Selective halogen dance reactions at 5,5'-dibromo-2,2'-bithiophene

Article abstract of DOI:10.3987/COM-08-S(N)84

Selective single and double halogen migrations were achieved at 5,5'-dibromo-2,2'-bithiophene by varying the amount of lithiation reagent, and a number of tri- and tetrasubstituted bithiophenes was obtained by quenching the lithio intermediates with various electrophiles. Some of the mono-rearranged products were subjected to a second migration in order to introduce two different substituents. Finally, the potential of the resulting compounds to undergo lithiuminduced ring opening reactions was demonstrated on a few examples.

Full text of DOI:10.3987/COM-08-S(N)84

HETEROCYCLES, Vol. 76, No. 2, 2008
1249
HETEROCYCLES, Vol. 76, No. 2, 2008, pp. 1249 - 1259. © The Japan Institute of Heterocyclic Chemistry
Received, 1st April, 2008, Accepted, 13th May, 2008, Published online, 19th May, 2008. COM-08-S(N)84
SELECTIVE HALOGEN DANCE REACTIONS AT
5,5’-DIBROMO-2,2’-BITHIOPHENE
Roman Bobrovsky, Christian Hametner, Wolfram Kalt, and Johannes
Fröhlich*
Vienna University of Technology, Institute of Applied Synthetic Chemistry,
Getreidemarkt 9/163, 1060 Vienna, Austria
E-mail: johannes.froehlich+e163@tuwien.ac.at
Abstract – Selective single and double halogen migrations were achieved at
5
,5’-dibromo-2,2’-bithiophene by varying the amount of lithiation reagent, and a
number of tri- and tetrasubstituted bithiophenes was obtained by quenching the
lithio intermediates with various electrophiles. Some of the mono-rearranged
products were subjected to a second migration in order to introduce two different
substituents. Finally, the potential of the resulting compounds to undergo lithium-
induced ring opening reactions was demonstrated on a few examples.
th
Dedicated to Prof. Ryoji Noyori on the occasion of his 70 birthday
INTRODUCTION
The term “halogen dance” (HD, also known as halogen migration or scrambling) refers to a reaction of a
(
hetero)aromatic system, during which a halogen atom changes its position under the influence of a base.
1
When first observed, it was regarded as an unexpected side reaction without any preparative usefulness. In
the meantime, its mechanism is well understood and a large number of synthetic applications has been
developed, mostly using a lithium dialkylamide as base and quenching the final lithio intermediate with an
2
electrophile in order to introduce an additional substituent.
Our own work in this field started with migrations at bromothiophenes and –furans, providing access to
3
several series of trisubstituted derivatives. In the present paper we extend the HD methodology to
brominated 2,2’-bithiophenes, a class of compounds with numerous potential applications, e.g. synthesis of
polythiophenes and highly conjugated building blocks.

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HETEROCYCLES, Vol. 76, No. 2, 2008
RESULTS AND DISCUSSION
In general, a halogen dance reaction may take place when a halogenated aromatic system is metalated in a
way that the resulting substitution pattern is not the thermodynamically most stable one. If in such a case the
metalated species and the starting material are present together in the reaction mixture, a cascade of
metal-halogen exchange steps can take place leading to the final, most stable intermediate. This in turn can
then be quenched by an electrophile to form the final product. In some cases the reaction can also be
conducted in a way that prevents the transmetalation cascade and thus leads to a product with the original
halogen pattern retained, although this course of the reaction is usually more difficult to achieve.
Hal
Hal
E
+
E
Halogen
dance (HD)
Ar
Ar
Ar
Met
H
Met
Hal
Ar
Ar
Hal
+
E
E
Prevention of HD
Hal
Scheme 1. General pathways for halogen dance and its prevention.
5
,5’-Dibromo-2,2’-bithiophene (1) fulfills the above requirements in a way similar to 2,5-dibromo-
4
thiophene, the halogen migration of which has already been studied. The principal prerequisites thus being
met, the crucial question for 1 to serve as a useful substrate for selective HD reactions is: to what extent
does the metalation of one thiophene ring influence the reactivity of the other?
Initial experiments were carried out by rapid addition of 1 to one equivalent of LDA, a method which in
many cases provides quick metalation, but also sufficient contact between the starting material and the
primary lithiated species for the halogen dance to proceed smoothly. However, in this case varying
mixtures of single (3) and double (9) rearrangement products together with some remaining 1 were
obtained after quenching with TMSCl. Therefore we changed to a method that allows much better control
of the lithiation process: the slow addition of a pre-formed LDA solution to the substrate, sometimes
referred to as “inverse addition”. By using 1.25 equiv. of LDA at -20 °C it was indeed possible to obtain
rearrangement at only one ring almost exclusively, together with less than 5 % of the double migration
product, which could easily be removed during the purification step. Using this procedure a number of
trisubstituted 2,2’-bithiophene derivatives was synthesized (see Scheme 2, Table 1).
