Comparison of ullmann/RCM and ullmann/bis-hydrazone coupling reactions; New access to benzodithiophenes for dye-sensitized solar cell and thiahelicene applications

Article abstract of DOI:10.1055/s-0033-1340667

The use of CuTC (Liebeskind's catalyst), followed by methylenation and ring-closing metathesis, or bis-hydrazone coupling reactions is described. This approach establishes an alternative non-photochemical synthesis of the strategically important 1,2-b:4,3-b′ BDT regioisomer, which has previously been underused in applications such as dye-sensitized solar cells and nonlinear optics because of the difficulty of synthesis on a large scale. Georg Thieme Verlag Stuttgart. New York.

Full text of DOI:10.1055/s-0033-1340667

LETTER
▌701
lCettoermparison of Ullmann/RCM and Ullmann/Bis-hydrazone Coupling Reac-
tions; New Access to Benzodithiophenes for Dye-Sensitized Solar Cell and
Thiahelicene Applications
Ullmann/RCM and Ullmann/Bis-hydrazone Coupling Reactions
G. Richard Stephenson,*a Silvia Cauteruccio,b Julien Doulceta
a
School of Chemistry, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK
Fax +44(1603)592003; E-mail: g.r.stephenson@uea.ac.uk
b
Dipartimento di Chimica, Università degli Studi di Milano, via Golgi 19, 20133 Milano, Italy
Received: 21.10.2013; Accepted after revision: 31.12.2013
S
Abstract: The use of CuTC (Liebeskind’s catalyst), followed by
S
S
methylenation and ring-closing metathesis, or bis-hydrazone cou-
pling reactions is described. This approach establishes an alterna-
tive non-photochemical synthesis of the strategically important 1,2-
b:4,3-b′ BDT regioisomer, which has previously been underused in
applications such as dye-sensitized solar cells and nonlinear optics
because of the difficulty of synthesis on a large scale.
S
1
2
benzo[1,2-b:4,3-b']dithiophene
benzo[1,2-b:4,5-b']dithiophene
S
Key words: benzodithiophene, Liebeskind’s catalyst, bis-hydra-
zone coupling, alkene metathesis, non-photochemical synthesis
S
S
S
3
4
benzo[2,1-b:4,3-b']dithiophene
benzothienobenzothiophene
R
R
S
S
The combination of thiophenes and benzene rings in high-
performance chromophores has proved to be a powerful
strategy1 because of the lower aromatic resonance energy
of thiophene compared to benzene.2 Linear and fused-ring
structures, of which the simplest (examples are shown in
Figure 1) are benzothiophenes (BTs), benzodithiophenes
(BDTs, e.g. 1,2,3) and benzothienobenzothiophenes (BT-
BTs, e.g. 4). These have found significant commercial ap-
plications in organic field-effect transistors3 (OFETs),
organic light-emitting diodes4 (OLEDs) and solar cells.5
In practice, isomers 2 and 3 are by far the most widely
studied, and are of growing importance,6 however, recent
papers describing applications in dye-sensitized solar
cells (DSCs) point out that the symmetrical isomer 1 is un-
derused.7 For our own interests in tetrathia[7]helicenes as
components in nonlinear optics 8,9 and in novel chelating
diphosphine ligands,10 regioisomer 1 is a well-established
key intermediate which, of the available BTDs, has a
unique role because its extension (by incorporating addi-
tional fused rings) is ideal for helix formation.11 The most
efficient access12 to tetrathia[7]helicenes employs a pho-
tochemical electrocyclic reaction of 5 combined with ox-
idative rearomatisation as the final step. Currently, this
type of photochemical cyclisation is also used for the
preparation of regioisomer 1, but this approach is slow
and inconvenient in the unsubstituted series because the
Z-isomer of the alkene is required for photocyclisation. In
most cases, applications have involved substituted exam-
ples, which are easier to prepare.13
5
S
S
Figure 1 Structures of thiophene-based cores of high-performance
chromophores 1–4 and the tetrathia[7]helicene precursor 5
We describe here chemical syntheses14 of benzo[1,2-
b:4,3-b′]dithiophenes that will not only make 1 more eas-
ily available for tetrathia[7]helicene synthesis, but will
also open up opportunities for more rapid development for
commercial applications, where previous reliance on pho-
tochemical steps cause complications in production
chemistry that has held back evaluation of the 1,2-b:4,3-b′
isomer series.
Development of the two strategies shown in Scheme 1
both required diformyl bithiophene 12a (Scheme 2),
which we approached by using the Liebeskind
modification15 of Ullmann coupling or the mild copper(I)
iodide triethylphosphite method of Ziegler.16 The stan-
dard dimerisation method involving (2-formyl-3-thie-
nyl)boronic acid gave the product in only 18% yield17 and
required three steps from 3-bromo-2-formylthiophene (9).
From 12a, formation of the bis-hydrazone18 or dimethyl-
enation should give easy access to precursors for the cy-
clisation step. The novel intermediate 2,2′-divinyl-3,3′-
bithiophene (6) was also expected to be important for the
formation of BDT by alkene metathesis, which should be
an efficient strategy because the corresponding metathesis
reaction of 2,2′-divinylbiphenyl to form phenanthrene is
known to work well.19
SYNLETT 2014, 25, 0701–0707
Advanced online publication: 05.02.2014
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0033-1340667; Art ID: ST-2013-D0987-L
© Georg Thieme Verlag Stuttgart · New York

702
G. R. Stephenson et al.
LETTER
change and quenching with I2 to form 10.28 Unfortunately,
the Ullmann coupling was not significantly improved by
using iodoimine derivative 10, and the required product
was obtained in only 29% yield (Table 1, entry 3). The si-
lyl-protected aldehyde intermediate 11 was also examined
in the Ullmann step (14% yield; Table 1, entry 5). This
was compared with the Ziegler method,16 which was
found to perform similarly (15% yield; Table 1, entry 4)
with our substrate.29 The direct palladium-catalyzed
coupling30 of the 3-bromo-2-formylthiophene starting
material 9 was also investigated because it would save a
step, and this gave the required product in 35% yield (Ta-
ble 1, entry 1).31
S
S
alkene
metathesis
6
Ullmann coupling
N
S
S
then olefination
S
or hydrazone
formation
NHTs
NHTs
1
N
N
Br
hydrazone
coupling
7
S
S
8
Scheme 1 Strategies for the non-photochemical preparation of ben-
zo[1,2-b:4,3-b′]dithiophene 1
Cy
S
N
Cy
S
N
Cy
S
N
O
O
O
a
b
c
O
X
Y
S
see Tables
1 and 2
S
S
I
Br
Br
I
S
S
Me3Si
Me3Si
Me3Si
R
R
R
7
14
10
11
R
7 (R = H, X = N-Cy, Y = Br)
9 (R = H, X = O, Y = Br)
10 (R = SiMe3, X = N-Cy, Y = I)
11 (R = SiMe3, X = O, Y = I)
12a (R = H)
12b (R = SiMe3)
13a (R = H)
13b (R = SiMe3)
Scheme 3 Preparation of iodothiophenes 10 and 11. Reagents and
conditions: (a) LDA, Me3SiCl, THF, N2, 99%; (b) n-BuLi, I2, THF,
N2, 90%; (c) AcOH, CH2Cl2, H2O, 88%.
