Reactivity of long conjugated systems: Selectivity of Diels-Alder cycloaddition in oligofurans

Article abstract of DOI:10.1021/ol202987e

Taking advantage of the synthetic availability and solubility of long oligofurans, their reactivity toward dienophiles was studied as a model for the rarely investigated reactivity of long conjugated systems. Unlike oligoacenes, the reactivity of oligofurans decreases or remains constant with increasing chain length. Terminal ring cycloadducts of oligofurans are kinetically and thermodynamically favored, whereas central ring cycloadducts are preferred in oligoacenes, because of the different driving forces in the two reactions: π-conjugation in oligofurans and aromatization/dearomatization in oligoacenes.

Full text of DOI:10.1021/ol202987e

ORGANIC
LETTERS
2012
Vol. 14, No. 2
502–505
Reactivity of Long Conjugated Systems:
Selectivity of DielsÀAlder Cycloaddition
in Oligofurans
Ori Gidron,† Linda J. W. Shimon,‡ Gregory Leitus,‡ and Michael Bendikov*,†
Department of Organic Chemistry and Department of Chemical Research Support,
Weizmann Institute of Science, Rehovot, 76100, Israel
michael.bendikov@weizmann.ac.il
Received November 19, 2011
ABSTRACT
Taking advantage of the synthetic availability and solubility of long oligofurans, their reactivity toward dienophiles was studied as a model for the
rarely investigated reactivity of long conjugated systems. Unlike oligoacenes, the reactivity of oligofurans decreases or remains constant with
increasing chain length. Terminal ring cycloadducts of oligofurans are kinetically and thermodynamically favored, whereas central ring
cycloadducts are preferred in oligoacenes, because of the different driving forces in the two reactions: π-conjugation in oligofurans and
aromatization/dearomatization in oligoacenes.
π-Conjugated systems, such as oligothiophenes and
oligoacenes, are the most important building blocks for
organic electronic materials.1 Despite recent interest in
these materials,2 very little is known about their reactivity.
The reactivity of these electron-rich compounds toward
dienophiles is of particular interest because it holds the key
to both their stability and their diverse chemistry. Acenes
become more reactive with increasing length: while ben-
zene is a very weak diene, pentacene undergoes DielsÀ
Alder (DA) cycloaddition readily.3 The poor stability of
higher acenes is a major impediment to the application of
acene-based compounds in electronic devices.
Although π-conjugated oligomers and polymers have
been known for a long time, studies of the reactivity of long
conjugated systems are rare.1,3b,4 The site selectivity prob-
lem associated with oligoenes was studied over 60 years
ago by Alder and Schumacher, who proposed that the
addition of maleic anhydride proceeds to the central
double bonds of an oligoene system.5 In the study of DA
addition of maleic anhydride to conjugated tetraene sys-
tems it was found that the addition is selective to the
terminal bonds.6 The initial growth of carbon nanotube
fragments by DA cycloaddition was also studied.7 Gaining
understanding and control of the reactivity of long con-
jugated systems is required for the future progress of the
whole field of organic electronic materials and will be an
important step toward understanding the reactivity of
conducting polymers.
† Department of Organic Chemistry.
‡ Department of Chemical Research Support.
€
€
(1) (a) Geerts, Y.; Klarner, G.; Mullen, K. In Electronic Materials:
The Oligomer Approach; M€ullen, K., Wagner, G., Eds.; Wiley-VCH:
Weinheim, 1998; Chapter 1. (b) Reynolds, J.; Skotheim, T. A. Handbook
of Conducting Polymers, 3rd ed.; CRC Press: Boca Raton, FL, 2007.
(2) (a) Perepichka, I. F. Perepichka, D. F. Handbook of Thiophene-
Based Materials; Wiley-VCH: Weinheim, Germany, 2009. (b) Fichou, D.
Handbook of Oligo- and Polythiophenes; Wiley-VCH: Weinheim,
The reaction of furan with maleimide is a classical
textbook reaction that was studied by Diels and Alder
(4) Petrukhina, M. A., Scott, L. T., Eds. Fragments of Fullerenes and
Carbon Nanotubes: Designed Synthesis, Unusual Reactions, and Coordi-
nation Chemistry; Wiley-VCH: Weinheim, 2011.
