Para-coupling of phenols with C2/C3-substituted benzothiophene S-oxides

Article abstract of DOI:10.1016/j.tet.2020.131315

C2 and C3 substituted benzothiophenes are common structures in medicinal and materials chemistry. The cross-coupling of phenols with benzothiophenes is a useful route towards these important molecules. In this report we reveal an efficient C–H/C–H-type cross-coupling of benzothiophenes, activated as their S-oxides, with phenols to give C2/C3 arylated benzothiophenes. Whereas previous reports describe cross-coupling at the ortho-position between phenols and sulfoxides, this procedure allows para-functionalization of phenols that typically have their ortho positions blocked.

Full text of DOI:10.1016/j.tet.2020.131315

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Para-coupling of phenols with C2/C3-substituted benzothiophene S-oxides
Zhen He, Tony Biremond, Gregory J.P. Perry, David J. Procter
PII:
S0040-4020(20)30469-5
https://doi.org/10.1016/j.tet.2020.131315
TET 131315
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 24 March 2020
Revised Date: 22 May 2020
Accepted Date: 25 May 2020
Please cite this article as: He Z, Biremond T, Perry GJP, Procter DJ, Para-coupling of phenols
with C2/C3-substituted benzothiophene S-oxides, Tetrahedron (2020), doi: https://doi.org/10.1016/
j.tet.2020.131315.
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Para-coupling of phenols with C2/C3-
substituted benzothiophene S-oxides
Leave this area blank for abstract info.
Zhen He, Tony Biremond, Gregory J. P. Perry and David J. Procter
Department of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL

1
Tetrahedron
journal homepage: www.elsevier.com
Para-coupling of phenols with C2/C3-substituted benzothiophene S-oxides
a
a
a
a∗
Zhen He, Tony Biremond, Gregory J. P. Perry, and David J. Procter
a
Department of Chemistry, University of Manchester, Oxford Road, Manchester, M13 9PL, UK
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
C2 and C3 Substituted benzothiophenes are common structures in medicinal and materials
chemistry. The cross-coupling of phenols with benzothiophenes is a useful route towards these
important molecules. In this report we reveal an efficient C–H/C–H-type cross-coupling of
benzothiophenes, activated as their S-oxides, with phenols to give C2/C3 arylated
benzothiophenes. Whereas previous reports describe cross-coupling at the ortho-position
between phenols and sulfoxides, this procedure allows para-functionalization of phenols that
typically have their ortho positions blocked.
Available online
Keywords:
Benzothiophene
Phenol
2
009 Elsevier Ltd. All rights reserved.
Cross-Coupling
Sulfoxide
Pummerer
—
——
∗
Corresponding author. e-mail: david.j.procter@manchester.ac.uk

2
Tetrahedron
1
. Introduction
applied this reactivity in the sulfoxide-catalyzed homocoupling
12
and sulfoxide-mediated cross-couplings of phenols.
Benzothiophene and phenol motifs combine to lend function
In this report, we describe further studies on the use of sulfur
oxidation to enable the C–H/C–H cross-coupling of
benzothiophenes with phenols (Scheme 1D). We demonstrate
that phenols undergo cross-coupling with benzothiophenes,
activated as their S-oxides, in the presence of trifluoroacetic
anhydride (TFAA). Substitution is tolerated at various positions
on either coupling partner, including at both the C2 and C3
positions of the benzothiophene S-oxide. Importantly, this
transformation can occur at the para-position of the phenol,
whereas previous reports have involved only ortho-
to a range of important molecules. For example, raloxifene is an
important drug molecule for the prevention and treatment of
1
osteoporosis.
Other bioactive molecules that boast
benzothiophene and phenol substructures include antibacterials
2
and cancer treatments. There also exists a range of useful
organic materials, for example the benzothieno[3,2-b]benzofuran
(
BTBF) family, that is based on a benzothiophene-phenol
3
containing core.
The most common route to biaryls involves transition metal-
catalyzed cross-coupling reactions. This strategy has been used to
10,11
functionalization.
