Selective synthesis of dibenzo[a,c]cyclooctatetraenes via palladium-catalyzed [4+4] cyclic homocoupling of borylvinyl iodobenzene derivatives

Article abstract of DOI:10.1039/c0cc02380a

Dibenzo[a,c]cyclooctatetraenes were selectively generated in good yields from the palladium-catalyzed [4+4] cyclic homocoupling of borylvinyl iodobenzene derivatives, which were prepared via the selective Suzuki-Miyaura cross-coupling of the gem-diboryl reagents with iodo compounds.

Full text of DOI:10.1039/c0cc02380a

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Selective synthesis of dibenzo[a,c]cyclooctatetraenes via
palladium-catalyzed [4+4] cyclic homocoupling of borylvinyl
iodobenzene derivativesw
Hui-jun Zhang,a Junnian Wei,a Fei Zhao,a Yun Liang,a Zitao Wanga and Zhenfeng Xi*ab
Received 6th July 2010, Accepted 16th August 2010
DOI: 10.1039/c0cc02380a
Dibenzo[a,c]cyclooctatetraenes were selectively generated in
good yields from the palladium-catalyzed [4+4] cyclic
homocoupling of borylvinyl iodobenzene derivatives, which were
prepared via the selective Suzuki–Miyaura cross-coupling of the
gem-diboryl reagents with iodo compounds.
We are recently working on the preparation and synthetic
applications of polyhalo and polyboryl compounds,5 expecting
cooperative effect among those polyfunctional groups. Since
the C–I bond and the C–B bond are known to react remarkably
differently, selective transformation might be possible upon
treatment of the styrene derivatives 5 with transition metal
complexes, for example, under the Suzuki–Miyaura coupling
reaction condition.6,7 With this expectation in mind, we first
investigated the synthesis of compounds 5.7 As shown in
Scheme 2, when the gem-diboryl compounds 4 were subjected
to the Suzuki–Miyaura reaction condition, a variety of
compounds 5 were obtained in good yields.z It is noteworthy
that this coupling reaction proceeds highly selectively. The
stereochemistry of compound 5c was determined by single-
crystal X-ray structural analysis (Fig. 1).
Dibenzocyclooctatetraenes, including dibenzo[a,c]cyclooctate-
traenes and dibenzo[a,e]cyclooctatetraenes, are a class of
fascinating cyclooctatetraene derivatives (COTs) with extra-
ordinary properties and reactivities, owing to their unique
structures.1–4 Although several general and efficient methods
are known for the preparation of dibenzo[a,e]cyclooctate-
traenes,2–4 there remains a great challenge for the selective
synthesis of the [a,c] form, since normally a mixture of two isomers
will be achieved with the [a,e] form as a major product.2–4 In
principle, the cyclic dimerization of functionalized vinylbenzene
derivatives 1 affords us a straightforward approach to the
synthesis of dibenzocyclooctatetraenes (Scheme 1). Takahashi
et al.,4a Itoh et al.,4b,c Xi et al.4e have applied such a strategy in
the case of E = E0 = [Cu] to generate COT derivatives or
dibenzo[a,e]cyclooctatetraenes. It can be expected that the
nature of functional groups E and E0 may play a key role in
determining the regioselectivity of such a homo-dimerization.
We then exposed the compounds 5 under the Suzuki–
Miyaura intramolecular coupling reaction condition. As given
in Scheme 3, cyclic homo-dimerization of the styrene
derivative 5 with one C–I bond and one C–B bond proceeded
smoothly in a highly regioselective coupling manner, affording
the dibenzo[a,c]cyclooctatetraene 6 in good isolated yields
with trace amount formation of the [a,e] isomer in some cases.y
It is noteworthy that substrates 5f and 5g bearing electron-
withdrawing groups on the phenyl ring could not afford the
Scheme 1 Synthetic strategy for dibenzocyclooctatetraenes.
a Beijing National Laboratory for Molecular Sciences,
Key Laboratory of Bioorganic Chemistry and Molecular Engineering
of Ministry of Education, College of Chemistry, Peking University,
Beijing 100871, China. E-mail: zfxi@pku.edu.cn;
Fax: +86 10 62759728; Tel: +86 10 62759728
b State Key Laboratory of Organometallic Chemistry,
Shanghai Institute of Organic Chemistry, Shanghai, 200032, China
w Electronic supplementary information (ESI) available: Experimental
details, X-ray data for 5c and 6b, and scanned NMR spectra of all new
products (PDF). CCDC 782988 (5c) and CCDC 775681 (6b). For ESI
and crystallographic data in CIF or other electronic format see DOI:
10.1039/c0cc02380a
