Synthesis and characterization of 1,8-naphthalimide with [6]helicene skeleton

Article abstract of DOI:10.1039/c2ob25223f

A 1,8-naphthalimide with [6]helicene derivative scaffold has been designed and synthesized. The (P)- and (M)-enantiomers of the [6]helicene derivative were resolved by HPLC on a chiral column. The single crystal of the [6]helicene derivative exhibits an intermolecular interactions of the 1,8-naphthalimide units. The Royal Society of Chemistry 2012.

Full text of DOI:10.1039/c2ob25223f

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COMMUNICATION
Synthesis and characterization of 1,8-naphthalimide with [6]helicene
skeleton†
Toshitaka Kogiso, Kosuke Yamamoto, Hiroshi Suemune* and Kazuteru Usui*
Received 31st January 2012, Accepted 27th February 2012
DOI: 10.1039/c2ob25223f
that may lead to a new class of materials with useful electronic
properties.
Herein, we describe the synthesis of 1,8-naphthalimide with
[6]helicene skeleton by photochemical cyclization.
A 1,8-naphthalimide with [6]helicene derivative scaffold has
been designed and synthesized. The (P)- and (M)-enantio-
mers of the [6]helicene derivative were resolved by HPLC on
a chiral column. The single crystal of the [6]helicene deriva-
tive exhibits an intermolecular interactions of the 1,8-
naphthalimide units.
Retrosynthetic analysis of a 1,8-naphthalimide-based helicene
molecule is shown in Fig. 1. We envisioned that the [6]helicene
derivative could be constructed from the mono(arylvinyl)arene
and bis(arylvinyl)arene via oxidative photocyclization. The
single- and double-oxidative photocyclization processes have
indeed proved to be very convenient for the preparation of heli-
cene derivatives, starting from readily accessible mono- and bis
(arylvinyl)arene intermediates.14
The synthesis of mono(arylvinyl)arene 2 is depicted in
Scheme 1 (top). Compound 6 was synthesized starting from
naphthalic anhydride 4 by regioselective bromination and sub-
sequent amidation. L-Proline catalyzed the coupling reaction of 6
with CuCN using Wang’s protocol, providing the nitrile-substi-
tuted derivative 7 in 82% yield,15 and the nitrile group was con-
verted to the corresponding aldehyde 8 with RANEY® Ni. The
aldehyde 8 was subsequently reacted with phosphonate 9 to
furnish 2.
Naturally occurring chiral helical architectures such as DNA
duplex and α-helix in peptides play critical roles in biological
functions. Helical molecules are also significant in materials
science and chemical processes as they are widely applied in
numerous fields such as enantioselective catalysis,1 chiral recog-
nition2 and self-assembly,3 nonlinear optics,4 and molecular
switches.5 In recent years, chiral π-conjugated molecules have
attracted attention in the field of organic electronic materials
because of their specific electronic properties.6
1,8-Naphthalimide derivatives have been used as supramole-
cular moieties in model compounds for photoinduced electron
transfer in photophysical studies,7 and for fluorescent probes in
the medical and biological fields.8 In addition, such N-substi-
tuted derivatives have also been used as ligands in asymmetric
reactions.9 Although some 1,8-naphthalimide derivatives with
chiral N-substituents have been designed and synthesized,10 1,8-
naphthalimide derivatives based on helical geometry have not
been reported except for twisted perylene bisimide.11 We became
particularly interested in the chiroptical properties of 1,8-
naphthalimide with a chiral helicene skeleton because helicenes
with well-defined helicoidal polyaromatic structures are known
to be photo-stable. [n]Helicene derivatives are helicoidally
shaped benzologues of phenanthrene comprising ortho-fused
aromatic and/or hetero-aromatic rings,12 which exhibit unique
structural features and have a wide range of potential appli-
cations in chiral materials and asymmetric synthesis.13 One
important challenge with regard to further expanding the poten-
tial of helicenes is to develop new frameworks with functionality
The synthesis of bis(arylvinyl)arene 3 was performed as
shown in Scheme 1 (bottom). The vinyl moiety of 10 was
installed by Stille coupling using tributyl(vinyl)tin. The
Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1
Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. E-mail: usui@phar.
kyushu-u.ac.jp; Fax: +81 92-642-6605; Tel: +81 92-642-6605
†Electronic supplementary information (ESI) available: Details of prep-
aration and characterization, NMR spectra of all the synthesized com-
pounds, and HPLC analysis of the racemic compound. CCDC 856591.
