Intermolecular Followed by Intramolecular Palladium-Catalyzed Direct Arylation for the Synthesis of π-Extended Aromatic Compounds Containing One or Two Heteroelements

Article abstract of DOI:10.1002/ejoc.201900775

Herein, we report that palladium-catalyzed C-H bond activation can overcome some of the challenges in the preparation of π-extended aromatics containing one or two heteroelements, which are important structures in organic materials science. The sequential

Full text of DOI:10.1002/ejoc.201900775

DOI: 10.1002/ejoc.201900775
Full Paper
C-H Bond Functionalization
Intermolecular Followed by Intramolecular Palladium-Catalyzed
Direct Arylation for the Synthesis of π-Extended Aromatic
Compounds Containing One or Two Heteroelements
Bilel Bouzayani,[a,b] Ridha Ben Salem,*[b] Jean-François Soulé,*[a] and Henri Doucet*[a]
Abstract: Herein, we report that palladium-catalyzed C-H bond bromination of the heteroarene unit with N-bromosuccinimide,
activation can overcome some of the challenges in the prepara- and finally palladium-catalyzed intramolecular direct arylation
tion of π-extended aromatics containing one or two heteroele- allowed the synthesis of the desired phenanthro[9,10-b]thio-
ments, which are important structures in organic materials sci- phenes, phenanthro[9,10-b]furans, phenanthro[9,10-b]thiazoles,
ence. The sequential palladium-catalyzed intermolecular direct acenaphtho[1,2-d]thiophenes, and acenaphtho[1,2-d]thiazoles
C5-arylation of heteroarenes by aryl bromides, followed by in only three steps.
Introduction
bond activation have been reported so far, and no examples of
preparation of acenaphtho[1,2-d]thiazoles has been described.
The synthesis of π-extended polycyclic heteroaromatic hydro-
carbons is currently a very hot topic in organic material science,
as the introduction of heteroelements in these π-extended
structures often induces a modification of their chemical and/
or physical properties. For example, they are employed for the
preparation of optoelectronic devices such as organic field-
effect transistors (OFETs).[1] Their unique properties are directly
linked to their structures. However, the synthesis of such com-
pounds often suffers from low functional group tolerance and/
or tedious access to the key intermediates due to multi-step
synthesis. Palladium-catalyzed direct functionalization through
C-H bond cleavage[2–4] can overcome some of the challenges
in the preparation of such organic materials.[5–9] Indeed, the
recent remarkable progress in the direct arylation of (hetero)-
aromatics has set the stage for the synthesis of complex mol-
ecules using sequential C-H bond activation/arylations. Such
transformations appear as one of the most suitable methods in
terms of i) number of synthetic steps, ii) functional group toler-
ance, iii) respect of the environment (only the formation of HX
associated with a base as side product and no requirement to
prepare and use sensitive organometallic reagents).
Scheme 1. Structures of some π-extended heteroaromatics.
In 2004 Höger et al. employed Pd-catalyzed C2- and C4-intra-
molecular direct arylations of a thiophene bearing a 2,5-di-
bromophenyl group at C3 position for the preparation of a
phenanthro[9,10-b]thiophene derivative in 28 % yield
(Scheme 2a).[5a] In 2015, Kanai, Kuninobu et al. prepared a
benzo[b]phenanthro[9,10-d]thiophene from a benzothiophene
substituted by an ortho-biphenyl group at C3 position via Pd-
catalyzed oxidative C-H/C-H coupling reaction.[5b] Then, in 2016
and 2017, our group reported the synthesis of phenanthro-
[9,10-b]thiophenes and phenanthro[9,10-b]thiazoles from thio-
phenes and thiazoles bearing 2-bromoaryl groups at the C4
position, via C5 arylations followed by an intramolecular cycliza-
tion (Scheme 2b).[5c,6] In 2017, using a diiodobiphenyl as π-
extending agent, Itami et al. produced a phenanthro[9,10-b]-
thiophene in one step;[5d,5e] whereas, Miao et al. employed di-
benzosiloles as π-extending agents (Scheme 2c).[5f] A single ex-
ample of synthesis of a phenanthro[9,10-b]furan via a domino
Suzuki–Miyaura coupling/intramolecular direct arylation using
2-bromophenylboronic acid has been described by Yoshikai et
al. in 2014 (Scheme 2d).[7c] By contrast, the preparation of ace-
naphtho[1,2-d]thiophene via C-H bond activation remain
To the best of our knowledge, only a few examples dealing
with the synthesis of phenanthro[9,10-b]thiophenes,[5] phen-
anthro[9,10-b]thiazoles,[6] phenanthro[9,10-b]furans,[7] ace-
naphtho[1,2-d]thiophenes[8] (Scheme 1) via Pd-catalyzed C-H
[a] CNRS, ISCR-UMR 6226, Univ Rennes,
F-35000 Rennes, France
E-mail: jean-francois.soule@univ-rennes1.fr
henri.doucet@univ-rennes1.fr
[b] Laboratoire de Chimie Organique LR 17ES08, Faculté des Sciences de Sfax,
Université de Sfax,
Route de la Soukra km 4, 3038 Sfax, Tunisia
E-mail: ridhabensalem@yahoo.fr
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under https://doi.org/10.1002/ejoc.201900775.
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scarce.[8] The first example, which was reported in 1999 by De- tained for the reaction of 2-acetyl-3-chlorothiophene with 2-
haen's group, deals with the ring closure of the 1,5-dichloro- bromobiphenyl. The reactions of 2-bromobiphenyl with a furan
9,10-diarylanthracenes to produce the corresponding thio- derivative, imidazo[1,2-a]pyridine and thiazole derivatives were
phene rubicene analogs (Scheme 2e).[8a]
also successful giving rise to the products 1e–1h in 52–96 %
yields. Then, we introduced a 1-naphthyl C5-substituent on
thiophene and thiazole derivatives using the same reaction
conditions, with the exception of the catalyst which was re-
placed by Pd(OAc)2, as it is known that the oxidative addition
of 1-bromonaphthalene proceeds nicely with this phosphane-
free catalyst.[11] In all cases, the expected products 1i and 1k–
1m were obtained in high yields. Similar yields were obtained
for the reactions of 2-acetylthiophene and 2-ibutylthiazole with
1-bromo-4-fluoronaphthalene affording 1j and 1n in 85 % and
91 % yield, respectively. 1-Bromopyrene was also employed as
the aryl source using thiophene and thiazole derivatives as re-
action partners. In all cases, using again 2 mol-% of Pd(OAc)2
catalyst, the expected pyren-1-yl-substituted heteroarenes 1o–
1s were obtained in high yields.
Scheme 2. Synthesis of O- or S-containing π-extended aromatics via a C-H
bond activation step using thiophenes, furans or thiazoles.
Herein, we report on the potential of sequential intermolec-
ular Pd-catalyzed direct C5-arylation of heteroaromatics, regio-
selective C4-bromination of the heteroarene unit, and intra-
molecular Pd-catalyzed direct arylation for the synthesis π-ex-
tended polycyclic heteroaromatic hydrocarbons.
Scheme 3. Pd-catalyzed direct C5-arylations of heteroarenes with 2-bromo-
biphenyl, 1-bromonaphthalenes and 1-bromopyrene.
