Convenient iterative synthesis of an octameric tetracarboxylate-functionalized oligophenylene rod with divergent end groups

Article abstract of DOI:10.1021/ol000204k

(matrix presented) Oligo(p-phenylene) rigid rod 10 is synthesized via a functional group-tolerant molecular doubling approach. Preparative chromatographic methods, protecting groups, boronic acid isolations, and Grignard or organolithium reagents are not used. The convenient synthesis of well-defined, polar-functionalized oligophenylene rigid rods could afford ready access to a variety of useful electronic organic materials.

Full text of DOI:10.1021/ol000204k

ORGANIC
LETTERS
2000
Vol. 2, No. 20
3201-3204
Convenient Iterative Synthesis of an
Octameric
Tetracarboxylate-Functionalized
Oligophenylene Rod with Divergent End
Groups
Mark W. Read, Jorge O. Escobedo, Douglas M. Willis, Patricia A. Beck, and
Robert M. Strongin*
Department of Chemistry, Louisiana State UniVersity, Baton Rouge, Louisiana 70803
rob.strongin@chem.lsu.edu
Received July 28, 2000
ABSTRACT
Oligo(p-phenylene) rigid rod 10 is synthesized via a functional group−tolerant molecular doubling approach. Preparative chromatographic
methods, protecting groups, boronic acid isolations, and Grignard or organolithium reagents are not used. The convenient synthesis of
well-defined, polar-functionalized oligophenylene rigid rods could afford ready access to a variety of useful electronic organic materials.
Well-defined conjugated oligomers are of current interest as
nondefected structures for catalysis and electronic device
fabrication, as models for property and characterization
studies of their larger polymeric congeners, and as compo-
nents of large-pocketed organic crystals.1 These latter as well
as related applications have inspired creative synthetic
strategies and important property studies of a variety of
conjugated oligomeric materials.1,2 Oligo(p-phenylene)s are
an important class of conjugated redox and chromophore
materials that have found use, for example, as chain-
stiffening building blocks in semiflexible polymers such as
polyimides and aromatic polyesters and as models for rodlike
polyaromatic and liquid crystalline materials.3 More recently,
oligophenylenes have been transformed to planarized ladder-
type materials2h,4 and relatively large polycyclic aromatic
hydrocarbons5 as well as novel macrocycles.6 Oligo(p-
phenylene)s have also led to the discovery of a new mode
of biomembrane recognition and depolarization7 as well as
fascinating biomimetic barrel-like folds,8 ion channels9 and
amphiphilic materials10 which form via supramolecular
preorganization.
A barrier toward the realization of the full potential of
soluble oligo(p-phenylene)s is their challenging synthesis,
(3) First efficient palladium-catalyzed synthesis of relatively long oli-
gophenylene rods and references on earlier property studies, see: Galda,
P.; Rehahn, M. Synthesis 1996, 614.
(4) Grimme, J.; Scherf, U. Macromol. Chem. Phys. 1997, 197, 2297.
(5) Muller, M.; Iyer, V. S.; Kubel, C.; Enkelmann, V.; Mullen, K. Angew.
Chem, Int. Ed. Engl. 1997, 36, 1607.
(6) (a) Hensel, V.; Lu¨tzow, K.; Jacob, J.; Gessler, K.; Saenger, W.;
Schlu¨ter, A.-D. Angew. Chem, Int. Ed. Engl. 1997, 36, 2654. (b) Hensel,
V.; Schlu¨ter, A. D. Eur. J. Org. Chem. 1999, 451. (c) Iyoda, M.; Kondo,
T.; Nakao, K.; Hara, K.; Kuwatani, Y.; Yoshida, M.; Matsuyama, H. Org.
Lett. 2000, 2, 2081, and references cited therein.
(1) Reviews: (a) Tour, J. M. Chem. ReV. 1996, 96, 537. (b) Mullen K.;
Wegner G. AdV. Mater. 1998, 10, 433. (c) Martin, R. E.; Diederich, F.
Angew. Chem., Int. Ed. 1999, 38, 1350.
(2) Reviews: (a) Moore, J. S. Acc. Chem. Res. 1997, 30, 402. (b) Roncali,
J. Chem. ReV. 1997, 97, 173. (c) Feuerbacher, N.; Vogtle, F. Top. Curr.
Chem. 1998, 197, 1. (d) Berresheim, A. J.; Muller, M.; Mullen, K. Chem.
ReV. 1999, 99, 1747. (e) Kugler, T.; Logdlund, M.; Salaneck, W. R. Acc.
