Convenient Synthesis of Thieno[3,2-b]indoles and Thieno[3,4-b]indoles by Sequential Site-Selective Suzuki and Double C–N Coupling Reactions

Article abstract of DOI:10.1002/ejoc.201601281

A convenient synthesis of thieno[3,2-b]indoles and thieno[3,4-b]indoles has been developed. The protocol involves a site-selective Suzuki reaction, followed by a double C–N coupling reaction using anilines, benzylamines, or alkylamines. The yields range from good to excellent.

Full text of DOI:10.1002/ejoc.201601281

A Journal of
Accepted Article
Title: Convenient synthesis of thieno[3,2-b]indoles and thieno[3,4-b]indoles by se-
quential site-selective Suzuki- and double C-N coupling reaction
Authors: Ngo N Pham; Silvio Parpart; Sevak Grigoryan; Thang N Ngo; Tuan T Dang;
Tariel V Ghochikyan; Ashot S Saghyan; Peter Ehlers; Peter Langer
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soon as possible and may be different to this Accepted Article as a result of editing.
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blished to ensure accuracy of information. The authors are responsible for the content
of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201601281
Link to VoR: https://doi.org/10.1002/ejoc.201601281
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European Journal of Organic Chemistry
10.1002/ejoc.201601281
1
Convenient synthesis of thieno[3,2-b]indoles and thieno[3,4-
b]indoles by sequential site-selective Suzuki- and double C-N
coupling reaction
Ngo Nghia Pham,a,b,c Silvio Parpart,a Sevak Grigoryan,a,d Thang Ngoc Ngo,a Tuan Thanh
Dang,a Tariel V. Ghochikyan,d Ashot S. Saghyan,d,e Peter Ehlers,a,b Peter Langer*a,b
a Institut für Chemie, Universität Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany. E-mail:
peter.langer@uni-rostock.de; Tel: +49 381 4986410; Fax: +49 381 4986412.
http://www.langer.chemie.uni-rostock.de/
b Leibniz Institut für Katalyse an der Universität Rostock e.V., Albert-Einstein-Str. 29a, 18059 Rostock,
Germany
c Faculty of Chemistry, VNU University of Science Hanoi (VNU-HUS), 19 Le Thanh Tong, Hoan Kiem,
Hanoi, Vietnam
d
Yerevan State University, Faculty of Pharmacy and Chemistry, Alex Manoogian Str. 1, 0025
Yerevan, Armenia
e
Scientific and Production Center “Armbiotechnology” of NAS RA, Gyurjyan Str. 14, 0056 Yerevan,
Armenia
Abstract: A convenient synthesis of thieno[3,2-b]indoles and thieno[3,4-b]indoles has been
developed. The protocol involves a site-selective Suzuki reaction, followed by a double C-N
coupling reaction using anilines, benzylamines as well as alkylamines. The yields range from
good to excellent.
Keywords: catalysis; cyclizations; cross-coupling reactions; regioselectivity; heterocycles
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European Journal of Organic Chemistry
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Introduction
Thiophene is a five-membered heterocycle which occurs on earth mostly as a minority in
petroleum. Despite this minority, thiophene possesses a great potential for application in
many fields of daily life. In pharmacology, thiophene is considered as a bioisostere of
benzene.1 Thus, replacing benzene by a thiophene moiety, scientists have discovered better
alternatives for previously known drugs.2 For instance, Olanzapine has been applied as a
thiophene-analog of Clozapine for the treatment of schizophrenia with lower risk of side
effects (Fig. 1).3 In biological research, thiophenes may incorporated into structures of
fluorescent markers for cell labeling, such as compound DTTO (Fig. 1).4 Finally, in material
science, thiophene is integrated in various organic electronic structures with low oxidation
potential and environmental stability.5 Among these polymers, those involving fused
thiophenes belong to the most studied classes, since they represent promising candidates
for OFET applications. For example, DTTQ (Fig. 1), which is a fused thiophene-quinoxaline
based polymer, possesses increased photochemical stability.6
In this regard, two fused derivatives comprised of thiophene and indole, namely thieno[3,2-
b]indoles and thieno[3,4-b]indoles, have been considered to represent potential candidates
for various applications. Former derivatives are known to possess antiviral properties.7 They
also can be employed as building blocks of polymers for solar cell applications. For example,
TI-DTBT3 (Fig. 1) is a donor-acceptor conjugated polymer which displays relatively high
charge carrier mobility.8 As a result, the development of their syntheses has attracted
increasing attention from synthetic chemists.
Olanzapine
Clozapine
DTTO
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DTTQ
TI-DTBT3
thieno[3,2-b]indole
thieno[3,4-b]indole
5-substituted thieno[3,2-b]indole
Figure 1: Relevant thiophene-related compounds
The first syntheses of thieno[3,2-b]indole and thieno[3,4-b]indole were carried out in 1982 by
treating (a) substituted indole with thioamide9 and (b) 3-hydroxythiophene with hydrazine10
(Scheme 1). Unfortunately, these syntheses are not modular, thus not enabling a pathway to
a large product library. Until 2000, there was no further report with respect to the
enhancement of the synthetic elaboration of these two classes. Fortunately, the access to
these thienoindoles has been facilitated during the last two decades owing to the
development of palladium cross-coupling chemistry. With the high potential for creating new
C-C and C-N bonds by palladium catalysts, a number of new synthetic methods for these
classes have been developed. Generally, these protocols start with a Suzuki reaction to
construct the C-C bond between the thiophene and the benzene ring, followed by different
types of ring closures, such as (c) nitrene insertion,11 (d) oxidative C-N coupling12 or (e)
Cadogan cyclisation13 to furnish the desired products (Scheme 1).
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European Journal of Organic Chemistry
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Scheme 1: Previously reported synthesis of thieno[3,2-b]indole and thieno[3,4-b]indole
Scheme 2: Retrosynthesis of thieno[3,2-b]indole and thieno[3,4-b]indole in this study
In an attempt to synthesize thieno[3,2-b]indoles and thieno[3,4-b]indoles, we also
disconnected these molecules first by a Suzuki reaction (Scheme 2). However, we chose
(2-bromophenyl)boronic acid to generate a biaryl derivative which is capable of undergoing a
subsequent double C-N coupling. This strategy has proven effective in our previous studies
related to the preparation of different fused indols.14 In this paper, we present our results for
the synthesis of thieno[3,2-b]indole and thieno[3,4-b]indole derivatives.
Results and discussion
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The synthesis of thieno[3,2-b]indoles was initiated by a site-selective Suzuki reaction of
2,3-dibromothiophene (1) adapting our previously documented conditions for the preparation
of diindolothiophene.14b Under these conditions, 3-bromo-2-(2-bromophenyl) thiophene (2)
was obtained in 82% yield (Scheme 3).
Scheme 3: Selective Suzuki reaction of 2,3-dibromothiophene
Subsequently, 3-bromo-2-(2-bromophenyl) thiophene (2) was employed as precursor for the
double C-N coupling. To optimize this reaction, a brief ligand screening was conducted using
the base NaOtBu in toluene with the palladium source Pd2dba3.14b, 15 During the optimization,
the bidentate ligand dppf performed most effectively, generating 3a in excellent 97% yield
(Table 1).
Table 1: Optimization for synthesis of thieno[3,2-b]indole 3a
Entry
Ligand [mol%]
Yielda
86%
97%
65%
67%
a
1
2
3
4
PtBu3∙HBF4 [10%]
dppfb [5%]
SPhosa [10%]
(S)-BINAPb [5%]
a The yields were referred to as isolated yields.
With these optimized conditions in hand, the scope for the double C-N coupling was
examined. In this regard, 15 different electron-rich amines were applied, giving
corresponding thienoindoles 3a-o in good to excellent yields (Table 2). For electron-poor,
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European Journal of Organic Chemistry
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benzylic and aliphatic amines, application of dppf as ligand gave low yields of desired
products. Thus, (S)-BINAP was employed as ligand, affording thienoindoles 3p-t in very
good yields (Table 2). Overall, the highest yield was obtained for the electron-rich system 3f
(98%), while the lowest occurred with the very large -system 3o (72%). The reaction
proceeded effectively even with sterically encumbering amines, in case of 3b and 3k in 77%
and 89% yield, respectively.
Table 2: Synthesis of thieno[3,2-b]indoles 3a-t
3a (97%)
3e (90%)
3i (87%)
3b (77%)
3f (98%)
3j (92%)
3c (83%)
3g (91%)
3k (89%)
3d (90%)
3h (92%)
3l (92%)
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European Journal of Organic Chemistry
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3m (92%)
3n (78%)
3o (72%)
3p (91%)*
3q (86%)*
3r (81%)*
3s (95%)*
3t (75%)*
* Pd2dba3 5 mol%, (S)-BINAP 5 mol%, NaOtBu 2.4 equiv., toluene, 100 °C, 14h
The yields were referred to as isolated yields.
Next, we turned our attention to the synthesis of thieno[3,4-b]indoles, which was obtained
starting from 3,4-dibromothiophene (4). Using the same conditions applied for the Suzuki
reaction of 2,3-dibromothiophene, 3-bromo-4-(2-bromophenyl)thiophene (5) was afforded
selectively in 78% yield (Scheme 4).
Scheme 4: Selective Suzuki reaction of 3,4-dibromothiophene
Again, we tested several ligands for the double C-N coupling of 5, under otherwise identical
conditions. In this case, we became aware that the monodentate ligand PtBu3∙HBF4 was
most suitable for the reaction, giving thieno[3,4-b]indole 6a in 95% yield (Table 3).
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Table 3: Optimization for the synthesis of thieno[3,4-b]indole 6a
Entry
Ligand [mol%]
PtBu3∙HBF4 [10%]
dppf [5%]
Yielda
95%
43%
65%
36%
1
2
3
4
SPhos [10%]
(S)-BINAP [5%]
a The yields were referred to as isolated yields.
Using optimized conditions, we assessed the scope of the double C-N coupling. Noticeably,
obtained yields for corresponding products were slightly lower than those for thieno[3,2-
b]indoles 3a-t (Table 4). The reason for this might refer to the lower stability of the thieno[3,2-
b]indole derivatives.
Table 4: Synthesis of thieno[3,4-b]indole 6a-f
6a (95%)
6b (65%)
6c (83%)
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European Journal of Organic Chemistry
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6d (85%)
6e (81%)
6f (78%)
The yields were referred to as isolated yields.
Finally, we probed the feasibility of the method for the preparation of more structurally
complex products, namely 5-substituted thieno[3,2-b]indoles. The synthesis started with two
sequential site-selective Suzuki-reaction of 2,3,5-tribromothiophene (7) using our previously
reported conditions.16 2,3,5-tribromothiophene (7) was first converted to 2,3-dibromo-5-
arylthiophenes 8a-d and finally to the corresponding products 9a-d (Table 5). Compared to
the unsubstituted dibromothiophenes (Scheme 3 and 4), the yield of products obtained by
the Suzuki reactions were remarkably lower in this case. It is most probably due to the
presence of an additional aryl group at position 5 which might modulate the entire electronic
nature of the molecule.
Table 5: Synthesis of 5-substituted precursors 9a-d for double C-N coupling
R
H
Cl
F
8 (% yield)a
a (60%)
9 (% yield)a
a (43%)
b (37%)
c (43%)
b (30%)
c (33%)
tBu
d (43%)
d (26%)
a The yields were referred to as isolated yields.
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European Journal of Organic Chemistry
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With starting materials 9a-d in hand, we tested different ligands for the double C-N coupling.
In this case, Buchwald’s biaryl ligand SPhos was most appropriate, furnishing corresponding
thienoindole 10a in 96% yield (Table 6).
Table 6: Optimization for the synthesis of 5-substituted thieno[3,2-b]indole 10a
Entry
Ligand [mol%]
PtBu3∙HBF4 [10%]
SPhos [10%]
dppe [5%]
Yielda
84%
96%
36%
43%
1
2
3
4
Xantphos [5%]
a The yields were referred to as isolated yields.
Applying optimized conditions, thienoindoles 10a-j were prepared with moderate to excellent
yield (Table 7). Evidently, the conditions can be applied for both electron-rich and electron-
poor aryl amines, generating corresponding thienoindoles 10a-j in the range of 45% to 95%
yield. The highest yield was obtained for thienoindole 10a (95%), while the lowest were
obtained from thienoindoles 10i and 10j (both 45%). No clear correlation between the yields
and chemical structures of 5-substituted thieno[3,2-b]indoles was observed.
Table 7: Synthesis of 5-substituted thieno[3,2-b]indoles 10a-j
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European Journal of Organic Chemistry
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10a (95%)
10d (90%)
10g (87%)
10j (45%)
10b (61%)
10e (62%)
10h (62%)
10c (62%)
10f (61%)
10i (45%)
The yields were referred to as isolated yields.