Results and Discussion
Then, the reactivity of the fifteen C5-arylated heteroarenes
First, we studied the C5-arylation of a set of heteroarenes with 1a–1o in bromination reaction using N-bromosuccinimide
2-bromobiphenyl using our previously reported reaction condi- (NBS) as easy to handle bromine source was investigated
tions (e.g., 2 mol-% PdCl(C3H5)(dppb) catalyst, KOAc as the base (Scheme 4). As the biphenyl-substituted thiophenes 1a–1c con-
in DMA at 150 °C) (Scheme 3).[10] Under these conditions, thio- tain two C-H bonds on the thiophene ring, mixtures of bromin-
phene derivatives bearing acetyl, cyclopropylmethanone or es- ated products might have been obtained. However, a few re-
ter C2-substituents gave the expected arylated products 1a–1c ports indicate that from thiophene derivatives bearing an elec-
in 89–94 % yields. A slightly lower yield of 78 % in 1d was ob- tron-withdrawing substituent at C2-position and an alkyl or an
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aryl at C5-position, the bromination mostly occurred at the C4- were isolated in 63 % and 68 % yield, respectively. It should be
position; whereas, the C-H bond at the C3-position remained mentioned that the pyrene-substituted thiophenes 2o–2q and
untouched.[12] To our delight, the desired 4-bromo-substituted thiazoles 2r and 2s could not be isolated from 1o–1s, as several
thiophene derivatives 2a–2c were obtained in high regioselec- unidentified products were formed in the course of these brom-
tivities and in 83–86 % yields. A good yield in 4-bromothio- ination reactions.
phene derivative 2d was also obtained for the bromination of
1d which contained an additional chloro-C3-substituent com-
pared to 1a. The C4-bromination of the furan ring[13a] of 1e was
also successful affording regioselectively 2e in 61 % yield.
From the imidazo[1,2-a]pyridine derivative 1f and NBS at 25 or
70 °C, no formation of the products 2f was observed by GC/MS
analysis of the crude mixtures, and 1f was recovered. To the
best of our knowledge, the bromination of the 5-membered
ring of imidazo[1,2-a]pyridine derivatives has been rarely de-
scribed.[13b] This result might come from an unfavorable combi-
nation of electronic and steric properties. Conversely, the brom-
ination of the C4-position of the thiazole rings[14] of 1g and 1h
proceeded nicely affording the expected products 2g and 2h
in 87 % and 64 % yield, respectively. The naphthyl-substituted
thiophenes 1i, 1k and 1l treated by NBS gave the desired prod-
ucts 2i, 2k and 2l in moderate yields, due to the moderate
regioselectivities of these reactions. Moreover, their purification
by silica chromatography afforded the expected products con-
taminated with unidentified side-products. The bromination of
1-(5-(4-fluoronaphthalen-1-yl)thiophen-2-yl)ethan-1-one 1j was
more selective affording the desired product 2j in 65 % yield
in pure form. The 5-naphthylthiazoles 1m and 1n were also
successfully brominated, and the desired products 2m and 2n
Finally, we investigated the Pd-catalyzed intramolecular C-H
bond arylations of 2a–2h and 2i–2n (Scheme 5 and Scheme 6).
We tested similar conditions employed for the C5-arylations of
heteroarenes of Scheme 3 – namely 2 mol-% of PdCl(C3H5)-
(dppb) in DMA at 150 °C – with 2 equiv. of PivOK as the base
instead of KOAc, as it was previously demonstrated that this
base is very effective to promote the C-H bond cleavage of
benzene derivatives.[6] The intramolecular arylations of 2a–2c
proceeded faster than the intermolecular reactions affording
the desired phenanthro[9,10-b]thiophenes 3a–3c in 84–87 %
yields. The presence of a chloro-substituent at C3-position on
the thiophene ring had a deleterious influence as no formation
of product 3d was detected from 2d. Part of the starting mate-
rial 2d was recovered and degradation products were also ob-
served. The intramolecular C-H bond arylation of the furan de-
rivative 1e proceeded nicely delivering the phenanthro[9,10-b]-
furan 2e in 84 % yield. A very clean cyclization reaction was
also observed with the 4-bromothiazole derivative 2g affording
the phenanthro[9,10-b]thiazole 3g in 90 % yield. Conversely, the
cyclisation of 2h was not successful, and only degradation prod-
ucts were obtained.
Scheme 5. Pd-catalyzed direct intramolecular arylations of bromo-substituted
heteroarenes 2a–2h.
To the best of our knowledge, the synthesis of ace-
naphtho[1,2-b]thiophenes has rarely been described[8,15] and
only one example of preparation of a acenaphtho[1,2-d]thiazole
has been reported.[16] Again, we employed 2 mol-% of
PdCl(C3H5)(dppb) with 2 equiv. of PivOK as base/ligand in DMA
to promote the cyclization of the 5-naphthylthiophenes 2i–2n
(Scheme 6). The desired acenaphtho[1,2-b]thiophenes 4i, 4k
and 4l were only obtained in 38–53 % yields, from 2i, 2k and
2l due to the formation of degradation side-products. Unex-
pectedly, no formation of the expected acenaphtho[1,2-b]thio-
phene was observed in GC/MS of the crude mixture using the
fluoro-substituted 5-naphthylthiophene 2j. In the course of this
Scheme 4. C4-brominations of the C5-arylated heteroarenes 1a–1s.
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and was not purified before use. 1H NMR spectra were recorded on
Bruker GPX (400 MHz) spectrometer. Chemical shifts (δ) were re-
ported in parts per million relative to residual chloroform (7.28 ppm
for 1H; 77.0 ppm for 13C), constants were reported in Hertz. 1H NMR
assignment abbreviations were the following: singlet (s), doublet
(d), triplet (t), quartet (q), doublet of doublets (dd), doublet of trip-
lets (dt), and multiplet (m). 13C NMR spectra were recorded at
100 MHz on the same spectrometer and reported in ppm. All rea-
gents were weighed and handled in air.
Preparation of the PdCl(C3H5)(dppb) Catalyst:[17] An oven-dried
40 mL Schlenk tube equipped with a magnetic stirring bar under
argon atmosphere, was charged with [Pd(C3H5)Cl]2 (182 mg,
0.5 mmol) and dppb (426 mg, 1 mmol). 10 mL of anhydrous di-
chloromethane were added, then, the solution was stirred at room
temperature for twenty minutes. The solvent was removed in vacuo.
The powder was used without purification. (31P 381 MHz, CDCl3)
δ = 19.3 (s).
Scheme 6. Pd-catalyzed direct intramolecular arylations of the 4-bromo-
substituted heteroarenes 2i–2n.
Procedure A (Direct Intermolecular Arylation of Heteroarenes):
To a 25 mL oven dried Schlenk tube, aryl bromide (1 mmol), hetero-
arene derivative (1.5 mmol), KOAc (0.196 g, 2 mmol), DMA (2 mL)
and PdCl(C3H5)(dppb) (12.2 mg, 0.02 mmol) or Pd(OAc)2 (4.4 mg,
0.02 mmol) (see scheme ) were successively added. The reaction
mixture was evacuated by vacuum-argon cycles (5 times) and
stirred at 150 °C (oil bath temperature) for 16 hours. After cooling
the reaction at room temperature and concentration, the crude mix-
ture was purified by silica column chromatography (diethyl ether/
heptane, 1:9) to afford the desired arylated products 1a–1r.
reaction, a complete conversion of 2j was observed, but only
unidentified side-products were formed. The Pd-catalyzed an-
nulation using 5-naphthylthiazole 2m was moderately success-
ful, as the desired acenaphtho[1,2-d]thiazole 4m was only ob-
tained in 21 % yield. With 4-bromo-5-(4-fluoronaphthalen-1-yl)-
2-isobutylthiazole 2n, a mixture of starting material and de-
brominated compound 1n was obtained; whereas, the ex-
pected acenaphtho[1,2-d]thiazole was not detected.
1-(5-([1,1′-Biphenyl]-2-yl)thiophen-2-yl)ethan-1-one (1a): Fol-
lowing the procedure A, from 2-acetylthiophene (0.189 g,
1.5 mmol), 2-bromobiphenyl (0.233 g, 1 mmol) and PdCl(C3H5)-
(dppb) (12.2 mg, 0.02 mmol), compound 1a was obtained in 94 %
yield (0.261 g) as a white solid: m.p. 109–111 °C. 1H NMR (400 MHz,
CDCl3) δ (ppm) 7.61–7.56 (m, 1H), 7.49–7.40 (m, 4H), 7.36–7.31 (m,
3H), 7.29–7.25 (m, 2H), 6.65 (d, J = 3.9 Hz, 1H), 2.50 (s, 3H). 13C NMR
(100 MHz, CDCl3) δ (ppm) 190.5, 152.1, 143.7, 141.2, 140.9, 132.6,
132.2, 131.1, 130.5, 129.4, 129.0, 128.3, 128.2, 127.9, 127.4, 26.6. Ele-
mental analysis: calcd. (%) for C18H14OS (278.37): C 77.67, H 5.07;
found C 77.92, H 5.02.
