An easy and multigram-scale synthesis of versatile AA- and AB-type w-terphenylenes as building blocks for kinked polyphenylenes

Article abstract of DOI:10.1002/ejoc.200900263

A set of m-terphenylenes having a readily functionalizable hydroxy group as well as either symmetric AA-type or unsymmetric AB-type halide termini have been prepared on a several-gram scale. The synthesis was carried out on the basis of the Suzuki-Miyaura

Full text of DOI:10.1002/ejoc.200900263

SHORT COMMUNICATION
DOI: 10.1002/ejoc.200900263
An Easy and Multigram-Scale Synthesis of Versatile AA- and AB-Type
m-Terphenylenes as Building Blocks for Kinked Polyphenylenes
Patrick Kissel,[a] Simon Breitler,[a] Viktoria Reinmüller,[a] Patrick Lanz,[a] Lukas Federer,[a]
A. Dieter Schlüter,[a] and Junji Sakamoto*[a]
Keywords: Cross-coupling / Masking / Macrocycles / Foldamers / Polymers
A set of m-terphenylenes having a readily functionalizable
hydroxy group as well as either symmetric AA-type or un-
symmetric AB-type halide termini have been prepared on a
several-gram scale. The synthesis was carried out on the ba-
sis of the Suzuki–Miyaura cross-coupling in combination
with a TMS masking strategy.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
Introduction
Results and Discussion
Building blocks for the central part of the m-terphenyl-
enes 1–3 (Figure 1) were 5 (for symmetric 1 and 2) and 6
(for unsymmetric 3) and prepared according to a known
procedure[6] adjusted to the present large-scale synthesis
(Scheme 1a). Starting from the commercially available com-
pound 4, product 5 was obtained by bromination, deamina-
tion, and then reduction of the benzoate to the correspond-
ing benzylic alcohol. Note that each of these steps pro-
ceeded nearly quantitative, and the products were easily
separated by recrystallization without any chromatographic
purification. This facilitated the synthesis and obtainment
of analytically pure 5 on a large scale (50 g). A portion of
5 was further converted to 6, which was needed for the syn-
thesis of the unsymmetric 3.[7] The synthesis of 6 involved
subsequently protection of benzylic OH with the tetra-
hydro-2H-pyran-2-yl (THP) group, silylation at one of the
brominated carbon atoms, and borylation at the other one.
Analytically pure 6 was obtained on a 25 g scale.
Oligo- and polyphenylenes attract increasing interest not
only in academic research but also for industrial applica-
tions due to their useful mechanical and optoelectronic
properties.[1] These properties are largely attributed to the
structure of the main chains, which are potentially conju-
gated, inherently stiff and also chemically stable. We here
report an easy and scalable synthesis of m-terphenylenes
having a readily functionalizable benzylic OH group as well
as symmetric AA-type and unsymmetric AB-type halide
termini (Figure 1). Due to their kinked shape, m-terphenyl-
enes are a key motif particularly in the skeletons of phenyl-
ene-based macrocycles,[2] foldamers[3] as well as tough
amorphous polymers,[4] etc. For polymer synthesis, they
have additional potential as monomers for the Suzuki poly-
condensation (SPC).[1,5]
On the other hand, “cornerstones” 9 (for 1–3) and 10
(for 3) were prepared according to rather simple procedures
(Scheme 1b). First, an efficient silylation took place at one
of the brominated carbon atoms of the commercially avail-
able dibromo compound 7. This was achieved through lithi-
ation and subsequent quenching with trimethylsilyl chloride
(TMSCl). For 10, this TMS group was further replaced to
afford the corresponding iodide (14 g) by reaction with io-
dine monochloride (ICl).[2] Product 9 (37 g) was prepared
by borylation at the remaining bromide of 8 through lithi-
ation.
Figure 1. Target m-terphenylene structures possessing a free ben-
zylic OH group as well as symmetric AA-type (1 and 2) or unsym-
metric AB-type (3) termini.
