Efficient Synthesis of Biindenylidene Derivatives via a Domino-Heck-Type Double Cyclization of Diaryldienynes

Article abstract of DOI:10.1021/ol035127i

(Equation presented) Synthesis of aromatic ring substituted (E)-1,1′-biindenylidene derivatives was achieved by a domino-Heck type double cyclization of (Z,Z)-1,6-diaryl-1,5-hexadien-3-ynes.

Full text of DOI:10.1021/ol035127i

ORGANIC
LETTERS
2003
Vol. 5, No. 19
3411-3414
Efficient Synthesis of Biindenylidene
Derivatives via a Domino-Heck-Type
Double Cyclization of Diaryldienynes
S. M. Abdur Rahman,† Motohiro Sonoda, Kayo Itahashi, and Yoshito Tobe*
Department of Chemistry, Faculty of Engineering Sciences, Osaka UniVersity, and
CREST, Japan Science and Technology Corporation (JST),
Toyonaka, Osaka 560-8531, Japan
tobe@chem.es.osaka-u.ac.jp
Received June 18, 2003 (Revised Manuscript Received August 20, 2003)
ABSTRACT
Synthesis of aromatic ring substituted (E)-1,1′-biindenylidene derivatives was achieved by a domino-Heck type double cyclization of (Z,Z)-
1,6-diaryl-1,5-hexadien-3-ynes.
Extensively conjugated molecular and polymeric materials
are critical components for a large number of advanced
technologies utilizing nonlinear optical (NLO),1 photo- and
electroluminescent,2 and molecule-based sensory devices.3
As a part of our research program directed toward the
synthesis of these materials, we are investigating the
development of a general and versatile method for construct-
ing highly extended π-systems composed by chrysene or
indenylidene units. We designed a general synthetic scheme
(Scheme 1), which is based on the tandem 6-endo or 5-exo
cyclization of (Z,Z)-diaryldienynes to give chrysene (2) and
indenylidene (3) derivatives, respectively.4
Because of their structural planarity, rigidity, and centro-
symmetric nature, biindenylidene derivatives and some other
benzo-fused fulvalenes are of considerable interest both as
ligands in the preparation of organometallic complexes5 and
as precursors to materials with novel electronic and conduc-
tive properties.6 Although (E)-1,1′-biindenylidene and some
functionalized derivatives were accessed via mostly oxidative
coupling of indene or indenyl derivatives,7 no biindenylidene
derivative with a functionalized aromatic ring(s) has been
synthesized to date. We herein, report the first synthesis of
aromatic ring-substituted biindenylidene derivatives via
tandem cyclization of diaryldienynes.
† On leave from the University of Dhaka, Bangladesh.
(1) (a) Munn, R. W.; Ironside, C. N. Principles and Application of
Nonlinear Optical Materials; Chapman & Hall: London, 1993. (b) Nie,
W. AdV. Mater. 1993, 5, 520. (c) Prasad, P. N.; Williams, D. J. Introduction
to Nonlinear Optical Effects in Molecules and Polymers; Wiley: New York,
1991.
Scheme 1
(2) Greenham, N. C.; Moratti, S. C.; Bradley, D. D.; Friend, R. H.;
Holmes, A. B. Nature 1993, 365, 628.
(3) Swager, T. M.; Marsella, M. J. AdV. Mater. 1994, 6, 595.
(4) Recently, we reported the synthesis of chrysene from 1 via flash
vacuum pyrolysis (FVP); see: Sonoda, M.; Itahashi, K.; Tobe Y. Tetra-
hedron Lett. 2002, 43, 5269.
(5) (a) McGovern, P. A.; Vollhardt, K. P. C. J. Chem. Soc., Chem.
Commun. 1996, 1593. (b) Waldbaum, B. R.; Kerber, R. C. Inorg. Chim.
Acta 1999, 291, 109.
(6) Wennerstro¨m, O. Macromolecules 1985, 18, 1977.
10.1021/ol035127i CCC: $25.00 © 2003 American Chemical Society
Published on Web 08/28/2003

