-
sulfonyl]benzo[d]thiazole (7a); Typical Procedure
Anal. Calcd for C14H9Cl2NO2S2: C, 46.93; H, 2.53; N, 3.91; S,
17.90. Found: C, 46.57; H, 2.54; N, 3.90; S, 17.51.
Under argon, sulfone 5a (0.200 g, 0.540 mmol, 1.00 equiv) was dis-
solved in anhyd MeCN (15 mL) and cooled to –30 °C. To the reac-
tion mixture, NaH (26.0 mg, 0.660 mmol, 1.20 equiv, 60% in
mineral oil) was added. After 15 min, solid NFSi (0.208 g,
0.660 mmol, 1.20 equiv) was added. The mixture was stirred at this
temperature for 20 h, warmed to r.t., and stirred for additional 4 h.
The mixture was quenched with brine (5 mL), the layers were sep-
arated and the aqueous layer was extracted with EtOAc (3 × 30
mL). The combined organic layers were washed with sat. aq
NaHCO3 (10 mL), H2O (10 mL) and brine (10 mL), dried (Na2SO4)
and the solvent was removed under reduced pressure. Column chro-
matography (silica gel, cHex–EtOAc, 19:1) yielded 7a (0.154 g,
0.400 mmol, 74%) as a colorless solid; Rf = 0.35 (cHex–EtOAc,
5:1).
2-(2-Trifluoromethyl)benzylsulfonylbenzo[d]thiazole (5d)
Yield: 1.01 g (2.81 mmol, 86%); colorless solid; Rf = 0.14 (cHex–
EtOAc, 10:1).
IR (KBr): 3065, 2987, 2945, 1958, 1924, 1805, 1466, 1418, 1332,
1316, 1121 cm–1.
1H NMR (400 MHz, CDCl3): d = 4.99 (s, 2 H, CH2), 7.51 (t, J = 7.6
Hz, 1 H, ArH-4¢), 7.50–7.72 (m, 5 H, ArH-5,6,3¢,5¢,6¢), 7.99 (dd,
J = 0.7, 8.0 Hz, 1 H, ArH-7), 8.25 (dd, J = 0.6, 8.1 Hz, 1 H, ArH-4).
13C NMR (100 MHz, CDCl3): d = 57.2, 122.3, 124.7, 125.7, 126.9,
127.8, 128.2, 129.5, 130.2, 130.5, 132.2, 133.5, 137.1, 152.6, 165.1.
19F NMR (376 MHz, CDCl3): d = –58.2.
IR (KBr): 3418, 3073, 2962, 2862, 2494, 2435, 2335, 1949, 1913,
1590, 1467, 1348, 1156 cm–1.
MS (70 eV, EI): m/z (%) = 357 (13, [M+]), 292 (57), 159 (100,
[C8H6F3 ]), 134 (13, [C7H4NS+]), 109 (33).
+
1H NMR (400 MHz, CDCl3): d = 7.19 (d, J = 45.4 Hz, 1 H, CHF),
7.41 (dt, J = 1.5, 7.5 Hz, 1 H, ArH-5¢), 7.46 (dt, J = 1.1, 7.7 Hz, 1
H, ArH-4¢), 7.62–7.76 (m, 3 H, ArH-5,6,3¢), 7.75 (dd, J = 1.7,
7.7 Hz, 1 H, ArH-6¢), 8.05 (dd, J = 1.4, 7.3 Hz, 1 H, ArH-7), 8.33
(dd, J = 1.4, 7.8 Hz, 1 H, ArH-4).
13C NMR (100 MHz, CDCl3): d = 100.3, 122.3, 124.7, 125.9, 126.7,
127.9, 128.5, 130.4, 133.0, 133.5, 137.6, 152.9, 162.6.
HR-EIMS: m/z calcd for C15H10F3NO2S2: 357.0105; found:
357.0107.
Anal. Calcd for C15H10F3NO2S2: C, 50.41; H, 2.82; N, 3.92; S,
17.94. Found: C, 50.79; H, 3.19; N, 3.79; S, 17.27.
2-(4-Trifluoromethyl)benzylsulfonylbenzo[d]thiazole (5e)
Yield: 0.170 g (0.455 mmol, >99%); white solid; Rf = 0.15 (cHex–
EtOAc, 10:1).
19F NMR (376 MHz, CDCl3): d = –169.8.
