The Regiospecific Preparation of 2-Substituted Tribenzotriquinacenes

Article abstract of DOI:10.1055/s-0032-1318143

Several substituted tribenzotriquinacene derivatives (TBTQ) carrying functional groups exclusively in the 2-position (OMe, OH, Br, CHO, CN, styryl, etc.) have been prepared by our new synthesis of the tribenzotriquinacene framework. The route has been ext

Full text of DOI:10.1055/s-0032-1318143

LETTER
▌453
letter
The Regiospecific Preparation of 2-Substituted Tribenzotriquinacenes
Preparation of 2-Substituted Tribenzotriquinacenes
a
a
a
b
a
Rajendran Saravanakumar, Georgios Markopoulos, Lucian Gabriel Bahrin, Peter G. Jones, Henning Hopf*
a
Institute of Organic Chemistry, Technische Universität Braunschweig, Hagenring 30, 38106 Braunschweig, Germany
Fax +49(531)3915288; E-mail: h.hopf@tu-bs.de
b
Institute of Inorganic and Analytical Chemistry, Technische Universität Braunschweig, Hagenring 30, 38106 Braunschweig, Germany
Fax +49(531)3915387; E-mail: p.jones@tu-bs.de
Received: 20.11.2012; Accepted after revision: 10.01.2013
diastereomers), which, in a final step, are cyclodehydrated
by treatment with polyphosphoric acid to the parent hy-
Abstract: Several substituted tribenzotriquinacene derivatives
(
(
TBTQ) carrying functional groups exclusively in the 2-position
OMe, OH, Br, CHO, CN, styryl, etc.) have been prepared by our
drocarbon 3a or to various 1-substituted derivatives (inter
1
new synthesis of the tribenzotriquinacene framework. The route has alia: Br, Me, OMe). These derivatives are chiral, and
been extended to the preparation of a double-cup molecule in which their enantiomers were resolved by chromatography using
two TBTQ moieties are fused by a benzene ring. The trans config-
uration of one of the diastereomers of this hydrocarbon was estab-
lished by X-ray structural analysis.
an optically active stationary phase (e.g., Chiralcel OD,
Chiralcel OJH, and Chiralpak AS). Whereas the parent
system 3a had already been prepared by Kuck during his
Key words: cuplike aromatics, Friedel–Crafts cyclizations, cyclo-
eliminations, convex molecules, chiral aromatics, double-cup
structures, single-crystal X-ray structural analysis
classical investigations of tribenzotriquinacene deriva-
tives,2 derivatives bearing substituents or functional
groups in the sterically shielded 1-position are generally
not readily accessible.3
In principle, our new route offers numerous possibilities
Recently, we have reported on a versatile new synthesis
to introduce functionality at all positions except for the
central position 12d, since the aromatic substituents in
for the preparation of tribenzotriquinacene (3a, Scheme 1)
and also of several derivatives bearing one or more sub-
substrate 1 can carry functional groups at every available
stituents (1-TBTQ) in their (sterically hindered) ortho po-
1
carbon atom. Furthermore, the aromatic substituents can
be replaced by heteroaromatic (e.g., thienyl) or condensed
substituents (e.g., naphthyl). The benzhydrylic hydrogen
atoms in 3 in principle could be replaced by substituents
by performing for example, a Grignard reaction on appro-
priately substituted derivatives of 1 followed by cyclode-
sition(s) (e.g., position 1 in compound 3).