1,6-Diphenyl-1,5-hexadien-3-yne (1a)4 was chosen for the
optimization process of the tandem cyclization reaction
(Table 1). Although we investigated a number of palladium
enhancement was not found by an increased catalyst loading
from 10 to 20 mol % (entries 3 and 4). When the amount of
base was increased to 3 equiv (entry 5), the yield improve-
ment was not so significant.11 However, a nearly 2-fold
increase of yield was noted when the molar concentration
of the substrate in DMF was reduced to 0.01 M, affording
3a and 4a in 54 and 15% yields, respectively (entry 6).
Further increase of base (entry 7) provided a lower yield.
When tri-o-tolylphosphine was employed as a ligand, yields
of the products were reduced.
Table 1. Optimization of the Reaction Conditions
Next, different solvents and additives were investigated.
Among the solvents investigated (CH3CN, DMSO, DMA,
DMI), only DMA gave the desired product, albeit in a
slightly lower yield than that in DMF.12 As shown in Table
2, changing the phase transfer catalyst from Bu4NBr to
DMF
yield (%)
Pd(OAc)2b PPh3
base
concen-
entry
(mol %)
(mol %)
(equiv)
tration (M)
3a
4a
1
2
3
4
5
6
7
8
10
30
10
20
20
20
20
20
20
none
20
40
40
40
40
40c
none
0.05
0.05
0.05
0.05
0.05
0.01
0.01
0.01
no reaction
K2CO3 (2)
K2CO3 (2)
K2CO3 (2)
K2CO3 (3)
K2CO3 (3)
K2CO3 (6)
K2CO3 (3)
trace
21
0
0
Table 2. Investigation on Bases and Additives
yield (%)
28
3
31
4
entry
base
additive
3a
4a
54
31
24
15
12
5
1
2
3
4
5
6
K2CO3
K2CO3
K2CO3
KOAC
Na2CO3
CsCO3
Bu4NBr
Pr4NBr
Bu4NBF4
Bu4NBr
Bu4NBr
Bu4NBr
54
36
47
40
25
36
15
trace
nd
15
12
a Optimum temperture was found to be 80 °C. While an elevated
temperature accelerates decomposition of 3a, below temperatures of 80 °C,
a substantial amount of starting material remains unreacted. b Among the
catalyst system, only Pd(OAc)2 gave the desired product. c Tri-o-tolylphos-
phine was used as a ligand instead of PPh3.
nd
Pr4NBr/Bu4NBF4 or the base from K2CO3 to KOAc/Na2CO3/
CsCO3 produced various results with no increase of the yield
of the desired product.13
catalysts,8 only Pd(OAc)2 furnished the desired product (E)-
1,1′-biindenylidene (3a),9 associated with a mixture of partly
cyclized side-products 4a ((E)- and (Z)-isomers).13 We found
that the reaction did not proceed at all in the absence of a
base (entry 1), and exclusion of the ligand triphenylphosphine
produced only a trace amount of 3a (entry 2). Abrupt yield
With this optimization result in hand, we assumed that
introduction of a substituent at an aromatic ring might
increase or decrease the yield depending on its nature
(electron withdrawing or electron releasing). Therefore, we
synthesized a number of (Z,Z)-diaryldienynes as shown in
Scheme 2. (Z)-Bromostyrenes 6b-e, were synthesized
selectively by a procedure similar to that of Uenishi.14 The
Sonogashira coupling of 6 with enyne 74 gave the corre-
sponding (Z,Z)-diaryldienynes 1b-e in very good yields with
a small amount of (E,Z)-isomers.15 Similarly, 1f was prepared
from 1-naphthaldehyde via steps with very good yields (67%
yield for three steps). However, a remarkable amount of
(E,Z)-isomer of 1f was produced (ZZ/EZ ) 77/23). Pure
(Z,Z)-isomers of 1a-f were obtained by recyclable prepara-
tive HPLC.
(7) For the synthesis of hitherto reported biindenylidene derivatives and
other related dibenzofulvalenes, see: (a) Tani, H.; Toda, F. Chem. Ind.
(London) 1963, 1083. (b) Toda, F.; Tani, H. Bull. Chem. Soc. Jpn. 1964,
37, 915. (c) Anastassiuo, A. G.; Setlife, F. L.; Griffin, G. W. J. Org. Chem.
1966, 31, 2705. (d) Lacy, P. H.; Smith, D. C. J. Chem. Soc. C 1971, 41. (e)
Bergamasco, R.; Porter, Q. N. Aust. J. Chem. 1977, 30, 1051. (f) Escher,
A.; Rutsch, W.; Neuenschwander, M. HelV. Chim. Acta 1986, 69, 1644.
(g) Escher, A.; Neuenschwander, M.; Engel, P. HelV. Chim. Acta 1987, 70,
1623. (h) Priebsch, W.; Hoch, M.; Rehdar, D. Chem. Ber. 1988, 121, 1971.
(i) Kelley, T. R.; Meghani, P. J. Org. Chem. 1990, 55, 3684. (j) Kerber, R.
C.; Waldbaum, B. Organometallics 1995, 14, 4742. (k) Capparelli, M. V.;
Machado, R.; De Sanctis, Y.; Arce, A. J. Acta Cryst. 1996, C52, 947. (l)
Taylor, B. M.; Joullie, M. M. Tetrahedron 1998, 54, 15121. (m) Stradiotto,
M.; Hazendonk, P.; Bain, A. D.; Brook, M. A.; McGlinchey, M. J.
Organometallics 2000, 19, 590. (n) Jonczyk, A.; Szymanek, P.; Juszczuk,
C. Pol. J. Chem. 2000, 74, 985.
(8) We found that Pd(PPh3)4, Pd(PPh3)2Cl2, Pd(dppf)Cl2, Pd(PhCN)2Cl2,
and Pd2(dba)3‚CHCl3 were ineffective.
(9) Similar type of domino-Heck double cyclization reaction was reported
recently by Tietze and co-workers; see: (a) Tietze, L. F.; Heitmann, K.;
Raschke, T. Synlett 1997, 35. (b) Tietze, L. F.; Kahle, K.; Raschke, T. Chem.
Eur. J. 2002, 8, 401.
(13) Exactly the same reaction conditions utilized by Tietze were also
applied for 1a. While the reaction conditions using Pd2(dba)3‚CHCl3/PPh3/
Ag2O/DMF described by Tietze9a were completely ineffective, utilization
of Pd(OAc)2/PPh3/KOAc/Pr4Br/DMF9b yielded 3a in a relatively lower yield.
Most probably, the substrates used by Tietze contained a free alkene with
a terminal trimethylsilyl group, which facilitated the second step of
cyclization compared to the aromatic ring present in 1a.
(10) Compound 4a consisted of an inseparable mixture (variable ratio)
of two stereoisomers, which showed two methyl and two sets of trans-
(14) Uenishi, J.; Kawahama, R.; Yonemitsu, O.; Tsuji, J. J. Org. Chem.
1998, 63, 8965.
1
coupled vinyl proton signals in the H NMR spectrum.
(11) Low yield of 3a is due to a gradual decomposition of the product
under the reaction conditions. This phenomenon was understood by
subjection of pure 3a to the reaction conditions.
(12) While employment of CH3CN as a solvent furnished a 2:1 mixture
of 1a and its (Z,E)-isomer, DMSO gave a complex mixture, and using DMA
afforded 3a and 4a in 43 and 5% yields, respectively.
(15) Minor isomer formed was the (E,Z)-isomer. This assignment was
accomplished by measuring the coupling constant of the vinyl proton signals
in the 1H NMR spectra and by comparing the change of the chemical shift
values of the corresponding vinyl protons for (E)- and (Z)-isomerization.
The (E,Z)-isomer was characterized by a set of trans-coupled (J ≈ 16 Hz)
and a cis-coupled (J ≈ 12 Hz) vinyl proton signals.
3412
Org. Lett., Vol. 5, No. 19, 2003

