Iterative synthesis of 1,3,5-polyphenylene dendrons via C-H activation

Article abstract of DOI:10.1021/ol8019605

(Equation Presented) An iterative synthesis of 1,3,5-polyphenylene dendrons via C-H activation/Suzuki-Miyaura coupling up to a third generation dendron is described. C-H bonds at the focal points of the dendrons are selectively borylated via iridium-catalyzed borylation, eliminating the need for reactive protecting groups. Sequential additions of low catalyst loadings efficiently borylate higher-generation dendrons, whereas higher initial catalyst loadings are less efficient.

Full text of DOI:10.1021/ol8019605

ORGANIC
LETTERS
2008
Vol. 10, No. 21
4851-4854
Iterative Synthesis of
1,3,5-Polyphenylene Dendrons via C-H
Activation
Aaron D. Finke and Jeffrey S. Moore*
Department of Chemistry, UniVersity of Illinois Urbana-Champaign, 600 S. Mathews
AVe., Urbana, Illinois 61801
jsmoore@illinois.edu
Received August 21, 2008
ABSTRACT
An iterative synthesis of 1,3,5-polyphenylene dendrons via C-H activation/Suzuki-Miyaura coupling up to a third generation dendron is
described. C-H bonds at the focal points of the dendrons are selectively borylated via iridium-catalyzed borylation, eliminating the need for
reactive protecting groups. Sequential additions of low catalyst loadings efficiently borylate higher-generation dendrons, whereas higher
initial catalyst loadings are less efficient.
The demand for new, efficient optoelectronic materials has
led to a surge of interest in conjugated small molecules.1
However, the facile preparation of novel organic materials
rarely keeps up with their demand, as the preparation of
discrete, conjugated organic molecules can be synthetically
rigorous. As a result, the need to develop and utilize new
synthetic methods in the preparation of novel materials is
equally vital to ensure their rapid utilization.
conjugated dendrimers.2 Extensive work on rigid conjugated
dendrimers has been undertaken with a diverse array of
chemistries including phenylacetylene,3 stilbene,4 truxene,5
and phenylene6 repeat units. Dendrimers containing 1,3,5-
polyphenylene linkages constitute one of the simplest yet
lesser-utilized rigid dendritic architectures. Since their first
reports nearly 20 years ago, dendrimers of this class have
(2) Lo, S. C.; Burn, P. L. Chem. ReV. 2007, 107, 1097.
(3) (a) Xu, Z. F.; Moore, J. S. Angew. Chem., Int. Ed. Engl. 1993, 32,
246. (b) Devadoss, C.; Bharathi, P.; Moore, J. S. J. Am. Chem. Soc. 1996,
118, 9635. (c) Moore, J. S. Acc. Chem. Res. 1997, 30, 402.
(4) (a) Pillow, J. N. G.; Halim, M.; Lupton, J. M.; Burn, P. L.; Samuel,
I. D. W. Macromolecules 1999, 32, 5985. (b) Lehmann, M.; Schartel, B.;
Hennecke, M.; Meier, H. Tetrahedron 1999, 55, 13377.
(5) Jiang, Y.; Lu, Y. X.; Cui, Y. X.; Zhou, Q. F.; Ma, Y.; Pei, J. Org.
Lett. 2007, 9, 4539.
In few areas are these gaps between demand and efficient
synthesis more apparent than in the preparation of rigid, fully
(1) (a) Organ Light-Emitting DeVices: Synthesis, Properties and Ap-
plications; Mullen, K., Scherf, U., Eds.; Wiley-VCH: Weinheim, 2006. (b)
Newkome, G. R.; Moorefield, C. N.; Vogtle, F. Dendrimers and Dendrons:
Concepts, Syntheses, Applications; Wiley-VCH: Weinheim, 2001.