For ESI and crystallographic data in CIF or other electronic format see
DOI: 10.1039/c2ob25223f
Fig. 1 Retrosynthetic approach to 1,8-naphthalimide with [6]helicene
skeleton.
2934 | Org. Biomol. Chem., 2012, 10, 2934–2936
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Scheme 2 Reagents and conditions: i, hv, I2, toluene, r.t.; ii, tributyl
(vinyl)tin, Pd2(dba)3, P(tBu)3, toluene, 80 °C (86%).
Table 1 Oxidative photochemical reaction of 3 and 13
Yield
(%) of
1
Yield
(%) of
16
Conc.
(mM)
Reaction
time (h)
Substrate Device
3
Batcha
Batcha
Batcha
1
1
72
72
4
16
19
55
27
Trace
Trace
Trace
13
13
13
Scheme 1 Synthesis of mono(arylvinyl)arene 2 and bis(arylvinyl)
arene 3. Reagents and conditions: i, Br2, Ag2SO4, H2SO4, 65 °C (93%);
ii, neopentylamine, dioxane, 100 °C (quant.); iii, CuCN, L-proline,
DMF, 160 °C (82%); iv, RANEY® Ni, HCO2H, reflux (29%); v, 9,
NaH, THF, 0 °C–r.t. (98%); vi, tributyl(vinyl)tin, Pd2(dba)3, P(tBu)3,
toluene, 80 °C (73%); vii, 4-bromobenzaldehyde, Pd(OAc)2, PPh3,
AcONa, DMF, 120 °C (96%); viii, 12, NaH, THF, 0–30 °C (79%); ix,
LiAlH4, AlCl3, THF, 0 °C–r.t. (76%).
0.25
72
Microreactorb 0.25
0.17c
a Black lights (20 W × 7 pieces, total 140 W) with a peak wavelength of
350 nm. b UV LEDs (250 mW × 6 pieces, total 1.5 W) with a peak
wavelength of 365 nm. c Residence time is given, which was calculated
according to the equation, t (h) × flow rate (μL h−1) = volume of
microchannel (μL).
Mizoroki–Heck cross-coupling reaction of vinyl-substituted 10
with a 4-bromobenzaldehyde afforded the mono(arylvinyl)arene
derivative 11 in 96% yield after purification by column chrom-
atography. The Horner–Wadsworth–Emmons (HWE) reaction of
compound 11 with phosphonate 12 gave 3 in 79% yield.
To complete the synthesis of [6]helicene 1, 2 and 3 were then
photocyclized in the presence of a stoichiometric amount of
iodine as an oxidizing agent and an excess amount of THF as a
hydrogen iodide scavenger.14d Oxidative photocyclization of 2 in
toluene on the scale of 1.5 mM did not give the desired 1, but
the corresponding 1,8-naphthalimide with dibenzo[a,k]tetra-
phene derivative 14 as a sole product was obtained in 91% yield
(Scheme 2). Structures of compound 14 and its vinyl derivative
15 were determined on the basis of COSY, NOESY, HSQC, and
HMBC correlations (see Fig. S1 in ESI†).
Oxidative photocyclization of 3 on the scale of 1.0 mM
afforded 1 and mono(arylvinyl)arene derivative 16 (Scheme 2,
Table 1). This result shows strong evidence that the double
photocyclization of 3 leading to 1 proceeds via intermediate 16
rather than intermediate 2. In the case of oxidative photocycliza-
tion using a reduced bis(arylvinyl)arene 13, compound 1 was
obtained in a better yield than that of 3 (Schemes 1 and 2). The
reaction yield of 1 was slightly improved by decreasing the reac-
tion concentration of the substrate from the scale of 1 mM to
0.25 mM. In addition, the use of a microflow system resulted in
a dramatic improvement of the yield of 1 (55%, Table 1).