In this route, cross-conjugated diones 1 – obtained by
Knoevenagel condensation of the corresponding 1,3-di-
ketones with aromatic aldehydes (selected yields are giv-
en in Scheme 1) – are reduced to the diols 2 (mixture of
OH
O
O
i
OH
ii
12d
1
R
2
R
5
4
3
R
1
2
3
1
2
3
R
%
R
H
%
R
%
a
b
c
d
e
f
H
66
93
H
32
15
68
17
OMe 82
–
Br
–
OMe 86
–
Br
–
OMe
OH
Br
iii
73
83
iv
v
TMS 81
vi
–
–
–
–
H
92
68
g
Tol-NH
Scheme 1 Preparation of 2-substituted tribenzotriquinacenes by cyclodehydration. Reagents and conditions: i) CeCl ·7H O, NaBH , MeOH,
3
2
4
CH Cl , –78 °C to 20 °C, 12 h; ii) polyphoshoric acid or H PO , chlorobenzene, 130 °C, 20 h; iii) BBr , CH Cl , –78 °C to 20 °C, 12 h; iv)
2
2
3
4
3
2
2
PdCl (PPh ) , TMSA, CuI, Ph P, Et N, toluene, 80 °C, 10 h; v) K CO , MeOH–THF (1:1), 20 °C, 3 h; vi) Pd (dba) , Xanthphos, NaOt-Bu, p-
2
3 2
3
3
2
3
2
3
toluidine, reflux, 24 h.
SYNLETT 2013, 24, 0453–0456
Advanced online publication: 25.01.2013
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3
6
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5
2
1
4
1
4
3
7
-
2
0
9
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DOI: 10.1055/s-0032-1318143; Art ID: ST-2013-B0995-L
Georg Thieme Verlag Stuttgart · New York
©

4
54
R. Saravanakumar et al.
LETTER
hydration of the resulting tertiary diol. In all these cases, starting material. Conversion of the aldehyde 3h into the
with a substituent already introduced at the substrate lev- corresponding oxime proceeded readily (NH OH·HCl,
2
el, regiospecifically functionalized tribenzotriquinacenes 76%) and its dehydration yielded nitrile 3i (Ac O, EtOH,
2
would result. This is a priori not the case if the substituents 60%; Scheme 2).
are introduced after construction of the tribenzotriquina-
cene framework (e.g. by electrophilic substitution).
Wittig reaction of 3h with benzyltriphenylphosponium
bromide and sodium hydroxide furnished the expected
In the present communication we describe the preparation styrene derivative 3j (77%) as a mixture of diastereomers.
of 2-substituted TBTQs, compounds which could be of Conversion of 3h into phenyl ketone 3l was accomplished
use, for example, for the construction of larger bowl- by first carrying out a Grignard reaction with phenyl mag-
shaped molecules (see below).
nesium bromide (formation of 3k, 50%) followed by a
Swern oxidation (91%). Clearly, both 3j and 3l are useful
starting materials for the preparation of tribenzotriquina-
cenes with a single-wing extension.9
We illustrate first the preparation of 2-substituted triben-
zotriquinacenes by the examples collected in Scheme 1.
Thus the p-methoxy-substituted substrate 1b was reduced
with sodium borohydride/cerium trichloride·heptahydrate We are also interested in the preparation of derivatives
4
(
Luche conditions) in good yield to diol mixture 2b, containing more than one TBTQ moiety (e.g., compounds
which on treatment with polyphosphoric acid in chloro- with a double or multiple cup structure).8 As a first ex-
,9
benzene furnished 2-methoxytribenzotriquinacene 3b periment in this direction we prepared the ‘dimeric’ struc-
(
15%). Likewise, the bromo compound 3d resulted when ture 7 using our new TBTQ synthesis (Scheme 3). Since
dione 1d was subjected to the same sequence (total yield the direct formylation of 3a to 3h was low-yielding (see
over all three steps: ca. 10%). The BBr -catalyzed ether above), we decided to prepare the more soluble trimethyl
3
10
cleavage of 3b caused the formation of phenol 3c (68%), derivative 4 in a sequence developed by Kuck (overall
whereas Sonogashira coupling of 3d with trimethylsi- yield from 3a to 4: 54%).
lylacetylene yielded 3e (81%), which was desilylated to
Condensation of aldehyde 4 with dibenzoylmethane fur-
the ethynyl derivative 3f by treatment with potassium car-
nished diketone 5 in good yield. And after reduction of
bonate in MeOH–THF in 92% yield. Finally, the second-
this intermediate to the diastereomeric diols 6, the latter
were cyclized as above to hydrocarbon 7, which was also
ary amine 3g was obtained from 3c by Buchwald coupling
with p-toluidine in the presence of Xanthphos, sodium
obtained as a mixture of diastereomers. Although we were
5
tert-butoxide, and Pd (dba) (68%). All new compounds
2
3
able to separate this mixture partially by column chroma-
tography on silica gel, single crystals suitable for an X-ray
investigation have so far been obtained only for the anti-
were characterized by the usual analytical and spectro-
6
scopic data.
