Synthesis and Study of 7,12,17-Trioxa[11]helicene

Article abstract of DOI:10.1021/acs.orglett.5b02948

Synthesis of the title compound 7,12,17-trioxa[11]helicene, a large oxygen-containing helicene, has been reported. The 11-membered heterohelicene was synthesized by a combination of two simple reactions involving oxidative coupling and dehydrative cyclization. The final helicene was characterized by single-crystal X-ray diffraction, fluorescence spectroscopy, and differential scanning calorimetric analysis.

Full text of DOI:10.1021/acs.orglett.5b02948

Letter
pubs.acs.org/OrgLett
Synthesis and Study of 7,12,17-Trioxa[11]helicene
M. Shyam Sundar and Ashutosh V. Bedekar*
Department of Chemistry, Faculty of Science, M.S. University of Baroda, Vadodara 390 002, India
S
* Supporting Information
ABSTRACT: Synthesis of the title compound 7,12,17-trioxa[11]helicene, a large oxygen-containing helicene,
has been reported. The 11-membered heterohelicene was synthesized by a combination of two simple
reactions involving oxidative coupling and dehydrative cyclization. The final helicene was characterized by
single-crystal X-ray diffraction, fluorescence spectroscopy, and differential scanning calorimetric analysis.
crew-shaped helical molecules comprising ortho-fused
aromatic rings acquire a unique shape in order to release
Scheme 1. Retrosynthesis of 7,12,17-Trioxa[11]helicene 1
S
internal strain. Such molecules have been widely studied in
recent years due to the unique properties associated with their
structure.1 Basically, there are two types of helical molecules:
carbahelicenes and heterohelicenes. Although early work was
more focused on the former class, recently, more interesting
properties have been observed for the latter type of helical
molecules containing one or different heteroatoms. Polycyclic
aromatic oxygen-containing molecules, particularly fused furans,
are expected to provide relatively high HOMO levels2 and are
known to show interesting utility in electronic devices as organic
light-emitting diodes3 or organic field-effect transistors.4 The
synthesis and study of oligonaphthofurans has also been reported
recently,5 where the systematic correlation of the number of
naphthofuran units and the physical properties is evaluated. The
compounds belonging to the general class of oxahelicenes have
been synthesized, and their various properties have been
studied.6 The special properties of helical molecules have been
attributed to the extended conjugation of the π electrons in the
framework. For larger helicenes with increasing numbers of
ortho-fused rings, the π electrons start to form additional layers
and contribute to the screw shape of the molecule. For
[n]helicenes, a double layer is formed when n = 7 and a triple
layer when n = 13. The synthesis of larger helicenes becomes
more challenging due to the difficulty of releasing the internal
strain. For a long time, [14]helicene, as synthesized by Martin
and Baes7 in 1975, remained the largest carba-helicene, until the
very recent report of [16]helicene by Murase, Fujita, and Mori,8
after nearly 40 years. Similarly, some of the heterohelicenes of
larger size, such as hexathia[13]helicene,9 carbon−sulfur-
containing [11]helicene,10 or poly(thiaheterohelicene),11 were
reported in the literature. In this communication, we report the
design and synthesis of one such large oxygen-containing
7,12,17-trioxa[11]helicene, which is expected to form nearly
1.5 rotations of a helical twist involving a considerable
delocalization of π electrons. In continuation of our work on
the synthesis and study of helicene-like compounds12a and
aza[n]helicenes,12b,c we present the synthesis of trioxa[11]-
helicene.
ring can be built by acid-catalyzed ether formation from the
corresponding binaphthol 2, according to the procedure
developed by Thongpanchang.6d Diol 2 can be synthesized by
oxidative coupling of 2-hydroxy-7-oxa[5]helicene 3 by a standard
procedure. The desired molecule 3 can be prepared by acid-
promoted selective ether formation from 1,1′-binaphthalenyl-
2,2′,7-triol 4, which can be obtained by oxidative cross-coupling
of 2-naphthol 5 and 2,7-dihydroxynaphthalene 6. Proposed
conversion of 3 to 2 by oxidative coupling is expected to be
difficult due to the steric considerations.