Scheme 2 Ullmann coupling of 3-bromo- and 3-iodothiophenes
The problem of low yields was initially addressed by us-
ing a microwave reactor32 (using 7 and 10), and it soon be-
came apparent that careful purification of the CuTC was
crucial for obtaining good results (Table 2). Further exam-
ination of reaction conditions to control competing deha-
logenation allowed 12a to be obtained in a satisfactory
67% isolated yield (Table 2, entry 8). On a large scale,
however, we found that simply heating 7 at 90 °C for
17 hours gave 12a in 68% isolated yield (e.g., Table 2, en-
try 9).
To gain access to the bis-formyl derivatives 12, we ex-
plored coupling chemistry using compounds 7, 9, 10, and
11 (Scheme 2). The N-formylpiperidine method could be
used to convert 3-bromothiophene into 9, improving the
yield from 72–86%20 to 97%, which is also an improved
yield over more common alternatives that use DMF21 or
N-formyl-N-methylaniline,22 or the Vilsmeier–Haack pro-
cess.23 The required imine 7 was easily made in quantita-
tive yield by heating 9 to reflux in toluene with
cyclohexylamine using a Dean–Stark trap.24
The BDT synthesis was completed by a simple Wittig re-
action to produce 2,2′-divinyl-3,3′-bithiophene (6),33 fol-
lowed by a ring-closing metathesis (RCM) step. For the
RCM step, we chose to use Iuliano conditions19 with the
1st generation Grubbs catalyst [Ru(Pcy3)2(CHPh)Cl2],
which has been reported19a to give 100% yield in the prep-
aration of phenanthrene in the case of divinylbiphenyl.
Gratifyingly, this does indeed appear to be a very efficient
and general RCM method, and in our case we achieved
90% yield of 1 at 5 mol% catalyst loading, which was im-
Our first attempt at the Ullmann coupling (Scheme 2) of
cyclohexylimine 7 with Liebeskind catalyst in N-methyl-
2-pyrrolidinone (NMP) at room temperature25 gave a dis-
appointing 25% yield (Table 1, entry 2). To prepare the
more reactive 3-iodothiophene analogue (Scheme 3), we
first protected the 5-position of 7 with a trimethylsilyl
group to give 1426 through selective C-5 lithiation, which
proceeded in the presence of the 3-bromo substituent by
using LDA.27 This was followed by bromine–lithium ex-
Table 1 Coupling Reactions to 2,2′-Diformyl-3,3′-bithiophenes 12a and 12b
Entry
Substrate
Catalyst (equiv)
Solvent
Temp (°C)
Time (h)
Yield (%)
1
9
7
Cu (10) / Pd(PPh3)4 (0.1)
CuTC (2.2)
DMSO
NMP
NMP
THF
100
15
60
60
60
60
35a
25b
29b
15b
14b
2
r.t.
3
10
10
11
CuTC (3.0)
r.t.
4
CuI-P(OEt)3 (1.5)
CuTC (3.0)
–78 to r.t.
r.t.
5
NMP
a Isolated yield.
b Based on NMR analysis of the crude bis-aldehyde 12a or 12b.
Synlett 2014, 25, 701–707
© Georg Thieme Verlag Stuttgart · New York

LETTER
Ullmann/RCM and Ullmann/Bis-hydrazone Coupling Reactions
703
proved to 96% yield by using 10 mol% catalyst (Scheme methylsilyl)-protected derivative 15,38 which was ob-
4).34
tained from 16 by bis-hydrazone coupling of 12b.39 The
conditions used to form 1 resemble those for the Bam-
ford–Stevens reaction,40 but the use of n-butyllithium in
the preparation of 11 is more typical of a Shapiro reac-
tion.41 Both the Bamford–Stevens and Shapiro procedures
employ arylsulfonylhydrazones and are generally consid-
ered to begin by deprotonation of the NH-SO2Ar,42 and
R = H
S
S
a
b
77%
R
96%
6
O
O
–
exploit the chemistry of arylsulfinate (ArSO2 ) leaving
c
X
S
S
S
S
groups, and the elimination of N2 to provide a powerful
driving force. Under aprotic conditions the Bamford–Ste-
vens reaction is believed to proceed by formation of a car-
bene,43,44 but with the bis-hydrazones shown in Scheme 4
it seems probable that the initial anion45 cyclises as shown
in Scheme 5 by intramolecular nucleophile addition to the
hydrazone and elimination of an arylsulfinate.46 Subse-
quent loss of two molecules of N2 and the second arylsul-
finate completes the benzo[1,2-b:4,3-b′]dithiophene ring.
The bis-hydrazone coupling reaction is useful, but re-
quires further optimisation, perhaps by the use of more
modern bases47 which have become popular in the Shap-
iro reaction.
R
R
R
12a (R = H)
12b (R = SiMe3)
1 (R = H)
15 (R = SiMe3)
NHTs
NHTs
d
e
N
N
R = H, SiMe3
S
S
R
R
8 (R = H)
16 (R = SiMe3)
Scheme 4 Cyclisation reactions to form benzo[1,2-b:4,3-b′]dithio-
phenes. Reagents and conditions: (a) n-BuLi, MePPh3Br, THF, N2,
77%; (b) CH2Cl2, [Ru(Pcy3)2(CHPh)Cl2] (0.1 equiv), r.t., 8 h, Ar,
96%; (c) TiCl3(DME)1.5/Zn(Cu), DME, 5%; (d) tosylhydrazide
(2 equiv), THF, 8: 100%, 16: 100%; (e) 8, NaH, N2, THF, 37% or 16,
n-BuLi, N2, THF, 32%.
Finally, because the highest yielding route to BDT 1 was
achieved by the application of the RCM reaction, we con-
sidered the possibility of coupling of 3-bromo-2-vinyl-
thiophene to make 2,2′-divinyl-3,3′-bithiophene (6) more
directly from 9 in just two steps. Wittig methylenation of
9, however, proceeded in only 30% yield. It is possible
that the ease of dimerisation and polymerisation of the re-
active vinyl group in 3-bromo-2-vinylthiophene limits the
efficiency of this reaction. Thus, Ullmann coupling prior
to Wittig methylenation is the better approach.
