Synthesis of chiral dotriacontanaphthalenes: How many naphthalene units are we able to elaborately connect?

Article abstract of DOI:10.1021/jo900463t

(Chemical Equation Presented) (S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S, S,S,S,S,S,S,S,S,S)-dotriacontanaphthalenes 32A-E alternately possessing butoxy and methoxy side chains were precisely constructed through a bottom-up synthesis, and their absolute

Full text of DOI:10.1021/jo900463t

under the same conditions)3 and (2) the high diastereoselec-
tivities in the oxidative homocoupling reactions are induced via
three different pathways controlled by the substituents on the
2,3-positions of the naphthalene rings (i.e., epimerization of the
axis along with diastereoselective crystallization, thermody-
namic, and kinetic control pathways).2c,d Our current challenge
is to determine how many naphthalene units can be elaborately
constructed by repeated homocoupling reactions via the above
three pathways. In the case of the naphthalene unit with a
methoxy group where diastereoselectivity is caused by epimer-
ization of the newly formed axis along with diastereoselective
crystallization, the synthesis of chiral 16mers are the upper limit
because of their low solubilities.2c Furthermore, for a naphtha-
lene unit with a diethylaminocarbonylmethoxy group in which
a rapid coupling reaction with a high homochiral diastereose-
lectivity and slow epimerization of the newly formed axis leads
to a kinetically controlled product, the construction of 24mers
is the upper limit because of their low stabilities and the
difficulty of isolations.2g Herein, we report our last endeavor in
the synthesis of oligonaphthalenes with n-butoxy side chains
where axial chirality is induced under thermodynamic control,
and the high solubilities and stabilities are attributed to the side
chains.
Synthesis of Chiral Dotriacontanaphthalenes:
How Many Naphthalene Units Are We Able To
Elaborately Connect?
Daisuke Sue,† Kazuto Takaishi,†,‡ Takunori Harada,§
Reiko Kuroda,§,| Takeo Kawabata,† and Kazunori Tsubaki*,
Institute for Chemical Research, Kyoto UniVersity, JST
ERATO-SORST Kuroda Chiromorphology Team, Graduate
School of Arts and Sciences, The UniVersity of Tokyo, and
Graduate School of Life and EnVironmental Science,
Kyoto Prefectural UniVersity
tsubaki@kpu.ac.jp
ReceiVed March 2, 2009
Scheme 1 outlines the synthesis for chiral oligonaphthalenes
with a butoxy substituent on naphthalene. Starting (S)-2 (total
ca. 170 g) was treated with CuCl2 in the presence of isopro-
pylamine to afford quaternaphthalene 4A as a diastereomeric
mixture with respect to the newly formed central axis. The
mixture was separated by column chromatography on SiO2 to
give all-(S)-4A (57% yield) as the major product and hetero-
(S,R,S)-4A (11% yield) as the minor fraction in total of 68%
yield and 68% diastereo excess (de). To determine the absolute
configuration,2e,g,4 each diastereomeric 4A was condensed with
tetraphenylporphyrin carboxylic acid (TPPCO2H) under WSC/
DMAP conditions to afford all-(S)-4B and hetero-4B in 79%
and 62% yields, respectively. Methylation of the central hydroxy
groups of all-(S)-4A (96% yield), followed by mono deprotec-
tion of the bottom benzyl group by Pd/C and H2 provided all-
(S)-4D (46% yield). Repeating the process sequence, octina-
(S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S)-
dotriacontanaphthalenes 32A-E alternately possessing bu-
toxy and methoxy side chains were precisely constructed
