Synthesis of substituted anthracenes, pentaphenes and trinaphthylenes via alkyne-cyclotrimerization reaction

Article abstract of DOI:10.1016/j.tetlet.2009.12.130

The [2+2+2] cycloaddition reaction of 1,6-diynes 3 with 4-aryl-2-butyn-1-ols 4 and the following oxidation of the resulting benzylic alcohols to the aldehydes 1 and then treatment with an acid catalyst provided annulated anthracenes 2 in good yields.

Full text of DOI:10.1016/j.tetlet.2009.12.130

Tetrahedron Letters 51 (2010) 1313–1316
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Tetrahedron Letters
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Synthesis of substituted anthracenes, pentaphenes and trinaphthylenes
via alkyne-cyclotrimerization reaction
Naoko Saino a, Tsuyoshi Kawaji b, Taichi Ito b, Yuko Matsushita b, Sentaro Okamoto b,
*
a New Products Development Division, Kanto Denka Kogyo Co., Ltd, 425 Kanai, Shibukawa, Gunma 377-0027, Japan
b Department of Material & Life Chemistry, Kanagawa University, 3-27-1 Rokkakubashi, Kanagawa-ku, Yokohama 221-8686, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
The [2+2+2] cycloaddition reaction of 1,6-diynes 3 with 4-aryl-2-butyn-1-ols 4 and the following oxida-
tion of the resulting benzylic alcohols to the aldehydes 1 and then treatment with an acid catalyst pro-
vided annulated anthracenes 2 in good yields.
Received 8 December 2009
Accepted 25 December 2009
Available online 7 January 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Anthracene and its derivatives are some of the most versatile
polycyclic aromatic compounds. Thus, they have received wide
utilities as a chromophor for sensors and markers in biological or
supramolecular systems, a key species in the design of luminescent
materials,
a photochromic molecule by their photo-induced
cycloaddition/cycloreversion and a core structure of organo-elec-
tronic materials.1 Therefore, various methods for construction of
anthracene framework have been developed, which include
Friedel–Crafts reaction,2 aromatic cyclodehydration,3 Elbs
reaction,4 Bradsher-type reaction of diarylmethanes,5 and [4+2]
cycloaddition reactions with napthoquinones, quinodimethanes,
radialenes, or benzynes.6 In addition, several transition metal-
mediated or -catalyzed cyclotrimerization processes have been
reported for the rapid assembly of acenes: Ni- and Co-catalyzed
or Zr-mediated alkyne-cyclotrimerization reactions via metallacy-
cles derived from 1,2-dipropargylaromatic compounds and Pd-cat-
alyzed benzyne cyclotrimerization.7 These methodologies are
useful for preparation of higher polycyclic aromatic hydrocarbons
(PAHs) and also synthesis of acenes having a heteroaromatic
substructure(s).
Based on our results of developing a highly practical procedure
for synthesizing substituted benzenes by the [2+2+2] alkyne-cyclo-
trimerization which is catalyzed by a CoCl2Á6H2O/Zn reagent in the
presence of an appropriate ligand,8 we planned a two-step prepa-
ration of benzyl aldehydes 1, which are the substrate of Bradsher-
type cyclization/aromatization reaction, by the cycloaddition of
diynes 3 and 4-aryl-2-butyn-1-ols 4 and the following oxidation
(Scheme 1). We have shown that the propargyl alcohols 4 are good
substrates for the selective cross-coupling with diynes 3, owing to
their coordination effect of the propargyl oxygen to the metal cen-
ter in an active catalyst. Herein we report the results of the study
for the three-step synthesis of substituted anthracenes 2 from al-
Scheme 1. Synthetic plan for anthracenes 2 from diynes 3 and benzyl alkynes 4.
kyne starting materials, which were applied to synthesis of substi-
tuted pentaphenes and trinaphthylenes.
Synthesis of 4-aryl-2-butyn-1-ols 4 required for the synthesis
was illustrated in Scheme 2. Compounds of type 4 were synthe-
sized by the cobalt-catalyzed coupling reaction9 of benzyl chlo-
rides with trimethylsilylethynyl–magnesium bromide, developed
by us, and the following protiodesilylation and hydroxymethyla-
tion reactions. Similarly, bis-propargyl alcohol 4c was prepared
from 1,3-di(chloromethyl)benzene in 51% overall yield.
With compounds 4a–c, we carried out three-step synthesis of
anthracenes 2 from diynes 3 and 4-aryl-2-butyn-1-ols 4 (Scheme
3). Thus, to a mixture of 3, 4 (1.18 equiv) and Zn powder
(10 mol %) in THF was added a solution of 2-(2,6-diisopropylimi-
no)methylpyridine (Dipimp, 6 mol %) and CoCl2Á6H2O (5 mol %) in
THF at room temperature and the mixture was stirred at ambient
temperature overnight. The mixture was filtered through a pad
of Celite with ether. The resulting adducts 5 were converted to
the corresponding aldehydes by treatment with PCC/Celite in
* Corresponding author. Tel.: +81 45 481 5661; fax: +81 45 413 9770.
E-mail address: okamos10@kanagawa-u.ac.jp (S. Okamoto).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.12.130

