Tribenzotriquinacene: A versatile synthesis and C3-chiral platforms

Article abstract of DOI:10.1002/anie.201207220

Fusing rings: A new synthesis of the bowl-shaped hydrocarbon tribenzotriquinacene is presented (see scheme). The synthesis allows easy access to ortho-functionalized and C₃-chiral derivatives that are attractive for supramolecular chemistry and

Full text of DOI:10.1002/anie.201207220

Angewandte
Chemie
DOI: 10.1002/anie.201207220
Bowl-Shaped Molecules
Tribenzotriquinacene: AVersatile Synthesis and C3-Chiral Platforms**
Georgios Markopoulos, Lars Henneicke, Jun Shen, Yoshio Okamoto, Peter G. Jones, and
Henning Hopf*
Dedicated to Professor Klaus Hafner on the occasion of his 85th birthday
Molecules belonging to point group C3 have recently
attracted much interest owing to their applications in
asymmetric catalysis and chiral recognition.[1–3] Nonetheless,
the number of C3-chiral molecules is still limited compared to
the numerous C2-chiral systems, and more entries to C3-chiral
molecules are needed. One way to obtain functional C3-chiral
molecules, which is the most common in the synthesis of
tripodal ligands, is to append three enantiopure handles to an
otherwise achiral platform. The second approach, which is
much more common in supramolecular chemistry, is to start
with a C3-chiral platform from the very beginning and to
extend it with achiral recognition units. The molecular bowl
tribenzotriquinacene (1; Scheme 1) constitutes an excellent
platform for the second strategy owing to its rigidity and
configurational stability.[4,5] However, the preparation of C3-
chiral derivatives is severely hampered by the lack of
regioselectivity.[6] Herein we wish to report a C3-specific
entry to this class of compounds, thereby providing a new
access to this novel family of C3-chiral molecules. The work is
based on a new and versatile synthesis of the parent hydro-
carbon 1 and its previously only poorly accessible ortho
derivatives. The latter furthermore provide a highly antici-
pated entry to extended carbon networks.[7–9]
Our synthesis of tribenzotriquinacene 1 starts off with the
benzylidene propanedione 2 (Scheme 1), which can be easily
obtained by Knoevenagel condensation.[10] Reduction to the
diastereomeric diols 3 had already been reported by Olah
et al. (32% yield), and we improved this step by developing
an optimized Luche procedure (93% yield).[10,11] Olahꢀs
motivation for accessing diols 3 was their study under
superacidic conditions (FSO3H/SO2ClF, À808C), whereby
he observed a cyclodehydrated intermediate, presumably of
form 4. While working with diols 3, we found that isomer-
izations and cyclodehydrations took place even under mildly
acidic conditions (cat. p-toluenesulfonic acid in CH2Cl2, RT)
and hypothesized that such cyclizations might eventually lead
to tribenzotriquinacene (1). Application of Kuckꢀs cyclo-
dehydration conditions[5b] (H3PO4, chlorobenzene, 1308C,
20 h) to diols 3 indeed gave tribenzotriquinacene in 28%
yield. Switching to polyphosphoric acid (PPA) as dehydrating
agent increased the yield to 32%, making 1 available in gram
quantities for the first time. Other acids were also tested, but
did not prove effective (acetic acid, trifluoroacetic acid,
methanesulfonic acid, Eatonꢀs reagent, trifluoromethanesul-
fonic acid (TfOH), Tf2O, H2SO4). The reaction presumably
proceeds through a series of intramolecular Friedel–Crafts
alkylations with carbocation intermediates, which is sup-
ported by the fact that the yield did not depend on the
diastereomer of 3 being used. A reaction mechanism that also
explains the formation of the dihydroindenoindene byproduct
5 is proposed in the Supporting Information.[12] The synthesis
is higher-yielding than Kuckꢀs synthesis of the parent hydro-
carbon (over three steps: 19% vs. 5%).[5b] Moreover, as we
will show below, it allows the planned introduction of
aromatic substituents by varying the easily available benzal-
dehyde and dibenzoylmethane components of the Knoeve-
nagel adduct.