10.1021/ol8019605 CCC: $40.75
Published on Web 09/26/2008
2008 American Chemical Society

been used in several photophysical studies7 and perhaps most
notably in the incorporation of highly efficient organic light-
emitting diodes.8 While the optoelectronic properties of these
dendrimers are attractive, their preparation and synthetic
manipulation are not ideal. Typically limited to convergent
methods, the preparation of 1,3,5-polyphenylene dendrons
has almost exclusively relied upon the elucidation of a
“masked”boronicacidatthefocalpointpriortoSuzuki-Miyaura
coupling9 with an aryl halide and mask-containing branching
unit.10
Herein we describe a new method for the iterative
assembly of 1,3,5-polyphenylene dendrons incorporating 3,5-
di-tert-butyl-phenylene containing peripheral groups. The
method requires no “masked” focal point; instead, direct and
selective borylation of an aryl C-H bond via iridium-
catalyzed C-H activation generates the reactive pinacolbo-
ronate ester at the focal point. The dendron can then undergo
Suzuki-Miyaura coupling with an inexpensive, commer-
cially available 1,3-dihalobenzene to build the higher genera-
tions. We show that the process can be iterated to build a
third-generation polyphenylene dendron 6 in good yield
(Scheme 1). Utilizing highly efficient Suzuki-Miyaura
coupling conditions dramatically decreases reaction times and
inhibits byproduct formation.
predominantly controlled by sterics rather than electronics.13
Under these reaction conditions, a 1,3-disubstituted arene
preferentially borylates meta to both substituents, and typi-
cally in excellent yields. This methodology has been extended
to the borylation of substituted arenes and aromatic hetero-
cycles,14 but the borylation of larger aromatics has been
limited to porphyrins15 and simple polycyclic aromatics such
as naphthalene, pyrene, and perylene.16 The implementation
of this transformation into iterative methods for the prepara-
tion of novel materials has been limited to date, and to our
knowledge there are no examples of the Ir-catalyzed bory-
lation of oligoarenes.
The borylation of 1,3-di-tert-butylbenzene with bis(pina-
colato)diboron (B2pin2) as the borylating reagent to form
boronate ester 1 occurs in good yield in cyclohexane at 80
°C. It was found that, for all boronate esters in this work,
column chromatography on silica gel depreciated the yields
considerably, likely as a result of decomposition of the
product on silica gel. A short plug of silica gel was sufficient
to remove the catalyst, excess B2pin2, and boron-containing
byproducts, without apparent product decomposition. The
crude product, which typically contained small amounts
(<5%) of starting material and B2pin2, was taken on without
further purification and with no detriment to subsequent
transformations or purification.
The borylation of aromatic compounds via iridium-
catalyzed C-H bond activation has been extensively studied
since initial reports by Smith,11 Hartwig, Ishiyama, and
Miyaura.12 This reaction is unique with respect to other
aromatic substitution reactions because regioselectivity is
In most previous preparations of 1,3,5-polyphenylene
dendrons, Suzuki-Miyaura coupling was undertaken with
the standard palladium catalyst Pd(PPh3)4. However, coupling
of 1 with 1,3-diiodobenzene or 1,3-dibromobenzene to form
Scheme 1. Synthesis of Polyphenylene Dendrons
4852
Org. Lett., Vol. 10, No. 21, 2008

2 was very slow and tended to give significant amounts of
byproducts, including homocoupled17 and deboronated pi-
nacolboronate esters. Effective methods of converting the
relatively unreactive pinacolboronate esters to more reactive
boronic acids and aryltrifluoroborate salts are available;18
however, extra synthetic steps are undesirable. Instead, more
efficient catalyst systems were screened. The phosphine
ligand 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (S-
phos) developed by Buchwald19 is highly active toward
Suzuki-Miyaura cross-couplings and is particularly effective
in the coupling of sterically hindered boronic acids and aryl
halides. The syntheses of dendrons 2, 4, and 6 from boronate
esters 1, 3, and 5 using 5 mol % Pd(OAc)2/10 mol % S-phos
and aqueous NaOH in THF proceeded rapidly at 60 °C. All
three are readily purified by flash chromatography on silica
gel, eluting with hexane/dichloromethane mixtures. Analyti-
cal gel permeation chromatograms (GPC) of purified 2, 4,
and 6 give narrow bands with PDI values below 1.03 (see
Although K3PO4 is most commonly used as a base with
this ligand system, significant amounts of deboronated
starting material was generated in the syntheses of 4 and 6
if aqueous K3PO4 or K2CO3 was used. Homocoupling of the
pinacolboronate esters was detrimental to the purification of
4 and 6, as homocoupled 3 and 5 were difficult to isolate
from the desired product by most purification methods. It
was found that switching the base to aqueous NaOH and
using no more than 2 equiv of 3 or 5 attenuated homocou-
pling and deboronation, while only marginally lowering the
yield.20 Furthermore, switching to the more reactive 1,3-
diiodobenzene for the syntheses of 4 and 6 also decreased
byproduct formation.
