Facile photochemical synthesis of 5,10-disubstituted [5]helicenes by removing molecular orbital degeneracy

Article abstract of DOI:10.1021/ol5008718

Photocyclodehydrogenation is a key reaction to synthesize helicenes; however, because of overannulation, it is not applicable to the synthesis of [5]helicene. Introduction of a cyano group was found to remove the orbital degeneracy of the low-lying unoccupied MOs; consequently, the lowest excitation comprises a single transition involving the C₂-antisymmetric MO. Therefore, the problematic overannulation can be effectively suppressed. Moreover, in combination with the Knoevenagel reaction, a one-pot synthesis of 5,10-dicyano[5]helicene with 67% yield was accomplished.

Full text of DOI:10.1021/ol5008718

Letter
pubs.acs.org/OrgLett
Facile Photochemical Synthesis of 5,10-Disubstituted [5]Helicenes by
Removing Molecular Orbital Degeneracy
Natsuki Ito, Takashi Hirose, and Kenji Matsuda*
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Katsura,
Nishikyo-ku, Kyoto 615-8510, Japan
S
* Supporting Information
ABSTRACT: Photocyclodehydrogenation is a key reaction to
synthesize helicenes; however, because of overannulation, it is not
applicable to the synthesis of [5]helicene. Introduction of a cyano
group was found to remove the orbital degeneracy of the low-lying
unoccupied MOs; consequently, the lowest excitation comprises a
single transition involving the C2-antisymmetric MO. Therefore, the
problematic overannulation can be effectively suppressed. Moreover,
in combination with the Knoevenagel reaction, a one-pot synthesis of 5,10-dicyano[5]helicene with 67% yield was accomplished.
elicenes are helical polycyclic aromatic hydrocarbons in
which the ortho-position of the aromatic rings are
molecular orbitals (UMOs) exist in [5]helicene and the lowest
excitation is not composed of the single transition. Therefore,
the treatment beyond the use of the simple Woodward−
Hoffmann rules is required.28,29
H
angularly annulated with an adjacent aromatic ring.1−5 Their
intrinsic helical structure is very attractive for application in
organic nanomaterials because of the chiral π-conjugated
system. Since the chirality of the molecules can be attributed
to their helical structures, the whole molecule is involved in the
chirality. The applications of helicenes have now expanded into
several fields including photofunctional materials,6−11 supra-
molecular chemistry,12−17 and surface chemistry.18−20
We now report the facile photochemical synthesis of 5,10-
dicyano[5]helicene using a double photocyclodehydrogenation
reaction of 1,4-bis(2-cyano-2-phenylethenyl)benzene. By the
strategic introduction of a substituent in the precursor to
remove the orbital degeneracy, photoreactivity could be
controlled. By combining the Knoevenagel reaction, one-pot
synthesis of 5,10-dicyano[5]helicene with 67% yield was
accomplished from terephthalaldehyde and benzyl cyanide.
1,4-Distyrylbenzene 1a is known to undergo photocyclode-
hydrogenation upon irradiation with UV light in the presence
of iodine. However, the yield of [5]helicene 2a is generally low
due to overannulation, producing benzo[ghi]perylene 3a as a
main product (Scheme 1).26,30 By using 1,4-bis(2-cyano-2-
phenylethenyl)-2,3-dimethoxybenzene 1d instead of 1a, the
overannulation was suppressed to give [5]helicene 2d in 82%
yield. Therefore, we investigated the substituent effects on
photoreactivity. When compound 1b bearing the 2,3-dimethoxy
functionality was used, the overannulation was observed.
Photochemical methods are often used to prepare helicenes.
The 6π-photocyclization of stilbene-type compounds followed
by oxidation affords phenanthrene-type aromatic oligoacenes.
This photocyclodehydrogenation reaction can be used toward
the synthesis of very large helicene derivatives, such as
[14]helicene.21 By using this method, the preparation of
[5]helicene from 1,2-di(2-naphthyl)ethene or 1,4-distyrylben-
zene should be feasible. However, the [5]helicene product is
itself also photoreactive, which leads to the formation of
benzo[ghi]perylene as a result of overannulation. Since existing
photochemical methods are not applicable to the synthesis of
[5]helicenes, several research groups have developed alternative
synthetic methods using olefin metathesis,22 radical cycliza-
tion,23 and metal-catalyzed cross-coupling reactions.24
Regarding the photochemical synthesis of helicenes, several
methods have been proposed to overcome the limitation due to
overannulation. Collins et al. carried out a photocyclization
reaction of 1,2-di(2-naphthyl)ethene with Cu-based sensitizers
using visible light and reported a significant increase in the yield
of helicene.25 Katz et al. introduced a bromine atom close to
the reactive positions in the precursor to avoid secondary
annulation.26 In addition, Frimer et al. reported that [5]-
helicene with maleic anhydride resists secondary annulation.