Conclusions
In summary, we have investigated the potential of the inter-
molecular Pd-catalyzed direct C5-arylation of heteroaromatics
followed by their regioselective C4-bromination and intra-
molecular Pd-catalyzed annulation reaction for the synthesis of
π-extended aromatic compounds containing heteroelements.
With most heteroaromatics, the first step proceeded in high
yields using 2-bromobiphenyl, 1-bromonaphthalene or
1-bromopyrene as aryl sources and 2 mol-% of PdCl(C3H5)-
(dppb) as air-stable catalyst associated to KOAc as inexpensive
base. The resulting coupling products were submitted to C4-
bromination reactions of the heteroarene unit using N-bromo-
succinimide as bromination agent. Both biphenyl- and naphth-
yl-substituted thiophenes and thiazoles were regioselectively
brominated affording the target products; whereas, pyrene-sub-
stituted heteroarenes gave complex mixtures of products.
Finally, the intramolecular Pd-catalyzed annulation reaction af-
forded the π-extended aromatic compounds with phenanthro-
(5-([1,1′-Biphenyl]-2-yl)thiophen-2-yl)(cyclopropyl)methanone
(1b): Following the procedure A, from cyclopropyl(thiophen-2-yl)-
methanone (0.228 g, 1.5 mmol), 2-bromobiphenyl (0.233 g, 1 mmol)
and PdCl(C3H5)(dppb) (12.2 mg, 0.02 mmol), compound 1b was ob-
1
tained in 89 % yield (0.270 g) as a white solid: m.p. 128–130 °C. H
NMR (400 MHz, CDCl3) δ (ppm) 7.63–7.60 (m, 1H), 7.59 (d, J = 3.9 Hz,
1H), 7.50–7.40 (m, 3H), 7.40–7.25 (m, 5H), 6.68 (d, J = 3.9 Hz, 1H),
2.53–2.45 (m, 1H), 1.30–1.25 (m, 2H), 1.05–0.99 (m, 2H). 13C NMR
(100 MHz, CDCl3) δ (ppm) 192.7, 151.6, 144.2, 141.2, 141.0, 132.3,
131.7, 131.1, 130.6, 129.6, 128.9, 128.4, 127.8, 127.4, 17.8, 11.4. Ele-
mental analysis: calcd. (%) for C20H16OS (304.41): C 78.91, H 5.30;
found C 79.14, H 5.39.
[9,10-b]thiophene,
phenanthro[9,10-b]furan,
phenanthro-
[9,10-b]thiazole, acenaphtho[1,2-d]thiophene or acenaphtho-
[1,2-d]thiazole skeletons in low to high yields. Therefore, this
synthetic pathway should overcome some of the challenges in
the preparation of π-extended heteroaromatics containing one
or two heteroelements useful in organic material science.
Ethyl 5-([1,1′-Biphenyl]-2-yl)thiophene-2-carboxylate (1c): Fol-
lowing the procedure A, from ethyl thiophene-2-carboxylate
(0.234 g, 1.5 mmol), 2-bromobiphenyl (0.233 g, 1 mmol) and
PdCl(C3H5)(dppb) (12.2 mg, 0.02 mmol), compound 1c was obtained
1
in 91 % yield (0.280 g) as a yellow oil. H NMR (400 MHz, CDCl3) δ
(ppm) 7.63–7.57 (m, 2H), 7.39–7.34 (m, 3H), 7.34–7.27 (m, 5H), 6.67
(d, J = 3.9 Hz, 1H), 4.38 (q, J = 7.6 Hz, 2H), 1.40 (t, J = 7.6 Hz, 3H).
13C NMR (100 MHz, CDCl3) δ (ppm) 162.2, 150.5, 141.2, 140.9, 133.3,
132.3, 131.1, 130.6, 129.6, 128.8, 128.3, 127.9, 127.8, 127.4, 61.1, 14.5.
Elemental analysis: calcd. (%) for C19H16O2S (308.40): C 74.00, H 5.23;
Experimental Section
All reactions were carried out under argon atmosphere with stan-
dard Schlenk techniques. DMA was purchased from Acros Organics found C 73.78, H 4.98.
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1-(5-([1,1′-Biphenyl]-2-yl)-3-chlorothiophen-2-yl)ethan-1-one
(1d): Following the procedure A, from 1-(3-chlorothiophen-2-
yl)ethan-1-one (0.240 g, 1.5 mmol), 2-bromobiphenyl (0.233 g,
1 mmol) and PdCl(C3H5)(dppb) (12.2 mg, 0.02 mmol), compound
1d was obtained in 78 % yield (0.243 g) as a yellow oil. 1H NMR
(400 MHz, CDCl3) δ (ppm) 7.58–7.52 (m, 1H), 7.50–7.38 (m, 3H),
7.38–7.33 (m, 3H), 7.28–7.23 (m, 2H), 6.58 (s, 1H), 2.61 (s, 3H). 13C
NMR (100 MHz, CDCl3) δ (ppm) 189.7, 149.5, 141.2, 140.3, 137.0,
131.2, 131.1, 130.1, 130.0, 129.5, 129.4, 128.5, 128.0, 127.9, 127.7,
29.6. Elemental analysis: calcd. (%) for C18H13ClOS (312.81): C 69.11,
H 4.19; found C 69.30, H 4.28.
131.3, 129.5, 128.5, 128.4, 128.3, 126.9, 126.3, 125.2, 26.7. Elemental
analysis: calcd. (%) for C16H12OS (252.33): C 76.16, H 4.79; found
C 76.34, H 4.62.
1-(5-(4-Fluoronaphthalen-1-yl)thiophen-2-yl)ethan-1-one (1j):
Following the procedure A, from 2-acetylthiophene (0.189 g,
1.5 mmol), 1-bromo-4-fluoronaphthalene (0.225 g, 1 mmol) and
Pd(OAc)2 (4.4 mg, 0.02 mmol), compound 1j was obtained in 85 %
yield (0.229 g) as a white solid: m.p. 167–169 °C. 1H NMR (400 MHz,
CDCl3) δ (ppm) 8.23–8.14 (m, 2H), 7.79–7.75 (m, 1H), 7.64–7.56 (m,
2H), 7.55–7.49 (m, 1H), 7.28–7.17 (m, 2H), 2.61 (s, 3H). 13C NMR
(100 MHz, CDCl3) δ (ppm) 190.6, 159.2 (d, J = 255.5 Hz), 149.9, 144.3,
132.7, 132.6, 128.5, 128.2 (d, J = 8.6 Hz), 127.8, 127.6 (d, J = 4.5 Hz),
126.6 (d, J = 1.9 Hz), 125.3 (d, J = 2.3 Hz), 124.0 (d, J = 16.3 Hz),
121.0 (d, J = 5.6 Hz), 109.0 (d, J = 20.5 Hz), 26.7. Elemental analysis:
calcd. (%) for C16H11FOS (270.32): C 71.09, H 4.10; found C 71.25, H
Methyl 5-([1,1′-biphenyl]-2-yl)furan-2-carboxylate (1e): Follow-
ing the procedure A, from methyl furan-2-carboxylate (0.189 g,
1.5 mmol), 2-bromobiphenyl (0.233 g, 1 mmol) and PdCl(C3H5)-
(dppb) (12.2 mg, 0.02 mmol), compound 1e was obtained in 52 %
yield (0.144 g) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ (ppm) 4.32.
7.96 (d, J = 7.4 Hz, 1H), 7.47–7.34 (m, 5H), 7.34–7.24 (m, 3H), 6.97
Cyclopropyl(5-(naphthalen-1-yl)thiophen-2-yl)methanone (1k):
(d, J = 3.6 Hz, 1H), 5.56 (d, J = 3.6 Hz, 1H), 3.88 (s, 3H). 13C NMR
(100 MHz, CDCl3) δ (ppm) 159.2, 156.5, 142.9, 141.4, 140.4, 130.8,
129.1, 128.6, 128.4, 127.7, 127.5, 119.5, 111.1, 51.8. Elemental analy-
sis: calcd. (%) for C18H14O3 (278.31): C 77.68, H 5.07; found C 77.52,
H 4.88.
