An alternative approach to 3-(diphenylphosphino)hexahelicene

Article abstract of DOI:10.1016/j.tetlet.2009.04.116

3-(Diphenylphosphino)hexahelicene is synthesised in good yield and purity, via a three-step sequence involving a palladium-catalysed Mizoroki-Heck coupling reaction and classical oxidative photocyclisation. Mononuclear ruthenium and palladium complexes of

Full text of DOI:10.1016/j.tetlet.2009.04.116

Tetrahedron Letters 50 (2009) 4321–4323
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Tetrahedron Letters
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An alternative approach to 3-(diphenylphosphino)hexahelicene
*
Faouzi Aloui, 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:
3-(Diphenylphosphino)hexahelicene is synthesised in good yield and purity, via a three-step sequence
involving a palladium-catalysed Mizoroki–Heck coupling reaction and classical oxidative photocyclisa-
tion. Mononuclear ruthenium and palladium complexes of 3-(diphenylphosphino)hexahelicene are pre-
pared and characterised.
Received 4 February 2009
Revised 21 April 2009
Accepted 28 April 2009
Available online 3 May 2009
Ó 2009 Published by Elsevier Ltd.
Keywords:
Helicenes
Phosphines
Heck reaction
Photodehydrocyclisation
Helical complexes
Significant interest has been directed towards the construction
of polycyclic aromatic structures that exhibit distortions from pla-
narity, such as the helicenes.1 These helically shaped molecules
have found applications as potentially useful components in chiral
discotic liquid crystalline materials,2 as building blocks for helical
conjugated polymers3 and as rotors.4 Furthermore, functionalised
helicenes have proved successful as catalysts5 and ligands6 in
asymmetric synthesis due to their rigid framework and high opti-
cal stability.
Typically, most of the strategies adopted for the synthesis of
these compounds suffer from a lack of general applicability and
low yields. However, only a few approaches have been employed
for the synthesis of racemic or optically active phosphorus-con-
taining helicenes. In 1997, Terfort et al. reported the synthesis of
the first helical-chiral phosphane ligands in racemic form:
bis(diphenylphosphino)[5]- and [6]-helicenes.7
overall yield. A shorter access to phosphine 1 than that mentioned
above and/or by another higher yielding procedure would be desir-
able for examination of this compound as a ligand or for broader
exploitation. To our knowledge, no transition metal complex of 3-
(diphenylphosphino)hexahelicene has been described previously.
In recent years, we have utilised the palladium-catalysed
Mizoroki–Heck coupling reaction and classical oxidative photocyc-
lisation for the synthesis of various functionalised helically chiral
aromatic structures.12,13 In this Letter we report the use of the
same strategy for the synthesis of helically chiral hexacyclic phos-
phine 1 by taking advantage of an appropriate functional group to
introduce a phosphorus to a preformed helical derivative. Our syn-
thetic approach makes use of a benzo[c]phenanthrene as the start-
ing material for the synthesis of the helicene precursor which is
then easily converted into the corresponding helically chiral hexa-
cyclic system by oxidative photocyclisation.
In an independent study, Reetz et al. reported the synthesis of
optically active 2,15-bis(diphenylphosphino)hexahelicene and de-
scribed its use in both enantioselective hydrogenations8 and palla-
dium-promoted allylic substitutions.9 More recently, Katz has
synthesised optically active bidentate phosphines containing hexa-
Scheme 1 shows our general synthetic strategy to construct the
helical hexacyclic phosphine 1 which is based on a three-step reac-
tion sequence utilising Mizoroki–Heck couplings, photocyclisation
and lithiation–phosphinylation.
The Mizoroki–Heck coupling14 of the benzo[c]phenanthrene 2
with an excess of 3-bromostyrene in the presence of sodium acetate
and hepta-helicene skeletons.10 Teply et al. prepared 3-(diphenyl-
´
phosphino)hexahelicene 1 using a multistep procedure based on a
key intramolecular [2+2+2] cycloisomerisation of a substituted tri-
yne.11 The authors did not report the resolution of this helical phos-
phine or its use in catalysis. Moreover, in this sequence, the
phosphine was obtained using harsh reaction conditions in a low
and Herrmann’s palladacycle [trans-di(l-acetato)-bis[o-(di-o-toly-
lphosphino)benzyl]dipalladium] as the catalyst, in N,N-dimethyl-
acetamide (DMA), provided the helicene precursor 3 in 78% yield
after heating for 48 h at 140 °C (Scheme 1). The starting material,
2-bromobenzo[c]phenanthrene 2, is available in two steps and good
yield, by photocyclisation of 2-(4-bromostyryl)naphthalene, which
is conveniently prepared via a palladium-promoted Mizoroki–Heck
reaction.12b
* Corresponding author. Tel.: +216 73500279, fax: +216 73500278.