They showed that the symmetry of the LUMO is opposite to
that of the parent [5]helicene and explained the reactivity using
the Woodward−Hoffmann rules.27 However, as we will show in
the following text, two degenerate low-lying unoccupied
Scheme 1. Photochemical Synthesis of [5]Helicene from 1,4-
Distyrylbenzene
Received: March 24, 2014
Published: April 21, 2014
© 2014 American Chemical Society
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Figure 1. Orbital correlation diagram for compounds 2a−d. The blue/red arrows represent the transitions to the C2-symmetic/C2-antisymmetric
UMOs. The phase of the atomic orbitals in the C2-symmetric UMO is suitable for a photochemical conrotatory cyclization reaction.
However, when compound 1c bearing a cyano group at R2 was
used, overannulation was effectively suppressed to afford
[5]helicene 2c in 83% yield.31
The phases of the atomic orbitals in the LUMO positioned at
the reactive carbons (C-1 and C-14) are suitable for a
photochemical conrotatory cyclization, while a disrotatory
cyclization is predicted when a transition to the LUMO+1 is
considered. Between the alternative processes, we only
considered the conrotatory cyclization because it is both
thermodynamically and kinetically favorable; the conrotatory
product is more stable because of the disrotatory product has a
distorted geometry owing to the two hydrogens being on the
same side. In addition, a higher activation energy is expected for
the disrotatory cyclization because of the large displacement
required during the disrotatory process, whereas there is
geometrical similarity between the conrotatory product and the
original [5]helicene.34 The overannulation is considered to take
place for [5]helicene 2a owing to the following two reasons: (i)
an appropriate conical intersection or avoided surface crossings
connecting the photocyclized product35 is formed by the
contribution of the C2-symmetric UMO (59%) or (ii) the
activation energy in the excited state for the conrotatory
cyclization is sufficiently lowered by the positive orbital
interaction in the C2-symmetric UMO.36
To investigate the difference in reactivity, a TD-DFT
calculation32 was performed on 2a−d at the B3LYP/6-
31G(d) level.33 Not only the shape of the LUMO but also
the composition of the transition was analyzed. According to
the Woodward−Hoffmann rules, conrotatory cyclization is a
symmetry-allowed process in the excited state when dealing
with a 22π electron system, i.e., a (4n+2)π system. However, in
the [5]helicene framework, the degeneracy of the low-lying
UMOs, LUMO and LUMO+1, must be considered. As seen in
Figure 1, the lowest excitation of the parent [5]helicene 2a
consists of two transitions: (i) one from HOMO to LUMO and
(ii) the other from HOMO−1 to LUMO+1, both of which
contribute almost equally, 59 and 40%, respectively (Table 1).
Table 1. Composition of Transition and Product upon
a
Photo-irradiation
composition of transition
Of the two low-lying UMOs, the C2-antisymmetric UMO is
effectively stabilized by the cyano substituents in the C-5 and
C-10 positions (Figure 1). The C2-symmetric UMO of 2a has a
small orbital coefficient at the C-5 and C-10 positions, whereas
the C2-antisymmetric UMO has large coefficients. Therefore,
the C2-antisymmetric UMO could be selectively stabilized by
presence of electron-withdrawing groups at C-5 and C-10.
