A three-step synthetic approach to asymmetrically functionalized 4H-cyclopenta[2,1-b:3,4-b′]dithiophenes

Article abstract of DOI:10.1021/jo101405j

A convenient and efficient three-step route toward both symmetrically and asymmetrically functionalized 4H-cyclopenta[2,1-b:3,4-b′]dithiophenes has been developed. Using this method a broad collection of functionalized bridged bithiophenes can smoothly be accessed. Starting from 3-bromo-2,2′- bithiophene, prepared by Kumada coupling of 2-thienylmagnesium bromide with 2,3-dibromothiophene under Pd(dppf)Cl₂ catalysis, lithiation and subsequent reaction with dialkyl ketones afforded (a)symmetrically dialkylated tertiary alcohol derivatives. By means of final Friedel-Crafts dehydration cyclization in sulfuric acid medium, these derivatives were converted to 4,4-dialkyl-4H-cyclopenta[2,1-b:3,4-b′]dithiophenes. Upon replacement of the dialkyl ketone reagent by ethyl levulinate, an ester-functionalized 4H-cyclopenta[2,1-b:3,4-b′]dithiophene was prepared, representing an attractive precursor for variously functionalized cyclopentadithiophene compounds.

Full text of DOI:10.1021/jo101405j

pubs.acs.org/joc
A Three-Step Synthetic Approach to Asymmetrically Functionalized
0
4
H-Cyclopenta[2,1-b:3,4-b ]dithiophenes
†
Sarah Van Mierloo, Peter J. Adriaensens, Wouter Maes, Laurence Lutsen,
†
†,‡
§
†
Thomas J. Cleij, Edith Botek, Beno ıˆ t Champagne, and Dirk J. Vanderzande*
^
^
,†,§
†
Hasselt University, Institute for Materials Research (IMO), Agoralaan - Building D, B-3590 Diepenbeek,
Belgium, Molecular Design and Synthesis, Department of Chemistry, Katholieke Universiteit Leuven,
‡
§
Celestijnenlaan 200F, B-3001 Leuven, Belgium, IMEC, Division IMOMEC, Universitaire Campus -
^
Wetenschapspark 1, B-3590 Diepenbeek, Belgium, and Laboratoire de Chimie Th eꢀ orique, Facult eꢀ s
Universitaires Notre-Dame de la Paix (FUNDP), Rue de Bruxelles 61, B-5000 Namur, Belgium
dirk.vanderzande@uhasselt.be
Received July 16, 2010
A convenient and efficient three-step route toward both symmetrically and asymmetrically functio-
0
nalized 4H-cyclopenta[2,1-b:3,4-b ]dithiophenes has been developed. Using this method a broad
collection of functionalized bridged bithiophenes can smoothly be accessed. Starting from 3-bromo-
0
2
mothiophene under Pd(dppf)Cl catalysis, lithiation and subsequent reaction with dialkyl ketones
,2 -bithiophene, prepared by Kumada coupling of 2-thienylmagnesium bromide with 2,3-dibro-
2
afforded (a)symmetrically dialkylated tertiary alcohol derivatives. By means of final Friedel-Crafts
dehydration cyclization in sulfuric acid medium, these derivatives were converted to 4,4-dialkyl-4H-
0
cyclopenta[2,1-b:3,4-b ]dithiophenes. Upon replacement of the dialkyl ketone reagent by ethyl
0
levulinate, an ester-functionalized 4H-cyclopenta[2,1-b:3,4-b ]dithiophene was prepared, represent-
ing an attractive precursor for variously functionalized cyclopentadithiophene compounds.
Introduction
applied in the design of polymerization catalysts and conju-
Cyclopentadie-
1-7
gated polymers with various applications.
nyl ligands fused with thiophene units have been investigated
as structural subunits of homogeneous metallocene catalysts
During the last decades cyclopentadithiophenes have
emerged as attractive building blocks for the development of
novel materials. These heterocycles have for example been
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1) (a) Ewen, J. A.; Jones, R. L.; Elder, M. J.; Rheingold, A. L.; Liable-
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c)Sannicolo, F.;Brenna, E.; Benincori,T.;Zotti,G.;Zecchin, S.; Schiavon, G.;
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7
202 J. Org. Chem. 2010, 75, 7202–7209
Published on Web 10/06/2010
DOI: 10.1021/jo101405j
r 2010 American Chemical Society

Van Mierloo et al.
JOCArticle
8
h-j
SCHEME 1. State-of-the-Art Method toward Dialkyl-CPDTs
0
SCHEME 2. Novel Synthetic Route toward 4,4-Dialkyl-4H-cyclopenta[2,1-b:3,4-b ]dithiophenes
8
for the polymerization of 1-olefins, affording enhanced control
over the polymer microstructure not achievable by traditional
mostly symmetrically dialkylated cyclopentadithiophenes.
Consequently, finding a more economic, straightforward, and
versatile synthetic protocol would be beneficial and could also
facilitate optimization of the CPDT-based material features.
In this paper, a three-step pathway toward both symmetrically
and asymmetrically substituted dialkyl-CPDTs and functional
derivatives thereof is reported.
1
Ziegler-Natta catalysts. On the other hand, cyclopenta-
dithiophenes have become popular rigid precursors for poly-
2-7
meric (semi)conducting materials.
Zotti and others have
extensively studied the optical, electrochemical, and conduct-
ing properties of poly(cyclopentadithiophenes), immobilized
2,3
on surfaces by electrochemical polymerization. Such poly-
mers could be applied as sensor systems when well-established
supramolecular recognition elements (calixarenes or crown
Results and Discussion
2
c,h,3f
The first synthetic pathway toward the 4H-cyclopenta[2,1-
0
ethers) were appended.
Electrochromic polymers based
4
b:3,4-b ]dithiophene isomer was reported in 1968 by Wyn-
berg and co-workers, affording the parent CPDT 5 in a low
on cyclopentadithiophenes have also been reported recently,
whereas conducting cyclopentadithiophene-based matrices for
electrochemically controlled (DNA) delivery systems have
been developed by the group of Cougnon and Pilard.
Out of the six possible cyclopentadithiophene isomers,
4H-cyclopenta[2,1-b:3,4-b ]dithiophene has majorly been applied
for the construction of conjugated polymer materials, whereas
the 7H-cyclopenta[1,2-b:4,3-b ]dithiophene analogue has most
often been used for the development of metallocene catalysts.
8
a
overall yield. Although some improvements to this proce-
dure have been made over the years, synthetic progress has
More recently, Reynolds and Brze-
zinski described a three-step synthesis;one-pot double
5
8
b-g
been rather limited.
0
lithiation and iodination, oxidation, and Ullmann cou-
0
pling;toward 4H-cyclopenta[2,1-b:3,4-b ]dithiophen-4-one
(
0
4), the ketone analogue of the rigidly bridged bithiophene
8
h
unit (Scheme 1). This cyclic ketone could subsequently
be reduced with hydrazine according to a Huang-Minlon
modification of the Wolff-Kischner procedure, as reported
by Turner et al. (Scheme 1). Dialkylation at the methylene
bridge (4-position) of the planar bithiopheneunit, requiredfor
processability in solution, has been performed with various
0
The vast majority of 4H-cyclopenta[2,1-b:3,4-b ]dithiophene
(CPDT) building blocks reported to date have been synthe-
sized by rather laborious multistep procedures affording
8
i,j
(
6) A recent review article summarizes the wide variety of cyclopenta-
dithiophene-based electroactive materials: Coppo, P.; Turner, M. L. J. Mater.
