Oxidative cyclodimerization after tandem cyclization of dehydrobenzo[14]annulenes induced by alkyllithium

Article abstract of DOI:10.1002/anie.201210233

After eight: Reactions of dehydrobenzo[14]annulenes induced by the addition of n-butyllithium led to the discovery of an unprecedented oxidative cyclodimerization, which forms eight-membered ring products in up to 30 % yield. The product contains two inde

Full text of DOI:10.1002/anie.201210233

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DOI: 10.1002/anie.201210233
Polycycles
Oxidative Cyclodimerization After Tandem Cyclization of
Dehydrobenzo[14]annulenes Induced by Alkyllithium**
Shunpei Nobusue, Akihiro Shimizu, Kenji Hori, Ichiro Hisaki, Mikiji Miyata, and Yoshito Tobe*
Highly ethynylated compounds have the potential to be
transformed into polycyclic aromatic hydrocarbons by intra-
molecular cyclizations between the sp-carbon atoms because
of the high reactivity of carbon–carbon triple bonds.[1]
Particularly those with cyclic structures are useful for the
construction of new carbon frameworks which are otherwise
difficult to obtain. Moreover, cyclic precursors would limit the
number of possible reaction pathways because of steric
constraints. Indeed, a few examples of efficient transforma-
tions of dehydrobenzannulenes into polycyclic carbon frame-
works were reported as exemplified for octadehydrodiben-
zo[12]annulene,[2] hexadehydrotribenzo[12]annulene,[3] and
tetradehydrodibenzo[8]annulene.[4] The reactions are typi-
cally induced by attack of a nucleophile,[4a] an electrophi-
le,[2,4b] or a radical,[3c] or initiated by reduction to generate
a radical anion.[3a,b]
We envisaged that octadehydrotribenzo[14]annulene
([14]DBA) 1a[5] and its congeners 2–4 would serve as
intriguing substrates for multiple trasnannular bond forma-
tions to yield new polycyclic frameworks because of the
presence of four closely located triple bonds. Additionally, the
distorted butadiyne unit is expected to trigger reactions
induced by an electrophile[2a] or a nucleophile,[4a] which would
not occur for unactivated acetylenic bonds.[4a,6] We report
herein the results of the reactions of 1 and its congeners, 2–4,
with butyllithium (nBuLi). We discovered an unprecedented
oxidative cyclodimerization to form eight-membered ring
products, in which two indeno[2,1-a]fluorene components are
connected by a single and a double bond, following three
ꢀ
transannular C C bond formations.
First we envisioned the possible pathways for the tandem
transannular cyclizations of 1a as shown in Scheme 1. In the
initial step, we assume the formation of a five-membered ring
after the addition of a nucleophile to the diyne moiety of 1a to
give the intermediate 7 on the basis of the previous
reports.[2a,3,4a] For the second step, there are two options of
transannular bond formation: 1) formation of a four-mem-
bered ring to give 9 or 2) a five-membered ring to form the 5/
8/5 ring system 8. In the former case, the resulting nine-
membered ring can be further divided into 5/6 a ring system to
afford the tetracyclic intermediate 11 bearing an indeno[2,1-
a]fluorene substructure, or the 4/7 system 10 possessing two
benzocyclobutene units. As to the indeno[2,1-a]fluorene
framework, while Le Berre et al. reported the synthesis of
the unstable 11,12-diphenylderivatives 5a,[7] we succeeded
recently in the synthesis of the robust dimesityl-substituted
derivative 5b and clarified its physical properties including its
singlet diradical character.[8] These results suggest that the
expected product 12, formed by interception of 11 with an
electrophile, must be substantially reactive.