We also examined the formation of a bis-tosylhydrazone
in the double condensation reaction of 2,2′-diformyl-3,3′-
bithiophene (12a).35 This alternative18 to the McMurry
coupling36 of aldehydes gives direct access to the ben-
zo[1,2-b:4,3-b′]dithiophene ring system in 32–37% yield
and was successful both for 1 itself37 and the 2,7-di(tri-
Table 2 Control of Dehalogenation in the Coupling of Halothiophenes
Entry
Substrate
Conditions
Yield (%)
12
13
1
2
3
4
5
6
7
8
9
10
10
10
10
10
10
7
r.t., 48 h, CuTC (3.5 equiv)
12b (20a)
12b (29a)
12b (43b)
12b (48b)
12b (51b)
12b (55b)
12a (62b,d
13b (23a,c)
13b (60a,c)
13b (37b)
13b (26b)
13b (33b)
13b (21b)
60 °C, 60 h, CuTC (3 equiv), N2
r.t., 60 h, CuTC (3 equiv), N2
60 °C, MW, 20 min, CuTC (3 equiv), N2
90 °C, MW, 15 min, CuTC (3 equiv), Ar
60 °C, MW, 30 min, CuTC (3 equiv), N2
90 °C, MW, 15 min, CuTC (2.2 equiv), Ar
90 °C, MW, 25 min, CuTC (2.2 equiv), Ar
90 °C, 17 h, CuTC (2.2 equiv), Ar
)
13a (19a,b
13a (17b)
–
)
7
12a (67b,e
12a (68f)
)
7
a Based on NMR analysis of crude bis-aldehyde.
b Based on NMR analysis of crude bis-imine.
c Catalyst not pure.
d 52% isolated yield.
e 55% isolated yield.
f Isolated yield.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 701–707

704
G. R. Stephenson et al.
LETTER
H
N
H
N
H
N
H
TolO2S N–
N
SO2Tol
TolO2S
N
SO2Tol
base
N
TolO2S
N
N
N
N
N
S
S
S
S
S
S
–
TolSO2
R
R
R
R
R
R
8 (R = H)
16 (R = SiMe3)
TolO2S
SO2Tol
N–
–N
TolO2S
N
N–
base
S
S
N
N
N
N
R
R
–
1 (R = H)
15 (R = SiMe3)
TolSO2
2 N2
S
S
S
S
R
R
R
R
Scheme 5 Possible mechanism for the bis-hydrazone cyclisation. The monoanion formed by the first deprotonation step will be in equilibrium
with the dianion (see box) when one equivalent of base is used,38 but with an excess of base37 the dianion is likely to be formed before loss of
the first p-toluenesulfinate.45
100, thiophene is 81.5, see: Bird, C. W. Tetrahedron 1992,
48, 335.
In conclusion, we have shown that benzo[1,2-b:4,3-b′]di-
thiophene (1) is accessible in 50% overall yield in four
steps from 3-bromo-2-formylthiophene by Ullmann cou-
pling of the cyclohexylimine, methylenation, and ring-
closing metathesis in a simple reaction sequence that
avoids the use of photochemical conditions. The less cost-
ly alternative, bis-hydrazone route was found to be less ef-
fective than the metathesis route.
(3) (a) Amin, A. Y.; Khassanov, A.; Reuter, K.; Meyer-
Friedrichsen, T.; Halik, M. J. Am. Chem. Soc. 2012, 134,
16548. (b) Chen, H.; Cui, Q.; Yu, G.; Guo, Y.; Huang, J.;
Zhu, M.; Guo, X.; Liu, Y. J. Phys. Chem. C 2011, 115,
23984. (c) Didane, Y.; Kumagai, A.; Yoshimoto, Y.;
Videlot-Ackermann, C.; Brisset, H. Tetrahedron 2011, 67,
1628. (d) Gao, J.; Li, L.; Meng, Q.; Li, R.; Jiang, H.; Li, H.;
Hu, W. J. Mater. Chem. 2007, 17, 1421. (e) Nishide, Y.;
Osuga, H.; Saito, M.; Aiba, T.; Inagaki, Y.; Doge, Y.;
Tanaka, K. J. Org. Chem. 2007, 72, 9141. (f) Takimiya, K.;
Ebata, H.; Sakamoto, K.; Izawa, T.; Otsubo, T.; Kunugi, Y.
J. Am. Chem. Soc. 2006, 128, 12604. (g) Murphy, A. R.;
Fréchet, J. M. J. Chem. Rev. 2007, 107, 1066.
Acknowledgment
We thank EPSRC (EH/C009922) and EU Interreg IVA (project
4061) for financial support, Professors Emanuela Licandro and Ste-
fano Maiorana (University of Milan) for advice and discussions,
and Dr. Kenneth Hamilton (UEA) for preliminary experiments on
the attempted intramolecular McMurry cyclisation of 12a. S.C. ack-
nowledges the University of Milan for a postdoctoral fellowship.
We thank the EPSRC Mass Spectrometry Centre at the University
of Wales, Swansea for HRMS measurements.
(4) (a) Kumar, N. S.; Clement, J. A.; Mohanakrishnan, A. K.
Tetrahedron 2009, 65, 822. (b) Mikroyannidis, J. A.;
Moshopoulou, H. A.; Anastasopoulos, J. A.; Stylianakis, M.
M.; Fenenko, L.; Adachi, C. J. Polym. Sci., Part A: Polym.
Chem. 2006, 44, 6790. (c) Wu, C.-W.; Lin, H.-C.
Macromolecules 2006, 39, 7232. (d) Kulkarni, A. P.; Kong,
X.; Jenekhe, S. A. Macromolecules 2006, 39, 8699. (e) Zhu,
Y.; Gibbons, K. M.; Kulkarni, A. P.; Jenekhe, S. A.
Macromolecules 2007, 40, 804.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.SnoIufproig
m
iotSrat
ungIifoop
r
t
(5) (a) Dou, L.; Gao, J.; Richard, E.; You, J.; Chen, C.-C.; Cha,
K. C.; He, Y.; Li, G.; Yang, Y. J. Am. Chem. Soc. 2012, 134,
10071. (b) Zou, Y.; Najari, A.; Berrouard, P.; Beaupré, S.;
Aïch, B. R.; Tao, Y.; Leclerc, M. J. Am. Chem. Soc. 2010,
132, 5330. (c) Liang, Y.; Feng, D.; Wu, Y.; Tsai, S.-T.; Ray,
C.; Yu, L. J. Am. Chem. Soc. 2009, 131, 7792. (d) Jung, I.;
Lee, J. K.; Song, K. H.; Song, K.; Kang, S. O.; Ko, J. J. Org.
Chem. 2007, 72, 3652. (e) Colladet, K.; Fourier, S.; Cleij, T.