The obtained building blocks 5, 6, 9, and 10 were as-
sembled into the m-terphenylenes 1–3 by using the Suzuki–
Miyaura cross-coupling (SMC) protocol. For the symmetric
1 (Scheme 2a), compound 5 was subjected to a double SMC
with 2 equiv. of 9 to afford 11 (21 g) very efficiently. Product
11 was also found to be recrystallizable from hexane. A por-
[a] Laboratory of Polymer Chemistry, Department of Materials,
ETH Zurich,
Wolfgang-Pauli-Strasse 10, HCI J541, 8093 Zurich, Switzerland
Fax: +41-44-6331395
E-mail: sakamoto@mat.ethz.ch
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.200900263.
Eur. J. Org. Chem. 2009, 2953–2955
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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J. Sakamoto et al.
SHORT COMMUNICATION
Scheme 1. Synthetic procedure to prepare building blocks for (a)
the central parts, 5 (for symmetric 1 and 2) and 6 (for unsymmetric
3), as well as those for (b) the side parts, 9 (for 1–3) and 10 (for 3).
a: Br2, AcOH, 88%; b: NaNO2, H2SO4, 69%; c: LiAlH4, ether,
87%; d: 3,4-dihydro-2H-pyran, TsOH, dichloromethane, 98%; e:
1) BuLi, diethyl ether, 2) TMSCl, 93%; f: 1) BuLi, THF/diethyl
ether, 2) B(OiPr)3, 3) pinacol, toluene, 65%; g: 1) BuLi, THF,
2) TMSCl. 93%; h: 1) BuLi, THF/diethyl ether, 2) B(OMe)3, 3) pin-
acol, toluene, 67%; i: ICI, dichloromethane, 95%.
Scheme 2. Synthesis of the target m-terphenylenes 1–3 from the
building blocks 5, 6, 9, 10 by using the Suzuki–Miyaura cross-cou-
pling in combination with a TMS masking strategy. j: Pd(PPh3)4,
Na2CO3, toluene/water, 97%; k: ICl, dichloromethane, 87%; l:
Ac2O, pyridine, dichloromethane, 92%; m: NBS, NaBr, methanol,
76%; n: Pd(PPh3)4, Na2CO3, TBAB, toluene/water, 75%; o: TsOH,
MeOH/dichloromethane, 98%; p: ICl, dichloromethane, 93%; q:
Pd(PPh3)4, Na2CO3, TBAB, toluene/water, 42%;[12] r: ICl, dichlo-
romethane, 80%.
tion of 11 was then converted into the corresponding diio-
dide to obtain 1 by reaction with a stoichiometric amount
of ICl. Note that the benzylic OH group was kept unprotec-
ted here for the ease of synthesis. However, it could be re-
placed with chloride in varying degrees particularly when
excess amounts of ICl were used. During the conversion of
11 to 2 with N-bromosuccinimide/NaBr,[8] the oxidation of
the alcohol functionality to the corresponding aldehyde
could be observed. To retard this side reaction, the benzylic
OH group was acetylated prior to the TMS/Br exchange,
while the acetyl group was incidentally removed to afford 2
directly.[9] Thus, analytically pure products 1 and 2 were
obtained on 7 g and 4 g scales, respectively, by recrystalli-
zation from ethyl acetate.
Conclusions
A set of m-terphenylenes 1–3, which are equipped with
either symmetric AA-type or unsymmetric AB-type termini
have been prepared. These compounds are considered to be
used for novel polymer synthesis: the former can copoly-
merize with other BB-type monomers having e.g. diboron
functionalities, whereas the latter can serve as a precursor
of monomers having e.g. one bromo and one boron func-
tionality which are able to homopolymerize by SPC.[11] The
synthesis of 1–3 was carried out by using the SMC in com-
bination with a TMS masking strategy,[2] and the target
compounds have been obtained on multigram scales
eventually. These compounds also carry a free benzylic OH
group, which opens a variety of options for further func-
tionalizations. Investigations aiming at polymer synthesis
are now in progress.[5]
For the synthesis of 3 with its more complex unsymmet-
ric structure,
a
stepwise procedure was employed
(Scheme 2b).[10] Compound 6 was first subjected to SMC
with 10 to afford 12 (14 g). Note that this reaction selec-
tively proceeded to give 12 by exploiting the significant re-
activity difference between iodo and bromo aromatics in
palladium-mediated cross-coupling.[10] This was followed
successively by deprotection of the THP group and TMS/I
exchange using a stoichiometric amount of ICl. Product 13
was then subjected to a second SMC with 9 to furnish 14
followed by iodation again with a stoichiometric amount of
ICl. The unsymmetric 3 with AB-type termini was obtained
on a 4 g scale. Note that 3 was also found to be recrystalliz-
able from ethyl acetate, which guaranteed a purity high
enough (Ͼ 99%) for these compounds to be considered as
monomers for SPC.[1a]
Supporting Information (see footnote on the first page of this arti-
cle): All experimental procedures and NMR and MS data.