Following the procedure A, from cyclopropyl(thiophen-2-yl)methan-
one (0.228 g, 1.5 mmol), 1-bromonaphthalene (0.207 g, 1 mmol)
and Pd(OAc)2 (4.4 mg, 0.02 mmol), compound 1k was obtained in
79 % yield (0.220 g) as a white solid: m.p. 162–164 °C. 1H NMR
(400 MHz, CDCl3) δ (ppm) 8.24 (d, J = 8.2 Hz, 1H), 7.97–7.90 (m, 3H),
7.63 (dd, J = 7.1, 1.0 Hz, 1H), 7.62–7.50 (m, 3H), 7.32 (d, J = 3.8 Hz,
1H), 2.68–2.56 (m, 1H), 1.38–1.30 (m, 2H), 1.14–1.05 (m, 2H). 13C
NMR (100 MHz, CDCl3) δ (ppm) 192.9, 150.1, 144.6, 133.9, 131.7,
131.3, 129.4, 128.5, 128.4, 128.3, 126.9, 126.3, 125.3, 125.2, 18.0, 11.4.
Elemental analysis: calcd. (%) for C18H14OS (278.37): C 77.67, H 5.07;
found C 77.62, H 5.00.
3-([1,1′-Biphenyl]-2-yl)imidazo[1,2-a]pyridine (1f): Following the
procedure A, from imidazo[1,2-a]pyridine (0.177 g, 1.5 mmol), 2-
bromobiphenyl (0.233 g, 1 mmol) and PdCl(C3H5)(dppb) (12.2 mg,
0.02 mmol), compound 1f was obtained in 96 % yield (0.259 g) as
a yellow oil. 1H NMR (400 MHz, CDCl3) δ (ppm) 7.52 (s, 1H), 7.51–
7.33 (m, 6H), 7.14–6.98 (m, 5H), 6.91–6.86 (m, 1H), 6.31 (t, J = 6.7 Hz,
1H). 13C NMR (100 MHz, CDCl3) δ (ppm) 145.3, 141.5, 140.5, 133.6,
131.9, 130.6, 129.3, 128.3, 127.9, 127.8, 127.2, 127.1, 124.9, 123.8,
123.4, 117.5, 111.5. Elemental analysis: calcd. (%) for C19H14N2
(270.34): C 84.42, H 5.22; found C 84.59, H 5.00.
Ethyl 5-(Naphthalen-1-yl)thiophene-2-carboxylate (1l):[18] Fol-
lowing the procedure A, from ethyl thiophene-2-carboxylate
(0.234 g, 1.5 mmol), 1-bromonaphthalene (0.207 g, 1 mmol) and
Pd(OAc)2 (4.4 mg, 0.02 mmol), compound 1l was obtained in 81 %
1
5-([1,1′-Biphenyl]-2-yl)-2-isobutylthiazole (1g): Following the
yield (0.228 g) as a colorless oil. H NMR (400 MHz, CDCl3) δ (ppm)
procedure A, from 2-isobutylthiazole (0.211 g, 1.5 mmol), 2-bromo- 8.25 (d, J = 8.2 Hz, 1H), 7.97–7.88 (m, 3H), 7.61 (dd, J = 7.1, 1.1 Hz,
biphenyl (0.233 g, 1 mmol) and PdCl(C3H5)(dppb) (12.2 mg,
1H), 7.59–7.51 (m, 2H), 7.50 (d, J = 7.2 Hz, 1H), 7.26 (d, J = 3.8 Hz,
0.02 mmol), compound 1g was obtained in 95 % yield (0.278 g) as
1H), 4.48 (q, J = 7.6 Hz, 2H), 1.47 (t, J = 7.6 Hz, 3H). 13C NMR
a colorless oil. 1H NMR (400 MHz, CDCl3) δ (ppm) 7.57–7.52 (m, 1H), (100 MHz, CDCl3) δ (ppm) 162.3, 149.0, 133.9, 133.7, 133.6, 131.5,
7.43 (s, 1H), 7.41–7.38 (m, 3H), 7.34–7.30 (m, 3H), 7.30–7.23 (m, 2H), 131.4, 129.4, 128.6, 128.3, 128.1, 126.9, 126.3, 125.3, 125.2, 61.3, 14.5.
2.78 (d, J = 7.6 Hz, 2H), 2.11–2.00 (m, 1H), 0.97 (d, J = 7.6 Hz, 6H).
2-Isobutyl-5-(naphthalen-1-yl)thiazole (1m): Following the pro-
13C NMR (100 MHz, CDCl3) δ (ppm) 170.5, 141.3, 140.9, 140.5, 137.2,
cedure A, from 2-isobutylthiazole (0.211 g, 1.5 mmol), 1-bromo-
130.6, 130.4, 130.2, 129.7, 128.3, 128.2, 127.7, 127.3, 42.2, 29.8, 22.3.
naphthalene (0.207 g, 1 mmol) and Pd(OAc)2 (4.4 mg, 0.02 mmol),
Elemental analysis: calcd. (%) for C19H19NS (293.43): C 77.77, H 6.53;
compound 1m was obtained in 93 % yield (0.248 g) as a yellow oil.
found C 77.59, H 6.35.
1H NMR (400 MHz, CDCl3) δ (ppm) 8.19 (d, J = 8.2 Hz, 1H), 7.91–
1-(5-([1,1′Biphenyl]-2-yl)thiazol-2-yl)ethan-1-one (1h): Following
the procedure A, from 2-acetylthiazole (0.190 g, 1.5 mmol), 2-
bromobiphenyl (0.233 g, 1 mmol) and PdCl(C3H5)(dppb) (12.2 mg,
0.02 mmol), compound 1h was obtained in 91 % yield (0.254 g) as
a white solid m.p. 117–119 °C. 1H NMR (400 MHz, CDCl3) δ (ppm)
7.57 (s, 1H), 7.55 (d, J = 8.1 Hz, 1H), 7.50–7.38 (m, 3H), 7.34–7.30 (m,
3H), 7.23–7.17 (m, 2H), 2.64 (s, 3H). 13C NMR (100 MHz, CDCl3) δ
(ppm) 191.7, 166.1, 146.1, 143.3, 141.7, 140.2, 131.0, 130.7, 129.5,
129.4, 129.0, 128.5, 127.9, 127.8, 25.7. Elemental analysis: calcd. (%)
for C17H13NOS (279.36): C 73.09, H 4.69; found C 73.25, H 4.47.
7.81 (m, 3H), 7.57–7.47 (m, 3H), 7.45 (t, J = 7.6 Hz, 1H), 2.98 (d, J =
7.6 Hz, 2H), 2.32–2.17 (m, 1H), 1.11 (d, J = 7.6 Hz, 6H). 13C NMR
(100 MHz, CDCl3) δ (ppm) 170.5, 141.2, 135.5, 133.8, 131.9, 129.0
(m), 128.6, 128.5, 126.8, 126.2, 125.3, 125.2, 42.5, 29.9, 22.5. Elemen-
tal analysis: calcd. (%) for C17H17NS (267.39): C 76.36, H 6.41; found
C 76.50, H 6.65.