J.; Lutsen, L.; Gelan, J.; Vanderzande, D.; Nguyen, L. H.;
Neugebauer, H.; Sariciftci, S.; Aguirre, A.; Janssen, G.;
Goovaerts, E. Macromolecules 2007, 40, 65. (f) Eckert, J.-
F.; Nicoud, J.-F.; Nierengarten, J.-F.; Liu, S.-G.; Echegoyen,
L.; Barigelletti, F.; Armaroli, N.; Ouali, L.; Krasnikov, V.;
Hadziioannou, G. J. Am. Chem. Soc. 2000, 122, 7467.
(6) (a) Zhou, E.; Cong, J.; Hashimoto, K.; Tajima, K.
Macromolecules 2013, 46, 763. (b) Morvillo, P.; Parenti, F.;
Diana, R.; Fontanesi, C.; Mucci, A.; Tassinari, F.; Schenetti,
L. Sol. Energy Mater. Sol. Cells 2012, 104, 45. (c) Najari,
A.; Beaupré, S.; Berrouard, P.; Zou, Y.; Pouliot, J.-R.;
Lepage-Pérusse, C.; Leclerc, M. Adv. Funct. Mater. 2011,
References and Notes
(1) For recent examples, see: (a) Lu, X.; Hu, B.; Sun, J.;
Ouyang, M.; Yu, C.; Fu, Z.; Zhang, C. J. Electrochem. Soc.
2013, 160, H87. (b) Faist, M. A.; Kirchartz, T.; Gong, W.;
Ashraf, R. S.; McCulloch, I.; de Mello, J. C.; Ekins-Daukes,
N. J.; Bradley, D. D. C.; Nelson, J. J. Am. Chem. Soc. 2012,
134, 685. (c) Logtenberg, H.; van der Velde, J. H. M.; de
Mendoza, P.; Areephong, J.; Hjelm, J.; Feringa, B. L.;
Browne, W. R. J. Phys. Chem. C 2012, 116, 24136.
(d) Piliego, C.; Manca, M.; Kroon, R.; Yarema, M.;
Szendrei, K.; Andersson, M. R.; Heiss, W.; Loi, M. A.
J. Mater. Chem. 2012, 22, 24411. (e) Hermet, P.; Bantignies,
J.-L.; Lère-Porte, J.-P.; Serein-Spirau, F. Chem. Phys. Lett.
2012, 535, 116. (f) Okada, A.; Makino, Y.; Hotta, S.;
Yamao, T. Phys. Status Solidi C. 2012, 9, 2545.
(2) (a) Katritzky, A. R.; Jug, K.; Oniciu, D. C. Chem. Rev. 2001,
101, 1421. (b) On the aromaticity index, with benzene at
Synlett 2014, 25, 701–707
© Georg Thieme Verlag Stuttgart · New York

LETTER
Ullmann/RCM and Ullmann/Bis-hydrazone Coupling Reactions
705
21, 718. (d) For a review, see: Spanggaard, H.; Krebs, F. C.
Sol. Energy Mater. Sol. Cells 2004, 83, 125.
(17) (a) Cateni, F.; Zacchigna, M.; Pedemonte, N.; Galietta, L. J.
V.; Mazzei, M. T.; Fossa, P.; Giampieri, M.; Mazzei, M.
Bioorg. Med. Chem. 2009, 17, 7894. (b) Prugh, J. D.;
Hartman, G. D.; Mallorga, P. J.; McKeever, B. M.;
Michelson, S. R.; Murcko, M. A.; Schwam, H.; Smith, R. L.;
Sondey, J. M.; Springer, J. P.; Sugrue, M. F. J. Med. Chem.
1991, 34, 1805. (c) Gronowitz, S.; Bugge, A. Acta Chem.
Scand. 1965, 19, 1271. (d) Demir, A. S.; Reis, Ö.;
(7) (a) Gao, P.; Tsao, H. N.; Grätzel, M.; Nazeeruddin, M. K.
Org. Lett. 2012, 14, 4330. (b) Longhi, E.; Bossi, A.; Di
Carlo, G.; Maiorana, S.; De Angelis, F.; Salvatori, P.;
Petrozza, A.; Binda, M.; Roiati, V.; Mussini, P. R.; Baldoli,
C.; Licandro, E. Eur. J. Org. Chem. 2013, 84.
(8) Bossi, A.; Licandro, E.; Maiorana, S.; Rigamonti, C.;
Righetto, S.; Stephenson, G. R.; Spassova, M.; Botek, E.;
Champagne, B. J. Phys. Chem. C 2008, 112, 7900.
(9) (a) Fenili, F.; Rigamonti, C.; Bossi, A.; Ferruti, P.; Manfredi,
A.; Maiorana, S.; Baldoli, C.; Cauteruccio, S.; Licandro, E.;
Ranucci, E. J. Polym. Sci., Part A: Polym. Chem. 2010, 48,
4704. (b) Kim, C.; Marks, T. J.; Facchetti, A.; Schiavo, M.;
Bossi, A.; Maiorana, S.; Licandro, E.; Todescato, F.;
Toffanin, S.; Muccini, M.; Graiff, C.; Tiripicchio, A. Org.
Electron. 2009, 10, 1511. (c) Champagne, B.; André, J.-M.;
Botek, E.; Licandro, E.; Maiorana, S.; Bossi, A.; Clays, K.;
Persoons, A. ChemPhysChem 2004, 5, 1438. (d) Clays, K.;
Wostyn, K.; Persoons, A.; Maiorana, S.; Papagni, A.; Daul,
C. A.; Weber, V. Chem. Phys. Lett. 2003, 372, 438. (e) Daul,
C. A.; Ciofini, I.; Weber, V. Int. J. Quantum Chem. 2003, 91,
297. (f) See also ref. 8.
(10) Monteforte, M.; Cauteruccio, S.; Maiorana, S.; Benincori,
T.; Forni, A.; Raimondi, L.; Graiff, C.; Tiripicchio, A.;
Stephenson, G. R.; Licandro, E. Eur. J. Org. Chem. 2011,
5649.
(11) For reviews, see: (a) Gingras, M.; Félix, G.; Peresutti, R.
Chem. Soc. Rev. 2013, 42, 1007. (b) Shen, Y.; Chen, C.-F.
Chem. Rev. 2012, 112, 1463.
Emrullahoglu, M. J. Org. Chem. 2003, 68, 10130.
(18) (a) Jung, I. E.; Hagiwara, A. Tetrahedron Lett. 1991, 32,
3025. (b) For the original H2NNH2/HOAc method, see:
Bacon, R. G. R.; Lindsay, W. S. J. Chem. Soc. 1958, 1375.
(19) (a) Iuliano, A.; Piccioli, P.; Fabbri, D. Org. Lett. 2004, 6,
3711. (b) Walker, E. R.; Leung, S. Y.; Barrett, A. G. M.