Acknowledgments
The authors thank F. Weibel, B. Hohl and T. Mingarcha (ETH
Zurich) for their help in synthesis, Dr. X. Zhang and his team
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Building Blocks for Kinked Polyphenylenes
[5]
(ETH Zurich) for mass measurements, and Dr. T. Wigglesworth
(ETH Zurich) for drawing our attention to ref.[8] Financial support
by the ETH Zurich grant (TH-05 07-1) is gratefully acknowledged.
Polymer synthesis with these compounds as monomers is to be
published elsewhere.
O. Henze, Ph. D. Thesis, FU Berlin, 2000.
G. Manickam, A. D. Schlüter, Synthesis 2000, 442–446.
A. Operamolla, O. H. Omar, F. Babudri, G. M. Farinola, F.
[6]
[7]
[8]
[1] See the following reviews for example: a) J. Sakamoto, M. Re-
hahn, G. Wegner, A. D. Schlüter, Macromol. Rapid Commun.,
in press; b) E. List, W. Jachim, U. Scherf in Handbook of Con-
ducting Polymers, 3rd ed. (Eds.: T. A. Skotheim, J. R. Reyn-
olds), CRC Press LLC, Boca Raton, 2007, vol. 1, pp. 5/1–5/35;
c) A. C. Grimsdale, K. Müllen, Angew. Chem. Int. Ed. 2005,
44, 5592–5629; d) G. Wegner, Macromol. Chem. Phys. 2003,
204, 347–357; e) A. D. Schlüter, J. Polym. Sci., Part A: Polym.
Chem. 2001, 39, 1533–1556.
[2] See for example: a) V. Hensel, A. D. Schlüter, Chem. Eur. J.
1999, 5, 421–429; b) V. Hensel, A. D. Schlüter, Eur. J. Org.
Chem. 1999, 451–458; c) C. Grave, D. Lentz, A. Schaefer, P.
Samori, J. P. Rabe, P. Franke, A. D. Schlüter, J. Am. Chem. Soc.
2003, 125, 6907–6918.
[3] See for example: a) A. Zhang, J. Sakamoto, A. D. Schlüter,
Chimia 2008, 62, 776–782; b) T. Ben, H. Goto, K. Miwa, H.
Goto, K. Morino, Y. Furusho, E. Yashima, Macromolecules
2008, 41, 4506–4509.
[4] R. Kandre, K. Feldman, H. E. H. Meijer, P. Smith, A. D.
Schlüter, Angew. Chem. Int. Ed. 2007, 46, 4956–4959.
Naso, J. Org. Chem. 2007, 72, 10272–10275.
[9] The acetyl protection actually helped to retard the oxidation
to achieve an improved yield of the desired product 2, while
the formation of the aldehyde was not fully suppressed never-
theless. However, this side product can be reduced back to 2
by treatment with NaBH4 (see ref.[12]).
[10] See for example: a) D. M. Opris, P. Franke, A. D. Schlüter, Eur.
J. Org. Chem. 2005, 822–837; b) J. Sakamoto, A. D. Schlüter,
Eur. J. Org. Chem. 2007, 2700–2712.
[11] Selective borylation at the iodated terminus is feasible.
[12] This rather low yield of 14 is presumably due to an aged cata-
lyst batch which happened to be used for this particular experi-
ment. This caused unexpected oxidation at the benzyl alcohol
as detrimental side reaction. However, the resultant aldehyde
was quantitatively reduced back to 14 by treatment with
NaBH4 in a mixed solvent of ethanol/THF (1:1).
Received: March 11, 2009
Published Online: May 7, 2009
Eur. J. Org. Chem. 2009, 2953–2955
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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