The cross-coupling of 2-naphthol 5 with other substituted
naphthol derivatives is a well-studied reaction.13 However, cross-
coupling reaction between two naphthol units, both possessing
electron-releasing substituents, tends to be less selective, and the
desired cross-coupling products are accompanied by the
The retrosynthesis for the target molecule 7,12,17-trioxa[11]-
Received: October 12, 2015
helicene 1 is presented in Scheme 1. The central naphthofuran
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.5b02948
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Letter
formation of the homocoupling compounds. A good selectivity
can be achieved in a cross-coupling reaction between the two
coupling partners possessing considerable difference in the
electron density.13a However, in the present case, we need to
couple two electron-rich naphthol derivatives, 5 and 6, and thus
we expect formation of the corresponding homocoupled
products 7 and 8 (Scheme 2). The optimized condition of
FeCl3-catalyzed cross-coupling in aqueous medium is presented
here, while the detailed investigations will be disclosed later.
Scheme 2. Oxidative Cross-Coupling of Naphthols
Figure 1. Possible modes of homocoupling of 3.
Scheme 4. Coupling of 2-Hydroxy-7-oxo[5]helicene 3
A pure sample of triol 4 was subjected to the acid-catalyzed
ether formation by the standard procedure developed earlier.6d
The desired product 2-hydroxy-7-oxa[5]helicene 3 was obtained
in good yield from the reaction mixture by simple workup and
column chromatography over silica gel (Scheme 3). The
Scheme 3. Synthesis of 2-Hydroxy-7-oxa[5]helicene
dehydration reaction of 4 appears to be difficult as it involves
conversion of a nearly perpendicular structure of the binaphthyl
framework to a more planar moiety of oxa[5]helicene 3. The
dihedral angle of a dinaphthofuran system similar to 4, about 85°,
changes to merely ∼15° when such cyclization occurs.5a Due to
small dihedral angle, the helical isomers of 3 are expected to
possess a low isomerization barrier, resulting in fast inter-
conversion, and hence, no attempts were made to resolve them.
The oxidative homocoupling of 2-hydroxy-7-oxa[5]helicene 3
may possibly follow four different pathways (Figure 1). Out of
these orientations, modes B, C, and D will lead to the steric
crowding, and hence, the coupling is expected to follow the more
feasible mode A. The homocoupling between two molecules of 3
should be the key step in the synthesis of the target molecule.
The homocoupled product 2 (in mode A) can then be subjected
to acid-catalyzed ether formation to obtain the final compound 1.
The above conversion requires interaction between the two
almost perpendicularly oriented hydroxyl groups and may also
pose a considerable challenge.
The homocoupling of 3 was initially screened with aqueous
FeCl3; however, the reaction resulted in a complex mixture, and
no significant product was isolated. Hence, another routinely
used catalyst system of CuCl2−TMEDA was screened in dry
methyl alcohol at room temperature (Scheme 4). Coupling
product 2 was found to be difficult to purify on a silica gel
column. However, another deep orange-colored, nonpolar
crystalline compound was isolated from the reaction mixture.
This bright-colored compound was characterized to be 1,1-
dimethoxy-2-oxo-12-hydroxy-7-oxo[5]helicene 9, isolated in low
yield. This unexpected compound was formed in several repeat
experiments when performed in methyl alcohol. All other
fractions were collected, presumably containing the required
homocoupling product 2, and subjected to acid-catalyzed ether
formation. Repeated attempts to separate and access a pure
sample of 2 were not successful. The above coupling reaction also
failed in other solvents such as ethyl alcohol, 2-propanol, or 1,4-
dioxane. Cyclization of crude 2 was performed with p-TSA in
refluxing toluene, and the desired oxahelicene 1 was isolated in
moderate yield as light yellow needles.