Tetrahedron Lett. 2005, 46, 6537.
(20) (a) Fuller, L. S.; Iddon, B.; Smith, K. A. J. Chem. Soc.,
Perkin Trans. 1 1997, 3465. (b) Youn, J.; Huang, P.-Y.;
Huang, Y.-W.; Chen, M.-C.; Lin, Y.-J.; Huang, H.; Ortiz, R.
P.; Stern, C.; Chung, M.-C.; Feng, C.-Y.; Chen, L.-H.;
Faccetti, A.; Marks, T. J. Adv. Funct. Mat. 2012, 22, 48.
(c) Coombs, B. A.; Rutter, S. R.; Goeta, A. E.; Sparkes, H.
A.; Batsanov, A. S.; Beeby, A. RSC Adv. 2012, 2, 1870.
(21) (a) Mishra, S. P.; Palai, A. K.; Kumar, A.; Srivastava, R.;
Kamalasanan, M. N.; Patri, M. Macromol. Chem. Phys.
2010, 211, 1890. (b) Kawabata, K.; Takeguchi, M.; Goto, H.
Macromolecules 2013, 46, 2078.
(22) Jeeva, S.; Lukoyanova, O.; Karas, A.; Dadvand, A.; Rosei,
F.; Perepichka, D. F. Adv. Funct. Mater. 2010, 20, 1661.
(23) Suspene, C.; Simonato, J.-P. PCT Int. Appl 2010142864,
2010; Chem. Abstr. 2012, 157, 329418.
(12) (a) Waghray, D.; Nulens, W.; Dehaen, W. Org. Lett. 2011,
13, 5516. (b) Rigamonti, C.; Ticozzelli, M. T.; Bossi, A.;
Licandro, E.; Giannini, C.; Maiorana, S. Heterocycles 2008,
76, 1439. (c) Licandro, E.; Rigamonti, C.; Ticozzelli, M. T.;
Monteforte, M.; Baldoli, C.; Giannini, C.; Maiorana, S.
Synthesis 2006, 3670. (d) Maiorana, S.; Papagni, A.;
Licandro, E.; Annunziata, R.; Paravidino, P.; Perdicchia, D.;
Giannini, C.; Bencini, M.; Clays, K.; Persoons, A.
(24) Preparation of N-[(3-Bromothiophen-2-
yl)methylene]cyclohexylimine (7): In a 1-L three-necked
round-bottom flask, equipped with a Dean–Stark trap, a
solution of 3-bromo-2-formylthiophene 9 (84.15 g, 0.44
mol, 1 equiv) and cyclohexylamine (54.6 g, 0.55 mol, 1.25
equiv) in toluene (700 mL) was heated at reflux under
nitrogen for 16 h. The solution was then evaporated to afford
an orange oil (120 g, 100%) which was used directly in the
next step. IR (ATR): 3075, 2925, 2851, 1623 cm–1. 1H NMR
(CDCl3, 400 MHz): δ = 8.44 (s, 1 H), 7.34 (dd, J = 5.3,
1.1 Hz, 1 H), 7.00 (d, J = 5.2 Hz, 1 H), 3.22 (m, 1 H), 1.51–
1.85 (m, 7 H), 1.18–1.41 (m, 3 H). 13C NMR (CDCl3, 100
MHz): δ = 151.0, 136.5, 130.5, 128.4, 113.5, 69.8, 34.1,
25.5, 24.7. HRMS (GC, CI+): m/z [M–H]– calcd for
C11H13BrNS: 269.9947; found: 269.9947.
Tetrahedron 2003, 59, 6481. (e) Larsen, J.; Bechgaard, K.
Acta Chem. Scand. 1996, 50, 71. (f) Kellogg, R. M.; Groen,
M. B.; Wynberg, H. J. Org. Chem. 1967, 32, 3093.
(13) (a) Nishide, Y.; Osuga, H.; Iwata, K.; Tanaka, K.; Sakamoto,
H. Bull. Chem. Soc. Jpn. 2008, 81, 1322. (b) Fischer, E.;
Larsen, J.; Christensen, J. B.; Fourmigue, M.; Madsen, H.
G.; Harrit, N. J. Org. Chem. 1966, 61, 6997. (c) Maiorana,
S.; Licandro, E.; Longhi, E.; Cauteruccio, S.; Abbotto, A.;
Baldoli, C.; De Angelis, F. PCT Int. Appl WO 2012107488
A2 20120816, 2012; Chem. Abstr. 2011, 154, 54075.
(14) Recently, non-photochemical syntheses of four specific
BDT derivatives have been reported; see: (a) Shimozu, M.;
Nagao, I.; Tomioka, Y.; Hiyama, T. Angew. Chem. Int. Ed.
2008, 47, 8096. (b) Xia, Y.; Qu, P.; Liu, Z.; Ge, R.; Xiao, Q.;
Zhang, Y.; Wang, J. Angew. Chem. Int. Ed. 2013, 52, 2543.
(c) Rajca, A.; Pink, M.; Xiao, S.; Miyasaka, M.; Rajca, S.;
Das, K.; Plessel, K. J. Org. Chem. 2009, 74, 7504. For a
recent example with a benzannulated central ring, see:
(d) Waghray, D.; de Vet, C.; Karypidou, C.; Dehaen, W.
J. Org. Chem. 2013, 78, 11147.
(25) General Procedure: N-[(3-Bromothiophen-2-
yl)methylene]cyclohexylimine (7; 1 equiv) was dissolved in
anhydrous NMP under argon, CuTc (2.2 equiv) was added in
several portions (to achieve good mixing), and the reaction
mixture was stirred at 90 °C under argon for 17 h. After
cooling, the mixture was filtered through a pad of kieselguhr,
which was then washed with EtOAc until no more brown
colour was released from the filter cake. The filtrate was
washed with 15% aqueous ammonia, producing a clear
deep-blue aqueous layer. The organic layer was separated
and retained, and the aqueous layer was extracted with
EtOAc. The combined organic layers were washed with
brine to remove as much NMP as possible, dried over
MgSO4, filtered, and evaporated under reduced pressure.
The brown oily residue was dissolved in CH2Cl2 and 15%
aqueous AcOH was added and mixture was at stirred r.t.
overnight. The organic layer was separated and retained, and
the aqueous layer was extracted with CH2Cl2. The combined
organic layers were washed with brine, filtered through a
MgSO4/neutral alumina pad, and evaporated under reduced
pressure to give a solution of crude product in NMP (despite
the washing, the NMP was not removed completely). The
(15) (a) Allred, G. D.; Liebeskind, L. S. J. Am. Chem. Soc. 1996,
118, 2748. (b) Zhang, S.; Zhang, D.; Liebeskind, L. S.