However it should be pointed out that to achieve this high level of selectivity very careful observance of the
protocol is absolutely necessary. As the reaction starts with a suspension of 1 instead of a solution, it is of

HETEROCYCLES, Vol. 76, No. 2, 2008
1251
particular importance to keep the addition of LDA slow, especially from the beginning of the reaction
until all of 1 has dissolved, otherwise a local excess of the metalation agent might arise and trigger the
second rearrangement step. Also any excess of diisopropylamine should be avoided during the
preparation of LDA, as this seriously interferes with the initial lithiation step. Finally it proved necessary
to adjust the excess of LDA to the actual scale on which the reaction is performed: while the mentioned
amount of 1.25 LDA was optimal for 1 g of 1 (~ 3 mmol), best results for reactions on a 5-fold scale were
obtained with only 1.1 equivalents. This can be attributed to the relatively higher losses occurring when
the external preparation and especially the transfer of LDA is carried out with small amounts.
As the protocol for single rearrangement also allows the gradual addition of a larger extent of LDA, we
also tried to employ it for the double migration reaction by stepwise increasing the amount of the
lithiation reagent. By applying 2.5 equivalents of LDA complete conversion to the double rearranged
pattern was obtained, and again a number of products were synthesized by quenching with various
electrophiles (see Scheme 2, Table 1). Having in hand the results for single and double migration, the
initial question for the influence of the first metalation step on the bithiophene system can be answered:
the presence of a lithium atom in one thiophene ring does reduce the reactivity of the second ring towards
metalation considerably, otherwise a selective single rearrangement would not be possible; however the
second lithiation is still possible by applying a significant excess of reagent.
Br
Br
Br
a
b
Br
E
Br
Br
E
E
S
S
S
S
S
S
2
- 7
1
8 - 13
+
+
Scheme 2. Single and double halogen dance at 1: (a) 1.25 LDA, E ; (b) 2.5 LDA, E .
Table 1. Single and double rearrangement products of 1.
Br
Br
Br
Br
E
E
E
S
S
S
S
Electrophile
E
Compd
Yield (%)
Compd
Yield (%)
MeOH
TMS-Cl
TBDMS-Cl
MeI
-H
-TMS
-TBDMS
-Me
2
3
4
5
6
7
68
89
91
76
51
63
8
74
79
71
83
61
67
9
10
11
12
13
MeSSMe
DMF
-SMe
-CHO

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HETEROCYCLES, Vol. 76, No. 2, 2008
Having synthesized double rearrangement products with two identical substituents, our next effort was
towards compounds with two different residues by subjecting some of the single-migrated substances to a
second, independent migration step. As the first substituent of potential substrates for such a reaction
obviously has to be inert towards lithiation conditions, our experiments started with the trimethylsilyl
derivative 3. However, the TMS group turned out to be unstable in the presence of some of the aryl
lithium compounds occurring in the rearrangement reaction. Therefore its TBDMS analogue 4 was used,
and by applying a similar method as above, the desired mixed-substituted bithiophenes were obtained,
although in this case a more classical halogen dance protocol (rapid addition of the substrate to 0.95 equiv.
of LDA, stirring for 15 minutes and completing the reaction with another 0.25 equiv. of LDA) provided
better yields and purity. Despite some doubts concerning side chain metalation, we also applied the
procedure to the methyl derivative 5, and succeeded in the synthesis of another series of tetrasubstituted
bithiophenes (see Scheme 3, Table 2).
Br
Br
Br
Br
E1
E2
E1
S
S
S
S
4
, E = TBDMS
14 - 17, E = TBDMS
1
1
5
, E = Me
18 - 21, E = Me
1
1
Scheme 3. Second migration reaction at 4 and 5.
Table 2. Unsymmetrically tetrasubstituted 2,2’-bithiophenes.
Br
E2
Br
TBDMS
Br
E2
Br
Me
S
S
S
S
Electrophile
E
2
Compd
Yield (%)
Compd
Yield (%)
MeOH
TMS-Cl
MeI
-H
-
18
19
-
81
64
-TMS
-Me
14
15
16
17
53
45
80
53
MeSSMe
DMF
-SMe
-CHO
20
21
70
70
Finally, a few of the silyl-substituted bithiophenes were subjected to a lithium-induced ring opening
reaction. By carefully controlling the amount of BuLi used, it was possible to obtain cleavage of one or
both thiophene rings in a selective manner. Quenching the thiolate anion formed by the ring opening with

HETEROCYCLES, Vol. 76, No. 2, 2008
1253
methyl iodide then provided access to compounds of potential interest as highly unsaturated building
blocks (see Scheme 4).