of the cyano nucleophile with the Pd species discouraged
the formation of 3d. Introduction of a trifluoromethyl
substituent afforded 3e, albeit in a relatively lower yield. An
extended π-system 3f was also synthesized from 1f, albeit
in a lower yield (entry 6).17
Scheme 2
To explore the scope of this double-cyclization reaction
and to understand the mechanistic clues, the (Z,E)-isomer
of 1c, compound 9, was prepared20 and subjected to the
reaction conditions (Scheme 3). The desired product 3c and
Scheme 3a
a Reaction conditions: Pd(OAc)2, PPh3, K2CO3, Bu4NBr, DMF,
80 °C.
The results of the domino-Heck-type tandem cyclization
reaction of (Z,Z)-diaryldienynes to form biindenylidene
derivatives are summarized in Table 3. A relatively larger
scale reaction of 1a yielded 3a and 4a (mixture) in 47 and
15% yields, respectively.16 Electron-releasing substituents
such as methyl and methoxy groups did not cause any
significant alteration of yields (entries 2 and 3). A substrate
bearing an electron-withdrawing CN group at the para
position only gave the undesired acetates in 22% yield, and
desired product 3d was not accessible. Possibly, coordination
the corresponding acetates 4c were obtained in 15 and 26%
yields, respectively. In contrast, the (E,Z)-isomer of 1f, i.e.,
10, did not undergo this cyclization reaction and the starting
material remained unchanged.
The reaction and the selective formation of (E)-1,1′-
biindenylidene derivatives can be explained by a typical
mechanism of Pd-catalyzed reactions (Scheme 4).21 Oxidative
addition of Pd0 to 1 gave the aryl palladium species 11, which
was transformed to the intermediate 12 by the syn addition
of the triple bond into the aryl palladium bond via a 5-exo-
dig mode.22 The second phase of cyclization would generate
(16) General Procedure. A flame-dried flask was loaded with palladium
acetate (20 mol %), triphenylphosphine (40 mol %), anhydrous potassium
carbonate (3 eqiuv), and tetrabutylammonium bromide (1 equiv). A dilute
solution (0.01 M) of diaryldieneyne was then added to the flask; the resulting
mixture was heated to 80 °C for 20 min, and the reaction temperature was
maintained at 80 °C until the reaction was complete. The reaction was cooled
to room temperature, and water and ether were added sequentially. The
mixture was extracted with ether three times. Organic layers were combined
and washed with brine, dried over MgSO4, and filtered. The filtrate was
evaporated to give a dark residue, which was purified by column
chromatography to yield the corresponding products.
Table 3. Tandem Cyclization of (Z,Z)-Diaryldienynes
(17) Formation of compound 3f rather than the product with the
phenafulvene substructure was judged by comparing the coupling constant
of the olefinic proton signal of 3f with those of the reported compounds.
While the usual coupling constant for the olefinic protons of phenafulvenes
occurs around 10 Hz,18 that of indenylidenes occurs between 5 and 6 Hz.19
(18) Morita, N.; Asao, T. Chem. Lett. 1975, 71.
(19) See the coupling constant values for the pentacyclic olefinic protons
in 3b-e in Supporting Information. See also: Launikonis, A.; Sasse, W.
H. F.; Willing, I. R. Aust. J. Chem. 1993, 46, 427.
(20) Compound 9 was prepared via the Sonogashira coupling of 7 and
bromoalkene 17.
(21) Tsuji, J. Palladium Reagents and Catalysts; John Wiley & Sons,
Ltd.: Chichester, UK, 1995.
Org. Lett., Vol. 5, No. 19, 2003
3413