[*] S. Nobusue, Dr. A. Shimizu,[+] Prof. Y. Tobe
Division of Frontier Materials Science
Graduate School of Engineering Science, Osaka University
1-3 Machikaneyama, Toyonaka, Osaka 560-8531 (Japan)
E-mail: tobe@chem.es.osaka-u.ac.jp
Prof. K. Hori
Division of Material Sciences, Graduate School of Science and
Engineering, Yamaguchi University, Yamaguchi (Japan)
Dr. I. Hisaki, Prof. M. Miyata
Department of Material and Life Science, Graduate School of
Engineering, Osaka University, Osaka (Japan)
[+] Present address: Department of Synthetic and Biological Chemistry,
Graduate School of Engineering, Kyoto University, Kyoto (Japan)
[**] This work was supported by a The Grants-in-Aid for Scientific
Research on Innovative Areas “Organic Synthesis based on
Reaction Integration” (No. 2105). The synchrotron radiation
experiments were performed at the BL38B1 of SPring-8 with the
approval of the Japan Synchrotron Radiation Research Institute
(JASRI) (proposal No. 2009B1969 and 2010A1427). We are grateful
to Dr. K. Miura, Dr. S. Baba, and Dr. N. Mizuno for crystallographic
data collection, and Prof. Kendall N. Houk of the University of
California, Los Angeles for his advice on the theoretical studies.
When the di-tert-butyl[14]DBA 1b was treated with
nBuLi at ꢀ788C in THF and subsequently quenched with
water or 1-iodobutane at the same temperature, the products
13a and 13b were obtained in 61 and 67% yields, respectively
(Scheme 2). The 13C NMR spectra (see Figures S10 and S11 in
the Supporting Information) of these products exhibited four
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201210233.
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Scheme 3. Tandem transannular cyclization of 1a and 1b induced by
nBuLi.
Scheme 1. A working hypothesis for tandem transannular cyclizations
of 1a. Energies (kcalmolꢀ1), relative to 11, were calculated by a DFT
((R)B3LYP/6-31G*) method and are shown within parentheses.
crystallographic analysis of the corresponding product 14a
which is derived from 1a (see below).
The reaction of 1a under similar reaction conditions
afforded the corresponding products 14a, 15a, and 16a in 13,
1.3, and 1.0% yields, respectively (Scheme 3). In addition, the
oxidative dimer 17 was isolated in 7.3% yield. The NMR
spectra of 17 indicate that it has an unsymmetric structure,
which is in contrast to 14a. The much lower yields of the
products than those in the case of 1b may be due to facile
intermolecular reactions because of the absence of tert-butyl
groups which would suppress such processes.
The structures of the dimers 14a and 17 were determined
by X-ray crystallographic analysis for the crystals obtained by
recrystallization from a mixture of CHCl3/MeCN and CH2Cl2/
MeCN, respectively.[11] The structure of 14a shows that it
possesses two indeno[2,1-a]fluorene frameworks which are
connected with a single and a double bond at the respective
five-membered rings to form an eight-membered ring in the
center (Figure 1a). The indenofluorene units are facing each
other but twisted because of steric repulsion between the
closely located benzene rings. The two n-butyl groups stretch
above and below the plane of the molecule.
The crystal structure of 17 reveals that it also consists of
two indeno[2,1-a]fluorene frameworks which are connected
with a single and a double bond (Figure 1b). However, here
the single bond is formed between a five-membered ring of
one of the indenofluorene units and a benzene ring of the
second indenofluorene unit, and the double bond is formed
between two five-membered rings similar that in 14a. The two
indenofluorene units are oriented in opposite directions and
are offset from each other to form a seven-membered ring in
the center.
Scheme 2. Transannular cyclization of 1b at low temperature.