(5) Alder, K.; Schumacher, M. Liebigs Ann. Chem. 1950, 570, 178.
(6) Turner, C. I.; Paddon-Row, M. N.; Willis, A. C.; Sherburn, M. S.
J. Org. Chem. 2005, 70, 1154.
€
Germany, 1999. (c) Mishra, A.; Ma, C.-Q.; Bauerle, P. Chem. Rev. 2009,
109, 1141. (d) Perepichka, I. F.; Perepichka, D. F.; Meng, H.; Wudl, F.
€
Adv. Mater. 2005, 17, 2281. (e) Bauerle, P. In Electronic Materials: The
Oligomer Approach; M€ullen, K., Wagner, G., Eds.; Wiley-VCH: 1998;
Chapter 2.
(3) (a) Clar, E. Ber. Dtsch. Chem. Ges. 1939, 72, 1817. (b) Bendikov,
M.; Wudl, F.; Perepichka, D. F. Chem. Rev. 2004, 104, 4891.
(7) Fort, E. H.; Donovan, P. M.; Scott, L. T. J. Am. Chem. Soc. 2009,
131, 16006.
r
10.1021/ol202987e
Published on Web 01/11/2012
2012 American Chemical Society

more than 80 years ago8 and led to applications in many
fields, such as medicinal chemistry, dendrimer formation,9
self-healing polymers,10 etc. Recently, we prepared a series
of R-oligofurans consisting of up to 9 rings.11 Long
oligofurans have several advantages over the extensively
studied oligothiophenes, such as higher rigidity, better
solubility, better packing, and higher fluorescence. In
addition, we showed that oligofurans have mobilities in
Field Effect Transistors (FETs) that are similar to those of
the corresponding oligothiophenes.12À15
longer oligofurans as well: the reaction of 5F with
maleimide in dichlorobenzene at 150 °C proceeds selec-
tively to the terminal ring to yield 2b (Scheme 1; see also SI).
High temperature is required in order to fully dissolve 5F.
The terminal selectivity of oligofurans is in sharp contrast to
the selectivity of oligoacenes but similar to that of oligoenes
(the selectivity of oligoenes was studied for relatively short
systems, which have only four conjugated double bonds).6
In order to verify that the exclusive site selectivity in DA
cycloaddition is a result of electronic and not steric factors,
One of the greatest advantages of molecular semicon-
ductors is the potential for solution processing, which is
expected to reduce the cost of device fabrication consider-
ably. In this regard, several solution processable pentacene
precursors have been synthesized, where the soluble unit
can be thermally removed by retro DA reaction after
casting of the film.16 In order to apply similar processes
to long oligofurans, their DA reactivity should be investi-
gated. Here, we report a combined experimental and
computational study of the DA reactivity of conjugated
oligofurans, which importantly serves as a case study for
the reactivity and selectivity of long conjugated systems in
general.
Scheme 1. Reactions of 3F, DM-3F, and 5F with Maleimide
The reaction of terfuran (3F) and maleimide in ethyl
acetate proceeds at rt to yield the cycloadduct 1a, which in
turn aromatizes to the thermodynamic product 2a (Scheme 1).
Compound 1a was confirmed by X-ray crystallography as
the exo cycloadduct (Figure 1).17 The cycloaddition of 3F
with maleimide to produce 1a is reversible18 at rt: when the
isolated cycloadduct 1a is redissolved in acetone-d6, the
reverse reaction yields 3F and maleimide after several days
(see Supporting Information (SI)). Importantly, the pro-
ducts of cycloaddition to the central ring (3a and 4a)
were not observed. The same trend was observed for
(8) (a) Diels, O.; Alder, K. Ber. Dtsch. Chem. Ges. 1929, 62, 554.
(b) For review of DA reactions with furan, see: Kappe, O. C.; Murphree,
S. S.; Padwa, A. Tetrahedron 1997, 53, 14179.
(9) McElhanon, J. R.; Wheeler, D. R. Org. Lett. 2001, 3, 2681.