Chem. 2005, 15, 1123.
(
7) (a) Asawapirom, U.; Scherf, U. Macromol. Rapid Commun. 2001, 22,
46. (b) Wu, C.-G.; Hsieh, C.-W.; Chen, D.-C.; Chang, S.-J.; Chen, K.-Y.
7
(8) Synthetic procedures toward CPDTs: (a) Kraak, A.; Wiersema,
A. K.; Jordens, P.; Wynberg, H. Tetrahedron 1968, 24, 3381. (b) Jordens,
P.; Rawson, G.; Wynberg, H. J. Chem. Soc. C 1970, 273. (c) Wiersema, A.;
Gronowitz, S. Acta Chem. Scand. 1970, 24, 2593. (d) Jeffries, A. T.; Moore,
K. C.; Ondeyka, D. M.; Springsteen, A. W.; MacDowell, D. W. H. J. Org.
Chem. 1981, 46, 2885. (e) Kozaki, M.; Tanaka, S.; Yamashita, Y. J. Org.
Chem. 1994, 59, 442. (f) Beyer, R.; Kalaji, M.; Kingscote-Burton, G.;
Murphy, P. J.; Pereira, V. M. S. C.; Taylor, D. M.; Williams, G. O. Synth.
Met. 1998, 92, 25. (g) Lucas, P.; El Mehdi, N.; Ho, H. A.; B ꢀe langer, D.;
Breau, L. Synthesis 2000, 9, 1253. (h) Reynolds, J. R.; Brzezinski, J. Z.
Synthesis 2002, 8, 1053. (i) Coppo, P.; Cupertino, D. C.; Yeates, S. G.;
Turner, M. L. J. Mater. Chem. 2002, 12, 2597. (j) Coppo, P.; Cupertino,
D. C.; Yeates, S. G.; Turner, M. L. Macromolecules 2003, 36, 2705. (k) Park,
J. H.; Lee, B. Y. Bull. Korean Chem. Soc. 2010, 31, 1064.
Synth. Met. 2005, 155, 618. (c) M u€ hlbacher, D.; Scharber, M.; Morana, M.;
Zhu, Z.; Waller, D.; Gaudiana, R.; Brabec, C. Adv. Mater. 2006, 18, 2884. (d)
Zhang, M.; Tsao, H. N.; Pisula, W.; Yang, C.; Mishra, A. K.; M u€ llen, K.
J. Am. Chem. Soc. 2007, 129, 3472. (e) Peet, J.; Kim, J. Y.; Coates, N. E.; Ma,
W. L.; Moses, D.; Heeger, A. J.; Bazan, G. C. Nat. Mater. 2007, 6, 497. (f) De
Cremer, L.; Vandeleene, S.; Maesen, M.; Verbiest, T.; Koeckelberghs, G.
Macromolecules 2008, 41, 591. (g) Hou, J.; Chen, H.-Y.; Zhang, S.; Li, G.;
Yang, Y. J. Am. Chem. Soc. 2008, 130, 16144. (h) Bijleveld, J. C.; Shahid, M.;
Gilot, J.; Wienk, M. M.; Janssen, R. A. J. Adv. Funct. Mater. 2009, 19, 3262.
(
i) Jung, I. H.; Yu, J.; Jeong, E.; Kim, J.; Kwon, S.; Kong, H.; Lee, K.; Woo,
H. Y.; Shim, H.-K. Chem.;Eur. J. 2010, 16, 3743. (j) Horie, M.; Majewski,
L. A.; Fearn, M. J.; Yu, C.-Y.; Luo, Y.; Song, A.; Saunders, B. R.; Turner,
M. L. J. Mater. Chem. 2010, 20, 4347.
J. Org. Chem. Vol. 75, No. 21, 2010 7203

Van Mierloo et al.
SCHEME 3. Ring Closure vs Alkene Formation
JOCArticle
TABLE 1. Tested (Lewis) Acidic Reaction Conditions for the Alkylative
Cyclization Reaction toward CPDT 12a
(
Lewis)
acid
reaction
time (h)
T
(ꢀC)
12a
(%)
entry
equiv
solvent
a
1
2
3
4
5
6
7
8
9
BF
BF
BF
BF
HCl
HCl
3
3
3
3
OEt
OEt
OEt
OEt
2
2
2
2
159
80
80
1
8.5
8.5
12
12
12
12
12
12
12
3
2
3
12
4
12
12
12
12
12
12
2
CH
CH
CH
CH
2
Cl
2
Cl
2
Cl
2
Cl
2
2
2
2
rt
rt
rt
rt
120
120
rt
rt
rt
rt
rt
80
rt
-
3
3
3
3
a
-
a
-
a
-
a
AcOH
AcOH
-
n-octane
-
-
a
-
a
HNO
p-TsOH
3
-
a
-
a
H
H
H
H
H
3
2
2
2
2
PO
4
-
45
b
1
1
1
1
0
1
2
3
a
SO
SO
SO
4
4
4
-
b
n-octane
AcOH
55
a
-
35
b
CrO
4
12
Mainly a mixture of 13 and 14, sometimes accompanied by small
b
amounts of 12a. No remaining alkene isomers.
8
i,j
alkyl halides, either employing KOH in DMSO (Scheme 1)
2
or by stepwise lithiation and alkylation.
a,9
The synthetic protocol as summarized in Scheme 1 represents
the most efficient route toward dialkylated CPDTs to date and
is hence applied frequently for the construction of CPDT-based
materials. This state-of-the-art synthetic procedure can, how-
ever, be regarded as comparatively laborious and more suitable
0
of bithiophene moieties toward 4H-cyclopenta[2,1-b:3,4-b ]-
12,13
dithiophenes has been performed.
Scherf et al. described
a series of ring closure reactions promoted by borontrifluor-
ide dietherate (BF OEt ) toward thiophene-phenylene and
thiophene-naphthalene stepladder copolymers. However,
application of the same reaction conditions to tertiary
alcohol derivative 11a (Table 1, entry 1) afforded majorly
alkene Z and E isomers 13 and 14 by simple dehydration
(Scheme 3). Under all tested reaction conditions (variation
of the number of equivalents of BF OEt and the reaction
time), formation of these alkene isomers remained dominant
9
3
3
2
for symmetrically dialkylated CPDT derivatives. This encour-
14
aged us to search for an alternative synthetic method, which
would be applicable toward a wide range of CPDTs. The major
goals were the ability to introduce, using one single straightfor-
ward approach, two identical or different alkyl chains simulta-
neously and to enable introduction of basic functional groups
on these alkyl chains.
3
3
2
Our novel synthetic approach comprises three main steps,
as depicted in Scheme 2. 4,4-Diethyl-4H-cyclopenta[2,1-
(
Table 1, entries 1-4). Several attempts were carried out to
perform the cyclization reaction with Br o€ nsted acids. How-
ever, this effort did not lead to any noticeable improvement
0
b:3,4-b ]dithiophene (12a) was used as the model compound
during this study, but the optimized procedures were readily
extended to other (asymmetrically) dialkylated derivatives
(
Table 1, entries 5-9). Finally, efficient ring closure was
achieved by means of addition of an excess of sulfuric acid
Table 1, entry 10). The as-formed orange solution was diluted
with water and dichloromethane followed by extraction and,
after purification of the crude oil by column chromatography,
CPDT 12a was obtained in a reasonable yield of 45%.
