Polymer-Supported Synthesis of Regioregular Head-to-Tail-Coupled Oligo(3-arylthiophene)s Utilizing a Traceless Silyl Linker

Article abstract of DOI:10.1021/jo991188b

The solid-phase synthesis of regioregular head-to-tail-coupled oligo(3-arylthiophene)s has been achieved in high yield and purity by using a traceless silyl ether linkage. In the first step, the solution-phase synthesis of this class of conjugated oligomers was investigated. Benzyl alcohol was chosen to serve as a mimic for the anchoring group of the hydroxymethyl-substituted polystyrene matrix. The development of a novel regioselective iodination process for silyl-protected thiophenes faciliates the successful application of the solution-phase protocol to the solid phase. Satisfactory loading was obtained by reaction of chlorosilyl-functionalized 3-arylthiophene with hydroxymethyl polystyrene in the presence of imidazole. The suitability of the following iterative halogenation and Suzuki cross-coupling sequence is illustrated by the preparation of a quater(3-arylthiophene), the first regioregular head-to-tail-coupled oligothiophene that is synthesized on solid support. Removal of the conjugated oligomers from the solid support could be effectively achieved by treatment with tetrabutylammonium fluoride.

Full text of DOI:10.1021/jo991188b

352
J . Org. Chem. 2000, 65, 352-359
P olym er -Su p p or ted Syn th esis of Regior egu la r
Hea d -to-Ta il-Cou p led Oligo(3-a r ylth iop h en e)s Utilizin g a Tr a celess
Silyl Lin k er
Christoph A. Briehn, Thomas Kirschbaum, and Peter Ba¨uerle*
Abteilung Organische Chemie II (Organic Materials and Combinatorial Chemistry), Universita¨t Ulm,
Albert-Einstein-Allee 11, D-89081 Ulm, Germany
Received J uly 26, 1999
The solid-phase synthesis of regioregular head-to-tail-coupled oligo(3-arylthiophene)s has been
achieved in high yield and purity by using a traceless silyl ether linkage. In the first step, the
solution-phase synthesis of this class of conjugated oligomers was investigated. Benzyl alcohol was
chosen to serve as a mimic for the anchoring group of the hydroxymethyl-substituted polystyrene
matrix. The development of a novel regioselective iodination process for silyl-protected thiophenes
faciliates the successful application of the solution-phase protocol to the solid phase. Satisfactory
loading was obtained by reaction of chlorosilyl-functionalized 3-arylthiophene with hydroxymethyl
polystyrene in the presence of imidazole. The suitability of the following iterative halogenation
and Suzuki cross-coupling sequence is illustrated by the preparation of a quater(3-arylthiophene),
the first regioregular head-to-tail-coupled oligothiophene that is synthesized on solid support.
Removal of the conjugated oligomers from the solid support could be effectively achieved by
treatment with tetrabutylammonium fluoride.
In tr od u ction
moderate yields often reported for aryl/aryl cross-coupling
steps in Stille or Suzuki reactions of longer oligomers,
the appearance of homocoupling products impedes the
purification processes.
There is a considerable interest in the development of
conjugated oligomers and polymers for applications in
electronic devices, including all-organic field-effect tran-
sistors1 and light emitting devices.2 Polythiophene-based
materials are particularly attractive, as these compounds
are characterized by an excellent environmental and
thermal stability.3 Due to the statistical nature of po-
lymerization processes, most synthetic reactions affording
polymeric materials generate polydisperse compounds.
As it became clear that regioregular head-to-tail-coupled
poly(3-alkylthiophene)s show decidedly improved elec-
tronic properties in comparison to corresponding regio-
random polymers, several research groups started to
selectively engineer this class of conducting polymers.4
It is important to realize that the investigation of
R-oligothiophenes as model compounds for the corre-
sponding polymers provides specific information concern-
ing their molecular and especially electronic properties.5
Very recently, several synthetic routes to regioregular
head-to-tail-coupled oligo(3-alkylthiophene)s were re-
ported, but the synthesis of these model compounds
generally faces some inherent problems.6-8 Besides the
To circumvent these time-consuming purification pro-
cesses and to increase the yields for the transition metal-
catalyzed cross-coupling reactions, a solid-phase strategy
for the synthesis of these conjugated oligomers should
perfectly overcome the problems of solution-phase syn-
thesis. The possibility to use the coupling components in
excess and to remove byproducts such as homocoupling
products by washing should faciliate a fast and high-
yielding synthesis. A few recent reports have demon-
strated that synthesis of conjugated oligomers can suc-
cessfully be performed on solid support.9 Malenfant and
Fre´chet9d more recently reported the first polymer-
supported synthesis of asymmetric oligothiophenes using
an ester linkage to the Merrifield resin. Starting from
an unsubstituted resin-bound bithiophene, alternating
sequences of bromination and Stille cross-coupling reac-
tions afforded an R-carboxy-substituted pentamer after
cleavage from the polymer matrix.
Now, solid-phase synthesis has been established as a
powerful methodology for preparing compound libraries
by automated parallel and combinatorial synthesis, ac-
celerating the search for new bioactive molecules.10
Recently, it was shown that combinatorial strategies can
be successfully applied to optimize lead structures in
* To whom correspondence should be addressed. E-mail:
peter.baeuerle@chemie.uni-ulm.de.
(1) Horowitz, G. Adv. Mater. 1998, 10, 365-377.
(2) Kraft, A.; Grimsdale, A. C.; Holmes, A. B. Angew. Chem., Int.
Ed. 1998, 37, 402-428.
(3) Handbook of Conducting Polymers, 2nd ed.; Skotheim, T. A.,
Elsenbaumer, R. L., Reynolds, J . R., Eds.; Marcel Dekker: New York,
1998.
(4) McCullough, R. D. Adv. Mater. 1998, 10, 93-116.
(5) (a) Ba¨uerle, P. Adv. Mater. 1992, 4, 102-107. (b) Ba¨uerle, P.
Oligothiophenes. In Electronic Materials: The Oligomeric Approach;
Mu¨llen, K., Wegner, G., Eds.; Wiley-VCH: Weinheim, 1998; pp 105-
197.
(6) (a) Barbarella, G.; Zambianchi, M.; Bongini, A.; Antolini, L. Adv.
Mater. 1994, 6, 561-564. (b) Arbizzani, C.; Bongini, A.; Mastragostino,
M.; Zanelli, A.; Barbarella, G.; Zambianchi, M. Adv. Mater. 1995, 7,
571-574.
(7) Kirschbaum, T.; Azumi, R.; Mena-Osteritz, E.; Ba¨uerle, P. New
J . Chem. 1999, 241-250.
(8) (a) Sone, T.; Umetsu, Y.; Sato, K. Bull. Chem. Soc. J pn. 1991,
64, 864-868. (b) Bidan, G.; De Nicola, A.; Enee, V.; Guillerez, S. Chem.
Mater. 1998, 10, 1052-1058.
(9) (a) Young, J . K.; Nelson, J . C.; Moore, J . S. J . Am. Chem. Soc.
1994, 116, 10841-10842. (b) Nelson, J . C.; Young, J . K.; Moore, J . S.
J . Org. Chem. 1996, 61, 8160-8168. (c) J ones, L.; Schumm, J . S.; Tour,
J . M. J . Org. Chem. 1997, 62, 1388-1410. (d) Malenfant, P. R. L.;
Fre´chet, J . M. J . Chem. Commun. 1998, 2657-2658. (e) Huang, S.;
Tour, J . M. J . Am. Chem. Soc. 1999, 121, 4908-4909.
10.1021/jo991188b CCC: $19.00 © 2000 American Chemical Society
Published on Web 12/29/1999

Synthesis of Regioregular Oligo(3-arylthiophene)s
J . Org. Chem., Vol. 65, No. 2, 2000 353
Sch em e 1
materials science. Mainly, inorganic materials libraries
for new luminescent phosphors, high-temperature su-
perconductors, and thin-film dielectric materials have
been created by using combinatorial methods.11
Our work is directed toward the development of a
combinatorial methodology for the synthesis of conju-
gated oligomer libraries with special electronic properties.
In this investigation, we focus our interest on the
preparation of head-to-tail-coupled oligo(3-arylthiophene)s.