Despite this, we also demonstrate that
4
link phenols with benzothiophenes, however, in many cases,
coupling at the ortho-position of the phenol is tolerated in this
system, including a method for difunctionalization in the
preparation of alternating benzothiophene-phenol units.
additional steps are required for the protection/deprotection of the
5
phenol hydroxyl group. Furthermore, prefunctionalized starting
materials (e.g. aryl halides/organometallics) are required in this
route (Scheme 1A). The coupling of unfunctionalized phenols
and benzothiophenes via C–H/C–H cross-coupling is a more
6
7
direct route for heterobiaryl formation. Kita and Waldvogel
have made key developments in this area by using iodonium
reagents or electrochemistry to mediate cross-coupling (Scheme
1
B). Another related example has been reported by You and co-
workers who described C–H/C–H coupling between
8
benzothiophenes and the phenol derivative, 2-phenoxypyridine.
In recent years, interest has grown in the use of sulfoxides to
9
mediate the functionalization of C–H bonds. In particular, the
10
Yorimitsu group (Scheme 1C, i) and our group (Scheme 1C,
11
ii)
have described sulfoxide-mediated coupling of
benzothiophenes with phenols.
activation, interrupted
A sequence of sulfoxide
Scheme 2. Scope of the benzothiophene S-oxide in the C–H/C–
H-type cross-coupling of benzothiophene S-oxides and phenols.
Conditions: 1 (0.1 mmol, 1.0 eq), 2a (0.1 mmol, 1.0 eq), TFAA
a
b
(
0.15 mmol, 1.5 eq), TFA (1.0 mL). CH Cl used as solvent.
2 2
Scheme 1. Methods for the cross-coupling of benzothiophenes
NMR yield.
and phenols.
2
. Results and discussion
Pummerer reaction and [3.3]-sigmatropic rearrangement has been
proposed to account for the selectivity of these reactions that
provide ortho-functionalized phenols. More recently, we have
We began our investigation by using phenol 2a as a model
substrate for the para-functionalization of phenols (Scheme 2).

3
11
Building on our previous reports, we attempted the coupling of
tolerated in the reaction, albeit the product was obtained in low
phenol 2a with 3-methylbenzothiophene S-oxide 1a in CH Cl ,
yield (3ab). Impressively, 2,5-disubstituted phenol 2c, which has
the potential to undergo reaction at either the ortho- or para-
position, provided the para-substituted product 3ac with
complete regioselectivity. This example provides an insight into
the mechanism of the reaction (vide infra). Ortho-coupling at
phenol was also possible using this reaction system, as shown in
2
2
using TFAA as an activator. Under these conditions, <15% of the
desired cross-coupled product 3aa was obtained. Having
previously reported that the para-functionalization of phenols
12b
can occur in trifluoroacetic acid (TFA), we also tested this
process in TFA and were pleased to obtain 90% isolated yield of
the desired product 3aa. With suitable conditions in hand, we
investigated the scope of the reaction with respect to the
benzothiophene S-oxide 1. The methyl group at C3 could be
switched with a phenyl group without loss in reactivity; 3ba was
isolated in 95% yield. Various substituents on the phenyl group
at C3 were also tolerated (3ba-3fa), however, the presence of
electron-withdrawing substituents (e.g. CF3) significantly
lowered the yield of the reaction (3fa). Similarly, substitution at
the C5 position of the benzothiophene was also tolerated (3ga,
14
the preparation of 3ad. Interestingly, when using 4-substituted
phenols, twofold ortho-functionalization was observed to give
product 4. This suggests that the current method is more reactive
than previous procedures, which are selective for mono-
10,11,15
functionalization.
Furthermore, the alternating arene-
(benzo)thiophene unit, as seen in product 4, is a common motif in
16
organic materials.
