Thieme Chemistry Journal Awardees - Where are They Now? The Influence of Electron-Withdrawing Groups at the 2- and 2′-Positions of Dibenzothienylethenes on Molecular Switching

Article abstract of DOI:10.1055/s-0036-1588796

Three dibenzothienylethenes that carry a methyl, a trifluoromethyl, or a fluoro substituent in the 2- and 2′-position were synthesised in short multistep syntheses, respectively. The trifluoromethyl and fluoromethyl substituents significantly improve the absorption properties of the corresponding open and closed isomers (both in the UV-A and in the visible range). The increasing electron deficiency (i) enlarges the portion of the closed and coloured diarylethene isomer in the corresponding photostationary states and slows down the closing and opening isomerisation, (ii) the switching reactions, both closing and opening, are slowed down, and (iii) the switching quantum yields are lowered.

Full text of DOI:10.1055/s-0036-1588796

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Georg Thieme Verlag Stuttgart · New York
2017, 28, A–E
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Synlett
R. Hofsäß et al.
Letter
Thieme Chemistry Journal Awardees – Where are They Now?
The Influence of Electron-Withdrawing Groups at the 2- and 2′-
Positions of Dibenzothienylethenes on Molecular Switching
Robert Hofsäß
David Rombach
Hans-Achim Wagenknecht*
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Karlsruhe Institute of Technology (KIT), Institute of Organic
Chemistry, Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany
Wagenknecht@kit.edu
Received: 13.02.2017
Accepted after revision: 28.03.2017
Published online: 02.05.2017
DOI: 10.1055/s-0036-1588796; Art ID: st-2017-b0105-l
Abstract Three dibenzothienylethenes that carry a methyl, a trifluoro-
methyl, or a fluoro substituent in the 2- and 2′-position were synthe-
sised in short multistep syntheses, respectively. The trifluoromethyl and
fluoromethyl substituents significantly improve the absorption proper-
ties of the corresponding open and closed isomers (both in the UV-A
and in the visible range). The increasing electron deficiency (i) enlarges
the portion of the closed and coloured diarylethene isomer in the corre-
sponding photostationary states and slows down the closing and open-
ing isomerisation, (ii) the switching reactions, both closing and open-
ing, are slowed down, and (iii) the switching quantum yields are
lowered.
Hans-Achim Wagenknecht studied chemistry in Freiburg (Germany),
got his PhD in 1998 in bioorganic chemistry (enzyme models, with
Wolf-D. Woggon) in Basel (Switzerland) and worked as postdoc on
DNA-mediated electron transfer (with Jacqueline K. Barton) at Caltech
Key words molecular switches, photoswitches, diarylethenes, quan-
tum yields, kinetics, photochromism
(
USA). His independent career started in 2000 at the Technical Universi-
ty Munich (Germany) and the habiliation on DNA-mediated charge
transfer in synthetically modified DNA in 2003. In 2005, he got a profes-
sorship at Regensburg (Germany), and since 2010 he holds the chair for
organic chemistry at KIT (Germany). His research is focused on bioor-
ganic chemistry with nucleic acids and peptides, fluorescent imaging,
DNA architectonics with optoelectronic properties, and chemical pho-
tocatalysis.
Molecular switches exist in two different molecular
structures (isomers) that can be reversibly interconverted
by light. In this class of organic compounds, diarylethenes
play a central role, since they can be switched between the
colourless ring-opened isomer and the coloured ring-closed
isomer by irradiation with UV light (forward) and visible
light (backwards) only. These so-called p-type switches
typically show no thermal switching and high thermosta-
bility of both isomers. Diarylethenes are also increasingly
important for switching functions in biomolecules, in par-
1,2
electron-withdrawing groups, mainly trifluoromethylated
1
2
and pentafluorosulfanylated phenyl groups at the thiazole
and thiophene part,13 also enhance the stability of diaryle-
thenes during the switching cycles. In nearly all published
diarylethenes, the 2- and 2′-positions of the thiophene
moieties where the C–C bond formation to the closed iso-
mer takes place is simply alkylated, mainly methylated, to
prevent irreversible oxidation by dehydrogenation of the
closed isomer. Electron-withdrawing groups at these posi-
tions should significantly influence the switching proper-
3
4
ticular proteins and nucleic acids. More recently, our
group, Jäschke et al.7–9 and others prepared and evaluat-
ed nucleoside-based diarylethenes to allow molecular
switching in DNA.