5-(4-Fluoronaphthalen-1-yl)-2-isobutylthiazole (1n): Following
the procedure A, from 2-isobutylthiazole (0.211 g, 1.5 mmol), 1-
bromo-4-fluoronaphthalene (0.225 g, 1 mmol) and Pd(OAc)2
(4.4 mg, 0.02 mmol), compound 1n was obtained in 91 % yield
1-(5-(Naphthalen-1-yl)thiophen-2-yl)ethan-1-one (1i): Following (0.259 g) as a white solid: m.p. 109–111 °C. 1H NMR (400 MHz,
the procedure A, from 2-acetylthiophene (0.189 g, 1.5 mmol), 1- CDCl3) δ (ppm) 8.03–7.95 (m, 2H), 7.62 (s, 1H), 7.42–7.35 (m, 2H),
bromonaphthalene (0.207 g, 1 mmol) and Pd(OAc)2 (4.4 mg,
7.28 (dd, J = 7.9, 5.4, 1H), 6.97 (dd, J = 10.0, 7.9 Hz, 1H), 2.84 (d, J =
0.02 mmol), compound 1i was obtained in 82 % yield (0.206 g) as
7.6 Hz, 2H), 2.20–2.00 (m, 1H), 0.98 (d, J = 7.6 Hz, 6H). 13C NMR
1
a white solid: m.p. 113–115 °C. H NMR (400 MHz, CDCl3) δ (ppm) (100 MHz, CDCl3) δ (ppm) 170.5, 158.7 (d, J = 254.8 Hz), 141.2, 134.6,
8.21 (d, J = 8.2 Hz, 1H), 7.97–7.90 (m, 2H), 7.79 (d, J = 3.8 Hz, 1H),
7.63–7.50 (m, 4H), 7.30 (d, J = 3.8 Hz, 1H), 2.65 (s, 3H). 13C NMR
(100 MHz, CDCl3) δ (ppm) 190.7, 150.7, 144.2, 133.8, 132.7, 131.4,
133.1 (d, J = 4.9 Hz), 128.3 (d, J = 8.6 Hz), 127.5, 126.4 (d, J = 1.8 Hz),
125.2 (d, J = 2.6 Hz), 124.9 (d, J = 4.5 Hz), 123.8 (d, J = 16.3 Hz),
120.8 (d, J = 5.7 Hz), 108.9 (d, J = 20.5 Hz), 42.4, 29.7, 22.4. Elemental
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analysis: calcd. (%) for C17H16FNS (285.38): C 71.55, H 5.65; found C
71.48, H 5.36.
25 °C for 16 hours. After concentration, the crude mixture was fil-
tered by silica column chromatography (diethyl ether/heptane, 1:4)
to afford the desired brominated products which were used without
further purification.
Cyclopropyl(5-(pyren-1-yl)thiophen-2-yl)methanone (1o): Fol-
lowing the procedure A, from cyclopropyl(thiophen-2-yl)methan-
one (0.228 g, 1.5 mmol), 1-bromopyrene (0.281 g, 1 mmol) and
Pd(OAc)2 (4.4 mg, 0.02 mmol), compound 1o was obtained in 84 %
yield (0.296 g) as a white solid: m.p. 193–195 °C. 1H NMR (400 MHz,
CDCl3) δ (ppm) 8.49 (d, J = 9.3 Hz, 1H), 8.30–8.16 (m, 3H), 8.15–8.02
(m, 5H), 7.98 (d, J = 3.8 Hz, 1H), 7.44 (d, J = 3.8 Hz, 1H), 2.70–2.61
(m, 1H), 1.40–1.32 (m, 2H), 1.16–1.07 (m, 2H). 13C NMR (100 MHz,
CDCl3) δ (ppm) 192.9, 150.8, 145.1, 131.8, 131.7, 131.4, 130.8, 129.0,
128.9, 128.6, 128.5, 128.3, 128.1, 127.3, 126.3, 125.7, 125.4, 125.0,
124.7, 124.4, 18.0, 11.4. Elemental analysis: calcd. (%) for C24H16OS
(352.45): C 81.79, H 4.58; found C 81.90, H 4.38.
1-(5-(Pyren-1-yl)thiophen-2-yl)ethan-1-one (1p):[19] Following
the procedure A, from 2-acetylthiophene (0.189 g, 1.5 mmol), 1-
bromopyrene (0.281 g, 1 mmol) and Pd(OAc)2 (4.4 mg, 0.02 mmol),
compound 1p was obtained in 79 % yield (0.257 g) as a white solid
m.p. 116–118 °C. 1H NMR (400 MHz, CDCl3) δ (ppm) 8.46 (d, J =
9.3 Hz, 1H), 8.24–8.01 (m, 8H), 7.83 (d, J = 3.8 Hz, 1H), 7.40 (d, J =
3.8 Hz, 1H), 2.68 (s, 3H). 13C NMR (100 MHz, CDCl3) δ (ppm) 190.8,
151.6, 144.7, 132.9, 131.8, 131.5, 130.9, 129.1, 129.0, 128.7, 128.6,
128.5, 128.2, 127.4, 126.5, 125.9, 125.5, 125.1, 124.8, 124.7, 124.4,
26.9.
1-(5-([1,1′-Biphenyl]-2-yl)-4-bromothiophen-2-yl)ethan-1-one
(2a): Following the procedure B, from 1-(5-([1,1′-biphenyl]-2-yl)thio-
phen-2-yl)ethan-1-one 1a (0.278, 1 mmol), compound 2a was ob-
1
tained in 86 % yield (0.307 g) as a colorless oil. H NMR (400 MHz,
CDCl3) δ (ppm) 7.60–7.42 (m, 5H), 7.33–7.24 (m, 5H), 2.50 (s, 3H).
13C NMR (100 MHz, CDCl3) δ (ppm) 189.7, 147.3, 143.3, 142.5, 140.3,
134.9, 131.6, 130.6, 130.4, 129.9, 129.3, 128.2, 127.4, 127.3, 111.0,
26.4.
(5-([1,1′-Biphenyl]-2-yl)-4-bromothiophen-2-yl)(cyclopropyl)-
methanone (2b): Following the procedure B, from (5-([1,1′-bi-
phenyl]-2-yl)thiophen-2-yl)(cyclopropyl)methanone 1b (0.307,
1 mmol), compound 2b was obtained in 85 % yield (0.325 g) as a
yellow oil. 1H NMR (400 MHz, CDCl3) δ (ppm) 7.62–7.42 (m, 5H),
7.30–7.20 (m, 5H), 2.46–2.35 (m, 1H), 1.26–1.19 (m, 2H), 1.06–0.99
(m, 2H). 13C NMR (100 MHz, CDCl3) δ (ppm) 192.0, 146.7, 143.7,
142.5, 140.4, 134.1, 131.7, 130.6, 130.5, 129.9, 129.3, 128.2, 127.4,
127.3, 111.1, 17.8, 11.9.
Ethyl 5-([1,1′-biphenyl]-2-yl)-4-bromothiophene-2-carboxylate
(2c): Following the procedure B, from ethyl 5-([1,1′-biphenyl]-2-
yl)thiophene-2-carboxylate 1c (0.308, 1 mmol), compound 2c was
obtained in 83 % yield (0.321 g) as a colorless oil. 1H NMR (400 MHz,
CDCl3) δ (ppm) 7.63 (s, 1H), 7.58–7.42 (m, 4H), 7.35–7.25 (m, 5H),
4.35 (q, J = 7.6 Hz, 2H), 1.38 (t, J = 7.6 Hz, 3H). 13C NMR (100 MHz,
CDCl3) δ (ppm) 161.2, 145.5, 142.6, 140.4, 135.6, 133.6, 131.9, 130.6,
130.4, 129.9, 129.3, 128.2, 127.4, 127.3, 111.0, 61.6, 14.4.
Ethyl 5-(pyren-1-yl)thiophene-2-carboxylate (1q): Following the
procedure A, from ethyl thiophene-2-carboxylate (0.234 g,
1.5 mmol), 1-bromopyrene (0.281 g, 1 mmol) and Pd(OAc)2 (4.4 mg,
0.02 mmol), compound 1q was obtained in 82 % yield (0.292 g) as
1
a white solid: m.p. 146–148 °C. H NMR (400 MHz, CDCl3) δ (ppm)
8.47 (d, J = 9.3 Hz, 1H), 8.29–8.17 (m, 3H), 8.16–8.03 (m, 5H), 7.97
(d, J = 3.8 Hz, 1H), 7.38 (d, J = 3.8 Hz, 1H), 4.45 (q, J = 7.6 Hz, 2H),
1.46 (t, J = 7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ (ppm) 162.3,
149.7, 134.1, 133.6, 131.6, 131.4, 130.8, 129.0, 128.6, 128.4, 128.3,
128.2, 127.3, 126.3, 125.7, 125.4, 125.0, 124.7, 124.6, 124.4, 61.3, 14.4.