Our mechanistic hypothesis for this reaction is displayed in
Scheme 4, using phenol 2c as a model substrate. Firstly, as the
addition of (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) did
not significantly impact the efficiency of the reaction, we believe
3
ha), although electron-withdrawing substituents proved
detrimental to reactivity. By using C2-substituted
benzothiophene S-oxides, functionalization at the C3-position of
the benzothiophene was also achieved. Both alkyl and phenyl
substituted benzothiophene S-oxides were applicable (3a’a,
17
a pathway involving radical intermediates is unlikely. We
propose that this reaction is initiated by reaction of the
benzothiophene S-oxides 1 with TFAA to give the activated
sulfoxides I. In previous reports, we and others have suggested
that activated sulfoxides can undergo an interrupted Pummerer
3
b’a). The para-selectivity of the reaction was confirmed by X-
13
ray crystallographic analysis of 3b’a.
1
0,11
reaction to give aryloxysulfonium salt intermediates II.
This
species is then susceptible to ortho-functionalization of the
phenol via [3,3]-sigmatropic rearrangement and aromatization to
give products ortho-III. However, in the current report, the
reaction of 2c does not provide products of ortho-
functionalization. This suggests another mechanism is operating.
We propose that the activated sulfoxides I can engage directly at
the para-position of phenol 2c to give products para-III by a
vinylogous Pummerer-type mechanism. In order to obtain C2-
substituted benzothiophene products when a C3 substituent is
present, direct C3 addition may be followed by subsequent 1,2-
11b,18
migration to C2.
Alternatively, a direct, extended vinylogous
Pummerer addition to C2 is also possible.
3
. Conclusion
We have described a novel method for the union of
benzothiophenes and phenols that relies on the activation of the
benzothiophene partner by sulfur oxidation, and constitutes a
formal C–H/C–H cross-coupling process. The reaction is
selective for functionalization at the para position of the phenol
partner and can give either C2 or C3 arylated benzothiophenes. In
comparison to related sulfoxide-mediated cross-couplings, the
observed para-selectivity suggests the reaction proceeds through
a mechanistically distinct vinylogous Pummerer pathway.
Scheme 3. Scope of the phenol partner in the C–H/C–H-type
cross-coupling of benzothiophene S-oxides and phenols.
Conditions: 1a (0.1 mmol, 1.0 eq), 2 (0.1 mmol, 1.0 eq), TFAA
a
b
(
0.15 mmol, 1.5 eq), TFA (1.0 mL). NMR yield. 0.1 mL
c
d
CH Cl added. 2c (0.2 mmol, 2.0 eq). 1a (0.22 mmol, 2.2
2
2
equiv of benzothiophene S-oxide).
By investigating the scope of the phenolic coupling partner
(Scheme 3), we found that other 2,6-disubstituted phenols were

4
Tetrahedron
Ar
OMe
OH
F
S
O
F
II
Ar
S
MeO
TFAA
Ar
HO
F
ortho-III
Ar
S
+
O
S
OH
O
MeO
F
OH
MeO
O
I
1
2c
CF3
OMe
Ar
S
F
O
O
Ar
I
CF
3
S
para-III
(observed)
Scheme 4. Proposed mechanism for the para-selective cross-coupling of benzothiophene S-oxides and phenols.
1
38.3 (ArC), 138.4 (ArC), 139.2 (ArC), 141.6 (ArC), 146.8
+
4
. Experimental section
(ArC) ppm. HRMS (ESI): Calcd. for C H O S (M+H ),
24 23 3
4
.1. General Procedure
3
91.1349; found 391.1352.
Benzothiophene (1, 0.1 mmol, 1 equiv) and phenol (2, 0.1
mmol, 1.0 equiv) were dissolved in TFA (1 mL, 0.1 M) in an
2
,6-Dimethoxy-4-(3-(3-methoxyphenyl)benzo[b]thiophen-2-
oven-dried tube flushed with N . TFAA (20 uL, 0.15 mmol, 1.5
2
yl)phenol (3da)
equiv) was then added at room temperature and the reaction
1
stirred for 30 min. Saturated aqueous NaHCO was then added
3
H NMR (400 MHz, CDCl ) δ = 3.69 (s, 6H, OCH ), 3.76 (s, 3H,
3
3
and the aqueous phase was extracted with CH Cl (3 × 3 mL).
2
2
OCH ), 5.54 (s, 1H, OH), 6.59 (s, 2H, ArCH), 6.91-6.97 (m, 3H,
3
The combined organic layers were dried over MgSO4 and
concentrated in vacuo. The crude product was purified by column
chromatography on silica gel eluting with n-hexane/EtOAc.