Scheme 2 Suzuki–Miyaura coupling of diboryl reagents 4.
Chem. Commun., 2010, 46, 7439–7441 7439
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Fig. 1 ORTEP drawing of 5c with 30% thermal ellipsoids. Hydrogen
atoms omitted for clarity.
Scheme 4 A proposed catalytic cycle.
which might undergo a second oxidative addition with another
molecule of 5 to form the intermediate B. Selective reductive
elimination of the intermediate B would afford the inter-
mediate C. A second intramolecular Suzuki–Miyaura type
coupling reaction of the intermediate C led to the formation
of the dibenzo[a,c]cyclooctatetraenes 6. Since the palladium-
catalyzed homo-couplings of aryl iodides and of arylboronic
acids are well-known,11 other pathways leading to compounds
6 via homo-coupling of CAr–CAr bond and of Cvinyl–Cvinyl
bond of 5, though less likely compared with that shown in
Scheme 4, cannot be ruled out.
In summary, we have described for the first time a palladium
catalyzed highly selective method for the preparation of
dibenzo[a,c]cyclooctatetraenes. This new synthetic methodology
involves an unprecedented homo-dimerization of two molecules
of borylvinyl iodobenzene derivatives. The scope and mechanistic
details of this methodology are in progress.
Scheme 3 Palladium-catalyzed coupling reaction of compounds 5.
This work was supported by Natural Science Foundation of
China and the Major State Basic Research Development
Program (2006CB806105). The Cheung Kong Scholars
Programme, Qiu Shi Science & Technologies Foundation,
Dow Corning Corporation, Eli Lilly China and BASF are
gratefully acknowledged.
corresponding dibenzocyclooctatetraenes. The structure of 6b
was identified by X-ray single crystal structural analysis
(Fig. 2). To the best of our knoweldege, this is the first efficient
method for the synthesis of dibenzo[a,c]cyclooctatetraenes.
Based on the above results, a possible catalytic cycle for the
cyclic homo-dimerization of compounds
5 is given in
Notes and references
Scheme 4. The first step is proposed to proceed via an
intramolecular Suzuki–Miyaura coupling to afford the indenyl
palladacycle A.8–10 Palladacycles have been frequently proposed
as important reactive intermediates in Pd-catalyzed reactions
and have attracted considerable attention.9,10 In our case,
substrate 5 reacted with Pd(0) via tandem oxidative addition/
intramolecular transmetallation affording the palladacycle A,
z A typical procedure for the preparation of styrene derivatives 5: to a
4 mL solution of ArI (0.6 mmol) and Pd(OAc)2 (0.025 mmol) in
MeOH were added gem-diboryl reagent 4 (0.5 mmol) and K2CO3
(1.5 mmol), and the mixture was stirred at room temperature while the
reaction was monitored by TLC. Then the MeOH was removed under
reduced pressure and the residue was purified by column chromato-
graphy using silica gel (PE : Et2O = 20 : 1) to afford the final
products. 5a: colorless liquid, isolated yield 59%. 1H NMR (CDCl3,
300 MHz) d 0.86 (s, 12H), 1.88 (s, 3H), 6.84–6.89 (m, 1H), 7.15–7.28
(m, 7H), 7.72–7.75 (d, J = 7.5 Hz, 1H); 13C NMR (CDCl3, 75.4 MHz)
d 21.9, 24.2, 24.3, 83.0, 98.8, 126.0, 127.6, 128.0, 128.1, 128.7, 128.9,
138.5, 140.8, 149.6, 151.4. HRMS calcd for [C21H24BIO2]H+
447.0992, found 447.0985.
y A typical procedure for the preparation of dibenzo[a,c]cyclooctate-
traene 6: to a 3 mL solution of styrene derivative 5 (0.3 mmol) and
Pd(PPh3)4 (0.015 mmol) in DMF was added Cs2CO3 (0.9 mmol) and
the mixture was stirred for 8 h at 120 1C. Then the resulting mixture
was diluted with saturated aq. NH4Cl and extracted with Et2O three
times. The organic layers were combined, washed with brine, dried
over MgSO4, and concentrated in vacuo. The residue was purified by
column chromatography using silica gel (PE : Et2O = 50 : 1) to
Fig. 2 ORTEP drawing of 6b with 30% thermal ellipsoids. Hydrogen
atoms omitted for clarity.
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afford the final product. 6a: colorless liquid, isolated yield 67%.
1H NMR (CDCl3, 300 MHz) d 1.28 (s, 6H), 6.42–6.48 (m, 4H),
6.56–6.78 (m, 6H), 6.80–6.82 (m, 2H), 6.84–6.90 (m, 2H), 6.92–7.02
(m, 4H); 13C NMR (CDCl3, 75.4 MHz) d 21.6, 126.3, 126.4, 126.6,
127.0, 127.6, 128.6, 129.1, 133.9, 140.5, 140.6, 144.6. HRMS calcd for
[C30H24]H+ 385.1956, found 385.1948.
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