Synthesis and reactivity of anthracenyl-substituted arenediynes

Article abstract of DOI:10.1016/j.tetlet.2015.01.011

Cyclization reaction pathways of aryl-substituted arenediynes depend on the interplay between the steric interactions and electronic properties of the aryl substituents. Herein, to further probe the impact of bulky and electron rich aryl substituents on t

Full text of DOI:10.1016/j.tetlet.2015.01.011

Tetrahedron Letters 56 (2015) 3155–3159
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis and reactivity of anthracenyl-substituted arenediynes
Gavvalapalli Nagarjuna a, , Yi Ren a, , Jeffrey S. Moore a,b,
⇑
a Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States
b Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
Cyclization reaction pathways of aryl-substituted arenediynes depend on the interplay between the ste-
ric interactions and electronic properties of the aryl substituents. Herein, to further probe the impact of
bulky and electron rich aryl substituents on the cyclization of arenediynes, anthracenyl-substituted aren-
ediynes (1–3) with different ortho substituents were synthesized and their thermal, photo, and radical
initiated cyclization reactions were studied.
Received 20 November 2014
Revised 23 December 2014
Accepted 2 January 2015
Available online 17 January 2015
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
Cyclization
Anthracenyl arenediynes
Sterics and electronics
Fulvene
Cyclization reactions of enediynes with aliphatic groups at the
alkyne terminus are well studied compared to their aryl substi-
tuted counterparts.1–4 Cyclization of aryl-substituted arenediynes
yields a 5-membered ring (via C1–C5 cyclization) or a 6-membered
ring (via C1–C6 Bergman cyclization), hence the reaction is a useful
synthetic method to generate polycyclic aromatic hydrocarbons
and fulvenes.3,5–14 Polycyclic aromatic hydrocarbons with
extended p-conjugation exhibit useful optical and charge transport
properties for applications in photovoltaics and organic transis-
tors.12,14–16 Moreover, the photophysical properties of polycyclic
aromatic hydrocarbons containing the 5-membered ring are unu-
sual compared to the analogous molecules with 6-membered
rings.3,5–13,15 It is thus of interest to develop a better understanding
of the structure–property relationships of the 5-membered ring
containing polycyclic aromatic hydrocarbons. Cyclization of aryl-
substituted arenediynes proceeds via C1–C5 cyclization (5-mem-
bered cyclic product) or C1–C6 Bergman cyclization (6-membered
cyclic product) pathway that can be modulated by the sterics
and electronics of aryl substituents. For example, phenyl-substi-
tuted arenediyne generates both Bergman and C1–C5 cyclized
product whereas the bulky trichlorophenyl-susbstituted arene-
diyne yields only C1–C5 cyclized products upon thermal induced
cyclization (Scheme 1).7,17 Electronic effects on the cyclization
pathway are more apparent in the case of naphthalenyl-
substituted arenediynes.9 Photoreaction of electron rich napht-
halenyl-substituted arenediyne (6-methoxy naphthalen-2-yl
Scheme 1. Previously reported products from cyclization of aryl-substituted
arenediynes.
derivative) yields a Bergman cyclized product whereas the napht-
halenyl-substituted arenediynes (naphthalen-1-yl and naphtha-
len-2-yl derivatives) do not generate the expected cyclized
products.9 Photoreaction of dianthracene-homo-enediyne in which
only one of the anthracenylacetylene is in p-conjugation with aryl
moiety generates a cyclized product with benzene which is used as
a solvent for the reaction.18
In this work, to further probe the interplay between steric and
electronic effects of the aryl substituents on arenediyne cyclization
reactions, 9-anthracenylethynyl arenediynes 1–3 (Fig. 1) in which
both the anthracenylacetylenes are in p-conjugation with the aryl
moiety were synthesized and their thermal, photo, and radical
initiated cyclization reactions are studied. We expect the
⇑
Corresponding author. Tel.: +1 2172445289; fax: +1 2172440181.
E-mail address: jsmoore@illinois.edu (J.S. Moore).
These authors contributed equally.
http://dx.doi.org/10.1016/j.tetlet.2015.01.011
0040-4039/Ó 2015 Elsevier Ltd. All rights reserved.