5,6
10
Using benzothiophenes instead of thiophenes signifi-
cantly improves the fatigue resistance of diarylethene-type
11
switches. Recently, Hecht et al. showed alternatively that
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R. Hofsäß et al.
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ties of diarylethenes. Irie et al. studied the influence of the
14
15
cyano and fluoro groups as 2,2′-substituents of dithio-
phenylethenes. We herein present the synthesis and optical
properties of two new dibenzothienylethenes that carry
trifluoromethyl groups (2) or fluoro substituents (3) in the
S
4
1
) n-BuLi, THF, 1 h
2
) MeI
2) NFSI
–78 °C to r.t.
6 h
9
7%
59%
2- and 2′-positions (Scheme 1) and compare it to the con-
–78 °C, 3 h
1
ventional switch with methyl groups (1).
CH3
F
B(OH)2
F
F
F
F
S
S
S
F
F
F
F
5
9
7
F
F
300 nm
30 nm
F
F
NaSO2CF3
TBHP, CuCl
MeOH/CH2Cl2/
H2O
Br2,
Br2,
NaOAc
CHCl3
r.t., 2 h
NaOAc
CHCl3
r.t., 2 h
5
9
6%
76%
77%
R
S
R
S
S
S
RR
1c, 2c, 3c
0 °C, 12 h
Br
Br
R = CH3 : 1
CF3 : 2
F : 3
1
o, 2o, 3o
open isomers
colourless)
closed isomer
(coloured)
CH3
F
CF3
(
S
S
S
10
8
6
Scheme 1 Dibenzothienylethenes 1–3 and their molecular switching
n-BuLi,
process between open and closed isomers
identical
to 10 --> 3
identical
to 10 --> 3
OFCP
THF
7
3%
46%
75%
r.t., 20 h
The syntheses of diarylethenes 1–3 follow a direct syn-
1,2
F
F
thetic route (Scheme 2). For diarylethene 1, methylation
of the 2-position of thiophene (4) by n-BuLi and MeI gives 5
F
F
F
F
R = CH3 : 1
CF3 : 2
F : 3
16
in a very good yield of 97%. The position 3 is selectively
R
activated by electrophilic bromination with Br , again in
2
17
S
S
very good yield. The subsequent treatment of 6 with n-
BuLi exchanges the bromine substituent by lithium, and
this intermediate acts as a nucleophile in the subsequent
double vinylic substitution at octafluorocyclopentene.18
This gives the diarylethene 1 in 67% yield over three steps.
A similar synthetic route was initially applied for diary-
lethene 2. First, the trifluoromethyl group is introduced to
the 2-position of thiophene (4) in 77% yield using oxidative
R
Scheme 2 Synthesis of dibenzothienyl switches 1–3. NFSI = N-fluoro-
benzenesulfonimide, TBHP = tert-butyl hydroperoxide, OFCP = octafluo-
rocyclopentene.
All three dibenzothienyl compounds 1–3 were charac-
terised by their UV/Vis absorption properties and their
switching behavior. The closing was induced by irradiation
using a Hg-Xe lamp equipped with a bandpass filter that
completely eliminates light between 390 nm and 650 nm to
avoid excitation in the visible range (see Supporting Infor-
mation). Thereby a strong excitation in the UV-A range be-
tween 290 and 330 nm is achieved that fits well to the ab-
sorption maxima of the open isomers 1o, 2o, and 3o, that
were found at 291, 309 and 304 nm, respectively (Table 1).
The opening was induced by irradiation using a 530 nm
LED, which fits well to the absorption maxima of the closed
isomers 1c, 2c, and 3c at 517, 506, and 519 nm, respectively
(Table 1 and Figure 1).
19
and radical conditions by CuCl, NaSO CF , and t-BuOOH.