Elemental analysis: calcd. (%) for C23H16O2S (356.44): C 77.50, H 4.52;
found C 77.26, H 4.67.
1-(5-([1,1′-Biphenyl]-2-yl)-4-bromo-3-chlorothiophen-2-yl)eth-
an-1-one (2d): Following the procedure B, from 1-(5-([1,1′-bi-
phenyl]-2-yl)-3-chlorothiophen-2-yl)ethan-1-one 1d (0.313,
1 mmol), compound 2d was obtained in 78 % yield (0.305 g) as a
white solid: m.p. 151–153 °C. 1H NMR (400 MHz, CDCl3) δ (ppm)
7.60–7.42 (m, 4H), 7.33–7.28 (m, 3H), 7.27–7.21 (m, 2H), 2.67 (s, 3H).
13C NMR (100 MHz, CDCl3) δ (ppm) 189.3, 145.8, 142.4, 140.0, 137.3,
131.4, 130.7, 130.5, 129.2, 129.0, 128.3, 127.5, 127.4, 114.4, 29.7.
2-Isobutyl-5-(pyren-1-yl)thiazole (1r): Following the procedure A,
from 2-isobutylthiazole (0.211 g, 1.5 mmol), 1-bromopyrene
(0.281 g, 1 mmol) and Pd(OAc)2 (4.4 mg, 0.02 mmol), compound 1r
was obtained in 91 % yield (0.310 g) as a yellow oil. 1H NMR
(400 MHz, CDCl3) δ (ppm) 8.38 (d, J = 9.2 Hz, 1H), 8.15–8.09 (m, 2H),
8.07–7.94 (m, 6H), 7.93 (s, 1H), 3.05 (d, J = 7.6 Hz, 2H), 2.36–2.24 (m,
1H), 1.17 (d, J = 7.6 Hz, 6H). 13C NMR (100 MHz, CDCl3) δ (ppm)
171.0, 141.5, 136.2, 131.3, 131.2, 130.8, 129.2, 128.4, 128.2, 128.0,
127.2, 126.2, 126.0, 125.5, 125.2, 124.9, 124.6, 124.5, 124.3, 42.6, 30.0,
22.5. Elemental analysis: calcd. (%) for C23H19NS (341.47): C 80.90, H
5.61; found C 81.14, H 5.39.
Methyl 5-([1,1′-biphenyl]-2-yl)-4-bromofuran-2-carboxylate
(2e): Following the procedure B, from methyl 5-([1,1′-biphenyl]-2-
yl)furan-2-carboxylate 1e (0.278, 1 mmol), compound 2e was ob-
tained in 61 % yield (0.218 g) as a white solid: m.p. 96–98 °C. 1H
NMR (400 MHz, CDCl3) δ (ppm) 7.62 (d, J = 8.0 Hz, 1H), 7.57–7.47
(m, 2H), 7.44 (t, J = 7.8 Hz, 1H), 7.34–7.26 (m, 3H), 7.24–7.18 (m, 2H),
7.14 (s, 1H), 3.79 (s, 3H). 13C NMR (100 MHz, CDCl3) δ (ppm) 158.2,
154.7, 143.4, 142.7, 140.6, 130.5, 130.4, 128.7, 128.2, 127.3, 127.2,
126.7, 121.7, 100.1, 52.0.
5-([1,1′-Biphenyl]-2-yl)-4-bromo-2-isobutylthiazole (2g): Follow-
ing the procedure B, from 5-([1,1′-biphenyl]-2-yl)-2-isobutylthiazole
1g (0.293, 1 mmol), compound 2g was obtained in 87 % yield
1-(5-(Pyren-1-yl)thiazol-2-yl)ethan-1-one (1s): Following the pro-
cedure A, from 2-acetylthiazole (0.190 g, 1.5 mmol), 1-bromopyrene
(0.281 g, 1 mmol) and Pd(OAc)2 (4.4 mg, 0.02 mmol), compound 1s
was obtained in 81 % yield (0.265 g) as a yellow solid m.p. 98–
1
(0.323 g) as a colorless oil. H NMR (400 MHz, CDCl3) δ (ppm) 7.59–
1
7.40 (m, 4H), 7.33–7.21 (m, 5H), 2.76 (d, J = 7.6 Hz, 2H), 2.09–1.98
(m, 1H), 0.94 (d, J = 7.6 Hz, 6H). 13C NMR (100 MHz, CDCl3) δ (ppm)
170.7, 142.8, 140.4, 133.8, 132.1, 131.9, 130.3, 129.4, 128.8, 128.1,
127.3, 124.9, 123.8, 42.4, 29.7, 22.2.
100 °C. H NMR (400 MHz, CDCl3) δ (ppm) 8.35 (d, J = 9.2 Hz, 1H),
8.28–8.19 (m, 4H), 8.18–8.12 (m, 2H), 8.11–8.03 (m, 3H), 2.82 (s, 3H).
13C NMR (100 MHz, CDCl3) δ (ppm) 191.8, 166.9, 145.3, 144.1, 132.1,
131.3, 130.7, 129.2, 129.0, 128.7, 128.4, 127.2, 126.5, 126.0, 125.7,
124.9, 124.7, 124.6, 124.5, 123.8, 25.9. Elemental analysis: calcd. (%)
for C21H13NOS (327.40): C 77.04, H 4.00; found C 76.69, H 3.68.
1-(5-([1,1′-Biphenyl]-2-yl)-4-bromothiazol-2-yl)ethan-1-one
(2h): Following the procedure B, from 1-(5-([1,1′biphenyl]-2-yl)thi-
azol-2-yl)ethan-1-one 1h (0.279, 1 mmol), compound 2h was ob-
Procedure B (Bromination of compounds 1a–1s): To a 25 mL
oven dried Schlenk tube, the arylated heteroarene derivatives 1a–
1s (1 mmol), N-bromosuccinimide (0.356 g, 2 mmol) and DMF
(2 mL) were successively added. The reaction mixture was stirred at
1
tained in 64 % yield (0.229 g) as a white solid: m.p. 107–109 °C. H
NMR (400 MHz, CDCl3) δ (ppm) 7.63–7.55 (m, 1H), 7.54–7.45 (m,
3H), 7.32–7.28 (m, 3H), 7.22–7.18 (m, 2H), 2.68 (s, 3H). 13C NMR
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(100 MHz, CDCl3) δ (ppm) 190.7, 165.4, 142.7, 142.1, 139.8, 131.5,
130.6, 130.2, 129.3, 128.3, 127.8, 127.6, 127.5, 126.7, 25.6.
(oil bath temperature) for 3 or 16 hours (see Scheme 5). After cool-
ing the reaction at room temperature and concentration, the crude
mixture was purified by silica column chromatography (diethyl
ether/heptane, 2:3) to afford the desired products.
1-(4-Bromo-5-(naphthalen-1-yl)thiophen-2-yl)ethan-1-one (2i):
Following the procedure B, from 1-(5-(naphthalen-1-yl)thiophen-2-
yl)ethan-1-one 1i (0.252, 1 mmol), compound 2i was obtained in
48 % yield in an impure form (85 % purity, 0.187 g) as a yellow
1-(Phenanthro[9,10-b]thiophen-2-yl)ethan-1-one (3a): Following
the procedure C, from 1-(5-([1,1′-biphenyl]-2-yl)-4-bromothiophen-
2-yl)ethan-1-one 2a (0.179 g, 0.5 mmol), compound 3a was ob-
tained in 87 % yield (0.120 g) as a yellow solid: m.p. 218–220 °C. 1H
NMR (400 MHz, CDCl3) δ (ppm) 8.70–8.62 (m, 2H), 8.47 (s, 1H), 8.31–
8.25 (m, 1H), 8.15 (d, J = 7.8 Hz, 1H), 7.76–7.61 (m, 4H), 2.75 (s, 3H).