E-mail address: bechirbenhassine@yahoo.fr (B.B. Hassine).
0040-4039/$ - see front matter Ó 2009 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2009.04.116

4322
F. Aloui, B. B. Hassine / Tetrahedron Letters 50 (2009) 4321–4323
1%[Pd], NaOAc
+
DMA, 140 °C, 48 h
78%
Br
Br
2
3
Br
hν, cyclohexane
a) n-BuLi, THF
propylene oxide, I2
50%
b) ClPPh2, THF
-78 °C, to rt
Br
P(X)Ph2
75%
1
5
X = lone pair
X = O, 98%
4
H2O2, CH2Cl2
rt, 30 min
Scheme 1. Synthetic strategy for the synthesis of the helical phosphine 1.
Alkene 3 underwent photocyclisation in the presence of a stoi-
advantage that tedious and difficult purification of the product is
avoided.
chiometric amount of iodine and an excess of propylene oxide.15
Photolysis of 3 was performed on a 200 mg scale per run in a
one litre reactor for about 120 min to afford the expected 3-bromo-
hexahelicene 4 in 50% yield, after purification by column chroma-
tography.16 No other isomer was isolated from the reaction
mixture, indicating that ring closure of 3 had occurred from the
opposite side of the tetracyclic system.
The last step of the synthetic sequence is the formation of the
phosphine which can be achieved through lithiation/phosphinyla-
tion of 4. Thus, metallation of 3-bromohexahelicene 4 proceeded
well via metal-halogen exchange using n-butyllithium at À78 °C.
Subsequent treatment of the resulting lithiated species with chlo-
rodiphenylphosphine yielded the desired 3-(diphenylphos-
phino)hexahelicene 1 in 75% yield and in 29% overall yield over
three steps, starting from the readily available benzo[c]phenan-
threne 2 (Scheme 1). Oxidation of helical phosphine 1, using 35%
hydrogen peroxide solution, provided the corresponding phos-
phine oxide 5 in excellent yield. Compound 5 is more stable than
phosphine 4 and could be resolved, by HPLC, using a column
For the photoconversion of larger amounts of alkene 3 it was
preferable to carry out irradiation using portions of 0.55 mmol or
less. The total irradiation time required for complete conversion
of a large amount of 3 was not affected significantly by dividing
the reactant into small batches, and the irradiated batches were
combined for work-up. Also, this photochemical method has the
CH2Cl2, rt
61%
+
1/2 [(p-cymene)RuCl2]2
Ph
Ph
PPh2
P
6
Ru
Cl
Cl
1
7
Scheme 2. Synthesis of the helically chiral ruthenium complex 7.
CF3
O
O
O
CF3
N
Pd
CH2Cl2, rt
70%
1/2
+
Pd
Ph
P
O
O
N
PPh2
O
Pd
N
Ph
CF3
9
1
8
Scheme 3. Synthesis of the helically chiral palladium complex 9.

F. Aloui, B. B. Hassine / Tetrahedron Letters 50 (2009) 4321–4323
4323
12. (a) Aloui, F.; El Abed, R.; Marinetti, A.; Ben Hassine, B. Tetrahedron Lett. 2008,
49, 4092–4095; (b) Aloui, F.; El Abed, R.; Ben Hassine, B. Tetrahedron Lett. 2008,
49, 1455–1457; (c) Aloui, F.; El Abed, R.; Marinetti, A.; Ben Hassine, B. C.R. Chim.
2009, 12, 284–290; (d) Aloui, F.; El Abed, R.; Marinetti, A.; Ben Hassine, B.
Tetrahedron Lett. 2007, 48, 2017–2020; (e) Aloui, F.; El Abed, R.; Guerfel, T.; Ben
Hassine, B. Synth. Commun. 2006, 11, 1557–1567.
packed with cellulose-tris(3,5-dimethylphenylcarbamate) and n-
heptane/2-propanol (80:20) mixture as the mobile phase.12a,d
Having established a short procedure for the synthesis of the
monophosphine 1, we then further proceeded to explore its coor-
dinating ability towards transition metals. To achieve this,
phosphine 1 was first allowed to react with 0.5 equiv of [(p-cyme-
ne)RuCl2]2 complex 6 in dichloromethane at room temperature to
13. El Abed, R.; Aloui, F.; Genêt, J.-P.; Ben Hassine, B.; Marinetti, A. J. Organomet.
Chem. 2007, 692, 1156–1160.