Synthesis 2010, No. 20, 3439–3448 © Thieme Stuttgart · New York

PAPER
Novel Aromatic Fluoroolefins
3445
MS (70 eV, EI): m/z (%) = 385/387 (0.2/0.2, [M+]), 321/322/324
(19/17/2, [C14H9BrFNS+]), 242 (58), 187/189 (100/69,
[C7H5BrF+]), 134 (17, [C7H4NS+]).
HR-EIMS: m/z calcd for C15H9F4NO2S2: 375.0010; found:
375.0008.
2-[(2-Chloropyridin-3-yl)fluoromethylsulfonyl]benzo[d]thia-
zole (7f)
Yield: 0.060 g (0.174 mmol, 56%); white solid; Rf = 0.09 (cHex–
EtOAc, 10:1).
HR-EIMS: m/z calcd for C14H9BrFNO2S2: 384.9242; found:
384.9239.
Anal. Calcd for C14H9BrFNO2S2: C, 43.53; H, 2.35; N, 3.63; S,
16.60. Found: C, 43.70; H, 2.66; N, 3.54; S, 16.25.
IR (KBr): 3087, 2922, 2855, 2639, 2501, 2263, 1955, 1925, 1801,
1714, 1578, 1461, 1409, 1352, 1320, 1282, 1232, 1159, 1118, 1078,
1041, 964, 926, 850, 808, 762, 737, 725 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.15 (d, J = 45.6 Hz, 1 H, CHF),
7.43 (dd, J = 7.7, 4.8 Hz, 1 H, ArH-4¢), 7.63–7.71 (m, 2 H, ArH-
4,7), 8.08 (m, 1 H, ArH-6¢), 8.13 (ddd, J = 1.9, 3.5, 7.8 Hz, 1 H,
ArH-5¢), 8.34 (ddd, J = 1.4, 3.2, 7.7 Hz, 1 H, ArH-6), 8.62 (ddd, J =
1.8, 4.7, 25.8 Hz, 1 H, ArH-5).
13C NMR (100 MHz, CDCl3): d = 97.6, 122.6, 122.3 (+, C-Ar-4),
122.8, 125.9, 128.0, 128.7, 137.5, 139.1, 151.3, 152.3, 152.8, 161.8.
19F NMR (376 MHz, CDCl3): d = –172.3.
2-[(4-Chlorophenyl)fluoromethylsulfonyl]benzo[d]thiazole (7b)
Yield: 0.123 g (0.358 mmol, 58%); white solid; Rf = 0.41 (cHex–
EtOAc, 5:1).
IR (KBr): 3092, 3065, 2952, 2551, 2492, 2436, 2304, 2028, 1964,
1919, 1796, 1735, 1595, 1552, 1490, 1464, 1409, 1350, 1318, 1278,
1262, 1238, 1221, 1155, 1088, 1049, 1014, 924 cm–1.
1H NMR (400 MHz, CDCl3): d = 6.62 (d, J = 45.7 Hz, 1 H, CHF),
7.47 (d, J = 8.3 Hz, 2 H, ArH-3¢,5¢), 4.57 (d, J = 8.6 Hz, 2 H, ArH-
2¢,6¢), 7.62–7.71 (m, 2 H, ArH-5,6), 8.05 (m, 1 H, ArH-4), 8.28 (m,
1 H, ArH-7).
13C NMR (100 MHz, CDCl3): d = 101.2, 122.3, 125.7, 127.9, 128.5,
129.2, 129.6, 129.7, 132.3, 137.5, 138.0, 152.8, 162.4.
MS (70 eV, EI): m/z (%) = 342 (0.2, [M+]), 307 (3, [M – Cl+]), 261
(37), 243 (67), 162 (61), 144 (100, [C6H4ClFN+]).
MS (FAB): m/z (%) = 344/343/342 [M + H+], 278 [M + H – SO2 ],
HR-EIMS: m/z calcd for C13H8FClN2O2S2: 341.9699; found:
+
+
197 [C7H4NO2S2 ], 182.
341.9703.
FAB-HRMS: m/z calcd for C14H10ClFNO2S2: 341.9825; found:
341.9821.
Fluoroolefins 10; General Procedure
Fluorinated BT-sulfone 7 (1.20 equiv) and aldehyde 9 (0.080–0.510
mmol, 1.00 equiv) were dissolved in anhyd THF (33 mL/mmol 9)
at 0 °C. To the mixture, LiHMDS (2.40 equiv) was added dropwise
and stirred 1.5 h at 0 °C. The reaction was quenched with sat. aq
NaHCO3 (10 mL/mmol 9) and extracted with EtOAc (3 × 30 mL/
mmol 9). The combined organic layers were washed with brine (10
mL/mmol 9) and dried (Na2SO4). The solvent was evaporated and
the crude product was purified by column chromatography (cHex–
EtOAc).
