Intramolecular reductive double cyclization of o,o-bis(arylcarbonyl) diphenylacetylenes: Synthesis of ladder π-conjugated skeletons

Article abstract of DOI:10.1021/ol901148p

Upon the treatment of bis(arylcarbonyl)diphenylacetylenes with lithium naphthalenide, the carbonyl reduction dominantly occurs over the acetylene reduction. The produced bis(radical anion) intermediate undergoes a synchronous double-radical 5-endo-dig cyc

Full text of DOI:10.1021/ol901148p

ORGANIC
LETTERS
2009
Vol. 11, No. 14
3076-3079
Intramolecular Reductive Double
Cyclization of o,o′-Bis(arylcarbonyl)-
diphenylacetylenes: Synthesis of Ladder
π-Conjugated Skeletons
Hongyu Zhang, Takashi Karasawa, Hiroshi Yamada, Atsushi Wakamiya, and
Shigehiro Yamaguchi*
Department of Chemistry, Graduate School of Science, Nagoya UniVersity,
Furo, Chikusa, Nagoya 464-8602, Japan
yamaguchi@chem.nagoya-u.ac.jp
Received May 23, 2009
ABSTRACT
Upon the treatment of bis(arylcarbonyl)diphenylacetylenes with lithium naphthalenide, the carbonyl reduction dominantly occurs over the
acetylene reduction. The produced bis(radical anion) intermediate undergoes a synchronous double-radical 5-endo-dig cyclization. This simple
reduction procedure produces two intriguing classes of ladder π-conjugated skeletons, i.e., emissive methylene-bridged stilbenes and
dibenzo[a,e]pentalenes regarded as a cyclic 1,4-diphenylbutadiene.
The intramolecular cyclizations of o-substituted phenylacety-
lenes to furnish a 5-membered ring fused to the benzene ring
(eq 1)1 are typical tools for the synthesis of indenes2 and
various benzoheterocycles, such as indole, benzofuran, and
benzothiophene.3 Simply doubling this methodology using
o,o′-disubstituted diphenylacetylenes as precursors provides
a new basis for the construction of fused polycyclic skeletons,
as shown in eq 2.4 The produced ladder-type bridged
stilbenes have rigid and coplanar skeletons that give rise to
intriguing properties, such as intense luminescence. These
skeletons would be useful building units for new functional
materials in organic electronics, including organic light-
emitting diodes and organic transistors. Indeed, this double-
cyclization methodology enabled us to synthesize a series
(1) (a) Zeni, G.; Larock, R. C. Chem. ReV. 2006, 106, 4644. (b) Patil,
N. P.; Yamamoto, Y. Chem. ReV. 2008, 108, 3395.
(2) Nakamura, I.; Bajracharya, G. B.; Wu, H.; Oishi, K.; Mizushima,
Y.; Gridnev, I. D.; Yamamoto, Y. J. Am. Chem. Soc. 2004, 126, 15423.
(3) For recent examples, see the following. E ) O: (a) Nakamura, I.;
Mizushima, Y.; Yamamoto, Y. J. Am. Chem. Soc. 2005, 127, 15022. (b)
Fu¨rstner, A.; Davies, P. W. J. Am. Chem. Soc. 2005, 127, 15024. (c)
Anderson, S.; Taylor, P. N.; Verschoor, G. L. B. Chem.sEur. J. 2004, 10,
518. (d) Bates, C. G.; Saejueng, P.; Murphy, J. M.; Venkataraman, D. Org.
Lett. 2002, 4, 4727. (e) Dai, W.-M.; Lai, K. W. Tetrahedron Lett. 2002,
43, 9377. E ) S: (f) Nakamura, I.; Sato, T.; Terada, M.; Yamamoto, Y.
Org. Lett. 2007, 9, 4081. (g) Hessian, K. O.; Flynn, B. L. Org. Lett. 2003,
5, 4377. (h) Larock, R. C.; Yue, D. Tetrahedron Lett. 2001, 42, 6011. E )
NR: (i) Shimada, T.; Nakamura, I.; Yamamoto, Y. J. Am. Chem. Soc. 2004,
126, 10546. (j) Barluenga, J.; Trincado, M.; Rubio, E.; Gonza´lez, J. M.
Angew. Chem., Int. Ed. 2003, 42, 2406. (k) Cacchi, S.; Fabrizi, G.; Parisi,
L. M. Org. Lett. 2003, 5, 3843. (l) Rodriguez, A. L.; Koradin, C.; Dohle,
W.; Knochel, P. Angew. Chem., Int. Ed. 2000, 39, 2488.
of ladder π-electron systems containing NR,5 SiR2,6 S and
10
Se,7-9 BR2 and PR2 , and P(dO)R11 as the bridging
-
+
moieties. As a new family of these reactions, we now disclose
(4) Yamaguchi, S.; Tamao, K. Chem. Lett. 2005, 34, 2.
(5) Kaszynski, P.; Dougherty, D. A. J. Org. Chem. 1993, 58, 5209.
(6) (a) Yamaguchi, S.; Xu, C.; Tamao, K. J. Am. Chem. Soc. 2003, 125,
13662. (b) Xu, C.; Wakamiya, A.; Yamaguchi, S. J. Am. Chem. Soc. 2005,
127, 1638. (c) Xu, C.; Wakamiya, A.; Yamaguchi, S. Org. Lett. 2004, 6,
3707.
10.1021/ol901148p CCC: $40.75
Published on Web 06/18/2009
 2009 American Chemical Society

