Synthesis and characterization of a new hexacyclic helicene

Article abstract of DOI:10.1016/j.tetlet.2012.04.014

A new helically chiral hexacyclic system, bearing an acetoxymethyl group, was prepared from a simple naphthalene building block in good yield and purity, via a four-step sequence involving palladium-catalysed Heck couplings and oxidative photocyclizations

Full text of DOI:10.1016/j.tetlet.2012.04.014

Tetrahedron Letters 53 (2012) 3216–3219
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Tetrahedron Letters
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Synthesis and characterization of a new hexacyclic helicene
⇑
Faouzi Aloui, Souad Moussa, Béchir Ben Hassine
Laboratoire de Synthèse Organique Asymétrique et Catalyse Homogène (O1UR1201), Faculté des Sciences, Avenue de l’environnement, 5019 Monastir, Tunisia
a r t i c l e i n f o
a b s t r a c t
Article history:
A new helically chiral hexacyclic system, bearing an acetoxymethyl group, was prepared from a simple
naphthalene building block in good yield and purity, via a four-step sequence involving palladium-
catalysed Heck couplings and oxidative photocyclizations. Suitable crystals of the latter indicate that
its conformation closely resembles that of unsubstituted [6]helicene, whose idealized symmetry is C2.
The optical properties of the hexacyclic helicene were investigated and show interesting behaviour.
Ó 2012 Elsevier Ltd. All rights reserved.
Received 26 January 2012
Revised 15 March 2012
Accepted 4 April 2012
Available online 12 April 2012
Keywords:
Helicenes
Heck coupling
Photocyclization
Fused-rings
Helicenes are polycyclic aromatic hydrocarbons composed of
ortho-fused aromatic rings resulting in helical chiral and highly
conjugated structures. Their specific chiral structure is due to the
repulsive steric interactions between the terminal aromatic rings
resulting in left and right-handed chiral helical structures of M
and P configurations, respectively.1 They exhibit specific optical
rotation depending on the gross structure, and fine geometry and
electronic interactions.2 The unique structure of helicenes makes
them very stable towards acids, bases and relatively high
temperature.3
did not report the resolution of this helical alcohol or its use in
catalysis. The first enantiomerically-enriched helical alcohol with
a
[6]helicene skeleton, named HELIXOL, was prepared by
Reetz and Sostmann and used as an enantioselective fluores-
cent sensor.13 Shortly after, Wachsmann et al.14 prepared 2,
15-dihydroxymethyl[6]helicene, the resolution of which was
achieved by chiral HPLC.
We have previously reported the synthesis and characterization
of some interesting helically chiral aromatic structures,15 using pal-
ladium-promoted Mizoroki–Heck coupling reactions and classical
oxidative photocyclization, while searching for new chiral ligands.
Due to the small number of oxygen-containing [6]helicenes, we
wanted to extend the same approach to the design and synthesis
of a heterohelicene with an acetoxymethyl group at a selected posi-
tion on the terminal aromatic group. Our synthetic strategy makes
use of benzo[c]phenanthrene 1 as a key building block for the prep-
aration of the helicene-precursor 2. The precursor is then easily
converted into the corresponding helically chiral hexacyclic system
3 by oxidative photocyclization. The acetoxymethyl group in this
chiral compound serves as an appropriate functional group for
increasing the solubility of the helicene in organic solvents.
The synthetic route to the helical compound 3 began with the
Helical backbones, which combine electron delocalization and
non-planarity of the
p-electron network, demonstrate various
properties and applications such as circularly polarized lumines-
cence,4,5 non linear optical6 and the ability to act as potentially
useful components in chiral discotic liquid crystalline materials,7
as building blocks for helical conjugated polymers8 and as rotors.9
In particular, functionalized hexahelicenes and larger [n]helicenes
are promising candidates for chiral catalysts10 and ligands11 in
asymmetric syntheses because of their rigid framework, high opti-
cal stability and resistance to isomerization.
The preparation of heterohelicenes has been studied extensively
in order to exploit the particular properties of these helically shaped
molecules. However, most of the strategies adopted for their synthe-
sis suffer from a lack of general applicability and low yields. A few
reports have described the synthesis of oxygen-containing helicenes
with applications in some branches of chemistry.
coupling of 2-bromonaphthalene with 4-bromostyrene via
Mizoroki–Heck reaction in the presence of sodium acetate and
Herrmann’s palladacycle {trans-di( -acetato)-bis[o-(di-o-toly-
a
l
lphosphino)-benzyl]dipalladium} as the catalyst, in N,N-dimethyl-
acetamide (DMA). The mixture was heated at 140 °C for about 48 h
to afford the corresponding diarylethene 4 in 65% yield (Scheme 1).
No product of homo-coupling of 4-bromostyrene was evident.
Previously, we demonstrated that the coupling reaction between
2-vinylnaphthalene and 1,4-dibromobenzene, using Heck condi-
tions, produced the same olefin 4 in good yield.16 The resulting
In an independent study, Tepl et al. reported the synthesis of 2-
hydroxyhexahelicene using a route based on a key intramolecular
[2+2+2] cycloisomerization of a substituted triyne.12 The authors
⇑
Corresponding author. Tel.: +216 73500279; fax: +216 73500278.
E-mail address: bechirbenhassine@yahoo.fr (B.B. Hassine).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.04.014