through a bottom-up synthesis, and their absolute configura-
tions and fluorescence quantum yields were determined.
There are two major synthetic routes for constructing over-
nanosized molecules promising new functional materials. One
is the polymer synthesis method, and the other is a bottom-up
synthesis procedure beginning with small building blocks.
Although these two approaches have both merits and demerits,
the notable merit of the bottom-up synthesis is that complicated
molecules can be precisely constructed without a molecular-
weight distribution.1
We have focused on optically active (especially helical) rod-
shaped oligo(2,3-dioxyfunctionalized)naphthalenes, which are
connected at their 1,4-positions in CuCl2/amine-promoted oxida-
tive coupling reactions.2,3 Through our previous investigations,
we have revealed that (1) the newly formed axis bond between
naphthalene rings is easily epimerized under the coupling
conditions employed (the other axis bonds are not epimerized
(2) (a) Tsubaki, K. Org. Biomol. Chem. 2007, 5, 2179–2188. (b) Takaishi,
K.; Tsubaki, K.; Tanaka, H.; Miura, M.; Kawabata, T. Yakugaku Zasshi 2006,
126, 779–787. (c) Tsubaki, K.; Miura, M.; Morikawa, H.; Tanaka, H.; Kawabata,
T.; Furuta, T.; Tanaka, K.; Fuji, K. J. Am. Chem. Soc. 2003, 125, 16200–16201.
(d) Tsubaki, K.; Tanaka, H.; Takaishi, K.; Miura, M.; Morikawa, H.; Furuta, T.;
Tanaka, K.; Fuji, K.; Sasamori, T.; Tokitoh, N.; Kawabata, T. J. Org. Chem.
2006, 71, 6579–6587. (e) Tsubaki, K.; Takaishi, K.; Tanaka, H.; Miura, M.;
Kawabata, T. Org. Lett. 2006, 8, 2587–2590. (f) Tsubaki, K.; Miura, M.;
Nakamura, A.; Kawabata, T. Tetrahedron Lett. 2006, 47, 1241–1244. (g) Tsubaki,
K.; Takaishi, K.; Sue, D.; Kawabata, T. J. Org. Chem. 2007, 72, 4238–4241.
(h) Tsubaki, K.; Takaishi, K.; Sue, D.; Matsuda, K.; Kanemitsu, Y.; Kawabata,
T. J. Org. Chem. 2008, 73, 4279–4282.
(3) (a) Brussee, J.; Jansen, A. C. A. Tetrahedron Lett. 1983, 24, 3261–3262.
(b) Brussee, J.; Groenendijk, J. L. G.; te Koppele, J. M.; Jansen, A. C. A.
Tetrahedron 1985, 41, 3313–3319. (c) Smrcˇina, M.; Lorenc, M.; Hanusˇ, V.;
Sedmera, P.; Kocˇovsky´, P. J. Org. Chem. 1992, 57, 1917–1920. (d) Smrcˇina,
M.; Pola´kova´, J.; Vyskocˇil, S.; Kocˇovsky´, P. J. Org. Chem. 1993, 58, 4534–
4538. (e) Habaue, S.; Seko, T.; Okamoto, Y. Macromolecules 2003, 36, 2604–
2608.
(4) (a) Harada, N.; Nakanishi, K. Acc. Chem. Res. 1972, 5, 257–263. (b)
Matile, S.; Berova, N.; Nakanishi, K.; Novkova, S.; Philipova, I.; Blagoev, B.
J. Am. Chem. Soc. 1995, 117, 7021–7022.
† Kyoto University.
‡ Present address: Supramolecular Science Laboratory, RIKEN (The Institute
of Physical and Chemical Research).
§ JST ERATO-SORST Kuroda Chiromorphology Team.
| The University of Tokyo.
Kyoto Prefectural University.
(1) For bottom-up construction of giant molecules: (a) Aratani, N.; Osuka,
A.; Kim, Y. H.; Jeong, D. H.; Kim, D. Angew. Chem., Int. Ed. 2000, 39, 1458–
1462. (b) Izumi, T.; Kobashi, S.; Takimiya, K.; Aso, Y.; Otsubo, T. J. Am. Chem.
Soc. 2003, 125, 5286–5287. (c) Aratani, N.; Takagi, A.; Yanagawa, Y.;
Matsumoto, T.; Kawai, T.; Yoon, Z. S.; Kim, D.; Osuka, A. Chem.sEur. J.
2005, 11, 3389–3404.
(5) We tried several times to measure HRMS and/or elemental analysis of
32Es; however, because of their huge molecular weights and chemical instabili-
ties, the attempts were not fruitful.
3940 J. Org. Chem. 2009, 74, 3940–3943
10.1021/jo900463t CCC: $40.75 2009 American Chemical Society
Published on Web 04/16/2009