14. (a) El Abed, R.; Ben Hassine, B.; Genêt, G.-P.; Gorsane, M.; Marinetti, A. Eur. J.
}
Org. Chem. 2004, 1517–1522; (b) Herrmann, W. A.; Brossmer, C.; Ofele, K.;
afford the mononuclear ruthenium complex
7 in 61% yield
Reisinger, C. P.; Priermeir, T.; Beller, M.; Fisher, H. Angew. Chem., Int. Ed. Engl.
1995, 34, 1844–1848.
(Scheme 2). This compound was isolated as an orange-red, air sta-
ble solid and was characterised by NMR and mass spectrometry.17
15. Liu, L.; Yang, B.; Katz, T. J.; Poindexter, M. K. J. Org. Chem. 1991, 56, 3769–3775.
16. Spectral data for 3-bromohexahelicene 4: pale yellow solid, showing a violet
fluorescence when dissolved; Rf = 0.41 (cyclohexane/ethyl acetate, 98:2);
mp = 196–198 °C; 1H NMR (300 MHz, CDCl3): d (ppm): 6.72–6.79 (m, 2H),
7.27 (t, J = 6.9 Hz, 1H, H-14 or H-15), 7.46 (d, J = 9.3 Hz, 1H), 7.56 (d,
J = 8.4 Hz, 1H), 7.81 (d, J = 8.7 Hz, 1H), 7.85 (d, J = 8.1 Hz, 1H), 7.93–8.03 (m,
8H); 13C NMR: (75 MHz, CDCl3): d (ppm): 119.43 (C), 123.87 (C), 125.05
(CH), 125.90 (CH), 126.19 (CH), 126.78 (CH), 126.95 (CH), 127.22 (CH),
127.32 (CH), 127.54 (CH), 127.60 (2CH), 127.67 (CH), 127.72 (CH), 127.81
(C), 127.82 (C), 128.12 (CH), 128.63 (C), 129.33 (CH), 129.60 (CH), 129.61
(C), 131.21 (C), 131.43 (C), 131.85 (C), 133.15 (C), 133.32 (C); MS (EI): m/
z = 407 [M+]; Anal. Calcd for C26H15Br: C, 76.67; H, 3.71. Found: C, 76.57;
H, 3.69.
Phosphine 1 was also reacted with the [PhCH2N(Me)2Pd(g3
–
OCOCF3)]2 complex 8 at room temperature for 15 min to produce
the mononuclear palladium complex 9 in 70% yield as an air stable,
pale yellow compound (Scheme 3).18
In conclusion, we have developed a straightforward method for
the preparation of helically chiral hexacyclic phosphine 1 starting
from readily available and inexpensive materials. We completed
the synthesis of the helical framework of 1 in three steps and in
29% overall yield. This class of compounds is known to possess
interesting catalytic activities, and we feel that this method when
combined with a simple resolution procedure will further facilitate
the exploration of this helical phosphine.
17. Spectral data for the Ru-complex 7: orange–red solid; mp = 195–197 °C; 1H NMR
(300 MHz, CDCl3): d (ppm): 0.99 (d, J = 7.2 Hz, 3H, Me), 1.03 (d, J = 7.2 Hz, 3H,
Me), 1.74 (s, 3H, Me), 2.77 (m, 1H, CHMe2), 4.68 (d, J = 6 Hz, 1H, CHp-cym), 4.80
(d, J = 6 Hz, 1H, CHp-cym), 5.00 (d, J = 5.8 Hz, 1H, CHp-cym), 5.12 (d, J = 5.7 Hz,
1H, CHp-cym), 6.68 (ddd, J1 = 8 Hz, J2 = 7.2 Hz, J3 = 1.2 Hz, 1H), 6.93 (td,
J1 = 9 Hz, J2 = 1.8 Hz, 1H, H-15), 7.10–7.35 (m, 8H), 7.49–7.63 (m, 5H), 7.80
(d, J = 8.1 Hz, 1H), 7.82–7.94 (m, 7H), 7.97 (d, J = 8.4 Hz, 1H), 8.36 (dd, J = 1.5 Hz,
JH–P = 11.7 Hz, 1H, H-4); 13C NMR (75 MHz, CDCl3): d (ppm): 18.47 (Me), 22.26
(Me), 22.38 (Me), 30.71 (CHp-cym), 87.53 (CHp-cym), 87.59 (CHp-cym), 88.19
(CHp-cym), 89.06 (CHp-cym), 96.45 (Cp-cym), 111.30 (Cp-cym), 124.42 (C),
124.92 (CH), 125.90 (CH), 126.86 (CH), 127.42 (CH), 127.62 (CH), 127.63 (CH),
127.77 (d, JC–P = 8.67 Hz, CH), 128.04 (CH), 128.08 (2CH), 128.19 (CH), 128.22
(CH), 128.25 (CH), 128.28 (CH), 128.31 (CH), 128.53 (CH), 128.56 (CH), 129.08
(d, JC–P = 8.17 Hz, CH), 130.36 (CH), 130.49 (CH), 131.09 (C), 131.11 (C), 131.24
(C), 131.59 (C), 131.87 (C), 132.41 (C), 132.49 (C), 133.25 (C), 133.43 (C), 133.61
(C), 133.87 (C), 134.05 (C), 134.63 (CH), 134.72 (2CH), 134.88 (CH), 135.33 (d,
JC–P = 11.70 Hz, CH); 31P NMR (121.5 MHz, CDCl3): d (ppm): 25.07 (s); ESI-MS:
m/z = 818.1 [M+]; HRMS (MALDI-TOF) calcd for C48H39Cl2PRu [M+]: 818.12099.