F. Aloui et al. / Tetrahedron Letters 53 (2012) 3216–3219
3217
Br
Br
Br
1%[Pd], NaOAc
+
DMA, 140 °C, 48 h
65%
4
hν, cyclohexane
Br
propylene oxide, I2
80%
1
Scheme 1. Synthesis of 2-bromobenzo[c]phenanthrene (1).
O
O
O
O
1%[Pd], NaOAc
+
DMA, 140 °C, 48 h
75%
Br
2
O
1
O
OH
KOH (3 M)
98%
hν, toluene
propylene oxide, I2
88%
3
5
Scheme 2. Synthesis of 2-hydroxymethylhexahelicene (5).
Figure 1. Crystal structure (ORTEP) of ( )-2-acetoxymethylhexahelicene (3).

3218
F. Aloui et al. / Tetrahedron Letters 53 (2012) 3216–3219
Table 1
Table 3
Selected inner and outer bond lengths (Å) and distances between non-bonded atoms
Physical properties of the helically chiral compounds 3 and 5
in ( )-3
Abs
Compound
Eg (eV)
k
(nm)
max
Inner C–C bond lengths
C1–C16E
3
5
269
264
3.18
3.30
1.412
1.448
1.442
1.453
1.447
1.406
C16D–C16E
C16C–C16D
C16B–C16C
C16A–C16B
C16–C16A
reactor for about 150 minutes to afford the expected 2-acetoxym-
ethylhexahelicene 3 in 88% yield, and overall 34% yield (Scheme
2).19 No other regioisomer was isolated from the reaction mixture
indicating that ring-closure of the diarylethene 2 had occurred at
the peri position of the tetracyclic moiety. Treatment of compound
3 with potassium hydroxide solution (3 M) provided 2-hydroxym-
ethylhexahelicene 5 in 98% yield (Scheme 2).20
Outer C–C bond lengths
C3–C4
C5–C6
C7–C8
C9–C10
1.356
1.332
1.323
1.346
1.350
C11–C12
Distance between non-bonded atoms
Suitable crystals of 2-acetoxymethylhexahelicene 3 were ob-
tained as pale yellow plates by slow evaporation of a methylene
chloride solution at room temperature. X-ray analysis of helicene
3 was carried out on a single crystal obtained from the racemic
form as shown in Figure 1. The outer bonds C(5)–C(6), C(7)–C(8),
C(9)–C(10) and C(11)–C(12) are shortened to 1.32–1.35 Å with re-
spect to the averaged bond length in benzene (1.39 Å), whereas the
inner bond distances C(1)–C(16E), C(16D)–C(16E), C(16C)–C(16D),
C(16B)–C(16C), C(16A)–C(16B) and C(16)–C(16A) are lengthened
to 1.40–1.45 Å (Table 1).
C1–C16
C2–C15
C3–C14
3.108
4.288
5.300
Table 2
Torsion angles of ( )-3 and hexahelicene
Compound
Torsion angle (°)a
u
1
u
2
u
3
u4
The torsion angles along the inner helical rim (C16–C16A–
3
15.2
11.2
29.0
30.0
14.6
15.2
26.3
30.3
C16B–C16C,
C16C–C16D–C16E–C1,
C16B–C16C–C16D–C16E,
Hexahelicene
C16A–C16B–C16C–C16D), which vary from 14.6° to 29.0°, are also
a convenient measure of the helicity and are in accordance with
those observed in hexahelicene (Table 2).21 The terminal inner
helical torsion angles (C16–C16A–C16B–C16C and C16C–C16D–
