A Diels-Alder approach to trans-trisbicyclo[2.2.1]heptabenzene derivative

Article abstract of DOI:10.1016/j.tetlet.2008.08.007

A new route to the synthesis of a trans-tris(bicyclo[2.2.1]hexeno)benzene derivative, using Diels-Alder reaction as critical step, was investigated. The compound with six methoxycarbonyl groups was successfully synthesized in good yield without any organometallic reagents. Some useful by-products from dimethyl but-2-ynedioate were also isolated from the last step. Perhaps due to stereo-hindrance or electrostatic repulsion in the cis-isomer, trans-isomer was found to be the only isomer in the crystal and its structure was proved by X-ray diffraction.

Full text of DOI:10.1016/j.tetlet.2008.08.007

Tetrahedron Letters 49 (2008) 6126–6128
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A Diels–Alder approach to trans-trisbicyclo[2.2.1]heptabenzene derivative
*
Zhong-Qiang Gao, Jun-Fa Wei , Xian-Ying Shi, Jun Yu
School of Chemistry and Materials Science, Shaanxi Normal University, Shaanxi 710062, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A new route to the synthesis of a trans-tris(bicyclo[2.2.1]hexeno)benzene derivative, using Diels–Alder
reaction as critical step, was investigated. The compound with six methoxycarbonyl groups was success-
fully synthesized in good yield without any organometallic reagents. Some useful by-products from
dimethyl but-2-ynedioate were also isolated from the last step. Perhaps due to stereo-hindrance or elec-
trostatic repulsion in the cis-isomer, trans-isomer was found to be the only isomer in the crystal and its
structure was proved by X-ray diffraction.
Received 10 May 2008
Revised 30 July 2008
Accepted 5 August 2008
Available online 8 August 2008
Keywords:
Ó 2008 Elsevier Ltd. All rights reserved.
Diels–Alder cycloaddition
Trisbicyclo[2.2.1]heptabenzene
Mills–Nixon effect
X-ray diffraction
In the recent years, much attention has been focused on the
synthesis of the compounds that possess cyclohexatriene motif,
which could potentially lead to new materials to broaden the scope
of molecular recognition and supramolecular chemistry.1 These
compounds have also been used as precursors of subunits of fuller-
ene2 and trindane structures.3 In addition, there exists a phenom-
enon of bond alternation (or localization) in benzenoid structures
of these compounds, which is associated with the Mills–Nixon
effect,4 and this has been the subject of considerable theoretical
investigations.5
Such compounds are generally synthesized through the cyclo-
trimerization of trimethylstannylalkenes, using different metal
catalysts.6 For example, F. Fabris developed an original reaction
involving trimerization of vicinal bromotrimethylstannyl olefins
with a copper promoter.6g The reaction of polycyclic bromotrim-
ethylstannyl olefins with alkenes in the presence of copper(II) ni-
trate in THF was reported to produce a mixture of syn and anti
isomers.6a The antiselective synthesis of the cyclotrimer has been
achieved efficiently, using a Pd(0) catalyst.6c However, the synthe-
sis still faces great challenges as it involves hypersensitive organo-
metallic precursors, which are difficult to be prepared. Therefore,
the search for a better synthetic strategy to prepare these com-
pounds is highly desirable.
Trindane 1 was obtained in a yield of 31% from cyclopentanone
and ZrCl4 according to the literature,7 but under microwave irradi-
ation.8 1,3,4,6,7,9-hexabromotrindane 2 is produced by the broma-
tion reaction of 1 with Br2 in 82% yield, according to the method we
reported previously.9
The most critical step of this route is the Diels–Alder reaction of
1,3,4,6,7,9-hexabromotrindanes
2 with a dienophile, such as
dimethyl but-2-ynedioate, in which compound 2 eliminates six
bromine atoms to generate a tri-diene intermediate. Dimethyl
but-2-ynedioate was selected as the dienophile due to its high
reactivity in Diels–Alder reaction and simplicity of the expected
products. The target compound 310 was obtained in 32% yield by
reacting 1 equiv of compound 2 with 8 equiv of zinc powder, and
a large excess of ca. 20 equiv of dimethyl but-2-ynedioate in
DMF under ultrasonic irradiation (Scheme 2). The use of ultrasonic
irradiation in the reaction improved the yield of compound 3.
The control experiment showed that a lower yield of 20% of the
desired product was obtained without ultrasonic irradiation. An
explanation for this improvement could be the impact and cavita-
tion effects of ultrasonic irradiation to keep the surface of Zn metal
fresh.
The excessive but-2-ynedioate is necessary in the reaction,
since the tri-diene intermediate might be formed firstly in the
debromation of compound 2 by Zn powders and carried out the
Diels–Alder reaction with but-2-ynedioate to give the desired
product. Since the intermediate is highly active, the side reactions,
Recently, we designed a four-step route to synthesize tris-
(bicyclo[2.2.1]hexeno)benzene derivative from cyclopentanone
(Scheme 1). This method may lead to the synthesis of a large vari-
ety of new compounds.
including polymerization and [1,5]
r-migration, are easy to take
place. Accordingly, the excessive but-2-ynedioate can improve
the yield of the desired Diels–Alder reaction.
The structure of compound 3 was confirmed by IR, 1H NMR, 13
NMR spectroscopy, and elemental analyses. The absorption around
C
* Corresponding author. Tel.: +86 29 85303734; fax: +86 29 85307774.
E-mail address: weijf@snnu.edu.cn (J.-F. Wei).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.08.007