Conclusion
In conclusion, we developed a new synthetic pathway to thieno[3,2-b]indoles and
thieno[3,4-b]indoles by site-selective Suzuki-reaction followed by double C-N coupling. In this
protocol, electron-rich and electron-poor as well as aliphatic amines are compatible
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European Journal of Organic Chemistry
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nucleophiles. Despite the similarity of the starting materials, it became apparent that the
choice of ligand is crucial for the final ring-closing double C-N coupling.
Experimental section
General information
If not otherwise stated, employed chemicals were obtained from commercial sources without
further purifications. Chemicals used for work-up and purification were distilled prior usage.
Column chromatography was carried out with silica gel with particle size between 0.006 and
0.043 mm. Product characterization was carried out using following devices. Melting point:
Micro-Hot-Stage GalenTM III Cambridge Instrument.NMR: Bruker AVANCE 250 II, Bruker
AVANCE 300 III and Bruker AVANCE 500 built 2006, 2007 and 2001, respectively.IR:
Nicolet 380 FT-IR spectrometer using ATR sampling technique. GC/MS (EI, 70 eV): Finnigan
MAT 95-XP device using HP-5 capillary column with helium carrier gas and electron
ionization (EI) scan technique at 90 eV. HRMS: Finnigan MAT 95 XP device.
Melting point was carried out without further correction. For HRMS measurement, only
signals with deviations of less than ±2 mDa were accounted as correct. NMR-peaks were
1
calibrated using standard peaks of chloroform (7.260 ppm for H, 72.160 ppm for 13C) and
acetone (2.050 ppm for 1H, 29.840 ppm for 13C). For peak descriptions, following
abbreviations were used. NMR spectroscopy: s (singlet), d (doublet), t (triplet), dd (doublet
doublet), dt (doublet triplet), td (triplet doublet), ddd (doublet doublet doublet). IR
spectroscopy: w (weak), m (medium), s (strong).
General procedure for the site-selective Suzuki reaction of 2,3-dibromothiophene and
3,4-dibromothiophene
2,3- or 3,4-Dibromothiophene (3 mmol), (2-bromophenyl)boronic acid (3.3 mmol), Pd(PPh3)4
(0.15 mmol), Na2CO3 (6 mmol) were added to a dried glass pressure tube. Next, the tube
was evacuated and backfilled three times with argon. Afterwards, the solids were solved in 8
ml of 1,4-dioxane and 2 ml of distilled water. The tube was sealed by a Teflon cap and
heated to 100 °C for 14 hours. After the reaction was finished (monitored by TLC), it was
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European Journal of Organic Chemistry
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allowed to cool to room temperature and Na2SO4 was added to the mixture, diluted with ethyl
acetate and filtered. The solvent was removed under reduced pressure. The crude oil was
purified by column chromatography using heptane.
3-Bromo-2-(2-bromophenyl)thiophene (2): White solid, mp. 63 – 64 °C, 82% yield.
3
1H NMR (500 MHz, Chloroform-d) δ = 7.69 (d, J = 8.0 Hz, 1H, CHAr), 7.42 – 7.34 (m, 3H,
3
3
4
3
CHAr), 7.28 (ddd, J = 8.0 Hz, J = 6.7 Hz, J = 2.5 Hz, 1H, CHAr), 7.07 (d, J = 5.3 Hz, 1H,
CHthiophene). 13C NMR (126 MHz, CDCl3) δ = 137.3 (CAr), 134.0 (CAr), 133.1 (CHAr), 132.9
(CHAr), 130.6 (CHAr), 130.3 (CHAr), 127.3 (CHAr), 126.2 (CHAr), 125.2 (CAr), 111.2 (CAr). IR
(ATR, cm-1): ṽ = 3110 (w), 3085 (w), 3059 (w), 1528 (w), 1463 (m), 1419 (m), 1340 (m), 1148
(w), 1024 (m), 857 (m), 756 (s), 712 (s), 654 (m), 620 (m), 522 (m), 446 (m). MS (EI, 70 eV):
m/z (%) = 318 [M]+ (45), 239 (22), 158 (100), 114 (30), 79 (21). HRMS (EI): Calculated for
C10H6Br2S [M]+ 315.85515 found 315.85464, calculated for C10H6Br81BrS [M]+ 317.85310
81
found 317.85281, calculated for C10H6 Br2S [M]+ 319.85105 found 319.85069.
1
3-Bromo-4-(2-bromophenyl)thiophene (5): Colorless oil, 78% yield. H NMR (500 MHz,
3
Chloroform-d) δ = 7.67 (d, J = 8.1 Hz, 1HAr), 7.39 – 7.34 (m, 2H, CHAr), 7.31 – 7.24 (m, 3H,
CHAr). 13C NMR (126 MHz, CDCl3) δ = 141.5 (CAr), 136.6 (CAr), 132.9 (CHAr), 132.0 (CHAr),
129.8 (CHAr), 127.2 (CHAr), 124.9 (CHAr), 124.5 (CAr), 123.3 (CHAr), 112.4 (CAr). IR
(ATR, cm-1): ṽ = 3107 (w), 3057 (w), 1560 (w), 1525 (w), 1464 (m), 1425 (m), 1339 (m), 1257
(w), 1081 (w), 1026 (m), 921 (m), 852 (m), 792 (m), 751 (s), 710 (m), 653 (m), 451 (m). MS
(EI, 70 eV): m/z (%) = 320 (23), 318 [M]+ (43), 239 (31), 158 (100), 114 (26), 113 (20), 79
(24). HRMS (EI): Calculated for C10H6Br2S [M]+ 315.85515 found 315.85490, calculated for
81
C10H6Br81BrS [M]+ 317.85310 found 317.85301, calculated for C10H6 Br2S [M]+ 319.85105
found 319.85073.
General procedure for
thiophene
the one-fold selective Suzuki reaction of 2,3,5-tribromo-
2,3,5-Tribromothiophene (10 mmol), arylboronic acid (11 mmol) and Pd(PPh3)4 (0.5 mmol)
were dissolved in a mixture of 100 ml 1,4-dioxane/toluene (1:1) under argon atmosphere. To
the reaction was added 40 ml aqueous 2M K2CO3. The reaction was heated to 80 °C for 8
hours. After the reaction was finished (monitored by TLC), it was allowed to cool to room
temperature. The mixture was extracted with dichloromethane three times. The combined
organic phases were collected and dried with Na2SO4, filtered and concentrated under
vacuum. The residue was purified by column chromatography using heptane to obtain the
pure product.
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European Journal of Organic Chemistry
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1
2,3-Dibromo-5-phenylthiophene (8a): White solid, mp. 68 – 69 °C, 60 % yield. H NMR
(250 MHz, Chloroform-d) δ = 7.53 – 7.45 (m, 2H, CHAr), 7.44 – 7.32 (m, 3H, CHAr), 7.10 (s,
13
1H, CHthiophene). C NMR (63 MHz, CDCl3) δ = 145.6 (CAr), 132.9 (CAr), 129.4 (2CHAr), 128.8
(CHAr), 125.8 (CHAr), 125.7 (2CHAr), 114.8 (CAr), 110.3 (CAr). IR (ATR, cm-1): ṽ = 3056 (w),
1579 (w), 1486 (m), 1446 (m), 1320 (w), 1292 (w), 1069 (w), 997 (m), 948 (w), 815 (s), 747
(s), 682 (s), 625 (w), 549 (w). MS (EI, 70 eV): m/z (%) = 320 [M+, 81Br] (43), 318 [M+] (88),
316 (41), 158 (58), 114 (12), 91 (14), 82 (18), 79 (26), 77 (5), 69 (10), 44 (15), 43 (9), 32
(100). HRMS (EI): Calculated for C10H6Br2S [M]+ 315.85526 found 315.85515, calculated for
81
C10H6Br81BrS [M]+ 317.85310 found 317.85326, calculated for C10H6 Br2S [M]+ 319.85105
found 319,85119.
2,3-Dibromo-5-(4-chlorophenyl)thiophene (8b): White solid, mp. 104 – 105 °C, 37% yield.
1H NMR (250 MHz, Chloroform-d) δ = 7.45 – 7.32 (m, 4H, CHAr), 7.08 (s, 1H, CHthiophene).
13C NMR (63 MHz, CDCl3) δ = 144.2 (CAr), 134.7 (CAr), 131.4 (CAr), 129.6 (2CHAr), 126.9
(2CHAr), 126.2 (CHthiophene), 115.0 (CAr), 110.7 (CAr). IR (ATR, cm-1): ṽ = 3088 (w), 3033 (w),
1484 (m), 1429 (w), 1402 (w), 1318 (w), 1091 (m), 997 (w), 801 (s), 733 (w), 674 (m), 575
(w), 546 (w). MS (EI, 70 eV): m/z (%) = 356 (16), 355 (8), 354 [M+, 81Br] (72), 353 (12), 352
[M+] (100), 350 (43), 194 (17), 192 (46), 157 (11), 113 (15), 96 (8). HRMS (EI): Calculated
for C10H5Br2ClS [M]+ 349.81618 found 349.81584, calculated for C10H5Br81BrClS 351.81413
found 351.81374, calculated for C10H5Br81Br37ClS [M]+ 351.81323 found 351.81323,
calculated for C10H5Br81Br37ClS [M]+ 353.81118 found 353.81139, calculated for
81
81
37
C10H5 Br2ClS [M]+ 353.81208 found 353.81139, calculated for C10H5 Br2 ClS
[M]+
355.80913 found 355.80899.
2,3-Dibromo-5-(4-fluorophenyl)thiophene (8c): White solid, mp. 95 – 96 °C, 43% yield.
3
3
1H NMR (300 MHz, Chloroform-d) δ = 7.44 (dd, J = 8.8 Hz, J = 5.1 Hz, 2H, CHAr), 7.08 (t,
3J = 8.6 Hz, 2H, CHAr), 7.02 (s, 1H, CHAr). 19F NMR (282.4 MHz, CDCl3): δ = -112.5 (FCAr).
1
13C NMR (75 MHz, CDCl3) δ = 163.1 (d, JC-F = 249.2 Hz, CAr), 144.4 (CAr), 129.2 (d,
4JC-F = 3.4 Hz, FCAr), 127.5 (d, 3JC-F = 8.2 Hz, 2CHAr), 125.8 (CHthiophene), 116.4 (d, 2JC-F = 22.0
Hz, 2CHAr), 114.8 (CAr), 110.2 (CAr). IR (ATR, cm-1): ṽ = 3089 (w), 1595 (w), 1494 (s), 1299
(m), 1232 (s), 1157 (m), 993 (m), 829 (s), 807 (s), 691 (m), 585 (m), 547 (m).MS (EI, 70 eV):
m/z (%) = 336 [M]+ (100), 334 (48), 213 (6), 211 (6), 177 (8), 177 (76), 139 (6), 132 (20), 131
(13), 88 (11), 81 (7), 75 (6), 74 (4), 69 (6). HRMS (EI): Calculated for C10H5Br2FS [M]+
333.84573 found 333.84563, calculated for C10H5Br81BrFS [M]+ 335.84368 found 335.84353,
81
calculated for C10H5 Br2FS [M]+ 337.84163 found 337.84146.
2,3-Dibromo-5-(4-(tert-butyl)phenyl)thiophene (8d): White solid, mp. 59 – 60 °C,
43% yield. 1H NMR (300 MHz, Chloroform-d) δ = 7.42 (m, 4H, CHAr), 7.07 (s, 1H, CHthiophene),
13
1.34 (s, 9H, tBu). C NMR (75 MHz, CDCl3) δ = 152.0 (CAr), 145.6 (CAr), 130.1 (CAr), 126.4
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European Journal of Organic Chemistry
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(2CHAr), 125.2 (2CHAr), 125.2 (CHthiophene), 114.7 (CAr), 109.7 (CAr), 34.9 (CtBu), 31.4 (3CH3).
IR (ATR, cm-1): ṽ = 2958 (m), 2865 (w), 1496 (m), 1362 (m), 1267 (w), 1186 (w), 996 (m),
834 (m), 810 (s), 732 (m), 565 (s). MS (EI, 70 eV): m/z (%) = 376 (22), 374 [M+, 81Br] (42),
272 [M+] (21), 362 (7), 361 (52), 360 (15), 159 (100), 157 (50), 333 (9), 331 (16), 329 (8), 165
(10). HRMS (EI): Calculated for C14H14Br2S [M]+ 371.91775, found 371.91695, calculated for
C14H14Br81BrS [M]+ 373.91570, found 373.91505, calculated for C14H1481Br2S [M]+ 375.91365,
found 375.91293.