Chem. Res. 1999, 32, 225. (f) Gao, Y. L. Acc. Chem. Res. 1999, 32, 2:
247. (g) Schwab, P. F. H.; Levin, M. D.; Michl, J. Chem. ReV. 1999, 99,
1863. (h) Scherf, U. Top. Curr. Chem. 1999, 201, 163.
(7) Winum, J.-Y.; Matile, S. J. Am. Chem. Soc. 1999, 121, 7961.
(8) Baumeister, B.; Matile, S. J. Chem. Soc., Chem. Commun. 2000, 913.
(9) Baumeister, B.; Sakai, N.; Matile, S. Angew. Chem., Int. Ed. 2000,
39, 1955.
(10) Sidorov, V.; Douglas, T.; Dzekunov, S. M.; Abdallah, D.; Ghem-
bremariam, B.; Roepe, P. D.; Matile, S. J. Chem. Soc., Chem. Commun.
1999, 1429.
10.1021/ol000204k CCC: $19.00 © 2000 American Chemical Society
Published on Web 09/02/2000

Scheme 1
isolation, and purification.11 A recent major advance toward
and the final target are purified without preparative thin layer
or column chromatography.
well-defined, relatively long oligo(p-phenylene)s in multi-
gram amounts is based on repetitive growth strategies.12 As
part of our broader program which involves the discovery
of new palladium-catalyzed coupling reactions13 and the
creation of three-dimensional oligoaromatic architectures14
for optical and fluorescence bioanalytical sensing,15 we herein
describe the synthesis of the new oligo(p-phenylene) rigid
rod 10. Compound 10 possesses divergent end groups for
potential telechelic applications as well as readily intercon-
vertible carboxylate side groups. The molecular doubling
synthesis involves no formal protecting groups or organo-
lithium12a or Grignard chemistry.12b Each synthetic transfor-
mation is thus tolerant of pendant polar functional groups.
The potentially troublesome isolation and characterization
of aryl boronic acids16 is avoided. All of the intermediates
The synthesis of 10 (Scheme 1) begins with the Suzuki
coupling17 of methyl ester 118 (20 g, 0.0722 mol) to
commercially available 4-bromophenylboronic acid 2 (16.0
g, 0.080 mol) in the presence of K2CO3 (22.5 g, 0.163 mol)
and Pd(PPh3)4 (1.99 g, 1.72 mmol) in anhydrous MeOH
deoxygenated by purging with N2. The reaction mixture is
heated at 60 °C for 12 h under N2. After filtration through
Celite, concentration of the filtrate, extraction, and removal
of the solvent in vacuo, the residue is dissolved in CH2Cl2
and passed through a short silicagel plug to afford biaryl 3
(19.8 g), after drying, in 89.7% yield.19 Compound 3 (3.02
g, 0.99 mmol) is transformed to the corresponding iodide
upon dissolution in anhydrous PhH in the presence of I2 (1.51
g, 5.94 mmol) and t-BuONO (90%, 1.40 mL, 10.6 mmol) at
0 °C.20 After warming to 60 °C for 10 min, H2O is added
and the reaction mixture is extracted, dried, and concentrated.
(11) The difficulties associated with the synthesis of multiply substituted
phenylenes have been very recently noted: Robert, F.; Winum, J.-Y.; Sakai,
N.; Gerard, D.; Matile, S. Org. Lett. 2000, 2, 37.
(12) (a) Liess, P.; Hensel, V.; Schlu¨ter, A.-D. Liebigs Ann. 1996, 1037.
(b) A very different large scale synthesis of a sexiphenyl rod has also been
reported: Kauffman, J. M. Synthesis 1999, 6, 918.
(13) For example, the cross-coupling of aniline-derived aryldiazonium
tetrafluoroborate salts with arylboronic esters: Willis, D. M.; Strongin, R.
M. Tetrahedron Lett. 2000, 41, 6271.
(14) (a) Lewis, P. T.; Davis, C. J.; Saraiva, M.; Treleaven, D.; McCarley,
T.; Strongin, R. M. J. Org. Chem. 1997, 62, 6110. (b) Lewis, P. T.; Strongin,
R. M. J. Org. Chem. 1998, 63, 6065.
(15) (a) Davis, C. J.; Lewis, P. T.; McCarroll, M. E.; Read, M. W.; Cueto,
R.; Strongin, R. M.Org. Lett. 1999, 1, 331. (b) Lewis, P. T.; Davis, C. J.;
Cabell, L. A.; He, M.; Read, M. W.; McCarroll, M. E.; Strongin, R. M.
Org. Lett. 2000, 2, 589.
(16) Hensel, V.; Schlu¨ter, A.-D. Liebigs Ann. 1997, 303.
(17) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457.
(18) Synthesis: Venuti, M. C.; Stephenson, R. A.; Alvarez, R.; Bruno,
J. J.; Strosberg, A. M. J. Med. Chem. 1988, 31, 2136.
1
(19) Data for 3: mp 138-139 °C. H NMR (CDCl3): δ 3.91 (s, 3H),
5.88 (bs, 2H), 6.78 (d, J ) 8.56 Hz, 1H), 7.40 (d, J ) 8.63 Hz, 2H), 7.51
(d, J ) 8.59 Hz, 2H), 7.51 (dd, J ) 2.31, 8.62 Hz, 1H), 8.09 (d, J ) 2.28
Hz, 1H). 13C NMR (CDCl3): δ: 51.3, 110.8, 117.2, 120.4, 127.7, 129.3,
131.7, 132.5, 139.3, 149.9. HRMS m/z calcd for C14H12BrNO2: 305.0051,
found 305.0063.
(20) For a highly useful alternative for transforming anilines to aryl
iodides, see: Moore, J. S.; Weinstein, E. J.; Wu, Z. Y. Tetrahedron Lett.
1991, 32, 2465.
3202
Org. Lett., Vol. 2, No. 20, 2000

The residual solid is triturated with hexanes to afford iodide
4 (3.18 g) in 77.9% yield.21 Compound 3 (3.02 g, 9.86 mmol)
is converted to boronate ester 6 via dissolution in a solution
of anhydrous, deoxygenated DMF along with commercially
available bis(pinacolato)diboron 5 (2.81 g, 11.1 mmol),
KOAc (3.24 g, 33.0 mmol), and PdCl2(dppf) (0.163 g, 0.290
mmol).22 The mixture is heated at 60 °C for 12 h under N2,
filtered through Celite, extracted, and dried. The solid is
redissolved in CH2Cl2 and filtered through a short silicagel
plug, dried, triturated with hexanes, and dried again to furnish
biarylboronate 6 (3.17 g) in 91.5% yield.23
Tetrameric p-phenylene 7 is afforded via the coupling of
4 (3.00 g, 7.19 mmol) and 6 (2.80 g, 7.93 mmol) which are
dissolved in a deoxygenated 4:1 DMF/H2O solution heated
to 60 °C for 12 h under N2 in the presence of K2CO3 (2.09
g, 15.1 mmol) and Pd(PPh3)4 (0.249 g, 0.216 mmol). After
filtration, concentration of the filtrate, extraction, and drying,
the residual solid is redissolved in CH2Cl2 and passed through
a silica gel plug to afford 7 (1.44 g, 38.8%) after drying.24
Compound 7 (0.300 g, 0.582 mmol) and I2 (0.092 g, 0.36
mmol) are dissolved in anhydrous PhH. t-BuONO (90%, 1.40
mL, 10.6 mmol) is added to the solution cooled to 0 °C.
The solution is warmed to rt, stirred for 12 h, and heated at
60 °C for 10 min. After H2O addition, the reaction mixture
is extracted, dried, and concentrated. The residual solid is
triturated with hexanes to afford iodide 8 (0.364 g, 89.3%).25
The corresponding boronate 9 is synthesized by dissolving
7 (0.603 g, 1.17 mmol), 5 (0.370 g, 1.45 mmol), KOAc
(0.478 g, 4.87 mmol), and PdCl2(dppf) (0.037 g, 0.067 mmol)
in anhydrous DMF deoxygenated by purging with N2. The
solution is heated at 60 °C for 12 h under N2 and cooled,
the mixture is filtered, and the filtrate is concentrated,
extracted, and dried. The residue is redissolved in CH2Cl2
and filtered through a silica gel plug and dried to afford 9
(0.702 g, 97.4%).26
To overcome potential solubility problems anticipated for
longer phenylenes, we functionalized the tetrameric boronate
with a lauryl moiety. Compound 9 (0.477 g, 0.85 mmol),
di-tert-butylpyridine (0.25 mL, 1.25 mmol), and lauroyl
chloride (0.26 mL, 1.12 mmol) are dissolved in CH2Cl2 at 0
°C, warmed to rt, and stirred for 12 h. After extraction, the
crude amide is directly coupled to iodide 8.
The lauryl amide of 9 (0.589 g, 0.79 mmol), compound 8
(0.408 g, 0.650 mmol), K2CO3 (0.226 g, 1.64 mmol), and
Pd(PPh3)4 (0.032 g, 0.0278 mmol) are mixed in DMF, and
the solution is deoxygenated and heated at 60 °C for 12 h
under N2. The solution is filtered, the filtrate is concentrated,
and the solid is washed with H2O and MeOH, dissolved in
10% MeOH in CH2Cl2, and filtered through a short silicagel
plug to afford 0.309 g (42.5%) of octamer 10 in overall
10.1% yield from 1.27
In conclusion, we have efficiently synthesized a highly
functional octameric oligo(p-phenylene) using a molecular
doubling approach. Transesterification of the side groups to,
for instance, glycolate esters at the tetramer stage or earlier
should allow the repetitive scheme to continue without end
group functionalization with a solubilizing moiety, thereby
affording longer rigid rods if needed.28 Decarboxylation to
remove the side groups would furnish novel telechelic rigid
rod phenylenes with unsubstituted repeat units. The use of
5 in this scheme also allows for further synthetic streamlining
via the application of one-pot arylborylation/cross-coupling
methods.22c Further successful synthetic transformations and
the incorporation of new rigid rod oligo(p-phenylene)s into
unique, well-defined nanoscale oligoaromatic architectures
has now also been achieved in our laboratory and will be
reported in due course.
Acknowledgment. We gratefully acknowledge the Ar-
nold and Mabel Beckman Foundation for support through
the Beckman Young Investigator program. J.O.E. thanks the
Fulbright Foundation and Conacyt for generous graduate
fellowship support. D.M.W. thanks the Graduate Education
for Minorities (GEM) and Huel Perkins Foundations as well
as Procter and Gamble and Louisiana State University for
generous graduate fellowships. P.A.B. thanks the Louisiana
(21) Data for 4: mp 99.5-101 °C. 1H NMR (CDCl3): δ: 3.96 (s, 3H),
7.33 (dd, J ) 2.26, 8.25 Hz, 1H), 7.44 (d, J ) 8.38 Hz, 2H), 7.58 (d, J )
8.41 Hz, 2H), 7.98 (d, J ) 2.32 Hz, 1H), 8.05 (d, J ) 8.25 Hz, 1H). 13C
NMR (CDCl3): δ: 52.6, 93.0, 122.5, 128.4, 129.3, 130.8, 132.1, 135.6,
138.0, 140.0, 141.9, 156.8. HRMS m/z calcd for C14H10BrIO2: 415.8909,
found 415.8914.
(22) (a) Ishiyama, T.; Murata, M.; Miyaura, N. J. Org. Chem. 1995, 60,
7508. (b) Ishiyama, T.; Itoh, Y.; Kitano, T.; Miyaura, N. Tetrahedron Lett.
1997, 38, 3447. (c) Arylboronates from diboron pinacol used in one-pot
cross-coupling reactions: Giroux, A.; Han, Y. X.; Prasit, P. Tetrahedron
Lett. 1997, 38, 3841.
(26) Data for 9: 1H NMR (CDCl3): δ: 1.26 (s, 12H), 3.71 (s, 3H),
3.92 (s, 3H), 6.79 (d, J ) 8.52 Hz, 1H), 7.40 (d, J ) 8.28 Hz, 2H), 7.49 (d,
J ) 7.98 Hz, 1H), 7.61 (d, J ) 8.25 Hz, 2H), 7.62 (dd, J ) 2.28, 8.48 Hz,
1H), 7.68 (d, J ) 8.10 Hz, 2H), 7.78 (dd, J ) 1.99, 8.00 Hz, 1H), 7.92 (d,
J ) 8.51 Hz, 2H), 8.09 (d, J ) 1.93 Hz, 1H), 8.20 (d, J ) 2.24 Hz, 1H).
13C NMR (CDCl3): δ: 24.9, 51.7, 52.2, 83.9, 111.2, 117.5, 125.9, 126.3,
127.1, 128.5, 128.8, 128.9, 129.0, 129.5, 129.9, 131.3, 132.7, 135.4, 139.0,
139.3, 139.9, 141.1, 142.2, 149.4, 168.5, 169.2. HRMS m/z calcd for C34H34-
BNO6: 563.2479, found 563.2488.
1
(23) Data for 6: mp decomposed at 157.9-159 °C. H NMR (CDCl3):
δ: 1.29 (s, 12H), 3.84 (s, 3H), 6.71 (d, J ) 8.55 Hz, 1H), 7.48 (d, J ) 8.24
Hz, 2H), 7.54 (dd, J ) 2.27, 8.49 Hz, 1H), 7.78 (d, J ) 8.24 Hz, 2H), 8.09
(d, J ) 2.23 Hz, 1H). 13C NMR (CDCl3): δ: 24.9, 51.7, 83.7, 111.2, 117.5,
125.4, 129.5, 129.6, 132.9, 135.3, 142.9, 149.2, 168.5. HRMS m/z calcd
for C20H24BNO4: 353.1798, found 353.1780.
(24) Data for 7: mp decomposed at 192-195 °C. 1H NMR (CDCl3):
δ: 3.64 (s, 3H), 3.85 (s, 3H), 6.72 (d, J ) 8, 54 Hz, 1H), 7.30-7.57 (m,
10H), 7.66 (dd, J ) 2.06, 8.03 Hz, 1H), 7.95 (d, J ) 1.96 Hz, 1H), 8.13 (d,
J ) 2.22 Hz, 1H). 13C NMR (CDCl3): δ: 51.7, 52.2, 111.4, 117.0, 122.1,
125.9, 127.2, 127.4, 128.3, 128.6, 128.8, 128.9, 129.5, 131.4, 131.9, 132.1,
132.8, 138.6, 138.9, 141.3, 168.5, 169.1. HRMS m/z calcd for C28H22-
BrNO4: 515.0732, found 515.0748.
(27) Data for 10: mp gels at 206-208 °C. 1H NMR (CDCl3): δ: 0.88
(t, J ) 6.85 Hz, 3H), 1.26 (m, 16H), 1.78 (p, J ) 7.12 Hz, 2H), 2.48 (t, J
) 7.32 Hz, 2H), 3.73 (s, 3H), 3.75 (s, 6H), 3.98 (s, 3H), 7.45-7.88 (m,
23H), 8.06 (d, J ) 1.92 Hz, 1H), 8.17 (d, J ) 1.74 Hz, 2H), 8.35 (d, J )
2.22 Hz, 1H), 8.86 (d, J ) 8.84 Hz, 1H), 11.01 (bs, 1H). 13C NMR
(CDCl3): δ: 14.1, 22.7, 25.6, 29.2, 29.3, 29.5, 29.6, 31.9, 38.8, 52.2, 52.4,
115.1, 120.9, 122.2, 126.4, 126.8, 127.6, 128.4, 128.6, 129.0, 129.1, 129.6,
129.8, 131.2, 131.4, 132.1, 133.1, 134.6, 138.6, 139.2, 139.8, 140.1, 140.4,
140.5, 140.9, 141.1, 168.8, 168.9, 172.4. HRMS m/z calcd for C68H64-
BrNO9: 1117.3764, found 1117.3748.
1
(25) Data for 8: mp 128-130 °C. H NMR (CDCl3): δ: 3.73 (s, 3H),
3.97 (s, 3H), 7.42 (d, J ) 8.29 Hz, 1H), 7.44 (d, J ) 8.21 Hz, 2H), 7.47 (d,
J ) 8.01 Hz, 1H), 7.52 (d, J ) 8.52 Hz, 3H), 7.60 (d, J ) 8.52 Hz, 2H),
7.64 (d, J ) 8.28 Hz, 2H), 7.73 (dd, J ) 2.02, 7.97 Hz, 1H), 8.06 (d, J )
8.02 Hz, 1H), 8.08 (dd, J ) 2.32, 8.68 Hz, 1H). 13C NMR (CDCl3): δ:
52.2, 52.5, 92.7, 122.2, 126.6, 128.3, 128.4, 128.6, 129.0, 129.5, 129.6,
131.0, 131.4, 132.1, 135.5, 137.9, 138.5, 139.2, 140.6, 140.7, 141.0, 141.8,
166.9, 168.7. HRMS m/z calcd for C28H20BrIO4: 625.9590, found 625.9587.
(28) For the properties of glycol-functionalized oligo(phenylene ethyn-
ylene), see, for example: Prince, R. B.; Saven, J. G.; Wolynes, P. G.; Moore,
J. S. J. Am. Chem. Soc. 1999, 121, 3114.
Org. Lett., Vol. 2, No. 20, 2000
3203

1
State Board of Regents for graduate fellowship support. We
also thank the Mass Spectrometry Service Laboratory at the
University of Minnesota and the Nebraska Center for Mass
Spectrometry at the University of Nebraska for acquiring
high resolution mass spectrometric data.
Supporting Information Available: H NMR spectra and
detailed experimental procedures for the preparation of 3,
4, and 6-10. This material is available free of charge via
the Internet at http://pubs.acs.org.
OL000204K
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