ArCH), 7.31-7.37 (m, 3H, ArCH), 7.57-7.59 (m, 1H, ArCH),
13
7
5
.84-7.87 (m, 1H, ArCH) ppm; C NMR (100 MHz, CDCl ) δ =
3
5.5 (OCH ), 56.2 (OCH ), 106.6 (ArCH), 113.3 (ArCH), 115.9
3
3
(
(
ArCH), 122.1 (ArCH), 123.0 (ArCH), 123.3 (ArCH), 124.58
ArCH), 124.63 (ArCH), 125.3 (ArC), 129.9 (ArCH), 132.5
2
,6-Dimethoxy-4-(3-methylbenzo[b]thiophen-2-yl)phenol (3aa)
(ArC), 134.7 (ArC), 137.5 (ArC), 138.4 (ArC), 139.8 (ArC),
41.1 (ArC), 146.9 (ArC), 160.1 (ArC) ppm. HRMS (ESI):
1
1
H NMR (400 MHz, CDCl ) δ = 2.47 (s, 3H, CH ), 3.94 (s, 6H,
+
3
3
Calcd. for C H O S (M+H ), 393.1155; found 393.1145.
23
21
4
OCH ), 5.62 (s, 1H, OH), 6.76 (s, 2H, ArCH), 7.34 (ddd, J = 8.3,
3
7
.1, 1.3 Hz, 1H, ArCH), 7.41 (ddd, J = 8.1, 7.1, 1.2 Hz, 1H,
ArCH), 7.71 (d, J = 7.6 Hz, 1H, ArCH), 7.82 (d, J = 7.7 Hz, 1H,
13
2,6-Dimethoxy-4-(3-(4-methoxyphenyl)benzo[b]thiophen-2-
yl)phenol (3ea)
ArCH) ppm; C NMR (100 MHz, CDCl ) δ = 12.9 (CH ), 56.5
3
3
(
OCH ), 106.8 (ArCH), 122.1 (ArCH), 122.2 (ArCH), 124.3
3
1
(ArCH), 124.4 (ArCH), 125.9 (ArC), 127.1 (ArC), 134.8 (ArC),
H NMR (400 MHz, CDCl ) δ = 3.69 (s, 6H, OCH ), 3.85 (s, 3H,
3
3
1
38.4 (ArC), 138.7 (ArC), 141.3 (ArC), 147.1 (ArC) ppm.
,6-Dimethoxy-4-(3-phenylbenzo[b]thiophen-2-yl)phenol (3ba)
OCH ), 5.55 (s, 1H, OH), 6.57 (s, 2H, ArCH), 6.97 (d, J = 8.8
3
Hz, 2H, ArCH), 7.28 (d, J = 8.8 Hz, 2H, ArCH), 7.32-7.36 (m,
2
H, ArCH), 7.56-7.58 (m, 1H, ArCH), 7.84-7.86 (m, 1H, ArCH)
13
2
ppm; C NMR (100 MHz, CDCl ) δ = 55.5 (OCH ), 56.2
3
3
(
(
(
OCH ), 106.6 (ArCH), 114.4 (ArCH), 122.1 (ArCH), 123.3
ArCH), 124.5 (ArCH), 124.6 (ArCH), 125.6 (ArC), 128.3
ArC), 131.7 (ArCH), 132.4 (ArC), 134.6 (ArC), 138.4 (ArC),
1
3
H NMR (400 MHz, CDCl ) δ = 3.66 (s, 6H, OCH ), 5.54 (s, 1H,
3
3
OH), 6.56 (s, 2H, ArCH), 7.31-7.45 (m, 7H, ArCH), 7.55-7.58
(
MHz, CDCl ) δ = 56.1 (OCH ), 106.6 (ArCH), 122.1 (ArCH),
1
1
13
m, 1H, ArCH), 7.85-7.87 (m, 1H, ArCH) ppm; C NMR (100
1
39.4 (ArC), 141.4 (ArC), 146.9 (ArC), 159.1 (ArC), ppm.