So far, no synthetic studies have appeared in the litera-
ture concerning solution- or solid-phase synthesis of this
type of oligomers. A systematic investigation including
suitable screening methods could clearly elucidate the
influence of different aryl substituents on molecular and
especially electronic properties. Structure/property rela-
tionships obtained from this study will provide us with
the possibility to develop new poly- and oligothiophene-
based materials.
As a first step to a combinatorial approach, we devel-
oped an efficient synthetic route to this class of conju-
gated oligomers in solution in order to mimic the follow-
ing polymer-supported synthesis. Transfer of this model
to a solid-phase protocol will be an essential step toward
the automated parallel synthesis and therefore to a
combinatorial approach.
wide range of reagents and various synthetic methodolo-
gies. Cleavage of the aryl-silicon bond and thus the
release of the oligomer can be mildly affected by fluoride-
mediated protiodesilylation leaving no residual function-
ality from linkage to the solid support. Moreover, the silyl
linker provides a broad versatility to further functionalize
the linear conjugated oligomers in the R-position by
cleavage of the heteroaryl-silicon bond in the presence
of electrophilic halogen or acyl sources.14 Furthermore,
fluoride-mediated transition metal-catalyzed cross-coup-
ling reactions with aryl halides would result in unsym-
metric aryl end-capped oligothiophenes.15
Herein, we report the synthesis of regioregular head-
to-tail-coupled oligo(3-arylthiophene)s in solution and the
application of the solution-phase protocol to solid support.
Several linker systems enable first the attachment of
the core moieties to the solid support and second the
cleavage of the generated oligomers after solid-phase
synthesis. For example, carboxy and traceless triazene
linkers were successfully applied to the solid-phase
synthesis of conjugated oligomers.9 Given that the pres-
ence of polar functionalities on the oligomeric backbone
may bestow undesirable electrochemical and physico-
chemical properties, we aimed for nonfunctionalized
oligothiophenes by using a traceless linker technology.
The first and by far most widely explored of these
traceless linkers is the silyl linker.12 We chose a diiso-
propylsilyl ether linkage which was developed by Boehm
and Showalter for the synthesis of 3-arylbenzofurans.13
An attractive feature of this linker, besides the incorpo-
ration of two sterically demanding isopropyl groups, is
the silyl ether functionality, which decidedly enhances
the stability of the resin-linker-compound connection.
Therefore, this traceless linkage is compatible with a
Resu lts a n d Discu ssion
Mon om er Syn th esis for th e Solu tion - a n d Solid -
P h a se Ap p r oa ch es. The syntheses of the monomeric
thiophene building blocks for the solution- and solid-
phase approaches are depicted in Scheme 1. Terminal
diisopropylsilyl groups were affixed to 3-arylthiophenes
by lithium-halogen exchange of 2-bromo-3-arylthiophenes
1a ,b16 with n-butyllithium and subsequent quenching
with dichlorodiisopropylsilane. Chloro(diisopropyl)silyl-
thiophenes 2a ,b were prepared in 65% and 60% yield,
respectively. Furthermore, bromides 1a ,b were converted
to the boronic esters 3a ,b in 69% and 74% yield,
respectively, by adding 2,2′-propane-1,3-diyldioxybori-
nane to the Grignard reagent of 1a ,b, and treatment of
the intermediates with boron trifluoride etherate.
Oligom er Syn th esis in Solu tion . To implement our
strategy for the solid-phase synthesis of oligo(3-aryl-
thiophene)s, we investigated a model oligomer synthesis
in a solution-phase study. Benzyl alcohol was chosen to
serve as a mimic for the anchoring group of the polysty-
rene matrix. Regioregular head-to-tail-coupled oligo(3-
(10) (a) Fru¨chtel, J . S.; J ung, G. Angew. Chem., Int. Ed. Engl. 1996,
35, 17-42. (b) Terrett, N. K.; Gardner, M.; Gordon, D. W.; Kobylecki,
R. J .; Steele, J . Tetrahedron 1995, 51, 8135-8173. (c) Thompson, L.
A.; Ellman, J . A. Chem. Rev. 1996, 96, 555-600.
(11) (a) Xiang, X.-D.; Sun, X.; Briceno, G.; Lou, Y.; Wang, K.-A.;
Chang, H.; Wallace-Freedman, W. G.; Chen, S.-W.; Schultz, P. G.
Science 1995, 268, 1738-1740. (b) Briceno, G.; Chang, H.; Sun, X.;
Schultz, P. G.; Xiang, X.-D. Science 1995, 270, 273-275. (c) Hsieh-
Wilson, L. C.; Xiang, X.-D.; Schultz, P. G. Acc. Chem. Res. 1996, 29,
164-170. (d) Sun, X.-D.; Gao, C.; Wang, J .; Xiang, X.-D. Appl. Phys.
Lett. 1997, 70, 3353-3355. (e) Sun, X.-D.; Wang, K.-A.; Yoo, Y.;
Wallace-Freedman, W. G.; Gao, C.; Xiang, X.-D.; Schultz, P. G. Adv.
Mater. 1997, 9, 1046-1049. (f) Wang, J .; Yoo, Y.; Gao, C.; Takeschi,
I.; Sun, X.; Chang, H.; Xiang, X.-D.; Schultz, P. G. Science 1998, 279,
1712-1714. (g) Van Dover, R. B.; Schneemeyer, L. F.; Fleming, R. M.
Nature 1998, 392, 162-164.
(12) (a) Randolph, J . T.; McClure, K. F.; Danishefsky, S. J . J . Am.
Chem. Soc. 1995, 117, 5712-5719. (b) Plunkett, M. J .; Ellman, J . A.
J . Org. Chem. 1997, 62, 2885-2893. (c) Hone, N. D.; Davies, S. G.;
Devereux, N. J .; Taylor, S. L.; Baxter, A. D. Tetrahedron Lett. 1998,
39, 897-900. (d) Hu, Y.; Porco, J . A.; Labadie, J . W.; Gooding, O. W.;
Trost, B. M. J . Org. Chem. 1998, 63, 4518-4521.
(14) Han, Y.; Walker, S. D.; Young, R. N. Tetrahedron Lett. 1996,
37, 2703-2706.
(15) (a) Hiyama, T.; Hatanaka, Y. Pure Appl. Chem. 1994, 66, 1471-
1478. (b) Ito, H.; Sensui, H.; Arimoto, K.; Miura, K.; Hosomi, A. Chem.
Lett. 1997, 639-640. (c) Shibata, K.; Miyazawa, K.; Goto, Y. Chem.
Commun. 1997, 1309-1310.
(13) Boehm, T. L.; Showalter, H. D. H. J . Org. Chem. 1996, 61,
6498-6499.
(16) Donald, D. J . P.; Copeland, R. A.; Covington, M. B.; Pitts, W.
J .; Batt, D. G. Bioorg. Med. Chem. Lett. 1996, 6, 2907-2912.

354 J . Org. Chem., Vol. 65, No. 2, 2000
Briehn et al.
Sch em e 2a
a
Reagents: (a) PhCH2OH, imidazole, DMF. (b) (1) Hg(OAc)2, CHCl3; (2) I2. (c) 3a , Pd(PPh3)4 (5 mol %), NaHCO3, DME. (d) TBAF,
THF.
Sch em e 3
arylthiophene)s should be available via a stepwise acti-
vation-elongation sequence as shown in Scheme 2.
Silylated thiophene 2a was treated with benzyl alcohol
in the presence of imidazole at ambient temperature,
yielding 85% of the desired benzyloxysilylthiophene 4.
As reported by Tour and Wu17 for alkylated thiophenes
bearing an R-trimethylsilyl group, the use of silica gel in
chromatographic purifications partly resulted in the
desilylation of the silylthiophene. To completely retain
the silyl group on the monomer and oligomer termini,
we used basic Al2O3 for purification processes.