Scheme 1. The synthesis of tribenzotriquinacene (1).
[*] G. Markopoulos, L. Henneicke, Prof. H. Hopf
Institut fꢀr Organische Chemie
Technische Universitꢁt Braunschweig
Hagenring 30, 38106 Braunschweig (Germany)
E-mail: h.hopf@tu-bs.de
Prof. J. Shen, Prof. Y. Okamoto
Polymer Materials Research Center
Harbin Engineering University
145 Nantong Street, Harbin 150001 (P. R. China)
Prof. P. G. Jones
Institut fꢀr Anorganische und Analytische Chemie
Technische Universitꢁt Braunschweig
Hagenring 30, 38106 Braunschweig (Germany)
[**] We thank Dietmar Kuck and Michael S. Sherburn for discussions. G.
M. was supported by the Fonds der chemischen Industrie and the
Studienstiftung des deutschen Volkes. Y. O. has a second affiliation
at Nagoya University (Japan).
Functionalization of the aromatic rings in tribenzotriqui-
nacene has largely been limited to the outer rim positions, as
these are easily accessible by electrophilic aromatic substitu-
tion.[7,13] Ortho functionalization of tribenzotriquinacenes is
rare and limited in scope. One example is known in which
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201207220.
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
These are not the final page numbers!

.
Angewandte
Communications
a metal carbonyl complex of 12d-methyltribenzotriquinacene
was functionalized at one of the inner ortho positions.[14] More
recently, Krꢁger and co-workers prepared ortho-methylated
tribenzotriquinacenes by a variation of Kuckꢀs procedure.[8]
By a Scholl reaction, Mughal and Kuck achieved the
formation of a cycloheptatriene unit between two opposing
and unfunctionalized ortho positions.[9] By starting with
Knoevenagel adducts derived from 2-bromo or 2-methoxy
benzaldehyde, our Scheme allows the regiospecific synthesis
of various ortho-functionalized tribenzotriquinacenes (7a–c,
Scheme 2). While cyclization of the brominated diols 6a
2%. We therefore switched to the trimethyl-substituted diol
8c, hoping that its electronic or steric properties might be
more favorable. Notably, a yield of 33% was found for 9c,
which compares well with the result for parent hydrocarbon
1 (32%). We wish to emphasize at this point that the
formation of the unsymmetric C1-chiral derivative is intrinsi-
cally precluded. The C3-specific nature of the cyclization and
the regiospecific formation of byproducts 10a–c can be
explained by the mechanism presented in the Supporting
Information.
An interesting feature of the mono- and trisubstituted
tribenzotriquinacenes is their chirality: 7a–c and 9a–c are C1-
and C3-chiral, respectively, and we were able to resolve their
enantiomers by chiral-phase HPLC (see Supporting Informa-
tion).[17,18] A crystal structure was obtained for the C3-chiral
tribenzotriquinacene 9c (Figure 1).[19,20] The compound crys-
Scheme 2. Synthesis of ortho-substituted tribenzotriquinacenes.
proceeded smoothly to 7a (27%), we were surprised to see
that the yield for the methoxy derivative 7b dropped to 13%.
A control experiment demonstrated that the methoxy group
is stable under the employed reaction conditions. Evidently,
the electron-donating property of the methoxy group has
a negative effect on the desired reaction sequence.[15] This is
also reflected by the significantly reduced yield of the
monosubstituted dihydroindenoindene byproducts (7% for
OMe vs. 13% for Br). Deprotection of ether 7b was achieved
in 88% yield, leading to chiral phenol 7c.