(10) Chen, X.; Dam, M. A.; Ono, K.; Mal, A.; Shen, H.; Nutt, S. R.;
Sheran, K.; Wudl, F. Science 2002, 295, 1698.
(11) Gidron, O.; Diskin-Posner, Y.; Bendikov, M. J. Am. Chem. Soc.
2010, 132, 2148.
(12) Gidron, O.; Dadvand, A.; Sheynin, Y.; Bendikov, M.; Perepichka,
D. F. Chem. Commun. 2011, 47, 1976.
(13) For highlight on oligofurans, see: Bunz, U. H. F. Angew. Chem.,
Int. Ed. 2010, 49, 5037.
Figure 1. ORTEP representation (50% elipsoid probability) of
1a (gray, carbon; red, oxygen; blue, nitrogen).
(14) For recent computational studies of oligofurans, see: (a) Huang,
J.-D.; Wen, S.-H.; Deng, W.-Q.; Han, K.-L. J. Phys. Chem. B 2011, 115,
2140. (b) Mohakud, S.; Alex, A. P.; Pati, S. K. J. Phys. Chem. C 2010,
114, 20436.
(15) For recent applications of bifuran and terfuran fragments in
solar cells and in OFETs, see: (a) Woo, C. H.; Beaujuge, P. M.;
methyl groups were introduced at the terminal positions of
3F, yielding dimethyl-terfuran (DM-3F) (Scheme 1; for
preparation of DM-3F, see SI). DM-3F was reacted with
maleimide in the same manner as described above for 3F.
The only observed product is 2c, which is the terminal
cycloadduct after aromatization. Thus, steric factors can
be ruled out in the selective terminal addition of dieno-
philes to oligofurans.
When 3F was reacted with 1 equiv of dimethylacetylene
dicarboxylate (DMAD) in ethyl acetate at rt overnight,
cycloadduct 5 was observed along with the aromatization
product 6(Scheme 2). Again, cycloaddition occurs exclusively
ꢀ
Holcombe, T. W.; Lee, O. P.; Frechet, J. M. J. J. Am. Chem. Soc.
2010, 132, 15547. (b) Bijleveld, J. C.; Karsten, B. P.; Simon, G. J. M.;
Wienk, M. M.; de Leeuw, D. M.; Janssen, R. A. J. J. Mater. Chem. 2011,
21, 1600. (c) Li, Y.; Sonar, P.; Singh, S. P.; Zeng, W.; Soh, M. S. J. Mater.
Chem. 2011, 21, 10829.
(16) (a) Brown, A. R.; Pomp, A.; Hart, C. M.; de Leeuw, D. M.;
€
Klassen, D. B. M.; Havinga, E. E.; Herwig, P.; Mullen, K. J. Appl. Phys.
1996, 79, 2136. (b) Afzali, A.; Dimitrakopoulos, C. D.; Breen, T. L.
J. Am. Chem. Soc. 2002, 124, 8812.
(17) The exo cycloadduct of the furan-maleimide reaction was pre-
viously shown to be thermodynamically more stable than the endo
conformation (although the endo is slightly preferred kinetically).
ꢁ ꢁ
^ ꢁ
Rulısek, L.; Sebek, P.; Havlas, Z.; Hrabal, R.; Capek, P.; Svatos, A.
´
J. Org. Chem. 2005, 70, 6295.
(18) Woodward, R. B. J. Am. Chem. Soc. 1940, 62, 1478.
Org. Lett., Vol. 14, No. 2, 2012
503

between M06-2X and B3LYP methods, and since the dif-
ferences between these two methods are large, we provide
the values for both methods. We believe that the most ac-
curate values should be somewhere in between the values
obtained at the M06-2X and B3LYP methods.