General procedure for the site-selective Suzuki reaction of 5-substituted 2,3-
dibromothiophene
5-Substituted 2,3-dibromothiophene (3 mmol), (2-bromophenyl)boronic acid (3.3 mmol) and
Pd(PPh3)4 (0.15 mmol) were dissolved in 30 ml of mixture 1,4-dioxane/toluene (1:1) under
argon atmosphere. To the reaction was added 12 ml aqueous 2M K2CO3. The reaction was
heated to 80 °C for 12 hours (monitored by TLC). After cooling to room temperature, it was
extracted with dichloromethane three times. The organic phases were collected and dried
with Na2SO4, filtered and concentrated under reduced pressure. The crude oil was subjected
to column chromatography using heptane to obtain the pure product.
3-Bromo-2-(2-bromophenyl)-5-phenylthiophene (9a): White solid, mp. 83 – 84 °C,
1
3
4
43% yield. H NMR (250 MHz, Chloroform-d) δ = 7.70 (dd, J = 8.0 Hz, J = 1.3 Hz, 1H,
CHAr), 7.62 – 7.53 (m, 2H, CHAr), 7.47 – 7.27 (m, 6H, CHAr), 7.25 (s, 1H, CHthiophene). 13C NMR
(63 MHz, CDCl3) δ = 144.7 (CAr), 136.4 (CAr), 134.0 (CHAr), 133.3 (CHAr), 133.0 (CAr), 130.7
(CHAr), 129.3 (2CHAr), 128.5 (CHAr), 127.4 (CHAr), 126.0 (CHAr), 125.8 (2CHAr), 125.2 (CAr),
111.6 (CAr). IR (ATR, cm-1): ṽ = 3094 (w), 1538 (w), 1473 (m), 1447 (m), 1331 (w), 1073 (w),
1052 (w), 1027 (m), 823 (w), 757 (s), 749 (s), 722 (m), 688 (s), 649 (m), 572 (w). MS
(EI, 70 eV): m/z (%) = 397 (9), 396 (53), 395 (18), 394 [M+] (100), 392 (51), 235 (14), 234
(69), 233 (14), 232 (10), 202 (16), 189 (29), 121 (17), 113 (16), 77 (17), 51 (12), 51 (12).
HRMS (EI): Calculated for C16H10Br2S [M]+ 391.88645 found 391.88593, calculated for
C16H10Br81BrS [M]+ 393.88440, calculated for C16H1081Br2S1 [M]+ 395.88209 found
395.88209.
3-Bromo-2-(2-bromophenyl)-5-(4-chlorophenyl)thiophene (9b): Yellow oil, 37% yield.
1H NMR (300 MHz, Chloroform-d) δ = 7.73 – 7.68 (m, 1H, CHAr), 7.52 (m, 2H, CHAr), 7.46 –
7.34 (m, 4H, CHAr), 7.31 (m, 1H, CHAr), 7.25 (s, 1H, CHthiophene). 13C NMR (75 MHz, CDCl3)
δ = 143.3 (CAr), 136.7 (CAr), 134.3 (CAr), 133.7 (CAr), 133.2 (CHAr), 132.9 (CHAr), 131.7 (CAr),
130.7 (CHAr), 129.4 (2CHAr), 127.4 (CHAr), 127.0 (2CHAr), 126.3 (CHAr), 125.1 (CAr), 111.8
(CAr). IR (ATR, cm-1): ṽ = 3053 (w), 1502 (w), 1472 (s), 1446 (m), 1402 (w), 1324 (w), 1091
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European Journal of Organic Chemistry
10.1002/ejoc.201601281
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(s), 1054 (m), 1012 (m), 974 (w), 812 (s), 750 (s), 704 (w), 669 (m), 642 (w). MS (EI, 70 eV):
m/z (%) = 432 (17), 431 (16), 430 (73), 429 (17), 428 [M+] (100), 426 (42), 270 (13), 268 (35),
232 (12), 189 (14). HRMS (EI): Calculated for C16H9Br2ClS [M]+ 425.84725 found 425.84725,
37
calculated for C16H9Br81BrClS [M]+ 427.84543 found 427.84523, calculated for C16H9Br2 ClS
81
[M]+ 427.84453 found 427.84526, calculated for C16H9 Br2ClS [M]+ 429.84338 found
79
429.84322, calculated for C10H5 Br81Br37ClS [M]+ 429.84248 found 429.84322.
3-Bromo-2-(2-bromophenyl)-5-(4-fluorophenyl)thiophene (9c): White solid, mp. 66 –
1
67 °C, 33% yield. H NMR (250 MHz, Chloroform-d) δ = 7.82 – 7.76 (m, 1H, CHAr), 7.68 –
7.58 (m, 2H, CHAr), 7.55 – 7.43 (m, 2H, CHAr), 7.43 – 7.33 (m, 1H, CHAr), 7.28 (s, 1H,
CHthiophene), 7.24 – 7.13 (m, 2H, CHAr). 19F NMR (235 MHz, CDCl3) δ = -113.03 (CFAr).
1
13C NMR (63 MHz, CDCl3) δ = 162.9 (d, JC-F = 248.5 Hz, FCAr), 143.6 (CAr), 133.8 (CAr),
3
133.3 (CHAr), 133.0 (CHAr), 130.7 (CHAr), 129.6 (CAr), 129.5 (CAr), 127.6 (d, JC-F = 8.2 Hz,
4
2
2CHAr), 127.4 (CHAr), 126.0 (d, JC-F = 1.3 Hz, CHAr), 125.1 (CAr), 116.3 (d, JC-F = 21.9 Hz,
2CHAr), 111.7 (CAr). IR (ATR, cm-1): ṽ = 3040 (w), 1539 (w), 1508 (m), 1480 (s), 1423 (m),
1330 (m), 1300 (s), 1162 (s), 1097 (m), 1053 (m), 972 (m), 944 (m), 828 (s), 809 (s), 765 (s),
728 (s), 702 (m), 686 (s), 644 (s), 579 (s). MS (EI, 70 eV): m/z (%) = 414 (52), 413 (18), 412
[M+] (100), 410 (49), 253 (10), 252 (61), 220 (12), 207 (21), 139 (10). HRMS (EI): Calculated
for C16H9Br2FS [M]+ 409.87703 found 409.87680, calculated for C16H9Br81BrFS [M]+
411.87498 found 411.87474, calculated for C20H1881Br2FS [M]+ 413.87293 found 413.87281.
3-Bromo-2-(2-bromophenyl)-5-(4-(tert-butyl)phenyl)thiophene (9d): White solid, mp. 96 –
1
3
4
97 °C, 26% yield. H NMR (300 MHz, Chloroform-d) δ = 7.70 (dd, J = 7.9 Hz, J = 0.9 Hz,
1H, CHAr), 7.55 – 7.50 (m, 2H, CHAr), 7.45 – 7.42 (m, 2H, CHAr), 7.42 – 7.40 (m, 1H, CHAr),
7.37 (dd, 3J = 7.6, 4J = 1.3 Hz, 1H, CHAr), 7.33 – 7.27 (m, 1H, CHAr), 7.22 (s, 1H, CHthiophene),
13
1.35 (s, 9H, tBu). C NMR (63 MHz, CDCl3) δ = 151.8 (CAr), 144.8 (CAr), 135.9 (CAr), 134.1
(CAr), 133.3 (CHAr), 133.1 (CHAr), 130.6 (CAr), 130.5 (CHAr), 127.4 (CHAr), 126.2 (2CHAr),
125.6 (2CHAr), 125.5 (CHAr), 125.2 (CAr), 111.5 (CAr), 34.9 (CtBu), 31.5 (3CH3). IR (ATR, cm-1):
ṽ = 2959 (m), 2864 (w), 1480 (m), 1458 (m), 1362 (w), 1268 (w), 1109 (w), 974 (w), 817 (s),
752 (s), 726(m), 671(m), 578 (w), 545(s). MS (EI, 70 eV): m/z (%) = 453 (11), 452 (37), 451
(16), 450 [M+] (75), 448 (35), 438 (12), 437 (55), 436 (24), 435 (100), 433 (52), 407 (11), 260
(11), 258 (11), 234 (14), 202 (11), 189 (9), 124 (15), 115 (10), 113 (12), 41 (19). HRMS (EI):
Calculated for C20H18Br2S [M]+ 447.94905 found 447.94886, calculated for C20H18Br81BrS [M]+
449.94700 found 449.94680, calculated for C20H1881Br2S [M]+ 451.94495 found 451.94491.
General procedure for the synthesis of thieno[3,2-b]indoles
3-Bromo-2-(2-bromophenyl)thiophene (0.15 mmol), amine (0.225 mmol), Pd2dba3 (0.0075
mmol), dppf or (S)-BINAP (0.0075 mmol) and NaOtBu (0.36 mmol) were added to a dried
glass pressure tube. The tube was evacuated and backfilled three times with argon. 2 ml of
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European Journal of Organic Chemistry
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dried toluene was added. The mixture was heated to 100 °C for 14 hours until completion
(monitored by TLC). After cooling to room temperature, the solvent was removed under
reduced pressure. The crude oil was subjected to column chromatography (heptane/ethyl
acetate) to obtain the pure product.
1
4-(p-Tolyl)-4H-thieno[3,2-b]indole (3a): Yellow solid, mp. 92 – 93 °C, 97% yield. H NMR
(300 MHz, Chloroform-d) δ = 7.82 – 7.77 (m, 1H, CHAr), 7.55 – 7.50 (m, 1H, CHAr), 7.47 (d,
3J = 8.3 Hz, 2H, CHAr), 7.40 – 7.33 (m, 3H, CHAr), 7.30 – 7.19 (m, 2H, CHAr), 7.08 (d, 3J = 5.2
Hz, 1H, CHthiophene), 2.47 (s, 3H, CH3). 13C NMR (75 MHz, CDCl3) δ = 145.3 (CAr), 141.6 (CAr),
136.8 (CAr), 136.4 (CAr), 130.5 (2CHAr), 126.9 (CHAr), 125.2 (2CHAr), 123.0 (CHAr), 122.4
(CAr), 120.2 (CHAr), 119.1 (CHAr), 117.8 (CAr), 111.6 (CHAr), 111.2 (CHAr), 21.3 (CH3). IR
(ATR, cm-1): ṽ = 3393 (w), 3109 (w), 3080 (w), 3056 (w), 3030 (w), 2917 (w), 2857 (w), 1600
(m), 1510 (s), 1450 (s), 1392 (m), 1337 (m), 1200 (m), 1085 (m), 1044 (m), 847 (m), 812 (m),
709 (s), 663 (m), 650 (m), 568 (m), 506 (m), 433 (m). MS (EI, 70 eV): m/z (%) = 264 (20),
263 [M]+ (100), 262 (15), 248 (7), 247 (6), 128 (5). HRMS (EI): Calculated for C17H13NS [M]+
263.07632 found 263.07598.
4-(o-Tolyl)-4H-thieno[3,2-b]indole (3b): Yellow oil, 77% yield. 1H NMR (250 MHz,
Chloroform-d) δ = 7.74 – 7.68 (m, 1H, CHAr), 7.34 – 7.29 (m, 2H, CHAr), 7.28 – 7.24 (m, 2H,
3
CHAr), 7.23 (d, J = 5.2 Hz, 1H, CHthiophene), 7.15 – 7.10 (m, 2H, CHAr), 7.01 – 6.95 (m, 1H,
3
CHAr), 6.70 (d, J = 5.2 Hz, 1H, CHthiophene), 1.94 (s, 3H, CH3). 13C NMR (63 MHz, CDCl3)
δ = 145.8 (CAr), 142.3 (CAr), 137.2 (CAr), 136.5 (CAr), 131.6 (CHAr), 128.6 (CHAr), 128.6 (CHAr),
127.2 (CHAr), 127.0 (CHAr), 122.9 (CHAr), 122.0 (CAr), 119.9 (CHAr), 119.0 (CHAr), 117.1 (CAr),
111.3 (CHAr), 111.2 (CHAr), 17.9 (CH3). IR (ATR, cm-1): ṽ = 3048 (w), 2917 (w), 1601 (w),
1505 (m), 1486 (m), 1451 (m), 1486 (m), 1450 (s), 1332 (m), 1082 (m), 820 (m), 734 (s), 649
(s), 431 (m). MS (EI, 70 eV): m/z (%) = 264 (21), 263 [M]+ (100), 262 (47), 230 (16), 218 (11),
217 (13), HRMS (EI): Calculated for C17H13NS [M]+ 263.07632 found 263.07591.