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G. Nagarjuna et al. / Tetrahedron Letters 56 (2015) 3155–3159
9-Anthracenylethynyl arenediyne derivatives 1–3, possessing
ortho substituents of increasing steric demand –H (1), –CH3 (2),
and –TMS (3) were synthesized (Scheme 2). Compounds 1 and 2
were prepared starting from 9-bromoanthracene (5). Sonogashira
coupling of 5 with TMS acetylene followed by TMS deprotection
yielded anthracenylacetylene (7). Sonogashira coupling of
7
with 1,2-diiodobenzene or 3,4,5,6-tetramethyl-1,2-diiodobenzene
yielded 1 and 2, respectively.9 Unfortunately, in the case of 3, Sono-
gashira coupling of 7 with (2,3-dibromo-1,4-phenylene)bis(tri-
methylsilane) afforded only the mono-substituted product due to
the influence of the bulky –TMS groups. Thus, 3 was synthesized
following an alternative route via Sonogashira coupling of 9-bro-
moanthracene with 10 ((2,3-diethynyl-1,4-phenylene)bis(trimeth-
ylsilane)).21 Compound 10 was prepared in three steps from
dibromobenzene (8).
Cyclization reactions of arenediynes depend on the distance
between the alkyne groups and the nature of the aryl substitu-
ents.1–4 Single crystals of molecules 1–3 were grown to determine
the distance between alkyne groups and the preferred intramolec-
ular orientation of anthracenyl moieties (Fig. 2). From the crystal
structures, it is evident that the intramolecular distance between
the alkynes and anthracene groups as well as their orientation with
Figure 1. Chemical structures of anthracenyl-substituted arenediynes synthesized
and studied in this work.
cyclization of compounds 1–3 to proceed via C1–C5 cyclization
pathway given that anthracene is more sterically demanding than
naphthalene. In addition, anthracene is also electron rich compared
to naphthalene due to extended p-conjugation. In arenediynes, it is
also known that the ortho substituents on the phenyl ring impact
the kinetics of the cyclization reaction.19,20 Thus, we have also var-
ied the size of the ortho substituents (–H, –CH3, and –TMS) on the
phenyl ring and studied its impact on the conformation of anth-
racenyl groups and the cyclization reaction.
Scheme 2. Synthesis of anthracenyl arenediynes 1–3.
C6
C5
C4
C3
C2
C1
1
2
3
Figure 2. ORTEP view of crystal structures of 1–3.

