New chiral cyclooctatriene-based polycyclic architectures

Article abstract of DOI:10.1021/ol201804h

The synthesis and properties of new chiral polycyclic architectures that display both helicity and a saddle-type shape are described. The enantiomers have been separated, and their absolute configuration was determined by VCD and ECD. The unprecedented mo

Full text of DOI:10.1021/ol201804h

ORGANIC
LETTERS
2011
Vol. 13, No. 16
4450–4453
New Chiral Cyclooctatriene-Based
Polycyclic Architectures
†
Gregory Pieters, Anne Gaucher,* Jerome Marrot, Franc-ois Maurel,
,†
†
‡
ꢀ
ꢀ ^
§
§
§
ꢁ
Jean-Valere Naubron, Marion Jean, Nicolas Vanthuyne, Jeanne Crassous, and
Damien Prim*,†
ꢀ
Universite de Versailles-Saint-Quentin-en-Yvelines, Institut Lavoisier de Versailles,
UMR CNRS 8180, 45 Avenue des Etats-Unis, F-78035 Versailles, France, Sciences
ꢀ
Chimiques de Rennes, UMR CNRS 6226, Universite de Rennes 1, Campus de Beaulieu,
ꢀ ꢀ
ꢀ
ꢀ
Av. du General Leclerc, F-32045 Rennes Cedex, France, Universite Paul Cezanne ꢀ
ꢀ
Spectropole & UMR CNRS 6263 ꢀ Case A62 Avenue Escadrille Normandie-Niemen
13397 Marseille Cedex 20, France, and Laboratoire Interfaces, Traitements,
ꢁ
ꢀ
Organisation et Dynamique des Systemes (ITODYS), CNRS UMR 7086, Universite
Paris 7 - Paris Diderot, Batiment Lavoisier, 15 rue Jean Antoine de Baıf, 75205 Paris
¨
^
Cedex 13, France
prim@chimie.uvsq.fr; anne.gaucher@chimie.uvsq.fr
Received July 6, 2011
ABSTRACT
The synthesis and properties of new chiral polycyclic architectures that display both helicity and a saddle-type shape are described. The
enantiomers have been separated, and their absolute configuration was determined by VCD and ECD. The unprecedented molecular architecture
is based on a cyclooctatriene core surrounded by an association of benzo[c]fluorene and ortho-phenylene units.
Unusual topologies of polycyclic hydrocarbons have
been the subject of continuous and considerable attention.
Within this large family of chemical compounds, architec-
tures based on a central ring surrounded by several cyclic
subunits are of particular interest mainly because such
molecules display various shapes such as planar (PL),
bowl-shaped (BS), or saddle-shaped (SS).1If the central
ring size deeply impacts the overall shape, it may be
affected or even modified by several additional parameters
such as (i) the surrounding lattice of fused aromatics, (ii)
the substitution of a six- by a five-membered ring in the
outer circular arrangement, and (iii) rupture of annelation
and introduction of sp3-hybridized carbon atoms. For
example, in the circulene series, moving from [5]- to [6]-
and further [7]-circulene induces shape modifications from
BS to PL and further to SS respectively.2 PL [6]-circulene
and BS sumanene differ from each other by the ring size of
some surrounding cycles.3 In this context, five-, six-, or
seven-membered central rings are common cores. In con-
trast, the next higher eight-membered homologues are so
far less described. The most prominent examples described
in the literature appear to be highly symmetrical molecules
(2) (a) Steinberg, B. D.; Jackson, E. A.; Filatov, A. S.; Wakamiya, A.;
Petrukhina, M. A.; Scott, L. T. J. Am. Chem. Soc. 2009, 131, 10537. (b)
Boedigheimer, H.; Ferrence, G. M.; Lash, T. D. J. Org. Chem. 2010, 75,
2518. (c) Yamamoto, K.; Harada, T.; Nakazaki, M.; Nakao, T.; Kai, Y.;
Harada, S.; Kasai, N. J. Am. Chem. Soc. 1983, 105, 7171.
(3) (a) Sakurai, H.; Daiko, T.; Sakane, H.; Amaya, T.; Hirao, T. J.
Am. Chem. Soc. 2005, 127, 11580. (b) Yamamoto, K.; Harada, T.;
Okamoto, Y.; Chikamatsu, H.; Nakazaki, M.; Kai, Y.; Nakao, T.;
Tanaka, M.; Harada, S.; Kasai, N. J. Am. Chem. Soc. 1988, 110, 3578.
†
ꢀ
Universite de Versailles-Saint-Quentin-en-Yvelines.
‡
§
ꢀ
Universite Paris 7 - Paris Diderot.
ꢀ
ꢀ
Universite Paul Cezanne.
ꢀ
Universite de Rennes 1.
(1) For a recent review, see: Hoheisel, T. N.; Schrettl, S.; Szilluweit,
R.; Frauenrath, H. Angew. Chem., Int. Ed. 2010, 49, 6496.
r
10.1021/ol201804h
Published on Web 07/26/2011
2011 American Chemical Society