Found: 818.12023.
Acknowledgement
The authors are grateful to DGRSRT (Direction Générale de la
Recherche Scientifique et de la Rénovation Technologique) of the
Tunisian Ministry of Higher Education, Scientific Research and
Technology for the financial support.
References and notes
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18. Spectral data for the Pd-complex 9: pale yellow solid; mp = 208–210 °C; 1H
NMR (500 MHz, CDCl3): d (ppm): 2.78 (m, 6H, 2CH3), 4.00 (d, J = 13.5 Hz,
1H), 4.14 (d, J = 13.5 Hz, 1H), 6.41 (m, 2H), 6.79 (t, J = 7.5 Hz, 1H), 6.88 (t,
J = 7 Hz, 1H), 7.02 (d, J = 8.5 Hz, 1H), 7.06 (dd, J = 8.5 Hz, JH–P = 1.5 Hz, 1H),
7.28–7.52 (m, 8H), 7.61 (d,
J = 9 Hz, 1H), 7.87 (d, J = 8 Hz, 1H), 7.92–8.03 (m, 7H), 8.05 (d, J = 8 Hz, 1H),
8.59 (dd, J = 1.5 Hz, JH–P = 14 Hz, 1H, H-4); 13C NMR (75 MHz, CDCl3):
J = 8.5 Hz, 1H), 7.64–7.70 (m, 3H), 7.84 (d,
d
(ppm): 49.86 (Me), 49.98 (Me), 71.57 (CH2), 121.57 (CH), 122.63 (CH),
124.13 (C), 124.67 (CH), 125.19 (d, JC–P = 5.55 Hz, CH), 125.33 (CH), 125.50
(C), 126.21 (CH), 126.92 (CH), 127.13 (d, JC–P = 4.72 Hz, CH), 127.40 (C),
127.48 (CH), 127.62 (CH), 127.67 (C), 127.72 (d, JC–P = 3 Hz, CH), 127.97 (CH),
128.11 (CH), 128.19 (d, JC–P = 3 Hz, CH), 128.35 (CH), 129.59 (d, JC–P = 9 Hz,
CH), 129.80 (CH), 129.92 (CH), 130.18 (CH), 130.40 (d, JC–P = 2.32 Hz, CH),
130.62 (d, JC–P = 2.30 Hz, CH), 130.68 (C), 130.82 (d, JC–P = 1.87 Hz, C), 130.99
(C), 131.32 (CH), 131.41 (C), 131.46 (C), 131.91 (C), 132.19 (C), 133.19 (C),
134.30 (CH), 134.46 (CH), 134.63 (CH), 134.79 (CH), 137.66 (CH), 137.88
(CH), 137.96 (CH), 138.11 (CH), 141.54 (C), 143.63 (d, JC–P = 3.37 Hz, C),
148.36 (d, JC–P = 2.10 Hz, C); 31P NMR (121.5 MHz, CDCl3): d (ppm): 41.12
(s); 19F NMR (282 MHz, CDCl3): d (ppm): À74.75 (d, JF–P = 105.46 Hz); ESI-
MS: m/z = 866.1 [M+H]+; Anal. Calcd for C49H37NO2F3PPd: C, 67.94; H, 4.31;
N, 1.62. Found: C, 67.74; H, 4.29; N, 1.62.
´
´
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