Br
E
22, E = TMS
23, E = TBDMS
a
E
S
Br
Br
SMe
E
E
S
S
b
MeS
E
2
4, E = TMS
9
1
, E = TMS
0, E = TBDMS
25, E = TBDMS
E
SMe
Scheme 4. Ring opening reactions: (a) 1.0 BuLi, MeI; (b) 2.1 BuLi, MeI.
In conclusion, we have shown that selective single and double halogen dance reactions at
,5’-dibromo-2,2’-bithiophene can be achieved using an “inverse addition” protocol by varying the
5
amount of metalating agent. Some of the mono-rearranged products were successfully subjected to a
second migration step. In total, four series of mostly novel tri- and tetrasubstituted 2,2’-bithiophene
derivatives were synthesized by quenching the lithio intermediates with various electrophiles. Finally the
suitability of the obtained compounds for ring-opening reactions was demonstrated on a few examples.
EXPERIMENTAL
General. Chemicals were purchased from commercial suppliers and purified before use. All solvents
were distilled prior to use. Dry diethyl ether and dry tetrahydrofuran were obtained by distillation over
sodium/benzophenone. All reactions were carried out under an atmosphere of dry nitrogen. Flash column
chromatography was performed on silica gel 60 from Merck (40 – 63 µm). Melting points were
determined using a Kofler-type Leica Galen III micro-hot-stage microscope and are uncorrected.
Elemental analyses were carried out in the Microanalytical Laboratory, University of Vienna. NMR
1
spectra were recorded from solutions in CDCl
3
on a Bruker AC-200 spectrometer (200 MHz for H, 50
1
3
MHz for C) and chemical shifts are reported in ppm using Me
4
Si as internal standard.
5
2
,5’-Dibromo-2,2’-bithiophene (1) was synthesized via Ni-catalyzed homo-coupling of
5
6
-bromothiophene and bromination of the resulting 2,2’bithiophene using NBS. The synthesis of
7
compounds 8 and 13 has previously been described by other methods.
General procedure for single halogen migration. Compounds 2-7. n-Butyllithium (3.86 mmol) was

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HETEROCYCLES, Vol. 76, No. 2, 2008
added to a solution of diisopropylamine (0.39 g, 3.86 mmol) in dry THF (20 mL) at -40 °C and stirred for
5 min. This solution was then slowly transferred via a Teflon cannula into another flask containing a
1
suspension of 1 (1 g, 3.09 mmol) in dry THF (10 mL) at -20 °C over a period of 10 min and stirred for
another 15 min. At the same temperature a solution of the appropriate electrophile (4 mmol) in dry THF
(
5 mL) was added. The mixture was allowed to reach 0 °C, poured onto water and extracted with Et
2
O.
The combined organic layers were washed with water, dried over Na SO and evaporated.
2
4
4,5’-Dibromo-2,2’-bithiophene (2). Instead of an electrophile, MeOH (1 mL) was added to the reaction
mixture. The crude product was triturated with dry MeOH to yield 0.68 g (68%) of 2 as yellow crystals.
1
Mp 72-74 °C. H-NMR: δ = 7.12 (d, 1H, J = 1.6 Hz), 7.01 (d, 1H, J = 1.6 Hz), 6.98 (d, 1H, J = 3.8 Hz),
1
3
6
.91 (d, 1H, J = 3.8 Hz) ppm. C-NMR: δ = 137.5 (s), 137.3 (s), 130.7 (d), 126.3 (d), 124.5 (d), 121.8 (d),
12.1 (s), 110.4 (s) ppm. Anal. Calcd for C Br (324.06): C 29.65; H 1.24. Found: C 29.48; H 1.05.
1
8
H
4
2 2
S
4
,5’-Dibromo-5-trimethylsilyl-2,2’-bithiophene (3). Chlorotrimethylsilane (0.43 g) was used as
electrophile. The crude product was purified by bulb-to-bulb distillation to yield 1.09 g (89%) of 3 as
1
yellow oil. Bp 90-95 °C / 0.02 torr. H-NMR: δ = 7.09 (s, 1H), 6.97 (d, 1H, J = 3.8 Hz), 6.91 (d, 1H, J =
1
3
3
1
3
.8 Hz), 0.42 (s, 9H) ppm. C-NMR: δ = 141.0 (s), 137.3 (s), 134.0 (s), 130.6 (d), 128.7 (d), 124.2 (d),
17.4 (s), 111.9 (s), -0.8 (q) ppm. Anal. Calcd for C11
3.25; H 2.95.