Z.-Q. Gao et al. / Tetrahedron Letters 49 (2008) 6126–6128
6127
R
R
R
R
Br
Br
Br
R
R
O
Br
Br
R
R
Br
2
1
3
Scheme 1.
Br
Br
Br
CO2Me
CO2Me
Br
Br
Zn powder, ultrasonic
DMF
+
Br
2
CO2Me
CO2Me
MeO2C
MeO2C
MeO2C
MeO2C
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
3-trans
CO2Me
3-cis
H3CO
CO2CH3
CO2CH3
MeO2C
CO2Me
5
4
CO2Me
MeO2C
MeO2C
CO2Me
MeO2C
MeO2C
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
6
CO2Me
7: not observed
Scheme 2.
Figure 1. Top: overall perspective drawing of 3-trans; bottom: clarified drawing of
3-trans (all methoxycabonyls are omitted for clarity); selected bond lengths (Å),
angles (°): C1–C2 = 1.364(5), C2–C3 = 1.432(5), C1–C6 = 1.429(5), C1–C7 = 1.519(5),
1737 cmÀ1 demonstrated the existence of C@O. The chemical shifts
of CH, CH2, and CH3 groups of compound 3 appeared at 2.12–2.15
(d, 3H), 2.46–2.51 (m, 3H), 3.74 (s, 18H), and 4.30–4.35 (d, 6H),
respectively. Compounds 4–6, derived from dimethyl but-2-yne-
dioate,11 were also isolated from the reaction mixture in the yields
of 5.2%, 3.1%, and 7.8%. Compound 6 is an important compound
that can be used in the study of a novel dual fluorescence phenom-
enon.12 Compound 7, the precursor of sumanene derivatives, how-
ever, was not isolated from the reaction mixture, presumably due
to the large size of the bay regions or the possible severe strain that
exists in the structure.
The X-ray crystal structural analysis of 3 revealed that only the
3-trans isomer can be found in the crystal (Fig. 1),13 while 3-cis is
absent. For 3-cis, all the methoxycarbonyl groups have to be on one
side of the central six-membered ring, which would possibly intro-
duce strong steric hindrance as well as electrostatic repulsion.
C3–C4 = 1.351(5),
C4–C5 = 1.423(5),
C5–C6 = 1.357(5),
C11–C12 = 1.484(6),
O1–C12 = 1.207(5), C10–C14 = 1.483(5), O3–C14 = 1.319(5), O3–C15 = 1.448(5);
C2–C1–C6 = 119.5(3), C2–C1–C7 = 134.4(4), C1–C2–C3 = 120.0(4), C4–C3–C2 =
119.7(3), C9–C8–C7 = 94.0(3), C10–C11–C7 = 107.4(3), O1–C12–C11 = 124.0(4),
C12–O2–C13 = 116.7(4).
Recently, the phenomenon of bond alternation (or localization)
in benzene, which is associated with the Mills–Nixon effect, has
become the renewed attention.14 Siegel et al. have reported the
synthesis of tris(bicyclo[2.1.1]hexeno) benzene, as the first
example of mononuclear benzenoid hydrocarbon with a cyclo-
hexatriene-like geometry
(
D
R = Rendo À Rexo = 0.089 Å).15 Obvi-
ously, compound 3 presents a useful model to study the Milles–
Nixon effect. As expected, the central six-membered ring is planar,
and all internal bond angles of the ring are almost 120ꢀ. The bond
lengths are alternately shorter (average 1.357 Å) and longer