2
3
In contrast to the synthetic route to diarylethene 1, a care-
ful screening of several bromination conditions (with Br2,
HBr, and NBS, together with several Lewis acid catalysts) re-
vealed that the 3-brominated derivative of 7 could not be
achieved by this type of reaction. The brominations did not
work at all or gave complicated mixtures of differently sub-
stituted products. Due to the electron-withdrawing effect
of the trifluoromethyl group of 7, direct treatment with n-
BuLi allows the incorporation of the lithium group into the
20
3
-position. The reaction of this intermediate with octafluo-
21
rocyclopentene completes the synthesis of diarylethene 2
in 58% yield over two steps.
The open switches bearing the electron-withdrawing
substituents 2o and 3o show an enhanced extinction
around 300 nm, which facilitates the selective irradiation
that is required for closing these switches. Especially at
310 nm, the switch 2o shows a remarkable, nearly threefold
extinction compared to the standard methylated switch 1o.
Obviously, the trifluoromethyl groups of 2o increase the
charge-transfer character and thereby enhance the absorp-
tion around 300 nm. The additional mesomeric electron-
donating effect by the lone pairs of the fluoro groups of 3o
broaden the absorption by different exciplex-type states.
The synthesis of the fluoro-substituted diarylethene 3
again follows the route described for 1. The only step that
differs is the fluorination by N-fluorobenzenesulfonimide
as a source of electrophilic fluoride that reacts with the n-
22
BuLi-treated thiophene 4. The bromination of 9 and the
23
24
subsequent reaction of 10 to the diarylethene 3 follows
the previously described procedures and yields 3 in 21%
over three steps.
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R. Hofsäß et al.
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Table 1 Optical Properties of Dibenzothienylethenes 1–3
Compd
Closing: λexc = 300 nma
PSS
Opening: λexc = 530 nmb
–
1
(M–1 cm–1)c
λ
max, open
ε
o
(300 nm; M
Φ
t (s)
λ
max, closed (nm) PSS
ε
c
Φ
t (s)
–
1
(
nm)
cm )
1
2
291
0.10
7,000
7,200
7,200
0.12
20
60
90
517
0.99
21,400
39,200
10,700
0.14
6
20
299
299
0.15
0.54
0.10
0.08
360
506
0.99
0.99
0.026
0.002
309
3
304
379
360
519
a
Excitation by Hg-Xe lamp with band pass filter.
Excitation by Nichia high-power LED.
Extinction coefficients of the pure closed isomers determined by HPLC analysis at 517 nm, 506 nm and 519 nm for 1c, 2c, and 3c, respectively.
b
c
This improves the UV-A photostationary state (PSS; which
was determined by HPLC analysis, see Supporting Informa-
tion) from 10% for switch 1 to 15% for switch 2 and remark-
able 53% for switch 3. Moreover, the closed switches 2c and
and 0.08 for 3. The quantum yields for the opening also de-
crease from 0.14 for 1 to 0.026 for 2 and 0.002 for 3. In par-
ticular, the observation that closing and opening of switch 1
occurs with very similar quantum yields is consistent with
the published values,26 although our determined quantum
yields are lower. Overall, the photophysical characterisation
of molecular switches 1–3 shows that the trifluoromethyl
and fluoro substituents significantly improve the absorp-
tion properties of the corresponding opened and closed iso-
mers. Furthermore, the quantum yields of the closing reac-
tion are slightly diminished, whereas the quantum yields
3c show also a significantly enhanced absorption in the vis-
ible range. Compound 3c (at 519 nm) shows an approxi-
mately twofold and 2c (at 505 nm) an approximately four-
fold extinction compared to 1c (at 517 nm). Since all open
isomers show no absorption in the visible range, there
should be no back reaction when opening the switches by
irradiation at 530 nm. The resulting Vis PSS of >99% for
switches 1–3 was confirmed by HPLC. In contrast to in-
creasing the PSS, the switching kinetics slow down by the
electron-withdrawing character of the 2,2′-substituents.
The reference switch 1 closes in 20 s and opens in 6 s
whereas the fluorinated switch 3 closes in 90 s and opens in
360 s. The trifluoromethylated switch 2 is in an intermedi-
ate position, with 60 s for closing and 20 s for opening.