Ta ble 1. Electr op h ilic Ar om a tic Ha logen a tion of
Silylth iop h en e 4
Two different synthetic routes to halogenated silyl-
thiophenes and oligothiophenes were investigated. Gen-
erally, iodination of the protected 3-phenylthiophene 4
should be possible, on one hand, by iodination of an in
situ-generated lithiothiophene or by electrophilic aro-
matic substitution with elemental iodine. Treatment of
4 with n-butyllithium afforded the lithiated derivative,
which subsequently reacted with iodine to afford iodosi-
lylthiophene 6b in 75% yield. On the other hand, we
investigated the feasibility of an iodination by electro-
philic aromatic substitution. As the silyl protecting group
is not orthogonally stable to reactive electrophiles, it is
obvious that both R-positions of the electronically acti-
vated 3-phenylthiophene 4 can be attacked by halogen
electrophiles. The reaction of thiophene 4 with halogen
entry
reagenta
1a ,c (%)
6a ,b (%)
1
2
3
4
NBS
I2
89
-
48
11
-
52
b
b
I2, Hg(OAc)2
(1) Hg(OAc)2, (2) I2
<1
>99
a
Reaction conditions: solvent chloroform, equimolar ratio of 4
b
and reagent. Starting compound remained unchanged after 48
h.
of 1c and 6b (entry 3). Interestingly, no trace of undesired
mercuration/desilylation was observed when mercuric
acetate was added in a first step. The addition of iodine
afforded then, in a high selectivity, the desired 2-iodo-
5-silylthiophene 6b (entry 4). The reason for the selectiv-
ity of this halogenation reaction is the formation of an
R′-mercurated silylthiophene 5 as an intermediate, which
can be further iododemercurated to iodosilylthiophene 6b
in 91% yield. The reason for the high selectivity of the
mercuration reaction seems to be preliminary coordina-
tion of a mercury atom to the thiophene sulfur atom.18
As the mercuration/halodemercuration procedure results
in nearly quantitative yield, we certainly prefer this
halogenation method for the oligomer activation in solu-
tion.
electrophiles affords
a mixture of 2-halo-3-phenyl-
thiophene 1a or 1c and the desired substitution product
6a or 6b, as shown in Scheme 3. As indicated by the
results summarized in Table 1, the product ratio is
greatly dependent on the electrophile reactivity. As
shown by entry 1, the substitution reaction with bromine
as electrophile is not sensitive to the steric hindrance of
the two diisopropyl groups in the vicinity of the site of
electrophilic attack. The use of the mild electrophile NBS
resulted in a preferred formation of 1a (1a :6a ) 89:11).
Elemental iodine showed no conversion of the starting
material 4 after 48 h (entry 2). Activation of elemental
iodine with mercuric acetate led to a nearly 1:1 mixture
Palladium-catalyzed cross-coupling reactions have been
reported to proceed cleanly for substituted R-iodothio-
(18) Clementi, S.; Linda, P.; Marino, G. J . Chem. Soc. (B) 1970,
1153-1156.
(17) Tour, J . M.; Wu, R. Macromolecules 1992, 25, 1901-1907.

Synthesis of Regioregular Oligo(3-arylthiophene)s
J . Org. Chem., Vol. 65, No. 2, 2000 355
Sch em e 4a
a
Reagents: (a) 2b, imidazole, DMF. (b) (1) LDA, THF; (2) I2. (c) 3b, Pd(PPh3)4 (5 mol %), NaHCO3, THF. (d) (1) Hg(OCOC5H11)2,
CH2Cl2; (2) I2. (e) TBAF, THF.
phenes.7,8b,19 The silyl-protected iodothiophene 6b under-
went facile Suzuki reaction with boronic ester 3a to
provide bithiophene 7 in 84% yield. Similarly to silyl-
thiophene 4, bithiophene 7 was iodinated after mercu-
ration to afford iodide 8 in 86% yield. As in the case of
iodothiophene 6b , iodobithiophene 8 was treated with
excess boronic ester 3a and Pd catalyst to afford silylated
head-to-tail-coupled triphenylterthiophene 9 in 81% yield.
Cleavage of the protecting group can be smoothly
effected at any stage of the synthesis by using tetrabu-
tylammonium fluoride (TBAF) in THF at ambient tem-
perature. This fluoride-mediated desilylation proceeds
nearly quantitatively, and, e.g., deprotection of silylter-
thiophene 9 afforded purely head-to-tail-coupled tri-
phenylterthiophene 10 in 91% yield. Silanol and siloxane
substrates immobilized on polystyrene resins is inher-
ently complicated by the reactivity of the solid support
itself. Successful examples of electrophilic aromatic
substitutions involving resin-bound compounds usually
involve an activated aromatic system, or the functionality
is achieved by methods avoiding this problematic reac-
tion.12b,20,21 In our approach, we were not able to attach
or couple halogenated building blocks to the resin and
the growing oligomer. Therefore, we were dependent on
halogenation methods that selectively react with the
thiophene moieties. Since thiophenes, in contrast to the
polystyrene phenyl units, have in the R-position an
extremely high reactivity to electrophiles and, moreover,
the R-positions can be easily deprotonated by suitable
bases, the mercuration/halodemercuration procedure and
the lithiation/halodelithiation reaction should be selective
methods for introducing halogen into a resin-bound
thiophene.
1
byproducts were observed in the crude mixtures by H
NMR and GC/MS which easily could be removed by
filtration over silica.
Thiophene-derivatized resin R12 was subjected to the
novel mercuration/iododemercuration procedure. In con-
trast to the solution-phase chemistry, however, in this
case a remarkably high portion of halodesilylation was
observed. This discrepancy in reactivity between the
resin-bound silylthiophene R12 and the corresponding
thiophene 4 in solution is so far not clearly understood.
Alternatively, directed ortho-lithiation of the reactive
R-position in R12 and subsequent reaction with iodine
afforded nearly quantitatively iodinated resin R13. Lithi-
ation was performed using 3 equiv of LDA at room
temperature. The following Suzuki reaction of thiophene
boronic ester 3b with the solid-phase attached 2-iodo-4-
arylthiophene R13 was carried out using typical solution-
Oligom er Syn th esis on Solid Su p p or t. To success-
fully transfer the reported solution-phase protocol to solid
support, we chose commercially available hydroxymethyl-
substituted polystyrene R11 (R ) resin) as a matrix for
the oligomer growth. Scheme 4 outlines the synthetic
methodology for the solid-phase synthesis of regioregular
aryl-substituted thiophene oligomers from the monomer
to the tetramer. The resin-bound 3-(p-tolyl)thiophene
R12 was obtained by reaction of chloro(diisopropyl)-
silylthiophene 2b with hydroxymethylated polystyrene
R11 in the presence of imidazole. To maximize the
loading, we used excessive chlorosilylated thiophene 2b
(2.5 equiv) for adaption to the solid-phase.
In the next step, halogenation of the resin-bound
thiophene R12 was investigated. In contrast to solution-
phase synthesis, electrophilic aromatic substitution of
(20) Kobayashi, S.; Moriwaki, M. Tetrahedron Lett. 1997, 38, 4251-
4254.
(21) Havez, S.; Begtrup, M.; Vedso, P. J . Org. Chem. 1998, 63, 7418-
7420.
(19) Gronowitz, S.; Peters, D. Heterocycles 1990, 30, 645-658.

356 J . Org. Chem., Vol. 65, No. 2, 2000
Briehn et al.
Ta ble 2. P r od u ct Con cen tr a tion in th e Resin s R12-R18
a n d Con ver sion a n d Isola ted Yield s of Th iop h en es a n d
Oligoth iop h en es 12-18
phase Suzuki conditions [excess of boronic ester, 5 mol
% Pd(PPh3)4]. Although DME was the solvent of choice
for the solution-phase reaction, presumably as a result
of its superior resin-swelling ability, THF was preferred
for solid-phase synthesis. Slightly more than 2 equiv of
boronic ester 3b was necessary to drive the reaction to
completion. The typical use of fluoride salts as bases in
nonaqueous Suzuki coupling reactions7 would mediate
the cleavage of the oligothiophene from the polymer
matrix. Therefore, aqueous conditions with NaHCO3 as
an activating base were used and proved to be suitable.
