Synthesis of a configurationally locked [5]helicene derivative

Article abstract of DOI:10.1055/s-2004-831229

The photochemical cyclisation-dehydrogenation of the bis-styrylbenzene 3, where the terminal aryl moieties are connected by a suitable chiral tether derived from 1,3-pentanediol, led to a chiral, configurationally locked [5]helicene derivative. An X-ray diffraction study showed that an (5,5)-configuration of the chiral auxiliary induces a (P)-configuration of the helical framework.

Full text of DOI:10.1055/s-2004-831229

PAPER
2513
Synthesis of a Configurationally Locked [5]Helicene Derivative
Synthesis of
a
Co
i
nfigura
a
tionally Lo
d
cked
[
5]Heli
h
c
ene
D
erivative El Abed,a Béchir Ben Hassine,*a Jean-Pierre Genêt,*b Mohamed Gorsane,a Jonathan Madec,b Louis Ricard,c
Angela Marinetti*b
a
Laboratoire de Synthèse Organique Asymétrique et Catalyse Homogène, Faculté des Sciences de Monastir, Avenue de l’Environnement,
5019 Monastir, Tunisia
b
Laboratoire de Synthèse Sélective Organique et Produits Naturels, UMR 7573, E.N.S.C.P. 11, rue Pierre et Marie Curie, 75231 Paris
Cedex 06, France
Fax +33(1)44071062; E-mail: marinet@ext.jussieu.fr
c
Laboratoire Hétéroéléments et Coordination, Ecole Polytechnique, 91128 Palaiseau Cedex, France
Received 26 March 2004; revised 24 June 2004
parent [5]helicene, which displays a t1/2 of 62 min at
57 °C. Nevertheless, samples of optically enriched [5]he-
licene could be prepared by either crystallization from a
racemic mixture by using (+)-TAPA [2-(2,4,5,7-tetrani-
Abstract: The photochemical cyclisation–dehydrogenation of the
bis-styrylbenzene 3, where the terminal aryl moieties are connected
by a suitable chiral tether derived from 1,3-pentanediol, led to a
chiral, configurationally locked [5]helicene derivative. An X-ray
diffraction study showed that an (S,S)-configuration of the chiral tro-9-fluorenylideneaminoxy)propionic acid] as the re-
auxiliary induces a (P)-configuration of the helical framework.
solving agent, or starting from optically pure binaphthyl
derivatives. The non-racemic samples of [5]helicenes
were thus isolated at 0 °C and displayed [a]578 values of
–1670° and +2270° (2430°) respectively.14,10b
Key words: helical structures, chiral auxiliaries, diols, photochem-
istry, stereoselectivity
An increased configurational stability can be attained by
introducing substituents on the 1,14 positions of [5]heli-
cene derivatives, which create higher steric hindrance.
Thus, for instance, the optically pure 1,14-dimethyl sub-
stituted [5]helicene I (Figure 1) {[a]D –754 (MeOH)}
showed no optical rotation change after refluxing its etha-
nol solution for 24 h.15
Since their discovery by Newman and Lednicer,1 enantio-
merically pure helicene derivatives have attracted atten-
tion because of their unique chiral structure and very high
optical rotation values. To date, their potential as chiral
ligands,2 catalysts,3 auxiliaries,4 molecular recognition
agents5 and materials6 is well established.7
A number of helicenes have been obtained in enantiomer-
ically enriched form mainly by separation of racemic mix-
tures through crystallisation,1 HPLC techniques8 or
chromatographic separation of the diastereoisomeric mix-
tures formed with stoichiometric chiral auxiliaries.4a,9
Some studies have been also reported, where chirality
transfer or retention from enantiomerically enriched start-
ing materials are applied to helicene syntheses,10 while
enantioselective catalytic methods are at a very early stage
and afford to date only moderate enantiomeric excesses.11
Finally, some asymmetric syntheses have been performed
which make use of chiral auxiliaries covalently bonded to
the starting material, in the key, enantio-determining
step.12
4
5
6
3
2
O
O
O
O
O
O
7
8
1
14
13
12
9
I15
11
10
Figure 1
Here we report on the synthesis of a new [5]helicene de-
rivative where the helical chirality has been set by means
of a chiral tether connecting the 2,13 positions.
Concerning the application of helicenes in chiral techno-
logies, a major issue is their configurational stability,
which appeared to be surprising low. The easy racemiza-
tion of helical frameworks is usually assigned to twisting
distributed over a large number of aromatic bonds.
In this work, the configurationally locked [5]helicene 4
has been prepared by using a chiral tether derived from
(R,R)-2,4-pentanediol, which is connected to the 2,13 po-
sitions of the final helicene through ether functions. The
choice of the chiral tether was based on the known high ef-
ficiency of the 2,4-pentanediol bis-ether moiety as a chiral
auxiliary in many diastereoselective intramolecular reac-
tions.16 Notably, the highly diastereoselective synthesis of
atropoisomeric biaryls has been performed via the copper-
promoted coupling of tethered bis-aryl derivatives.17 In-
tramolecular carbene insertion reactions18 and [2 + 2]-cy-
cloaddition reactions have also been described.19
Among simple, unsubstituted carbohelicenes, a sequence
of at least six aromatic rings is required to ensure config-
urational stability at room temperature.13 Lower members
are known to racemize quite easily. This is the case for the
SYNTHESIS 2004, No. 15, pp 2513–2516
x
x.
x
x
.
2
0
0
4
Advanced online publication: 22.09.2004
DOI: 10.1055/s-2004-831229; Art ID: T03304SS
© Georg Thieme Verlag Stuttgart · New York
Our synthetic strategy is shown in Scheme 1.