4-Phenyl-4H-thieno[3,2-b]indole (3c): Yellow oil, 83% yield. 1H NMR (300 MHz,
Chloroform-d) δ = 7.86 – 7.79 (m, 1H, CHAr), 7.66 – 7.54 (m, 5H, CHAr), 7.45 – 7.39 (m, 1H,
3
3
CHAr), 7.38 (d, J = 5.2 Hz, 1H, CHthiophene), 7.34 – 7.21 (m, 2H, CHAr), 7.12 (d, J = 5.2 Hz,
1H, CHthiophene). 13C NMR (75 MHz, CDCl3) δ = 145.1 (CAr), 141.4 (CAr), 139.0 (CAr), 129.9
(2CHPh), 127.0 (CHAr), 126.9 (CHAr), 125.2 (2CHPh), 123.2 (CHAr), 122.5 (CAr), 120.4 (CHAr),
119.1 (CHAr), 118.1 (CAr), 111.6 (CHAr), 111.2 (CHAr). IR (ATR, cm-1): ṽ = 3083 (w), 3050 (w),
1594 (m), 1505 (s), 1449 (s), 1392 (m), 1337 (m), 1201 (m), 1086 (m), 839 (m), 779 (m), 737
(s), 696 (s), 653 (s), 430 (m). MS (EI, 70 eV): m/z (%) = 249 [M]+ (100), 217 (6), 204 (9), 172
(5), 128 (8), 77 (9), 51 (13). HRMS (EI): Calculated for C16H11NS [M]+ 249.06067 found
249.06073.
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European Journal of Organic Chemistry
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4-(3,5-Dimethylphenyl)-4H-thieno[3,2-b]indole (3d): Yellow solid, mp. 112 – 113 °C,
1
90% yield. H NMR (250 MHz, Chloroform-d) δ = 7.73 – 7.67 (m, 1H, CHAr), 7.51 – 7.44 (m,
3
1H, CHAr), 7.27 (d, J = 5.2 Hz, 1H, CHthiophene), 7.22 – 7.09 (m, 4H, CHAr), 7.01 (d,
3J = 5.2 Hz, 1H, CHthiophene), 6.95 (s, 1H, CHAr), 2.33 (s, 6H, CH3). 13C NMR (63 MHz, CDCl3)
δ = 145.2 (CAr), 141.4 (CAr), 139.7 (2CAr), 138.8 (CAr), 128.6 (CHAr), 126.8 (CHAr), 123.0
(CHAr), 122.9 (2CHAr), 122.4 (CAr), 120.2 (CHAr), 119.1 (CHAr), 117.8 (CAr), 111.8 (CHAr),
111.3 (CHAr), 21.5 (2CH3). IR (ATR, cm-1): ṽ = 3051 (w), 3006 (w), 2956 (m), 2915 (m), 2851
(w), 1731 (m), 1594 (m), 1504 (m), 1449 (m), 1343 (m), 1173 (m), 1090 (m), 839 (m), 815
(m), 738 (s), 701 (m), 568 (s). MS (EI, 70 eV): m/z (%) = 278 (21), 277 (100), 276 (7), 262
(8), 260 (7), 228 (5), 77 (5). HRMS (EI): Calculated for C18H15NS [M]+ 277.09197 found
277.09166.
4-(2,3-Dihydro-1H-inden-5-yl)-4H-thieno[3,2-b]indole (3e): Yellow solid, mp. 81 – 82 °C,
1
90% yield. H NMR (250 MHz, Chloroform-d) δ = 7.74 – 7.68 (m, 1H, CHAr), 7.49 – 7.42 (m,
1H, CHAr), 7.37 – 7.20 (m, 4H, CHAr), 7.15 (m, 2H, CHAr), 7.00 (d, 3J = 5.2 Hz, 1H, CHthiophene),
3
3
2.92 (t, J = 7.4 Hz, 4H, CH2), 2.10 (p, J = 7.5 Hz, 2H, CH2). 13C NMR (63 MHz, CDCl3)
δ = 146.2 (CAr), 145.4 (CAr), 143.1 (CAr), 141.7 (CAr), 137.1 (CAr), 126.8 (CHAr), 125.4 (CHAr),
123.3 (CHAr), 123.0 (CHAr), 122.3 (CAr), 121.4 (CHAr), 120.1 (CHAr), 119.0 (CHAr), 117.6 (CAr),
111.7 (CHAr), 111.3 (CHAr), 33.2 (CH2), 32.7 (CH2), 25.8 (CH2). IR (ATR, cm-1): ṽ = 2933 (w),
2837 (w), 1606 (w), 1505 (m), 1486 (m), 1451 (m), 1344 (m), 1099 (m), 820 (m), 736 (s), 648
(s), 426 (m). MS (EI, 70 eV): m/z (%) = 289 [M]+ (100), 255 (5), 172 (12), 115 (10). HRMS
(EI): Calculated for C19H15NS [M]+ 289.09197 found 289.09201.
4-(4-(Methylthio)phenyl)-4H-thieno[3,2-b]indole (3f): White solid, mp. 91 – 92 °C, 1H NMR
(250 MHz, Chloroform-d) δ = 7.69 – 7.63 (m, 1H, CHAr), 7.41 – 7.27 (m, 5H, CHAr), 7.21 (d,
3
3J = 5.2 Hz, 1H, CHthiophene), 7.15 – 7.08 (m, 2H, CHAr), 6.92 (d, J = 5.2 Hz, 1H, CHthiophene),
2.41 (s, 3H, SCH3). 13C NMR (63 MHz, CDCl3) δ = 145.0 (CAr), 141.3 (CAr), 137.1 (CAr), 136.1
(CAr), 127.9 (2CHAr), 127.1 (CHAr), 125.6 (2CHAr), 123.1 (CHAr), 122.5 (CAr), 120.4 (CHAr),
119.1 (CHAr), 118.0 (CAr), 111.4 (CHAr), 111.0 (CHAr), 16.2 (SCH3). IR (ATR, cm-1): ṽ = 3381
(w), 3095 (w), 3082 (w), 3046 (w), 2917 (w), 1591 (w), 1505 (s), 1491 (s), 1450 (s), 1393 (m),
1339 (m), 1294 (m), 1094 (m), 1044 (m), 1012 (m), 814 (s), 750 (s), 709 (m), 662 (s), 506
(m). MS (EI, 70 eV): m/z (%) = 295 [M]+ (100), 280 (68), 247 (22), 148 (10). HRMS (EI):
Calculated for C17H13NS2 295.04839 found 295.04844.
4-(4-Methoxyphenyl)-4H-thieno[3,2-b]indole (3g): White solid, mp. 124 – 125 °C,
1
91% yield. H NMR (250 MHz, Chloroform-d) δ = 7.77 – 7.65 (m, 1H, CHAr), 7.46 – 7.34 (m,
3H, CHAr), 7.27 (d, 3J = 5.2 Hz, 1H, CHthiophene), 7.22 – 7.08 (m, 2H, CHAr), 6.99 (m, 2H, CHAr),
6.95 (d, 3J = 5.2 Hz, 1H, CHthiophene), 3.82 (s, 3H, OCH3). 13C NMR (63 MHz, CDCl3) δ = 158.5
(CAr), 145.6 (CAr), 141.9 (CAr), 131.8 (CAr), 126.9 (CHAr), 126.8 (2CHAr), 123.0 (CHAr), 122.2
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European Journal of Organic Chemistry
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(CAr), 120.1 (CHAr), 119.1 (CHAr), 117.5 (CAr), 115.1 (2CHAr), 111.4 (CHAr), 111.0 (CHAr), 55.7
(OCH3). IR (ATR, cm-1): ṽ = 3140 (w), 3097 (w), 3082 (w), 2838 (w), 1510 (m), 1243 (m),
1024 (m), 824 (m), 754 (s), 713 (m). MS (EI, 70 eV): m/z (%) = 279 [M]+ (100), 264 (45), 236
(15), 191 (9), 140 (8). HRMS (EI): Calculated for C17H13ONS [M]+ 279.07124 found
279.07129.
1
4-(3-Methoxyphenyl)-4H-thieno[3,2-b]indole (3h): Yellow oil, 92% yield. H NMR (300
MHz, Chloroform-d) δ = 7.73 – 7.67 (m, 1H, CHAr), 7.54 – 7.48 (m, 1H, CHAr), 7.36 (t, 3J = 8.1
Hz, 1H, CHAr), 7.26 (d, 3J = 5.2 Hz, 1H, CHthiophene), 7.22 – 7.12 (m, 2H, CHAr), 7.12 – 7.06 (m,
3
4
5
1H, CHAr), 7.06 – 7.00 (m, 2H, CHAr), 6.84 (ddd, J = 8.4 Hz, J = 2.5 Hz, J = 0.9 Hz, 1H,
CHAr), 3.76 (s, 3H, OCH3). 13C NMR (75 MHz, CDCl3) δ = 160.8 (CAr), 145.0 (CAr), 141.3
(CAr), 140.1 (CAr), 130.6 (CHAr), 127.0 (CHAr), 123.2 (CHAr), 122.6 (CAr), 120.4 (CHAr), 119.1
(CHAr), 118.2 (CAr), 117.4 (CHAr), 112.5 (CHAr), 111.7 (CHAr), 111.3 (CHAr), 111.0 (CHAr), 55.6
(OCH3). IR (ATR, cm-1): ṽ = 3392 (w), 3084 (w), 3051 (w), 3000 (w), 2956 (w), 2833 (w),
1589 (s), 1505 (s), 1489 (s), 1450 (s), 1391 (m), 1340 (m), 1313 (m), 1278 (m), 1252 (m),
1233 (m), 1193 (m), 1160 (m), 1086 (m), 1036 (m), 821 (m), 777 (m), 738 (s), 695 (s), 656
(s), 431 (m). MS (EI, 70 eV): m/z (%) = 279 (100), 236 (23), 204 (5), 191 (8), 139 (9). HRMS
(EI): Calculated for C17H13ONS [M]+ 279.07124 found 279.07131.
4-(2-Methoxyphenyl)-4H-thieno[3,2-b]indole (3i): Yellow oil, 87% yield. 1H NMR (300 MHz,
Chloroform-d) δ = 7.81 – 7.76 (m, 1H, CHAr), 7.50 – 7.41 (m, 2H, CHAr), 7.32 (d, 3J = 5.2 Hz,
3
1H, CHthiophene), 7.25 – 7.18 (m, 3H, CHAr), 7.18 – 7.08 (m, 2H, CHAr), 6.88 (d, J = 5.2 Hz,
13
1H, CHthiophene), 3.77 (s, 3H, OCH3). C NMR (75 MHz, CDCl3) δ = 155.1 (CAr), 145.8 (CAr),
142.2 (CAr), 129.1 (CHAr), 128.7 (CHAr), 127.2 (CAr), 126.5 (CHAr), 122.8 (CHAr), 122.3 (CAr),
121.2 (CHAr), 119.9 (CHAr), 118.9 (CHAr), 117.4 (CAr), 112.8 (CHAr), 112.1 (CHAr), 111.7
(CHAr), 55.8 (OCH3). IR (ATR, cm-1): ṽ = 3396 (w), 3048 (w), 3006 (w), 2958 (w), 2930 (w),
2835 (w), 1594 (m), 1509 (s), 1449 (s), 1393 (m), 1337 (m), 1273 (m), 1243 (m), 1118 (m),
1083 (m), 1021 (m), 702 (m), 654 (m), 430 (m). MS (EI, 70 eV): m/z (%) = 279 (100), 263
(20), 236 (11), 204 (5), 191 (7), 139 (8). HRMS (EI): Calculated for C17H13ONS [M]+
279.07124 found 279.07092.
1
4-(3,5-Dimethoxyphenyl)-4H-thieno[3,2-b]indole (3j): Yellow oil, 92% yield. H NMR (300
MHz, Chloroform-d) δ = 7.74 – 7.66 (m, 1H, CHAr), 7.59 – 7.52 (m, 1H, CHAr), 7.28 (d,
3
3J = 5.2 Hz, 1H, CHthiophene), 7.24 – 7.11 (m, 2H, CHAr), 7.07 (d, J = 5.2 Hz, 1H, CHthiophene),
4
6.67 (d, 4J = 2.3 Hz, 2H, CHAr), 6.42 (t, J = 2.3 Hz, 1H, CHAr), 3.76 (s, 6H, OCH3). 13C NMR
(75 MHz, CDCl3) δ = 160.8 (2CArOCH3), 143.9 (CAr), 140.3 (CAr), 139.6 (CAr), 126.0 (CHAr),
122.2 (CHAr), 121.6 (CAr), 119.5 (CHAr), 118.1 (CHAr), 117.2 (CAr), 110.9 (CHAr), 110.5 (CHAr),
102.5 (2CHAr), 98.0 (CHAr), 54.7 (2OCH3). IR (ATR, cm-1): ṽ = 3084 (w), 3050 (w), 2959 (w),
2930 (w), 2837 (w), 1590 (s), 1505 (m), 1477 (m), 1449 (s), 1362 (m), 1285 (m), 1267 (m),
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European Journal of Organic Chemistry
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1202 (m), 1150 (s), 1062 (m), 1037 (m), 813 (m), 737 (s). MS (EI, 70 eV): m/z (%) = 310
(20), 309 [M]+ (100), 266 (12), 251 (13), 234 (5). HRMS (EI): Calculated for C18H15O2NS [M]+
309.08180 found 309.08198.