Owing to the stabilization of the C2-antisymmetric UMO, the
lowest excitation of 2c is mainly composed of the transition
from the HOMO−1 to LUMO up to 80%, in which the phase
of the LUMO is not suitable for the conrotatory cyclization
reaction (Table 1). Hence, the photoreactivity of 2c and 2d was
successfully suppressed by the cyano substituents. On the other
hand, methoxy substitution at the C-7 and C-8 positions does
not affect the energy level of the MO and therefore the
reactivity.37
b
b
helicene
C2-symmetric
C2-antisymmetric
product (yield, %)
c
c
2a
2b
2c
2d
4
0.59
0.42
0.18
0.11
0.03
0.34
0.47
0.40
0.57
0.80
0.88
0.95
0.61
0.50
benzoperylene (16)
benzoperylene (32)
c
[5]helicene (83)
c
[5]helicene (82)
d
[5]helicene (88)
e
5
[5]helicene (82)
e
6
benzoperylene (98)
a
When benzo[ghi]perylene was obtained, [5]helicene was not
b
detected and vice versa. The contributions of transitions in the
c
lowest excitation state. 1,4-Distyrylbenzene derivative 1a−d (0.15
mmol) and I2 (0.15 mmol) in toluene (45 mL) were irradiated by a
superhigh-pressure Hg lamp for 36 h (this work). The byproduct of
the photoreaction was not determined. For the photoirradiation of 1a
and 1b, monocyclized products have been detected by mass
d
e
spectrometry. Reference 27. Reference 38.
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To check the effect of the electron-withdrawing substituents
on the photoreactivity, a photoirradiation experiment was
performed using 2a and 2c, and the dimethyl ester derivative of
Scheme 3. 5,10-Functionalization of [5]Helicene
1
8c (9). The reactions were monitored by H NMR spectros-
copy (Figures S1 and S2, Supporting Information). The MOs
of 2c and 9 were very similar (Figure S3, Supporting
Information). The parent [5]helicene 2a was converted to
benzoperylene 3a in 73% yield after irradiation with UV light
for 1 h, whereas the cyano-substituted compound 2c and the
carbonyl-substituted compound 9 remained intact under the
same reaction conditions. Therefore, it was confirmed
experimentally that the electron withdrawing group at the C-
5 and C-10 positions provides remarkable photostability to
[5]helicenes.
An interesting feature of the molecular orbitals in [5]helicene
is the existence of nearly degenerate MOs near the HOMO and
LUMO. Figure 3 shows the orbital correlation diagram of the
We also checked the validity of our theoretical predictions.
The [5]helicenes 427 and 538 have been reported to display no
photoreactivity, and 638 was reported to be photoreactive
(Figure 2).39 Using DFT calculations, the ratio of excitation to
Figure 2. [5]Helicenes whose photoreactivity was reported.
the C2-symmetric UMO has been calculated to be 3%, 34%, and
47% for 4, 5, and 6, respectively. These results indicate that
when the ratio of excitation to the C2-symmetric UMO is larger
than 42%, the photoreaction can proceed; however, when the
ratio is smaller than 34%, the photoreaction does not proceed.
The starting materials for the photocyclodehydrogenation, 1c
and 1d, were synthesized via the Knoevenagel condensation
reaction. Therefore, a one-pot synthesis was performed starting
from terephthalaldehyde and benzyl cyanide (Scheme 2). A
Figure 3. Orbital correlation diagram of 1a and 1c.
reactants in the photochemical reaction, (cis,cis)-1,4-distyr-
ylbenzene 1a and (cis,cis)-1,4-bis(2-cyano-2-phenylethenyl)-
benzene 1c. As shown in this diagram, there is no degeneracy
in the frontier orbitals. The lowest excitation is dominantly the
HOMO to LUMO transition. Therefore, the only possible
pericyclic reaction is the conrotatory cyclization in the excited
state, which is typical for (4n+2)π systems. This feature is
utilized in the design of photochromic compounds, such as
diarylethenes or fulgides.41−43
Scheme 2. One-Pot Synthesis of [5]Helicene Derivative
Starting from Terephthalaldehyde and Benzyl Cyanide
Moreover, as shown in Figure 3, cyano substitution does not
influence the relative orbital energy of compound 1, which is
the reason why the reactivity of the first photocyclization was
retained even after the cyano substitution. These results show
that the cyclization of [5]helicenes is different from regular (4n
+2)π electron pericyclic reactions, which is in a marked contrast
to the first cyclization. The unique degeneracy of MOs allows
us to control the photoreactivity by cyano substitution. The
utilization of this unique MO has potential application in both
photochemical and thermal pericyclic reactions.