A slightly higher yield (55%) could be achieved upon dilution
of the reagents in n-octane (Table 1, entry 11), whereas
addition of acetic acid afforded once more the alkene mixture
(
vide infra). According to the reported protocol by J u€ ttner
and co-workers, 3-bromo-2,2 -bithiophene (9) was synthe-
sized through a Kumada coupling of the Grignard reagent of
(
1
0
0
2
Pd(dppf)Cl catalysis. The next step involved regiospecific
-bromothiophene (7) with 2,3-dibromothiophene (8) under
2
formation of the lithio derivative by bromo-lithio exchange.
The lithiated compound was then in situ reacted with
3
-pentanone (1 equiv) affording tertiary alcohol derivative
(
Table 1, entry 12). As an alternative Br o€ nsted acid to promote
1
1a. Subsequently, after tedious optimization of the ring
1
1
closure conditions, an acid-catalyzed (H SO ) cyclization
cyclization, chromic acid could also be used (Table 1, entry 13).
It can be assumed that after dehydration the formed alkene
Z and E isomers 13 and 14 undergo protonation of the double
bond and subsequent intramolecular alkylation (Scheme 3).
Several test reactions indicated that immediate workup after
addition of sulfuric acid to the alcohol derivative 11a afforded
alkene isomers 13 and 14. On the other hand, all traces of
alkenes were converted into ring closed CPDT 12a after 1 h.
Treatment of the isolated alkene mixture with H SO also
2
4
reaction afforded the desired diethyl-CPDT 12a.
To the best of our knowledge, there are no literature
reports in which (Lewis) acid-catalyzed alkylative cyclization
(
9) A few asymmetrically dialkylated CPDTs have been reported by Zotti
et al. (refs 2e, 2f, and 2i).
10) Harm, U.; B u€ rgler, R.; F u€ rbeth, W.; Mangold, K.-M.; J u€ ttner, K.
Macromol. Symp. 2002, 187, 65.
11) Abarca, B.; Asensio, G.; Ballesteros, R.; Varea, T. J. Org. Chem.
991, 56, 3224.
(
2
4
(
afforded 12a. Summarizing these observations, the cyclization
seems to be thermodynamically controlled with the CPDT
as the thermodynamic sink. To support this interpretation,
1
(12) A spirodithiophenefluorene derivative in which the 7H-cyclopenta-
1,2-b:4,3-b ]dithiophene isomeric structure can be recognized has been
0
[
synthesized by Friedel-Crafts dehydration cyclization in a mixture of HCl
and AcOH: Xie, L.-H.; Hou, X.-Y.; Hua, Y.-R.; Huang, Y.-Q.; Zhao, B.-M.;
Liu, F.; Peng, B.; Wei, W.; Huang, W. Org. Lett. 2007, 9, 1619.
(14) (a) Scherf, U.; M u€ llen, K. Makromol. Chem., Rapid Commun. 1991,
12, 489. (b) Scherf, U.; Bohnen, A.; M u€ llen, K. Makromol. Chem. 1992, 193,
1127. (c) B u€ nnagel, T. W.; Nehls, B. S.; Galbrecht, F.; Schottler, K.; Kudla,
C. J.; Volk, M.; Pina, J.; Seixas de Melo, J. S.; Burrows, H. D.; Scherf, U.
J. Polym. Sci., Part A: Polym. Chem. 2008, 46, 7342.
(13) (a) Qiu, S.; Lu, P.; Liu, X.; Shen, F.; Liu, L.; Ma, Y.; Shen, J.
Macromolecules 2003, 36, 9823. (b) Wong, K.-T.; Chao, T.-C.; Chi, L.-C.;
Chu, Y.-Y.; Balaiah, A.; Chiu, S.-F.; Liu, Y.-H.; Wang, Y. Org. Lett. 2006, 8,
5
033.
7
204 J. Org. Chem. Vol. 75, No. 21, 2010

Van Mierloo et al.
JOCArticle
FIGURE 1. Optimized structures of CPDT 12a (top: front and side
view) and alkenes 13 and 14 (bottom).
theoretical calculations on the alkene isomers and diethyl-
CPDT 12a were carried out. At the MP2/6-311þG** level of
approximation, the ring closed structure was found to be about
8-9 kcal/mol more stable than the alkene-containing species.
As shown in Figure 1, compound 12a is planar whereas large
deviations from planarity are observed for the alkenes.
The two alkene stereoisomers 13 and 14 could not readily be
separated resulting in complex NMR spectra for the alkene
mixture. The intensity difference of the signals due to the ratio
of the two isomers enabled the distinction of the signals for each
isomer, i.e. one isomer was formed in 35%, whereas the other
15
was formed in 65%. Complete assignment of the proton and
carbon resonances was accomplished by a combination of 2D-
1
13
HETCOR and one-dimensional NMR techniques ( H, C,
DEPT, and APT) (cf. the Supporting Information). All che-
mical shift data of both isomers could be collected, but since
they were not separable, NOE(-dif) experiments were required
to establish a clear distinction. Two data sets were acquired in
one of which selective preirradiation was applied. In Figure 2
only the part of the spectra is shown which changed in intensity.
Upon preirradiation at 1.47 ppm, saturating the methyl pro-
tons (H ) of the isomer found in the biggest amount, NOE
7
enhancement was observed for the β-thienyl proton (H ) at
3
6.77 ppm (Figure 2). This gave a first indication that Z isomer
13 is formed in excess resulting in the highest peak intensities. In
addition, NOE enhancement was also observed for the vinyl
proton (H ) at 5.62 ppm (Figure 2). Upon preirradiation at
6
5.57 ppm, saturating the resonance corresponding to the vinyl
proton (H ) of the isomer formed in the smallest amount, NOE
6
enhancement was observed for the β-thienyl proton (H ) at
3
6.85 ppm (Figure 2). This confirmed that the Z alkene 13 is
majorly formed, whereas the E isomer 14 is produced in smaller
amounts. In addition, NOE enhancement was also observed
for the methyl protons (H ) at 1.74 ppm. No further NOE’s
were observed.
Hence, Zalkene 13 was formed in 65%, whereas the Ealkene
14 represented only 35%. This observation might indicate that
the Z alkene is slightly more thermodynamically stable than the
7
FIGURE 2. NOE spectra for the mixture of alkene isomers 13 and
1
4: preirradiation at 1.47 (top) and 5.57 ppm (bottom);(control)
spectrum without preirradiation (bottom), NOE spectrum (middle),
and difference spectrum (top).
E alkene. These results were also confirmed by theoretical
ΔG calculations. Using the MP2/6-311þG** method and
accounting for solvent effects (AcOH), a slightly lower energy
(15) The studied alkene mixture was obtained from the attempt to per-
form the cyclization with HCl in AcOH (Table 1, entry 6).
J. Org. Chem. Vol. 75, No. 21, 2010 7205

Van Mierloo et al.