C16E–C1) show somewhat unequal, but relatively small widening
at 15.2° and 14.6°.22
a
u
1 = C16–C16A–C16B–C16C;
u
2 = C16A–C16B–C16C–C16D;
u
3 = C16C–
C16D–C16E–C1; 4 = C16B–C16C–C16D–C16E.
u
alkene 4 was subjected to photocyclization in cyclohexane using a
500 W high-pressure mercury immersion lamp. The photolysis
was carried out on 800 mg scale per run in a reactor containing
cyclohexane (1.5 L), for about 2 h in the presence of iodine as an
oxidizing agent and excess propylene oxide as a hydrogen iodide
scavenger17 to provide the expected 2-bromobenzo[c]phenan-
threne (1) in 80% yield, after purification by column chromatogra-
phy (Scheme 1).
The UV/vis absorption spectra of dilute helicene solutions in
chloroform (1.5 Â 10À6 M) are shown in Figure 2. The samples
show strong absorption below 400 nm. The absorption of hexahe-
licene 3 in the high energy region is well structured containing
three prominent bands at 268, 322 and 336 nm, respectively. These
absorption bands are associated with
p–p
transitions23 and are
similar to the characteristic vibration patterns of other helicene
derivatives.6 No broad absorption band in the low energy region
was observed.
The optical band gap (Eg) determined from the absorption edge
of the solution spectra is given in Table 3. The optical energy band
gap of the hexahelicene 3 was calculated as 3.18 eV from the onset
of the absorption around 389 nm.
In conclusion, we have prepared a new hexahelicene derivative
starting from readily available and inexpensive materials. We
completed the synthesis of the helical framework of 3 in only four
steps with an overall 34% yield. The optical resolution of 3 is
Having obtained the key building block 1, we were able to com-
plete the convergent synthesis of the acetoxymethylhexahelicene
3. Thus, benzo[c]phenanthrene 1 and 4-acetoxymethylstyrene
(1.5 equiv) underwent a Mizoroki–Heck coupling using 1% of
Hermann’s catalyst. The desired coupled product 2, possessing
E-stereochemistry at the double bond, based on the 1H NMR
spectrum,18 was obtained in 75% yield after heating for 48 h at
140 °C (Scheme 2).
Alkene 2 underwent photocyclization in the presence of a stoi-
chiometric amount of iodine and an excess of propylene oxide. The
photolysis was performed on 350 mg scale per run, in a one litre
1.2
1.2
1.0
0.8
0.6
0.4
0.2
0.0
5
3
1.0
0.8
0.6
0.4
0.2
0.0
250
300
350
400
450
500
250
300
350
400
450
500
Wavelengh (nm)
Wavelengh (nm)
Figure 2. UV/vis absorption spectra of the helically chiral compounds 3 and 5 in dilute (1.5 Â 10À6 M) chloroform solutions.