2 2
H12Br S Si (396.24): C 33.34; H 3.05. Found: C
4
,5’-Dibromo-5-((1,1-dimethylethyl)dimethylsilyl)-2,2’-bithiophene (4). Chloro-(1,1dimethylethyl)-
dimethylsilane (0.6 g) was used as electrophile. The crude product was purified by bulb-to-bulb
1
distillation to yield 1.23 g (91%) of 4 as yellow oil. Bp 110-115 °C / 0.02 torr. H-NMR: δ = 7.09 (s, 1H),
1
3
6
.97 (d, 1H, J = 3.8 Hz), 6.92 (d, 1H, J = 3.8 Hz), 0.99 (s, 9H), 0.41 (s, 6H) ppm. C-NMR: δ = 141.4 (s),
137.3 (s), 132.2 (s), 130.7 (d), 129.1 (d), 124.3 (d), 118.0 (s), 112.0 (s), 26.8 (q), 18.2 (s), -0.4 (q) ppm.
Anal. Calcd for C14
2 2
H18Br S Si (438.32): C 38.36; H 4.14. Found: C 38.63; H 3.93.
4,5’-Dibromo-5-methyl-2,2’-bithiophene (5). Methyl iodide (0.57 g) was used as electrophile. The
crude product was recrystallized from dry EtOH to yield 0.79 g (76%) of 5 as yellow crystals. Mp
1
1
00-102 °C. H-NMR: δ = 6.95 (d, 1H, J = 3.8 Hz), 6.91 (s, 1H), 6.83 (d, 1H, J = 3.8 Hz), 2.37 (s, 3H)
1
3
ppm. C-NMR: δ = 137.7 (s), 133.6 (s), 133.3 (s), 130.5 (d), 126.1 (d), 123.6 (d), 111.2 (s), 109.6 (s),
9 6 2 2
14.6 (q) ppm. Anal. Calcd for C H Br S (338.09): C 31.97; H 1.79. Found: C 32.01; H 1.76.
4,5’-Dibromo-5-methylthio-2,2’-bithiophene (6). Dimethyl disulfide (0.38 g) was used as electrophile.
The product was purified by flash chromatography (hexane) to yield 0.58 g (51%) of 6 as yellow oil.
1
TLC: R
f
= 0.48 (hexane). H-NMR: δ = 6.98-6.93 (m, 2H) 6.86 (d, 1H, J = 3.8 Hz), 2.48 (s, 3H) ppm.

HETEROCYCLES, Vol. 76, No. 2, 2008
1255
1
3
C-NMR: δ = 137.6 (s), 137.1 (s), 131.9 (s), 130.6 (d), 126.6 (d), 124.2 (d), 115.9 (s), 112.1 (s), 20.3 (q)
ppm. Anal. Calcd for C Br (370.15): C 29.21; H 1.63. Found: C 29.35; H 1.67.
9
H
6
2 3
S
4,5’-Dibromo-2,2’-bithiophene-5-carbaldehyde (7). Dimethyl formamide (0.29 g) was used as
electrophile. The crude product was recrystallized from diisopropyl ether to yield 0.69 g (63%) of 7 as
1
yellow crystals. Mp 141-143 °C. H-NMR: δ = 9.92 (s, 1H), 7.13-7.07 (m, 2H), 7.05 (d, 1H, J = 3.8 Hz)
1
3
ppm. C-NMR: δ = 182.5 (d), 145.2 (s), 136.2 (s), 134.8 (s), 131.4 (d), 127.4 (d), 126.7 (d), 120.8 (s),
15.2 (s) ppm. Anal. Calcd for C Br OS (352.07): C 30.70; H 1.15. Found: C 30.73; H 0.92.
1
9
H
4
2
2
General procedure for double halogen migration. Compounds 8-13. n-Butyllithium (7.73 mmol) was
added to a solution of diisopropylamine (0.78 g, 7.73 mmol) in dry THF (20 mL) at -40 °C and stirred for
15 min. This solution was then slowly transferred via a Teflon cannula into another flask containing a
suspension of 1 (1 g, 3.09 mmol) in dry THF (10 mL) at -20 °C over a period of 10 min and stirred for
another 15 min. At the same temperature a solution of the appropriate electrophile (7.8 mmol) in dry THF
(
5 mL) was added. The mixture was allowed to reach 0 °C, poured onto water and extracted with Et
2
O.
The combined organic layers were washed with water, dried over Na SO and evaporated.
2
4
4,4’-Dibromo-2,2’-bithiophene (8). Instead of an electrophile, MeOH (1 mL) was added to the reaction
mixture. The crude product was recrystallized from dry MeOH to yield 0.74 g (74%) of 8 as beige
1
13
crystals. Mp 121-123 °C. H-NMR: δ = 7.15 (d, 2H, J = 1.6 Hz), 7.08 (d, 2H, J = 1.6 Hz) ppm. C-NMR:
8 4 2 2
δ = 137.0 (s), 126.6 (d), 122.2 (d), 110.5 (s) ppm. Anal. Calcd for C H Br S (324.06): C 29.65; H 1.24.