such as the nonplanar tetraphenylene,4 several bridged
tetraphenylenes,5 and the planar octathio[8]circulene, also
called sulflower.6
membered rings. Precursors 3 and 4 are easily obtained in
two steps starting from 1,8-dibromonaphthalene as re-
cently described (Scheme 1).7 Benzylic carbocations are
generated upon treatment with Lewis acids and undergo
electrophilic aromatic substitutions featuring the construc-
tion of target architectures.
Refluxing 3 in DCM, in the presence of a catalytic
amount of aluminum chloride, afforded a complete con-
version after 24 h. 1H NMR spectra confirmed the presence
of a nonsymmetrical structure containing both a cyclopen-
tadiene and a cyclooctatriene unit (see Supporting Infor-
mation (SI)). Under FriedelꢀCrafts alkylation conditions,
3 afforded compound 5 in a fair 45% yield. Gratifyingly,
the constrained helical architecture 6 was selectively ob-
tained in a high 70% yield, starting from bismonobromo-
diarylnaphthalene 4. Crystals suitable for single crystal
X-ray diffraction analysis could be obtained from slow
evaporation of a chloroform solution of 5 (Figure 2).
Figure 1. Polycyclic architectures based on an eight-membered ring.
We report herein the synthesis of new polycyclic hydro-
carbon architectures containing a central eight-membered
ring that bridges four six-membered and one five-mem-
bered unit together as illustrated in Figure 1. In addition to
the short synthesis, the structural determination, the com-
puted reaction pathway, and conformational barriers are
described. For 6, the enantiomers were separated by chiral
HPLC, their absolute configurations were assigned using
VCD, ECD, their chiroptical properties, and enantiomer-
ization barriers were determined.
Figure 2. Single crystal X-ray diffraction analysis of constrained
architecture 5.
Scheme 1. Synthesis of Polycyclic Architectures
The joint presence of the benzo[c]fluorene unit, the
cyclooctatriene core, and the benzylic moiety imposes the
twisting of the A, B, C, D ring sequence, which accounts
for the helical fragment of the architecture. Examination of
5 in the solid state deserves some additional comments: (i)
The presence of both P and M enantiomers, as shown in
Figure 2, confirmed the chiral nature of the architecture. (ii)
Edge-to-face interactions between the orthogonal E and C
rings as well as weak πꢀπ interactions between two ortho-
gonal E rings of each molecule set the design of the dimeric
arrangement. Within this set, both perpendicular E rings and
cyclooctatriene units arranged anti to each other with regards
to the central A, B, C, D ring sequence (Figure 2).
The nonplanar conformation of the cyclooctatriene
moiety forces the E ring to adopt an almost perpendicular
position with regards to the condensed A, B, C, D. The
association of both cyclooctatriene and the perpendicular
isolated ortho-phenylene ring is responsible for the curva-
ture region in 5. Thus, both substructures impact the
flexibility, torsion, and overall design of the molecular
architecture. During the AlCl3 promoted double electro-
philic aromatic cyclization, both the five- and the eight-
membered rings are generated. The molecular architecture
of 5 and 6 is due to the selective formation of the five-/
eight-membered ring combination over a plausible five-/
five-membered ring system.
Our approach relies upon a key double electrophilic
aromatic cyclization to install both the five- and eight-
(4) For recent literature, see: (a) Rajca, A; Rajca, S. Angew. Chem.,
Int. Ed. 2010, 49, 672. (b) Hilton, C. L.; Crowfoot, J. M.; Rempala, P.;
King, B. T. J. Am. Chem. Soc. 2008, 130, 13392. (c) Iglesias, B.; Cobas,
ꢀ
A.; Perez, D.; Guitian, E. Org. Lett. 2004, 6, 3557.
(5) (a) Hellwinkel, D.; Reiff, G. Angew. Chem. 1970, 82, 516. (b)
Hellwinkel, D.; Reiff, G.; Nykodym, V. J. Liebigs Ann. Chem. 1977,
1013.
(6) Chernichenko, K. Y.; Sumerin, V. V.; Shpanchenko, R. V.;
Balenkova, E. S.; Nenajdenko, V. G. Angew. Chem., Int. Ed. 2006, 45,
7367.
(7) (a) Pieters, G.; Gaucher, A.; Prim, D.; Marrot, J. Chem. Commun.
2009, 4827. (b) Pieters, G.; Terrasson, V.; Gaucher, A.; Prim, D.;
Marrot, J. Eur. J. Org. Chem. 2010, 30, 5800.
This unusual combination posed the question of the
reaction pathway and more precisely which ring (five or
Org. Lett., Vol. 13, No. 16, 2011
4451