JOCArticle
TABLE 2. Selected Optimized Parameters for Z Alkene 13 and
E Alkene 14
SCHEME 4. Synthetic Strategy toward Ester-Functionalized
CPDT 12h
0
0
parameters
Z: R=Me, R =H (13) E: R=H, R =Me (14)
˚
bond lengths (A)
C
C
C
C
C
C
5
4
6
6
;C
;C
;C
dC14
14;R15
9
6
7
1.454
1.483
1.514
1.351
1.504
1.089
1.458
1.481
1.520
1.354
1.091
1.502
0
14;R 16
torsion angles (deg)
S
1
;C
5
;C
9
;S10
;C
dR14
;R
50.6
5.0
67.8
6.0
3.6
178.0
73.4
C
C
C
C
C
6
3
;C
;C
4
dC
;C
;C
5
9
8.7
56.2
71.0
5.1
4
6
14dC
6
7
8
4
4
;C
;C
6
dC14;R15
0
6
dC14;R 16
185.0
Conclusions
(
by 1 kcal/mol) was found for Z alkene 13 as compared to
In summary, we have designed an elegant and convenient
0
E alkene 14. This difference in favor of the Z form is attributed
to the important deviation from planarity, i.e., to the larger
interthiophene-ring dihedral angle (S ;C ;C ;S ) of the
approach toward 4H-cyclopenta[2,1-b:3,4-b ]dithiophenes,
shortening the currently applied route while concomitantly
extending its synthetic possibilities. Simple variation of the
ketone reagent opens new perspectives in the synthesis of
(asymmetrically) functionalized CPDT derivatives, and the
final ring closing step was optimized. The functionalization
scope can be extended further by a versatile ester-functiona-
lized CPDT scaffold. Experimental observations on the
plausible reaction pathway have been supported by detailed
NMR spectroscopy and theoretical energy calculations.
1
5
9
10
E form and the larger distortion of its double bond planarity
0
C ;C dC ;R and C ;C dC ;R 16), resulting in a
4 6 14 15 4 6 14
(
slightly larger C dC bond length (Figure 1, Table 2).
6
14
The main advantages of the presented route compared to the
traditionally applied route are the shortened straightforward
sequence and the ability to synthesize different materials simply
by changing the ketone reagent applied in the formation of the
tertiary alcohol. In this way a number of dialkylated CPDTs
12b-g, both symmetrical and asymmetrical derivatives, have
Experimental Section
been prepared. Reaction with the dialkyl ketone and ring clo-
sure both proceeded in moderate to good yields (18-75% for
NMR chemical shifts (δ) in ppm were determined relative to
13
3
the residual CHCl absorption (7.26 ppm) or the C resonance
1
7
1
1a-g, 16-57% for 12a-g). Once again, the yield for the cycli-
shift of CDCl3 (77.16 ppm). Gas chromatography-mass
spectrometry (GC-MS) analyses were carried out applying
Chrompack Cpsil5CB or Cpsil8CB capillary columns. Exact
mass measurements were performed in the EI mode at a resolu-
tion of 10 000. Solution UV-vis absorption measurements were
performed with a scan rate of 600 nm/min in a continuous
run from 200 to 800 nm. Infrared spectra were collected with a
zation step could be improved by dilution of the alcohol pre-
cursor in n-octane (from 17% to 57% for 12d, from 30% to
1
6
5
3% for 12g).
The newly developed three-step procedure also readily
allows introduction of functional groups on (one of) the alkyl
substituents based upon a versatile ester-functionalized CPDT
-
1
resolution of 4 cm (16 scans), using films drop-casted on a
NaCl disk from a CHCl solution. Unless stated otherwise, all
0
scaffold. Reaction of the lithio derivative of 3-bromo-2,2 -
bithiophene (9) with ethyl levulinate (ethyl 4-oxopentanoate
3
reagents and chemicals were obtained from commercial sources
and used without further purification. Diethyl ether was dried
by distillation from Na/benzophenone.
15) afforded lactone 16 by intramolecular transesterification of
the intermediate tertiary alcohol with the terminal ethyl ester
moiety (Scheme 4). Ring-opening of the lactone in ethanol
under acid-catalyzed conditions resulted in alkene isomers 17
and 18 (25:75 ratio), which were converted to ester-functiona-
lized CPDT 12h with the aid of sulfuric acid (Scheme 4).
Starting from this ester derivative (or, alternatively, the lactone
precursor), basic functional group conversions (or lactone
ring-opening reactions) should enable access to variously
substituted CPDT building blocks.
0
3-Bromo-2,2 -bithiophene (9) was synthesized according to a
1
literature procedure. Material identity and purity was con-
0
1
13
firmed by MS, IR, and H and C NMR.
5-Ethylpentadecan-7-one (10d). A Grignard solution of
-ethylhexylmagnesium bromide in dry diethyl ether (1.0 M,
10 mL, 0.11 mol) was slowly added via a syringe to a stirred
2
1
mixture of n-octylcyanide (4.66 g, 55 mmol) in dry diethyl ether
(
100 mL) at 0 ꢀC under N atmosphere. After being stirred for
2
1
2 h at reflux temperature, the reaction was quenched with an
(16) Intermolecular reaction (oligomer formation) was observed as a
minor side reaction by ESI-MS (less pronounced upon dilution).
(17) Gottlieb, H. E.; Kotlyar, V.; Nudelman, A. J. Org. Chem. 1997, 62,
7512.
7
206 J. Org. Chem. Vol. 75, No. 21, 2010

Van Mierloo et al.
JOCArticle
aqueous HCl solution (2.0 M) at 0 ꢀC and subsequently vigor-
ously stirred for an additional 3 h at rt. The organic phase was
separated and the aqueous phase was extracted with diethyl
ether. The combined organic phases were washed with a satu-
1H), 7.02 (d, J = 5.3 Hz, 1H), 1.92 (s, 1H), 1.80-1.64 (m, 4H),
1.57-1.50 (m, 2H), 0.91 (d, J = 6.3 Hz, 6H), 0.71 (d, J = 6.6 Hz,
1
3
6H); C NMR (75 MHz, CDCl
3
) δ 145.7, 135.6, 129.5 (CH),
128.8 (CH), 128.4, 127.3 (CH), 126.8 (CH), 124.9 (CH), 79.3
-1
rated bicarbonate solution and brine, dried with MgSO
evaporated under reduced pressure to give a yellow oil. The
4
, and
2 3 3
(C-OH), 52.7 (CH ), 24.6 (CH ), 24.4 (CH ); IR (NaCl, cm )
ν
max 3587 (m, OH), 3106/3074 (w, unsaturatedC-H), 2955/2928/
-
2
crude oil was purified by vacuum distillation (75 ꢀC, 10 mbar)
resulting in a pure slightly yellow oil (4.51 g, 32%). GC-MS (EI)
2868 (s, saturated C-H).
7-([2,2 -Bithiophen]-3-yl)-5-ethylpentadecan-7-ol (11d). 11d was
obtained according to general procedure 1 with 3-bromo-2,2 -
0
þ
0
m/z 254 [M ]; HRMS (EI) calcd for C17
m/z 254.2612; H NMR (300 MHz, CDCl
H
34O 254.2610, found
1
3
) δ 2.37 (t, J = 7.5 Hz,
bithiophene (9) (1.00 g, 4.08 mmol), dry diethyl ether (70 mL),
n-BuLi (1.6 M in hexane, 2.50 mL, 4.08 mmol), and 5-ethylpenta-
decan-7-one (10d) (1.00 g, 4.08 mmol); eluent gradient hexane to
2
2
H), 2.30 (d, J = 6.6 Hz, 2H), 1.89-1.81 (m, 1H), 1.60-1.53 (m,
13
H), 1.26-1.18 (m, 18H), 0.91-0.81 (m, 9H); C NMR (75
) δ 212.0 (CO), 47.6 (CH ), 43.5 (CH ), 35.3 (CH),
), 32.0 (CH ), 29.6 (CH ), 29.4 (CH ), 29.3 (CH ), 29.0
MHz, CDCl
3.3 (CH
3
2
2
hexane/ethyl acetate 90:10; yield 34% (0.583 g). GC-MS (EI) m/z
420.2521, found m/z
þ
3
2
2
2
2
2
420 [M ]; HRMS (EI) calcd for C25
H
40OS
2
1
(
(
CH ), 26.5 (CH ), 24.0 (CH ), 23.1 (CH ), 22.8 (CH ), 14.2
2
420.2492; H NMR (300 MHz, CDCl ) δ7.37 (dd, J =5.2/1.2Hz,
2
2
2
2
3
-
1
CH
3
), 11.0 (CH
3
), 10.9 (CH
3
); IR (NaCl, cm ) νmax 2959/
1H), 7.24 (d, J = 5.3 Hz, 1H), 7.10 (dd, J = 3.5/1.2 Hz, 1H), 7.02
(dd, J = 5.2/3.5 Hz, 1H), 6.97 (d, J = 5.3 Hz, 1H), 1.93 (s, OH),
2
926/2859 (s, saturated C-H), 1717 (m, CO).