an intramolecular reductive double cyclization of o,o′-
bis(arylcarbonyl)diphenylacetylenes, as shown in Scheme 1.
In addition to its novelty in the cyclization mode, this reaction
produces two important classes of cyclized products, i.e.,
methylene-bridged stilbenes and dibenzo[a,e]pentalenes, both
of which would be promising building units for extended
π-electron materials. To demonstrate their potentials, we also
carried out further derivatization of the cyclized skeletons.
Scheme 1. Reductive Double Cyclization of
Bis(arylcarbonyl)diphenylacetylenes
We first examined the reaction of o,o′-bis(p-tolylcarbonyl)-
diphenylacetylene 1a with lithium naphthalenide (LiNaph)
(Scheme 1). A THF solution of 1a was reacted with 4 mol
amounts of LiNaph at room temperature for 4 h. Aqueous
workup followed by column chromatography produced the
trans and cis isomers of hydroxymethylene-bridged stilbene
2a in 31 and 21% yields, respectively, together with
unexpected dibenzo[a,e]pentalene 3a in 8% yield. Elongation
of the reaction period from 4 to 8 h resulted in the increment
of the yield of the dibenzopentalene 3a up to 23%. However,
use of an excess amount of LiNaph (8 mol amounts) only
produced a trace amount of 3a, and the bridged stilbene
products were not obtained. When compound 1b was reacted
with 4 mol amounts of LiNaph for 8 h, compounds 2b and
3b were obtained in comparable yields. The stereochemistry
of 2b (trans and cis) was determined by X-ray crystal-
lography.12 These results demonstrate that this type of
substrate indeed undergoes the double cyclization to give
the cyclized products.
these reactions is interesting for us. We elucidate the reaction
mechanism of the present cyclization based on the following
theoretical and experimental considerations.
The first process of this cyclization should be the one-
electron reduction. To gain an insight into the produced
radical anion, theoretical calculations of 1b were carried out
at the UB3LYP/6-31+G(d) level. The optimized structure
of the radical anion 1b•- has a SOMO delocalized over the
entire molecule (Figure 1a), suggesting that the carbonyl and
As a precedent of the reductive double cyclization, we
previously reported the transformation from o,o′-bis(silyl)-
diphenylacetylenes to silylene-bridged stilbenes (E ) E′ )
SiR2 in eq 2),6 which proceeds through a stepwise two-
electron reduction of the acetylene moiety.6c In contrast, the
present precursor 1 has two kinds of reducible functional
moieties, i.e., the carbonyl groups as well as the acetylene
moiety. Therefore, the similarity or dissimilarity between
(7) Sashida, H.; Yasuike, S. J. Heterocycl. Chem. 1998, 35, 725.
(8) Takimiya, K.; Kunugi, Y.; Konda, Y.; Ebata, H.; Toyoshima, Y.;
Otsubo, T. J. Am. Chem. Soc. 2006, 128, 3044.
Figure 1.
Optimized structures of (a) 1b•-, (b) 1b•-·Li+(OMe2)3,
and (c) 1b2-·2[Li+(OMe2)3] with the pictorial drawings of SOMOs,
calculated at the UB3LYP/6-31+G(d) level.
(9) (a) Okamoto, T.; Kudoh, K.; Wakamiya, A.; Yamaguchi, S.
Chem.sEur. J. 2007, 13, 548. (b) Mouri, K.; Wakamiya, A.; Yamada, H.;
Kajiwara, T.; Yamaguchi, S. Org. Lett. 2007, 9, 93.
(10) Fukazawa, A.; Yamada, H.; Yamaguch, S. Angew. Chem., Int. Ed.
2008, 47, 5582.
acetylene moieties have a comparable susceptibility to
reduction. However, the calculation of 1b•-·Li+(OMe2)3,
taking a counter Li+ ion and solvents into consideration,
afforded a totally different structure, in which the radical
and anion charge are localized mostly on one of the carbonyl
groups, as shown in Figure 1b. This suggests that the
Li+· · ·carbonyl Lewis acid-base interaction makes the
(11) Fukazawa, A.; Hara, M.; Okamoto, T.; Son, E.-C.; Xu, C.; Tamao,
K.; Yamaguchi, S. Org. Lett. 2008, 10, 913.
(12) Crystal data for trans-2b, cis-2b, and 7: see the Supporting
Information. CCDC-705782 (trans-2b), CCDC-705783 (cis-2b), and CCDC-
705784 (7) contain the supplementary crystallographic data for this paper.
These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/
data_request/cif, by emailing data_request@ccdc.cam.ac.uk, or by contacting
the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge
CB2 1EZ, UK; fax: 44 1223 335033.
Org. Lett., Vol. 11, No. 14, 2009
3077