4-(2,4-Dimethoxyphenyl)-4H-thieno[3,2-b]indole (3k): Colorless solid, mp. 165 – 166 °C,
89% yield. 1H NMR (250 MHz, Chloroform-d) δ = 7.83 – 7.76 (m, 1H, CHAr), 7.36 (d, 3J = 8.6
3
Hz, 1H, CHAr), 7.32 (d, J = 5.2 Hz, 1H, CHthiophene), 7.25 – 7.16 (m, 3H, CHAr), 6.87 (d,
3J = 5.2 Hz, 1H, CHthiophene), 6.71 (d, 4J = 2.6 Hz, 1H, CHAr), 6.63 (dd, 3J = 8.6 Hz, 4J = 2.6 Hz,
1H, CHAr), 3.91 (s, 3H, OCH3), 3.73 (s, 3H, OCH3). 13C NMR (63 MHz, CDCl3) δ = 160.5
(CAr), 156.3 (CAr), 146.2 (CAr), 142.5 (CAr), 129.4 (CHAr), 126.4 (CHAr), 122.7 (CHAr), 122.1
(CAr), 120.2 (CAr), 119.7 (CHAr), 118.9 (CHAr), 116.9 (CAr), 111.9 (CHAr), 111.5 (CHAr), 104.8
(CHAr), 100.2 (CHAr), 55.8 (OCH3), 55.8 (OCH3). IR (ATR, cm-1): ṽ = 3087 (w), 3045 (w), 3005
(w), 2965 (w), 2931 (w), 2835 (w), 1611 (m), 1584 (m), 1518 (s), 1451 (s), 1305 (m), 1204
(s), 1158 (s), 1050 (m), 1022 (m), 928 (w), 827 (m), 740 (s), 651 (m), 581 (m). MS
(EI, 70 eV): m/z (%) = 309 (100), 294 (19), 251 (12), 223 (8). HRMS (EI): Calculated for
C18H15O2NS [M]+ 309.08180 found 309.08151.
4-(3,4,5-Trimethoxyphenyl)-4H-thieno[3,2-b]indole (3l): White solid, mp. 94 – 95 °C,
1
92% yield. H NMR (250 MHz, Chloroform-d) δ = 7.75 – 7.67 (m, 1H, CHAr), 7.52 – 7.46 (m,
3
3
1H, CHAr), 7.30 (d, J = 5.2 Hz, 1H, CHthiophene), 7.26 – 7.10 (m, 2H, CHAr), 7.02 (d, J = 5.2
Hz, 1H, CHthiophene), 6.72 (s, 2H, CHAr), 3.87 (s, 3H, OCH3), 3.80 (s, 6H, OCH3). 13C NMR (63
MHz, CDCl3) δ = 154.1 (2CArOCH3), 145.2 (CAr), 141.6 (CAr), 137.0 (CAr), 134.7 (CAr), 127.1
(CHAr), 123.2 (CHAr), 122.4 (CAr), 120.4 (CHAr), 119.2 (CHAr), 117.9 (CAr), 111.6 (CHAr), 111.2
(CHAr), 103.0 (2CHAr), 61.2 (OCH3), 56.5 (2OCH3). IR (ATR, cm-1): ṽ = 3082 (w), 3051 (w),
2926 (m), 2824 (w), 1593 (m), 1505 (m), 1450 (m), 1415 (m), 1289 (m), 1226 (m), 1124 (s),
1007 (m), 818 (m), 740 (m), 655 (m). MS (EI, 70 eV): m/z (%) = 339 (100), 324 (75), 296
(10), 266 (9), 210 (9), 172 (13), 154 (8). HRMS (EI): Calculated for C19H17O3NS [M]+
339.09237 found 339.09217.
1
4-(4-(tert-Butyl)phenyl)-4H-thieno[3,2-b]indole (3m): Yellow oil, 92% yield. H NMR (250
MHz, Chloroform-d) δ = 7.75 – 7.67 (m, 1H, CHAr), 7.52 – 7.39 (m, 5H, CHAr), 7.26 (d,
3
3J = 5.2 Hz, 1H, CHthiophene), 7.20 – 7.12 (m, 2H, CHAr), 7.02 (d, J = 5.2 Hz, 1H, CHthiophene),
13
1.32 (s, 9H, tBu). C NMR (63 MHz, CDCl3) δ = 149.9 (CAr), 145.2 (CAr), 141.5 (CAr), 136.3
(CAr), 126.9 (CHAr), 126.7 (2CHAr), 124.7 (2CHAr), 123.0 (CHAr), 122.4 (CAr), 120.2 (CHAr),
119.1 (CHAr), 117.8 (CAr), 111.7 (CHAr), 111.3 (CHAr), 34.9 (CtBu), 31.6 (3CH3). IR (ATR, cm-1):
ṽ = 3049 (w), 2959 (m), 2901 (w), 2865 (w), 1602 (w), 1519 (s), 1451 (s), 1394 (m), 1337
(m), 1267 (m), 1205 (m), 1112 (m), 1086 (m), 1046 (m), 1016 (m), 922 (w), 825 (m), 705 (m),
648 (m), 552 (m). MS (EI, 70 eV): m/z (%) = 305 (100), 290 (95), 275 (16), 262 (11), 172
(17), 131 (11). HRMS (EI): Calculated for C20H19NS [M]+ 305.12327 found 305.12374.
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European Journal of Organic Chemistry
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4-(Naphthalen-1-yl)-4H-thieno[3,2-b]indole (3n): Colorless solid, mp. 141 – 142 °C,
1
78% yield. H NMR (300 MHz, Acetone-d6) δ = 8.19 – 8.09 (m, 2H, CHAr), 7.92 – 7.87 (m,
3
3
4
1H, CHAr), 7.79 – 7.70 (m, 2H, CHAr), 7.61 (ddd, J = 8.2 Hz, J = 6.8 Hz, J = 1.3 Hz, 1H,
3
3
3
4
CHAr), 7.54 (d, J = 5.2 Hz, 1H, CHthiophene), 7.45 (ddd, J = 8.2 Hz, J = 6.8 Hz, J = 1.3 Hz,
1H, CHAr), 7.32 – 7.27 (m, 1H, CHAr), 7.27 – 7.16 (m, 2H, CHAr), 7.06 – 6.99 (m, 1H, CHAr),
3
6.79 (d, J = 5.2 Hz, 1H, CHthiophene). 13C NMR (75 MHz, Acetone-d6) δ = 147.6 (CAr), 144.0
(CAr), 135.8 (CAr), 135.6 (CAr), 131.2 (CAr), 129.8 (CHAr), 129.5 (CHAr), 128.4 (CHAr), 128.0
(CHAr), 127.7 (CHAr), 126.9 (CHAr), 126.7 (CHAr), 123.9 (CHAr), 123.8 (CHAr), 123.0 (CAr),
121.1 (CHAr), 119.7 (CHAr), 117.9 (CAr), 112.3 (CHAr), 112.1 (CHAr). IR (ATR, cm-1): ṽ = 3047
(m), 1592 (w), 1575 (w), 1504 (m), 1448 (m), 1401 (m), 1327 (m), 1211 (m), 1110 (m), 1076
(m), 1914 (m), 800 (m), 773 (m), 735 (s), 657 (m). MS (EI, 70 eV): m/z (%) = 299 (100), 265
(18), 149 (8), 127 (7). HRMS (EI): Calculated for C20H13NS [M]+ 299.07632 found 299.07610.
4-(Anthracen-2-yl)-4H-thieno[3,2-b]indole (3o): Yellow solid, mp. 176 – 177 °C, 72% yield.
1H NMR (250 MHz, Chloroform-d) δ = 8.53 (s, 1H, CHAr), 8.47 (s, 1H, CHAr), 8.25 – 8.14 (m,
2H, CHAr), 8.05 (m, 2H, CHAr), 7.90 – 7.78 (m, 1H, CHAr), 7.78 – 7.65 (m, 2H, CHAr), 7.59 –
7.47 (m, 2H, CHAr), 7.42 (d, 3J = 5.2 Hz, 1H, CHthiophene), 7.37 – 7.18 (m, 3H, CHAr). 13C NMR
(63 MHz, CDCl3) δ = 145.2 (CAr), 141.5 (CAr), 135.7 (CAr), 132.3 (CAr), 131.9 (CAr), 131.7
(CAr), 130.2 (CHAr), 130.1 (CAr), 128.3 (CHAr), 128.0 (CHAr), 127.0 (CHAr), 126.5 (CHAr), 126.1
(CHAr), 126.0 (CHAr), 125.7 (CHAr), 123.7 (CHAr), 123.1 (CHAr), 122.6 (CAr), 122.3 (CHAr),
120.5 (CHAr), 119.1 (CHAr), 118.3 (CAr), 111.8 (CHAr), 111.4 (CHAr). IR (ATR, cm-1): ṽ = 3049
(w), 2954 (w), 1670 (w), 1592 (w), 1504 (m), 1450 (m), 1321 (m), 887 (m), 738 (s), 652 (m),
603 (m), 469 (m), 429 (m). MS (EI, 70 eV): m/z (%) = 349 (100), 315 (4), 176 (7). HRMS (EI):
Calculated for C24H15NS [M]+ 349.09197 found 349.09165.
4-(4-Fluorophenyl)-4H-thieno[3,2-b]indole (3p): White solid, mp. 117 – 118 °C, 91% yield.
1H NMR (300 MHz, Chloroform-d) δ = 7.75 – 7.68 (m, 1H, CHAr), 7.50 – 7.41 (m, 2H, CHAr),
3
7.40 – 7.36 (m, 1H, CHAr), 7.28 (d, J = 5.2 Hz, 1H, CHthiophene), 7.23 – 7.11 (m, 4H, CHAr),
6.95 (d, 3J = 5.2 Hz, 1H, CHthiophene). 19F NMR (282 MHz, CDCl3) δ = -114.59 (FCAr). 13C NMR
1
(75 MHz, CDCl3) δ = 161.2 (d, JC-F = 246.7 Hz, CFAr), 145.2 (CAr), 141.6 (CAr), 134.6 (d,
3
4JC-F = 3.1 Hz, CAr), 127.1 (CHAr), 127.0 (d, JC-F = 8.5 Hz, 2CHAr), 123.2 (CHAr), 122.3 (CAr),
120.4 (CHAr), 119.1 (CHAr), 118.0 (CAr), 116.7 (d, 2JC-F = 22.8 Hz, 2CHAr), 111.2 (CHAr), 110.9
(CHAr). IR (ATR, cm-1): ṽ = 3106 (w), 3093 (w), 3050 (w), 1600 (w), 1510 (s), 1451 (m), 1340
(m), 1218 (m), 1090 (m), 826 (m), 740 (s), 708 (m), 571 (m), 515 (m). MS (EI, 70 eV):
m/z (%) = 267 (100), 235 (9), 222 (9), 128 (5), 75 (10). HRMS (EI): Calculated for C16H10NFS
[M]+ 267.05125 found 267.05098.
4-(4-Chlorophenyl)-4H-thieno[3,2-b]indole (3q): Colorless solid, mp. 114 – 115 °C,
1
86% yield. H NMR (250 MHz, Chloroform-d) δ = 7.76 – 7.69 (m, 1H, CHAr), 7.46 (m, 5H,
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European Journal of Organic Chemistry
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3
3
CHAr), 7.31 (d, J = 5.2 Hz, 1H, CHthiophene), 7.25 – 7.13 (m, 2H, CHAr), 6.99 (d, J = 5.2 Hz,
1H, CHthiophene). 13C NMR (63 MHz, CDCl3) δ = 144.8 (CAr), 141.2 (CAr), 137.6 (CAr), 132.4
(CAr), 130.1 (2CHAr), 127.3 (CHAr), 126.4 (2CHAr), 123.4 (CHAr), 122.6 (CAr), 120.7 (CHAr),
119.3 (CHAr), 118.5 (CAr), 111.3 (CHAr), 110.9 (CHAr). IR (ATR, cm-1): ṽ = 3099 (w), 3084 (w),
3050 (w), 2959 (w), 2920 (w), 2848 (w), 1592 (w), 1505 (s), 1488 (m), 1452 (m), 1390 (m),
1356 (w), 1338 (m), 1204 (m), 1088 (s), 1012 (m), 823 (s), 748 (s), 708 (s), 661 (m), 646 (m),
509 (m), 479 (m), 431 (w). MS (EI, 70 eV): m/z (%) = 285 (32), 283 (100), 247 (12), 128 (10),
75 (18). HRMS (EI): Calculated for C16H10NClS 283.02170 found 283.02225, calculated for
C16H10N37ClS [M]+ 285.01875 found 285.01936.