0
13
3-([2,2 -Bithiophen]-3-yl)pentan-3-ol (11a): General Procedure
A solution of 3-bromo-2,2 -bithiophene (9) (3.0 g, 12 mmol) in
1.77-1.58 (m, 4H), 1.44-1.05 (m, 21H), 0.89-0.69 (m, 9H); C
0
1
dry diethyl ether (100 mL) was added slowly to a solution of
NMR (75 MHz, CDCl ) δ 145.7, 135.7, 129.5 (CH), 128.7, 128.5
3
(CH), 127.3 (CH), 126.8 (CH), 124.9 (CH), 78.8 (C-OH), 47.7
(CH ), 43.4 (CH ), 34.7 (CH), 33.9 (CH ), 32.0 (CH ), 29.7 (CH ),
2 2 2 2 2
29.4 (CH ), 28.7 (CH ), 27.1 (CH ), 23.7 (CH ), 23.22 (CH ),
2 2 2 2 2
n-BuLi (1.6 M in hexane, 7.5 mL, 12 mmol) in dry diethyl ether
(
100 mL) at-78ꢀC over 2 hunderN . The mixturewas stirred for
2
1
(
5 min at the same temperature. Freshly distilled 3-pentanone
1.29 mL, 12 mmol) was added via a syringe to the mixture at
23.16 (CH ), 22.8 (CH ), 14.2 (CH ), 10.7 (CH ), 10.6 (CH ); IR
2 2 3 3 3
-
1
(NaCl, cm ) νmax 3589/3490 (m, OH), 3105/3073 (w, unsaturated
C-H), 2956/2926/2856 (s, saturated C-H).
6-([2,2 -Bithiophen]-3-yl)undecan-6-ol (11e). 11e was obtained
-
quenched with an aqueous NH Cl solution (2.5 M) and water
78 ꢀC, followed by stirring overnight at rt. The reaction was
0
4
0
at 0 ꢀC. The organic phase was separated and the aqueous phase
was extracted with diethyl ether. The combined organic phases
according to general procedure 1 with 3-bromo-2,2 -bithiophene
(9) (0.500 g, 2.04 mmol), dry diethyl ether (40 mL), n-BuLi (1.6 M
were washed with brine, dried with MgSO , and concentrated
4
in hexane, 1.25 mL, 2.04 mmol), and 6-undecanone (0.42 mL, 2.04
mmol); eluent hexane/ethyl acetate 90:10; yield 62% (0.425 g).
under reduced pressure to give a crude oil. The oily residue was
purified by column chromatography (silica, eluent hexane/ethyl
acetate 90:10) to afford the title compound as a slightly yellow oil
þ
GC-MS (EI) m/z 336 [M ]; HRMS (EI) calcd for C19
H
28OS
2
1
336.1582, found m/z 336.1580; H NMR (300 MHz, CDCl
3
) δ
þ
(
C H OS 252.0643; found m/z 252.0652; H NMR (300 MHz,
1.7 g, 56%). GC-MS (EI) m/z 252 [M ]; HRMS (EI) calcd for
7.37 (d, J = 5.2/1.3 Hz, 1H), 7.25 (d, J = 5.4 Hz, 1H), 7.10 (dd,
J = 3.5/1.3 Hz, 1H), 7.02 (dd, J = 5.2/3.5 Hz, 1H), 6.99 (d, J =
5.4 Hz, 1H), 1.80-1.59 (m, 4H), 1.26-1.16 (m, 12H), 0.85 (t, J =
1
1
3
16
2
CDCl
7
(
3
) δ 7.37 (dd, J = 5.0/1.2 Hz, 1H), 7.26 (d, J = 5.4 Hz, 1H),
13
.13 (dd, J = 3.4/1.2 Hz, 1H), 7.03 (dd, J = 5.0/3.4 Hz, 1H), 6.98
d, J = 5.4 Hz, 1H), 2.01 (s, 1H), 1.82-1.69 (m, 4H), 0.83 (t, J =
3
7.1 Hz, 6H); C NMR (75 MHz, CDCl ) δ 145.5, 135.6, 129.4
(CH), 128.7, 128.4 (CH), 127.3 (CH), 126.8 (CH), 124.9 (CH),
78.2 (C-OH), 43.1 (CH ), 32.3 (CH ), 23.5 (CH ), 22.7 (CH ),
13
7
.4 Hz, 6H); C NMR (75 MHz, CDCl ) δ 144.8, 135.6, 129.5
3
2
2
2
2
-1
(
7
CH), 129.2, 128.4 (CH), 127.3 (CH), 126.9 (CH), 125.0 (CH),
3
14.2 (CH ); IR (NaCl, cm ) νmax 3584/3474 (m, OH), 3104/3073
-1
2 3
8.8 (C-OH), 35.3 (CH ), 8.3 (CH ); IR (NaCl, cm ) νmax 3584
(w, unsaturated C-H), 2954/2929/2859 (s, saturated C-H).
1-([2,2 -Bithiophen]-3-yl)cyclohexanol (11f). 11f was obtained
0
(
(
w, OH), 3105/3073 (w, unsaturatedC-H), 2966/2931/2877/2854
0
m, saturated C-H).
according to general procedure 1 with 3-bromo-2,2 -bithiophene
(9) (0.50 g, 2.04 mmol), dry diethyl ether (40 mL), n-BuLi (1.6 M
0
2-([2,2 -Bithiophen]-3-yl)undecan-2-ol (11b). 11b was obtained
according to general procedure 1 with 3-bromo-2,2 -bithiophene
0
in hexane, 1.25 mL, 2.04 mmol), and cyclohexanone (0.21 mL,
2.04 mmol); eluent hexane/ethyl acetate 90:10; yield 49% (0.264
(
9) (1.00 g, 4.08 mmol), dry diethyl ether (70 mL), n-BuLi (1.6 M in
þ
hexane, 2.50 mL, 4.0 mmol), and 2-undecanone (0.84 mL, 4.08
mmol); eluent hexane/ethyl acetate 90:10; yield 63% (0.86 g). GC-
MS (EI) m/z 336 [M ]; HRMS (EI) calcd for C H OS
g). GC-MS (EI) m/z 264 [M ]; HRMS (EI) calcd for C14
H
16OS
2
1
264.0643, found m/z 264.0648; H NMR (300 MHz, CDCl
3
) δ
þ
7.37 (dd, J = 5.2/1.2 Hz, 1H), 7.24 (d, J = 5.4 Hz, 1H), 7.18 (dd,
J = 3.6/1.2 Hz, 1H), 7.11 (d, J = 5.4 Hz, 1H), 7.04 (dd, J = 5.2/
19
28
2
1
3
36.1582, found m/z 336.1583; H NMR (300 MHz, CDCl ) δ
3
13
7.37 (dd, J = 5.1/1.1 Hz, 1H), 7.24 (d, J = 5.4 Hz, 1H), 7.14 (dd,
J = 3.5/1.1 Hz, 1H), 7.07 (d, J = 5.4 Hz, 1H), 7.03 (dd, J = 5.1/
3.6 Hz, 1H), 1.87-1.82 (m, 4H), 1.70-1.50 (m, 6H); C NMR
(75 MHz, CDCl ) δ 147.7, 136.0, 130.0, 129.5 (CH), 127.6 (CH),
127.2 (CH), 127.0 (CH), 124.9 (CH), 73.5 (C-OH), 39.0 (CH ),
3
3
.5 Hz, 1H), 2.12 (s, 1H), 1.82-1.68 (m, 2H), 1.51 (s, 3H),
2
13
-1
1
.28-1.15 (m, 14H), 0.89 (t, J = 6.6 Hz, 3H); C NMR (75
) δ 146.8, 135.6, 129.5 (CH), 129.0, 128.1 (CH), 127.2
CH), 126.9 (CH), 124.8 (CH), 75.2 (C-OH), 44.0 (CH ), 32.0
), 24.3
); IR (NaCl, cm ) νmax 3451 (m,
2 2
25.5 (CH ), 22.1 (CH ); IR (NaCl, cm ) νmax 3553/3441 (m,
MHz, CDCl
3
OH), 3104(w, unsaturated C-H), 2932/2851(s, saturated C-H).