Found: C 29.74; H 1.44.
4
,4’-Dibromo-5,5’-bis(trimethylsilyl)-2,2’-bithiophene (9). Chlorotrimethylsilane (0.84 g) was used as
electrophile. The crude product was triturated with dry MeOH to yield 1.14 g (79%) of 9 as light-yellow
1
13
crystals. Mp 110-112 °C. H-NMR: δ = 7.15 (s, 2H), 0.41 (s, 18H) ppm. C-NMR: δ = 140.6 (s), 134.5
s), 129.0 (d), 117.5 (s), -0.8 (q) ppm. Anal. Calcd for C14 Si (468.42): C 35.90; H 4.30. Found:
C 35.82; H 4.25.
(
H20Br
2
S
2
2
4,4’-Dibromo-5,5’-bis((1,1-dimethylethyl)dimethylsilyl)-2,2’-bithiophene (10). Chloro-(1,1dimethyl-
ethyl)dimethylsilane (1.18 g) was used as electrophile. The crude product was recrystallized from dry
1
EtOH to yield 1.21 g (71%) of 10 as beige crystals. Mp 97-98 °C. H-NMR: δ = 7.17 (s, 2H), 0.99 (s,
1
3
1
8H), 0.42 (s, 12H) ppm. C-NMR: δ = 140.8 (s), 132.6 (s), 129.3 (d), 117.9 (s), 26.7 (q), 18.1 (s), -4.4
(
q) ppm. Anal. Calcd for C20 Si (552.58): C 43.47; H 5.84. Found: C 43.46; H 5.85.
H
32Br
2
S
2
2
4,4’-Dibromo-5,5’-dimethyl-2,2’-bithiophene (11). Methyl iodide (1.11 g) was used as electrophile. The
crude product was recrystallized from dry MeOH to yield 0.91 g (83%) of 11 as yellow crystals. Mp

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HETEROCYCLES, Vol. 76, No. 2, 2008
1
13
1
10-111 °C. H-NMR: δ = 6.90 (s, 2H), 2.38 (s, 6H) ppm. C-NMR: δ = 133.3 (2s), 125.7 (d), 109.5 (s),
14.6 (q) ppm. Anal. Calcd for C10
8 2 2
H Br S (352.11): C 34.11; H 2.29. Found: C 33.92; H 2.12.
4
,4’-Dibromo-5,5’-bis(methylthio)-2,2’-bithiophene (12). Dimethyl disulfide (0.73 g) was used as
electrophile. The crude product was recrystallized from dry MeOH to yield 0.78 g (61%) of 12 as yellow
1
13
crystals. Mp 90-92 °C. H-NMR: δ = 7.01 (s, 2H), 2.50 (s, 6H) ppm. C-NMR: δ = 136.8 (s), 132.8 (s),
1
26.8 (d), 115.6 (s), 20.2 (q) ppm. Anal. Calcd for C10
8.71; H 1.71.
8 2 4
H Br S (416.25): C 28.86; H 1.94. Found: C
2
4,4’-Dibromo-2,2’-bithiophene-5,5’-dicarbaldehyde (13). DMF (0.57 g) was used as electrophile. The
crude product was recrystallized from CHCl
3
to yield 0.78 g (67%) of 13 as yellow crystals. Mp
1
13
2
1
0
58-260 °C. H-NMR: δ = 9.89 (s, 2H), 7.90 (s, 2H) ppm. C-NMR: δ = 183.1 (d), 142.1 (s), 136.8 (s),
31.3 (d), 120.7 (s) ppm. Anal. Calcd for C10
.90.
4 2 2 2
H Br O S (380.08): C 31.60; H 1.06. Found: C 31.54; H
General procedure for second halogen migration at 4. Compounds 14-17. n-Butyllithium (2.17 mmol)
was added to a solution of diisopropylamine (0.22 g, 2.17 mmol) in dry THF (20 mL) at -30 °C and
stirred for 15 min. Then a solution of 4 (1 g, 2.28 mmol) in dry THF (5 mL) was added quickly and the
mixture stirred for 15 min at -20 °C. Diisopropylamine (0.06 g, 0.57 mmol) dissolved in dry THF (5 mL)
and n-butyllithium (0.57 mmol) were mixed in a dropping funnel and added to the reaction mixture
within 5 min at -20 °C. After stirring for another 5 min a solution of the appropriate electrophile (3 mmol)
in dry THF (5 mL) was added. The mixture was allowed to reach 0 °C, poured onto water and extracted
with Et
2 2 4
O. The combined organic layers were washed with water, dried over Na SO and evaporated.
4
,4’-Dibromo-5-((1,1-dimethylethyl)dimethylsilyl)-5’-trimethylsilyl-2,2’-bithiophene (14). Chloro-
trimethylsilane (0.32 g) was used as electrophile. The crude product was recrystallized from dry MeOH to
1
yield 0.61 g (53%) of 14 as white crystals. Mp 82-83 °C. H-NMR: δ = 7.16 (s, 1H), 7.15 (s, 1H), 0.99 (s,
1
3
9
1
4
H), 0.42 (s, 15H) ppm. C-NMR: δ = 141.0 (s), 140.5 (s), 134.7 (s), 132.7 (s), 129.3 (d), 129.1 (d),
18.0 (s), 117.5 (s), 26.8 (q), 18.3 (s), -0.8 (q), -4.4 (q) ppm. Anal. Calcd for C17
0.00; H 5.13. Found: C 39.74; H 4.98.