2514
R. El Abed et al.
PAPER
compound is +975 (c 0.5, CHCl3), which suggests a (P)-
configuration of the helical moiety.
The (P)-helicity of 4 was confirmed by an X-ray diffrac-
tion study [relative stereochemistry with respect to the
known (S,S)-configuration of the diether moiety]. An
ORTEP drawing of 4 is shown in Figure 3.
Scheme 1 Reagents and conditions: (a) Diethyl azodicarboxylate
(DEAD), PPh3, THF, 40 °C, 18 h; (b) EtOLi, EtOH, 50 °C, 18 h; (c)
hn, I2, propylene oxide, toluene, 15 min
The (R,R)-2,4-pentanediol was used as the enantiomeri-
cally pure starting material for the synthesis of the bis-
ether derivative 2, through a Mitsunobu reaction with two
equivalents of p-hydroxybenzaldehyde.
The formyl groups of 2 were then involved in an inter–in-
tramolecular bis-Wittig reaction with the bis-phospho-
nium salt of a,a¢-dibromo-p-xylene.20 The macrocyclic
bis-ether 3 was obtained in moderate yield (35%), proba-
bly because of concurrent intermolecular reactions. It is
assumed to have a Z,Z stereochemistry, based on the C2-
Figure 3 Crystal structure of 4: ORTEP drawing, selected bond
distances and dihedral angles.
1
symmetric structure highlighted by the H NMR spec-
trum.
The helicene moiety was formed then by the classical
photochemical cyclisation–dehydrogenation reaction21 of
the bis-styryl derivative 3, where the chiral bis-ether
bridge links the terminal aromatic rings. Photolysis of the
macrocyclic bis-ether (S,S)-3 (Heraeus high-pressure
mercury lamp, 150 Watt) was performed in toluene, for
about 15 min, on a 700 mg scale, and afforded the corre-
sponding [5]helicene 4. Prolonged reaction times led to
the formation of the substituted perylene 5 as the main
product (Figure 2).22
The helical twisting of 4 is defined by the dihedral angles
given in Figure 3, with a mean value of about 20°. The
outer bonds are shortened (mean value of 1.35 Å) with re-
spect to the benzene ring (1.39 Å) whereas the inner bond
distances are lengthened to about 1.45 Å.
NMR studies suggest that the bis-ether tether locks the
configuration of the helical framework, at least in the tem-
perature range from –40 °C to 80 °C. No epimerization
was observed by heating 4 at about 80 °C for more than
ten hours.
Substituents on the 2,13 positions are not expected to have
a severe effect on the configurational stability of [5]heli-
cene derivatives.23 Thus the observed stabilization should
be mainly assigned to the presence of the configurational-
ly defined tether. The [5]helicene derivative shown in
Figure 3 should represent the thermodynamically favored
epimer of 4.
O
O
5
In conclusion, we have disclosed here a stereoselective
approach to the [5]helicene 4, where the presence of the
chiral tether prevents epimerization of the helical frame-
work at room temperature. The broad range of potential
uses of chiral helicenes in material science and catalysis,
for instance, suggests interesting application fields for 4 in
future work.
Figure 2
Based on the slow racemisation of [5]helicene at room
temperature, the formation of a mixture of two diastereo-
isomers of 4 could be expected, which might equilibrate
slowly at room temperature. The [5]helicene derivative 4
was obtained as a single isomer. The [a]D value for this
Synthesis 2004, No. 15, 2513–2516 © Thieme Stuttgart · New York