The above experiments demonstrated for the first time the
installation of various functional groups in the ortho position
of tribenzotriquinacene. We then wondered whether our
strategy could also be applied to trisubstituted systems. Most
importantly, this would provide a C3-specific entry to ortho-
functionalized tribenzotriquinacenes, a family of compounds
that is not accessible by current methods. No selective entry to
C3-chiral tribenzotriquinacenes is known as yet, and is in
particular unknown for the hardly accessible ortho positions.[6]
By starting with o,o’-disubstituted dibenzoylmethanes[16] and
2-substituted benzaldehydes, we synthesized the trisubsti-
tuted diols 8a–c (Scheme 3). Cyclization of 8a,b indeed gave
the C3-chiral tribromo and trimethoxy tribenzotriquinacenes
9a,b in a selective fashion; however, only in yields of less than
Figure 1. ORTEP of C3-chiral tribenzotriquinacene 9c (ellipsoids set at
50% probability).
¯
tallized in the triclinic space group P1, but C3 symmetry was
maintained to a good approximation (r.m.s. deviation from C3
symmetry = 0.18 ꢂ). Interestingly, 9c did not exhibit the
columnar stacking that is known for the parent hydrocarbon
1 and its 12d-methyl derivative.[4a,b,13] CH/p-mediated layers
of bowls with opposite orientation were formed, and the
methyl substituents, even when hidden in the ortho positions,
seem to have a pronounced effect on the solid-state struc-
ture.[21] Crystal structures were also obtained for byproducts 5
and 10a–c.[19]
With respect to potential applications of C3-chiral triben-
zotriquinacenes in supramolecular recognition,[22] it is inter-
esting to compare the geometric parameters of derivative 9c
with those of other C3-symmetric platforms. We limit our
discussion to aromatic platforms that have been functional-
ized with recognition units, and we show crystallographic data
Scheme 3. Synthesis of C3-chiral tribenzotriquinacenes.
2
www.angewandte.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
These are not the final page numbers!

Angewandte
Chemie
Angew. Chem. Int. Ed. 2006, 45, 4721 – 4723; c) S. E. Gibson,
M. P. Castaldi, Angew. Chem. 2006, 118, 4834 – 4837; Angew.
Chem. Int. Ed. 2006, 45, 4718 – 4720.
of relevant reference molecules in Figure 2. The distances
between the sites of functionalization in these tripodal
molecules range between 5.0 and 10.0 ꢂ.[23] C3-Chiral triben-
[3] a) M. J. Hardie, Chem. Soc. Rev. 2010, 39, 516 – 527; b) A. R. A.
Palmans, E. W. Meijer, Angew. Chem. 2007, 119, 9106 – 9126;
Angew. Chem. Int. Ed. 2007, 46, 8948 – 8968; c) M. L. Bushey, T.-
Q. Nguyen, W. Zhang, D. Horoszewski, C. Nuckolls, Angew.
Chem. 2004, 116, 5562 – 5570; Angew. Chem. Int. Ed. 2004, 43,
5446 – 5453.
[4] a) D. Kuck, Chem. Rev. 2006, 106, 4885 – 4925; b) D. Kuck, Pure
Appl. Chem. 2006, 78, 749 – 775; c) D. Kuck, Synlett 1996, 949 –
965.
[5] a) D. Kuck, E. Neumann, A. Schuster, Chem. Ber. 1994, 127,
151 – 164; b) D. Kuck, T. Lindenthal, A. Schuster, Chem. Ber.
1992, 125, 1449 – 1460; c) D. Kuck, A. Schuster, B. Ohlhorst, V.
Sinnwell, A. de Meijere, Angew. Chem. 1989, 101, 626 – 628;
Angew. Chem. Int. Ed. Engl. 1989, 28, 595 – 597; d) D. Kuck,
Angew. Chem. 1984, 96, 515 – 516; Angew. Chem. Int. Ed. Engl.
1984, 23, 508 – 509.
[6] Electrophilic aromatic substitution at the outer rim favors the
statistically preferred unsymmetric tribenzotriquinacene, which
is difficult to separate from the C3-chiral derivative; see: a) J.
Tellenbrçker, D. Kuck, Beilstein J. Org. Chem. 2011, 7, 329 – 337;
b) J. Strꢁbe, B. Neumann, H.-G. Stammler, D. Kuck, Chem. Eur.