reduction of the carbonyl group dominant over the reduction
of the acetylene moiety.
The mechanism for the formation of the dibenzo[a,e]pen-
talene is also puzzling. We assume that the over-reduction
of the cyclized intermediate 4 with the remaining LiNaph
produces 3 through the elimination of Li2O.14 To confirm
this possibility, we carried out the reaction of the isolated
trans-2b with 4 mol amounts of LiNaph, which indeed gave
3b in 49% yield (Scheme 4).
In addition, the cyclic voltammetry of 1b in THF showed
two-step irreversible one-electron reduction waves at the peak
potential Epc of -2.30 and -2.42 V (vs Fc/Fc+). Considering
the close proximity of these two reduction potentials, we
should also consider a two-electron-reduced intermediate.
The theoretical optimization of 1b2-·2[Li+(OMe2)3] demon-
strated that this intermediate also has a two carbonyl group-
reduced structure (Figure 1c). The formation of this dianionic
intermediate was experimentally supported. Thus, the reac-
tion of 1a with 4 mol amounts of LiNaph at low temperature
(-10 °C) followed by quenching with water produced
dialcohol 5 in 15% yield (Scheme 2). This result also implies
Scheme 4. Reduction of Dihydroxymethylene-Bridged Stilbene
Scheme 2
.
Reduction of Bis(arylcarbonyl)diphenylacetylene at
Low Temperature
Both cyclized products have intriguing π-conjugated
skeletons. The methylene-bridged stilbenes are well-known
to have intense luminescences.15 Indeed, the hydroxy-
substituted derivatives 2b show intense blue emissions (trans-
2b: λem ) 410 nm, ΦF ) 0.55; cis-2b: λem ) 410 nm, ΦF )
0.47 in THF). On the other hand, the dibenzo[a,e]pentalene
can be regarded as a fused-cyclic analogue of 1,4-diphe-
nylbutadiene. Its fused-cyclic skeleton perturbs the electronic
structure so as to make the HOMO-LUMO gap narrower
than those of the noncyclized analogues (Supporting Infor-
mation). In addition, the fused-cyclic structure would enhance
the stability of both the oxidized and reduced species.16
Because of these electronic features, this skeleton has
attracted increasing attention.16-18 However, while there are
several reports on the modification of the substituents at the
5,10 positions,18 only a little attention has been directed to
the functionalization at other positions in the dibenzopen-
talene skeleton. As a new access to the π-extended materials
containing this skeleton, we therefore examined further
derivatization of 3.
that a certain thermal condition is required to promote the
subsequent cyclization.
The next query is how the cyclization proceeds from these
intermediates. To examine the possibility of the radical
5-endo-dig cyclization13 from 1b•-·Li+ (route a in Scheme
1), we conducted the reaction of o-(phenylcarbonyl)diphe-
nylacetylene 6 with 1 mol amount of LiNaph (Scheme 3).
Scheme 3. Reduction of Mono(arylcarbonyl)diphenylacetylene
For the functionalization, we employed the orthometalation
using the alkoxy group as the directing groups. Thus, the
3,8-dimethoxy-substituted 3c was prepared by the double
cyclization. After screening several bases, we found that
iBu3Al(TMP)Li19 was effective for the dimetalation of 3c,
without reacting with the reactive diene moiety. Subsequent
(14) Elimination of Li2O: (a) Chen, J.; Song, Q.; Li, P.; Guan, H.; Jin,
X.; Xi, Z. Org. Lett. 2002, 4, 2269. (b) Xi, Z.; Song, Q. J. Org. Chem.
2000, 65, 9157.
(15) (a) Saltiel, J.; Zafiriou, O. C.; Megarity, E. D.; Lamola, A. A. J. Am.
Chem. Soc. 1968, 118, 11974. (b) Saltiel, J.; Marinari, A.; Chang, D. W. L.;
Mitchener, J. C.; Megarity, E. D. J. Am. Chem. Soc. 1979, 101, 2982.
(16) (a) Brown, R. F. C.; Eastwood, F. W.; Wong, N. R. Tetrahedron
Lett. 1993, 34, 3607. (b) Kendall, J. K.; Shechter, H. J. Org. Chem. 2001,
66, 6643. (c) Saito, M.; Nakamura, M.; Tajima, T.; Yoshioka, M. Angew.
Chem., Int. Ed. 2007, 46, 1504. (d) Saito, M.; Nakamura, M.; Tajima, T.
Chem.sEur. J. 2008, 14, 6062.
However, we could not obtain any intramolecularly cyclized
product but isolated a dimeric product 7 in 22% yield.12 The
other byproduct was an undefined complex mixture. There-
fore, it is more likely that the present cyclization proceeds
not through 1b•-·Li+ but through 1b2-·2Li+ with a synchro-
nous double-radical 5-endo-dig cyclization mechanism (route
b in Scheme 1). This is a new mode of reaction for the double
cyclization shown in eq 2.
(17) (a) Babu, G.; Orita, A.; Otera, J. Chem. Lett. 2008, 37, 1296. (b)
Levi, Z. U.; Tilley, T. D. J. Am. Chem. Soc. 2009, 131, 2796. (c) Kawase,
T.; Konishi, A.; Hirao, Y.; Matsumoto, K.; Kurata, H.; Kubo, T.
Chem.sEur. J. 2009, 15, 2653
(18) (a) Yang, J.; Lakshmikantham, M. V.; Cava, M. P. J. Org. Chem.
2000, 65, 6729. (b) Preda, D. V.; Scott, L. T. Org. Lett. 2000, 2, 1489
.
.
(13) Alabugin, I. V.; Timokhin, V. I.; Abrams, J. N.; Manoharan, M.;
Abrams, R.; Ghiviriga, I. J. Am. Chem. Soc. 2008, 130, 10984.
(19) Uchiyama, M.; Naka, H.; Matsumoto, Y.; Ohwada, T. J. Am. Chem.
Soc. 2004, 126, 10526.
3078
Org. Lett., Vol. 11, No. 14, 2009