PAPER
Synthesis of a Configurationally Locked [5]Helicene Derivative
MS (CI, NH3): m/z (%) = 379 (M + H, 100%).
2515
Photo-cyclizations were performed in a water-cooled Quartz photo-
reactor using a high-pressure mercury immersion lamp (Heraeus
TQ 150). NMR spectra were recorded on either a Bruker AM 200
or an AM 400 spectrometer. Silica gel 60 mesh was used for column
chromatography. The p-xylylenebis(triphenylphosphonium) bro-
mide was prepared from PPh3 and a,a¢-dibromoxylene in refluxing
DMF, according to the usual procedure.24
HRMS (CI): m/z calcd for C27H23O2: 379.1698; found: 379.1700.
The second epimer (S,S)-(M)-4, could not be identified in the reac-
tion mixture or produced by thermal isomerization of (S,S)-(P)-4.
Perylene 5
Perylene 5 was obtained as the main product when 3 was photolysed
for about 1 h, under the same experimental conditions as above. Its
structure was assigned from the 1H and 13C NMR data.
1H NMR (CDCl3): d = 1.64 (d, J = 6.4 Hz, 6 H, Me), 2.48 (t, J = 5.0
Hz, 2 H, CH2), 5.25 (m, 2 H, CHO), 7.75 (d, J = 8.6 Hz, 2 H), 7.97
(d, J = 8.8 Hz, 2 H), 8.03 (d, J = 8.8 Hz, 2 H), 8.08 (d, J = 8.6 Hz, 2
H), 8.25 (s, 2 H).
13C NMR (CDCl3): d = 23.4 (Me), 45.1 (CH2), 73.7 (OCH), 116.9
(CH-o-O), 118.6 (C-o-O), 124.2 (C), 124.8, 125.5, 126.3 (CH),
126.6, 128.6, 128.7 (C), 156.3 (CO).
(S,S)-2,4-Bis(4-formylphenyloxy)pentane (2)
A solution containing 4-hydroxybenzaldehyde (5.4 g, 44 mmol) and
diethyl azodicarboxylate (DEAD, 6.4 mL, 41 mmol) in THF (40
mL) was prepared under argon. A solution of (R,R)-2,4-pentanediol
(2.1 g, 20 mmol) and PPh3 (10.5 g, 40 mmol) in THF (60 mL) was
added dropwise, at r.t. The mixture was stirred overnight at 45 °C.
After evaporation of the solvent, the residue was taken up in EtOAc,
filtered and purified by chromatography (silica gel; cyclohexane–
EtOAc, 90:10). (S,S)-2 was isolated.
Yield: 3.4 g (54%); pale yellow oil; Rf = 0.3; [a]D +114 (c 1,
CHCl3).
HRMS (CI): m/z calcd for C27H21O2: 377.1542; found: 377.1538.
1H NMR (CDCl3): d = 1.37 (d, J = 6.1 Hz, 6 H, Me), 2.05 (dd,
J = 7.0, 5.5 Hz, 2 H, CH2), 4.7 (m, 2 H, CHO), 6.88 (4 H), 7.71 (4
H), 9.83 (s, 2 H, CHO).
13C NMR (CDCl3): d = 20.0 (Me), 44.4 (CH2), 70.8 (OCH), 115.7