G. Nagarjuna et al. / Tetrahedron Letters 56 (2015) 3155–3159
3157
respect to each other changes as the ortho substituents are varied.
The distance between the C1–C6 carbons in 1, 2, and 3 is 4.27, 4.02,
and 4.18 Å, respectively, and the distance between C1–C5 carbons
in 1, 2, and 3 is 3.75, 3.52, and 3.61 Å, respectively. Furthermore,
the anthracene moieties in 1 and 2 are interacting in an edge-to-
face fashion whereas the anthracene moieties in 3 are interacting
in face-to-face fashion.
for the observed trend. Additionally, the activation energy for
C1–C5 cyclization is ca. 5–7 kcal/mol lower than that for the Berg-
man cyclization pathway, indicating that the bulky anthracenyl
group should direct the cyclization toward the C1–C5 cyclization
pathway as expected.
Compounds 1–3 were subjected to thermal, photo, and radical
induced cyclization reaction conditions. To determine the thermal
reactivity of 1–3, differential scanning calorimetry (DSC) of com-
pounds 1–3 were recorded. It has been shown that the cyclization
reaction in enediynes is associated with an exothermic peak in
DSC.6,22–25 Thermogravimetric analyses (TGA) (Supporting infor-
mation Fig. S1) and DSC (Fig. 4) of 1–3 were recorded to determine
the decomposition temperature and the onset temperature for the
cyclization reaction. The decomposition temperatures of 1, 2, and 3
were found to be 383, 191, and 237 °C, respectively. The DSC of 1
shows both endothermic (maximum: 215 °C) and exothermic
peaks (maximum: 265 °C) while 2 and 3 do not show any peaks
below their decomposition temperature. The endothermic peak
at 215 °C matches with the experimentally determined melting
point of 1, while the exothermic peak at 265 °C might be associated
with the cyclization reaction. The absence of exothermic peaks in 2
and 3 below their decomposition temperatures indicates that the
cyclization reaction in these compounds in solid state is adversely
affected by the geometrically constrained environment created by
the bulky ortho (–CH3 and –TMS in 2 and 3) and/or anthracenyl
substituents. Since 1 showed an exothermic peak in DSC corre-
sponding to a thermal induced reaction, a cyclization reaction of
1 was carried out in 1,4-cyclohexadiene17,19 in a sealed tube at
250 °C, which is the onset temperature determined from the DSC
analysis. Thermal induced cyclization reaction of 1 resulted in a
mixture of products. The 1H NMR spectra of the isolated products
were complex and could not be assigned to the expected cyclized
product, thus making it difficult to deduce the actual chemical
structures. Subsequent reactions that were carried out at a lower
temperature (200 °C) in toluene with alternative proton sources
such as 1,4-cyclohexadiene and phenol were also unsuccessful.
Cyclization reactions of 2 and 3 in a mixture of toluene and 1,4-
cyclohexadiene at 150 °C, below their decomposition temperature,
were unsuccessful. Although the calculated thermal activation
energy barriers for cyclization of the phenyl-, trichlorophenyl-,
and anthracenyl-substituted arenediynes are very close, the anth-
racenyl derivative does not result in the expected cyclized prod-
ucts. Failure to observe the expected cyclized products in the
case of anthracenyl-substituted arenediynes could be due to the
Absorption and fluorescence spectra (Fig. 3) were recorded to
gain further insights into the intramolecular interaction between
the anthracene groups in molecules 1–3. Absorption spectra of
1–3 are red shifted compared to phenyl and naphthalenyl-substi-
tuted arenediynes due to enhanced pi-conjugation.9 Absorption
spectra of 1–3 are similar except that the peaks in 1 and 2 are gen-
erally broader than those for 3. This could be because of the
restricted rotational freedom of the anthracene moieties in 3 due
to the bulky –TMS groups. Emission spectra of 1–3 (Fig. 3) are also
similar. The absorption and emission spectra of 1–3 indicate that
there are no significant differences in the intramolecular interac-
tions between the anthracene moieties in all three compounds.
Bulky aryl groups are known to increase the activation energy
for the cyclization reaction and favor C1–C5 cyclized products over
Bergman cyclized products.9,17 In order to predict the preferred
cyclization pathways in 1–3, activation energies (D
Gà) for the for-
mation of both C1–C5 and Bergman cyclized products in 1–3 were
calculated at the B3LYP/6-31G(d) level of theory (Table 1).16 The
activation energy for both C1–C5 and Bergman cyclization
decreases as the size of the ortho substituents increases in 1–3.
The decrease in intramolecular distance between the alkyne car-
bons in 1–3 as a result of the increased steric repulsion between
the ortho substituents and the alkyne carbons could be the reason
Figure 3. Normalized absorption (solid line) and emission (dotted line) of 1 (red), 2
(blue), and 3 (green) in chloroform.
Table 1
Activation energies for cyclization reactions of 1–3a
d
Molecule
D
Gà C1–C5b
D
Gà C1–C6c
DDGà(5–6)
(kcal/mol)
(kcal/mol)
(kcal/mol)
1
2
3
42.73
41.70
39.01
49.72
48.84
44.24
À6.99
À7.14
À5.23
a
b
c
calculations are performed using B3LYP/6-31G(d) level of theory.
activation energy for C1–C5 cyclization.
activation energy for Bergman cyclization.
d
difference in activation energies for C1–C5 and Bergman cyclization.
Figure 4. DSC curves of 1 (red), 2 (blue), and 3 (green) (heating rate: 10 °C/min).