4-Benzyl-4H-thieno[3,2-b]indole (3r): Yellow oil, 81% yield. 1H NMR (250 MHz,
3
4
5
Chloroform-d) δ = 7.69 (ddd, J = 7.6 Hz, J = 1.5 Hz, J = 0.7 Hz, 1H, CHAr), 7.25 (dd,
5
3
4J = 1.4 Hz, J = 0.8 Hz, 1H, CHAr), 7.23 (d, J = 5.2 Hz, 1H, CHthiophene), 7.21 – 7.11 (m, 5H,
CHAr), 7.11 – 7.03 (m, 2H, CHAr), 6.84 (d, 3J = 5.2 Hz, 1H, CHthiophene), 5.36 (s, 2Haliphatic, CH2).
13C NMR (63 MHz, CDCl3) δ = 145.6 (CAr), 141.7 (CAr), 137.3 (CAr), 128.9 (2CHAr), 127.7
(CHAr), 127.0 (CHAr), 126.8 (2CHAr), 122.7 (CHAr), 122.1 (CAr), 119.5 (CHAr), 119.1 (CHAr),
116.7 (CAr), 110.7 (CHAr), 110.3 (CHAr), 48.9 (CH2). IR (ATR, cm-1): ṽ = 3422 (w), 3081 (w),
3054 (w), 3025 (w), 2921 (w), 2852 (w), 1733 (w), 1583 (w), 1507 (m), 1463 (m), 1349 (m),
1161 (m), 736 (s), 695 (m), 654 (s), 430 (m). MS (EI, 70 eV): m/z (%) = 264 (15), 263 [M]+
(71), 172 (27), 128 (13), 91 (100), 65 (17). HRMS (EI): Calculated for C17H13NS [M]+
263.07632 found 263.07642.
1
4-(4-methoxybenzyl)-4H-thieno[3,2-b]indole (3s): Colorless oil, 95% yield. H NMR (250
MHz, Chloroform-d) δ = 7.68 (m, 1H, CHAr), 7.28 (d, 3J = 8.3, 1H, CHAr), 7.22 (d, 3J = 5.2 Hz,
3
1H, CHthiophene), 7.20 – 7.12 (m, 1H, CHAr), 7.12 – 7.04 (m, 1H, CHAr), 7.00 (d, J = 8.6 Hz,
3
3
2H, CHAr), 6.82 (d, J = 5.2 Hz, 1H, CHthiophene), 6.70 (d, J = 8.6 Hz, 2H, CHAr), 5.28 (s,
2Haliphatic, CH2), 3.65 (s, 3H, OCH3). 13C NMR (63 MHz, CDCl3) δ = 159.2 (CAr), 145.5 (CAr),
141.7 (CAr), 129.4 (CAr), 128.2 (2CHAr), 126.9 (CHAr), 122.7 (CHAr), 122.1 (CAr), 119.4 (CHAr),
119.1 (CHAr), 116.6 (CAr), 114.3 (2CHAr), 110.7 (CHAr), 110.3 (CHAr), 55.4 (OCH3), 48.4 (CH2).
IR (ATR, cm-1): ṽ = 3105 (w), 3051 (w), 3024 (w), 2997 (m), 2955 (m), 2915 (w), 2832 (m),
1613 (m), 1584 (m), 1508 (s), 1457 (s), 1439 (m), 1348 (m), 1245 (s), 1161 (s), 1025 (m),
807 (s), 735 (s), 653 (s), 430 (m). MS (EI, 70 eV): m/z (%) = 294 (6), 293 [M]+ (28), 121
(100), 78 (10). HRMS (EI): Calculated for C18H15ONS [M]+ 293.08689 found 293.08643.
4-Pentyl-4H-thieno[3,2-b]indole (3t): Yellow oil, 75% yield. 1H NMR (250 MHz,
Chloroform-d) δ = 7.76 (ddd, 3J = 7.8 Hz, 4J = 1.3 Hz, 5J = 0.7 Hz, 1H, CHAr), 7.43 – 7.35 (m,
3
3
4
2H, CHAr), 7.34 – 7.26 (m, 1H, CHAr), 7.17 (ddd, J = 8.1 Hz, J = 7.0 Hz, J = 1.2 Hz, 1H,
3
3
CHAr), 7.08 (d, J = 5.2 Hz, 1H, CHthiophene), 4.27 (t, J = 7.1 Hz, 2Haliphatic, CH2), 2.00 – 1.74
(m, 2Haliphatic, CH2), 1.34 (m, 4Haliphatic, 2CH2), 0.98 – 0.80 (m, 3Haliphatic, CH3). 13C NMR (63
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European Journal of Organic Chemistry
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MHz, CDCl3) δ = 145.5 (CAr), 141.4 (CAr), 126.8 (CHAr), 122.4 (CHAr), 121.9 (CAr), 119.1
(CHAr), 119.0 (CHAr), 116.0 (CAr), 110.5 (CHAr), 110.0 (CHAr), 45.4 (CH2, pentyl), 29.6 (CH2,
pentyl), 29.4 (CH2, pentyl), 22.5 (CH2, pentyl), 14.1 (CH3, pentyl). IR (ATR, cm-1): ṽ = 3081
(w), 3052 (w), 2954 (m), 2927 (m), 2856 (m), 1610 (w), 1509 (m), 1123 (m), 1348 (m), 1317
(m), 1162 (m), 1079 (m), 1017 (w), 815 (w), 735 (s), 653 (m), 431 (m). MS (EI, 70 eV):
m/z (%) = 243 [M]+ (30), 186 (100), 115 (12). HRMS (EI): Calculated for C15H17NS [M]+
243.10762 found 243.10811.
General procedure for the synthesis of thieno[3,4-b]indoles
3-Bromo-2-(2-bromophenyl)thiophene (0.15 mmol), amine (0.225 mmol), Pd2dba3 (0.0075
mmol), PtBu3∙HBF4 (0.015 mmol) and NaOtBu (0.36 mmol) were added to a dried glass
pressure tube. The tube was evacuated and backfilled three times with argon. 2 ml of dried
toluene was added. The mixture was heated to 100 °C for 14h until the reaction completed
(monitored by TLC). After cooling to room temperature, the solvent was removed under
reduced pressure. The crude oil was subjected to column chromatography (heptane/ethyl
acetate) to obtain the pure product.
4-(p-Tolyl)-4H-thieno[3,4-b]indole (6a): Yellow oil, 95% yield. 1H NMR (250 MHz,
3
4
Chloroform-d) δ = 7.86 (dt, J = 7.6 Hz, J = 1.0 Hz, 1H, CHAr), 7.54 (m, 1H, CHAr), 7.50 (s,
1H, CHAr), 7.49 (s, 1H, CHAr), 7.31 – 7.21 (m, 4H, CHAr), 7.14 (ddd, 3J = 7.6 Hz, 3J = 6.6 Hz,
4J = 1.7 Hz, 1H, CHAr), 6.59 (m, 1H, CHAr), 2.36 (s, 3H, CH3). 13C NMR (63 MHz, CDCl3)
δ = 148.1 (CAr), 146.3 (CAr), 136.8 (CAr), 136.1 (CAr), 133.5 (CAr), 130.5 (2CHAr), 126.5 (CHAr),
124.4 (2CHAr), 121.5 (CHAr), 120.3 (CAr), 119.8 (CHAr), 110.6 (CHAr), 109.9 (CHAr), 92.6
(CHAr), 21.3 (CH3). IR (ATR, cm-1): ṽ = 3399 (w), 3101 (w), 3030 (w), 2917 (w), 2859 (w),
1608 (w), 1576 (m), 1512 (s), 1449 (m), 1397 (m), 1321 (m), 1223 (m), 1152 (m), 1108 (w),
1020 (w), 928 (w), 816 (m), 740 (s), 619 (m), 499 (m). MS (EI, 70 eV): m/z (%) = 263 (100),
247 (8), 218 (12), 128 (7). HRMS (EI): Calculated for C17H13NS [M]+ 263.07632 found
263.07634.
4-(o-Tolyl)-4H-thieno[3,4-b]indole (6b): Yellow oil, 65% yield. 1H NMR (300 MHz,
4
Acetone-d6) δ = 8.02 – 7.92 (m, 2H, CHAr), 7.89 – 7.79 (m, 1H, CHAr), 7.79 (d, J = 2.5 Hz,
1H, CHthiophene), 7.58 (d, 3J = 8.2 Hz, 1H, CHAr), 7.48 – 7.32 (m, 2H, CHAr), 7.16 (m, 1H, CHAr),
3
4
6.93 (d, J = 8.2 Hz, 1H, CHAr), 6.51 (d, J = 2.5 Hz, 1H, CHthiophene), 2.22 (s, 3H, CH3).
13C NMR (75 MHz, Acetone-d6) δ = 149.9 (CAr), 147.5 (CAr), 141.0 (CAr), 137.8 (CAr), 134.1
(CAr), 131.2 (CHAr), 129.5 (CHAr), 127.5 (CHAr), 126.9 (CHAr), 122.3 (CHAr), 121.3 (CHAr),
120.8 (CAr), 120.4 (CHAr), 112.0 (CHAr), 110.5 (CHAr), 93.2 (CHAr), 18.2 (CH3). IR (ATR, cm-1):
ṽ = 3412 (w), 3103 (w), 3052 (w), 2919 (w), 2853 (w), 1577 (m), 1499 (m), 1450 (m), 1395
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European Journal of Organic Chemistry
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(m), 1316 (m), 1227 (m), 1151 (m), 824 (m), 741 (s), 622 (m), 445 (m). MS (EI, 70 eV):
m/z (%) = 264 (21), 263 [M]+ (100), 262 (41), 260 (11), 231 (16), 228 (11), 218 (20), 217 (32),
216 (11), 204 (15), 128 (17). HRMS (EI): Calculated for C17H13NS [M]+ 263.07632 found
263.07567.
1
4-(4-(tert-Butyl)phenyl)-4H-thieno[3,4-b]indole (6c): Yellow oil, 83% yield. H NMR (250
MHz, Chloroform-d) δ = 7.78 (m, 1H, CHAr), 7.48 (m, 4H, CHAr), 7.41 (s, 1HAr), 7.33 (ddd,
3J = 8.3 Hz, 4J = 1.2 Hz, 5J = 0.7 Hz, 1H, CHAr), 7.25 (dd, 3J = 7.1 Hz, 4J = 1.3 Hz, 1H, CHAr),
13
7.18 (s, 1H, CHAr), 7.09 – 7.02 (m, 1H, CHAr), 1.33 (s, 9H, tBu). C NMR (63 MHz, CDCl3)
δ = 149.2 (CAr), 148.1 (CAr), 146.2 (CAr), 136.8 (CAr), 133.5 (CAr), 126.8 (2CHAr), 126.5 (CHAr),
123.9 (2CHAr), 121.5 (CHAr), 120.4 (CAr), 119.8 (CHAr), 110.5 (CHAr), 110.0 (CHAr), 92.7
(CHAr), 34.8 (CtBu), 31.6 (3CH3). IR (ATR, cm-1): ṽ = 3401 (w), 3053 (w), 2958 (m), 2865 (w),
1605 (w), 1578 (m), 1517 (s), 1451 (m), 1399 (m), 1323 (m), 1224 (m), 1190 (m), 1152 (m),
1017 (w), 827 (m), 742 (s), 622 (m), 552 (m). MS (EI, 70 eV): m/z (%) = 305 [M]+ (97), 290
(100), 275 (18), 262 (8), 172 (20), 131 (40), 109 (9). HRMS (EI): Calculated for C20H19NS
[M]+ 305.12327 found 305.12400.