Quantum yields are the most precise parameter to
properly describe the switching processes. In general, the
chemical quantum yield for a given product of a photo-
chemical reaction is defined as the ratio of the amount of
product formed vs. the amount of photons absorbed. The
determination of the quantum yield of a molecular switch
requires not only the determination of the amount of
switched molecules, but also the quantification of the
amount of light absorbed. The chemical yield of the closing
reaction was determined for the switches 1, 2, and 3 by
careful HPLC analysis (see Supporting Information).
Based on the used amount of each switch and based on
the previously determined extinction coefficients of the
pure isomers 1o, 2o, and 3o, the extinction coefficients of
the closed isomers were determined. To determine the
amount of photons the photon flux and the absorbed pho-
tons that induce the switching have to be distinguished. We
applied a quantum yield determination setup as physical
device that allows to measure the amount of incident pho-
tons by a quantifiable electrical signal, which was validated
Figure 1 UV/Vis absorption of opened (top) and closed (middle) iso-
–
5
–5
mers of dibenzothienylethenes 1–3 (2·10 M and 3·10 M in hexane
for 1, 3 and 2, respectively). Bottom: Kinetic observation of the closing
by irradiation with UV-A light (0–120 s; see text) for opening and clos-
ing by 530 nm LEDs (120–500 s) 1: λobs = 515 nm, 2: λobs = 505 nm, 3:
λ
obs = 519 nm). The graph of 3 is cut off to show the kinetic difference
25
between 1 and 2. The full graph and the change of absorption under
irradiation are shown in the Supporting Information.
by actinometry. The determined quantum yields for the
closing of the switches decrease from 0.12 for 1 to 0.10 for 2
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R. Hofsäß et al.
Letter
for the opening reaction are reduced in a more significant
way. Taken together, the bathochromic broadening of the
visible band of the closed isomer 3c and the decrease in the
cycloreversion quantum yield indicate that the fluorine
substituents serve as electron-donating groups by their π-
conjugated lone pairs rather than as strong electron-with-
drawing groups. In contrast, the trifluoromethyl substitu-
ents of 2 influence the optical properties by their pure elec-
tron-withdrawing effect.
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0036-1588796.
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References and Notes
15
(
(
1) Irie, M. Chem. Rev. 2000, 100, 1685.
2) Irie, M.; Fukaminato, T.; Matsuda, K.; Kobatake, S. Chem. Rev.
014, 114, 12174.
2
Finally, the fatigue resistance of the molecular switches
(3) Szymanski, W.; Beierle, J. M.; Kistemaker, H. A. V.; Velema, W.
1
–3 was tested by 18 consecutive closing and opening reac-
A.; Feringa, B. L. Chem. Rev. 2013, 113, 6114.
tions (see Supporting Information). The conventional
switch 1 showed close to no loss in absorption. Switch 2 has
the weakest fatigue resistance and loses 2.5% of absorption
changes per cycle. Switch 3 is comparable to 1 with 1.3%
loss per cycle.
(4) Lubbe, A. S.; Szymanski, W.; Feringa, B. L. Chem. Soc. Rev. 2017,
6, 1052.
4
(
(
5) Barrois, S.; Beyer, C.; Wagenknecht, H.-A. Synlett 2012, 23, 711.
6) Barrois, S.; Wagenknecht, H.-A. Beilstein J. Org. Chem. 2012, 8,
905.
(
(
7) Singer, M.; Jäschke, A. J. Am. Chem. Soc. 2010, 132, 8372.
8) Cahova, H.; Jäschke, A. Angew. Chem. Int. Ed. 2013, 52, 3186.
(9) Singer, M.; Nierth, A.; Jäschke, A. Eur. J. Org. Chem. 2013, 2766.
(10) Wang, H.-X.; Xi, D.-D.; Xie, M.-S.; Wang, H.-X.; Qu, G.-R.; Guo,
H.-M. ChemBioChem 2016, 17, 1216.
11) Hanazawa, M.; Sumiya, R.; Horikawa, Y.; Irie, M. J. Chem. Soc.,
Chem. Commun. 1999, 747.