signals corresponding to sp-carbon atoms, thus implying that
addition of nBuLi took place at the diyne moiety with
a subsequent transannular cyclization to form a five-mem-
bered ring. In the 1H NMR spectrum of 13a, the signal for the
vinyl proton appears at a high field (d = 8.75 ppm), which is
consistent with the E configuration of the double bond in
view of the similar anisotropic effects resulting from the
proximate triple bonds reported for the related dehydro-
annulenes.[9]
On the contrary, when 1b was treated with nBuLi
(3 equiv)[10] at ꢀ788C and the mixture was warmed up to
room temperature before quenching with water, three
products 14b, 15b, and 16b were isolated in 18, 20, and
16% yields, respectively (Scheme 3). Most surprisingly, the
mass spectrum of 14b indicates that the molecular formula
(C76H74) corresponds to a dimer of 1b which is a two-electron
For the structures of 15a,b and 16a,b, the mass and 1H and
13C NMR spectra indicate that 15a,b contain three n-butyl
groups and one hydrogen atom, and are therefore a two-
electron oxidation products from 1a,b, whereas 16a,b possess
two n-butyl groups and four hydrogen atoms and are two-
electron reduction products. However, because crystals
1
oxidation product. H and 13C NMR spectra (see Figure S12
in the Supporting Information) of 14b imply that 14b has
a symmetric structure, in which tribenzofused tetracyclic
frameworks are connected with a single and a double bond.
The final structural determination of 14b was done by X-ray
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formed to generate 11, it undergoes dimerization to give 14
and 17 through a pathway discussed below. Multiple additions
of nucleophiles as well as dimerizations which proceed
through redox processes are reported in a number of
reactions of [60]fullerene with nucleophiles.[14]
A tentative mechanism for the oxidative cyclodimeriza-
ꢀ
tion step is shown in Scheme 4. It consists of initial C C bond
formation between intermediate 11 to give 18, which under-
goes rotation about the single bond to give 20 with subsequent
Figure 1. Top views of ORTEP drawings of a) 14a and b) 17. Displace-
ment ellipsoids are drawn at 30% probability level.
suitable for X-ray analysis were not obtained, the structures
of 15b and 16b were elucidated on the basis of HMQC and
HMBC using the tert-butyl group as the pivotal groups for the
correlations, as described in detail in the Supporting Infor-
mation.[12] The structures of 15a and 16a were determined by
the similarities of their spectra to those of 15b and 16b,
respectively. As a result, we were able to propose the
structures of 15a,b to be tribenzofused tetracyclic 4/4/5/7
systems and those of 16a,b to be tribenzofused tricyclic 5/5/8
systems formed by three and two transannular bond forma-
tions, respectively (Scheme 3).
The formation of the three types products, 14–16, are
interpreted in terms of the pathways shown in Scheme 1. The
relative energies of the organolithium intermediates esti-
mated by DFT calculations at the B3LYP/6-31G* level of
theory are also shown in parentheses. The calculated energies
suggest that the cyclization pathway leading to 7 is energeti-
cally favored though both of the second steps (7!8 and 7!9)
are endoergic. This is consistent with the fact that 7 was
intercepted as 13a,b when the reaction was conducted at low
temperature. Although the formation of 8 is energetically
more favored than that of 9, a considerable amount of product
via the latter intermediate was obtained.[13] Addition of
another n-butyl group to 8 accompanied by a two-electron
reduction gives 16a,b after quenching with water. In the third
bond-formation step from 9, though the formation of 10 is
energetically much less favorable than the cyclization to 11,
substantial amounts of 15a,b were obtained via 10, after
addition of two n-butyl groups accompanied by a two-
electron oxidation.[13] In contrast, when the 5/6 rings are
Scheme 4. A tentative reaction mechanism for the oxidative dimer
formation. For theoretical calculations using a model compound, see
the Supporting Information.
bond formation to give 21. Subsequent oxidation, either
in situ by the species present in the reaction mixture or by
oxygen during the workup,[15] furnishes the observed major
ꢀ
dimeric product 14a,b. In contrast, C C bond formation in 18
at the proximal carbon atoms with subsequent hydrogen
transfer and oxidation give the minor dimer 17 via 19.[16]
To know the scope of the oxidation cyclodimerization with
regard to nucleophiles, several reagents, including MeLi and
tBuLi, were investigated.[17] However, only when the ethyl-
lithium/sec-butyllithium complex[18] was used did the corre-
sponding cyclic dimeric product 14c form and was isolated in
23% yield (Scheme 5).