The resin-bound bithiophene R14 was generated in high
yield. Since in comparison to the iodination of the
support-bound thiophene R12 the yield of the iodination
of polymer-bound bithiophene R14 decreases consider-
ably when LDA is used for metalation, we reacted the
resin-bound bithiophene R14 with mercuric caproate,
which was used instead of the corresponding acetate
taken in the solution synthesis. This reaction condition
was elaborated for solid-phase synthesis because the
caproate has markedly higher solubility in CH2Cl2. Since
mercurated thiophene 5 could be unambiguously proven,
it is very likely that, at the resin, an analogous species
was also formed. The synthesis of the iodinated bithio-
phene R15 was finally completed by addition of iodine
to the resin-bound organometallic compound. To control
whether desilylation occurred, the resin washings were
concentrated but did not provide any UV-active material
in the TLC. The fact that mercuration occurred along
with a complete lack of electrophilic desilylation demon-
strates the power of this halodemercuration reaction also
on solid support. As in the case of iodothiophene R13,
resin-bound iodobithiophene R15 underwent an efficient
Suzuki cross-coupling reaction and afforded terthiophene
R16 under the same reaction conditions. An additional
iteration of the halogenation/Suzuki coupling sequence
gave the resin-bound quaterthiophene R18.
resin
conca (mmol/g)
convb (%)
isolated yieldc (%)
R12
R13
R14
R15
R16
R17
R18
0.56
0.49
0.46
0.38
0.34
0.27
0.26
>99d
>98e
>98e,f
>90e
93 (of 12)
91 (of 13)
87 (of 14)
71 (of 15)
68 (of 16)
54 (of 17)
48 (of 18)
g
-
h
-
i
-
a
Product concentration in the resin determined by resin weight
b
difference (average of three experiments). With respect to the
resin. c Compounds 12-18 were purified after cleavage by silica
gel chromatography or preparative HPLC. Yields based on 0.67
mmol/g hydroxymethyl substitution of polstyrene R11 given by
the manufacturer. Determined by infrared analysis. e Deter-
d
mined from relative peak areas of 1H NMR spectra in the crude
product mixture after protiodesilylation. f Determined by GC
g
integration. Determination was problematic by HPLC because
only bithiophene 14 as a product of Pd-mediated deiodination was
detected besides product 16. Ratio 16:14 ) 81:19 (determination
h
i
at 215 nm). No determination possible. Determination was
problematic by HPLC because only terthiophene 16 as a product
of Pd-mediated deiodination was detected besides product 18. Ratio
18:16 ) 69:31 (determination at 215 nm).
coupling reaction sequence. Therefore, we estimated the
product concentration in the final resins by weight
change. The concentration of R12 calculated by weight
change was confirmed by infrared analysis and thus used
as a basis for further calculations. According to the
literature,9c these calculated concentrations are only a
rough estimation, as the results are often not reliable.
Additionally, we estimated the conversion of the reactions
by liberating the oligomers from the polymer-supports
1
followed by H NMR, GC, and HPLC analysis.
Su m m a r y
In conclusion, our work proves the suitability of a solid-
phase approach to conjugated oligomers using a traceless
silyl linkage. In particular, we have demonstrated the
first two steps of a combinatorial approach to regioregular
head-to-tail-coupled oligo(3-arylthiophene)s: the synthe-
sis in solution and the consequent transfer to solid
support. Our approach involves the first application of a
traceless silyl linker for the preparation of conjugated
oligomers, and this linkage proved to be compatible with
the required activation and cross-coupling sequences. In
solution-phase studies, we developed a novel halogena-
tion method for silyl-protected thiophenes based on a
mercuration/halodemercuration process. Taking advan-
tage of the optimized reactions, this solution-phase
synthesis has been successfully adapted to a solid-state
protocol. Growing oligomers were attached to hydroxy-
methylated polystyrene by a traceless silyl linker. Iodi-
nation was effected by using either a mercuration/
halodemercuration procedure or the reaction of the
lithiated thiophene with elemental iodine. The Pd-
catalyzed Suzuki cross-coupling reaction was carried out
with excess of boronic ester and the iodinated resin-bound
thiophenes. Removal of the conjugated oligomers from
solid support could be effectively achieved by TBAF
treatment.
We observed facile and clean removal of compounds
12-18 from the resin in high isolated yields when TBAF
in THF was used at 70 °C for 1 h. For example, mild
protiodesilylation of quaterthiophene-derivatized resin
R18 afforded the corresponding regioregular head-to-tail-
coupled tetraarylated quaterthiophene 18 in 48% overall
yield. This corresponds to an average yield of 91% over
eight reaction steps, including attachment, halogenation,
coupling, and cleavage reactions. Contaminants observed
were the corresponding bi- and terthiophenes, which
could be easily removed by HPLC purification. Table 2
provides detailed information on product concentrations
in final resins R12-R18, conversions, and isolated
overall yields of thiophenes 12-18 after protiodesilyla-
tion.
Monitoring the progress of the solid-phase reactions
by FTIR spectroscopy caused some problems since the
compounds did not include typical functional groups with
characteristic absorption bands. The attachment of chlo-
rosilylthiophene 2b to hydroxymethyl polystyrene R11
could be quantitatively controlled by infrared analysis
using KBr pellets. A sharp band at 3573 cm-1 and a broad
band at 3449 cm-1, which are attributed to the free and
intraresin hydrogen-bonded hydroxy groups of resin R11,
disappeared when anchoring of the chlorosilylthiophene
2b was complete. Determined by this spectroscopic
method, the product concentration in R12 was greater
than 98%. However, the on-bead analysis failed for
monitoring the progress of the halogenation/cross-
Owing to the ease of the reactions carried out to build
up the oligomeric backbone on solid support, a parallel
preparation of these compounds incorporating para-
substituted 3-arylthiophenes by automated synthesis

Synthesis of Regioregular Oligo(3-arylthiophene)s
J . Org. Chem., Vol. 65, No. 2, 2000 357
(diisopropyl)silane (15 mmol) in 40 mL of diethyl ether at -30
°C. After the mixture was stirred at ambient temperature for
1 h, solvent and excessive dichlorodiisopropylsilane were
evaporated. Distillation of the residue afforded 2a ,b as color-
less solids.
seems to be possible and is under active investigation.
The diversity of an oligothiophene library generated by
varying the 3-aryl substituents in the resulting oligomers
together with rapid characterization methods will provide
us a way to the accelerated investigation on structure/
property relationships needed to design new oligo- and
polythiophene-based materials.
2-[Ch lor o(d iisop r op yl)silyl]-3-p h en ylt h iop h en e (2a ).
From 1a (2.39 g, 10.0 mmol), 2.00 g (65%) of the title product
was obtained, bp 153 °C/0.78 mbar. 1H NMR (200 MHz,
CDCl3): δ 0.88 (d, J ) 6.4 Hz, 6H), 0.99 (d, J ) 6.4 Hz, 6H),
1.07 (sp, J ) 6.4 Hz, 1H), 1.11 (sp, J ) 6.4 Hz, 1H), 7.16 (d, J
) 4.7 Hz, 1H), 7.35-7.38 (m, 5H), 7.66 (d, J ) 4.7 Hz, 1H).
13C NMR (50 MHz, CDCl3): δ 15.82, 17.14, 17.28, 127.66,
128.00, 128.45, 128.98, 131.52, 131.72, 138.56, 151.19. MS
(EI): m/z 308 (M+), 265 (M+ - C3H7), 229 (M+ - C3H7 - Cl).
Exp er im en ta l Section
Gen er a l Rem a r k s. Solvents and reagents were purified
and dried by usual methods prior to use. Preparative column
chromatography was performed on silica gel 60 (0.020-0.200
nm) or aluminum oxide 90 (basic, activity stage II-III, 0.063-
0.200). Melting points were determined with a Bu¨chi B-545
melting point apparatus and are uncorrected. Infrared spectra
IR (KBr): 1599, 1481, 1461, 1384, 1361, 1104, 1003, 880 cm-1
.
Anal. Calcd for C16H21ClSSi: C, 62.20; H, 6.85; S, 10.38.
Found: C, 62.38; H, 6.89; S, 10.27.
2-[Ch lor o(d iisop r op yl)silyl]-3-(p-tolyl)th iop h en e (2b).
From 1b (2.53 g, 10.0 mmol), 1.94 g (60%) of the title product
was obtained, bp 146 °C/0.45 mbar. 1H NMR (200 MHz,
CDCl3): δ 0.88 (d, J ) 6.4 Hz, 6H), 1.00 (d, J ) 6.4 Hz, 6H),
1.07 (sp, J ) 6.4 Hz, 1H), 1.11 (sp, J ) 6.4 Hz, 1H), 2.39 (s,
3H), 7.14 (d, J ) 4.7 Hz, 1H), 7.12-7.26 (m, 4H), 7.64 (d, J )
4.7 Hz, 1H). 13C NMR (50 MHz, CDCl3): δ 15.84, 17.18, 17.34,
21.22, 128.24, 128.73, 128.87, 131.59, 131.69, 135.63, 137.38,
151.25. MS (EI): m/z ) 322 (M+), 279 (M+ - C3H7), 243 (M+
- C3H7 - Cl). IR (KBr): 1489, 1466, 1099, 990, 884 cm-1. Anal.