12) Herder, M.; Schmidt, B. M.; Grubert, L.; Pätzel, M.; Schwarz, J.;
Hecht, S. J. Am. Chem. Soc. 2015, 137, 2738.
In conclusion, three dibenzothienylethenes were pre-
pared as molecular switches that carry a methyl group (1),
a trifluoromethyl group (2), and a fluoro substituent (3) in
the 2- and 2′-position. The central synthetic step was the
double vinylic substitution of octafluorocyclopentene by
the corresponding brominated benzothiophenes 6 and 10
that yields the switches 1 and 2. In case of switch 3 this
coupling works even without the bromine substituents di-
rectly from benzopthiophene 7. The increased electron-
withdrawing character of the 2,2′-substituents significantly
influences the optical and thereby the switching properties.
The trifluoromethyl and fluoro substituents significantly
improve the absorption properties of the corresponding
open (2o and 3o) and closed isomers (2c and 3c), both in
the UV-A range (350–400 nm) and in the visible range
(
(
(13) Herder, M.; Eisenreich, F.; Bonasera, A.; Grafl, A.; Grubert, L.;
Pätzel, M.; Schwarz, J.; Hecht, S. Chem. Eur. J. 2017, 23, 3743.
14) Morimitsu, K.; Kobatake, S.; Nakamura, S.; Irie, M. Chem. Lett.
(
(
(
2003, 32, 858.
15) Higashiguchi, K.; Matsuda, K.; Asano, Y.; Murakami, A.;
Nakamura, S.; Irie, M. Eur. J. Org. Chem. 2005, 91.
16) Under inert conditions benzo[b]thiophene (7.00 g, 51.1 mmol,
1
.00 equiv) was dissolved in dry THF and stirred for 30 min at
–78 °C. n-BuLi (26.6 mL, 2.5 M in hexane, 66.5 mmol, 1.30
equiv) was added slowly, and the mixture was stirred for 30
min. MeI (4.90 mL, 11.2 g, 78.9 mmol, 1.54 equiv) was added
over 15 min. The reaction was stirred for 20 min at –78 °C, for 3
h at r.t., quenched with water (100 mL), and extracted with
EtOAc (4 × 50 mL). The organic layer was dried over Na SO , and
(450–550 nm). With enhanced electron-withdrawing effect
from methyl over trifluoromethyl to fluoro substituents, (i)
the switching reactions, both closing and opening, are
slowed down, and (ii) the switching quantum yields are
lowered. These properties were elucidated under nonspe-
cialised conditions (oxygen atmosphere, no exclusion of
moisture) to set the path to their application in biopoly-
mers. In contrast to a recent report on the improvement of
the fatigue resistance of dithienylethene switches by at-
tachment of electron-withdrawing phenyl substituents on
the 5- and 5′-positions, the dibenzothienyl switches 2 and
3
1
thenes in order to completely explore the substituent ef-
fects on this type of molecular switch and can therefore
help to push the development of new potent switches.
2
4
the solvents were removed in vacuo. After purification by flash
chromatography (silica, hexane), 5 could be obtained as a
colourless solid in 97% yield (7.26 g, 49.0 mmol). TLC (SiO , hex-
2
1
ane): R
= 0.54. H NMR (400 MHz, DMSO-d
): δ = 7.85 (dp, J =
f
6
7.8, 0.7 Hz, 1 H), 7.74–7.64 (m, 1 H), 7.35–7.21 (m, 2 H), 7.12 (p,
13
J = 1.2 Hz, 1 H), 2.56 (d, J = 1.2 Hz, 3 H) ppm. C NMR (101 MHz,
DMSO-d ): δ = 140.57, 140.09, 138.88, 124.19, 123.46, 122.57,
11
6
+
122.05, 121.78, 15.74 ppm. MS (EI): m/z [M] calcd for C H S:
9
8
show reduced or comparable fatigue resistance to switch
. Nevertheless, 2 and 3 represent important new diaryle-
148.0342; found: 148.0341.