+
3
3
HRMS (ESI): Calcd. for C H O S (M-H ), 391.1010; found
3
23
19
4
23.2 (ArCH), 124.56 (ArCH), 124.60 (ArCH), 125.4 (ArC),
27.5 (ArCH), 128.9 (ArCH), 130.6 (ArCH), 132.7 (ArC), 134.7
91.1006.
(
1
3
ArC), 136.2 (ArC), 138.4 (ArC), 139.8 (ArC), 141.2 (ArC),
46.9 (ArC) ppm. HRMS (ESI): Calcd. for C H O S (M-H ),
22 17 3
61.0904; found 361.0901.
+
2
,6-Dimethoxy-4-(3-(4-
(trifluoromethyl)phenyl)benzo[b]thiophen-2-yl)phenol (3fa)
1
H NMR (400 MHz, CDCl ) δ = 3.66 (s, 6H, OCH ), 5.54 (s, 1H,
3
3
4
-(3-(3,5-Dimethylphenyl)benzo[b]thiophen-2-yl)-2,6-
OH), 6.48 (s, 2H, ArCH), 7.36-7.40 (m, 2H, ArCH), 7.49-7.55
(m, 3H, ArCH), 7.70 (d, J = 8.0 Hz, 2H, ArCH), 7.87-7.89 (m,
dimethoxyphenol (3ca)
13
1
H, ArCH) ppm. C NMR (150 MHz, CDCl ) δ = (1 × ArC
3
1
H NMR (400 MHz, CDCl ) δ = 2.32 (s, 6H, CH ), 3.68 (s, 6H,
3
3
missing), 56.1 (OCH ), 106.7 (ArCH), 122.3 (ArCH), 122.8
3
OCH ), 5.52 (s, 1H, OH), 6.61 (s, 2H, ArCH), 6.98-7.01 (m, 3H,
ArCH), 7.30-7.33 (m, 2H, ArCH), 7.51-7.54 (m, 1H, ArCH),
7
3
(ArCH), 124.3 (q, J = 272.0 Hz, CF ), 124.8 (ArC), 124.9
3
(ArCH), 124.9 (ArCH), 125.8 (q, J = 3.7 Hz, ArCH), 129.7 (q, J
13
.83-7.85 (m, 1H, ArCH) ppm; C NMR (100 MHz, CDCl ) δ =
3
= 32.6 Hz, ArC), 131.1 (ArCH), 135.0 (ArC), 138.6 (ArC), 140.1
(1 × ArCH missing) 21.4 (CH ), 56.1 (OCH ), 106.5 (ArCH),
3 3
(ArC), 140.5 (ArC), 141.1 (ArC), 147.0 (ArC) ppm. HRMS
+
1
22.0 (ArCH), 123.4 (ArCH), 124.5 (ArCH), 125.6 (ArC), 128.2
(
ESI): Calcd. for C H F O S (M-H ), 429.0767; found
23
16
3
3
(ArCH), 129.1 (ArCH), 133.0 (ArC), 134.6 (ArC), 136.1 (ArC),
4
29.0770.