1
4-(3,5-Dimethoxyphenyl)-4H-thieno[3,4-b]indole (6d): Yellow oil, 85% yield. H NMR (300
3
MHz, Chloroform-d) δ = 7.85 (m, 1H, CHAr), 7.52 – 7.45 (m, 2H, CHAr), 7.33 (ddd, J = 8.4
3
Hz, 3J = 7.3 Hz, 4J = 1.3 Hz, 1H, CHAr), 7.15 (td, J = 7.3 Hz, 4J = 1.3 Hz, 1H, CHAr), 6.81 (d,
4
4
4J = 2.3 Hz, 2H, CHAr), 6.68 (d, J = 2.5 Hz, 1H, CHthiophene), 6.45 (t, J = 2.3 Hz, 1H, CHAr),
3.85 (s, 6H, OCH3). 13C NMR (75 MHz, CDCl3) δ = 161.9 (2CAr), 147.7 (CAr), 145.8 (CAr),
141.2 (CAr), 133.5 (CAr), 126.6 (CHAr), 121.5 (CHAr), 120.6 (CAr), 120.1 (CHAr), 110.8 (CHAr),
110.4 (CHAr), 102.6 (2CHAr), 98.4 (CHAr), 93.3 (CHAr), 55.7 (2OCH3). IR (ATR, cm-1): ṽ = 3388
(w), 3102 (w), 3056 (w), 2998 (w), 2929 (w), 2837 (w), 1591 (s), 1498 (m), 1451 (s), 1293
(m), 1258 (s), 1202 (s), 1149 (s), 1056 (m), 929 (m), 823 (m), 742 (s), 689 (m), 627 (m). MS
(EI, 70 eV): m/z (%) = 310 (21), 309 [M]+ (100), 294 (22), 264 (8), 251 (19), 250 (18), 234
(10), 191 (6), 178 (11), 128 (9). HRMS (EI): Calculated for C18H15O2NS [M]+ 309.08180 found
309.08182.
4-(3,4,5-Trimethoxyphenyl)-4H-thieno[3,4-b]indole (6e): Colorless solid, mp. 96 – 97 °C,
81% yield. 1H NMR (300 MHz, Chloroform-d) δ = 7.87 (ddd, 3J = 7.7 Hz, 4J = 1.3 Hz, 5J = 0.7
4
3
4
Hz, 1H, CHAr), 7.50 (d, J = 1.8 Hz, 1H, CHthiophene), 7.40 (ddd, J = 8.2 Hz, J = 1.3 Hz,
5J = 0.7 Hz, 1H, CHAr), 7.33 (ddd, 3J = 8.2 Hz, 3J = 7.0 Hz, 4J = 1.3 Hz, 1H, CHAr), 7.16 (ddd,
3
4
4
3J = 7.7 Hz, J = 7.0 Hz, J = 1.3 Hz, 1H, CHAr), 6.85 (s, 2H, CHAr), 6.61 (d, J = 2.5 Hz, 1H,
CHthiophene), 3.94 (s, 3H, CH3), 3.89 (s, 6H, CH3). 13C NMR (75 MHz, CDCl3) δ = 154.2
(2CArOCH3), 148.1 (CAr), 146.3 (CAr), 136.5 (CAr), 135.1 (CAr), 133.4 (CAr), 126.6 (CHAr), 121.6
(CHAr), 120.4 (CAr), 120.0 (CHAr), 110.9 (CHAr), 110.0 (CHAr), 102.2 (2CHAr), 92.7 (CHAr), 61.2
(OCH3), 56.5 (2OCH3). IR (ATR, cm-1): ṽ = 3101 (m), 3056 (w), 2999 (m), 2929 (m), 2829
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European Journal of Organic Chemistry
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(w), 1592 (m), 1502 (m), 1450 (m), 1416 (m), 1354 (m), 1262 (m), 1226 (m), 1123 (s), 998
(m), 823 (m), 736 (s). MS (EI, 70 eV): m/z (%) = 339 (100), 324 (78), 296 (6), 280 (8), 238
(10), 210 (8), 172 (14). HRMS (EI): Calculated for C19H17O3NS [M]+ 339.09237 found
339.09241.
4-(Anthracen-2-yl)-4H-thieno[3,4-b]indole (6f): Light yellow solid, mp. 171 – 172 °C,
78% yield. 1H NMR (250 MHz, Chloroform-d) δ = 8.50 (s, 1H, CHAr), 8.44 (s, 1H, CHAr), 8.24
– 8.13 (m, 2H, CHAr), 8.11 – 7.96 (m, 2H, CHAr), 7.91 (ddd, 3J = 7.5 Hz, 4J = 1.3 Hz, 5J = 0.7
4
Hz, 1H, CHAr), 7.79 (dd, 3J = 9.0 Hz, J = 2.1 Hz, 1H, CHAr), 7.59 – 7.44 (m, 4H, CHAr), 7.36
3
3
4
3
4
(ddd, J = 8.3 Hz, J = 7.3 Hz, J = 1.3 Hz, 1H, CHAr), 7.20 (td, J = 7.5 Hz, J = 1.0 Hz, 1H,
CHAr), 6.76 (d, 4J = 2.5 Hz, 1H, CHthiophene). 13C NMR (63 MHz, CDCl3) δ = 147.9 (CAr), 146.0
(CAr), 136.4 (CAr), 133.5 (CAr), 132.4 (CAr), 132.0 (CAr), 131.9 (CAr), 130.4 (CHAr), 130.1 (CAr),
128.4 (CHAr), 128.1 (CHAr), 126.7 (CHAr), 126.6 (CHAr), 126.1 (CHAr), 125.9 (CHAr), 125.7
(CHAr), 123.2 (CHAr), 121.6 (CHAr), 121.3 (CHAr), 120.7 (CAr), 120.3 (CHAr), 110.9 (CHAr),
110.2 (CHAr), 93.2 (CHAr). IR (ATR, cm-1): ṽ = 3093 (w), 3050 (w), 2956 (w), 1628 (w), 1573
(m), 1451 (m), 1389 (w), 1216 (w), 891 (m), 742 (s), 472 (m). MS (EI, 70 eV): m/z (%) = 349
(100), 304 (48), 174 (24), 152 (20), 128 (6). HRMS (EI): Calculated for C24H15NS [M]+
349.09197 found 349.09161.
General procedure for the synthesis of 5-substituted thieno[3,2-b]indoles
5-substituted 3-bromo-2-(2-bromophenyl)thiophene (0.15 mmol), amine (0.225 mmol),
Pd2dba3 (0.0075 mmol), SPhos (0.015 mmol) and NaOtBu (0.36 mmol) were added to a
dried glass pressure tube. The tube was evacuated and backfilled three times with argon. 2
ml of dried toluene was added. The mixture was heated to 100 °C for 14h until the reaction
completed (monitored by TLC). After cooling to room temperature, the solvent was removed
under reduced pressure. The crude oil was subjected to column chromatography
(heptane/ethyl acetate) to obtain the pure product.
2-Phenyl-4-(p-tolyl)-4H-thieno[3,2-b]indole (10a): White solid, mp. 164 – 165 °C,
1
95% yield. H NMR (300 MHz, Chloroform-d) δ = 7.75 – 7.69 (m, 1H, CHAr), 7.65 – 7.58 (m,
2H, CHAr), 7.48 – 7.40 (m, 3H, CHAr), 7.37 – 7.29 (m, 4H, CHAr), 7.25 – 7.15 (m, 4H, CHAr),
13
2.42 (s, 3H, CH3). C NMR (63 MHz, CDCl3) δ = 145.9 (CAr), 145.4 (CAr), 141.1 (CAr), 137.0
(CAr), 136.3 (CAr), 135.5 (CAr), 130.5 (2CHAr), 129.1 (2CHAr), 127.7 (CHAr), 125.8 (2CHAr),
125.3 (2CHAr), 123.1 (CHAr), 122.5 (CAr), 120.4 (CHAr), 119.0 (CHAr), 116.9 (CAr), 111.1
(CHAr), 107.6 (CHAr), 21.3 (CH3). IR (ATR, cm-1): ṽ = 3047 (m), 2916 (w), 1594 (m), 1512 (s),
1451 (s), 1421 (m), 1336 (m), 1211 (w), 1113 (w), 1068 (m), 917 (w), 827 (m), 802 (m), 755
(s), 727 (s), 689 (s), 619 (w), 574 (w). MS (EI, 70 eV): m/z (%) = 341 (8), 340 (26), 339 [M+]
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European Journal of Organic Chemistry
10.1002/ejoc.201601281
26
(100), 338 (11), 324 (8), 323 (5), 170 (8), 162 (7), 146 (10). HRMS (EI): Calculated for
C23H17NS [M]+ 339.10762 found 339.10710.
2,4-Diphenyl-4H-thieno[3,2-b]indole (10b): White solid, mp. 156 – 157 °C, 61% yield.
1H NMR (250 MHz, Chloroform-d) δ = 7.84 – 7.69 (m, 2H, CHAr), 7.68 – 7.66 (m, 1H, CHAr),
7.48 – 7.34 (m, 5H, CHAr), 7.47 – 7.35 (m, 4H, CHAr), 7.33 – 7.23 (m, 3H, CHAr). 13C NMR (63
MHz, CDCl3) δ = 146.0 (CAr), 145.2 (CAr), 141.0 (CAr), 138.9 (CAr), 135.4 (CAr), 130.0 (2CHAr),
129.1 (2CHAr), 127.8 (CHAr), 127.0 (CHAr), 125.8 (2CHAr), 125.4 (2CHAr), 123.2 (CHAr), 122.7
(CAr), 120.6 (CHAr), 119.1 (CHAr), 117.2 (CAr), 111.1 (CHAr), 107.6 (CHAr). IR (ATR, cm-1):
ṽ = 3047 (w), 2921 (w), 1593 (m), 1526 (w), 1500 (s), 1450 (s), 1421 (m), 1342 (m), 1213
(w), 1069 (w), 819 (m), 752 (s), 741 (s), 691 (s), 663 (m), 615 (w). MS (EI, 70 eV):
m/z (%) = 327 (6), 326 (24), 325 [M+] (100), 324 (22), 323 (7), 322(4), 291 (6), 146 (4).
HRMS (EI): Calculated for C22H15NS [M]+ 325.09197 found 325.09163.
4-(4-Methoxyphenyl)-2-phenyl-4H-thieno[3,2-b]indole (10c): White solid, mp. 149 –
1
150 °C, 62% yield. H NMR (250 MHz, Chloroform-d) δ = 7.80 – 7.73 (m, 1H, CHAr), 7.68 –
3
7.61 (m, 2H, CHAr), 7.48 (d, J = 8.9 Hz, 2H, CHAr), 7.43 – 7.38 (m, 1H, CHAr), 7.35 (d,
3J = 7.6 Hz, 2H, CHAr), 7.31 – 7.18 (m, 4H, CHAr), 7.07 (d, 3J = 8.9 Hz, 2H, CHAr), 3.88 (s, 3H,
OCH3). 13C NMR (63 MHz, CDCl3) δ = 158.6 (CAr), 145.9 (CAr), 145.7 (CAr), 141.5 (CAr), 135.5
(CAr), 131.6 (CAr), 129.1 (2CHAr), 127.7 (CHAr), 127.0 (2CHAr), 125.8 (2CHAr), 123.1 (CAr),
122.4 (CHAr), 120.3 (CHAr), 119.0 (CHAr), 116.6 (CAr), 115.1 (2CHAr), 110.9 (CHAr), 107.4
(CHAr), 55.7 (CH3). IR (ATR, cm-1): ṽ = 2925 (w), 1509 (s), 1490 (m), 1451 (s), 1245 (s), 1212
(m), 1193 (m), 1179 (m), 1168 (m), 1151 (m), 1106 (m), 1070 (m), 1028 (s), 833 (m), 804
(m), 752 (s), 736 (s), 687 (s), 653 (w), 583 (s), 563 (w). MS (EI, 70 eV): m/z (%) = 357 (8),
356 (25), 355 [M]+ (100), 340 (13), 312 (9), 311 (4), 310 (6), 278 (4), 178 (4). HRMS (EI):
Calculated for C23H17ONS [M]+ C23H17ONS 355.10254 found 355.10253.
4-(4-Fluorophenyl)-2-phenyl-4H-thieno[3,2-b]indole (10d): White solid, mp. 120 – 121 °C,
1
90% yield. H NMR (250 MHz, Chloroform-d) δ = 7.83 – 7.75 (m, 1H, CHAr), 7.71 – 7.63 (m,
2H, CHAr), 7.63 – 7.52 (m, 2H, CHAr), 7.49 – 7.35 (m, 3H, CHAr), 7.34 – 7.23 (m, 6H, CHAr).
19F NMR (282 MHz, CDCl3) δ = -114.40 (FCAr). 13C NMR (63 MHz, CDCl3) δ = 161.41 (d,
1JC-F = 247.0 Hz, FCAr), 146.2 (CAr), 145.4 (CAr), 141.2 (CAr), 135.3 (CAr), 134.9 (d, 4JC-F = 3.0
Hz, CFAr), 129.1 (2CHAr), 127.9 (CHAr), 127.3 (d, 3JC-F = 8.5 Hz, 2CHAr), 125.8 (2CHAr), 123.3
(CHAr), 122.6 (CAr), 120.7 (CHAr), 119.1 (CHAr), 117.1 (CAr), 117.0 (d, 2JC-F = 22.8 Hz, 2CHAr),
110.8 (CHAr), 107.2 (CHAr). IR (ATR, cm-1): ṽ = 3076 (w), 2923 (w), 1506 (s), 1451 (s), 1424
(m), 1342 (m), 1210 (s), 1149 (w), 1092 (m), 1069 (m), 1012 (w), 843 (s), 803 (s), 684 (s),
652 (w), 575 (m), 562 (m). MS (EI, 70 eV): m/z (%) = 345 (7), 344 (25), 343 [M]+ (100), 342
(20), 309 (7), 171 (6), 154 (7), 146 (4), 121 (4), 120 (6), 95 (4), 77 (4), 75 (7). HRMS (EI):
Calculated for C22H14NFS [M]+ 343.08255 found 343.0823.