2 2 2
H26Br S Si (510.50): C
4
,4’-Dibromo-5-((1,1-dimethylethyl)dimethylsilyl)-5’-methyl-2,2’-bithiophene (15). Methyl iodide
(0.42 g) was used as electrophile. The crude product was recrystallized from dry MeOH to yield 0.46 g
1
(
45%) of 15 as beige crystals. Mp 71-73 °C. H-NMR: δ = 7.08 (s, 1H), 6.99 (s, 1H), 2.40 (s, 3H), 0.99 (s,
1
3
9
H), 0.42 (s, 6H) ppm. C-NMR: δ = 141.5 (s), 134.1 (s), 132.9 (s), 132.0 (s), 128.7 (d), 126.6 (d), 117.9
Si (452.35): C 39.83;
(
s), 109.8 (s), 26.8 (q), 18.2 (s), 14.8 (q), -4.3 (q) ppm. Anal. Calcd for C15
H20Br
2
S
2

HETEROCYCLES, Vol. 76, No. 2, 2008
1257
H 4.46. Found: C 39.86; H 4.32.
4,4’-Dibromo-5-((1,1-dimethylethyl)dimethylsilyl)-5’-methylthio-2,2’-bithiophene (16). Dimethyl
disulfide (0.28 g) was used as electrophile. The product was purified by flash chromatography (light
f
petroleum) to yield 0.83 g (80%) of 16 as yellow crystals. TLC: R = 0.36 (light petroleum). Mp
1
5
2-54 °C. H-NMR: δ = 7.12 (s, 1H), 7.06 (s, 1H), 2.50 (s, 3H), 0.98 (s, 9H), 0.42 (s, 6H) ppm.
1
3
C-NMR: δ = 140.7 (s), 137.0 (s), 132.8 (s), 132.5 (s), 129.1 (d), 127.0 (d), 118.0 (s), 115.7 (s), 26.7 (q),
2
0.3 (q), 18.1 (s), -4.5 (q) ppm. Anal. Calcd for C15
6.89; H 3.87.
2 3
H20Br S Si (484.42): C 37.19; H 4.16. Found: C
3
4,4’-Dibromo-5’-((1,1-dimethylethyl)dimethylsilyl)-2,2’-bithiophene-5-carbaldehyde (17). DMF
(0.22 g) was used as electrophile. The crude product was recrystallized from light petroleum to yield 0.56
1
g (53%) of 17 as yellow crystals. Mp 122-124 °C. H-NMR: δ = 9.92 (s, 1H), 7.32 (s, 1H), 7.20 (s, 1H),
1
3
0
.99 (s, 9H), 0.42 (s, 6H) ppm. C-NMR: δ = 182.5 (d), 144.6 (s), 139.7 (s), 136.3 (s), 135.2 (s), 131.4
d), 127.8 (d), 120.7 (s), 118.6 (s), 26.8 (q), 18.2 (s), -4.4 (q) ppm. Anal. Calcd for C15 OS Si
466.33): C 38.63; H 3.89. Found: C 38.33; H 3.62.
(
(
H18Br
2
2
General procedure for second halogen migration at 5. Compounds 18-21. n-Butyllithium (3.55 mmol)
was added to a solution of diisopropylamine (0.38 g, 3.73 mmol) in dry THF (25 mL) at -40 °C and
stirred for 15 min. This solution was then slowly transferred via a Teflon cannula into another flask
containing a solution of 5 (1 g, 2.96 mmol) in dry THF (40 mL) at -20 °C over a period of 15 min and
stirred for another 15 min. At the same temperature a solution of the appropriate electrophile (3.85 mmol)
in dry THF (5 mL) was added. The mixture was allowed to reach 0 °C, poured onto water and extracted
with Et
2 2 4
O. The combined organic layers were washed with water, dried over Na SO and evaporated.
4
,4’-Dibromo-5-methyl-2,2’-bithiophene (18). Instead of an electrophile, MeOH (1 mL) was added to
the reaction mixture. The crude product was recrystallized from dry EtOH to yield 0.81 g (81%) of 18 as
1
yellow crystals. Mp 55-57 °C. H-NMR: δ = 7.10 (d, 1H, J = 1.6 Hz), 7.00 (d, 1H, J = 1.6 Hz), 6.98 (s,
1
3
1
H), 2.40 (s, 3H) ppm. C-NMR: δ = 137.5 (s), 134.3 (s), 133.0 (s), 126.6 (d), 125.9 (d), 121.6 (d), 110.4
(
s), 109.7 (s), 14.8 (q) ppm. Anal. Calcd for C Br (338.09): C 31.97; H 1.79. Found: C 32.22; H
9
H
6
2 2
S
1.70.