The structure of 9 was established by spectral analysis and
1
confirmed by a single-crystal X-ray diffraction study. The H
NMR of 9 showed only one singlet at δ 3.22 for six hydrogens,
indicating rapid interconversion between the two isomers during
the measurement at ambient conditions. The same was observed
in 13C NMR when the methoxy carbon showed a single peak at δ
51.87. The α,β-unsaturated ketone system was established by
observing the resonance peaks of two doublets in the 1H NMR at
δ 6.27 and 9.62. The formation of such an unexpected compound
can be attributed to the trapping of a radical intermediate 10 by
B
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methyl alcohol during the coupling reaction. Formation of such
keto-radical intermediate was proposed earlier.13a Product 9 was
not observed when other alcohols were used as solvents, so
probably the trapping of intermediate 10 was only feasible with
the smaller methyl alcohol.
C10−C33, 3.360 Å; and C16−C32; 3.226 Å). Along the b-axis,
the shape of the molecule looks like the letter “Z” with a diagonal
length of about 10.1 Å, and the width is about 9.9 Å, while the
intramolecular pitch of the outer helicene is about 4.8 Å (Figure
4). The interplanar angle in 1 was found to be 24.37° (angle
The structure of 9 was established by single-crystal X-ray
analysis (Figure 2).14 The dihedral angle in this compound was
observed to be 15.4°, which was crystallized in the Pna21 space
group.
Figure 4. Side view and dimensions of 1 (distances in Å).
created by the intersection of planes passing through C1−C2−
C3−C4−C4a−C23j and C14a−C15−C16−C16a−C23c−
C23d) and agrees well with the known observation for larger
helicenes where it tends to decrease for elongated structures.16
The torsional angle between the inner carbon atoms of 1 was
found to be 4.39° (C23−C23a−C23b−C23c), 10.95° (C23a−
C23b−C23c−23Cd), 23.71° (C23b−C23c−C23d−C23e),
19.30° (C23c−C23d−C23e−C23f), and 2.66° (C23d−C23e−
C23f−C23g), suggesting different degrees of distortion in the
aromatic rings. As a consequence of torsional strain generated
due to the helical shape, the bond lengths in the skeleton are
different. In comparison of the standard bond length of benzene
(1.393 Å),17 the range of carbon−carbon bond lengths of the
inner helix was observed to be 1.429−1.437 Å, while the same on
the outer periphery was shorter, as seen in the range of 1.347−
1.360 Å. It was also interesting to see the difference between the
bond lengths of the two fused furan rings. The bond length of the
side furan rings C23b−C23c (and C23h−C23i) was 1.461 Å,
while the same for the central furan ring C23e−C23f was found
to be slightly elongated to be 1.471 Å, clearly due to much greater
strain exerted in the inner portion.
Figure 2. ORTEP diagram of 9.
After the less polar compound 9 was isolated on the silica gel
column, it was quickly further eluted with ethyl acetate and the
mixture of polar compounds, presumably containing 2, was
collected. The mixture was then subjected to acid-catalyzed
cyclization with p-TSA in refluxing toluene to obtain the desired
target compound 1, purified by careful chromatography over
silica gel. Compound 1 was obtained as light yellow crystals from
ethyl acetate and characterized by spectral techniques and single-
crystal X-ray diffraction analysis.14 The H NMR showed 10
1
signals indicating the symmetrical nature of the molecule.
Hydrogen attached to C2 (and C22) appears as typical triplet-
type multiplet at δ 6.26 due to the shielding effect of the terminal
ring.8 The proton attached to the next carbon C3 (and C21)
appears to have shifted downfield and shows a similar multiplet at
δ 6.95, as it is in the deshielding zone of the terminal ring. All
other signals appear as doublets, in agreement of the structure.
Similarly, 10 signals for the aromatic carbons were seen in the 13C
NMR due to the symmetrical nature, while a molecular ion peak
was observed at 548 m/z, which is also the base peak.