Scheme 2. Reaction of 3F with DMAD
Table 1. Calculated, at M06-2X/6-31G(d) (M06) and B3LYP/
6-31G(d) (B3L) Levels (in kcal/mol), Activation Energies (ΔE‡)
and Reaction Energies (ΔE) for the Cycloaddition of Maleimide
to Oligofurans (nF), Oligoacenes (nA), and Oligothiophenes
(nT) as well as to Dimethyl-terfuran, DM-3F (M) in Terminal
(ter.) and Central (cent.) Rings
Figure 2. ORTEP representation (50% elipsoid probability) of 7
(gray, carbon; red, oxygen).
in a terminal position. The use of 2 equiv of DMAD
(either in a one-pot reaction or via stepwise addition of 1
equiv followed by a second equivalent) resulted in a doubly
aromatized compound 7 where both additions proceeded
at the terminal rings. The crystal structure of 7 reveals a
completely planar structure with a conjugated backbone
(Figure 2). This reaction should be useful for the introduc-
tion of various substituted phenyl groups to furan oligo-
mers or for the synthesis of multisubstituted benzenes.19
Regioselectivity and reactivity as a function of chain
length in the reaction of oligofurans with maleimide were
studied using DFT calculations at the M06-2X/6-31G(d)
and B3LYP/6-31G(d) levels (Table 1 and Figures 3 and 4;
for benchmark calculations using different basis sets and
high level ab initio methods, see SI).20,21 For comparison,
similar computational studies were performed for oligoacenes
and oligothiophenes. Since benchmark studies are falling
(19) (a) Padwa, A.; Dimitroff, M.; Waterson, A. G.; Wu, T. J. Org.
ꢀ
ꢀ
Chem. 1997, 62, 4088. (b) Moreno, A.; Gomez, M. V.; Vazquez, E.; de la
Hoz, A.; Dıaz-Oritz, A.; Prieto, P.; Mayoral, J. A.; Pires, E. Synlett 2004,
7, 1259.
´
(20) All calculations were performed using Gaussian 09 software.
Frisch, M. J.; et al. Gaussian 09, revision A.02; Gaussian, Inc.:
Wallingford, CT, 2009. See Supporting Information for full reference.
(21) The B3LYP/6-31G(d) level was chosen since it is known to be a
reliable method for studying DA reactions (see Goldstein, E.; Beno, B.;
Houk, K. N. J. Am. Chem. Soc. 1996, 118, 6036), although this method is
also known to overestimate the activation barriers of a DA reaction by a
few kcal/mol, which is in agreement with our benchmark calculations.
The M06-2X/6-31G(d) level was chosen since it is known to reproduce
dispersion interaction in organic systems correctly, which is important
for studying the transition state of DA reactions (see Zhao, Y.; Truhlar,
D. Acc. Chem. Res. 2008, 41, 157).
Figure 3. Calculated (at M06-2X/6-31G(d), in kcal/mol; values
at B3LYP/6-31G(d) are given in parentheses) pathway for the
reaction of 3F and maleimide.
504
Org. Lett., Vol. 14, No. 2, 2012

7.2 kcal/mol at M06-2X (8.0 kcal/mol at B3LYP) higher
for 5T compared to 5F (Table 1).
In oligofurans, conjugation is the driving force of re-
activity. Since addition to the central ring leads to the
interruption of conjugation along the backbone it is dis-
favored. In oligoacenes, aromaticity is the driving force of
reactivity and addition to the central ring leads to the
formation of two aromatic subunits (e.g., addition to the
central ring of pentacene leads to two naphthalene subunits).
Importantly, since conjugation in oligofurans increases
with chain length, long oligofurans are not more reactive
than shorter ones, while the reactivity of oligoacenes in-
creases strongly with chain length.
Figure 4. Activation energies (at B3LYP/6-31G(d)) of DielsÀ
Alder reactions between oligofurans (nF) or oligacenes (nA) and
maleimide at terminal and central rings.
In summary, the reactivity of oligofurans toward dieno-
philes was studied (experimentally and computationally)
as a test case of the reactivity of long conjugated systems.