J. Org. Chem. 1997, 62, 2312. (c) Beletskaya, I. P.;
Cheprakov, A. V. Coord. Chem. Rev. 2004, 248, 2337.
(16) (a) Ziegler, F. E.; Chliwner, I.; Fowler, K. W.; Kanfer, S. J.;
Kuo, S. J.; Sinha, N. D. J. Am. Chem. Soc. 1980, 102, 790.
(b) Ziegler, F. E.; Fowler, K. W.; Rodgers, W. B.; Wester, R.
T. Org. Synth., Coll. Vol. 8 1993, 556.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 701–707

706
G. R. Stephenson et al.
LETTER
resultant brown oil was taken up in H2O and shaken until the
product precipitated. The mixture was then filtered and the
residue was washed with H2O and dissolved in CH2Cl2, dried
over MgSO4, filtered and evaporated. The solid residue was
washed with a mixture of hexanes and EtOAc (8:1 v/v) and
dried under vacuum to give [3,3′-bithiophene]-2,2′-
with H2O and the reaction mixture was diluted with CH2Cl2,
and 15% aqueous AcOH was added. The mixture was at
stirred r.t. overnight, then the organic layer was separated
and retained and the aqueous layer was extracted with
CH2Cl2. The combined organic layers were washed with
brine, filtered through a MgSO4/neutral alumina pad and
evaporated under reduced pressure. Crude material was
purified by column chromatography (silica; hexanes–
EtOAc, 100:0 to 2:1 v/v) to give 5,5′-bis(trimethylsilyl)-
[3,3′-bithiophene]-2,2′-dicarbaldehyde (12b); for yields, see
Table 1.
dicarboxaldehyde 12a; for yields, see Table 1 and Table 2.
(26) Preparation of N-{[3-Bromo-5-(trimethylsilyl)thiophen-
2-yl]methylene}cyclohexylimine (14): A solution of n-
BuLi (1.6 M in hexanes, 53 mL, 84.5 mmol, 1.15 equiv) was
added dropwise to diisopropylamine (12 mL, 8.5 g, 84.5
mmol, 1.15 equiv) in anhydrous THF (600 mL) at 0 °C under
nitrogen. After stirring for 45 min at 0 °C, N-[(3-
(30) Some, S.; Dutta, B.; Ray, J. K. Tetrahedron Lett. 2006, 47,
1221.
bromothiophen-2-yl)methylene]cyclohexylimine (7; 20 g,
73.5 mmol, 1 equiv) in anhydrous THF (50 mL) was added
dropwise over 10 min. After stirring for a further 45 min at
0 °C under nitrogen, the reaction mixture was cooled to
–78 °C and trimethylsilyl chloride (10.7 mL, 9.2 g, 84.5
mmol, 1.15 equiv) was added dropwise. After stirring for 1 h
at –78 °C, the reaction mixture was allowed to warm to r.t.,
sat. aq NH4Cl (700 mL) was added, and the organic layer
was separated and retained. The aqueous layer was extracted
with EtOAc (2 × 400 mL) and the combined organic layers
were washed with brine (500 mL), filtered through a
MgSO4/basic alumina pad, and evaporated to give 14 (25.2
g, 99%) as an orange oil. IR (ATR): 2927, 2853, 1624 cm–1.
1H NMR (CDCl3, 400 MHz): δ = 8.43 (s, 1 H), 7.10 (s, 1 H),
3.22 (m, 1 H), 1.22–1.87 (m, 10 H), 0.31 (s, 9 H). 13C NMR
(CDCl3, 100 MHz): δ = 151.0, 144.4, 140.5, 136.5, 114.5,
70.0, 34.1, 25.5, 24.7, –0.6. HRMS (ESI): m/z [M+H]+ calcd
for C14H23BrNSSi: 344.0498; found: 344.0503.
(31) Preparation of [3,3′-Bithiophene]-2,2′-dicarboxaldehyde
(12a): Anhydrous DMSO (50 mL) was degassed under
nitrogen for 30 min, then 3-bromo-2-formylthiophene (9; 1
equiv) was added and nitrogen gas was bubbled through the
resulting solution for 10 min. Pd(PPh3)4 (0.1 equiv) and
copper powder (3 equiv) were added and the solution was
stirred and heated to 100 °C, under nitrogen for 15 h and
then at 120 °C for 8 h. The progress of the reaction was
monitored by TLC (hexanes–EtOAc, 3:1 v/v). The solution
was cooled to r.t. before adding EtOAc (200 mL) and
filtration through a pad of kieselghur. The filtrate was
washed with H2O (2 × 150 mL) and brine (150 mL), dried
over MgSO4, filtered and evaporated under reduced pressure
to give a brown oil that was purified by chromatography
(silica; hexanes–EtOAc, 95:5 to 3:1 v/v) to afford 12a (405
mg, 35%) as a yellow powder.
(32) General Procedure: A dried 20-mL microwave vial was
flushed with argon. To a solution N-[(3-bromothiophen-2-
yl)methylene]cyclohexylimine (7; 1 equiv) in NMP (15
mL), CuTC (2.2 equiv) was added with stirring. The
microwave vial was then sealed, vacuum was applied, and
then the vial was filled with argon. The reaction mixture was
irradiated (see Table 2), then diluted with EtOAc and 15%
aqueous ammonia was added to produce a clear deep-blue
aqueous layer. The organic layer was separated and retained
and the aqueous layer was extracted with EtOAc. The
organic layers were combined and evaporated and the
resultant crude product (green oil) was dissolved in Et2O.
This solution was washed with brine, dried over MgSO4,
filtered, and evaporated to leave a brown oil, which was
dissolved in CH2Cl2 (50 mL), 15% aqueous AcOH (50 mL)
was added and mixture was stirred overnight at r.t. The
organic layer was separated and retained and the aqueous
layer was extracted with CH2Cl2. The combined organic
layers were washed with brine, dried over MgSO4, filtered
and evaporated (first under reduced pressure on a rotary
evaporator and then under high vacuum using a vacuum line)
to give a brown oil. The oil was purified by column
chromatography (silica; hexanes–EtOAc, 100:0 to 2:1 v/v)
to afford [3,3′-bithiophene]-2,2′-dicarbaldehyde 12a as a
yellow solid (for yields, see Table 2).
(27) Rajca, A.; Wang, H.; Rajca, S. Angew. Chem. Int. Ed. 2000,
39, 4481.