We proposed that the species responsible for the oxidation of
the benzylic position to yield the 1,8-naphthalimide was the
iodine radical, generated from I2 and/or HI under light irradiation
(see Fig. S5 in ESI†). Subsequently, the produced radical species
is reacted with molecular oxygen, followed by dehydration to
afford the ketone.16 Since the rate constants for H-atom abstrac-
tion by radical species should be related to the bond dissociation
enthalpy (BDE) of the relevant C–H bond, we calculated the C–
H BDE by a density functional theory (DFT)-based approach
with the B3LYP functional. As a result, it was shown that the
BDE at the benzylic carbon with neighboring N-atom is lower
than that of other model compounds (see Table S1 in ESI†).
The structure of 1 was confirmed by single-crystal X-ray
analysis (Fig. 2). The interplanar angle between the terminal
rings of 1 in a solid state was 45.7°. Furthermore, inspection of
the crystal structure of 1 revealed that the packing is mainly gov-
erned by antiparallel π–π stacking interactions between naphtha-
limide chromophores of opposite helicity (Fig. 2).17
The absorption of UV/vis spectra of the racemic mixtures 1 in
CHCl3 is shown in Fig. 3 (top).
The separation of the enantiomers was accomplished via
HPLC on a chiral column (Daicel Chiralpak IA, 4.6 mm ×
250 mm) using a UV light detector at 254 nm. The chromatogram
showed successful separation of the enantiomers (see Fig. S4 in
ESI†). The absolute stereochemistry of (P)-(+)- and (M)-(−)-1
was determined by their optical rotation ([a]D = +2294 (c = 5.0
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as depicted in Fig. 3 (bottom). In the region of 290–450 nm of
the CD spectra, a broad monosignated peak with a maximum at
342 nm can be seen, which properly correlates with the absorp-
tion maximum at 342 nm (Fig. 3, top).
In conclusion, we demonstrated the first synthesis of novel
optical active 1,8-naphthalimide with [6]helicene derivative 1
from the oxidative photocyclization of a bis(arylvinyl)arene. The
oxidative photocyclization of 13 involves concomitant oxidation
at the benzylic position. Further functionalization at the reactive
bromine site of 1 is currently underway in our group.
This work was financially supported by a Grant-in-Aid for
Young Scientists (B) from the Japan Society for the Promotion
of Science (No. 23790013).
Notes and references
1 For the case of DNA, see: (a) A. J. Boersma, R. P. Megens, B. L. Feringa
and G. Roelfes, Chem. Soc. Rev., 2010, 39, 2083; (b) S. Juliá, J. Guixer,
J. Masana, J. Rocas, S. Colonna, R. Annuziata and H. Molinari, J. Chem.
Soc., Perkin Trans. 1, 1982, 1317; For the case of synthetic chiral com-
pounds, see:(c) T. Ooi and K. Maruoka, Angew. Chem., Int. Ed., 2007,
46, 4222; (d) S. D. Dreher, T. J. Katz, K.-C. Lam and A. L. Rheingold, J.
Org. Chem., 2000, 65, 815.
2 T. W. Bell and N. M. Hext, Chem. Soc. Rev., 2004, 33, 589.
3 (a) C. Maeda, T. Kamada, N. Aratani and A. Osuka, Coord. Chem. Rev.,
2007, 251, 2743; (b) D. K. Smith, Chem. Soc. Rev., 2009, 38, 684.
4 L. M. Haupert and G. J. Simpson, Annu. Rev. Phys. Chem., 2009, 60,
345.
Fig. 2 X-ray structure of compound 1. (a) The ellipsoid drawn at 50%
probability level, H atoms and THF solvents omitted for clarity. Views
of the 1,8-naphthalimide π–π stack of 1 perpendicular (b) and parallel
(c) to the arene plane.
5 B. L. Feringa, R. A. van Delden, N. Koumura and E. M. Geertsma,
Chem. Rev., 2000, 100, 1789.