trapping with iodine gave the 2,7-diiodide 8. This compound
was readily transformed into the 2,7-diaryl-substituted
derivatives 9-11 through the Pd-catalyzed cross-coupling
or nucleophilic aromatic substitution, as shown in Scheme
5. These are just the examples of the functionalization of
Scheme 5. Functionalization of Dibenzo[a,e]pentalenes
Figure 2
ments conditions: sample (1 mM) with n-Bu4NPF6 (0.1 M) at a
scan rate of 100 mV s-1
. Cyclic voltammograms of 9-11 in CH2Cl2. Measure-
.
In summary, we have developed an intramolecular reduc-
tive double cyclization using o,o′-bis(arylcarbonyl)diphenyl-
acetylenes. This methodology is valuable not only as a new
example of the cyclization proceeding through a synchronous
double radical 5-endo-dig cyclization mechanism but also
as a simple synthesis of the two intriguing ladder π-skeletons.
Further investigation on the application of the extended
dibenzopentalenes to the organic electronic devices is cur-
rently in progress in our laboratory.
the dibenzopentalene skeleton. The present method would
allow us to synthesize various types of the extended
dibenzopentalene derivatives, some of which would be
promising for the utilization in organic electronics. In fact,
in the cyclic voltammetry, all of the produced dibenzopen-
talenes 9-11 show reversible one-electron reduction waves
Acknowledgment. This work was partly supported by
Grants-in-Aid (No. 19675001 and 17069011) from the
Ministry of Education, Culture, Sports, Science, and Tech-
nology, Japan.
1/2
with the reduction potentials Ered of -1.71, -1.66, and
-1.59 V for 9, 10, and 11, respectively (vs Fc/Fc+) (Figure
2). These values demonstrate their high electron-accepting
properties. Notably, 9 and 11 also show reversible oxidation
waves at Eox1/2 ) +0.58 and +0.80 V, respectively, indicative
of their potential use as an ambipolar carrier transporting
material. Advantageously, these diaryl-extended derivatives
exhibited relatively high decomposition temperatures (Td5)
with a 5% weight loss at 331, 321, and 313 °C for 9, 10,
and 11, respectively.
Supporting Information Available: Experimental details,
spectral data, and theoretical calculations, crystallographic
data (CIF), and ORTEP drawings of trans-2b, cis-2b, and
7. This material is available free of charge via the Internet
at http://pubs.acs.org.
OL901148P
Org. Lett., Vol. 11, No. 14, 2009
3079