(28) Preparation of N-{[3-Iodo-5-(trimethylsilyl)thiophen-2-
yl]methylene}cyclohexylimine (10): A solution of N-{[3-
bromo-5-(trimethylsilyl)thiophen-2-
yl]methylene}cyclohexylimine (14; 6.94 g, 20.2 mmol, 1
equiv) in anhydrous THF (350 mL) was cooled to –78 °C,
under nitrogen. n-BuLi (1.6 M in hexanes, 13.9 mL, 22.2
mmol, 1.1 equiv) was added dropwise. The mixture was
stirred for 30 min at –78 °C and a solution of iodine (7.7 g,
30.3 mmol, 1.5 equiv) in anhydrous THF (25 mL) was added
dropwise until the red iodine colour persisted. After 15 min
at –78 °C, the reaction mixture was allowed to warm to r.t.,
H2O (350 mL) was added and the mixture was extracted with
CH2Cl2 (3 × 250 mL). The combined organic layers were
concentrated to 300 mL, washed with sat. aq sodium sulfite
(2 × 300 mL), dried over MgSO4, filtered, and evaporated to
give 10 (7.12 g, 90%) as a brown oil, that crystallised upon
standing. Mp 59 °C. IR (ATR): 2928, 2851, 1618 cm–1. 1H
NMR (CDCl3, 400 MHz): δ = 8.34 (s, 1 H), 7.20 (s, 1 H),
3.24 (br. m, 1 H), 1.85–1.57 (m, 7 H), 1.38–1.23 (m, 3 H),
0.31 (s, 9 H). 13C NMR (CDCl3, 100 MHz): δ = 153.2, 145.4,
143.7, 141.4, 85.1, 69.9, 34.2, 25.5, 24.7, –0.5. HRMS (ESI):
m/z [M–H]– calcd for C14H21NISSi: 390.0203; found:
390.0203.
(33) Preparation of 2,2′-Divinyl-3,3′-bithiophene (6): To a
suspension of methyltriphenylphosphonium bromide (1.7 g,
4.75 mmol, 2.2 equiv) in distilled THF (50 mL), n-BuLi (1.6
M in hexanes, 2.96 mL, 4.75 mmol, 2.2 equiv) was added
dropwise at –10 °C under nitrogen. The deep-orange
solution was stirred at r.t. for 30 min, then a solution of [3,3′-
bithiophene]-2,2′-dicarbaldehyde (12a; 460 mg, 2.16 mmol,
1 equiv) in distilled THF (10 mL) was added dropwise. The
mixture was stirred at r.t. under nitrogen for 17 h, then the
reaction was quenched with sat. aq NH4Cl (20 mL). The
aqueous layer was extracted with CHCl3 (3 × 50 mL) and the
combined organic layers were washed with brine (100 mL),
dried over MgSO4, and evaporated. The crude product was
(29) General Procedure: A solution of N-{[3-bromo-5-
(trimethylsilyl)thiophen-2-yl]methylene}cyclohexylimine
14 (1 equiv) in anhydrous THF was cooled to –78 °C under
nitrogen. n-BuLi (1.05 equiv) was added dropwise and the
mixture was stirred at –78 °C for 30 min. Then CuI-P(OEt)3
(1.5 equiv) was added in one portion and the mixture was
stirred for a further 30 min at –78 °C before a solution of N-
{[3-iodo-5-(trimethylsilyl)thiophen-2-
yl]methylene}cyclohexylimine 10 in anhydrous THF was
added dropwise. The reaction mixture was allowed to warm
to r.t. and stirred at r.t. for 60 h. The reaction was quenched
Synlett 2014, 25, 701–707
© Georg Thieme Verlag Stuttgart · New York

LETTER
Ullmann/RCM and Ullmann/Bis-hydrazone Coupling Reactions
707
purified by column chromatography (silica; hexanes), to
mL) and stirred at r.t. overnight. The THF solution was dried
over Na2SO4, and transferred to a 500-mL three-necked
round-bottom flask that had been flame-dried under
nitrogen. The reaction mixture was cooled to –78 °C, n-BuLi
(1.6 M in hexanes, 4.7 mL, 7.5 mmol, 1.05 equiv) was added
dropwise and the mixture was stirred for 5 min at –78 °C.
The reaction mixture was allowed to warm to r.t., then
heated at reflux for 5 h. After cooling, sat. aq NH4Cl (200
mL) was added and the mixture was extracted with EtOAc
(200 mL). The organic layer was concentrated under reduced
pressure to 100 mL, diluted with Et2O (200 mL), washed
with brine (2 × 250 mL), dried over MgSO4, filtered, and
evaporated to leave a brown solid (5.1 g). Crude material
was purified by column chromatography (silica; hexanes) to
afford 15 (770 mg, 32%) as colourless crystals. Mp 128 °C.
IR (ATR): 3053, 2985, 2959, 2897 cm–1. 1H NMR (CDCl3,
400 MHz): δ = 7.88 (s, 2 H), 7.80 (s, 2 H), 0.44 (s, 18 H).
13C NMR (CDCl3, 100 MHz): δ = 142.3, 140.4, 135.9, 128.7,
118.4, –0.2. HRMS (ESI): m/z [M]+ calcd. for C16H22S2Si2:
334.0696; found: 334.0696.
afford 6 (350 mg, 77%) as a viscous oil. The product was
kept in the freezer in the dark, and used as soon as possible.
IR (ATR): 3103, 3066, 3005, 2957, 2925, 2869, 1800,
1616 cm–1. 1H NMR (CDCl3, 400 MHz): δ = 7.19 (dd, J =
5.3, 0.8 Hz, 1 H), 6.94 (d, J = 5.3 Hz, 1 H), 6.66 (ddd, J
=17.3, 11.0, 0.8 Hz, 1 H), 5.58 (d, J = 17.3 Hz, 1 H), 5.13 (d,
J = 11.0 Hz, 1 H). 13C NMR (CDCl3, 100 MHz): δ = 139.1,
134.2, 130.1, 129.2, 123.1, 113.7. HRMS (ESI): m/z [M+H]+
calcd for C12H11S2: 219.0299; found: 219.0297.
(34) Preparation of Benzo[1,2-b:4,3-b′]dithiophene (1) by
RCM: Under argon, Grubbs’ 1st generation catalyst
[Ru(Pcy3)2(CHPh)Cl2] (30 mg, 0.1 equiv) was added to a
solution of 2,2′-divinyl-3,3′-bithiophene (6; 80 mg, 0.36
mmol, 1 equiv) in anhydrous CH2Cl2 (25 mL). The reaction
mixture was stirred at r.t. for 8 h, then the solvent was
removed under reduced pressure and the crude product was
purified by column chromatography (silica; hexanes), to
afford 1 (67 mg, 96%).