5
4
-(3,5-Dimethylbenzo[b]thiophen-2-yl)-2,6-dimethoxyphenol
5-Fluoro-2-methoxy-4-(3-methylbenzo[b]thiophen-2-yl)phenol
(3ac)
(3ga)
1
1
H NMR (400 MHz, CDCl ) δ = 2.45 (s, 3H, CH ), 2.51 (s, 3H,
H NMR (400 MHz, CDCl ) δ = 2.33 (d, J = 1.9 Hz, 3H, CH ),
3 3
3
3
CH ), 3.94 (s, 6H, OCH ), 5.62 (s, 1H, OH), 6.76 (s, 2H, ArCH),
3.91 (s, 3H, OCH ), 5.83 (s, 1H, OH), 6.81 (d, J = 10.1 Hz, 1H,
3
3
3
7
8
.18 (d, J = 8.0 Hz, 1H, ArCH), 7.50 (s, 1H, ArCH), 7.69 (d, J =
ArCH), 6.88 (d, J = 6.6 Hz, 1H, ArCH), 7.35 (ddd, J = 8.3, 7.3,
1.3 Hz, 1H, ArCH), 7.41 (ddd, J = 8.0, 7.2, 1.2 Hz, 1H, ArCH),
7.73 (d, J = 7.5 Hz, 1H, ArCH), 7.83 (d, J = 7.7 Hz, 1H, ArCH),
13
.0 Hz, 1H, ArCH) ppm; C NMR (100 MHz, CDCl ) δ = 12.8
3
(CH ), 21.7 (CH ), 56.5 (OCH ), 106.8 (ArCH), 121.8 (ArCH),
3 3 3
13
1
22.2 (ArCH), 126.0 (ArCH), 126.1 (ArC), 126.8 (ArC), 134.0
ppm; C NMR (100 MHz, CDCl ) δ = 12.9 (d, J = 3.6 Hz, CH ),
3
3
(
1
3
ArC) 134.8 (ArC), 135.8 (ArC), 138.5 (ArC), 141.6 (ArC),
56.6 (OCH ), 103.3 (d, J = 28.0 Hz, ArCH), 112.7 (d, J = 17.4
Hz, ArC), 113.4 (d, J = 4.2 Hz, ArCH), 122.2 (ArCH), 122.3
(ArCH), 124.3 (ArCH), 124.5 (ArCH), 130.2 (ArC), 131.3
3
+
47.1 (ArC) ppm. HRMS (ESI): Calcd. for C H O S (M-H ),
18
17
3
13.0904; found 313.0900.
(ArC), 139.5 (ArC), 140.7 (ArC), 143.0 (d, J = 2.4 Hz, ArC),
1
47.0 (d, J = 12.4 Hz, ArC), 154.6 (d, J = 242.0 Hz, ArCF) ppm.
4
-(5-Chloro-3-methylbenzo[b]thiophen-2-yl)-2,6-
dimethoxyphenol (3ha)
2
-Chloro-4-methoxy-6-(3-methylbenzo[b]thiophen-2-yl)phenol
1
H NMR (400 MHz, CDCl ) δ = 2.43 (s, 3H, CH ), 3.94 (s, 6H,
3
3
(3ad)
OCH ), 5.63 (s, 1H, OH), 6.74 (s, 2H, ArCH), 7.30 (d, J = 8.4
Hz, 1H, ArCH), 7.67 (s, 1H, ArCH), 7.71 (d, J = 8.4 Hz, 1H,
ArCH) ppm; C NMR (100 MHz, CDCl ) δ = (1 × ArC
3
1
H NMR (400 MHz, CDCl ) δ = 2.34 (s, 3H, CH ), 3.79 (s, 3H,
3
3
13
OCH ), 5.39 (s, 1H, OH), 6.84 (d, J = 2.8 Hz, 1H, ArCH), 7.00
3
3
missing), 12.8 (CH ), 56.6 (OCH ), 106.8 (ArCH), 121.8
(d, J = 2.8 Hz, 1H, ArCH), 7.37-7.46 (m, 2H, ArCH), 7.76 (d, J =
3
3
1
3
(ArCH), 123.2 (ArCH), 124.7 (ArCH), 125.4 (ArC), 126.5
8.0 Hz, 1H, ArCH), 7.85 (d, J = 8.0 Hz, 1H, ArCH) ppm;
C
(
1
3
ArC), 130.7 (ArC), 135.2 (ArC), 136.8 (ArC), 140.6 (ArC),
NMR (100 MHz, CDCl ) δ = (1 × ArC missing), 12.8 (CH ),
3
3
+
47.2 (ArC) ppm. HRMS (ESI): Calcd. for C H ClO S (M-H ),
56.1 (OCH ), 115.6 (ArCH), 116.4 (ArCH), 121.0 (ArC), 122.40
17
14
3
3
33.0358; found 333.0352.