2-{Fluoro-[2-(trifluoromethyl)phenyl]methylsulfonyl}ben-
zo[d]thiazole (7d)
Yield: 0.255 g (0.681 mmol, 49%); colorless solid; Rf = 0.45
(cHex–EtOAc, 5:1).
IR (KBr): 3100, 2022, 1795, 1605, 1552, 1465, 1414, 1353, 1316,
1281, 1159, 1127 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.07 (d, JH,F = 45.8 Hz, 1 H, CHF),
7.67 (m, 3 H, ArH-7,3¢,4¢), 7.76 (t, J = 7.3 Hz, 1 H, ArH-5¢), 7.84
(d, J = 7.6 Hz, 1 H, ArH-4), 8.07 (t, J = 7.2 Hz, 2 H, ArH-5,6), 8.34
(d, J = 7.8 Hz, 1 H, ArH-6¢).
13C NMR (100 MHz, CDCl3): d = 97.1, 122.1, 122.3, 124.8, 125.1,
126.0, 126.7, 128.0, 128.6, 130.8, 131.9, 132.4, 137.5, 152.8, 162.7.
19F NMR (376 MHz, CDCl3): d = –164.0, –56.8.
1-Bromo-2-{1-fluoro-2-[2-(trifluoromethyl)phenyl]vinyl}ben-
zene (10a)
Yield: 0.064 g (0.220 mmol, 61%); colorless oil.
Z-Isomer
Rf = 0.50 (cHex).
MS (70 eV, EI): m/z (%) = 375 (1, [M+]), 310 (38), 242 (18), 177
(100, [C8H5F4 ]), 127 (9).
IR (KBr): 3073, 1672, 1605, 1490, 1454, 1315, 1163, 1121 cm–1.
+
1H NMR (400 MHz, CDCl3): d = 6.47 (dd, JH,F = 1.8, 34.8 Hz, 1 H,
CH=CF), 7.29 (m, 1 H, ArH-5¢), 7.39 (dt, J = 1.0, 7.6 Hz, 2 H, ArH-
4,5), 7.48 (d, J = 7.2 Hz, 1 H, ArH-6¢), 7.52 (t, J = 7.7 Hz, 1 H,
ArH-4¢), 7.60 (d, J = 8.0 Hz, 1 H, ArH-6), 7.70 (d, J = 7.9 Hz, 1 H,
ArH-3), 8.02 (d, J = 7.9 Hz, 1 H, ArH-3¢).
13C NMR (100 MHz, CDCl3): d = 106.9, 121.9, 122.8, 125.6, 125.9,
127.4, 127.9, 128.3, 130.83, 131.1, 131.2, 131.8, 133.8, 134.1,
157.2.
HR-EIMS: m/z calcd for C15H9F4NO2S2: 375.0010; found:
375.0007.
Anal. Calcd for C15H9F4NO2S2: C, 48.00; H, 2.42; N, 3.73; S, 17.08.
Found: C, 48.15; H, 2.47; N, 3.69; S, 17.62.
2-{Fluoro-[4-(trifluoromethyl)phenyl]methylsulfonyl}ben-
zo[d]thiazole (7e)
Yield: 0.035 g (0.092 mmol, 33%); white solid; Rf = 0.16 (cHex–
EtOAc, 10:1).
19F NMR (376 MHz, CDCl3): d = –97.7, –59.9.
MS (70 eV, EI): m/z (%) = 344 (26, [M+]), 245 (66), 196 (100).
IR (KBr): 3068, 2962, 2439, 1939, 1815, 1729, 1620, 1552, 1464,
1419, 1351, 1319, 1236, 1158, 1137, 1065, 1018, 964, 854, 796,
766 cm–1.
1H NMR (400 MHz, CDCl3): d = 6.71 (d, J = 46.0 Hz, 1 H, CHF),
7.68 (m, 2 H, ArH-5,6), 7.77 (s, 4 H, ArH-2¢,3¢,5¢,6¢), 8.07 (m, 1 H,
ArH-7), 8.29 (m, 1 H, ArH-4).
13C NMR (100 MHz, CDCl3): d = 101.0, 122.4, 125.8, 125.8, 126.5,
128.0, 128.6, 128.7, 128.7, 130.2, 133.5, 137.5, 152.8, 162.1.
19F NMR (376 MHz, CDCl3): d = –174.4, –62.8.
HR-EIMS: m/z calcd for C15H9BrF4: 343.9823; found: 343.9821.
E-Isomer
Rf = 0.60 (cHex).
IR (KBr): 3071, 1679, 1591, 1577, 1469, 1429, 1317, 1282, 1222,
1190, 1165, 1124 cm–1.
1H NMR (400 MHz, CDCl3): d = 6.84 (dd, JH,F = 2.1, 17.2 Hz, 1 H,
CH=CF), 6.94 (d, J = 7.5 Hz, 1 H, ArH-3), 7.20 (m, 5 H, ArH-
4,5,6,4¢,5¢), 7.63 (d, J = 7.6 Hz, 2 H, ArH-3¢,6¢).
13C NMR (100 MHz, CDCl3): d = 108.7, 123.6, 124.2, 125.8, 127.3,
127.5, 128.6, 130.8, 131.3, 131.5, 131.9, 132.4, 133.3, 133.4, 158.6.
MS (70 eV, EI): m/z (%) = 375 (1, [M+]), 311 (51, [M – SO2H+]),
+
177 (100, [C8H5F4 ]), 127 (18).
Synthesis 2010, No. 20, 3439–3448 © Thieme Stuttgart · New York

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19F NMR (376 MHz, CDCl3): d = –87.0, –60.4.
MS (70 eV, EI): m/z (%) = 344 (67, [M+]), 245 (66), 196 (100).
MS (70 eV, EI): m/z (%) = 302/301/300 (32/16/100, [M+]), 283/
282/281 (1/4/2, [M – F+]), 265 (5, [M – Cl+]), 245 (15), 196 (28).
HR-EIMS: m/z calcd for C15H9ClF4: 300.0328; found: 300.0331.
HR-EIMS: m/z calcd for C15H9BrF4: 343.9823; found: 343.927.
Anal. Calcd for C15H9BrF4: C, 52.02; H, 2.63. Found: C, 51.97; H,
2.90.
(Z)-1-Bromo-2-{2-fluoro-2-[2-(trifluoromethyl)phenyl]vi-
nyl}benzene (10e)
Yield: 0.035 g (0.102 mmol, 20%); colorless oil; Rf = 0.35 (cHex).
(E)-3-[2-(2-Bromophenyl)-2-fluorovinyl]-2-chloropyridine
(10b)
Yield: 0.037 g (0.120 mmol, 57%); yellow oil; Rf = 0.35 (cHex–
EtOAc, 5:1).
IR (KBr): 3449, 3069, 1670, 1605, 1578, 1494, 1314, 1174, 1136
cm–1.
1H NMR (400 MHz, CDCl3): d = 6.41 (d, JH,F = 35.4 Hz, 1 H,
CH=CF), 7.16 (dt, J = 1.6, 7.8 Hz, 1 H, ArH-5), 7.36 (t, J = 7.6 Hz,
1 H, ArH-4), 7.56 (t, J = 7.6 Hz, 1 H, ArH-4¢), 7.62 (dd, J = 1.1, 8.0
Hz, 2 H, ArH-3,6), 7.67 (t, J = 8.8 Hz, 1 H, ArH-5¢), 7.78 (d, J =
7.7 Hz, 1 H, ArH-3¢), 7.95 (dd, J = 1.6, 7.9 Hz, 1 H, ArH-6¢).
13C NMR (100 MHz, CDCl3): d = 109.6, 123.5, 123.8, 126.8, 127.5,
128.7, 129.1, 129.9, 130.7, 131.1, 131.6, 131.9, 132.7, 132.8, 165.9.
IR (KBr): 3450, 3056, 2926, 1674, 1578, 1558, 1471, 1431, 1397,
1348, 1179, 1091 cm–1.
1H NMR (400 MHz, CDCl3): d = 6.70 (d, JH,F = 16.7 Hz, 1 H,
CH=CF), 6.92 (dd, J = 4.7, 7.7 Hz, 1 H, ArH-3¢), 7.07 (ddd, J = 0.5,
1.8, 7.6 Hz, 1 H, ArH-6¢), 7.27–7.30 (m, 3 H, ArH-4,5,5¢), 7.62–
7.66 (m, 1 H, ArH-4¢), 8.19 (dd, J = 1.9, 4.7 Hz, 1 H, ArH-6).
13C NMR (100 MHz, CDCl3): d = 107.9, 122.1, 123.4, 127.8, 128.7,
131.8, 132.0, 132.5, 133.5, 138.0, 148.2, 154.4, 160.6.
19F NMR (376 MHz, CDCl3): d = –84.1.
19F NMR (376 MHz, CDCl3): d = –60.7, –84.8.
MS (70 eV, EI): m/z (%) = 344/345/346 (61/60/9, [M+]), 245 (36,
+
[C15H8F3 ]), 196 (100, [C14H9F+]), 58 (29), 43 (61).
HR-EIMS: m/z calcd for C15H9BrF4: 343.9823; found: 343.9826.
MS (70 eV, EI): m/z (%) = 311/313/315 (61/80/19, [M+]), 232 (14,
[C13H8ClFN+]), 197 (100, [C13H8FN+]), 85 (27).
Anal. Calcd for C15H9BrF4: C, 52.20; H, 2.63. Found: C, 52.30; H,
2.73.
HR-EIMS: m/z calcd for C13H8NBrClF: 310.9512; found:
310.9510.
2-Fluoro-3-{2-fluoro-2-[4-(trifluoromethyl)phenyl]vinyl}pyri-
dine (10f)
4-[2-(2-Bromophenyl)-2-fluorovinyl]pyridine (10c)
Yield: 0.031 g (0.112 mmol, 51%); colorless oil; Rf = 0.29 (cHex–
EtOAc, 1:1).
Yield: 0.019 g (0.068 mmol, 85%); yellow solid; Rf = 0.19 (cHex–
EtOAc, 19:1).
IR (KBr): 3065, 2928, 1930, 1668, 1618, 1600, 1565, 1517, 1431,
1409, 1325, 1249, 1167, 1130, 1069, 1016, 976, 888, 849 cm–1.
IR (KBr): 3440, 3057, 2922, 2850, 1713, 1678, 1630, 1597, 1563,
1492, 1468, 1385, 1223, 1188, 1096, 1075, 1026, 992 cm–1.
1H NMR (500 MHz, CDCl3): d = 6.48 (d, J = 19.4 Hz, 1 H,
CH=CF), 6.62 (d, J = 38.3 Hz, 1 H, CH=CF), 7.04 (m, 1 Harom), 7.23
(ddd, J = 1.7, 4.9, 7.4 Hz, 1 Harom), 7.47 (dddd, J = 0.8, 1.9, 7.5, 9.5
Hz, 1 Harom), 7.51 (d, J = 8.7 Hz, 2 Harom), 7.60 (d, J = 8.6 Hz, 2
Harom), 7.62–7.72 (m, 3 Harom), 7.79 (d, J = 8.4 Hz, 1 Harom), 7.94
(ddd, J = 2.0, 7.5, 9.3 Hz, 1 Harom), 8.12 (d, J = 4.8 Hz, 1 Harom), 8.21
(ddd, J = 1.0, 1.9, 4.9 Hz, 1 Harom), 8.38 (ddd, J = 1.9, 7.8, 9.7 Hz, 1
1H NMR (400 MHz, CDCl3): d = 6.12 (d, J = 36.7 Hz, 1 H,
CH=CF), 6.48 (d, J = 17.8 Hz, 1 H, CHCF), 6.81 (d, J = 4.2 Hz, 2
Harom), 7.28–7.41 (m, 4 Harom), 7.50 (d, J = 4.1 Hz, 2 Harom), 7.55
(dd, J = 7.7, 1.5 Hz, 1 Harom), 7.66–7.74 (m, 3 Harom), 8.39 (br s, 2
Harom), 8.64 (br s, 2 Harom).
13C NMR (100 MHz, CDCl3): d = 109.4, 110.0, 121.5, 121.7, 127.5,
128.0, 128.3, 129.5, 130.7, 131.4, 131.8, 132.1, 133.6, 133.9, 140.6,
141.0, 149.7, 150.0, 151.1, 159.6, 160.2.
19F NMR (376 MHz, CDCl3): d = –90.2, –80.7.
Harom).
13C NMR (125 MHz, CDCl3): d = 102.7, 107.0, 121.1, 121.4, 121.8,
122.7, 123.6, 123.8, 124.9, 125.4, 125.6, 125.8, 126.0, 128.3, 130.8,
131.9, 132.0, 134.4, 135.2, 140.4, 143.5, 147.1, 158.6, 160.2, 160.7,
162.7.
19F NMR (376 MHz, CDCl3): d = –111.5, –92.0, –71.0, –68.2,
–63.5, –63.0.
MS (70 eV, EI): m/z (%) = 279/278/277 (42/7/42, [M+]), 199/198
(14/100, [M – Br+]), 170 (31).
HR-EIMS: m/z calcd for C13H9BrFN: 279.9902; found: 279.9900.