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N. Saino et al. / Tetrahedron Letters 51 (2010) 1313–1316
Scheme 2. Preparation of 4.
Scheme 4. Synthesis of pentaphene 2ac.
5ac smoothly to bis-annulated pentaphene 2ac. Cyclization/aro-
matization of dialdehyde 1ac could proceed regioselectively
through a possible intermediate i, illustrated in Scheme 4, to
provide pentaphene 2ac exclusively but not
a pentacene
derivative.5j
As shown in Scheme 5, cyclotrimerization approach enables
synthesis of more complex molecules from simple alkyne starting
materials. Thus, cyclotrimerization of 1-alkyne 7 followed by oxi-
dation/acid-catalyzed cyclization provided substituted trinaphth-
ylenes. o-Propargyl benzyl alcohol 7 could be synthesized by
using cobalt-catalyzed alkyne cycloaddition reaction: the [2+2+2]
cycloaddition reaction of 2,5-hexadiyne 610 and 1,6-diyne 3a cata-
lyzed by Dipimp/CoCl2Á6H2O/Zn in NMP proceeded selectively to
give a 7:3 mixture of adducts ii and iii and the following protiode-
silylation of the mixture provided 7 in 51% overall yield. Although
the compounds ii and iii were inseparable, treatment of the mix-
ture with K2CO3/MeOH gave 7 and unchanged iii, which could be
readily separated by silica gel column chromatography. The o-
propargyl benzylic alcohol 7 thus prepared was again subjected
to [2+2+2] cycloaddition catalysis: treatment of 7 with a Dipimp/
CoCl2Á6H2O/Zn catalyst gave intermolecularly cyclotrimelized
products 8 as a mixture of 1,3,5- and 1,2,4-regioisomers. After oxi-
dation of the crude mixture of 8 to the corresponding tri-aldehyde
9 (37% yield from 7 through two steps), cyclization of 9 by treat-
ment with trifluoroacetic acid in CH2Cl2 produced smoothly trina-
phthylene 10 in 87% yield. To the best of our knowledge, this is the
first example of the synthesis of trinaphthylenes via triple Bradsher
cyclization reactions on a single benzene ring. It is noteworthy that
high yield production of 10 from a regioisomeric mixture of trisub-
stituted benzene 9 indicated regioselective cyclizations of both
1,2,4- and 1,3,5-trisubstituted isomers through iv and v illustrated
in Scheme 5. Thus, the compound 10 was effectively synthesized
from non-aromatic substrates 6 and 3a through five steps. Trina-
phthylenes are analogues of triphenylenes, which are well-known
Scheme 3. Three-step synthesis of anthracenes 2 from 3 and 4.
CH2Cl2 at room temperature, which were successively treated with
a catalytic amount of CF3SO3H in CH2Cl2 at reflux temperature for
1 h to provide the desired anthracenes
2 in good yields.
Anthracenes having a carbocyclic as well as heterocyclic-saturated
ring which was originated from tether structure of diynes 3 were
obtained. Introduction of substitution(s) at the 1 and 4 positions
of 2 as the case of 2ba was readily carried out by use of the corre-
sponding substituted diynes 3. Substituent(s) at the 5–8 position(s)
may be possible by using the corresponding 4 as exemplified by
synthesis of 2ab.
Scheme 4 shows an efficient synthesis of pentaphenes via a
tandem cycloaddition reaction starting from dipropargylic com-
pound 4c. With the use of 4c as a mono-alkyne counterpart,
the cycloaddition of 1,6-diyne 3a proceeded in a tandem fash-
ion to yield bis-benzylic alcohol 5ac. The sequential reactions
of oxidation/acid-catalyzed cyclization converted the resulting