9-([2,2 -Bithiophen]-3-yl)heptadecan-9-ol (11g). 11g was ob-
0
(
(
(
2
0
CH
CH
2
), 30.4 (CH
), 22.8 (CH
2
), 30.0 (CH
), 14.2 (CH
2
), 29.6 (CH
2
), 29.4 (CH
2
tained according to general procedure 1 with 3-bromo-2,2 -
-
1
bithiophene (9) (5.00 g, 20 mmol), dry diethyl ether (340 mL),
n-BuLi (1.6 M in hexane, 12.8 mL, 20 mmol), and heptadecan-9-
one (5.08 g, 20 mmol); eluent gradient hexane to hexane/ethyl
2
2
3
OH), 3105/3087/3074 (w, unsaturated C-H), 2955/2925/2854 (s,
saturated C-H).
þ
0
4-([2,2 -Bithiophen]-3-yl)-2,6-dimethylheptan-4-ol (11c). 11c
was obtained according to general procedure 1 with 3-bromo-
acetate (90:10); yield 75% (6.3 g). GC-MS (EI) m/z 420 [M ];
HRMS (EI) calcd for C25
H
40OS
420.2521, found m/z 420.2521;
2
0
1
2
n-BuLi (1.6 M in hexane, 7.50 mL, 12 mmol), and 2,6-dimethyl-4-
,2 -bithiophene(9) (3.00 g, 12 mmol), dry diethyl ether (200 mL),
H NMR (300 MHz, CDCl ) δ 7.37 (dd, J = 5.2/1.1 Hz, 1H),
3
7.24 (d, J = 5.3 Hz, 1H), 7.10 (dd, J = 3.5/1.1 Hz, 1H), 7.02 (dd,
J = 5.3/3.5 Hz, 1H), 7.00 (d, J = 5.3 Hz, 1H), 1.98 (s, 1H),
heptanone(2.17mL, 12 mmol); eluent hexane/ethylacetate 90:10;
yield 18% (0.67 g). GC-MS (EI) m/z 308 [M ]; HRMS (EI) calcd
þ
1.78-1.63 (m, 4H), 1.31-1.14 (m, 24H), 0.87 (t, J = 6.6 Hz,
1
13
for C17
MHz, CDCl
Hz, 1H), 7.10 (dd, J = 3.6/1.3 Hz, 1H), 7.03 (dd, J = 5.2/3.6 Hz,
H
24OS
2
308.1269, found m/z 308.1264; H NMR (300
3
6H); C NMR (75 MHz, CDCl ) δ 145.6, 135.6, 129.4 (CH),
3
) δ 7.37 (dd, J = 5.2/1.3 Hz, 1H), 7.25 (d, J = 5.3
128.7, 128.4 (CH), 127.3 (CH), 126.8 (CH), 124.9 (CH), 78.2
(C-OH), 43.1 (CH ), 32.0 (CH ), 30.1 (CH ), 29.7 (CH ), 29.4
2
2
2
2
J. Org. Chem. Vol. 75, No. 21, 2010 7207

Van Mierloo et al.
JOCArticle
-
1
þ
(
CH ), 23.8 (CH ), 22.8 (CH ), 14.3 (CH ); IR (NaCl, cm
3
)
[M ]; HRMS (EI) calcd for C H S 318.1476, found m/z
2
2
2
2
19 26
1
318.1479; H NMR (300 MHz, CDCl
νmax 3588/3483 (m, OH), 3105/3073 (w, unsaturated C-H),
954/2925/2854 (s, saturated C-H).
3
) δ 7.16 (d, J = 4.8 Hz,
2
2H), 6.96 (d, J = 4.8 Hz, 2H), 1.88-1.82 (m, 4H), 1.24-1.09 (m,
0
13
4,4-Diethyl-4H-cyclopenta[2,1-b:3,4-b ]dithiophene (12a): General
8H), 1.03-0.93 (m, 4H), 0.80 (t, J = 7.0 Hz, 6H); C NMR (75
0
Procedure 2 H
bithiophen]-3-yl)pentan-3-ol (11a) (0.193 g, 0.77 mmol) in n-octane
10 mL) under stirring at rt. After additional stirring for 12 h,
CH Cl and water were added. The organic layer was separated and
2
SO
4
(0.5 mL) was added dropwise to 3-([2,2 -
MHz, CDCl ) δ 158.2, 136.6, 124.5 (CH), 121.7 (CH), 53.3, 37.8
3
(CH ), 32.4 (CH ), 24.3(CH ), 22.5 (CH ), 14.2 (CH ); IR(NaCl,
2
2
2
2
3
-1
(
cm ) νmax 3103/3070 (w, unsaturated C-H), 2955/2929/2858 (s,
2
2
saturated C-H); UV-vis (CHCl , nm) λ
3
max
(log ε) 249 (3.918),
the aqueous layer was extracted with CH Cl
2
organic extracts were successively washed with saturated NaHCO
and brine. After drying with MgSO , the solvent was removed in
2
. The combined
320 (4.114).
0
Spiro[4,5]([2,1-b:3,4-b ]dithieno)decane (12f). 12f was obtained
3
0
4
according to general procedure 2 with H SO (1.41 mL), 1-([2,2 -
2 4
vacuo. The crude oil was purified by column chromatography
(silica, eluent hexane) to afford a pure dark yellow oil (0.10 g, 55%).
GC-MS (EI) m/z 234 [M ]; HRMS (EI) calcd for C13
bithiophen]-3-yl)cyclohexanol (11f) (0.582 g, 2.20 mmol), and
n-octane (30 mL); eluent hexane; yield 40% (0.217 g). This
compound has been prepared before by Zotti et al. Material
þ
2g
H S
14 2
1
2
34.0537, found m/z 234.0546; H NMR (300 MHz, CDCl ) δ
identity and purity was confirmed by (HR)MS, IR, UV-vis, and
3
1
13
7
.17 (d, J = 5.0 Hz, 2H), 6.94 (d, J = 5.0 Hz, 2H), 1.91 (q, J = 7.7
H and C NMR. HRMS (EI) calcd for C H S 246.0537,
14 14 2
13
13
Hz, 4H), 0.60 (t, J = 7.7 Hz, 6H); C NMR (75 MHz, CDCl
57.5, 136.9, 124.6 (CH), 121.7 (CH), 54.4, 30.3 (CH ), 9.2 (CH
IR (NaCl, cm ) νmax 3423 (m, OH), 3102/3070 (w, unsaturated
C-H), 2964/2929/2874/2853 (s, saturated C-H); UV-vis (CHCl
nm) λmax (log ε) 249 (3.880), 320 (4.115).