MS (70 eV, EI): m/z (%) = 287/286/285 (1/14/100, [M+]), 267/266
1-[2-(4-Chlorophenyl)-2-fluorovinyl]-2-(trifluoromethyl)ben-
zene (10d)
Yield: 0.062 g (0.135 mmol, 65%); colorless oil; Rf = 0.77 (cHex).
(6/46, [M – F+]), 217/216 (2/11, [M – CF3 ]), 145 (1, [C7H4F3 ]).
+
+
HR-EIMS: m/z calcd for C14H8F5N: 285.0576; found: 285.0579.
IR (KBr): 3471, 2075, 2924, 1904, 1655, 1598, 1577, 1543, 1496,
1456, 1404, 1354, 1316, 1209, 1162, 1122, 1095, 1064, 1036, 1011,
957, 887 cm–1.
1H NMR (400 MHz, CDCl3): d = 6.55 (dq, J = 1.7, 36.4 Hz, 1 H,
CH=CF), 6.59 (dq, J = 1.8, 19.6 Hz, 1 H, CH=CF), 7.06 (d, J = 6.9
Hz, 1 Harom), 7.12 (d, J = 3.8 Hz, 1 Harom), 7.09–7.16 (m, 1 Harom),
7.24–7.40 (m, 7 Harom), 7.33 (d, J = 8.8 Hz, 1 Harom), 7.46–7.52 (m,
1 Harom), 7.63 (d, J = 7.6 Hz, 1 Harom), 7.62–7.65 (m, 2 Harom), 7.90
(d, J = 7.9 Hz, 1 Harom).
13C NMR (100 MHz, CDCl3): d = 101.5, 106.6, 124.3, 124.5, 125.9,
126.0, 126.1, 126.2, 127.0, 127.3, 127.4, 127.7, 128.1, 128.6, 129.0,
129.0, 129.4, 129.5, 129.7, 131.0, 131.1, 131.7, 131.8, 131.9, 135.6,
135.6, 157.2, 157.7.
3-[2-(2-Bromophenyl)-1-fluorovinyl]-2-chloropyridine (10g)
Yield: 0.024 g (0.078 mmol, 60%); colorless oil; Rf = 0.19 (Z), 0.25
(E) (cHex–EtOAc, 99:1).
IR (KBr): 3436, 3056, 2925, 2853, 1925, 1676, 1579, 1558, 1469,
1437, 1398, 1349, 1277, 1230, 1180, 1134, 1101, 1061, 1036, 1025,
1005, 947, 877 cm–1.
1H NMR (400 MHz, CDCl3): d = 6.75–6.88 (m, 3 H, CH=CF,
Harom), 6.99–7.07 (m, 3 Harom), 7.18 (m, 2 Harom), 7.37 (dd, J = 7.2
Hz, 1 Harom), 7.48–7.58 (m, 3 Harom), 7.63 (d, J = 8.0 Hz, 1 Harom),
7.95 (d, J = 7.7 Hz, 1 Harom), 8.34–8.42 (m, 2 H, ArH-6).
13C NMR (100 MHz, CDCl3): d = 111.7, 113.4, 122.2, 122.3, 124.1,
124.3, 127.4, 127.5, 129.0, 129.2, 129.4, 130.3, 130.3, 130.8, 132.4,
132.6, 132.8, 132.9, 133.1, 138.3, 139.3, 139.7, 140.8, 150.7, 153.8,
155.2.
19F NMR (376 MHz, CDCl3): d = –113.8, –97.2, – 61.4, –59.8.
Synthesis 2010, No. 20, 3439–3448 © Thieme Stuttgart · New York

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Novel Aromatic Fluoroolefins
3447
19F NMR (376 MHz, CDCl3): d = –104.5, –92.8.
Anal. Calcd for C21H13ClF4: C, 66.94; H, 3.48. Found: C, 66.86; H,
3.74.
MS (70 eV, EI): m/z (%) = 315/313/311 (17/66/54, [M+]), 278/276
(18/18), 232 (6, [M – Br+]), 197 (100).
2-Chloro-3-[2-(4¢-chlorobiphenyl-2-yl)-2-fluorovinyl]pyridine
(11b)
Yield: 8.00 mg (0.025 mmol, 25%); yellow oil; Rf = 0.32 (cHex–
HR-EIMS: m/z calcd for C13H8BrClFN: 310.9512; found:
310.9511.
EtOAc, 10:1).