Calcd for C17H23ClSSi: C, 63.22; H, 7.18; S, 9.93. Found: C,
63.25; H, 7.21; S, 10.05.
Gen er a l P r oced u r e for th e Syn th esis of 2-Th ien yl-
1,3,2-d ioxa bor in a n es 3a a n d 3b. To a Grignard reagent
prepared of 2-bromo-3-arylthiophene 1a ,b (10.0 mmol) and
magnesium turnings (10.0 mmol) in 40 mL of THF was added
dropwise at -30 °C 2,2′-propane-1,3-diyldioxybis[1,3,2]dioxa-
borinane (5.00 mmol). After being stirred at -30 °C for 1 h,
the mixture was allowed to come to room temperature. At -70
°C, boron trifluoride etherate (10.0 mmol) was added dropwise
to the solution. The mixture was stirred for 1 h at -70 °C and
heated to room temperature. After evaporation of the solvent,
the residue was dissolved in petroleum ether and filtrated over
Celite to afford 3a ,b as colorless solids in 88-92% purity which
were used without further purification.
were recorded on
a Perkin-Elmer FTIR Spectrum 2000;
absorptions are reported in cm-1. The 1H and 13C NMR spectra
were recorded at 500 and 200 MHz. Chemical shifts are
expressed in parts per million (δ) using residual solvent
protons as internal standard. Low- and high-resolution elec-
tron impact mass spectra were obtained operating at 70 eV.
Assignments of corresponding fragments are appended in
brackets. Elemental analyses were performed by the Ulm
University Analytical Department. HPLC analysis was ac-
complished using an UV absorbance detector and a Nucleosil
column (4 mm × 250 mm), 1.3 mL/min flow rate. Preparative
HPLC was performed using a UV detector and a Nucleosil
column (20 mm × 200 mm), 8 mL/min flow rate. All reactions
were performed under argon. Polymer loading was determined
by weighing the derivatized resins after extensive washing and
drying in vacuo.
Benzyl alcohol (Merck), boron trifluoride etherate (Merck),
n-butyllithium (Merck-Schuchardt), dichloro(diisopropyl)silane
(Fluka), imidazole (Merck), iodine (Fluka), LDA (2 M in THF)
(Fluka), magnesium turnings (Merck-Schuchardt), mercuric
acetate (Merck), NBS (Merck-Schuchardt), and tetrabutylam-
monium fluoride (Fluka) were purchased and used without
further purification. Tetrakis(triphenylphosphino)palladium-
(0),22 2-bromo-3-phenylthiophene (1b),16 3-(p-tolyl)thiophene,23
and 2,2′-propane-1,3-diyldioxybis[1,3,2]dioxaborinane24 were
prepared according to literature procedures. Hydroxymethyl
polystyrene R11 was purchased from Novabiochem with a
loading capacity of 0.67 mmol/g (100-200 mesh, 1% DVB).
2-Br om o-3-(p-tolyl)th iop h en e (1b).16 In the absence of
light, a solution of NBS (9.40 g, 52.8 mmol) in 100 mL of DMF
was added dropwise to a solution of 3-(p-tolyl)thiophene (10.0
g, 57.4 mmol) in 80 mL of DMF, and the mixture was stirred
for 20 h at ambient temperature, poured onto ice, and
extracted with diethyl ether. The organic phases were com-
bined, washed with water, and dried over sodium sulfate.
Evaporation of the solvent and distillation under reduced
pressure yielded 11.9 g (82%) of the title compound as a
slightly yellow liquid, bp 104 °C/0.03 mbar. 1H NMR (200 MHz,
CDCl3): δ 2.34 (s, 3H), 6.94 (d, J ) 5.7 Hz, 1H), 7.18 (d, J )
5.7 Hz, 1H), 7.16-7.42 (m, 4H). 13C NMR (50 MHz, CDCl3): δ
21.19, 108.13, 125.64, 128.41, 129.00, 129.02, 132.04, 137.30,
2-(3-P h en yl-2-th ien yl)-1,3,2-d ioxa bor in a n e (3a ). From
1a (2.39 g, 10.0 mmol), 1.68 g (69%) of the title product was
1
obtained. H NMR (200 MHz, CDCl3): δ 1.99 (qn, J ) 5.5 Hz,
2H), 4.03 (t, J ) 5.5 Hz, 4H), 7.18 (d, J ) 4.7 Hz, 1H), 7.24-
7.52 (m, 5H), 7.43 (d, J ) 4.7 Hz, 1H). 13C NMR (50 MHz,
CDCl3): δ 27.18, 61.88, 126.75, 127.47, 129.16, 130.02, 131.00,
137.66, 150.51. MS (EI): m/z 244 (M+).
2-(3-p-Tolyl-2-th ien yl)-1,3,2-d ioxa bor in a n e (3b). From
1b (2.53 g, 10.0 mmol), 1.90 g (74%) of the title product was
1
obtained. H NMR (200 MHz, CDCl3): δ 1.98 (qn, J ) 5.5 Hz,
2H), 2.37 (s, 3H), 4.04 (t, J ) 5.5 Hz, 4H), 7.14-7.41 (m, 4H),
7.16 (d, J ) 4.8 Hz, 1H), 7.49 (d, J ) 4.8 Hz, 1H). 13C NMR
(50 MHz, CDCl3): δ 21.18, 27.32, 61.99, 126.28, 128.34, 129.11,
129.99, 131.14, 134.84, 136.46. MS (EI): m/z 258 (M+).
2-[Ben zyloxy(d iisop r op yl)silyl]-3-p h en ylth iop h en e (4).
To a solution of 2a (0.50 g, 1.62 mmol) in 0.5 mL of DMF were
added benzyl alcohol (0.44 g, 4.05 mmol) and imidazole (0.28
g, 4.05 mmol). The reaction was stirred at ambient tempera-
ture for 18 h, poured into water, and extracted with cyclohex-
ane. The organic extracts were combined, washed with brine,
dried over sodium sulfate, filtered, and concentrated in vacuo.
The crude product was purified by flash chromatography
(Al2O3/pentane) to afford 0.52 g (85%) of the title compound
141.06. MS (EI): m/z 254 (M+), 173 (M+
1503, 1403, 1346, 1248, 984, 870, 815 cm-1. Anal. Calcd for
11H9SBr: C, 52.19; H, 3.58; S, 12.67. Found: C, 52.19; H,
-
81Br). IR (neat):
C
3.61; S, 12.70.
Gen er a l P r oced u r e for th e Syn th esis of 2-[Ch lor o-
(d iisop r op yl)silyl]-3-a r ylth iop h en es 2a a n d 2b.15b To a
solution of 2-bromo-3-arylthiophene 1a ,b (10.0 mmol) in 40
mL of diethyl ether was added n-butyllithium (11 mmol, 1.6
M, in hexane) at -70 °C. The mixture was warmed to room
temperature and added via cannula to a solution of dichloro-
1
as a colorless solid, mp 38 °C. H NMR (200 MHz, CDCl3): δ
0.87 (d, J ) 6.6 Hz, 6H), 0.96 (d, J ) 6.6 Hz, 6H), 1.01 (sp, J
) 6.6 Hz, 1H), 1.05 (sp, J ) 6.6 Hz, 1H), 4.63 (s, 2H), 7.09 (d,
J ) 4.7 Hz, 1H), 7.15-7.33 (m, 10H), 7.50 (d, J ) 4.7 Hz, 1H).
13C NMR (50 MHz, CDCl3): δ 14.02, 17.61, 17.71, 65.33,
125.96, 126.79, 127.19, 127.84, 128.08, 129.12, 129.85, 130.61,
131.50, 139.00, 140.99, 151.29. MS (EI): m/z 380 (M+), 337
(M+ - C3H7). IR (KBr): 1601, 1495, 1483, 1452, 1374, 1205,
1102, 1068, 880 cm-1. Anal. Calcd for C23H28OSSi: C, 72.58;
H, 7.41; S, 8.42. Found: C, 72.62; H, 7.43; S, 8.30.
(22) Coutts, I. C. G.; Goldschmidt, H. R.; Musgrave, O. C. J . Chem.
Soc. (C) 1970, 488-493.
(23) (a) Montheard, J .-P.; Delzant, J .-F.; Gazard, M. Synth. Com-
mun. 1984, 14, 289-292. (b) Wu, X.; Rieke, R. J . Org. Chem. 1995,
60, 6658-6659.