In conclusion, 5,10-dicyano[5]helicene was synthesized
photochemically using a double photocyclodehydrogenation
reaction of 1,4-bis(2-cyano-2-phenylethenyl)benzene. By in-
corporating the cyano or carbonyl substituents, the C2-
antisymmetric UMO of the two nearly degenerate low-lying
UMOs is selectively stabilized and the lowest excitation
becomes mainly composed of a single transition where the
phase of the UMO is not suitable for conrotatory cyclization.
quartz flask charged with terephthalaldehyde, benzyl cyanide,
sodium ethoxide, and ethanol was stirred at 50 °C for 4 h, and
then after the addition of iodine the mixture was irradiated
using a mercury lamp for 64 h to afford 5,10-dicyano[5]-
helicene 2c in 67% yield. The reaction was also successful for a
7,8-methoxy substituted compound 2d.
Using our method, the 5,10-dicyano-substituted [5]helicene
could be synthesized. Therefore, we have tried to extend the π-
conjugation at the C-5 and C-10 positions. 5,10-Diaryl-
substituted [5]helicenes have been synthesized using a
Suzuki−Miyaura coupling, but several steps are required.40
We have successfully converted the cyano group into the
carboxylic acid after synthesis of the [5]helicene skeleton
(Scheme 3). This facile modification allows our method to be
useful in extending the π-system at the C-5 and C-10 positions.
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By removing the orbital degeneracy, the photoreactivity was
successfully controlled. Moreover, in combination with the
Knoevenagel reaction, a one-pot synthesis of 5,10-dicyano[5]-
helicene in 67% yield from terephthalaldehyde and benzyl
cyanide was accomplished.
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ASSOCIATED CONTENT
* Supporting Information
Experimental details, 1H and 13C NMR spectra, Cartesian
coordinates of the optimized structures, and the calculated
excited states. This material is available free of charge via the
Internet at http://pubs.acs.org.
■
S
AUTHOR INFORMATION
Corresponding Author
■
(30) Scholz et al. obtained benzo[ghi]perylene in 11.5% yield by the
photolysis of 1,4-distyrylbenzene. See: Dietz, F.; Scholz, M.
Tetrahedron 1968, 24, 6845. Katz et al. obtained it in 33% yield
(ref 26). We have obtained it in 16% yield.
*E-mail: kmatsuda@sbchem.kyoto-u.ac.jp.
Notes
(31) Cis−trans isomerization of the double bond is a reversible
process, while photocyclodehydrogenation from the cis isomer is not.
The reaction therefore proceeds to the annulated product regardless of
cis−trans isomerization upon continuous photoirradiation.
(32) Adamo, C.; Jacquemin, D. Chem. Soc. Rev. 2013, 42, 845 and
references therein.
(33) Frisch, M. J. et al. Gaussian 09, Revision B.01; Gaussian, Inc.:
Wallingford, CT, 2009. See the Supporting Information for the full
reference.
(34) Bao, J.; Minitti, M. P.; Weber, P. M. J. Phys. Chem. A 2011, 115,
1508.
(35) Turro, N. J.; Ramamurthy, V.; Scaiano, J. C. Chapter 6: A
Theory of Molecular Organic Photochemistry. Principles of Molecular
Photochemistry An Introduction; University Science Books: Sausalito,
CA, 2009; pp 319−382.
(36) There are also two nearly degenerate high-lying occupied MOs,
which have opposite symmetry; therefore, the conrotatory thermal
cyclization is allowed. Scott et al. reported the thermal cyclization of
[5]helicene by flash vacuum pyrolysis: Xue, X.; Scott, L. T. Org. Lett.
2007, 9, 3937.
(37) The small substituent effect by the methoxy group alters the
order of the frontier orbitals; therefore, the HOMO to LUMO
transition in compound 2a corresponds to the HOMO−1 to LUMO
+1 transition in compound 2b.
(38) Bazzini, C.; Brovelli, S.; Caronna, T.; Gambarotti, C.; Giannone,
M.; Macchi, P.; Meinardi, F.; Mele, A.; Panzeri, W.; Recupero, F.;
Sironi, A.; Tubino, R. Eur. J. Org. Chem. 2005, 1247.
(39) Katz et al. reported in ref 7 that the reactivity was controlled by
the steric repulsion of the bromo substituents close to the reactive
position. Calculation results on these compounds are described in the
Supporting Information.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the NEXT program (No. GR062)
from the Japan Society for the Promotion of Science (JSPS),
Japan.
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