To investigate the above-mentioned electrophilic substi- isomer. The results of this study are shown in Figure 1.
tution of 3a we subjected this parent system to the Rieche
The molecule of anti-7 displays bond lengths and angles
7
,8
formylation. As expected, the substitution took place
exclusively at the outer rim of tribenzotriquinacene. How-
ever, the yield of this (not optimized) transformation was
poor (37%), most likely due to the low solubility of the
essentially as expected for the strained triquinacene sys-
tem; thus the single bonds to the central carbons (C18D
and C18E) are slightly lengthened at ca. 1.56 Å, and two
2
of the three bond angles at the formally sp atoms (e.g.,
i
ii, iii
3a
CHO
CN
(± ±-3h 37%
(± ±-3i 46%
iv
v
vi
OH
O
3j 77%
3k 50%
(± ±-3l 91%
Scheme 2 Preparation of 2-substituted tribenzotriquinacenes via initial electrophilic aromatic substitution. Reagents and conditions: i) TiCl ,
4
+
–
MeOCHCl , CH Cl , 20 °C, 24 h; ii) NH OH·HCl, KOH, EtOH–H O (1:1), reflux, 8 h; iii) Ac O, reflux, 2 h; iv) [PhCH PPh ] Br , NaOH,
2
2
2
2
2
2
2
3
CH Cl , 20 °C, 2 h; v) PhMgBr, THF, 20 °C, 0.5 h; vi) (COCl) , DMSO, Et N, CH Cl , –78 °C to 20 °C, 2 h.
2
2
2
3
2
2
Synlett 2013, 24, 453–456
© Georg Thieme Verlag Stuttgart · New York

LETTER
Preparation of 2-Substituted Tribenzotriquinacenes
455
Me
Me
Me
Me
i–iii
iv
3a
CHO
Ph
O
Me
Me
O
(± ±-4 54%
(± ±-5 60%
Ph
v
Me
Me
Me
Me
vi
Ph
Me
Me
HO
OH
Ph
7
10%
6 80%
Scheme 3 Preparation of the double bowl-shaped hydrocarbon anti-7. Reagents and conditions: i) Br , hν, CHCl , 20 °C, 30 min; ii) Al(CH ) ,
2
3
3 3
n-heptane, 50 °C, 15 min; iii) TiCl , MeOCHCl , CH Cl , 20 °C, 24 h; iv) dibenzoylmethane, piperidine, toluene, reflux 18 h; v) CeCl ·7H O,
4
2
2
2
3
2
NaBH , MeOH, CH Cl , –78 °C to 20 °C, 12 h; vi) polyphosphoric acid, chlorobenzene, reflux, 24 h.
4
2
2
C4C, C8A) common to five-membered and benzo rings
are distorted by ca. 7–8° from the ideal 120° [e.g., C5–
C4C–C4B 127.50(15)° and C8A–C4C–C4B 112.07(14)°].
The central carbons lie ca. 1.4 Å out of the plane of the ap-
2
propriate sp atoms (for C18D defined by C4C, C8A,
C8C, C18A, C18C, C4A and for C18E defined by C13A,
C9C, C9A, C17C, C17A, C13C). The molecules stack
parallel to the a-axis; neighboring molecules are related
by inversion. The average stacking repeat distance is a/2
11
=
5.299 Å. The steplike structure of the hydrocarbon is
recognizable particularly well in the side view of anti-7
Figure 2).