(ArCH), 122.43 (ArCH), 124.4 (ArCH), 124.9 (ArCH), 131.0
(
1
ArC), 131.7 (ArC), 139.8 (ArC), 140.5 (ArC), 143.7 (ArC),
+
53.0 (ArC) ppm. HRMS (ESI): Calcd. for C H ClO S (M-H ),
16 12 2
2
,6-Dimethoxy-4-(2-methylbenzo[b]thiophen-3-yl)phenol (3a’a)
303.0252; found 303.0248.
1
H NMR (400 MHz, CDCl ) δ = 2.51 (s, 3H, CH ), 3.91 (s, 6H,
3
3
OCH ), 5.62 (s, 1H, OH), 6.61 (s, 2H, ArCH), 7.29-7.32 (m, 2H,
3
4
-Methoxy-2,6-bis(3-methylbenzo[b]thiophen-2-yl)phenol (4)
ArCH), 7.52-7.54 (m, 1H, ArCH), 7.78-7.80 (m, 1H, ArCH)
13
1
ppm; C NMR (100 MHz, CDCl ) δ = 14.7 (CH ), 56.5 (OCH ),
H NMR (400 MHz, CDCl ) δ = 2.39 (s, 6H, CH ), 3.90 (s, 3H,
3 3
3
3
3
1
1
06.9 (ArCH), 122.1 (ArCH), 122.5 (ArCH), 123.9 (ArCH),
24.3 (ArCH), 126.4 (ArC), 134.1 (ArC), 134.2 (ArC), 136.0
OCH ), 5.23 (s, 1H, OH), 7.00 (s, 2H, ArCH), 7.37-7.46 (m, 4H,
3
ArCH), 7.77 (d, J = 7.6 Hz, 2H, ArCH), 7.86 (d, J = 8.0 Hz, 2H,
13
(ArC), 138.2 (ArC), 140.6 (ArC), 147.2 (ArC) ppm. HRMS
ArCH) ppm; C NMR (100 MHz, CDCl ) δ = 12.9 (CH ), 56.0
3
3
+
(ESI): Calcd. for C H O S (M-H ), 299.0736; found 299.0745.
(OCH ), 117.9 (ArCH), 121.9 (ArC), 122.40 (ArCH), 122.42
3
17
15
3
(ArCH), 124.4 (ArCH), 124.8 (ArCH), 130.9 (ArC), 132.4
(
ArC), 139.9 (ArC), 140.6 (ArC), 145.5 (ArC), 152.7 (ArC) ppm.
+
2
,6-Dimethoxy-4-(2-phenylbenzo[b]thiophen-3-yl)phenol (3b’a)
HRMS (ESI): Calcd. for C25
17.0971.
H
21
O
2
S
2
(M+H ), 417.0977; found
4
1
H NMR (400 MHz, CDCl ) δ = 3.74 (s, 6H, OCH ), 5.57 (s, 1H,
3
3
OH), 6.54 (s, 2H, ArCH), 7.24-7.28 (m, 3H, ArCH), 7.33-7.37
m, 4H, ArCH), 7.65-7.67 (m, 1H, ArCH), 7.85-7.88 (m, 1H,
(
13
Acknowledgments
ArCH) ppm; C NMR (100 MHz, CDCl ) δ = 56.4 (OCH ),
3
3
1
1
07.3 (ArCH), 122.3 (ArCH), 123.4 (ArCH), 124.6 (ArCH),
24.7 (ArCH), 126.5 (ArC), 127.8 (ArCH), 128.5 (ArCH), 129.6
We thank the EPSRC (EP/M005062/1; Postdoctoral
Fellowship to Z. H.; Established Career Fellowship to D. J. P.)
and The University of Manchester (Lectureship to G. J. P. P.).
(ArCH), 133.3 (ArC), 134.3 (ArC), 134.4 (ArC), 138.8 (ArC),
1
39.4 (ArC), 141.0 (ArC), 147.4 (ArC) ppm. HRMS (ESI):
+
Calcd. for C H O S (M+H ), 363.1049; found 363.1048.
22
19
3
References and notes
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Declaration of interests
☐
X The authors declare that they have no known competing financial interests or personal
relationships that could have appeared to influence the work reported in this paper.
☐
The authors declare the following financial interests/personal relationships which may be considered
as potential competing interests: