Rapid solid-phase synthesis of oligo(1,4-phenylene ethynylene)s by a divergent/convergent tripling strategy [9]

Full text of DOI:10.1021/ja984138h

4908
J. Am. Chem. Soc. 1999, 121, 4908-4909
was determined by cleaving the alcohol from the resin using PPTS
in 1:1 n-butanol/1,2-dichloroethane at 80 °C.8 Compound 5 (0.48
mequiv of 1/g) was subjected to Pd/Cu-catalyzed coupling
conditions9 with monomer 2 to afford the polymer-supported
trimer 6 that was deprotected to yield polymer-supported trimer
7. Attempts to generate 7 directly from 5 and 1,4-diethynylben-
zene failed, possibly due to rapid homocoupling of 1,4-diethy-
nylbenzene with trace oxygen present. Compound 7 was then
cross-coupled with 3 (5-6 mol of 3 per mol of 7) to afford
polymer-supported pentamer 8. Excess 3 was easily recovered
by filtration. One portion of 8 was coupled with 2 to produce the
polymer-supported heptamer 9 that was then desilylated to afford
polymer-supported heptamer 10. The remaining portion of
polymer-supported pentamer 8 was treated with acid to liberate
pentamer 11. Treatment of 10 with the liberated pentamer 11 (6-8
mol of 11 per mol of 10) under Pd/Cu cross-coupling conditions
(23 °C for 24 h, then 60-70 °C for 24 h) afforded the polymer-
supported 17-mer 12. Directly heating the mixture of 10 and 11
caused a much lower yield, possibly due to decomposition of the
polymer-supported R,ω-diyne 10. Recovery of excess 11 was
simply achieved by filtration from the beads, followed by passage
through silica gel. Finally, treatment of 12 with acid liberated
the 120-Å long 17-mer 13.10 The overall yield was 20% for the
seven-step sequence from 5.11
Rapid Solid-Phase Synthesis of Oligo(1,4-phenylene
ethynylene)s by a Divergent/Convergent Tripling
Strategy
Shenlin Huang and James M. Tour*,†
Department of Chemistry and Biochemistry
UniVersity of South Carolina
Columbia, South Carolina 29208
ReceiVed December 2, 1998
The preparation of large conjugated molecules of precise length
and constitution has attracted much interest recently.1 These
compounds can serve as models for the analogous bulk polymers,
and they can be used for the construction of nanoarchitectures
such as molecular wires and molecular-scale electronic devices.1,2
We and others previously used convergent/divergent doubling
methodologies for oligomer growth where the iodide portions
needed masking as diethyltriazenyl or bromide groups.3 We report
here a new method for the preparation of oligo(1,4-phenylene
ethynylene)s that more than triples the molecular length with each
iteration and avoids the masking and unmasking steps often
required for aryl iodides.
The syntheses of the three monomers were performed as shown
in eqs 1-3.4-7
Completion of each polymer-supported reaction step was
determined by FTIR analysis of the polymer-bound substrate.3b,d,12
Polymer-supported material was mixed with oven-dried KBr and
ground to a powder, and an FTIR spectrum was acquired from
the formed pellet. Absorptions at 3290 cm-1 (strong) and 2110
cm-1 (weak) are characteristic of the terminal alkynyl carbon-
hydrogen and carbon-carbon stretches, respectively, and a strong
absorption at 2150 cm-1 is characteristic of the carbon-carbon
stretch of the trimethylsilyl-terminated alkyne. As expected, we
observed that the coupling reaction of a polymer-supported aryl
diiodide with 2 was accompanied by the appearance of the 2150
cm-1 absorption. The trimethylsilyl removal step was confirmed
by the appearance of the 3290 cm-1 band and the diminution of
the 2150 cm-1 band. The coupling reaction of a polymer-
supported R,ω-dialkyne with aryl diiodide was accompanied by
The solid-phase iterative divergent/convergent synthetic ap-
proach is outlined in Scheme 1. 2-(Hydroxymethyl)-3,4-dihydro-
2H-pyran was coupled to Merrifield’s resin (1.0 mequiv of Cl/g,
2% DVB cross-linked, 200-400 mesh, Aldrich) in dimethylac-
etamide at room temperature to afford the dihydropyran-modified
resin 4.8 Compound 1 was then attached to 4 through the hydroxyl
group using PPTS in dichloroethane to afford 5. The loading level
3b,d,12
the disappearance of the 3290 cm-1 band.
While pentamer 11 afforded molecular ions by direct exposure
via electron impact mass spectrometry (MS), neither this ioniza-
(9) Suffert, J.; Ziessel, R. Tetrahedron Lett. 1991, 32, 757. (b) Sonagashira,
K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975, 4467. (c) Stephens, R.
D.; Castro, C. E. J. Org. Chem. 1963, 28, 3313.
† Current address: Rice University, Center for Nanoscale Science and
Technology, P.O. Box 1892, MS-222, Houston TX 77251.
(1) (a) Tour, J. M. Chem. ReV. 1996, 96, 537. (b) Mu¨ller, M.; Ku¨bel, C.;
Mu¨llen, K. Chem. Eur. J. 1998, 4, 2099.
(10) Compound 13 (310 mg yielding scale): FTIR (KBr) 3418, 2924, 2854,
1727, 1601, 1514, 1463, 1378, 1273, 1177, 1121, 1071, 894, 833, 721, 694
cm-1. 1H NMR (400 MHz, CDCl3) δ 7.62 (s, 2 H), 7.49 (br s, 34 H), 7.36 (br
s, 14 H), 3.65 (br t, J ) 6.4 Hz, 12 H), 2.81 (m, 36 H), 1.8-1.2 (m, 282 H),
0.85 (m, 36 H). 13C NMR (100 MHz, CDCl3) δ 142.19, 141.87, 139.38, 132.32,
132.25, 131.29, 123.00, 122.46, 94.22, 93.97, 93.81, 93.72, 90.48, 90.40, 90.28,
90.21, 64.20, 34.25, 34.15, 32.77, 32.04, 30.78, 30.45, 29.81, 29.78, 29.75,
29.67, 29.48, 25.73, 22.82, 14.27. λabs (CH2Cl2) 385 nm, ꢀ (THF) ) 1.1 ×
105. λemis (CH2Cl2, excitation at 385 nm) 415 nm. These assignments correlate
well with oligo(phenylene ethynylene)s previously synthesized.3 The initial
polydispersity index of 13 was 1.2, and all spectra were recorded at that purity
level. Preparative TLC on a portion was used to sharpen the index to 1.06.
(11) The overall yields of the final 17-mer 13 was determined by comparing
the loading of the monomer 1 on the polymer support (compound 5) and the
yield of the final oligomer when liberated from the polymer support: 5 (10.0
g, 4.8 mmol of loading of 1) f 6 (10.5 g) f 7 (10.3 g) f 8 (13.9 g) of
which only a 7.2% mass portion (1.00 g) was taken on in the polymer-
supported form f 9 (1.03 g) f 10 (0.98 g) f 12 (1.30 g) f 13 (0.31 g,
0.069 mmol). Starting from 4.8 mmol of 1 in 5 and using only 7.2% mass of
the material during the conversion of 8 f 9, gives a theoretical yield of 0.35
mmol and an actual yield of 0.069 mmol (20%) for 13.
(2) (a) Zhou, C.; Deshpande, M. R.; Reed, M. A.; Jones, L., II; Tour, J.
M. Appl. Phys. Lett. 1997, 71, 611. (b) Reinerth, W. A.; Jones, L., II; Burgin,
T. P.; Zhou, C.-W.; Muller, C. J.; Deshpande, M. R.; Reed, M. A.; Tour, J.
M. Nanotechnology 1998, 9, 246. (c) Tour, J. M.; Kozaki, M.; Seminario, J.
M. J. Am. Chem. Soc. 1998, 120, 8486. (d) Cygan, M. T.; Dunbar, T. D.;
Arnold, J. J.; Bumm, L. A.; Shedlock, N. F.; Burgin, T. P.; Jones, L., II;
Allara, D. L.; Tour, J. M.; Weiss, P. S. J. Am. Chem. Soc. 1998, 120, 2721.
(3) For routes to oligo(phenylene ethynylene)s, see: (a) Zhang, J.; Moore,
J. S. Angew. Chem., Int. Ed. Engl. 1992, 31, 922. (b) Young, J. K.; Nelson,
J. C.; Moore, J. S. J. Am. Chem. Soc. 1994, 116, 10841. (c) Godt, A.; Ziener,
U. J. Org. Chem. 1997, 62, 6137. (d) Jones, L., II; Schumm, J. S.; Tour, J.
M. J. Org. Chem. 1997, 62, 1388. (e) Schumm, J. S.; Pearson, D. L.; Tour,
J. M. Angew. Chem., Int. Ed. Engl. 1994, 33, 1360. For routes to oligo-
(thiophene ethynylene)s see: (f) Pearson, D. L.; Tour, J. M. J. Org. Chem.
1997, 62, 1376. (g) Pearson, D. L.; Schumm, J. S.; Tour, J. M. Macromolecules
1994, 27, 2348.
(4) Kumada, M.; Tamao, K.; Sumitani, K. Org. Synth. 1978, 58, 127.
(5) Suzuki, H.; Nakamura, K.; Goto, R. Bull. Chem. Soc. Jpn. 1966, 39,
128.
(12) Polymer-Supported Reactions in Organic Synthesis; Hodge, P.,
Sherrington, D. C., Eds.; Wiley: New York, 1980. (b) Yan, B.; Kumaravel,
G.; Anjaria, H.; Wu, A.; Petter, R. C.; Jewell, C. F., Jr.; Wareing, J. R. J.
Org. Chem. 1995, 60, 5736. (c) Grindley, T. B.; Johnson, D. F.; Katritzky,
A. R.; Keogh, H. J.; Thirkettle, C.; Topsom, R. D. J. Chem. Soc., Perkin
Trans. 2 1974, 3, 282. (d) Hodge, P. Chem. Soc. ReV. 1997, 26, 417.
(6) Weingarten, M. D.; Padwa, A. Tetrahedron Lett. 1995, 36, 4717.
(7) Takahashi, S.; Kuroyama, Y.; Sonagashira, K.; Hagihara, N. Synthesis
1980, 627.
(8) Thompson, L. A.; Ellman, J. A. Tetrahedron Lett. 1994, 35, 9333.
10.1021/ja984138h CCC: $18.00 © 1999 American Chemical Society
Published on Web 05/07/1999

Communications to the Editor
J. Am. Chem. Soc., Vol. 121, No. 20, 1999 4909
Scheme 1a
a Reagents: a. Pd(dba)2, PPh3, and CuI (5 mol %, 10 mol %, and 5 mol %, respectively, per iodide atom), Et2NH/THF (1:4). b. TBAF, THF. c. PPTS,
n-C4H9OH, ClCH2CH2Cl.
tion method nor FAB or electrospray MS sufficed for obtaining
a molecular ion of 17-mer 13. To obtain MS data on 13, it was
necessary to use matrix-assisted laser desorption/ionization mass
spectrometry (MALDI-MS) using R-cyano-4-hydroxycinnamic
acid matrix in positive ion mode. MALDI-MS of 13 afforded a
peak that was 254 amu lower than the actual molecular weight
of 13, corresponding to the molecular ion minus the two iodides.
Size-exclusion chromatography (SEC) was conducted after
benchtop chromatography on the obtained oligomers. The number
average molecular weight (Mn) values of rigid rod oligomers
should be significantly inflated relative to the randomly coiled
polystyrene standards.1a As expected, the Mn values of the
pentamer 11 (Mn ) 2200, PDI ) 1.18, actual molecular weight
) 1576), and 17-mer 13 (Mn ) 8000, PDI ) 1.06, actual
molecular weight ) 4468) were much greater than the actual
molecular weights. Additionally, SEC on a crude reaction mixture
was used to determine whether polymerization or oligomerization
could ensue using this synthetic protocol.12d The heptamer on 9
was cleaved from the polymer support, and the crude material
was analyzed. As expected, the site isolation inhibited polymer-
ization. However, in addition to the expected heptamer derived
from 9 (Mn ) 2700, PDI ) 1.01), there was an equal area
broadened peak at slightly higher molecular weight which likely
arose from undesired oligomer formation. This could have arisen
from several inter-site interactions along the synthetic sequence,
for example, coupling of 7 with 8 followed by capping with 2.
Therefore, although this technique inhibits polymer formation,
the conformational flexibility of Merrifield resin does not allow
the functionalized sites to be exclusively isolated from each other.
We may be able to overcome this problem in the future by using
a lower degree of loading and a more rigid matrix through higher
DVB cross-link levels.12d Additionally, although the final yield
of the 17-mer 13 was relatively high for the size of the oligomer
formed, using a more suitable polymer support would likely
provide higher yields and higher purities of the final products by
permitting definitive site isolation.
Acknowledgment. Financial support from the Office of Naval
Research and the Defense Advanced Research Projects Agency is
gratefully acknowledged. We thank FAR Research Inc. (Dr. I. Chester)
for a gift of trimethylsilylacetylene, FMC for a gift of alkyllithium
reagents, and Dr. Kevin Schey for obtaining the MALDI-MS data.
JA984138H