(17) A solution of Br2 (2.10 mL, 6.55 g, 41.5 mmol, 1.02 equiv) in
CHCl (60 mL) was slowly added to a solution of 5 (6.00 g, 40.8
3
mmol, 1.00 equiv) in CHCl (300 mL) over 5 h at r.t. The mixture
3
was stirred for 15 h at r. t., quenched with sat. aq Na SO3 (50
2
mL), and extracted with CH Cl (4 × 100 mL). The combined
2
2
organic layers were washed with sat. aq NaCl (2 × 100 mL),
dried over Na SO , and the solvents were removed in vacuo.
Purification by flash chromatography (silica, hexane) gave 6 as
Acknowledgment
2
4
Financial support by Karlsruhe School of Optics and Photonics (KSOP)
and KIT is gratefully acknowledged. D.R. thanks the Landesgraduier-
tenstiftung for the fellowship.
a colourless solid in 96% yield (8.68 g, 38.2 mmol). TLC (SiO
2
,
1
hexane): R
= 0.25. H NMR (400 MHz, DMSO-d
): δ = 8.00–7.94
f
6
(m, 1 H), 7.68–7.63 (m, 1 H), 7.51–7.38 (m, 2 H), 2.54 (s, 3 H)
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E

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Synlett
R. Hofsäß et al.
Letter
ppm. 13C NMR (101 MHz, DMSO-d ): δ = 137.62, 136.57, 135.65,
(22) Under inert conditions, benzo[b]thiophene (2.30 g, 17.2 mmol,
1.00 equiv) was dissolved in dry THF (140 mL) and stirred for 20
min at –78 °C. n-BuLi (12.8 mL, 2.5 M in hexane, 32.0 mmol,
1.86 equiv) was added dropwise, and the resulting mixture was
stirred for 1 h at –78 °C. N-Fluorobenzenesulfonimide (12.5 g,
39.7 mmol, 3.21 equiv) was added in two portions at an interval
of 15 min. The reaction mixture was stirred for 2 h at –78 °C, 16
h at r.t., stopped by addition of water (30 mL), and extracted
with EtOAc (4 × 50 mL). The organic layer was dried over
Na SO , and the solvents were removed in vacuo. After flash
6
1
25.38, 125.14, 122.75, 121.92, 105.78, 15.17 ppm. MS (EI): m/z
+
[
M] calcd for C H BrS: 225.9448; found: 225.9446.
9
7
(
18) Under inert conditions, a solution of 6 (1.33 g, 5.86 mmol, 1.00
equiv) in dry THF (8 mL) was stirred at –78 °C for 20 min. n-BuLi
(2.80 mL, 2.5 M in hexane, 7.00 mmol, 1.20 equiv) was added.
The mixture was stirred for 1 h. Octafluorocyclopentene (1.32
mL, 2.0 M in THF, 2.20 mmol, 0.38 equiv) was added. The reac-
tion was warmed up to r.t. overnight. Water (2 mL) was added,
and the reaction was extracted with Et O (4 × 20 mL). The
2
2
4
organic layer was washed with sat. aq NaCl (2 × 30 mL), dried
over Na SO , and the solvents were removed in vacuo. Flash
chromatography (silica, hexane) 9 could be obtained as a
colourless oil in 59 % yield (1.53 g, 10.1 mmol). TLC (SiO , hex-
2
4
2
1
chromatography (silica, hexane) gave 1 as a colourless solid in
ane): R = 0.71. H NMR (300 MHz, DMSO-d ): δ = 7.90 (d, J = 7.7
f
6
1
7
3% yield (1.00 g, 2.15 mmol, isomeric mixture). H NMR (400
Hz, 1H), 7.73 (d, J = 6.3 Hz, 1 H), 7.44–7.32 (m, 2 H), 7.11 (d, J =
13
MHz, DMSO-d ): δ = 7.92 (d, J = 8.0 Hz, 2 H), 7.88–7.79 (m, 2 H),
2.7 Hz, 1 H) ppm. C NMR (75 MHz, DMSO-d ): δ = 161.88,
6
6
7
.62 (d, J = 8.7 Hz, 4 H), 7.46 (t, J = 7.6 Hz, 2 H), 7.41–7.35 (m, 2
135.63, 131.20, 125.28, 124.51, 124.45, 123.60, 123.51, 122.81,
13
+
H), 7.26 (d, J = 9.2 Hz, 4 H), 2.27 (s, 6 H) ppm. C NMR (126
MHz, CDCl -d ): δ = 141.64, 141.13, 137.29, 137.16, 137.03,
104.09, 103.94 ppm. MS (EI): m/z [M] calcd for C H FS:
8
5
152.0091; found: 152.0092.