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European Journal of Organic Chemistry
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2-(4-Chlorophenyl)-4-(3,5-dimethylphenyl)-4H-thieno[3,2-b]indole (10e): White solid,
1
mp. 105 – 106 °C, 62% yield. H NMR (250 MHz, Chloroform-d) δ = 7.78 – 7.70 (m, 1H,
3
CHAr), 7.56 (d, J = 8.6 Hz, 2H, CHAr), 7.52 – 7.46 (m, 1H, CHAr), 7.40 – 7.35 (m, 1H, CHAr),
7.32 (d, 3J = 8.6 Hz, 2H, CHAr), 7.25 – 7.21 (m, 1H, CHAr), 7.20 – 7.13 (m, 3H, CHAr), 7.04 (m,
1H, CHAr), 2.41 (s, 6H, CH3). 13C NMR (63 MHz, CDCl3) δ = 145.3 (CAr), 144.2 (CAr), 141.2
(CAr), 139.8 (2CAr), 138.6 (CAr), 134.0 (CAr), 133.4 (CAr), 129.2 (2CHAr), 128.9 (CHAr), 126.9
(2CHAr), 125.9 (CAr), 123.3 (CHAr), 123.1 (2CHAr), 122.4 (CAr), 120.5 (CHAr), 119.1 (CHAr),
111.3 (CHAr), 108.1 (CHAr), 21.6 (2CH3). IR (ATR, cm-1): ṽ = 2916 (w), 2854 (w), 1595 (m),
1477 (m), 1451 (s), 1348 (m), 1314 (w), 1285 (w), 1169 (w), 1090 (m), 1011 (w), 828 (m),
801 (s), 737 (s), 703 (m), 687 (m), 672 (m), 551 (w). MS (EI, 70 eV): m/z (%) = 390 (11), 389
(42), 388 (31), 387 [M]+ (100), 372 (10), 193 (3), 168 (3). HRMS (EI): Calculated for
C24H18NClS [M]+ 387.08430 found 387.084213, calculated for C24H18N37ClS [M]+ 389.08135
found 389.08135.
4-(4-(tert-Butyl)phenyl)-2-(4-chlorophenyl)-4H-thieno[3,2-b]indole (10f): White solid,
1
mp. 137 – 138 °C, 61% yield. H NMR (250 MHz, Chloroform-d) δ = 7.75 – 7.69 (m, 1H,
CHAr), 7.57 – 7.49 (m, 5H, CHAr), 7.49 – 7.43 (m, 3H, CHAr), 7.32 – 7.25 (m, 2H, CHAr), 7.23 –
7.16 (m, 2H, CHAr), 1.38 (s, 9H, tBu). 13C NMR (63 MHz, CDCl3) δ = 150.1 (CAr), 145.3 (CAr),
144.3 (CAr), 141.1 (CAr), 136.0 (CAr), 134.0 (CAr), 133.3 (CAr), 129.2 (2CHAr), 126.9 (4CHAr),
124.9 (2CHAr), 123.3 (CHAr), 122.4 (CAr), 120.5 (CHAr), 119.1 (CHAr), 117.2 (CAr), 111.2
(CHAr), 108.0 (CHAr), 34.9 (CtBu), 31.6 (3CH3). IR (ATR, cm-1): ṽ = 2956 (m), 2902 (w), 1516
(m), 1487 (m), 1450 (s), 1361 (w), 1339 (w), 1261 (w), 1089 (s), 1012 (s), 834 (m), 802 (s),
791 (s), 746 (s), 672 (w), 628 (w), 551 (m). MS (EI, 70 eV): m/z (%) = 418 (11), 417 (39), 416
(28), 415 [M]+ (100), 402 (12), 401 (9), 400 (30), 385 (12), 186 (11). HRMS (EI): Calculated
for C26H22NClS [M]+ 415.11560 found 415.11531, calculated for C26H22N37ClS [M]+ 417.11265
found 417.11365.
2-(4-Chlorophenyl)-4-mesityl-4H-thieno[3,2-b]indole (10g): White solid, mp. 105 –
106 °C, 87% yield. 1H NMR (250 MHz, Chloroform-d) δ = 7.86 – 7.76 (m, 1H, CHAr), 7.57 (d,
3J = 8.6 Hz, 2H, CHAr), 7.33 (d, 3J = 8.6 Hz, 2H, CHAr), 7.28 – 7.20 (m, 2H, CHAr), 7.08 (s, 2H,
CHAr), 7.00 – 6.92 (m, 2H, CHAr), 2.43 (s, 3H, CH3), 1.91 (s, 6H, CH3). 13C NMR (63 MHz,
CDCl3) δ = 145.4 (CAr), 144.4 (CAr), 141.3 (CAr), 138.7 (CAr), 137.4 (2CAr), 134.1 (CAr), 133.3
(CAr), 132.9 (CAr), 129.4 (2CHAr), 129.2 (2CHAr), 126.8 (2CHAr), 123.2 (CHAr), 121.9 (CAr),
120.0 (CHAr), 119.1 (CHAr), 116.2 (CAr), 110.9 (CHAr), 107.4 (CHAr), 21.3 (CH3), 17.7 (2CH3).
IR (ATR, cm-1): ṽ = 2950 (w), 2916 (w), 1603 (w), 1501 (s), 1484 (s), 1450 (m), 1314 (m),
1213 (w), 1179 (w), 1010 (w), 852 (w), 827 (m), 800 (s), 739 (s), 677 (w), 552 (w). MS
(EI, 70 eV): m/z (%) = 404 (11), 403 (38), 402 (29), 401 [M]+ (100), 386 (4), 368 (3), 247 (3),
232 (3), 231 (3). HRMS (EI): Calculated for C25H20NClS [M]+ 401.09995 found 401.09960,
calculated for C25H20N37ClS [M]+ 403.09700 found: 403.09786.
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European Journal of Organic Chemistry
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28
4-(3-Fluorophenyl)-2-(4-fluorophenyl)-4H-thieno[3,2-b]indole
(10h):
White
solid,
1
mp. 156 – 157 °C, 62% yield. H NMR (250 MHz, Chloroform-d) δ = 7.80 – 7.73 (m, 1H,
3
4
CHAr), 7.66 – 7.58 (m, 2H, CHAr), 7.58 – 7.48 (m, 2H, CHAr), 7.41 (ddd, J = 8.0 Hz, J = 2.0
Hz, 5J = 1.1 Hz, 1H, CHAr), 7.37 – 7.30 (m, 1H, CHAr), 7.30 – 7.20 (m, 3H, CHAr), 7.16 – 7.03
19
(m, 3H, CHAr). F NMR (235 MHz, CDCl3) δ = -110.36 (FCAr), -114.04 (FCAr). 13C NMR (63
1
1
MHz, CDCl3) δ = 163.5 (d, JC-F = 248.1 Hz, CFAr), 162.6 (d, JC-F = 247.9 Hz, CFAr), 146.0
3
4
(CAr), 145.1 (CAr), 140.6 (CAr), 140.4 (d, JC-F = 10.0 Hz, CAr), 131.6 (d, JC-F = 3.5 Hz, CAr),
3
3
131.1 (d, JC-F = 9.2 Hz, CHAr), 127.4 (d, JC-F = 8.0 Hz, 2CHAr), 123.5 (CHAr), 122.8 (CAr),
4
2
121.1 (CHAr), 120.6 (d, JC-F = 3.2 Hz, CHAr), 119.2 (CHAr), 117.7 (CAr), 116.0 (d, JC-F = 21.9
2
2
Hz, 2CHAr), 113.8 (d, JC-F = 21.1 Hz, CHAr), 112.4 (d, JC-F = 23.4 Hz, CHAr), 111.0 (CHAr),
107.5 (CHAr). IR (ATR, cm-1): ṽ = 3052 (w), 1592 (m), 1531 (m), 1490 (s), 1452 (m), 1364 (w),
1261 (w), 1222 (s), 1145 (s), 1080 (w), 977 (w), 934 (w), 870 (w), 828 (m), 806 (s), 777 (m),
725 (s), 708 (m), 694 (s), 667 (s), 630 (w), 581 (w). MS (EI, 70 eV): m/z (%) = 363 (7), 361
[M]+ (100), 360 (21), 359 (6), 266 (4). HRMS (EI): Calculated for C22H13NF2S [M]+ 361.07313
found 361.07251.
4-(4-(tert-Butyl)phenyl)-2-(4-fluorophenyl)-4H-thieno[3,2-b]indole (10i): White solid,
1
mp. 118 – 119 °C, 85% yield. H NMR (300 MHz, Chloroform-d) δ = 7.72 – 7.67 (m, 1H,
CHAr), 7.59 – 7.41 (m, 7H, CHAr), 7.20 – 7.15 (m, 3H, CHAr), 7.04 – 6.95 (m, 2H, CHAr), 1.34
1
(s, 9H, tBu). 13C NMR (75 MHz, CDCl3) δ = 162.6 (d, JC-F = 247.5 Hz, CFAr), 150.1 (CAr),
4
145.3 (CAr), 144.6 (CAr), 141.1 (CAr), 136.1 (CAr), 131.9 (d, JC-F = 3.3 Hz, CAr), 127.5 (d,
3JC-F = 8.0 Hz, 2CHAr), 126.8 (2CHAr), 124.9 (2CHAr), 123.2 (CHAr), 122.6 (CAr), 120.5 (CHAr),
2
119.0 (CHAr), 116.9 (CAr), 116.1 (d, JC-F = 21.9 Hz, 2CHAr), 111.2 (CHAr), 107.8 (CHAr), 34.9
(CtBu), 31.6 (3CH3). IR (ATR, cm-1): ṽ = 2963 (w), 1602 (w), 1497 (m), 1451 (m), 1361 (w),
1342 (w), 1213 (s), 1159 (m), 1096 (w), 1013 (w), 840 (s), 804 (s), 787 (m), 738 (s), 674 (m),
633 (w), 552 (s). MS (EI, 70 eV): m/z (%) = 401 (8), 400 (29), 399 [M]+ (100), 385 (10), 384
(35), 369 (16), 342 (9), 266 (10), 192 (8), 178 (26). HRMS (EI): Calculated for C26H22NFS
[M]+ 399.14515 found 399.14496.
2-(4-(tert-Butyl)phenyl)-4-mesityl-4H-thieno[3,2-b]indole (10j): White solid, mp. 181 –
182 °C, 45% yield. 1H NMR (250 MHz, Chloroform-d) δ = 7.83 – 7.76 (m, 1H, CHAr), 7.58 (d,
3
3J = 8.6 Hz, 2H, CHAr), 7.39 (d, J = 8.6 Hz, 2H, CHAr), 7.20 (m, 2H, CHAr), 7.07 (s, 2H,
CHAr), 6.96 (s, 1H, CHthiophene), 6.95 – 6.90 (m, 1H, CHAr), 2.42 (s, 3H, CH3), 1.91 (s, 6H,
13
CH3), 1.34 (s, 9H, tBu). C NMR (63 MHz, CDCl3) δ = 150.8 (CAr), 146.1 (CAr), 145.5 (CAr),
141.2 (CAr), 138.6 (CAr), 137.5 (2CAr), 133.1 (CAr), 132.8 (CAr), 129.4 (2CHAr), 126.0 (2CHAr),
125.4 (2CHAr), 122.8 (CHAr), 122.1 (CAr), 119.8 (CHAr), 118.9 (CHAr), 115.5 (CAr), 110.8
(CHAr), 106.7 (CHAr), 34.8 (CtBu), 31.4 (3CH3), 21.3 (CH3), 17.7 (2CH3). IR (ATR, cm-1):
ṽ = 2957 (w), 2921 (w), 1502 (m), 1484 (m), 1452 (m), 1357 (w), 1335 (w), 1218 (w), 937 (w),
836 (m), 807 (s), 743 (s), 574 (w), 531 (m). MS (EI, 70 eV): m/z (%) = 425 (7), 424 (31), 423
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European Journal of Organic Chemistry
10.1002/ejoc.201601281
29
[M]+ (100), 410 (4), 409 (13), 408 (45), 393 (10), 204 (4), 190 (5). HRMS (EI): Calculated for
C29H29NS [M]+ 423.20152 found 423.20115.
Acknowledgement
Scholarship for N.N.P. by the DAAD is gratefully acknowledged.
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