eight) formed first. With the help of DFT calculations, we
calculated the activation energies for the cyclization reac-
tions (Scheme 2).
and 6 can be considered as helical architectures displaying
potential racemization energy barriers (REBs).
In the more classical carbohelicene series, the REB
mainly depends on two factors: the number of ortho-fused
rings8 and modulation of steric hindrance on terminal
positions of theinnerhelix.9,10 Asmolecules 5 and 6 display
both factors, it was thus of high interest to determine their
REB and rank such architecture into a classical carbohe-
licene REB scale. With this aim, the geometry of the
racemization transition state (RTS) has been optimized
at the B3LYP/6-31G(d) level. The RTS is strongly twisted
explaining the unexpected high calculated REB value of 31
Scheme 2. Computed Reaction Pathway
kcal molꢀ1 (see SI).
3
From 1,8-bisarylnaphthalene, the five-membered ring is
favored over the eight-membered product and the activa-
tion energies are found to be respectively (TS1) 11.4 and
(TS2) 18.8 kcal molꢀ1. A possible explanation of this
3
result is a better stabilization of the charge on the naphtha-
lene unit in the five-membered transition state than on the
phenyl group in the eight-membered transition state.
In a second step and starting from the five-membered
intermediate C4, the energy barriers for cyclization lead-
ing to the five/eight product is found to be (TS3) 5.4
kcal molꢀ1, a value significantly lower than the energy
3
barrier calculated for the formation of the five/five product
((TS4) 6.8 kcal molꢀ1). The HOMO of the five-membered
3
compound C4 is mainly localized on the D and C rings of
the benzo[c]fluorenyl unit while no contribution is ob-
served on the A ring (Figure 3).
Figure 4. IR and VCD spectra of 6 calculated for the (M)
enantiomer (in blue) and measured in CDCl3 for the first eluted
(in green) and the second eluted (in red) enantiomers.
The enantiomers of compound 6 were separated by
analytical liquid chromatography on a chiral stationary
phase. Semipreparative resolution was then performed to
obtain a few milligrams of each enantiomer with an ee
higher than 97%. The first eluted enantiomer corresponds
tothe(þ)ECD254 nm formaccordingtothe CDdetection in
the mobile phase. Modest specific rotations were measured
for the first and second eluted enantiomers (in CHCl3 at
different wavelengths, see SI). The enantiomerization bar-
rier of compound 6 was determined in refluxing butan-1-ol,
Figure 3. Frontier orbital contour plots of the five-membered
cation C4. The contour threshold is set to 0.05 au, and these
orbitals have been computed at the B3LYP/6-31G(d) level.
ΔG‡ = 31.4 kcal molꢀ1 (117 °C, butan-1-ol), in excellent
3
agreement with the calculated barrier. IR and VCD
Therefore a better HOMOꢀLUMO interaction is ex-
pected in the five/eight transition state and may explain the
calculated selectivity. Due to the curved shape of the
benzo[c]fluorenyl core as evidenced by X-ray analysis, 5
(8) Martin, R. H.; Marchant, M. J. Tetrahedron 1974, 30, 347.
€
(9) Janke, R. H.; Haufe, J. H.; Wurthwein, E.-U.; Borkent, J. H. J.
Am. Chem. Soc. 1996, 118, 6031.
(10) Pieters, G.; Gaucher, A.; Marque, S.; Maurel, F.; Lesot, P.;
Prim, D. J. Org. Chem. 2010, 75, 2096.
4452
Org. Lett., Vol. 13, No. 16, 2011

(Figure 4). The VCD spectrum of the second eluted
enantiomer (red line in Figure 4) matches the calculated
one for (M)-6 (blue line in Figure 4).
UV and ECD spectra of the enantiomers were recorded
inchloroformandcalculatedfor (M)-6 using TDDFT with
the CAM-B3LYP functional and 6-31þþG(d,p) basis set.
Comparison between experimental and calculated spectra,
particularly, the bands at 290 and 360 nm, confirm the
assignment of the (M) configuration to the second eluted
enantiomer (Figure 5).
In conclusion, we described the synthesis and properties
of new nonsymmetrical polycyclic architectures that
display both helicity and a saddle-type shape. The un-
precedented molecular chiral architecture is based on a
cylooctatriene coresurroundedby anassociation ofbenzo-
[c]fluorene and ortho-phenylene units. The reaction path-
way has been determined and evidenced the formation of
the five-membered ring prior to the construction of the
cyclooctatriene fragment. The enantiomers were stable
enough to be isolated by chiral chromatography and were
fully characterized. The absolute configuration, chiropti-
cal properties, and enantiomerization barrier of these new
chiral polycyles have been closely examined.
Figure 5. UV and ECD spectra of 6 calculated for the (M)
enantiomer (in blue) and measured in CHCl3 for the first eluted
(in green) and the second eluted (in red) enantiomers.
Acknowledgment. Authors gratefully thank MENRT,
CNRS, and the University of Versailles-St-Quentin-en-
Yvelines for a grant (G.P.) and financial support.
spectra of the enantiomers were measured and com-
pared with the calculated spectra for (M)-6. The geo-
metry optimizations, vibrational frequencies, IR ab-
sorption, and VCD intensities were calculated with
Density Functional Theory (DFT) using B3LYP com-
bined with the TZVP basis set. A very good agreement is
observed between the experimental and calculated spectra
Supporting Information Available. Experimental pro-
cedures, characterization data including emission spectra
of 5 and 6, chiral HPLC separation, ECD, VCD, and
enantiomerization barrier for the enantiomers of 6, full
geometry and energy information in the form of GAUS-
SIAN 03 archive entries. This material is available free of
charge via the Internet at http://pubs.acs.org.
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