(24) Srivastava, G. J . Indian Chem. Soc. 1962, 39, 203-207.

358 J . Org. Chem., Vol. 65, No. 2, 2000
Briehn et al.
Mer cu r a te 5. To a solution of 4 (0.19 g, 0.50 mmol) in 10
mL of chloroform was added mercuric acetate (0.16 g, 0.50
mmol) at 0 °C. The reaction was stirred at ambient temper-
ature for 8 h. Evaporation of the solvent afforded 5 as a
colorless oil. 1H NMR (200 MHz, CDCl3): δ 0.93 (d, J ) 7.0
Hz, 6H), 0.99 (d, J ) 7.0 Hz, 6H), 1.07 (sp, J ) 7.0 Hz, 1H),
1.10 (sp, J ) 7.0 Hz, 1H), 2.05 (s, 3H), 4.71 (s, 2H), 7.18-7.38
(m, 11H). 13C NMR (50 MHz, CDCl3): δ 14.07, 17.53, 17.62,
22.26, 65.39, 125.92, 126.84, 127.34, 127.90, 128.11, 129.05,
138.42, 138.47, 138.74, 140.83, 151.10, 177.09. MS (EI): m/z
640 (M+), 597 (M+ - C3H7).
Gen er a l P r oced u r e for t h e Iod in a t ion of Silylt h io-
p h en es 4 a n d 7. To a solution of 4 and 7 (2.00 mmol) in 40
mL of chloroform was added mercuric acetate (2.20 mmol) at
0 °C. The reaction was stirred at ambient temperature for 8
h. After addition of iodine (2.20 mmol) at 0 °C, the reaction
mixture was allowed to warm to room temperature and stirred
for 1 h. The reaction mixture was poured into aqueous sodium
hydrogencarbonate before being washed with aqueous sodium
thiosulfate. The organic layer was dried over sodium sulfate,
filtered, and concentrated in vacuo. The crude product was
purified by flash chromatography on Al2O3 to afford 6b and 8
as colorless oils.
1068, 1002, 878 cm-1. Anal. Calcd for C33H34OS2Si: C, 73.56;
H, 6.36; S, 11.90. Found: C, 73.38; H, 6.49; S, 11.70.
5-[B e n zy lo x y (d iis o p r o p y l)s ily l]-3′′,3′,4-t r ip h e n y l-
2′′,5′:2′,2-ter th iop h en e (9). From 8 (1.32 g, 2.00 mmol) was
obtained 1.13 g (81%) of the title product as a yellow solid after
1
flash chromtography on Al2O3 (95:5, cyclohexane:CH2Cl2). H
NMR (200 MHz, CDCl3): δ 0.89 (d, J ) 6.1 Hz, 6H), 0.91 (d,
J ) 5.8 Hz, 6H), 0.98 (sp, J ) 6.1 Hz, 1H), 1.02 (sp, J ) 5.8
Hz, 1H), 4.60 (s, 2H), 6.95 (s, 1H), 6.99 (s, 1H), 7.07 (d, J )
5.1 Hz, 1H), 7.19-7.47 (m, 21H). 13C NMR (50 MHz, CDCl3):
δ 13.96, 17.52, 17.65, 65.30, 124.24, 126.00, 126.76, 127.27,
127.57, 127.61, 127.84, 128.06, 128.27, 128.51, 128.95, 129.32,
129.67, 129.74, 130.53, 130.57, 130.78, 131.21, 131.49, 134.31,
135.92, 136.09, 138.61, 139.26, 139.29, 140.56, 140.89, 151.05.
MS (EI): m/z 696 (M+), 653 (M+- C3H7). IR (KBr): 1598, 1492,
1096, 1068 cm-1. Anal. Calcd for C43H40OS3Si: C, 74.09; H,
5.78; S, 13.80. Found: C, 74.03; H, 5.87; S, 14.02.
3′′,3′,4-Tr ip h en yl-2′′,5′:2′,2-ter th iop h en e (10). To a solu-
tion of 9 (55 mg, 0.07 mmol) in 5 mL of THF was added TBAF
(0.11 g, 0.35 mmol). The mixture was stirred for 3 h at ambient
temperature. The solvent was evaporated in vacuo and the
residue dissolved in cyclohexane. Washing with water and
brine afforded, after extraction with cyclohexane and drying
over sodium sulfate, a yellow solid. The crude product was
purified by flash chromatography (SiO2, 90:10, cyclohex-
ane:CH2Cl2) to yield 34 mg (91%) of the title compound as a
yellow oil. HPLC (85:15, n-hexane:CH2Cl2): tR ) 13.3 min. 1H
NMR (200 MHz, CDCl3): δ 6.96 (s, 1H), 7.08 (d, J ) 5.2 Hz,
1H), 7.17-7.48 (m, 18H). 13C NMR (50 MHz, CDCl3): δ 120.64,
124.25, 125.54, 126.21, 127.22, 127.60, 127.66, 128.41, 128.52,
128.75, 129.29, 129.35, 129.64, 129.66, 130.80, 131.49, 134.42,
135.47, 135.85, 136.09, 136.35, 139.12, 139.33, 142.14. MS
5-[B e n zy lo x y (d iis o p r o p y l)s ily l]-2-io d o -4-p h e n y l-
th iop h en e (6b). From 4 (0.76 g, 2.00 mmol) was obtained 0.92
g (91%) of the title compound after flash chromatography on
1
Al2O3 (cyclohexane). H NMR (200 MHz, CDCl3): δ 0.83 (d, J
) 6.7 Hz, 6H), 0.87 (d, J ) 6.6 Hz, 6H), 0.94 (sp, J ) 6.7 Hz,
1H), 0.97 (sp, J ) 6.6 Hz, 1H), 4.61 (s, 2H), 7.13 (s, 1H), 7.05-
7.24 (m, 10H). 13C NMR (50 MHz, CDCl3): δ 13.89, 17.47,
17.53, 65.35, 78.99, 125.85, 126.81, 127.51, 127.85, 128.04,
128.82, 137.53, 137.80, 140.56, 140.84, 152.65. MS (EI): m/z
(EI): m/z 476 (M+). IR (KBr): 1598, 1492, 1070, 841 cm-1
.
506 (M+), 463 (M+ - C3H7), 379 (M+ - I), 336 (M+ - C3H7
-
.
HRMS (EI): calcd for C30H20S3, 476.0727; found, 476.0729.
I). IR (neat): 1598, 1481, 1383, 1205, 1093, 1068, 939 cm-1
Resin -Bou n d Th iop h en e R12. To a suspension of hy-
droxymethyl polystyrene resin R11 (15.00 g, 0.67 mmol/g, 10.1
mmol), imidazole (1.71 g, 25.2 mmol), and DMF (80 mL) in a
preweighed fritted column was added 2b (6.52 g, 20.2 mmol).
The resulting mixture was shaken periodically at room tem-
perature for 52 h. The solvent was removed by filtration and
the polymer washed successively with DMF (2 × 60 mL), THF
(3 × 60 mL), and CH2Cl2 (3 × 60 mL), and dried to constant
mass in vacuo to afford the derivatized resin R12 (17.88 g,
∆w ) 2.88 g, 0.56 mmol/g) as a colorless solid. IR (KBr): 3082,
3025, 2923, 2852, 1941, 1870, 1802, 1742, 1601, 1492, 1452,
Anal. Calcd for C23H27IOSSi: C, 54.54; H, 5.37; S, 6.33. Found:
C, 54.51; H, 5.58; S, 6.13.
5-[Ben zyloxy(d iisop r op yl)silyl]-5′-iod o-3′,4-d ip h en yl-
2′,2-bith iop h en e (8). From 7 (1.08 g, 2.00 mmol) was obtained
1.14 g (86%) of the title compound after flash chromatography
on Al2O3 (80:20, petroleum ether:CH2Cl2). 1H NMR (200 MHz,
CDCl3): δ 0.90 (d, J ) 6.2 Hz, 6H), 0.92 (d, J ) 6.0 Hz, 6H),
1.00 (sp, J ) 6.2 Hz, 1H), 1.05 (sp, J ) 6.0 Hz, 1H), 4.61 (s,
2H), 7.02 (s, 1H), 7.19-7.37 (m, 16H). 13C NMR (50 MHz,
CDCl3): δ 13.95, 17.52, 17.64, 65.34, 72.24, 126.00, 126.80,
127.36, 127.81, 127.88, 128.08, 128.37, 128.94, 129.23, 130.86,
130.93, 134.86, 137.36, 138.48, 139.61, 140.01, 140.06, 140.85,
151.11. MS (EI): m/z 664 (M+), 621 (M+ - C3H7). IR (neat):
1601, 1492, 1446, 1380, 1108, 1068, 950, 881 cm-1. Anal. Calcd
for C33H34IOS2Si: C, 59.63; H, 5.00; S, 9.65. Found: C, 59.41;
H, 5.10; S, 9.37.