4
,4’-Dibromo-5-methyl-5’-trimethylsilyl-2,2’-bithiophene (19). Chlorotrimethylsilane (0.40 g) was
used as electrophile. The crude product was recrystallized from dry EtOH to yield 0.78 g (64%) of 19 as
1
orange crystals. Mp 101-104. H-NMR: δ = 7.08 (s, 1H), 6.98 (s, 1H), 2.40 (s, 3H), 0.40 (s, 9H) ppm.
1
3
C-NMR: δ = 141.0 (s), 134.0 (s), 133.8 (s), 132.9 (s), 128.4 (d), 126.4 (d), 117.3 (s), 109.7 (s), 14.7 (q),

1258
HETEROCYCLES, Vol. 76, No. 2, 2008
2 2
-0.9 (q) ppm. Anal. Calcd for C12H15Br S Si (410.27): C 35.13; H 3.44. Found: C 35.20; H 3.33.
4
,4’-Dibromo-5-methyl-5’-methylthio-2,2’-bithiophene (20). Dimethyl disulfide (0.36 g) was used as
electrophile. The crude product was recrystallized from dry EtOH to yield 0.66 g (70%) of 21 as orange
1
13
crystals. Mp 67-69 °C. H-NMR: δ = 6.97 (s, 1H), 6.93 (s, 1H), 2.50 (s, 3H), 2.40 (s, 3H) ppm. C-NMR:
δ = 137.8 (s), 134.2 (s), 132.7 (s), 131.7 (s), 126.4 (2d), 115.9 (s), 109.7 (s), 20.4 (q), 14.7 (q) ppm. Anal.
8 2 3
Calcd for C10H Br S (384.18): C 31.26; H 2.10. Found: C 31.62; H 2.00.
4,4’-Dibromo-5’-methyl-2,2’-bithiophene-5-carbaldehyde (21). DMF (0.30 g) was used as electrophile.
The crude product was recrystallized from dry EtOH to yield 0.76 g (70%) of 21 as orange crystals. Mp
1
13
1
60-163 °C. H-NMR: δ = 9.90 (s, 1H), 7.16 (s, 1H), 7.11 (s, 1H), 2.40 (s, 3H) ppm. C-NMR: δ = 182.3
d), 145.2 (s), 137.1 (s), 134.6 (s), 131.8 (s), 128.2 (d), 127.0 (d), 120.6 (s), 110.6 (s), 14.9 (q) ppm. Anal.
Calcd for C10 Br OS (366.10): C 32.81; H 1.65. Found: C 33.06; H 1.75.
(
H
6
2
2
General procedure for single ring opening. Compounds 22 and 23. n-Butyllithium (0.92 mmol) was
added to a solution of 9 or 10, resp. (0.91 mmol) in dry Et O (40 mL) within 1 min at -40 °C. The mixture
was allowed to reach ambient temperature and a solution of methyl iodide (0.71 g, 5 mmol) in dry Et
5 mL) was added. After stirring for 10 min the mixture was poured onto water and extracted with Et
The combined organic layers were washed with water, dried over Na SO and evaporated.
2
2
O
(
2
O.
2
4
3-Bromo-5-(1-methylthio-4-(trimethylsilyl)but-1-en-3-ynyl)-2-(trimethylsilyl)thiophene (22). 9 (0.43
g) was used as starting material. The product was purified by flash chromatography (light petroleum) to
1
yield 0.31 g (85%) of 22 as orange oil. TLC: R
f
= 0.26 (light petroleum). H-NMR: δ = 7.22 (s, 1H), 6.07
1
3
(
s, 1H), 2.45 (s, 3H), 0.39 (s, 9H), 0.23 (s, 9H) ppm. C-NMR: δ = 147.6 (s), 142.1 (s), 136.9 (s), 130.9
d), 117.4 (s), 109.0 (d), 105.5 (s), 102.2 (s), 17.3 (q), -0.2 (q), -0.9 (q) ppm. Anal. Calcd for
Si (403.56): C 44.64; H 5.74. Found: C 44.86; H 5.69.