Terminal ring cycloadducts of oligofurans are kinetically
and thermodynamically favored. We find that the reactivity
of oligofurans decreases or remains constant with increasing
chain length, which is the reverse of the trend known for
oligoacenes. We have shown that the factors underlying
this selectivity are electronic and not steric. These results are
explained by the different reaction driving forces: aromatiza-
tion/dearomatization in oligoacenes and π-conjugation in
oligofurans. The fact that the reactivity of oligofurans
remains constant with increasing chain length is related to
their high conjugation and has important implications for
understanding the chemical stability of long conjugated
polymers.1b,2a We have shown that the reactivity of long
conjugated systems occurs preferably at their terminals,
and this should contribute in many cases to the increased
stability of conjugated polymers compared to correspond-
ing conjugated oligomers. According to the computational
results, in reactions with dienophiles, oligothiophenes show
similar selectivity to oligofurans, while they have signifi-
cantly lower reactivity. The reaction of oligofurans with
both maleimide and DMAD leads to subsequent aromatiza-
tion and can be used as a method for the synthesis of multi-
substituted benzenes, as well as oligofurans connected to
substituted phenyl rings. This study, which is the first
conducted on the DielsÀAlder reactivity of long conjugated
oligomers, can serve as a model system for the reactivity and
stability of conjugated oligomers and polymers.
As an example, the activation energy (ΔE‡) and reaction
energy (ΔE) for the reaction of 3F with maleimide are
shown in Figure 3. Terminal cycloaddition is both kineti-
cally and thermodynamically preferred over cycloaddition
to the central ring, with an activation energy difference of
ΔΔE‡ = 2.5 kcal/mol and reaction energy difference of
ΔΔE = 4.3 kcal/mol at the M06-2X level. Terminal cyclo-
addition preference is significantly larger at the B3LYP level
(ΔΔE‡ = 6.8 kcal/mol, ΔΔE = 7.6 kcal/mol). Similar
results are obtained for the reaction of DM-3F and malei-
mide, with ΔΔE‡ = 2.6 kcal/mol and ΔΔE = 4.8 kcal/mol at
M06-2X and ΔΔE‡ = 4.5 kcal/mol and ΔΔE = 6.1 kcal/mol
at B3LYP. The computational results support the selectivity
observed in the experiments described above.
The reactivity trends (such as the chain length depen-
dence of reactivity and cycloaddition position) of oligo-
furans differ significantly from those of oligoacenes (Table 1
and Figure 4) and are similar to those of oligothiophenes
(although oligofurans generally have a higher reactivity
toward DA cycloaddition than oligothiophenes).22 While
the activation energy for the cycloaddition of oligoacenes
significantly decreases with increasing acene length (from
25.1 kcal/mol for benzene to 2.9 kcal/mol for cycloaddition
to the central ring of pentacene at M06-2X; corresponding
values at B3LYP are 36.6 and 15.9 kcal/mol), the activation
energy for oligofuran cycloaddition slightly increases from
1F to 2F and practically does not change for longer oligo-
mers. For oligoacenes, cycloaddition to the central ring is
preferred significantly over terminal ring cycloaddition; for
example, the difference between cycloaddition to the termi-
nal and central ring of pentacene is 11.5 kcal/mol at M06-
2X and 9.8 kcal/mol at B3LYP. The opposite trend is
observed for oligofurans, with a difference of 2.6 kcal/mol
at M06-2X (7.6 kcal/mol at B3LYP) in favor of terminal
cycloaddition over central ring cycloaddition for 5F. For
oligothiophenes, such as quinquethiophene 5T, terminal
ring cycloaddition is preferred over central ring cycloaddition
by 2.0 and 7.3 kcal/mol for M06-2X and B3LYP respectively,
while the activation energy for terminal cycloaddition is
Acknowledgment. We thank Dr. Dennis Sheberla
(Weizmann Institute) for help with benchmark calcula-
tions and the MINERVA Foundation and the Helen and
Martin Kimmel Center for Molecular Design for financial
support. M.B. is the incumbent of the Recanati career
development chair and a member ad personam of the Lise
Meitner-Minerva Center for Computational Quantum
Chemistry.
Supporting Information Available. Experimental proce-
dure, spectral data, X-ray structural data, CIF files, absolute
energies and XYZ coordinates at different levels of theory
for all calculated stationary points, and the coordinates of
their optimized structures. This material is available free of
charge via the Internet at http://pubs.acs.org.
(22) For computational work comparing the DA reactivity between
parent furan and thiophene, see: Dinadayalane, T. C.; Vijaya, R.;
Smitha, A.; Sastry, G. N. J. Phys. Chem. A 2002, 106, 1627–1633.
Org. Lett., Vol. 14, No. 2, 2012
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