13C NMR (100 MHz, CDCl3) δ (ppm) 191.4, 142.4, 142.2, 134.9, 129.9,
129.2, 128.6, 128.2, 128.1, 127.6 (m), 127.5, 126.7, 124.9, 123.9, 123.7,
123.6, 26.9. Elemental analysis: calcd. (%) for C18H12OS (276.35): C
78.23, H 4.38; found C 78.39, H 4.57.
1
solid: m.p. 116–118 °C. H NMR (400 MHz, CDCl3) δ (ppm) 7.97 (d,
J = 6.8 Hz, 1H), 7.93 (d, J = 7.2 Hz, 1H), 7.77–7.65 (m, 2H), 7.55–7.44
(m, 4H), 2.64 (s, 3H). 13C NMR (100 MHz, CDCl3) δ (ppm) 190.6, 149.5,
144.6, 132.6, 132.4, 132.2, 129.4, 128.8, 128.3, 127.8, 127.7, 127.6,
125.9, 124.4, 26.8.
1-(4-Bromo-5-(4-fluoronaphthalen-1-yl)thiophen-2-yl)ethan-1-
one (2j): Following the procedure B, from 1-(5-(4-fluoronaphthalen-
1-yl)thiophen-2-yl)ethan-1-one 1j (0.270, 1 mmol), compound 2j
was obtained in 65 % yield (0.226 g) as a white solid: m.p. 92–94 °C.
1H NMR (400 MHz, CDCl3) δ (ppm) 8.19 (d, J = 7.8 Hz, 1H), 7.75 (s,
1H), 7.72 (d, J = 8.0 Hz, 1H), 7.65–7.57 (m, 2H), 7.48 (dd, J = 7.9,
5.3 Hz, 1H), 7.24 (dd, J = 10.0, 8.0 Hz, 1H), 2.61 (s, 3H). 13C NMR
(100 MHz, CDCl3) δ (ppm) 189.7, 159.8 (d, J = 255.7 Hz), 144.6, 143.7,
135.0, 132.8 (d, J = 5.2 Hz), 129.2 (d, J = 8.9 Hz), 127.9, 126.7 (d, J =
1.9 Hz), 125.7 (d, J = 2.6 Hz), 125.4 (d, J = 4.5 Hz), 123.8 (d, J =
16.5 Hz), 121.1 (d, J = 5.6 Hz), 112.0, 109.0 (d, J = 20.6 Hz), 26.5.
Cyclopropyl(phenanthro[9,10-b]thiophen-2-yl)methanone (3b):
Following the procedure C, from (5-([1,1′-biphenyl]-2-yl)-4-bromo-
thiophen-2-yl)(cyclopropyl)methanone 2b (0.192 g, 0.5 mmol), com-
pound 3b was obtained in 85 % yield (0.128 g) as a yellow solid:
1
m.p. 247–249 °C. H NMR (400 MHz, CDCl3) δ (ppm) 8.68–8.60 (m,
3H), 8.31 (d, J = 6.4 Hz, 1H), 8.17 (d, J = 7.8 Hz, 1H), 7.70–7.62 (m,
4H), 2.81–2.72 (m, 1H), 1.40–1.30 (m, 2H), 1.20–1.10 (m, 2H). 13C
NMR (100 MHz, CDCl3) δ (ppm) 193.5, 142.9, 141.8, 135.0, 129.8,
129.2, 128.8, 128.0, 127.7, 127.6, 127.5, 127.2, 126.7, 124.8, 124.0,
123.7, 123.6, 18.2, 11.8. Elemental analysis: calcd. (%) for C20H14OS
(302.39): C 79.44, H 4.67; found C 79.32, H 4.79.
(4-Bromo-5-(naphthalen-1-yl)thiophen-2-yl)(cyclopropyl)meth-
anone (2k): Following the procedure B, from cyclopropyl(5-
(naphthalen-1-yl)thiophen-2-yl)methanone 1k (0.278, 1 mmol),
compound 2k was obtained in 45 % yield as a colorless oil in an
impure form (60 % purity, 0.269 g). 1H NMR (400 MHz, CDCl3) δ
(ppm) 8.00–7.65 (m, 4H), 7.58–7.47 (m, 4H), 2.64–2.51 (m, 1H), 1.38–
1.30 (m, 2H), 1.14–1.05 (m, 2H).
Ethyl phenanthro[9,10-b]thiophene-2-carboxylate (3c): Follow-
ing the procedure C, from ethyl 5-([1,1′-biphenyl]-2-yl)-4-bromothio-
phene-2-carboxylate 2c (0.193 g, 0.5 mmol), compound 3c was ob-
1
tained in 84 % yield (0.128 g) as a white solid: m.p. 190–192 °C. H
NMR (400 MHz, CDCl3) δ (ppm) 8.67 (d, J = 8.6 Hz, 2H), 8.64 (s, 1H),
8.34–8.30 (m, 1H), 8.15 (d, J = 7.8 Hz, 1H), 7.74–7.61 (m, 4H), 4.49
(q, J = 7.6 Hz, 2H), 1.50 (t, J = 7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3)
δ (ppm) 162.7, 141.1, 134.7, 132.2, 129.7, 129.2, 129.1, 128.6, 127.8,
127.7, 127.5, 126.6, 124.6, 124.2, 123.7, 123.5, 61.6, 14.4. Elemental
analysis: calcd. (%) for C19H14O2S (306.38): C 74.49, H 4.61; found C
74.67, H 4.90.
Ethyl 4-Bromo-5-(naphthalen-1-yl)thiophene-2-carboxylate (2l):
Following the procedure B, from ethyl 5-(naphthalen-1-yl)thio-
phene-2-carboxylate 1l (0.282, 1 mmol), compound 2l was obtained
in 49 % yield as a colorless oil in an impure form (75 % purity,
0.236 g). 1H NMR (400 MHz, CDCl3) δ (ppm) 7.97 (d, J = 6.8 Hz, 1H),
7.93 (d, J = 7.2 Hz, 1H), 7.85–7.73 (m, 2H), 7.57–7.47 (m, 4H), 4.46
(q, J = 7.6 Hz, 2H), 1.47 (t, J = 7.6 Hz, 3H).
Methyl Phenanthro[9,10-b]furan-2-carboxylate (3e): Following
the procedure C, from methyl 5-([1,1′-biphenyl]-2-yl)-4-bromofuran-
2-carboxylate 2e (0.178 g, 0.5 mmol), compound 3e was obtained
in 84 % yield (0.116 g) as a white solid: m.p. 156–158 °C. 1H NMR
(400 MHz, CDCl3) δ (ppm) 8.62 (d, J = 6.4 Hz, 2H), 8.44–8.40 (m, 1H),
8.06 (d, J = 7.0 Hz, 1H), 7.93 (s, 1H), 7.69–7.59 (m, 4H), 4.02 (s, 3H).
13C NMR (100 MHz, CDCl3) δ (ppm) 159.7, 151.3, 144.6, 130.6, 128.4,
127.5, 127.4, 127.3, 126.8, 126.0, 123.9, 123.6, 123.4, 121.8, 121.6,
120.5, 113.7, 52.2. Elemental analysis: calcd. (%) for C18H12O3
(276.29): C 78.25, H 4.38; found C 78.39, H 4.61.
4-Bromo-2-isobutyl-5-(naphthalen-1-yl)thiazole (2m): Following
the procedure B, from 2-isobutyl-5-(naphthalen-1-yl)thiazole 1m
(0.267, 1 mmol), compound 2m was obtained in 63 % yield (0.218 g)
as a white solid: m.p. 128–130 °C. 1H NMR (400 MHz, CDCl3) δ (ppm)
8.00–7.91 (m, 2H), 7.83–7.76 (m, 1H), 7.60–7.50 (m, 4H), 2.97 (d, J =
7.6 Hz, 2H), 2.31–2.17 (m, 1H), 1.12 (d, J = 7.6 Hz, 6H). 13C NMR
(100 MHz, CDCl3) δ (ppm) 171.1, 133.7, 132.0, 130.2, 129.9, 129.7,
128.5, 127.6, 126.9, 126.3, 125.6, 125.2, 124.5, 42.7, 29.8, 22.4.