When the naphthalene homologue 2 was subjected to the
reaction with nBuLi under similar reaction conditions, the
corresponding dimeric product 14d was isolated in 13% yield
(Scheme 5).[19] Conversely, when 3, having naphthalene units
at different positions, was used, a blue color developed after
quenching the reaction with water, thus suggesting the
formation of 14e, which gradually changed to orange during
purification by silica gel chromatography to give 22a as a final
product (isolated in 23% yield).[19] The structure of 22a was
established by X-ray crystallographic analysis as shown in
Figure S3 of the Supporting Information.[11] The formation of
ꢀ
22a is explained by dehydrogenative C C bond formation
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ꢀ
C C bond formation took place starting from the initial
dimers 14e,f, were obtained, thus demonstrating the general-
ity of the reaction for [14]DBA derivatives. Though the
mechanism of the reaction is not understood, and the
selectivity of the reaction is not very good (up to 30%), the
reaction provides a new approach to otherwise unaccessible
hydrocarbon framework which may be of interest for
optoelectronics.
Received: December 22, 2012
Published online: February 28, 2013
Keywords: annulenes · density functional calculations ·
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dimerization · lithium · polycycles
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between the proximate naphthalene units of 14e. Similarly, 4
having naphthalene rings at both ends of the [14]DBA gave
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cyclodimerization is a general reaction pathway for BuLi-
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The absorption spectra and cyclic voltammograms of
14a,b,d and 22a,b are shown in Figures S8 and S9, respec-
tively, in the Supporting Information. The optical and
electrochemical data obtained from experiments and the
relevant energy levels from calculations are summarized in
Table S5 in the Supporting Information. Whereas the com-
pounds 14a,b,d exhibit absorption maxima at l = 605 or
600 nm, the dehydrogenated dimers 22a,b show absorption
maxima at l = 513 nm, which is substantially hypsochromic
shifted from those of 14a,b,d. These shifts are consistent with
the larger HOMO–LUMO gaps of 22a,b, as estimated by the
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in the Supporting Information) also support the hypsochro-
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503 nm) compared with 14a,d (l = 600 and 602 nm, respec-
tively). It is worth mentioning that the 9,9’-bifluorenylidene
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recovered, thus giving a mixture products which did not contain
14b.
[11] CCDC 915201 (14a), 915203 (17), and 915204 (22a) contain the
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[14]DBAs 1a,b and 2–4 induced by an addition of nBuLi led
to the discovery of an unprecedented cyclodimerization to
form the eight-membered ring products 14a,b,d in which two
indeno[2,1-a]fluorene components are connected by a single
and a double bond, following three transannular bond
formations. In the case of the naphthalene congeners 3 and
4 the corresponding dimers 22a,b, in which dehydrogenative
[13] Though the reasons for these discrepancies are not understood,
one possible interpretation is the relatively low activation
energies for the four-membered ring formation (to give 9 from
7 or 10 from 9) compared to those for the five-membered ring
formation (to give 8 from 7 or 11 from 9), which result from the
proximity effect. Namely, the calculated distance between the
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membered ring formation (2.92 ꢀ) than for the five-membered
ring formation (3.69 ꢀ). In the case of 9, the corresponding
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distances are 2.82 and 3.24 ꢀ, respectively. Though this explan-
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modes), the steric constraint resulting from the medium-sized
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[17] The reaction of 1b with MeLi, tBuLi, and PhLi only gave
complex mixtures of products and did not contain products
corresponding to 14–16. The reason for this different reactivity is
not clear.
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[19] For the reactions of 2–4, tributylated (two-electron oxidized)
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to 15b and 16b were occasionally detected by 1H NMR spectra
of the chromatography fractions, but they were not isolated. For
the details, see the Experimental Section in the Supporting
Information.
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[15] Air oxidation of a dicyclopentadienyl dianion to a fulvalene
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[16] The activation energies for these processes were estimated by
using as-indacene as a model compound (for the details of the
calculations, see the Supporting Information). The transition-
state search was undertaken at TS-Technology Inc.
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