Initial attempts to borylate dendrons 2 and 4 were slow
and did not proceed to complete conversion, even with
extended heating and high catalyst loadings. Extensive GC
studies on the borylation of 2 were performed (Table 1).
1
Supporting Information). The H NMR of 6 was taken in
Table 1. Borylation of Sterically Hindered m-Terphenylsa
both CDCl3 and benzene-d6 (see Supporting Information).
The aromatic proton chemical shifts appear to have a high
degree of solvent dependence, as better dispersion of the
aromatic protons can be achieved with benzene as solvent,
whereas in CDCl3 there is significant overlap of many peaks.
Most notably, the peripheral aromatic protons are fully
resolved in benzene, but in CDCl3 both resonances convolute
to appear as a singlet.
(6) (a) Wiesler, U. M.; Weil, T.; Mullen, K. Dendrimers III: Design,
Dimension, Function; Springer: New York, 2001; Top. Curr. Chem. Vol.
212, p 1. (b) Watson, M. D.; Fechtenkotter, A.; Mullen, K. Chem. ReV.
2001, 101, 1267. (c) Liu, D. J.; De Feyter, S.; Cotlet, M.; Stefan, A.; Wiesler,
U. M.; Herrmann, A.; Grebel-Koehler, D.; Qu, J.; Mullen, K.; De Schryver,
F. C. Macromolecules 2003, 36, 5918. (d) Bernhardt, S.; Kastler, M.;
Enkelmann, V.; Baumgarten, M.; Mullen, K. Chem. Eur. J. 2006, 12, 6117.
(7) (a) Gong, L.; Pu, L. Tetrahedron Lett. 2001, 42, 7337. (b) Gong,
L. Z.; Hu, Q. S.; Pu, L. J. Org. Chem. 2001, 66, 2358. (c) Kimura, M.;
Shiba, T.; Muto, T.; Hanabusa, K.; Shirai, H. Macromolecules 1999, 32,
8237. (d) Kimura, M.; Shiba, T.; Muto, T.; Hanabusa, K.; Shirai, H. Chem.
Commun. 2000, 11. (e) Kimura, M.; Shiba, T.; Yamazaki, M.; Shirai, H.;
Kobayashi, N. J. Am. Chem. Soc. 2001, 123, 5636. (f) Zhao, L.; Li, C.;
Zhang, Y.; Zhu, X. H.; Peng, J. B.; Cao, Y. Macromol. Rapid Commun.
2006, 27, 914. (g) Capitosti, G. J.; Guerrero, C. D.; Binkley, D. E.; Rajesh,
C. S.; Modarelli, D. A. J. Org. Chem. 2003, 68, 247.
added after 4 h % convn (GC)
entry arene initial catalystb B2pin2 catalystb
4h
70
70
68
8h
74
77
91
95
75
91
91
1
2
3
2
2
2
2
2
2
7
2 mol %
2 mol %
2 mol %
2 mol %
2 mol %
6 mol %
2 mol %
n/ad
1 equiv
n/ad
n/ad
n/ad
2 mol %
4
1 equiv 2 mol %
67
5c
6
n/ad
n/ad
n/ad
n/ad
n/ad
n/ad
70
nde
nde
7
a Reactions were carried out with 1.0 equiv of arene, 1.0 equiv of B2pin2,
20 mol % HBpin, and the specified amount of catalyst. b mol % 1/2[Ir-
(COD)(OMe)]2 and dtbpy added. c 2 equiv of B2pin2 initally added.
d Nothing added. e Conversion not determined.
(8) Burn, P. L.; Lo, S. C.; Samuel, I. D. W. AdV. Mater. (Weinheim,
Ger.) 2007, 19, 1675.
(9) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457.