4-Bromo-5-(4-fluoronaphthalen-1-yl)-2-isobutylthiazole (2n):
Following the procedure B, from 5-(4-fluoronaphthalen-1-yl)-2-iso-
butylthiazole 1n (0.285, 1 mmol), compound 2n was obtained in
68 % yield (0.247 g) as a white solid: m.p. 99–101 °C. 1H NMR
(400 MHz, CDCl3) δ (ppm) 8.18 (d, J = 7.8 Hz, 1H), 7.73 (d, J = 8.0 Hz,
1H), 7.62–7.53 (m, 2H), 7.47 (dd, J = 7.9, 5.3 Hz, 1H), 7.20 (dd, J =
10.0, 8.0 Hz, 1H), 2.93 (d, J = 7.6 Hz, 2H), 2.26–2.24 (m, 1H), 1.07 (d,
J = 7.6 Hz, 6H). 13C NMR (100 MHz, CDCl3) δ (ppm) 171.2, 159.5 (d,
J = 255.3 Hz), 133.4 (d, J = 5.2 Hz), 129.6 (d, J = 8.9 Hz), 129.4, 127.8,
126.6 (d, J = 1.8 Hz), 125.6 (d, J = 2.5 Hz), 124.8, 123.9 (d, J =
16.5 Hz), 123.5 (d, J = 4.5 Hz), 121.0 (d, J = 5.5 Hz), 109.1 (d, J =
20.6 Hz), 42.7, 29.8, 22.4.
2-Isobutylphenanthro[9,10-d]thiazole (3g): Following the proce-
dure C, from 5-([1,1′-biphenyl]-2-yl)-4-bromo-2-isobutylthiazole 2g
(0.186 g, 0.5 mmol), compound 3g was obtained in 90 % yield
(0.131 g) as a yellow solid: m.p. 118–120 °C. 1H NMR (400 MHz,
CDCl3) δ (ppm) 8.93 (d, J = 7.6 Hz, 1H), 8.62–8.55 (m, 2H), 7.88–7.84
(m, 1H), 7.77 (t, J = 7.2 Hz, 1H),7.67 (t, J = 7.6 Hz, 1H), 7.58–7.54 (m,
2H), 3.12 (d, J = 7.6 Hz, 2H), 2.45–2.30 (m, 1H), 1.17 (d, J = 7.6 Hz,
6H). 13C NMR (100 MHz, CDCl3) δ (ppm) 169.5, 148.6, 130.5, 129.7,
128.7, 128.2, 127.3 (m), 127.2, 126.6, 126.3, 125.8, 124.9, 123.6, 123.0,
43.2, 30.0, 22.6. Elemental analysis: calcd. (%) for C19H17NS (291.41):
C 78.31, H 5.88; found C 78.61, H 5.74.
Procedure C (Direct intramolecular arylation of heteroarenes):
To a 25 mL oven dried Schlenk tube, heteroaryl bromide (0.5 mmol), 1-(Acenaphtho[1,2-b]thiophen-8-yl)ethan-1-one (4i):[20] Follow-
KOPiv (0.140 g, 1 mmol), DMA (2 mL) and PdCl(C3H5)(dppb) (6.1 mg,
0.01 mmol) were successively added. The reaction mixture was
evacuated by vacuum-argon cycles (5 times) and stirred at 150 °C
ing the procedure C, from 1-(4-bromo-5-(naphthalen-1-yl)thiophen-
2-yl)ethan-1-one 2i (0.166 g, 0.5 mmol), compound 4i was obtained
in 53 % yield (0.066 g) as a yellow solid: m.p. 149–151 °C. H NMR
1
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(400 MHz, CDCl3) δ (ppm) 7.96 (s, 1H), 7.88 (d, J = 7.5 Hz, 1H), 7.84
(d, J = 7.6 Hz, 1H), 7.81 (d, J = 8.2 Hz, 1H), 7.76 (d, J = 6.9 Hz, 1H),
7.63–7.57 (m, 2H), 2.65 (s, 3H). 13C NMR (100 MHz, CDCl3) δ (ppm)
190.9, 149.0, 146.9, 145.3, 134.0, 132.9, 132.4, 129.6, 128.3, 127.9
(m), 126.7, 125.0, 122.3, 121.2, 26.7.
[4]
[5]
Acenaphtho[1,2-b]thiophen-8-yl(cyclopropyl)methanone (4k):
Following the procedure C, from (4-bromo-5-(naphthalen-1-yl)thio-
phen-2-yl)(cyclopropyl)methanone 2k (0.179 g, 0.5 mmol), com-
pound 4k was obtained in 51 % yield (0.070 g) as a yellow solid:
m.p. 99–101 °C. 1H NMR (400 MHz, CDCl3) δ (ppm) 8.07 (s, 1H),
7.88–7.75 (m, 3H), 7.73 (d, J = 6.9 Hz, 1H), 7.61–7.55 (m, 2H), 2.66–
2.55 (m, 1H), 1.38–1.29 (m, 2H), 1.14–1.05 (m, 2H). 13C NMR
(100 MHz, CDCl3) δ (ppm) 193.1, 148.5, 147.5, 134.0, 133.0, 132.5,
129.5, 128.2, 127.9 (m), 126.7, 124.1, 122.2, 121.1, 18.0, 11.4. Elemen-
tal analysis: calcd. (%) for C18H12OS (276.35): C 78.23, H 4.38; found
C 77.98, H 4.25.
Ethyl Acenaphtho[1,2-b]thiophene-8-carboxylate (4l):[20] Follow-
ing the procedure C, from ethyl 4-bromo-5-(naphthalen-1-yl)thio-
phene-2-carboxylate 2l (0.181 g, 0.5 mmol), compound 4l was ob-
tained in 38 % yield (0.053 g) as a yellow solid: m.p. 178–180 °C. 1H
NMR (400 MHz, CDCl3) δ (ppm) 8.12 (s, 1H), 7.90–7.76 (m, 4H), 7.64–
7.58 (m, 2H), 4.44 (q, J = 7.6 Hz, 2H), 1.46 (t, J = 7.6 Hz, 3H).
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[9]
8-Isobutylacenaphtho[1,2-d]thiazole (4m): Following the proce-
dure C, from 4-bromo-2-isobutyl-5-(naphthalen-1-yl)thiazole 2m
(0.173 g, 0.5 mmol), compound 4m was obtained in 21 % yield
(0.028 g) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ (ppm) 8.02 (d,
J = 6.9 Hz, 1H), 7.81 (d, J = 8.1 Hz, 2H), 7.71 (d, J = 6.9 Hz, 1H), 7.61
(t, J = 8.1 Hz, 1H), 7.57 (t, J = 8.1 Hz, 1H), 3.04 (d, J = 7.6 Hz, 2H),
2.33–2.17 (m, 1H), 1.10 (d, J = 7.6 Hz, 6H). 13C NMR (100 MHz, CDCl3)
δ (ppm) 173.6, 160.4, 133.6, 131.9, 131.8, 130.9, 129.2, 127.8, 127.6,
127.3, 127.2, 121.8, 121.4, 43.4, 30.1, 22.4. Elemental analysis: calcd.
(%) for C17H15NS (265.37): C 76.94, H 5.70; found C 77.20, H 5.60.
Acknowledgments
We are grateful to the CNRS, Rennes Metropole and Scientific
Ministry of Higher Education and Research of Tunisia for provid-
ing financial support.
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Received: May 27, 2019
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Full Paper
C-H Bond Functionalization
B. Bouzayani, R. Ben Salem,*
J.-F. Soulé,* H. Doucet* .................... 1–9
Intermolecular Followed by Intra-
molecular Palladium-Catalyzed Di-
rect Arylation for the Synthesis of
π-Extended Aromatic Compounds
Containing One or Two Heteroele-
ments
The sequential palladium-catalyzed phenanthro[9,10-b]thiophenes, phen-
intermolecular direct arylation, brom- anthro[9,10-b]thiazoles, acenaphtho-
ination followed by intramolecular di- [1,2-d]thiophenes and acenaphtho-
rect arylation allowed the synthesis of [1,2-d]thiazoles in only three steps.
DOI: 10.1002/ejoc.201900775
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