(CH), 129.8 (C), 132.0 (CH), 163.1 (OC), 190.6 (CHO).
X-Ray Crystal Structure Determination of (S,S)-(P)-4
Single crystals of 4 were obtained by recrystallisation from Et2O–
pentane. X-ray data were recorded on a KappaCCD diffractometer.
Chemical formula C27H22O2, M = 378.45 crystal dimensions
0.22 × 0.20 × 0.20 mm, orthorhombic, P212121, a = 6.268(5),
b = 12.970(5), c = 24.185(5) Å, volume 1966.1(18) Å3, Z = 4,
EI MS: m/z (%) = 312 (M, 13), 149 (100), 121 (60).
r
calcd = 1.278 g/cm3, X-ray source MoKa, l = 0.71069 Å,
T = 150.0(10) K, measured reflections = 4464, independent
reflections = 4464, reflections used 3891, refinement type Fsqd, pa-
rameters refined 265, R1 = 0.0399, wR2 = 0.1085, Flack’s
parameter = 0.2(12).
(S,S)-3
Lithium ethoxide (0.25 M in EtOH, 80 mL, 20 mmol) was added to
a solution of p-xylylenebis(triphenylphosphonium) bromide (7.1 g,
9 mmol) and (S,S)-2,4-bis(4-formylphenyloxy)pentane (2.8 g, 9
mmol) in EtOH (500 mL) at r.t. The mixture was heated at 50 °C
for16 h. The reaction mixture was hydrolysed with H2O. After evap-
oration of the EtOH and extraction of the aq phase with CH2Cl2, the
crude product was purified by chromatography (cyclohexane–
EtOAc, gradient from 100:0 to 90:10). (S,S)-3 was obtained.
Acknowledgment
The authors are grateful to CMCU (Comité Mixte Franco-Tunisien
pour la Coopération Universitaire), the Ministry of Higher Educa-
tion, Scientific Research and Technology in Tunisia and EGIDE for
financial support and grants to R.E.A.
Yield: 1.2 g (35%); colorless solid; [a]D +204 (c 0.5, CHCl3).
1H NMR (CDCl3): d = 1.36 (d, J = 6.2 Hz, 6 H, Me), 1.91 (dd,
J = 7.2, 5.4 Hz, 2 H, CH2), 4,60 (m, 2 H, CHO), 6.63 (AB, J = 11.4
Hz, 2 H), 6.70 (AB, J = 11.4 Hz, 2 H), 6.72 (4 H), 6.77 (s, 4 H), 6.87
(4 H).
13C NMR (CDCl3): d = 21.0 (Me), 44.8 (CH2), 71.3 (OCH), 115.5,
128.6, 130.2, (CH), 130.7(C), 130.8, 131.4 (CH), 135.9 (C), 157.4
(OC).
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Photolysis of (S,S)-3 (700 mg, 1.8 mmol) was performed in toluene
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O).
Synthesis 2004, No. 15, 2513–2516 © Thieme Stuttgart · New York

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Synthesis 2004, No. 15, 2513–2516 © Thieme Stuttgart · New York