F. Aloui et al. / Tetrahedron Letters 53 (2012) 3216–3219
3219
18. Spectroscopic data for the diarylethene 2: colourless solid, showing violet
fluorescence when dissolved in CH2Cl2 or CHCl3; Rf = 0.33 (cyclohexane/EtOAc,
80:20); mp = 146–148 °C; 1H NMR (300 MHz, CDCl3): d (ppm): 2.14 (s, 3H,
CH3), 5.15 (s, 2H, CH2), 7.30 (d, J = 16.2 Hz, 1H, Hvinyl), 7.39–7.45 (m, 3H), 7.60-
7.63 (m, 2H), 7.65–7.70 (m, 1H), 7.73–7.79 (m, 1H), 7.81–7.94 (m, 5H), 8.01 (d,
J = 8.4 Hz, 1H), 8.05 (dd, J1 = 8.1 Hz, J2 = 1.5 Hz, 1H), 9.16 (s, 1H, H-1), 9.17 (d,
J = 8.1 Hz, 1H); 13C NMR (75 MHz, CDCl3): d (ppm): 21.07 (CH3), 66.11 (OCH2),
123.21 (CH), 125.93 (CH), 126.27 (CH), 126.74 (2CH), 126.88 (CH), 126.98 (CH),
127.14 (CH), 127.26 (CH), 127.38 (C), 127.62 (CH), 127.81 (CH), 128.56 (CH),
128.65 (CH), 128.79 (2CH), 128.98 (CH), 129.79 (CH), 130.34 (C), 130.64 (C),
131.37 (C), 133.14 (C), 133.58 (C), 135.02 (C), 135.32 (C), 137.47 (C), 170.90
currently in progress for the examination of this compound as a
ligand or for broader exploitation.
Acknowledgements
The authors are grateful to the DGRS (Direction Générale de la
Recherche Scientifique) of the Tunisian Ministry of Higher Educa-
tion and Scientific Research.
(CO); HRMS (MALDI-TOF) calcd for
402.16115.
C
29H22O2 [M]+: 402.16198, found:
References and notes
19. Spectroscopic data for the 2-acetoxymethylhexahelicene 3: pale yellow solid;
Rf = 0.35 (cyclohexane/EtOAc, 80:20); mp = 198-200 °C; 1H NMR (300 MHz,
CDCl3): d (ppm): 1.93 (s, 3H, CH3), 4.44 (d, J = 12.6 Hz, 1H, CH2), 4.59 (d,
J = 12.6 Hz, 1H, CH2), 6.68 (ddd, J1 = 1.5 Hz, J2 = 6.9 Hz, J3 = 8.7 Hz, 1H), 7.19–
7.26 (m, 2H), 7.57 (d, J = 8.4 Hz, 1H), 7.59 (s, 1H), 7.81-7.85 (m, 2H), 7.91–8.05
(m, 8H); 13C NMR (75 MHz, CDCl3): d (ppm): 20.93 (CH3), 66.00 (OCH2), 124.10
(C), 124.60 (CH), 125.15 (CH), 125.59 (CH), 126.26 (CH), 126.66 (CH), 126.98
(CH), 127.15 (CH), 127.24 (CH), 127.36 (2CH), 127.51 (3CH), 127.83 (C), 127.87
(C), 127.91 (2CH), 129.71 (C), 129.80 (C), 131.36 (C), 131.47 (C), 131.48 (C),
131.85 (C), 132.24 (C), 133.16 (C), 170.60 (CO); ESI-MS: m/z = 400.14 [M+];
Anal. Calcd for C29H20O2: C, 86.98; H, 5.03. Found: C, 86.91; H, 5.01.
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20. Spectroscopic data for the 2-hydroxymethylhexahelicene 5: pale-yellow solid;
Rf = 0.20 (cyclohexane/EtOAc, 80:20); mp = 134-136 °C; 1H NMR (300 MHz,
CDCl3): d (ppm): 3.95 (d, J = 12.3 Hz, 1H, CH2), 4.12 (d, J = 12.3 Hz, 1H, CH2),
6.68 (ddd, J1 = 1.2 Hz, J2 = 6.9 Hz, J3 = 8.1 Hz, 1H), 7.20-7.28 (m, 2H), 7.52 (s,
1H), 7.54 (d, J = 8.4 Hz, 1H), 7.83 (d, J = 8.4 Hz, 1H), 7.88 (d, J = 8.1 Hz, 1H), 7.90–
8.05 (m, 8H); 13C NMR (75 MHz, CDCl3): d (ppm): 65.73 (OCH2), 124.12 (C),
124.65 (CH), 125.27 (CH), 125.48 (CH), 126.55 (CH), 126.70 (CH), 126.83 (CH),
127.21 (CH), 127.23 (CH), 127.31 (CH), 127.33 (CH), 127.44 (CH), 127.62 (C),
127.67 (2CH), 127.75 (C), 128.11 (CH), 128.35 (CH), 129.53 (C), 130.05 (C),
131.40 (C), 131.55 (C), 131.60 (C), 131.67 (C), 133.25 (C), 137.34 (C); ESI-MS:
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m/z = 359.1 [M+H]+.
; HRMS (MALDI-TOF) Calcd for C27H19O :
[M+H]+.
359.13576. Found: 359.13489.
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22. Crystal data for compound 3 (C29H20O2) were recorded on a Bruker SMART CCD
diffractometer, M = 400.45, triclinic, space group P-1. a = 9.2722(12) Å,
b = 10.6879(14) Å, c = 23.532(3) Å, V = 2079.4(5) Å3, Z = 4,
q
calcd = 1.279 g/
cm3, X-ray source CuK
a,
k = 1.54187 Å, T = 293(2) K, measured
reflections = 7067, independent reflections = 2479, reflections used = 2479,
refinement type = Fsqd, parameters refined = 562, R1 = 0.0479, wR2 = 0.306.
Crystallographic data for the structure in this paper have been deposited with
the Cambridge Crystallographic Data Centre as supplementary publication
number CCDC 778370. These data can be obtained free of charge from the
Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ,
UK; fax: +44 (0) 1223 336033 or e-mail: deposit@ccdc.cam.ac.uk.
ˇ
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