6128
Z.-Q. Gao et al. / Tetrahedron Letters 49 (2008) 6126–6128
7. Shirai, H.; Amano, N.; Hashimoto, Y.; Fukui, E.; Ishii, Y. J. Org. Chem. 1991, 56, :
2253.
(average 1.428 Å) with the shorter bonds exocyclic to bicycloann-
elation. The R in 3-trans is ca. 0.071 Å.
D
8. Compound 1: To a flask containing 9 mL (0.1 mol) of cyclopentanone, ZrCl4
(0.94 g, 4.03 mmol) was added. After the reaction mixture was stirred and
refluxed under microwave irradiation for about 4 h, sodium hydroxide solution
was added until the pH 7. The reaction mixture was extracted by CHCl3
(15 mL Â 4). The organic phase was dried over MgSO4, and the crude product
was purified by column chromatography on silica gel (petroleum ether–ethyl
acetate = 5:1) to afford compound 1 as white needle crystals. Yield: 31%. Mp
96.1–97.2 °C; 1H NMR (CHCl3, 300 MHz, d ppm): 2.70ꢀ2.80 (t, 12H, J = 7.20 Hz),
2.00–2.10 (m, 6H). Anal. Calcd for C15H18: C, 90.85; H, 9.15. Found: C, 89.95; H,
In summary, we have developed a new protocol to prepare
tris(bicyclo[2.2.1]hexeno)benzene derivatives using Diels–Alder
reaction as the critical step. Compared to the previous routes, our
protocol neither needs toxic organometallic compounds nor
expensive catalysts. Further studies aimed at the preparation of
cis isomers by changing the dienophile are in progress.
9.06. IR (KBr disk,
m
cmÀ1): 2948, 2835, 1438, 1269.
Acknowledgments
9. Yu, J.; Wei, J. F.; Shi, X. Y.; Gao, Z. Q.; Ma X. Y. The Fifth Symposium of Chinese
Organic Chemistry, 2007, 106.
10. Compound 3: A mixture of zinc powder(0.46 g, 7.0 mmol), dimethyl but-2-
ynedioate (1.79 g, 9.0 mmol) and DMF (10 mL) was sonicated for 15–30 min,
and 0.672 g (1.0 mmol) of 2 was added to the mixture. After soincation for 3–
4 h, the mixture was stirred at 40–50 °C for 5 h, then poured into water
(200 ml), which was extracted with CHCl3 (30 mL Â 3). The combined organic
phases were dried over MgSO4, and then purified by column chromatography
on silica gel (petroleum ether–ethyl acetate = 5:1) to afford compound 3: Yield:
32%. Mp 249.2–251.0 °C; 1H NMR (CHCl3, 300 MHz, d ppm): 4.30–4.35 (d, 6H),
3.74 (s, 18H), 2.46–2.51 (m, 3H), 2.12–2.15 (d, 3H). Anal. Calcd for C33H30O12: C,
The authors are grateful to the National Foundation of Natural
Science (Grant No. 20572066), the Natural Science Foundation of
Shaanxi Province (Grant No. 2006B20).
References and notes
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64.08; H, 4.76. Found: C, 63.97; H, 4.92. IR (KBr disk,
1736, 1447, 1233, 983, 852.
m
cmÀ1): 3011, 2959, 2849,
11. Compound 4: Yield: 5.2%. Mp 106–107 °C; 1H NMR (CHCl3, 300 MHz, d ppm):
6.87 (s, 2H), 3.81 (s, 6H); 13C NMR (CHCl3, 300 MHz, d ppm): 52.26, 133.38,
165.35; Compound 5: Yield: 3.1%. M.p. 40 °C; 1H NMR (CHCl3, 300 MHz, d
ppm): 5.21 (s, 1H), 3.71–3.88 (m, 9H); 13C NMR (CHCl3, 300 MHz, d ppm): 51.5,
52.8, 56.9, 93.1, 93.1, 162.4, 166.2. Anal. Calcd for C7H10O5: C, 48.21; H, 5.75.
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10.0810(11) Å, b = 10.9031(12) Å, c = 14.4099(16) Å;
= 83.049ꢀ(CCDC reference: 696277).
a = 73.788ꢀ, b = 84.057ꢀ,
c
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