(
Acknowledgment
G. M. thanks the Fonds der Chemischen Industrie and the Studien-
stiftung des deutschen Volkes for scholarships; R. S. was supported
by a scholarship from the INDIGO program. We thank Prof. D.
Kuck (University of Bielefeld) very much for numerous helpful
discussions.
Figure 1 Structure of anti-7 in the solid state (top view, ellipsoids rep-
resent 30% probability levels)
References and Notes
(
1) Markopoulos, G.; Henneicke, L.; Shen, J.; Okamoto, Y.;
Jones, P. G.; Hopf, H. Angew. Chem. Int. Ed. 2012, 51,
1
2884; Angew. Chem. 2012, 124, 13057.
2) For the first syntheses of the TBTQ framework, see:
a) Kuck, D. Angew. Chem. Int. Ed. Engl. 1984, 23, 508;
(
(
Angew. Chem. 1984, 96, 515. (b) Kuck, D.; Lindenthal, T.;
Schuster, A. Chem. Ber. 1992, 125, 1449. (c) Kuck, D.;
Neumann, E.; Schuster, A. Chem. Ber. 1994, 127, 151. For
reviews on centropolyindanes, see: (d) Kuck, D. Chem. Rev.
2
006, 106, 4885. (e) Zhang, T. V.; Zhou, L.; Cao, X. P.;
Figure 2 Side view of anti-7 in the solid state
Kuck, D. Chin. J. Org. Chem. 2007, 27, 946.
(3) For some of the rare cases of ortho-substituted TBTQs, see:
(
a) Dullaghan, C. A.; Carpenter, G. B.; Sweigart, D. A.;
©
Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 453–456

4
56
R. Saravanakumar et al.
LETTER
Kuck, D.; Fusco, C.; Curci, R. Organometallics 2000, 19,
(7) For Rieche formylation reactions of several derivatives of
3a, see: Niu, W. X.; Wang, T.; Hou, Q. Q.; Li, Z. Y.; Cao, X.
P.; Kuck, D. J. Org. Chem. 2010, 75, 6704.
(8) Wang, T.; Hou, Q. Q.; Teng, Q. F.; Yao, X. J.; Niu, W. X.;
Cao, X. P.; Kuck, D. Chem. Eur. J. 2010, 16, 12412.
(9) Niu, W. X.; Yang, E. Q.; Shi, Z. F.; Cao, X. P.; Kuck, D. J.
Org. Chem. 2012, 77, 1422.
(10) Kuck, D.; Schuster, A.; Krause, R. A.; Tellenbröker, J.;
Exner, C. P.; Penk, M.; Bögge, H.; Müller, A. Tetrahedron
2001, 57, 3587; and references quoted therein.
(11) X-Ray Structure Determination of anti-7
Crystal Data
2233. (b) Kuck, D.; Hackfort, T.; Neumann, B.; Stammler,
H. G. Pol. J. Chem. 2007, 81, 875. (c) Kirchwehm, Y.;
Damme, A.; Kupfer, T.; Braunschweig, H.; Krüger, A.
Chem. Commun. 2012, 48, 1502. (d) Mughal, E. U.; Kuck,
D. Chem. Commun. 2012, 48, 8880.
(
(
4) Gemal, A. L.; Luche, J. L. J. Am. Chem. Soc. 1981, 103,
454.
5
5) (a) Wolfe, J. P.; Wagaw, S.; Buchwald, S. L. J. Am. Chem.
Soc. 1996, 118, 7215. (b) Lennartz, P.; Raabe, G.; Bolm, C.
Isr. J. Chem. 2012, 52, 171.
6) Preparation of the Amine 3g as Typical Experimental
Procedure
(
Monoclinic, P2 /c, a = 10.5987(8), b = 25.6904(16), c =
1
3
An oven-dried, two-necked round-bottomed flask was
charged with 2-bromotribenzotriquinacene (3d, 300 mg,
10.5725(8) Å, β = 104.749(8)°, V = 2783.9(3) Å , Z = 4, μ =
0.5 mm , D = 1.252 mg/m .