-Methyl-4-nonyl-4H-cyclopenta[2,1-b:3,4-b ]dithiophene (12b).
2b was obtained according to general procedure 2 with H SO and
3
) δ
found m/z 246.0526; C NMR (75 MHz, CDCl ) δ 159.5, 135.9,
3
1
2
3
);
124.2 (CH), 122.8 (CH), 50.0, 34.2 (CH ), 25.7 (CH ), 23.8 (CH );
IR (NaCl, cm ) νmax 3102/3079 (w, unsaturated C-H), 2927/
2
2
2
-
1
-1
3
,
2853 (s, saturated C-H); UV-vis (CHCl , nm) λ
(log ε) 249
3
max
(3.588), 320 (3.802).
4,4-Dioctyl-4H-cyclopenta[2,1-b:3,4-b ]dithiophene (12g). 12g
0
0
4
1
was obtained according to general procedure 2 with H SO (9.62
4
2
4
2
0
0
(
1.33 mL), and 2-([2,2 -bithiophen]-3-yl)undecan-2-ol (11b) (0.70 g,
mL) and 9-([2,2 -bithiophen]-3-yl)heptadecan-9-ol (11g) (6.32 g,
15 mmol); eluent hexane; yield 30% (1.81 g); or with H SO
(9.62 mL), 9-([2,2 -bithiophen]-3-yl)heptadecan-9-ol (11g) (6.32
g, 15 mmol), and n-octane (200 mL); eluent hexane; yield 53%
(3.20 g). This compound has been prepared before by several
2
3
3
6
1
.08 mmol); eluent hexane; yield 16% (0.106 g). GC-MS (EI) m/z
18 [M ]; HRMS (EI) calcd for C H S 318.1476, found m/z
2
4
þ
0
19
26 2
1
18.1472; H NMR (300 MHz, CDCl ) δ 7.15 (d, J = 4.9 Hz, 2H),
3
.96 (d, J = 4.9 Hz, 2H), 1.84-1.78 (m, 2H), 1.43 (s, 3H), 1.26-
.15 (m, 14H), 0.86 (t, J = 6.9 Hz, 3H); C NMR (75 MHz,
13
2a,7i,8j
groups.
and H and C NMR.
13Material identity and purity was confirmed by MS
1
CDCl ) δ 159.5, 136.0, 124.8 (CH), 121.4 (CH), 49.0, 39.2 (CH ),
3
2
0
3
2.0 (CH ), 30.1 (CH
2
2
), 29.7 (CH ), 29.6 (CH
2
2
), 29.4 (CH
2
), 25.1
(Z)-3-(Pent-2-en-3-yl)-2,2 -bithiophene (13). GC-MS (EI) m/z
234 [M ]; HRMS (EI) calcd for C H S 234.0537, found m/z
234.0524; H NMR (300 MHz, CDCl ) δ 7.21 (dd, J = 5.1/1.3
-
1
þ
(
CH
), 23.9 (CH ), 22.8 (CH
2 2
3 3
), 14.3 (CH ); IR (NaCl, cm ) νmax
1
3
14 2
1
3
103/3069 (w, unsaturated C-H), 2955/2925/2854 (s, saturated
3
C-H); UV-vis (CHCl , nm) λ
(log ε) 249 (3.819), 320 (4.007).
,4-Diisobutyl-4H-cyclopenta[2,1-b:3,4-b ]dithiophene (12c). 12c
Hz, 1H), 7.18 (dd, J = 3.7/1.3 Hz, 1H), 7.17 (d, J = 5.1 Hz, 1H),
6.99 (dd, J = 5.1/3.7 Hz, 1H), 6.79 (d, J = 5.1 Hz, 1H), 5.64 (q,
J = 7.3 Hz, 1H), 2.28 (q, J = 6.9 Hz, 2H), 1.47 (d, J = 7.3 Hz,
3
max
0
4
was obtained according to general procedure 2 with H
2
SO
4
(1.45
mL) and 4-([2,2 -bithiophen]-3-yl)-2,6-dimethylheptan-4-ol (11c)
0
13
3H), 1.01 (t, J = 6.9 Hz, 3H); C NMR (75 MHz, CDCl ) δ
3
(
(
0.688 g, 2.23 mmol); eluent hexane; yield 35% (0.226 g). GC-MS
138.2, 137.9, 136.7, 131.8, 130.3 (CH), 127.1 (CH), 125.1 (CH),
124.9 (CH), 123.9 (CH), 123.1 (CH), 31.2 (CH ), 14.9 (CH ),
þ
EI) m/z 290 [M ]; HRMS (EI) calcd for C17
H
22
S
2
290.1163,
) δ 7.14 (d, J =
.9 Hz, 2H), 6.93 (d, J = 4.9 Hz, 2H), 1.87 (d, J = 5.7 Hz, 4H),
2
3
1
-1
found m/z 290.1168; H NMR (300 MHz, CDCl
4
1
3
13.0 (CH ); IR (NaCl, cm ) νmax 3105/3069 (w, unsaturated
3
C-H), 2963/2926/2872/2854 (s, saturated C-H).
(E)-3-(Pent-2-en-3-yl)-2,2 -bithiophene (14). GC-MS (EI) m/z
1
3
0
.05-0.97 (m, 2H), 0.51 (d, J = 6.8 Hz, 12H); C NMR (75 MHz,
) δ 157.9, 136.8, 124.5 (CH), 122.1 (CH), 53.2, 48.8 (CH),
þ
CDCl
4.9 (CH
unsaturated C-H), 2954/2925/2867 (s, saturated C-H); UV-vis
3
234 [M ]; HRMS (EI) calcd for C H S 234.0537, found m/z
14 2
234.0524; H NMR (300 MHz, CDCl ) δ 7.21 (dd, J = 5.1/1.3
1
3
-
1
1
2
2
), 24.6 (CH
3
); IR (NaCl, cm ) νmax 3104/3067 (w,
3
Hz, 1H), 7.17 (dd, J = 3.9/1.3 Hz, 1H), 7.13 (d, J = 5.2 Hz, 1H),
6.99 (dd, J = 5.1/3.9 Hz, 1H), 6.86 (d, J = 5.2 Hz, 1H), 5.57 (q,
J = 7.0 Hz, 1H), 2.35 (q, J = 7.6 Hz, 2H), 1.76 (d, J = 7.0 Hz,
(
CHCl
3
, nm) λmax (log ε) 249 (3.932), 320 (4.094).
0
4-(2-Ethylhexyl)-4-octyl-4H-cyclopenta[2,1-b:3,4-b ]dithiophene
12d). 12d was obtained according to general procedure 2 with
1
3
(
H SO (0.38mL) and7-([2,2 -bithiophen]-3-yl)-5-ethylpentadecan-
3H), 0.93 (t, J = 7.6 Hz, 3H); C NMR (75 MHz, CDCl ) δ
3
0
2
4
141.5, 137.4, 136.8, 131.2, 130.3 (CH), 126.9 (CH), 126.0 (CH),
125.8 (CH), 125.1 (CH), 123.0 (CH), 24.3 (CH ), 14.3 (CH ),
7-ol (11d) (0.25 g, 0.60 mmol); eluent hexane; yield 17% (0.040 g);
or with H
2
3
0
-1
2
SO
4
(0.38 mL), 7-([2,2 -bithiophen]-3-yl)-5-ethylpenta-
decan-7-ol (11d) (0.25 g, 0.60 mmol), and n-octane (8 mL); eluent
13.8 (CH ); IR (NaCl, cm ) νmax 3105/3069 (w, unsaturated
3
C-H), 2963/2926/2872/2854 (s, saturated C-H).