3
1
1
1
1
33.18, 133.04, 131.60, 131.45, 128.11, 126.16, 126.07, 123.58,
(23) Under inert conditions, 9 (1.18 g, 7.72 mmol, 1.00 equiv) was
dissolved in dry CHCl3 (8 mL). NaOAc (1.17 g, 14.2 mmol, 1.85
equiv) was added, and the mixture was stirred for 15 min at r.t.
A solution of Br2 (394 μL 1.23 g, 7.72 mmol, 1.00 equiv) in dry
CHCl3 (2 mL) was added dropwise over 30 min. The solution
was stirred for 2 h at r.t., quenched with sat. aq Na SO , and
23.42, 123.33, 123.04, 121.18, 121.13, 121.06, 120.77, 120.62,
+
18.37, 115.15, 110.45, 97.33, 14.12 ppm. MS–FAB: m/z [M]
calcd for C23H14F S : 468.0438; found: 468.0436.
6
2
(
(
19) Ye, Y.; Künzi, S. A.; Sanford, M. A. Org. Lett. 2012, 14, 4979.
20) To a solution of benzo[b]thien-2-yl-boronic acid (1.00 g, 5.62
mmol, 1.00 equiv), CuCl (0.56 g, 5.62 mmol, 1.00 equiv), and
NaSO CF (2.63 g, 16.9 mmol, 3.00 equiv) in a mixture of
2
3
extracted with hexane (4 × 25 mL). The organic layer was dried
over Na SO , and the solvent was removed under reduced pres-
2
3
2
4
MeOH–CH Cl –H O (11.2 mL/11.2 mL/8.99 mL), tert-butyl
sure. Purification of the crude product was done by flash chro-
matography (silica, hexane). The product was dried in vacuo
overnight to remove last traces of the volatile starting material
9. The pure product 10 was isolated as pale yellow oil in 76%
2
2
2
hydroperoxide solution (3.82 mL, 70% in H O, 28.1 mmol, 5.00
2
equiv) were added at 0 °C and stirred overnight. Et O (90 mL)
2
was added, and the organic layer was washed with sat. aq
NaHCO (70 mL), sat. aq Na SO (25 mL), and dried over Na SO .
1
yield (1.35 g, 5.56 mmol). TLC (SiO , hexane): R = 0.76. H NMR
3
2
3
2
4
2
f
The solvents were removed in vacuo. Purification by flash chro-
(300 MHz, DMSO-d ): δ = 8.02 (d, J = 8.0 Hz, 1 H), 7.68 (d, J = 7.8
6
matography (silica, hexane) gave 8 as a colourless solid in 77%
Hz, 1 H), 7.55 (dd, J = 7.6 Hz, 1 H), 7.48 (dd, J = 7.7 Hz, 1 H) ppm.
1
13
yield (769 mg, 4.33 mmol). TLC (SiO , hexane): R = 0.64.
H
C NMR (75 MHz, DMSO-d ): δ = 160.02, 157.15, 133.58,
2
f
6
NMR (400 MHz, DMSO-d ): δ = 8.19–8.12 (m, 2 H), 8.06–8.01
129.34, 126.35, 126.08, 126.03, 123.69, 122.19, 122.13, 88.45,
6
13
(m, 1 H), 7.61–7.50 (m, 2 H) ppm. C NMR (101 MHz, DMSO-
88.32 ppm. MS (EI): m/z calcd for C H SFBr: 229.2; found: 230.1.