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G. Nagarjuna et al. / Tetrahedron Letters 56 (2015) 3155–3159
Scheme 3. (a) External radical initiated cyclization of 1; (b) ORTEP view of fulvene product (4).
underestimation of the steric effects imparted by the bulky anth-
racenyl group in the activation energy calculations.
To summarize, 9-ethynylanthracenyl arenediynes with differ-
ent ortho substituents were synthesized. Thermal, photo, and rad-
ical initiated cyclization reactions were investigated to elucidate
the effects of the size of the ortho as well as the anthracenyl sub-
stituents on the cyclization reactions. Optical absorption spectra
of 1–3 are red shifted compared to phenyl- and naphthalenyl-
substituted arenediynes due to enhanced pi-conjugation. Even
though the calculated activation energies for C1–C5 cyclization
reactions of 1–3 are close to the other reported arenediynes, no
cyclization products are observed in 1–3 upon thermal or photoini-
tiation. This could be due to the underestimation of the steric
effects imparted by the anthracenyl group in the calculations.
External radical activated reaction of 1 resulted in the correspond-
ing fulvene product (4) whereas the cyclization reactions of 2 and 3
were not successful due to the bulky ortho substituents. In the case
of external radical initiated reactions, ortho substituents played a
major role compared to the aryl substituent at the alkyne terminus.
After thermal conditions failed to initiate cyclization, com-
pounds 1–3 were subjected to photoinitiated cyclization condi-
tions. The reactions were performed in benzene as solvent and
1,4-cyclohexadiene as a proton source over 24 h using a 150 W light
source. All three samples yielded a mixture of products. 1H NMR
spectra of the isolated products were complex, making it difficult
to deduce structural information of the products. Efforts to grow
single crystals of the isolated products as well as the use of different
hydrogen sources (methanol and isopropanol) were also unsuccess-
ful. We hypothesize that undesired intramolecular 4+4 cycloaddi-
tion (between the anthracenyl groups) and intermolecular 4+2
cycloaddition (between the anthracenyl and the alkyne groups) as
well as the intended cyclization reaction are responsible for the
observed complex mixture of products.26,27 Failure to observe
cyclized products in 1–3 under thermal and photoinitiated condi-
tions compared to other aryl-substituted arenediynes (phenyl, tri-
chlorophenyl, and naphthalenyl derivatives) is likely due to the
increased steric demand of the anthracene groups. In the case of
naphthalenyl-substituted arenediynes (naphthalen-1-yl, naphtha-
len-2-yl, and 6-methoxy naphthalen-2-yl derivatives), only the
6-methoxy naphthalen-2-yl derivative resulted in the expected
Bergman cyclized product under photoinitiated cyclization.9 For
arenediynes with simple aryl substituents of varying bulkiness
(phenyl, naphthalen-1-yl, naphthalen-2-yl, and anthracen-9-yl
derivatives), only the phenyl derivative yields the expected cyclized
product. Thus, the aryl substituents on the arenediyne play a key
role in the photoreactivity of the arenediynes.
As attempts using thermal or photoreaction conditions to initi-
ate cyclization reaction were unsuccessful, compounds 1–3 were
subjected to radical initiated cyclization reaction conditions. Radi-
cal initiated reactions of phenyl-substituted arenediynes are
known to preferentially result in the formation of C1–C5 cyclized
products known as fulvenes.4,8 Radical initiated cyclization of com-
pounds 1–3 was performed by the addition of Bu3SnH/AIBN
(Scheme 3). The reaction mixture was quenched with HCl after
12 h. Compound 1 with no ortho substituents yielded the expected
fulvene product 4 with an isolated yield of 40% (Scheme 3). The
molecular structure of 4 was confirmed by NMR spectroscopy,
mass spectrometry, and single crystal structure data. Radical initi-
ated cyclization reactions of 2 and 3 gave a complex mixture of
products, which could not be analyzed. In the cases of 2 and 3,
the bulky ortho substituents (–CH3 and –TMS) might have pre-
vented the attack of tributyltin radical onto the alkynyl carbon
attached to phenyl. The ortho substituents on the phenyl ring seem
to play a major role on the external radical initiated cyclization
reaction pathway in anthracenyl-substituted arenediynes. Bulky
anthracenyl substituents on the alkyne terminus seem to have less
of an effect on the radical-mediated cyclization pathway, since 1
yielded the expected fulvene product with an external radical
initiator but did not yield the expected cyclized products under
thermal or photoinitiated conditions.
Acknowledgements
We acknowledge financial support from the Department of the
Navy, Office of Naval Research under Grant N00014-12-1-0828.
We thank Dr. Danielle Gray for the determination of the crystal
structures of 1–4. We also thank Dr. Taras V. Pogorelov and Dr.
David Woon for helpful discussion with Gaussian calculations.
Supplementary data
Crystallographic data for the structures in this Letter have been
deposited with the Cambridge Crystallographic Data Centre as sup-
plementary publication. CCDC 1035028 to 1035031 for compounds
1, 4, 2, and 3, respectively.
Supplementary data (detailed synthetic procedures, 1H and 13C
NMR spectra, thermogravimetric analyses of 1–3, absorption and
emission spectra of 4, computational methods, and crystallo-
graphic information files (CIF) for 1–4) associated with this article
can be found, in the online version, at http://dx.doi.org/10.1016/j.
tetlet.2015.01.011.
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