5-([2,2 -Bithiophen]-3-yl)-5-methyldihydrofuran-2-(3H)-one (16).
þ
0
hexane; yield 57% (0.137 g). GC-MS (EI) m/z 402 [M ]; HRMS
(
1
402.2415, found m/z 402.2412; H NMR
EI) calcd for C25
H S
38 2
16 was obtained according to general procedure 1 with 3-bromo-
0
(300 MHz, CDCl
3
) δ7.18 (d, J = 5.1 Hz, 2H), 7.02 (dd, J = 4.9/2.2
2,2 -bithiophene (9) (1.00 g, 4.08 mmol), dry diethyl ether (70 mL),
Hz, 2H), 2.02 (t, J = 7.5 Hz, 2H), 1.96-1.90 (m, 2H), 1.11-1.02
n-BuLi (1.6 M in hexane, 2.50 mL, 4.08 mmol), and ethyl levulinate
(15) (0.58 mL, 4.08 mmol); eluent CH Cl ; yield 36% (0.39 g). GC-
MS (EI) m/z264 [M ];HRMS(EI) calcdforC H O S 264.0279,
(
J = 7.2 Hz, 3H); C NMR (75 MHz, CDCl
m, 21H), 0.96 (t, J = 6.6 Hz, 3H), 0.87 (t, J = 6.9 Hz, 3H), 0.72 (t,
2
2
1
3
þ
1
3
) δ 157.85, 157.79,
), 35.3
13 12 2 2
1
36.8, 124.3 (CH), 121.9 (CH), 53.3, 41.9 (CH), 39.7 (CH
2
found m/z 264.0255; H NMR (300 MHz, CDCl ) δ 7.41 (dd, J =
3
(
CH ), 34.2 (CH ), 32.0 (CH ), 30.2 (CH ), 29.5 (CH ), 29.4 (CH ),
2
5.2/1.2 Hz, 1H), 7.28 (d, J = 5.4 Hz, 1H), 7.16 (d, J = 5.4 Hz, 1H),
7.11 (dd, J = 3.6/1.2 Hz, 1H), 7.06 (dd, J = 5.2/3.6 Hz, 1H),
2
2
2
2
2
2
8.7 (CH
2
), 27.4 (CH
), 10.8 (CH
rated C-H), 2957/2926/2855 (s, saturated C-H); UV-vis (CHCl ,
2
), 24.5 (CH
2
), 22.9 (CH
2
), 22.8 (CH
2
), 14.3
-
1
13
(
CH
3
3
); IR (NaCl, cm ) νmax 3104/3068 (w, unsatu-
2.60-2.15 (m, 4H), 1.70 (s, 3H); C NMR (75 MHz, CDCl ) δ
3
3
176.2 (CO), 142.7, 134.1, 130.0 (CH), 129.5, 127.5 (CH), 127.2
(CH), 125.6 (CH), 86.4, 35.1 (CH ), 29.1 (CH ), 29.0 (CH ); IR
nm) λ
(log ε) 249 (3.868), 320 (4.064).
max
2
2
3
0
-1
4
,4-Dipentyl-4H-cyclopenta[2,1-b:3,4-b ]dithiophene (12e). 12e
(0.63
(NaCl, cm ) νmax 3106 (m, unsaturated C-H), 2977/2931 (m,
saturated C-H), 1775 (s, CO-O lactone).
Ethyl 3-(4-Methyl-4H-cyclopenta[2,1-b:3,4-b ]dithiophen-4-yl)-
was obtained according to general procedure 2 with H SO
2
mL) and6-([2,2 -bithiophen]-3-yl)undecan-6-ol (11e) (0.33 g, 0.98
mmol); eluent hexane; yield 32% (0.10 g). GC-MS (EI) m/z 318
4
0
0
propanoate (12h). H SO (0.73 mL) was added dropwise to
2
4
7
208 J. Org. Chem. Vol. 75, No. 21, 2010

Van Mierloo et al.
JOCArticle
0
5
-([2,2 -bithiophen]-3-yl)-5-methyldihydrofuran-2-(3H)-one (16)
0.388 g, 1.47 mmol) in ethanol (20 mL) under stirring at rt and
and Technology in Flanders) for the financial support via the
SBO-project 060843 “PolySpec”. We also thank BELSPO in
the frame of the IAP P6/27 network and the FWO (Fund
forScientific Research - Flanders)viatheproject G.0091.07N
for their financial support. We further thank the EU for
the FP6 Marie-Curie-RTN “SolarNtype” (MRTN-CT-2006-
(
the reaction was continuously stirred for 12 h at rt. Workup acc-
ording to general procedure 2: The crude oily residue was purified
byflashcolumn chromatography (silica, eluent CH
a dark yellow oil (0.302 g, 70%). To the obtained crude alkene
mixture (17:18, 25:75 ratio) (0.302 g, 1.0 mmol) were added H SO
0.73 mL) and n-octane (15 mL) and the reaction was stirred for
2 h at rt. Workup according to general procedure 2: eluent hexane/
2 2
Cl ) toafford
2
4
0
35533). E.B. thanks IAP program no. P6-27 for her post-
(
1
doctoral grant. The calculations were performed on the
Interuniversity Scientific Computing Facility (iSCF), in-
stalled at the Facult ꢀe s Universitaires Notre-Dame de la Paix
(FUNDP, Belgium), for which the authors gratefully
acknowledge the financial support of the F.R.S.-FRFC for
the convention no. 2.4.617.07.F and of the FUNDP.
þ
ethyl acetate 90:10; yield 20% (60 mg). GC-MS (EI) m/z 292 [M ];
HRMS (EI) calcd for C H O S 292.0592, found m/z 292.0572;
1
5
16 2 2
1
H NMR (300 MHz, CDCl ) δ 7.16 (d, J = 5.0 Hz, 2H), 6.95 (d,
3
J = 5.0 Hz, 2H), 3.98 (q, J = 7.2 Hz, 2H), 2.28 (t, J = 7.9 Hz, 2H),
1.80 (t, J = 7.9 Hz, 2H), 1.47 (s, 3H), 1.15 (t, J = 7.2 Hz, 3H);
NMR (75 MHz, CDCl ) δ 173.6 (CO), 157.8, 136.6, 125.3 (CH),
13
C
3
1
21.2 (CH), 60.3, 48.2 (CH ), 33.7 (CH
2
2
), 29.9 (CH
2 3
), 24.2 (CH ),
-
1
Supporting Information Available: Details on the computa-
14.2 (CH
3
); IR (NaCl, cm ) νmax 3102/3070 (w, unsaturated
1
13
tional procedures, H and C NMR spectra for all novel
CPDTs and precursors, and complete NMR assignment of the
proton and carbon resonances of alkene isomers 13 and 14. This
material is available free of charge via the Internet at http://
pubs.acs.org.
C-H), 2974/2925/2869 (w, saturated C-H), 1731 (m, CO-O);
UV-vis (CHCl , nm) λ (log ε) 320 (3.104).
3
max
Acknowledgment. The authors gratefully acknowledge the
IWT (Institute for the Promotion of Innovation by Science
J. Org. Chem. Vol. 75, No. 21, 2010 7209