activation energy for the cyclization of the vinyl palladium
species 15 to 3 is lower than that of 12 to 13. This is well
understood by the twist angle of the central double bond of
3 and 13. Whereas compound 3a is calculated to be
completely planar (twist angle of 0°), 13 is nonplaner (twist
angle of 10° when R ) H).24
Scheme 4
Further isomerization of the pendant disubstituted double
bonds of 12 and 15 might take place to give 16, which can
be transformed to 4 (mixture) by the attack of an acetate
ligand. Isomerization of 12 or 15 to 16 is a reversible process,
which is evident from the formation of 3c from 9 in Scheme
3.
In conclusion, we have developed a general method for
the synthesis of hitherto unknown aromatic substituted (E)-
1,1-biindenylidene derivatives through a domino-Heck-type
double-cyclization method. Further elaboration of this method
toward the synthesis of more extended π-electronic and
heterocyclic systems and subsequent measurement of pho-
tonic and electronic properties will be the subjects of future
investigations.
Supporting Information Available: Experimental pro-
cedures and spectral data for 1b-f, 3a-f, 4a-f, 9, and 10
1
and H NMR spectra of all new compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
OL035127I
(23) This type of zwitterionic resonance form might be generated from
the formal donation of an electron pair by a d(8) palladium center.
Resonance stabilization of the negative charge in the indene fragment of
14 might be responsible for the participation of 14 in the transformation of
12 to 15. For isomerization via a zwitterionic resonance form, see: (a)
Zargarian, D.; Alper, H. Organometallics 1991, 10, 2914. (b) de Vall, P.;
Dedieu, A. J. Organomet. Chem. 1994, 478, 121. (c) Cacchi, S.; Fabrizi,
G.; Marinelli, F.; Moro, L.; Pace, P. Tetrahedron 1996, 52, 10225. (d)
Cacchi, S. J. Organomet. Chem. 1999, 576, 42. Participation of the
zwitterionic species 14 in the cis-trans isomerization may be supported
by the absence of such isomerization in the reaction of the related substrate
with saturated chains reported by Tietze.9 In addition, although we performed
the reaction with a saturated system, 1-(2-bromophenyl)-6-phenyl-3-hexyn-
2-ol, under similar conditions, neither the double-cyclization product nor
the acetate was formed.
the cis product 13. However, this was not t the case and the
trans isomer 3 was obtained selectively. Formation of 3 can
be explained by the isomerization of the vinyl palladium
species 12 to 15 via the zwitterionic resonance form 14.23
Selective generation of 3 was due to the fact that the
(22) Formation of a six-membered ring was not observed. This could
be explained by the low probability of a 6-endo-dig process.
(24) Lee-Ruff, E.; Grant, A.; Stynes, D. V.; Vernik, I. Struct. Chem.
2000, 11, 245.
3414
Org. Lett., Vol. 5, No. 19, 2003