Suzuki Coupling Reaction; 4¢-Chloro-2-{2-fluoro-2-[2-(trifluo-
romethyl)phenyl]vinyl}biphenyl (11e); Typical Procedure
Under argon, fluoroolefin 10e (20.0 mg, 0.060 mmol, 1.00 equiv),
4-chlorophenylboronic acid (12; 24.0 mg, 0.140 mmol, 2.40 equiv),
Pd(OAc)2 (1.0 mg, 0.003 mmol, 0.050 equiv), Ph3P (3.0 mg (0.009
mmol, 0.150 equiv), K2CO3 (25.0 mg, 0.180 mmol, 3.00 equiv)
were dissolved in anhyd DMF (5 mL). The flask containing the re-
action mixture was evacuated and flushed with argon. The mixture
was heated 3 d at 90 °C, quenched with aq 1 M HCl (5 mL), and ex-
tracted with Et2O (3 × 15 mL). The combined organic layers were
dried (Na2SO4) and the solvent was removed under reduced pres-
sure. Column chromatography (silica gel, cHex) of the crude prod-
uct afforded 11e (20.0 mg, 0.052 mmol, 86%, E/Z = 2.6:1.0) as a
colorless oil; Rf = 0.41 (cHex, E-isomer), 0.36 (cHex, Z-isomer).
IR (KBr): 3060, 2926, 1720, 1664, 1557, 1476, 1444, 1396, 1287,
1179, 1090 cm–1.
1H NMR (500 MHz, CDCl3): d = 6.18 [d, JH,F = 37.0 Hz, 1 H, (Z)-
CH=CF], 6.47 [d, JH,F = 19.2 Hz, 1 H, (E)-CH=CF], 6.86–8.31 (m,
22 Harom).
13C NMR (125 MHz, CDCl3): d = 100.3, 105.4, 121.7, 121.8, 122.0,
122.3, 122.6, 124.8, 126.9, 127.8, 128.2, 128.6, 128.8, 129.4, 129.8,
130.1, 130.2, 130.4, 130.5, 130.7, 130.9, 131.1, 131.3, 131.9, 133.5,
133.6, 138.3, 138.5, 138.6, 139.3, 139.4, 139.7, 147.8, 148.4, 148.1,
149.7, 160.0, 167.6.
19F NMR (376 MHz, CDCl3): d = –95.3, –91.9.
MS (70 eV, EI): m/z (%) = 343/344/345 (41/8/27, [M+]), 308 (26,
[C19H12ClFN+]), 272 (100), 254 (25, [C19H12N+]).
IR (KBr): 3084, 3053, 3026, 2926, 1912, 1844, 1668, 1604, 1579,
1494, 1471, 1448, 1396, 1315, 1175, 1125, 1105 cm–1.
HR-EIMS: m/z calcd for C19H12Cl2NF: 343.0330; found: 343.0329.
1H NMR (500 MHz, CDCl3): d = 5.86 [d, J = 35.8 Hz, 1 H, (Z)-
CH=CF], 6.58 [d, J = 19.9 Hz, 1 H, (E)-CH=CF] 7.31–7.61 (m, 20
Harom), 7.73 (d, J = 7.5 Hz, 1 H, Z-Harom), 7.76 (d, J = 7.7 Hz, 1 H,
E-Harom), 7.81 (d, J = 7.7 Hz, 1 H, E-Harom), 7.99 (d, J = 7.8 Hz, 1
H, Z-Harom).
13C NMR (125 MHz, CDCl3): d = 109.4, 111.1, 111.8, 112.1, 122.6,
124.7, 126.8, 126.9, 127.1, 127.3, 127.4, 127.5, 127.9, 128.2, 128.3,
128.4, 128.6, 127.7, 128.6, 129.0, 129.0, 129.7, 129.9, 130.0, 130.2,
130.8, 130.9, 131.0, 131.9, 132.1, 132.7, 133.2, 133.4, 139.8, 155.8,
156.0.
Crystal Structure Determinations of 5a and 7c/8c28
All single-crystal X-ray diffraction studies were carried out on a
Bruker-Nonius APEXII diffractometer (5a, Figure 2) or a Bruker-
Nonius Kappa-CCD diffractometer (8c, Figure 3) at 123(2) K using
MoKa radiation (l = 0.71073 Å). Direct methods (SHELXS-97)
were used for structure solution and refinement was carried out us-
ing SHELXL-97 (full-matrix least-squares on F2). Non-hydrogen
atoms were refined anisotropically (except disordered F atoms in
7c/8c), hydrogen atoms were localized by difference electron den-
sity determination and refined using a riding model. Semi-empirical
absorption corrections were applied. The crystal structure of 7c/8c
shows disorder of the F atoms. There is a sit occupancy disorder of
the difluorinated sulfone 8c and the (additionally positional disor-
dered) monofluorinated sulfone 7c in the ratio 1:3.