The optical and thermal properties of highly conjugated
helicene 1 were measured. The UV−vis and fluorescence spectra
indicated an absorption maxima at 352 nm and emission at 432
nm, with a shoulder peak at 450 nm (Figure 5), indicating a
Single-crystal X-ray analysis of 1 further established the
structure (Figure 3). The compound was crystallized in the P21/c
Figure 5. UV−vis and fluorescence spectra of 1 (c 9.12 × 10−5 M in
acetonitrile, 25 °C).
Figure 3. Stereoview and top view of the ORTEP diagram of 1.
space group; its unit cell consists of two molecules, one in “P”
conformation and the other in “M” conformation (see
Supporting Information). This indicates the absence of any
spontaneous resolution, a phenomenon occasionally observed in
some helical molecules during crystallization.15 Crystal structure
is packed in the alternate P and M channels along the a-axis, with
a helical pitch of 7.637 Å. Along each channel, consecutive
molecules are connected by π-stacking (C10−C32, 3.323 Å;
Stokes shift of 80 nm. The observed λem values and the nature of
the peaks are in the range observed for similar oligonaphthofur-
ans (364−486 nm).5b The fluorescence quantum yield (Φ) of 1
was observed to be 0.191, as determined using a standard
solution of quinine sulfate (0.1 M H2SO4, measured at an
excitation wavelength of 350 nm).
Thermal behavior of 1 was investigated by differential
scanning calorimetry, where the sample was heated at 10 °C/
C
DOI: 10.1021/acs.orglett.5b02948
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(d) Areephong, J.; Ruangsupapichart, N.; Thongpanchang, T.
Tetrahedron Lett. 2004, 45, 3067. (e) Nakano, K.; Hidehira, Y.;
Takahashi, K.; Hiyama, T.; Nozaki, K. Angew. Chem., Int. Ed. 2005, 44,
min from 35 to 385 °C under an inert atmosphere (see
Supporting Information). Analysis indicated that the compound
showed a melting point of 345.5 °C, and the glass transition
temperature was observed at 245.5 °C, indicating the high
thermal stability, expected of such helicenes.12b,18 The HPLC
analysis of 1 on a Chiralpak IC column showed the presence of
well-resolved peaks at 11.15 and 12.95 min (10% hexane in
isopropyl alcohol; 0.5 mL/min), indicating the presence of two
stable helical isomers.
In this communication, we report the synthesis of a large
oxygen-containing heterohelicene, 7,12,17-trioxa[11]helicene,
along with its characterization. The 11-membered helicene
shows good thermal stability and fluorescence properties.
7136. (f) Schneider, J.-F.; Nieger, M.; Nattinen, K.; Dotz, K. H. Synthesis
̈
̈
2005, 1109. (g) Campeau, L. C.; Parisien, M.; Jean, A.; Fagnou, K. J. Am.
Chem. Soc. 2006, 128, 581. (h) Tanaka, K.; Fukawa, N.; Suda, T.;
Noguchi, K. Angew. Chem., Int. Ed. 2009, 48, 5470. (i) Irie, R.; Tanoue,
A.; Urakawa, S.; Imahori, T.; Igawa, K.; Matsumoto, T.; Tomooka, K.;
Kikuta, S.; Uchida, T.; Katsuki, T. Chem. Lett. 2011, 40, 1343. (j) Salim,
M.; Akutsu, A.; Kimura, T.; Minabe, M.; Karikomi, M. Tetrahedron Lett.
2011, 52, 4518. (k) Goel, A.; Verma, D.; Pratap, R.; Taneja, G.;
Hemberger, Y.; Knauer, M.; Raghunandan, R.; Maulik, P. R.; Ram, V. J.;
Bringmann, G. Eur. J. Org. Chem. 2011, 2011, 2940. (l) Requet, A.;
Souibgui, A.; Pieters, G.; Ferhi, S.; Letaieff, A.; Carlin-Sinclair, A.;
Marque, S.; Marrot, J.; Hassine, B. B.; Gaucher, A.; Prim, D. Tetrahedron
Lett. 2013, 54, 4721. (m) Matsuno, T.; Koyama, Y.; Hiroto, S.; Kumar,
J.; Kawai, T.; Shinokubo, H. Chem. Commun. 2015, 51, 4607. (n) Hasan,
M.; Pandey, A. D.; Khose, V. N.; Mirgane, N. A.; Karnik, A. V. Eur. J. Org.