(10) (a) Miller, T. M.; Neenan, T. X. Chem. Mater. 1990, 2, 346. (b)
Miller, T. M.; Neenan, T. X.; Zayas, R.; Bair, H. E. J. Am. Chem. Soc.
1992, 114, 1018. (c) Lo, S.; Namdas, E.; Burn, P. L.; Samuel, I.
Macromolecules 2003, 36, 9721.
Interestingly, it was found that using low catalyst loadings
and sequential addition of a premade catalyst stock solution
containing [Ir(COD)(OMe)]2, 4,4′-di-tert-butyl-2,2′-bipyri-
dine (dtbpy), and pinacolborane (HBpin) (Table 1, entry 3)
gave higher conversions than using higher initial catalyst
loadings (Table 1, entry 6).21 Addition of excess B2pin2 after
4 h slightly enhanced conversion (Table 1, entry 4).
(11) Cho, J. Y.; Tse, M. K.; Holmes, D.; Maleczka, R. E.; Smith, M. R.
Science 2002, 295, 305.
(12) (a) Ishiyama, T.; Takagi, J.; Hartwig, J. F.; Miyaura, N. Angew.
Chem., Int. Ed. 2002, 41, 3056. (b) Ishiyama, T.; Takagi, J.; Ishida, K.;
Miyaura, N.; Anastasi, N. R.; Hartwig, J. F. J. Am. Chem. Soc. 2002, 124,
390.
(13) (a) Ishiyama, T.; Miyaura, N. J. Organomet. Chem. 2003, 680, 3.
(b) Boller, T. M.; Murphy, J. M.; Hapke, M.; Ishiyama, T.; Miyaura, N.;
Hartwig, J. F. J. Am. Chem. Soc. 2005, 127, 14263. (c) Chotana, G. A.;
Rak, M. A.; Smith, M. R. J. Am. Chem. Soc. 2005, 127, 10539.
(14) (a) Paul, S.; Chotana, G. A.; Holmes, D.; Reichle, R. C.; Maleczka,
R. E.; Smith, M. R. J. Am. Chem. Soc. 2006, 128, 15552. (b) Chotana,
G. A.; Kallepalli, V. A.; Maleczka, R. E.; Smith, M. R. Tetrahedron 2008,
64, 6103. (c) Mkhalid, I. A. I.; Coventry, D. N.; Albesa-Jove, D.; Batsanov,
A. S.; Howard, J. A. K.; Perutz, R. N.; Marder, T. B. Angew. Chem., Int.
Ed. 2006, 45, 489.
(16) Coventry, D. N.; Batsanov, A. S.; Goeta, A. E.; Howard, J. A. K.;
Marder, T. B.; Perutz, R. N. Chem. Commun. 2005, 2172.
(17) Moreno-Manas, M.; Perez, M.; Pleixats, R. J. Org. Chem. 1996,
61, 2346.
(18) Murphy, J. M.; Tzschucke, C. C.; Hartwig, J. F. Org. Lett. 2007,
9, 757.
(19) (a) Barder, T. E.; Walker, S. D.; Martinelli, J. R.; Buchwald, S. L.
J. Am. Chem. Soc. 2005, 127, 4685. (b) Martin, R.; Buchwald, S. L.; Acc.
Chem. Res. 2008, ASAP; DOI: 10.1021/ar800036s.
(15) Hata, H.; Yamaguchi, S.; Mori, G.; Nakazono, S.; Katoh, T.;
Takatsu, K.; Hiroto, S.; Shinokubo, H.; Osuka, A. Chem. Asian J. 2007, 2,
849.
(20) It is known that strong bases promote coupling of sterically-hindered
boronic acids. Watanabe, T.; Miyaura, N.; Suzuki, A. Synlett 1992, 207.
Org. Lett., Vol. 10, No. 21, 2008
4853

Previous studies on the effects of steric inhibition of
borylation by peripheral, non-ortho substituents are limited.
Borylation of N-(triisopropylsilyl)pyrrole occurs at the 3
position, in contrast to unsubstituted pyrrole, which borylates
at the 2 position.13a,22 Elegant studies by Hata demonstrated
that a m-phenylene-linked Zn-tetraarylporphyrin dimer bo-
rylates quantitatively at the focal point, but a similar dimer
with peralkylated porphyrins does not undergo borylation.15
To investigate the role of sterics, dendron 7, which is less
sterically hindered than 2, was prepared (see Supporting
Information) and subsequently borylated (Table 1, entry 7).