N. Saino et al. / Tetrahedron Letters 51 (2010) 1313–1316
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Table 1
UV absorption of anthracenes 2aa, 2ab, 2ba, pentaphene 2ac and trinaphthylene 10
a
Compound
kabs (nm)
2aa
11b
223, 260, 313, 328, 345, 362, 382
262, 310, 324, 345, 362, 382
2ab
233, 259, 318, 335, 353, 374, 393
261, 353, 372, 392
2ba
2ac
236, 255, 264, 296, 322, 332, 354, 364, 403
247, 259, 292, 305, 319, 343, 374, 393
10
Anthracene
252, 295, 312, 326, 342, 359, 378
312, 326, 342, 359, 37813
260, 320, 337, 354, 371, 39114
12c
13d
a
Unless otherwise indicated, UV absorption spectra were measured for a CHCl3
solution (0.1 mM). Wavelength underlined are kabs
.
max
b
See below.
c
In EtOH (see Ref. 13). For structure, see below.
d
In CH2Cl2 (see Ref. 14). For structure, see below.
Acknowledgment
We thank the Ministry of Education, Culture, Sports, Science
and Technology (Japan) for financial support.
References and notes
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Scheme 5. Synthesis of trinaphthylene 10.
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for their remarkable self-assembling and charge-transporting
properties,11 and are a simplest member of star-shaped angularly
fused oligoacenes (starphene).12 The synthesis of these molecules
is challenging.
Table 1 shows absorption spectral data of the new annulated
anthracene derivatives, that is, anthracenes 2aa, 2ab, 2ba, pen-
taphene 2ac, and trinaphthylene 10, the annulated structures of
which may cause a weak strain to aromatic ring(s). Comparing
with data for anthracene, introduction of five-membered ring
annulation onto anthracene, that is, in 2aa and 11, did not affect
UV absorption so much as observed for the known compound
12.13 Similarly, between 1,4-diphenyl derivatives 2ba and 1314
a
8. Saino, N.; Amemiya, F.; Tanabe, E.; Kase, K.; Okamoto, S. Org. Lett. 2006, 8, 1439;
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10. Diyne 6 was prepared by the reaction of Me3SiCCCH2OTs with propargyl
alcohol in the presence of CuI, NaI and K2CO3.
large difference was not observed.
In summary, we have demonstrated that catalytic [2+2+2]
cycloaddition reactions15 of alkynes play an efficient role as a key
reaction for construction of anthracene, penthaphene and trina-
phthylene structures.16 By taking advantage of the function of
annulated substructure(s) and/or further substituent(s) on anthra-
cene such as Ph groups in 2ba, functionalization of these anthra-
cenes might be expected. Study on utilization in this direction is
underway.

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N. Saino et al. / Tetrahedron Letters 51 (2010) 1313–1316
Org. Chem. 2005, 9, 1699; Gandon, V.; Aubert, C.; Malacria, M. Chem. Commun.
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Tetrahedron 1969, 25, 5639; Clar, E.; Schmidt, W. Tetrahedron 1975, 31, 2263;
Clar, E.; Schmidt, W. Tetrahedron 1979, 35, 2673; Biermann, D.; Schmidt, W. J.
Am. Chem. Soc. 1980, 102, 3173.
16. 1H NMR data of new anthracenes: 2aa: (CDCl3, 500 MHz) d 8.32 (s, 2H), 7.96
(dd, J = 3.5, 6 Hz, 2H), 7.80 (s, 2H), 7.42 (dd, J = 2.5, 6 Hz, 2H), 4.22 (q, J = 7.0 Hz,
4H), 3.74 (s, 4H), 1.26 (t, J = 7.0 Hz, 6H). Compound 2ab: (CDCl3, 500 MHz) d
8.24 (s, 1H), 8.17 (s, 1H), 7.85 (d, J = 9 Hz, 1H), 7.75 (s, 1H), 7.74 (s, 1H), 7.16 (d,
J = 2.5 Hz, 1H), 7.12 (dd, J = 2.3, 9.3 Hz, 1H), 4.22 (q, J = 7.0 Hz, 4H), 3.96 (s, 3H),
3.73 (s, 4H), 1.26 (t, J = 7.0 Hz, 6H). Compound 2ba: (CDCl3, 500 MHz) d 8.27 (s,
2H), 7.84 (dd, J = 3.0, 7.0 Hz, 2H), 7.48–7.53 (m, 10H), 7.38 (dd, J = 3.0, 6.5 Hz,
2H), 5.09 (s, 4H). Compound 2ac: (CDCl3, 500 MHz) d 9.09 (s, 2H), 8.14 (s, 2H),
7.93 (s, 2H), 7.80 (s, 2H), 7.57 (s, 2H), 4.23 (q, J = 7.0 Hz, 8H), 3.80 (s, 4H), 3.78
(s, 4H), 1.28 (t, J = 7.0 Hz, 12H). Compound 10: (CDCl3, 600 MHz) d 8.35 (s, 6H),
7.59 (s, 6H), 4.30 (q, J = 7.2 Hz, 12H), 3.80 (s, 12H), 1.33 (t, J = 7.2 Hz, 18H).
13. Amino acid derivatives of 1,2-dihydro-3H-cyclopenta[b]-anthracenes such as
12 have been reported: Lohier, J. F.; Wright, K.; Peggion, C.; Formaggio, F.;
Toniolo, C.; Wakselman, M.; Mazaleyrat, J.-P. Tetrahedron 2006, 62, 6203.
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M.; Aubert, C.; Renaud, J. L.. In Science of Synthesis: Houben–Weyl Methods of
Molecular Transformations; Lautens, M., Trost, B. M., Eds.; Georg Thieme:
Stuttgart, 2001; Vol. 1, pp 439–530; Varela, J. A.; Saá, C. Chem. Rev. 2003, 103,
3787; Yamamoto, Y. Curr. Org. Chem. 2005, 9, 503; Kotha, S.; Brahmachary, E.;
Lahiri, K. Eur. J. Org. Chem. 2005, 4741; Gandon, V.; Aubert, C.; Malacria, M. Curr.