Chem. 2015, 2015, 3702.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.5b02948.
(7) Martin, R. H.; Baes, M. Tetrahedron 1975, 31, 2135.
(8) Mori, K.; Murase, T.; Fujita, M. Angew. Chem., Int. Ed. 2015, 54,
6847.
(9) Larsen, J.; Bechgaard, K. Acta Chem. Scand. 1996, 50, 71.
(10) Miyasaka, M.; Rajca, A.; Pink, M.; Rajca, S. J. Am. Chem. Soc. 2005,
127, 13806.
X-ray data for 9 (CCDC No. 999893) (CIF)
X-ray data for 1 (CCDC No. 999892) (CIF)
Detail experimental procedures, analytical data, copies of
spectra, details of crystal structures (PDF)
(11) Iwasaki, T.; Kohinata, Y.; Nishide, H. Org. Lett. 2005, 7, 755.
(12) (a) Talele, H. R.; Sahoo, S.; Bedekar, A. V. Org. Lett. 2012, 14,
3166. (b) Upadhyay, G. M.; Talele, H. R.; Sahoo, S.; Bedekar, A. V.
Tetrahedron Lett. 2014, 55, 5394. (c) Upadhyay, G. M.; Bedekar, A. V.
Tetrahedron 2015, 71, 5644.
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: avbedekar@yahoo.co.in.
Notes
(13) (a) Hovorka, M.; Gunterova,
́
J.; Zav
́
ada, J. Tetrahedron Lett. 1990,
̈
31, 413. (b) Smrci
̌
na, M.; Lorenc, M.; Hanus,
̌
V.; Sedmera, P.; Kocovsky,
́
The authors declare no competing financial interest.
P. J. Org. Chem. 1992, 57, 1917. (c) Temma, T.; Habaue, S. Tetrahedron
Lett. 2005, 46, 5655. (d) Grandbois, A.; Mayer, M.-E.; Bedard, M.;
Collins, S. K.; Michel, T. Chem. - Eur. J. 2009, 15, 9655. (e) Habaue, S.;
Temma, T.; Sugiyama, Y.; Yan, P. Tetrahedron Lett. 2007, 48, 8595.
(f) Egami, H.; Matsumoto, K.; Oguma, T.; Kunisu, T.; Katsuki, T. J. Am.
ACKNOWLEDGMENTS
■
We are grateful to Science and Engineering Research Board
(SERB), New Delhi, for supporting this work under a sponsored
scheme (No. SR/S1/OC-74/2012), and DST-PURSE for the
single-crystal X-ray diffraction facility of the Faculty of Science.
We thank the Council of Scientific and Industrial Research
(CSIR), New Delhi, for the award of a Senior Research
Fellowship to M.S.S., and we are grateful to Prof. Sanjio Zade
of IISER, Kolkata, for his suggestions.
Chem. Soc. 2010, 132, 13633. (g) Holtz-Mulholland, M.; de Les
́ ́
eleuc,
M.; Collins, S. K. Chem. Commun. 2013, 49, 1835.
(14) Crystallographic data for the structures of compounds 9 (CCDC
No. 999893) and 1 (CCDC No. 999892) have been deposited with the
Cambridge Crystallographic Data Centre. Copies of the data can be
obtained from http://www.ccdc.cam.ac.uk/conts/retrieving.html or
from the Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CD21EZ, UK (fax: +44-1223-336-033; e-mail: deposit@
ccdc.cam.ac.uk).