19F NMR (376 MHz, CDCl3): d = –97.6, –85.7, –60.7, –60.1.
MS (70 eV, EI): m/z (%) = 376/377/378 (91/12/23, [M+]), 341 (8,
+
[C21H13F4 ]), 301 (100), 199 (15).
HR-EIMS: m/z calcd for C21H13ClF4: 376.0641; found: 376.0645.
5a
4¢-Chloro-2-{1-fluoro-2-[2-(trifluoromethyl)phenyl]vinyl}bi-
phenyl (11a)
Yield: 0.022 g (0.105 mmol, 75%); colorless oil; Rf = 0.37 (cHex).
Colorless crystals, C14H10BrNO2S2, M = 368.26, crystal size
0.20 × 0.16 × 0.08 mm, monoclinic, space group P21/n (No. 14),
a = 10.2305(4) Å, b = 11.0139(3) Å, c = 12.0621(5) Å, b =
96.008(2)°, V = 1351.66(9) Å3, Z = 4, r (calc) = 1.810 Mg m–3,
F(000) = 736, m = 3.349 mm–1, 6039 reflexes (2qmax = 50°), 2352
unique [Rint = 0.036], 181 parameters, R1 (I > 2s(I)) = 0.028, wR2
(all data) = 0.070, S = 1.07, largest diff. peak and hole 0.555 and –
0.466 e Å–3.
IR (KBr): 3448, 2927, 1671, 1605, 1475, 1452, 1317, 1166, 1127
cm–1.
1H NMR (400 MHz, CDCl3): d = 6.22 [dd, JH,F = 1.8, 35.0 Hz, 1 H,
(Z)-CH=CF], 6.53 [dd, JH,F = 2.3, 18.9 Hz, 1 H, (E)-CH=CF], 6.83
(d, J = 7.3 Hz, 1 Harom), 6.94 (d, J = 8.0 Hz, 1 Harom), 7.05–7.64 (m,
18 Harom), 7.70 (d, J = 7.8 Hz, 1 Harom), 7.88 (d, J = 7.4 Hz, 1 Harom),
8.67 (d, J = 8.2 Hz, 1 Harom), 8.69 (d, J = 8.9 Hz, 1 Harom).
13C NMR (100 MHz, CDCl3): d = 106.1, 107.7, 122.5, 122.5, 124.4,
125.8, 126.8, 127.3, 127.4, 127.4, 127.8, 127.8, 128.2, 128.3, 128.6,
129.1, 129.6, 129.7, 130.1, 130.3, 130.4, 130.7, 130.8, 131.1, 131.3,
131.5, 131.7, 132.4, 133.5, 133.2, 138.5, 139.5, 139.7, 140.9, 146.7,
161.4, 162.8.
7c/8c
Colorless crystals, C14H7.75Cl2F1.25NO2S2·[0.75(C14H8Cl2FNO2S2)·
0.25(C14H7Cl2F2NO2S2)], M = 380.73, crystal size 0.50 × 0.20 × 0.15
mm, monoclinic, space group P21/n (No. 14), a = 10.003(2) Å, b =
22.940(4) Å, c = 13.138(2) Å, b = 102.00(2)°, V = 2948.9(9) Å3, Z =
8, r (calc) = 1.715 Mg m–3, F(000) = 1536, m = 0.742 mm–1, 19480
reflexes (2qmax = 55°), 6714 unique [Rint = 0.031], 395 parameters,
18 restraintes, R1 (I > 2s(I)) = 0.040, wR2 (all data) = 0.097, S =
1.06, largest diff. peak and hole 1.019 and –0.731 e Å–3.
19F NMR (376 MHz, CDCl3): d = –96.0, –82.9, –60.6, –60.11.
MS (70 eV, EI): m/z (%) = 376 (67, [M+]), 341 (68, [C21H13F4 ]),
+
301 (100).
Acknowledgment
HR-EIMS: m/z calcd for C21H13ClF4: 376.0641; found: 376.0640.
We acknowledge Bayer CropScience for funding.
Synthesis 2010, No. 20, 3439–3448 © Thieme Stuttgart · New York

3448
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PAPER
Tomita, K.; Ohno, H.; Naito, T.; Kodama, E.; Matsuoka, M.;
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Synthesis 2010, No. 20, 3439–3448 © Thieme Stuttgart · New York