8
4
d ): δ = 139.43, 137.56, 129.01, 127.35, 127.19, 125.66, 123.79,
(24) Under inert conditions, n-BuLi (1.05 mL, 2.0 M in hexane, 2.10
mmol, 1.01 equiv) was dissolved in dry THF (1 mL) at –78 °C. A
solution of 10 (480 mg, 2.08 mmol, 1.00 equiv) in dry THF (700
μL) was added dropwise over 15 min and stirred for 45 min at
–78 °C. Octafluorocyclopentene (261 μL, 3.6 M in THF, 0.936
mmol, 0.45 equiv) was added, and the reaction mixture was
stirred for 24 h at r.t. The reaction was quenched with water (4
6
+
1
23.16, 121.28 ppm. MS (EI): m/z [M] calcd for C H F S:
9
5 3
202.0059; found: 202.0057.
(
21) Under inert conditions 8 (250 mg, 1.24 mmol, 1.00 equiv) were
dissolved in dry THF (5 mL) and stirred for 20 min at –78 °C. n-
BuLi (544 μL 2.0 M in hexane; 1.36 mmol, 1.10 equiv) were
added slowly, and the mixture was stirred for 1 h. Octafluorocy-
clopentene (279 μL, 2.0 M in THF, 0.560 mmol, 0.450 equiv)
were added, and the mixture was warmed to r.t. overnight. The
mL) and extracted with Et O (4 × 20 mL). The organic layer was
2
dried over Na SO , and the solvents were removed in vacuo. The
2
4
reaction was quenched with sat. aq NH Cl (4 mL) and extracted
product was purified by flash chromatography (silica, hexane)
4
with Et O (3 × 30 mL). The organic layer was dried over Na SO ,
and the solvents were removed in vacuo. Purification by flash
and 3 was isolated as a colourless solid in 46% yield (204 mg,
2
2
4
1
0.428 mmol, isomeric mixture). TLC (SiO , hexane): R = 0.35. H
2
f
chromatography (silica, hexane) gave 2 as a colourless solid in
NMR (500 MHz, CDCl -d ): δ = 7.61–7.55 (m, 1 H), 7.50 (dd, J =
6.5, 2.5 Hz, 1 H), 7.35–7.27 (m, 2 H) ppm. C NMR (126 MHz,
3 1
13
7
5% yield (267 mg, 0.463 mmol). TLC (SiO , hexane): R = 0.21.
2
f
1
H NMR (400 MHz, DMSO-d ): δ = 8.24 (dd, J = 6.4, 2.7 Hz, 1 H),
CDCl -d ): δ = 165.63, 163.24, 141.69, 138.37, 137.49, 137.28,
6
3
1
8
.14 (d, J = 7.9 Hz, 2 H), 8.06 (d, J = 8.1 Hz, 2 H), 7.78–7.65 (m,
137.06, 133.59, 130.58, 127.23, 126.00, 125.50, 125.47, 122.72,
122.16, 117.98, 117.97, 117.60, 115.92, 115.73, 115.54, 113.87,
113.68, 113.48, 113.28, 111.52, 111.31, 111.11, 109.35, 109.15,
108.95, 104.00, 103.94, 77.41, 77.16, 76.91 ppm. MS–FAB: m/z
calcd for C23H F S : 475.9934; found: 475.9935.
13
3
1
1
1
1
1
H), 7.59–7.46 (m, 4 H) ppm. C NMR (126 MHz, CDCl -d ): δ =
3 1
41.23, 141.00, 140.80, 140.53, 138.65, 138.44, 137.57, 136.80,
32.08, 131.78, 131.49, 131.16, 127.68, 127.46, 125.83, 125.54,
24.38, 124.36, 122.77, 122.34, 121.72, 120.56, 120.45, 118.40,
17.67, 117.47, 115.58, 115.41, 115.19, 113.50, 113.30, 113.13,
8
8 2
(25) Megerle, U.; Lechner, R.; König, B.; Riedle, E. Photochem. Photo-
biol. Sci. 2010, 9, 1400.
+
11.33, 111.13, 110.93 ppm. MS–FAB: m/z [M] calcd for
C23H8F12S2: 575.9870; found: 575.9869.
(26) Sumi, T.; Takagi, Y.; Yagi, A.; Morimoto, M.; Irie, M. Chem.
Commun. 2014, 50, 3928.
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E