Gen er a l P r oced u r e for th e Su zu k i Cou p lin g of th e
Iod osilylth iop h en es 6b a n d 8. To a degassed solution of 6b
and 8 (2.00 mmol) in 20 mL of DME was added Pd(PPh3)4 (5
mol %). The mixture was stirred for 10 min, and then boronic
ester 3a (3.00 mmol) and a solution of sodium hydrogencar-
bonate (20.0 mmol) in 1 mL of degassed water were added.
The mixture was refluxed for 8 h under an argon atmosphere.
The reaction was poured into water and the organic layer
extracted with diethyl ether. The organic layer was dried over
sodium sulfate, filtered, and concentrated in vacuo. The crude
mixture was purified by flash chromatography on Al2O3 to
afford 7 and 9.
5 -[B e n z y l o x y (d i i s o p r o p y l )s i l y l ]-3 ′,4 -d i p h e n y l -
2′,2-bith iop h en e (7). From 6b (1.01 g, 2.00 mmol) was
obtained 0.91 g (84%) of the title product as a colorless oil after
flash chromtography on Al2O3 (cyclohexane). 1H NMR (200
MHz, CDCl3): δ 0.83 (d, J ) 6.3 Hz, 6H), 0.85 (d, J ) 6.3 Hz,
6H), 0.91 (sp, J ) 6.3 Hz, 1H), 0.93 (sp, J ) 6.3 Hz, 1H), 4.54
(s, 2H), 6.98 (d, J ) 5.2 Hz, 1H), 7.00 (s, 1H), 7.11-7.34 (m,
16H). 13C NMR (50 MHz, CDCl3): δ 13.97, 17.54, 17.67, 65.30,
124.10, 126.01, 126.76, 127.24, 127.42, 127.83, 128.06, 128.27,
128.96, 129.34, 130.43, 130.49, 130.71, 131.44, 136.22, 138.67,
139.28, 140.90, 140.95, 151.15. MS (EI): m/z 538 (M+), 495
(M+ - C3H7). IR (neat): 1601, 1492, 1449, 1374, 1205, 1099,
1272, 1208, 1091, 1068, 1028, 880, 818, 756, 697 cm-1
.
Characteristic absorptions for the attached silylthiophene were
observed at 1097 (strong), 881 (weak), and 818 cm-1 (weak).
Resin -Bou n d Iod oth iop h en e R13. An oven-dried flask
was charged with polymer-supported thiophene 12 (10.00 g,
0.56 mmol/g, 5.60 mmol) and suspended in THF (80 mL). The
reaction mixture was cooled to -60 °C, and LDA (8.40 mL,
16.8 mmol, 2.0 M in hexane) was added dropwise via cannula.
After the addition was complete, the reaction mixture was
warmed to room temperature over 30 min and stirred for
additional 2 h. The resulting suspension of orange-colored
beads was treated, via cannula, with a premade THF solution
of iodine (4.26 g, 16.8 mmol) and stirred at room temperature
for 2 h. The polymer was collected by filtration in a preweighed
fritted filter, washed successively with CH2Cl2 (3 × 60 mL),
Et2O (2 × 60 mL), MeOH (2 × 60 mL), CH2Cl2 (2 × 60 mL),
and Et2O (2 × 60 mL), and dried to constant mass in vacuo to
afford the derivatized resin R13 (10.66 g, ∆w ) 0.66 g, 0.49
mmol/g) as a yellow solid. IR (KBr): 3080, 3022, 2919, 2850,
1942, 1868, 1802, 1740, 1598, 1489, 1449, 1377, 1108, 1088,
939, 815, 755, 695 cm-1. Characteristic bands are located in
the fingerprint region and overlap with resin absorbance.
However, weak infrared absorption at 939 cm-1 was charac-
teristic for the carbon-iodine bond.
Gen er a l P r oced u r e for th e Su zu k i Cou p lin g of Resin -
Bou n d Iod oth iop h en es w ith Bor on ic Ester 3b. An oven-
dried flask was charged with resin-bound monomeric or
oligomeric thiophene iodide (1.0 equiv) and catalytic tetrakis-
(triphenylphoshino)palladium(0) (5 mol %) and suspended in
degassed THF (10 mL/g of polymer). The reaction mixture was

Synthesis of Regioregular Oligo(3-arylthiophene)s
J . Org. Chem., Vol. 65, No. 2, 2000 359
stirred for 10 min, and then boronic ester 3b (2.5 equiv) and
a solution of sodium hydrogencarbonate (10 equiv) in degassed
water (1 mL/g of polymer) were added. The mixture was
refluxed for 8 h under an argon atmosphere. The supension
was then cooled to room temperature and diluted with water.
The polymer was collected by filtration in a preweighed fritted
filter, washed successively (40 mL/g of polymer) with water,
CH2Cl2, Et2O, MeOH, CH2Cl2, and Et2O, and dried to constant
mass in vacuo.
mmol) afforded after flash chromatography on SiO2 (cyclohex-
ane) 13 (142 mg, 91%) as a colorless solid. 1H NMR (200 MHz,
CDCl3): δ 2.35 (s, 3H), 7.17-7.43 (m, 4H), 7.38 (d, J ) 1.7
Hz, 1H), 7.48 (d, J ) 1.7 Hz, 1H). 13C NMR (50 MHz, CDCl3):
δ 21.13, 73.85, 125.40, 126.11, 129.52, 131.83, 136.02, 137.32,
144.10. MS (EI): m/z 300 (M+), 173 (M+ - I).
3′,4-Di(p-tolyl)-2′,2-bith iop h en e (14). Resin R14 (0.50 g,
0.46 mmol/g, 0.23 mmol), THF (2.5 mL), and TBAF (0.36 g,
1.15 mmol) afforded after flash chromatography on SiO2
(cyclohexane) 14 (77 mg, 87%) as a colorless solid. Analytical
data are in conformity with literature data.8a
Resin -Bou n d Bith iop h en e R14. Resin-bound thiophene
iodide R13 (5.00 g, 0.49 mmol/g, 2.45 mmol), THF (50 mL),
boronic ester 3b (1.58 g, 6.13 mmol), sodium hydrogen carbon-
ate (2.10 g, 24.5 mmol), and water (5 mL) afforded R14 (5.11
g, ∆w ) 0.11 g, 0.46 mmol/g) as slightly yellow beads. IR
(KBr): 3080, 3022, 2925, 2850, 1942, 1868, 1799, 1741, 1598,
5′-Iod o-3′,4-d i(p-tolyl)-2′,2-bith iop h en e (15). Resin R15
(0.50 g, 0.38 mmol/g, 0.19 mmol), THF (2.5 mL), and TBAF
(0.30 g, 0.95 mmol) afforded after preparative HPLC 15 (31
mg, 71%) as a yellow oil. HPLC (85:15, n-hexane:CH2Cl2): tR
1489, 1449, 1374, 1179, 1093, 1016, 878, 749, 695 cm-1
.
1
) 8.22 min. H NMR (200 MHz, CDCl3): δ 2.34 (s, 3H), 2.35
Resin -Bou n d Ter th ioph en e R16. Resin-bound bithiophene
iodide R15 (3.50 g, 0.38 mmol/g, 1.33 mmol), THF (35 mL),
boronic ester 3b (0.86 g, 3.33 mmol), sodium hydrogen carbon-
ate (1.11 g, 13.3 mmol), and water (3.5 mL) afforded R16 (3.56
g, ∆w ) 0.06 g, 0.34 mmol/g) as deep yellow beads. IR (KBr):
3080, 3022, 2919, 2850, 1939, 1868, 1799, 1741, 1601, 1489,
(s, 3H), 7.11-7.39 (m, 11H). 13C NMR (50 MHz, CDCl3): δ
21.12, 21.27, 72.03, 120.43, 125.93, 126.09, 129.05, 129.20,
129.47, 131.80, 132.60, 135.38, 137.09, 137.67, 140.13, 140.80,
142.16. MS (EI): m/z 472 (M+).
3′′,3′,4-Tr i(p-tolyl)-2′′,5′:2′,2-ter th ioph en e (16). Resin R16
(0.50 g, 0.34 mmol/g, 0.17 mmol), THF (2.5 mL), and TBAF
(0.27 g, 0.85 mmol) afforded after preparative HPLC 16 (29
mg, 68%) as a yellow oil. HPLC (85:15, n-hexane:CH2Cl2): tR
1452, 1372, 1179, 1093, 1019, 878, 755, 698 cm-1
.