(
C
15
H23BrS
2
2
3-Bromo-5-(1-methylthio-4-((1,1-dimethylethyl)dimethylsilyl)but-1-en-3-ynyl)-2-((1,1-dimethyl-
ethyl)dimethylsilyl)thiophene (23). 10 (0.50 g) was used as starting material. The product was purified
f
by flash chromatography (light petroleum) to yield 0.33 g (75%) of 23 as yellow oil. TLC: R = 0.31
1
(
light petroleum). H-NMR: δ = 7.22 (s, 1H), 6.11 (s, 1H), 2.44 (s, 3H), 0.99 (s, 9H), 0.97 (s, 9H), 0.40 (s,
1
3
6
H) 0.19 (s, 6H) ppm. C-NMR: δ = 148.0 (s), 142.0 (s), 135.0 (s), 131.2 (d), 117.9 (s), 109.5 (d), 104.1
(s), 102.8 (s), 26.8 (q), 26.1 (q), 18.2 (s), 17.4 (q), 16.8 (s), -4.4 (q), -4.7 (q) ppm. Anal. Calcd for
C
21
H35BrS
2
Si (487.72): C 51.73; H 7.23. Found: C 51.87; H 7.00.
2
General procedure for double ring opening. Compounds 24 and 25. n-Butyllithium (1.91 mmol) was
added to a solution of 9 or 10, resp. (0.91 mmol) in dry Et O (10 mL) within 1 min at ambient
2

HETEROCYCLES, Vol. 76, No. 2, 2008
1259
temperature. The mixture was stirred for 30 min and a solution of methyl iodide (0.71 g, 5 mmol) in dry
Et O (5 mL) was added. After stirring for another 15 min the mixture was poured onto water and
2
2 2 4
extracted with Et O. The combined organic layers were washed with water, dried over Na SO and
evaporated.
4
,5-Bis(methylthio)-1,8-bis(trimethylsilyl)octa-3,5-diene-1,7-diyne (24). 9 (0.43 g) was used as starting
material. The crude product was triturated with dry MeOH to yield 0.16 g (52%) of 24 as beige crystals.
1
13
Mp 104-106 °C. H-NMR: δ = 5.74 (s, 2H), 2.34 (s, 6H), 0.22 (s, 18H) ppm. C-NMR: δ = 149.4 (s),
1
09.1 (d), 105.1 (s), 100.9 (s), 15.3 (q), -0.2 (q) ppm. Anal. Calcd for C16
.74. Found: C 56.33; H 7.57.
26 2 2
H S Si (403.56): C 56.74; H
7
4,5-Bis(methylthio)-1,8-bis((1,1-dimethylethyl)dimethylsilyl)octa-3,5-diene-1,7-diyne (25). 10 (0.50
g) was used as starting material. The crude product was triturated with dry MeOH to yield 0.21 g (55%)
1
of 25 as beige crystals. Mp 93-95 °C. H-NMR: δ = 5.78 (s, 2H), 2.35 (s, 6H), 0.99 (s, 18H), 0.19 (s, 12H)
1
3
ppm. C-NMR: δ = 149.4 (s), 109.1 (d), 103.4 (s), 101.5 (s), 26.0 (q), 16.6 (s), 15.2 (q), -4.8 (q) ppm.
Anal. Calcd for C22 Si (422.85): C 62.49; H 9.06. Found: C 62.53; H 8.91.
H
38
S
2
2
ACKNOWLEDGEMENTS
J. F. is grateful to the Hochschuljubiläumsstiftung der Stadt Wien for financial support.
REFERENCES AND NOTES
1
2
3
4
. (a) A. Vaitiekunas and F. F. Nord, J. Am. Chem. Soc., 1953, 75, 1764. (b) J. H. Woitz and F. Huba, J.
Org. Chem., 1959, 24, 595.
. For reviews, see: (a) T. Frejd, Chem. Heterocycl. Comp., 1992, 44, 257. (b) G. W. Rewcastle and A. R.
Katritzky, Adv. Het. Chem., 1993, 56, 155. (c) J. Fröhlich, Prog. Heterocycl. Chem., 1994, 6, 1.
. An overview of our work in this area including a preview of results presented here can be found in ref.
2
. (c) and in this proceeding of a conference lecture: J. Fröhlich, Bull. Soc. Chim. Belg., 1996, 105, 615.
. (a) S. Kano, Y. Yuasa, T. Yokomatsu, and S. Shibuya, Heterocycles, 1983, 20, 2035. (b) H. Fröhlich
and W. Kalt, J. Org. Chem., 1990, 55, 2993.
5. E. Khor, S. C. Ng, H. C. Li, and S. Chai, Heterocycles, 1991, 32, 1805.
6. R. M. Kellog, A. P. Schaap, and H. Wynberg, J. Org. Chem., 1969, 34, 343.
7. U. Dahlmann and R. Neidlein, Helv. Chim. Acta, 1996, 79, 755.