J. 2009, 15, 2256 – 2260.
[7] J. Tellenbrçker, D. Kuck, Angew. Chem. 1999, 111, 1000 – 1004;
Angew. Chem. Int. Ed. 1999, 38, 919 – 922.
Figure 2. Structural parameters of selected platforms with threefold
symmetry (X-ray data).
[8] Y. Kirchwehm, A. Damme, T. Kupfer, H. Braunschweig, A.
Krꢁger, Chem. Commun. 2012, 48, 1502 – 1504.
[9] E. U. Mughal, D. Kuck, Chem. Commun. 2012, 48, 8880 – 8882.
[10] N. J. Head, G. A. Olah, G. K. S. Prakash, J. Am. Chem. Soc. 1995,
117, 11205 – 11210.
[11] a) J. L. Luche, J. Am. Chem. Soc. 1978, 100, 2226 – 2227; b) A. L.
Gemal, J. L. Luche, J. Am. Chem. Soc. 1981, 103, 5454 – 5459.
[12] Byproduct 5 was also observed in Kuckꢀs synthesis, albeit in
higher yield (see Refs [5a,b]).
[13] D. Kuck, A. Schuster, R. A. Krause, J. Tellenbrçker, C. P. Exner,
M. Penk, H. Bçgge, A. Mꢁller, Tetrahedron 2001, 57, 3587 – 3613.
[14] C. A. Dullaghan, G. B. Carpenter, D. A. Sweigart, D. Kuck, C.
Fusco, C. R. Curci, Organometallics 2000, 19, 2233 – 2236.
[15] The methoxy group might make the cation too stable for
subsequent Friedel–Crafts alkylation.
[16] o,o’-Disubstituted dibenzoylmethanes can be obtained by ester
condensation or a scalable three-step sequence (see the Sup-
porting Information for details).
zotriquinacene 9c exhibits a tripodal distance of 7.3 ꢂ and
bridges the gap between the mesitylene derivatives and the
other C3-symmetric platforms. It therefore offers new oppor-
tunities for the construction of chiral receptors.
In summary, we have developed a new preparative
method by which the tricyclic core of tribenzotriquinacenes
is assembled in one step from acyclic precursors. The
precursors themselves are available by simple reactions
using commercial starting materials. Our new route to
tribenzotriquinacene is of unprecedented variability and
offers direct access to C1- and C3-chiral derivatives that are
of interest to supramolecular chemists and the asymmetric
catalysis community alike. While the former might focus on
the chiral binding pocket,[28] the latter might consider these
chiral molecules as bulky phenyl groups. The C3-specific
cyclization is a particularly attractive feature of our synthesis,
and we will shortly report extensions of this strategy and the
use of functionalized and optically active tribenzotriquina-
cenes.
[17] T. Ikai, Y. Okamoto, Chem. Rev. 2009, 109, 6077 – 6101.
[18] For C1-chiral tribenzotriquinacenes with functionalization at the
outer rim, see: a) T. Wang, Q.-Q. Hou, Q.-F. Teng, X.-J. Yao, W.-
X. Niu, X.-P. Cao, D. Kuck, Chem. Eur. J. 2010, 16, 12412 – 12424;
b) W.-X. Niu, T. Wang, Q.-Q. Hou, Z.-Y. Li, X.-P. Cao, D. Kuck,
J. Org. Chem. 2010, 75, 6704 – 6707.
[19] CCDC 904629 (5), 904630 (9c), 904631 (10a), 904632 (10b) and
904633 (10c) contain the supplementary crystallographic data
for this paper. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre via www.ccdc.
cam.ac.uk/data_request/cif.
[20] Crystals of monosubstituted tribenzotriquinacenes 7a and 7c
were disordered.
[21] A crystal packing diagram for 9c is included in the Supporting
Information.