It was found that no additional catalyst was needed to get
high conversions for the borylation of 7 with low catalyst
loadings, indicating that steric hindrance from distal moieties
plays an important role in the efficiency of borylation.
Likewise, dendron 4 also required sequential addition of
catalyst to achieve full conversion. At present, we cannot
understand why sequential addition of low catalyst loadings
led to more effective borylation of sterically hindered arenes.
However, these data suggest a complex mechanistic pathway
for decomposition of the catalyst that is competitive with
C-H activation; the details will be investigated further in
subsequent studies.
The potential of these polyphenylene dendrons for use in
optoelectronic materials led us to characterize the thermal
and photophysical properties of 2, 4, and 6. Like previously
synthesized 1,3,5-polyphenylene dendrimers, all three exhibit
high thermal stability (see Supporting Information).11 TGA
studies run under N2 show that 4 and 6 are stable up to nearly
500 °C. Interestingly, DSC studies run under N2 showed no
melting for 4 and 6 up to 400 °C; 6 displays two glass
transitions at 230 and 330 °C. Not surprisingly, absorbance
and emission spectra of the dendrons show evidence for
disrupted conjugation between phenyl rings. Absorbance
spectra of the dendrons (Figure 1) indicate a slight redshift
in the λmax from 250 nm for 2 to 255 nm for 4 to 257 nm for
6. Fluorescence quantum yields measured for 4 (Φ ) 0.16)
and 6 (Φ ) 0.15) in methylcyclohexane upon excitation at
250 nm show low fluorescence efficiencies. However, low
fluorescence quantum yields do not preclude efficient energy
transfer upon covalent attachment of an acceptor moiety.
Crystals suitable for X-ray analysis were grown from slow
evaporation of solutions of 1 and 4 in dichloromethane and
THF, respectively (Supporting Information). The high degree
of biaryl twist in 4 is indicative of low π-overlap between
Figure 1. Absorbance and emission spectra of dendrons.
benzene rings, confirmed by the relative lack of redshift in
the absorbance spectra with increasing generation of dendron.
From these data, we conclude that the cross-conjugated
benzene rings in these dendrons are essentially behaving as
individual chromophores.
In summary, we have developed a novel method for the
preparation of 1,3,5-polyphenylene dendrons with 3,5-di-tert-
butylphenyl peripheral groups. To our knowledge, this is the
first example of an iterative synthetic method that utilizes
the direct C-H activation of an arene. For larger generations
of dendrons, sequential addition of the iridium catalyst is
necessary for high turnovers, presumably due in part to steric
hindrance caused by the peripheral tert-butyl groups. While
it is efficient for this particular example with 3,5-di-tert-
butyl peripheral groups, this method is generally limited to
the construction of 1,3,5-polyphenylene dendrons with
peripheral groups unreactive to borylation. Dendrons con-
taining unsubstituted arenes, alkynes, alkenes, nitro groups,
phenols, and primary or secondary amines are thus unsuit-
able. Future work will demonstrate the versatility of this
iterative approach, with the preparation of novel architectures
that would otherwise be extremely difficult to synthesize.
Acknowledgment. This work was supported by the
National Science Foundation under NSF Award CBET-
0730667. The authors gratefully acknowledge Carolyn S.
Wei and John F. Hartwig, University of Illinois Urbana-
Champaign, for helpful discussions.
Supporting Information Available: Synthetic procedures,
spectroscopic and thermal characterization of the new
compounds, GPC traces, and crystal structures of 1 and 4.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(21) The formation of the active trisboryl-iridium catalyst is accelerated
by addition of HBpin, but the use of HBpin is unnecessary. HBpin is an
impractical reagent because of its extreme moisture susceptibility. Sequential
addition of the precatalyst, ligand and B2pin2 without HBpin gave similar
results. Thus, HBpin was not used in the synthesis of 3 and 5. See refs 13b
and 14b and Supporting Information
(22) Beck, E. M.; Hatley, R.; Gaunt, M. J. Angew. Chem., Int. Ed. 2008,
47, 3004
.
.
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