–
1
3
x
0
[
0
.83 mmol), p-toluidine (107 mg, 1.0 mmol), Xanthphos
4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, 29 mg,
.05 mmol], NaOt-Bu (112 mg, 1.16 mmol), and Pd (dba)
Data Collection and Reduction
A colorless hexagonal plate 0.15 × 0.1 × 0.02 mm was
mounted on a glass fiber in inert oil and transferred to the
cold gas stream of the diffractometer (Oxford Diffraction
Nova A). A total of 53127 intensities were recorded to 2θmax
152° using mirror-focussed Cu Kα radiation (λ = 1.54184
Å); 5783 of these were independent (Rint = 0.073).
Absorption corrections were performed on the basis of
multiscans.
2
3
[tris(dibenzylideneacetone)dipalladium(0), 23 mg, 0.02
mmol]. The flask was evacuated and refilled with argon
three times. Toluene (100 mL) was added, and the reaction
mixture was refluxed for 20 h. After cooling to r.t., the
reaction mixture was diluted with EtOAc and passed through
a pad of silica gel. The solvent was removed in vacuo, and
the analytically pure amine 3g was obtained by flash
chromatography using silica and 5% EtOAc in pentane as
Structure Refinement
2
The structure was refined anisotropically on F using the
1
12
the eluent: 220 mg (68%) of 3g, mp 215–216 °C. H NMR
program SHELXL-97. Hydrogen atoms were included
(
400 MHz, CDCl , TMS): δ = 7.46–7.34 (m, 4 H), 7.28 (d, J
using a riding model starting from calculated positions. The
final wR2 for all reflections was 0.134 for 373 parameters,
with R1 = 0.049 for reflections with I > 2σ(I); S = 1.02, max.
3
=
6
8.0 Hz, 1 H), 7.17–7.13 (m, 5 H), 7.04 (d, J = 8.4 Hz, 2 H),
.92 (d, J = 8.0 Hz, 2 H), 6.83 (d, J = 8.0 Hz, 1 H), 5.54 (br
s, 1 H), 4.95–4.86 (m, 3 H), 4.47 (q, J = 9.6 Hz, 1 H), 2.28
s, 3 H) ppm. 13C NMR (100.6 MHz, CDCl ): δ = 147.0,
–
3
Δρ = 0.58 e Å .
(
Crystallographic data have been deposited with the
Cambridge Crystallographic Data Centre as supplementary
publication no. CCDC 909301. Copies of the data can be
obtained free of charge from
3
1
1
1
46.2, 145.9, 145.7, 145.6, 143.1, 140.9, 138.2, 130.2,
29.8, 127.3, 127.3, 127.2, 124.7, 124.2, 124.2, 118.0,
17.5, 113.2, 55.8, 55.8, 55.2, 51.6, 20.6 ppm. UV (CH Cl ):
2
2
λmax (lg ε) = 228 (4.21), 278 (4.18), 290 (4.25) nm. IR
www.ccdc.cam.ac.uk/data_request/cif.
(
(
powder): ν = 3395 (s), 3018 (s), 1606 (m), 1517 (ms), 1492
m), 1478 (m), 1330 (m), 806 (ms), 742 (vs), 573 (m) cm .
(12) Sheldrick, G. M. Shelxl-97, Program for the Refinement of
Crystal Structures; Universität Göttingen: Göttingen,
Germany, 1997, see also: Sheldrick G. M.; Acta
Crystallogr., Sect. A: Found. Crystallogr. 2008, 64, 112.
–
1
MS: m/z calcd: 385.18250; found: 385.18243. Anal. Calcd.
for C H N (385.50): C, 89.23; H, 6.02; N, 3.58. Found: C,
2
9
23
89.07; H, 6.03; N, 3.27.
Synlett 2013, 24, 453–456
© Georg Thieme Verlag Stuttgart · New York

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