Received: September 6, 2012
Published online: && &&, &&&&
Keywords: bowl-shaped molecules · chirality · cyclization ·
.
hydrocarbons · polyquinanes
[22] Extended achiral tribenzotriquinacenes have been shown to
bind C60; see, for example: T. Wang, Z.-Y. Li, A.-L. Xie, X.-J.
Yao, X.-P. Cao, D. Kuck, J. Org. Chem. 2011, 76, 3231 – 3323.
[23] For C3-symmetric platforms with tripodal distances above 10 ꢂ,
see the following examples and references cited therein: a) A. T.
Wright, Z. Zhong, E. V. Anslyn, Angew. Chem. 2005, 117, 5825 –
5828; Angew. Chem. Int. Ed. Angew. Chem. Int. Ed. Engl. 2005,
[1] a) S. E. Gibson, M. P. Castaldi, Chem. Commun. 2006, 3045 –
3062; b) M. Mikulꢃs, N. Rꢁck-Braun in Organic Synthesis
Highlights IV (Ed.: H.-G. Schmalz), Wiley-VCH, Weinheim,
2000, pp. 187 – 193; c) C. Moberg, Angew. Chem. 1998, 110, 260 –
281; Angew. Chem. Int. Ed. 1998, 37, 248 – 268.
[2] a) L. H. Gade, S. Bellemin-Laponnaz, Chem. Eur. J. 2008, 14,
4142 – 4152; b) C. Moberg, Angew. Chem. 2006, 118, 4838 – 4840;
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3
These are not the final page numbers!

.
Angewandte
Communications
44, 5679 – 5682; b) A. Frontera, C. Garau, D. QuiÇonero, P.
Ballester, A. Costa, P. M. Deyꢄ, Org. Lett. 2003, 5, 1135 – 1138;
c) S. Kubik, R. Goddard, Eur. J. Org. Chem. 2001, 311 – 322.
[24] See the following examples and references cited therein: a) A.
Ardꢃ, F. J. CaÇada, C. Nativi, O. Francesconi, G. Gabrielli, A.
Ienco, J. Jimꢅnez-Barbero, S. Roelens, Chem. Eur. J. 2011, 17,
4821 – 4829; b) A. L. Cresswell, M.-O. M. Piepenbrock, J. W.
Steed, Chem. Commun. 2010, 46, 2787 – 2789; c) M. Mazik, A.
Hartmann, P. G. Jones, Chem. Eur. J. 2009, 15, 9147 – 9159; d) S.-
G. Kim, K.-H. Kim, J. Jung, S. K. Shin, K. H. J. Ahn, J. Am.
Chem. Soc. 2002, 124, 591 – 596.
[25] For acyclic examples, see: T. K. Ronson, C. Carruthers, J. Fisher,
T. Brotin, L. P. Harding, P. J. Rizkallah, M. J. Hardie, Inorg.
Chem. 2010, 49, 675 – 685, and references therein.
[26] M. Schnopp, G. Haberhauer, Eur. J. Org. Chem. 2009, 4458 –
4467, and references therein.
[27] N. M. Boshta, M. Bomkamp, G. Schnakenburg, S. R. Waldvogel,
Chem. Eur. J. 2010, 16, 3459 – 3466, and references therein.
[28] C. Schmuck, D. Rupprecht, W. Wienand, Chem. Eur. J. 2006, 12,
9186 – 9195.
4
www.angewandte.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
These are not the final page numbers!

Angewandte
Chemie
Communications
Bowl-Shaped Molecules
Fusing rings: A new synthesis of the bowl-
shaped hydrocarbon tribenzotriquina-
cene is presented (see scheme). The
synthesis allows easy access to ortho-
functionalized and C3-chiral derivatives
that are attractive for supramolecular
chemistry and asymmetric catalysis.
G. Markopoulos, L. Henneicke, J. Shen,
Y. Okamoto, P. G. Jones,
H. Hopf*
&&&& — &&&&
Tribenzotriquinacene: A Versatile
Synthesis and C3-Chiral Platforms
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!