6 (a) A. Rajca and M. Miyasaka, Angew. Chem., Int. Ed., 2003, 42, 2448;
(b) C. Nuckolls, R. F. Shao, W. G. Jang, N. A. Clark, D. M. Walba and
T. Katz, Chem. Mater., 2002, 14, 773; (c) H. Osuga and K. Tanaka, J.
Synth. Org. Chem. Jpn., 2002, 60, 593.
7 A. Prasanna da Silva, H. Q. Nimal Gunaratne, J. L. Habib-Jiwan, C.
P. McCoy, T. E. Rice and J.-P. Soumillion, Angew. Chem., Int. Ed. Engl.,
1995, 34, 1728.
8 K. K. Dubey, R. K. Singh and K. Misra, Indian J. Chem., 1995, B34,
876.
9 P. Müller and A. Ghanem, Org. Lett., 2004, 6, 4347.
10 (a) J. Gawroński, M. Kwit and K. Gawrońska, Org. Lett., 2002, 4, 4185;
(b) Q. Yang, P. Yang, X. Qian and L. Tong, Bioorg. Med. Chem. Lett.,
2008, 18, 6210.
11 (a) Z. Xie and F. Würthner, Org. Lett., 2010, 12, 3204; (b) C.
L. Eversloh, Z. Liu, B. Müller, M. Stangl, C. Li and K. Müllen, Org.
Lett., 2011, 13, 5525.
12 Y. Shen and C.-F. Chen, Chem. Rev., 2011, DOI: 10.1021/cr200087r.
13 (a) D. Nakano and M. Yamaguchi, Tetrahedron Lett., 2003, 44, 4969;
(b) T. Kawasaki, K. Suzuki, E. Licandro, A. Bossi, S. Maiorana and
K. Soai, Tetrahedron: Asymmetry, 2006, 17, 2050; (c) J. Chen,
B. Captain and N. Takenaka, Org. Lett., 2011, 13, 1654; (d) M.
R. Crittall, H. S. Rzepa and D. R. Carbery, Org. Lett., 2011, 13, 1250.
14 For selected syntheses of helicene compounds using an electrocycliza-
tion/oxidation sequence see: (a) F. B. Mallory and C. W. Mallory, Org.
React., 1984, 30, 1, and references therein (b) P. Kovacic and M. B. Jons,
Chem. Rev., 1987, 87, 357; (c) C. Stammel, R. Fröhlich, C. Wolff,
H. Wenck, A. d. Meijere and J. Mattay, Eur. J. Org. Chem., 1999, 7,
1709; (d) H. R. Talele, M. J. Gohil and A. V. Bedekar, Bull. Chem. Soc.
Jpn., 2009, 82, 1182; (e) M. S. M. Pearson and D. R. Carbery, J. Org.
Chem., 2009, 74, 5320.
Fig. 3 UV/vis spectra (top, rac-[6]helicene 1) and CD spectra (bottom)
of (P)-1 (solid blue line) and (M)-1 (solid red line) enantiomers in dilute
CHCl3 solution.
15 D. Wang, L. Kuang, Z. Li and K. Ding, Synlett, 2008, 69.
16 S. Hirashima, T. Nobuta, N. Tada, T. Miura and A. Itoh, Org. Lett., 2010,
12, 3645.
17 (a) D. L. Reger, J. D. Elgin, R. F. Semeniuc, P. J. Pellechia and M.
D. Smith, Chem. Commun., 2005, 4068; (b) D. L. Reger, J. D. Elgin, M.
D. Smith and B. K. Simpson, Polyhedron, 2009, 28, 1469.
18 Positive and negative signs of [α]D are usually found for (P)- and (M)-[n]
helicenes, respectively. See: (a) K. P. Meurer and F. Vögtle, Top. Curr.
Chem., 1985, 127, 1; (b) W. H. Laarhoven and W. J. C. Prinsen, Top.
Curr. Chem., 1984, 125, 63.
× 10−3, 20 °C, CHCl3), [a]D = −2379 (c = 4.4 × 10−3, 20 °C,
CHCl3)).18
The CD spectra obtained for the enantiomers of (P)-1 (blue
trace) and (M)-1 (red trace) showed a mirror image relationship,
2936 | Org. Biomol. Chem., 2012, 10, 2934–2936
This journal is © The Royal Society of Chemistry 2012