(35) Preparation of N′,N′′-{[3,3′-Bithiophene]-2,2′-
diylbis(methanylylidene)}bis(4-
(39) Preparation of N′,N′′-{[5,5′-Bis(trimethylsilyl)-(3,3′-
bithiophene)-2,2′-diyl]bis(methanylylidene)}bis(4-
methylbenzenesulfonylhydrazone) (16): Using the method
employed for the synthesis of 8 (see ref. 35) 5,5′-
bis(trimethylsilyl)-(3,3′-bithiophene)-2,2′-dicarbaldehyde
(12b; 2 g, 5.45 mmol, 1 equiv) and tosylhydrazide (2.03 g,
10.9 mmol, 2 equiv) were dissolved in distilled THF (250
mL) and the mixture was stirred at r.t. overnight, dried over
MgSO4, and evaporated to afford 16 (3.83 g, 100%) as a
bright-yellow-orange solid foam. Mp 156 °C. IR (ATR):
3190, 3065, 2955, 2926, 2898, 2856, 1597 cm–1. 1H NMR
(DMSO-d6, 400 MHz): δ = 11.38 (s, 2 H), 7.74 (s, 2 H), 7.67
(d, J = 8.2 Hz, 4 H), 7.40 (dd, J = 8.2, 0.7 Hz, 4 H), 7.16 (s,
2 H), 2.36 (s, 6 H), 0.30 (s, 18 H). 13C NMR (DMSO-d6, 100
MHz): δ = 143.5, 142.5, 140.2, 139.2, 137.3, 137.0, 136.1,
129.7, 127.0, 21.0, –0.5. HRMS (ESI): m/z [M+H]+ calcd for
C30H39N4O4S4Si2: 703.1387; found: 703.1387.
(40) (a) Bamford, W. R.; Stevens, T. S. M. J. Chem. Soc. 1952,
4735. (b) Chamberlain, A. R.; Bloom, S. H. Org. React.
1990, 39, 1.
(41) (a) Shapiro, R. H.; Duncan, J. H.; Clopton, J. C. J. Am.
Chem. Soc. 1967, 89, 471. (b) Shapiro, R. H. Org. React.
1976, 23, 405. (c) Aldington, R. M.; Barrett, A. G. M. Acc.
Chem. Res. 1983, 16, 55.
methylbenzenesulfonylhydrazone) (8): [3,3′-
Bithiophene]-2,2′-dicarbaldehyde 12a (1.05 g, 4.7 mmol, 1
equiv) and tosylhydrazide (1.75 g, 9.4 mmol, 2 equiv) were
dissolved in distilled THF (300 mL) and stirred at r.t.
overnight. The reaction mixture was dried over MgSO4,
filtered and evaporated to give 8 (2.62 g, 100%) as a bright-
yellow-orange solid foam. Mp 129 °C. IR (ATR): 3176,
2958, 2923, 2867, 1645, 1594 cm–1. 1H NMR (400 MHz,
DMSO-d6): δ = 11.33 (s, 2 H), 7.77 (d, J = 0.9 Hz, 2 H), 7.69
(dd, J = 5.1, 0.7 Hz, 2 H), 7.67 (d, J = 8.4 Hz, 4 H), 7.40 (dd,
J = 8.1, 0.6 Hz, 4 H), 7.03 (d, J = 5.1 Hz, 2 H), 2.36 (s, 6 H).
13C NMR (100 MHz, DMSO-d6): δ = 143.7, 140.7, 136.4,
136.0, 134.7, 130.3, 129.8, 128.7, 127.2, 21.1. HRMS (ESI):
m/z [M+H]+ calcd for C24H23N4O4S4: 559.0597; found:
559.0587.
(36) The intramolecular McMurry cyclisation of 12a was
unsuccessful under a variety of conditions [e.g., TiCl4/Zn
and TiCl3(DME)1.5/Zn(Cu)], despite its use as an
intermolecular coupling reaction to obtain the 1,2-
dithiophenylethene starting material for the photochemical
route. For typical reaction conditions, see: (a) Yoshida, S.;
Fujii, M.; Aso, Y.; Otsubo, T.; Ogura, F. J. Org. Chem. 1994,
59, 3077. (b) See also ref. 15c.
(37) Preparation of Benzo[1,2-b:4,3-b′]dithiophene (1) by Bis-
hydrazone Coupling: [3,3′-Bithiophene]-2,2′-
(42) (a) Chamberlin, A. R.; Stemke, J. E.; Bond, F. T. J. Org.
Chem. 1978, 43, 147. (b) Miranda, R.; Hernandez, A.;
Angeles, E.; Cabrera, A.; Salmon, M.; Joseph-Nathan, P.
Analyst 1990, 115, 1483.
(43) Chamberlin, A. R.; Bond, F. T. J. Org. Chem. 1978, 43, 154.
(44) Carbene intermediates have also been proposed for the
Shapiro reaction, see ref. 41c.
(45) A referee has suggested that the dianion (see Scheme 5, box)
is the intermediate in the cyclisation reaction, which is
entirely reasonable, especially in the sodium hydride
procedure (see ref. 37) in which the base was used in excess,
but when 1.05 equiv butyllithium is employed (see ref. 38),
the second deprotonation is probably effected by the
toluenesulfinate anion in a reversible step that is driven,
ultimately, by the irreversible loss of nitrogen, and the
reaction then probably follows the mechanism drawn in
Scheme 5.
(46) Jung tentatively proposes (see ref. 18a) that when the base is
sodium hydride, both tosylhydrazones deprotonate and
eliminate the tosylsulphinate, before ring closure occurs.
(47) Kerr, W. J.; Morrison, A. J.; Pazicky, M.; Weber, T. Org.
Lett. 2012, 14, 2250.
dicarbaldehyde (12a; 4 g, 18 mmol, 1 equiv) and
tosylhydrazide (6.59 g, 36 mmol, 2 equiv) were dissolved in
distilled THF (850 mL), and the mixture was stirred at r.t.
overnight, dried over Na2SO4, and transferred to a 1 L three-
necked round-bottom flask that has been flame-dried under
nitrogen. The reaction mixture was cooled to 0 °C and NaH
(95%; 1.08 g, 45 mmol, 2.5 equiv) was added in portions.
The reaction mixture was allowed to warm to r.t. and then
heated at reflux for 3 h under nitrogen. After cooling, the
solution was concentrated under reduced pressure to 100
mL, and sat. aq NH4Cl (300 mL) was added. The mixture
was extracted with EtOAc (2 × 400 mL) and the combined
organic layers were dried over MgSO4, filtered, and
evaporated to leave a brown solid (4 g). The crude product
was purified by column chromatography (silica; hexanes) to
afford 1 (1.21 g, 37%) as colourless crystals.
(38) Preparation of 2,7-Bis(trimethylsilyl)benzo[1,2-b:4,3-
b′]dithiophene (15) by Bis-hydrazone Coupling: 5,5′-
Bis(trimethylsilyl)-[3,3′-bithiophene]-2,2′-dicarbaldehyde
(12b; 2.62 g, 7.15 mmol, 1 equiv) and tosylhydrazide (2.66
g, 15.30 mmol, 2 equiv) were dissolved in distilled THF (450
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 701–707