REFERENCES
■
(15) (a) Martin, R. H.; Flammang-Barbieux, M.; Cosyn, J. P.; Gelbcke,
M. Tetrahedron Lett. 1968, 9, 3507. (b) Martin, R. H.; Marchant, M. J.
(1) (a) Grimme, S.; Harren, J.; Sobanski, A.; Vogtle, F. Eur. J. Org.
̈
Chem. 1998, 1998, 1491. (b) Urbano, A. Angew. Chem., Int. Ed. 2003, 42,
3986. (c) Collins, S. K.; Vachon, M. P. Org. Biomol. Chem. 2006, 4, 2518.
(d) Rajca, A.; Miyasaki, M. In Functional Organic Materials; Muller, T. J.
J., Bunz, U. H. F., Eds.; Wiley-VCH: Weinheim, Germany, 2007; p 547.
(e) Shen, Y.; Chen, C.-F. Chem. Rev. 2012, 112, 1463. (f) Gingras, M.
Chem. Soc. Rev. 2013, 42, 968. (g) Gingras, M.; Felix, G.; Peresutti, R.
́
Chem. Soc. Rev. 2013, 42, 1007. (h) Gingras, M. Chem. Soc. Rev. 2013, 42,
1051.
Tetrahedron 1974, 30, 343. (c) Per
́
ez-García, L.; Amabilino, D. B. Chem.
Soc. Rev. 2002, 31, 342. (d) Stohr, M.; Boz, S.; Schar, M.; Nguyen, M.-T.;
̈
̈
Pignedoli, C. A.; Passerone, D.; Schweizer, W. B.; Thilgen, C.; Jung, T.
A.; Diederich, F. Angew. Chem., Int. Ed. 2011, 50, 9982.
(16) Bas, G. L.; Navaza, A.; Knossow, D. R. C. M. Cryst. Struct.
Commun. 1976, 5, 713.
(17) Allen, F. H.; Kennard, O.; Watson, D. G.; Brammer, L.; Orpen, A.
G.; Taylor, R. J. Chem. Soc., Perkin Trans. 2 1987, S1.
(18) Ben Braiek, M.; Aloui, F.; Moussa, S.; Tounsi, M.; Marrot, J.;
Hassine, B. B. Tetrahedron Lett. 2013, 54, 5421.
(2) Bunz, U. H. F. Angew. Chem., Int. Ed. 2010, 49, 5037.
(3) Tsuji, H.; Mitsui, C.; Ilies, L.; Sato, Y.; Nakamura, E. J. Am. Chem.
Soc. 2007, 129, 11902.
(4) (a) Mitsui, C.; Soeda, J.; Miwa, K.; Tsuji, H.; Takeya, J.; Nakamura,
E. J. Am. Chem. Soc. 2012, 134, 5448. (b) Nakano, M.; Niimi, K.;
Miyazaki, E.; Osaka, I.; Takimiya, K. J. Org. Chem. 2012, 77, 8099.
(5) (a) Nakanishi, K.; Sasamori, T.; Kuramochi, K.; Tokitoh, N.;
Kawabata, T.; Tsubaki, K. J. Org. Chem. 2014, 79, 2625. (b) Nakanishi,
K.; Fukatsu, D.; Takaishi, K.; Tsuji, T.; Uenaka, K.; Kuramochi, K.;
Kawabata, T.; Tsubaki, K. J. Am. Chem. Soc. 2014, 136, 7101.
(6) (a) Hogberg, H.-E. Acta Chem. Scand. 1973, 27, 2591. (b) Berg, J.-
̈
E.; Erdtman, H.; Hogberg, H.-E.; Karlsson, B.; Pilotti, A.-M.;
̈
̈
Soderholm, A.-C. Tetrahedron Lett. 1977, 18, 1831. (c) Lipshutz, B.
H.; Kayser, F.; Maullin, N. Tetrahedron Lett. 1994, 35, 815.
D
DOI: 10.1021/acs.orglett.5b02948
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