Resin -Bou n d Qu a ter th iop h en e R18. Resin-bound ter-
thiophene iodide R17 (2.50 g, 0.27 mmol/g, 0.68 mmol), THF
(25 mL), boronic ester 3b (0.44 g, 1.70 mmol), sodium hydrogen
carbonate (0.57 g, 6.80 mmol), and water (2.5 mL) afforded
R18 (2.53 g, ∆w ) 0.03 g, 0.24 mmol/g) as brown beads. IR
(KBr): 3080, 3022, 2919, 2850, 1942, 1868, 1799, 1741, 1598,
1
) 13.0 min. H NMR (200 MHz, CDCl3): δ 2.33 (s, 3H), 2.35
(s, 3H), 2.37 (s, 3H), 6.95 (s, 1H), 7.04 (d, J ) 5.2 Hz, 1H),
7.25 (d, J ) 5.2 Hz, 1H), 7.10-7.35 (m, 14H). 13C NMR (50
MHz, CDCl3): δ 21.11, 21.26, 21.29, 119.98, 124.06, 125.52,
126.11, 129.11, 129.16, 129.25, 129.43, 129.70, 130.89, 131.19,
132.76, 132.97, 133.12, 134.37, 136.40, 136.97, 137.35, 137.36,
139.07, 139.27, 142.05. MS (EI): m/z 518 (M+). IR (KBr): 1509,
1492, 1185, 1111, 875, 812 cm-1. HRMS (EI): calcd for
1489, 1449, 1374, 1179, 1113, 1016, 878, 812, 755, 695 cm-1
.
Gen er a l P r oced u r e for Iod in a tion of th e Resin -Bou n d
Oligot h iop h en es. To a suspension of resin-bound oligo-
thiophene (1.0 equiv) and CH2Cl2 (15 mL/g of polymer) in a
preweighed fritted column was added mercuric caproate (1.1
equiv). The resulting mixture was shaken periodically at room
temperature for 24 h. To the resulting suspension was added
dropwise a premade THF solution of iodine (1.1 equiv), and
the reaction mixture was shaken for an additional 2 h. The
solvent was removed by filtration and the polymer washed (40
mL/g of polymer) successively with CH2Cl2, MeOH, Et2O,
CH2Cl2, and Et2O, and dried to constant mass in vacuo.
Resin -Bou n d Bith iop h en e Iod id e R15. Resin-bound
bithiophene R14 (4.00 g, 0.46 mmol/g, 1.84 mmol), CH2Cl2 (60
mL), mercuric caproate (0.87 g, 2.02 mmol), and iodine (0.51
g, 2.02 mmol) afforded R15 (4.20 g, ∆w ) 0.20 g, 0.38 mmol/
g) as yellow beads. IR (KBr): 3080, 3022, 2919, 2850, 1939,
1868, 1796, 1748, 1598, 1489, 1449, 1374, 1179, 1093, 1025,
C
33H26S3, 518.1196; found, 518.1196.
5′′-Iod o-3′′,3′,4-tr i(p-tolyl)-2′′,5′:2′,2-ter th iop h en e (17).
Resin R17 (0.50 g, 0.27 mmol/g, 0.14 mmol), THF (2.5 mL),
and TBAF (0.22 g, 0.70 mmol) afforded after preparative
HPLC 17 (22 mg, 54%) as
a yellow oil. HPLC (85:15,
n-hexane:CH2Cl2): tR ) 11.9 min. 1H NMR (200 MHz,
CDCl3): δ 2.34 (s, 3H), 2.36 (s, 3H), 2.38 (s, 3H), 6.91 (s, 1H),
7.12-7.38 (m, 15H). 13C NMR (50 MHz, CDCl3): δ 21.12, 21.27,
21.31, 72.16, 120.17, 125.65, 126.09, 129.04, 129.11, 129.12,
129.15, 129.32, 129.44, 129.94, 131.71, 132.67, 132.72, 132.96,
136.10, 136.70, 137.02, 137.47, 137.81, 139.05, 140.41, 140.84,
142.08. MS (EI): m/z 644 (M+).
3′′′,3′′,3′,4-T e t r a (p -t o ly l)-2′′′,5′′:2′′,5′:2′,2-q u a t e r -
th iop h en e (18). Resin R18 (0.50 g, 0.24 mmol/g, 0.12 mmol),
THF (2.5 mL), and TBAF (0.19 g, 0.60 mmol) afforded after
preparative HPLC 18 (17 mg, 48%) as a yellow oil. HPLC
881, 812, 752, 695 cm-1
.
Resin -Bou n d Ter th iop h en e Iod id e R17. Resin-bound
terthiophene R16 (3.00 g, 0.34 mmol/g, 1.02 mmol), CH2Cl2
(45 mL), mercuric caproate (0.48 g, 1.12 mmol), and iodine
(0.28 g, 1.12 mmol) afforded R17 (3.10 g, ∆w ) 0.10 g, 0.27
mmol/g) as brown beads. IR (KBr): 3080, 3022, 2919, 2850,
1942, 1868, 1799, 1736, 1653, 1598, 1489, 1449, 1260, 1091,
1
(80:20, n-hexane:CH2Cl2): tR ) 13.8 min. H NMR (500 MHz,
CDCl3): δ 2.27 (s, 3H), 2.28 (s, 3H), 2.30 (s, 3H), 2.31 (s, 3H),
6.80 (s, 1H), 6.88 (s, 1H), 6.98 (d, J ) 5.1 Hz, 1H), 7.03-7.29
(m, 19H). 13C NMR (126 MHz, CDCl3): δ 21.11, 21.26, 21.31,
120.00, 124.09, 125.49, 126.09, 129.11, 129.13, 129.16, 129.23,
129.26, 129.42, 129.54, 129.94, 130.78, 130.84, 130.93, 131.16,
132.72, 132.84, 132.88, 133.06, 134.03, 134.44, 136.33, 136.98,
137.36, 137.39, 137.50, 138.98, 139.13, 139.30, 142.03. MS
(EI): m/z 690 (M+). IR (KBr): 1506, 1495, 1260, 1179, 1102,
1019, 873, 810 cm-1. HRMS (EI): calcd for C44H34S4, 690.1543;
found, 690.1544.
1019, 812, 752, 695 cm-1
.
P r oced u r e for Mon om er a n d Oligom er R em ova l by
P r otiod esilyla tion . To a suspension of polymer-supported
monomer or oligomer (1.0 equiv) and THF (5 mL/g of polymer)
in a flask was added TBAF (5 equiv). The reaction mixture
was heated for 1 h to 70 °C, cooled to room temperature, and
filtrated to remove the polymer. After evaporation of the
solvent, the residue was dissolved in diethyl ether, washed
with water and brine, dried, and concentrated. Flash chroma-
tography on SiO2 or preparative HPLC afforded the monomer
or oligomer thiophenes as pure compounds.
Ack n ow led gm en t. We gratefully acknowledge the
financial support of the Fonds der Chemischen Industrie
and the BMBF (Kekule´ Grant to C.A.B.).
3-(p-Tolyl)th iop h en e (12). Resin R12 (1.00 g, 0.56 mmol/
g, 0.56 mmol), THF (5 mL), and TBAF (0.88 g, 2.80 mmol)
afforded after flash chromatography on SiO2 (cyclohexane) 12
(91 mg, 93%) as a colorless solid. Analytical data are in
conformity with literature data.23
Su p p or t in g In for m a t ion Ava ila b le: 1H NMR and 13C
NMR spectra and mass spectra for 10, 16, and 18. This
material is available free of charge via the Internet at
http://pubs.acs.org.
2-Iod o-4-(p-tolyl)th iop h en e (13). Resin R13 (1.00 g, 0.49
mmol/g, 0.49 mmol), THF (5 mL), and TBAF (0.77 g, 2.45
J O991188B