SCHEME 1. Synthetic Route for the Oligonaphthalenesa
a Conditions: (a) CuCl2, iso-PrNH2, (b) separation of diastereomers, (c) MeI, K2CO3, (d) TPPCO2H, WSC, DMAP, (e) H2, Pd/C or Pd(OH)2, and (f)
TPP(Zn)CO2H, WSC, DMAP.
phthalenes 8A-D, hexadecanaphthalenes 16A-D, and
dotriacontanaphthalenes 32A-E were also constructed. In
the case of 32E, Zn-tetraphenylporphyrin carboxylic acid
(TPP(Zn)CO2H) was introduced instead of TPPCO2H because
of the latter’s chemical stability.5 It is noteworthy that the
diastereoselectivities in the homocoupling reaction of all-(S)-
substrates (2, 4D, 8D, and 16D) increased from 68%, 71%, and
88% to 93% de as the number of naphthalene units increased,
whereas the corresponding chemical yields decreased from 68%,
62%, and 50% to 41%. As expected, separation of the
J. Org. Chem. Vol. 74, No. 10, 2009 3941

FIGURE 3. CD and UV-vis spectra of the oligonaphthalenes with
two TPPs. Left: CD and UV-vis spectra of 4B, 8B, and 16B.
Conditions: CH2Cl2, c ) 1.0 × 10-5 M, 20 °C, light path length ) 1
mm. Right: CD and UV-vis spectra of 32E. Because it is difficult to
accurately weigh 32E because of the static electricity charge as well
as tiny amounts of 32E, the concentrations of the samples were
calculated on the basis of the molar absorbance coefficient (ε) of
TPP(Zn)CO2H (ε ) 523 000).
FIGURE 1. Recycling HPLC chart of (a) diastereomer 32A and (b)
diastereomer 16A. Conditions: COSMOSIL 5SL-II 20 × 250 mm
(Nacalai Tesque). (a) Eluent; CHCl3/Et2O ) 50/1, 3 mL/min. Fraction
1 (blue): all-(S)-32A. Fraction 2 (red): hetero-32A. (b) Eluent; CHCl3/
Et2O ) 100/1, 3.3 mL/min. Fraction 1 (green): all-(S)-16A. Fraction 1
(purple): hetero-16A.
tion, Figure SI-2). Compared to the chemical shifts of the
hydroxy proton in oligonaphthalenes with a mono hydroxy
group at the bottom, which is the starting material of the
corresponding homocoupling reaction, and those of the central
hydroxy groups of products, the hydroxy proton for the all-(S)-
oligonaphthalene was at a lower magnetic field, while that of
the hetero-oligonaphthalene appeared at a higher magnetic field.
These results indicate that the absolute configuration of the
newly formed axis can be predicted on the basis of the
corresponding chemical shifts and the purity of the product can
also be verified.
To determine the absolute configuration of the newly formed
axis, we applied the CD exciton chirality method to the
oligonaphthalenes with two TPPs. Thus, the sense of the CD
derived from the Soret band of the two TPPs should reflect the
torsion of the entire molecule and should reveal the chirality of
the target central axial bond.2e,g,4 The UV and CD spectra of
TPP-oligonaphthalenes are shown in Figure 3. The TPP-
oligonaphthalene showed a positive split Cotton effect, which
indicated that the absolute configuration of the target axis should
be S.
FIGURE 2. Partial 1H NMR (400 MHz) spectra of oligonaphthalenes
with the hydroxy group in CDCl3 at 20 °C.
diastereomeric mixtures of 4A, 8A, 16A, and 32A into single
diastereomers became more difficult as the number of naph-
thalene units increased. The synthesis of higher order oligo-
naphthalenes using all-(S)-32D as a starting material was also
attempted. After purifying and separating the products of the
coupling reaction by gel permeation chromatography (GPC) and
recycling HPLC on silica gel, a probable fraction could be
isolated. However, NMR analysis of benzylic and hydroxy
protons indicated that the fraction was still composed of several
materials (Supporting Information, Figure SI-1). Thus, the upper
limit of oligonaphthalenes with butoxy side chains was deter-
mined to be 32mers because of the difficulty of isolation and
separation.
Using systematically constructed oligonaphthalenes, which
have two hydroxy groups in the center (all-(S)-4A, all-(S)-8A,
all-(S)-16A, and all-(S)-32A), the fluorescence quantum yields
were measured (Figure 4). When the oligonaphthalenes were
excited at 320 nm, the intensity of the fluorescence increased
as the number of naphthalene units increased. Interestingly, the
fluorescence quantum yields were nearly independent of the
number of naphthalene units (Φ320 ) 0.152 (all-(S)-4A), Φ320
) 0.225 (all-(S)-8A), Φ320 ) 0.212 (all-(S)-16A), and Φ320
)
0.231 (all-(S)-32A)). In our previous study on oligonaphthalenes
with methoxy substituents, the quantum yields of these com-
pounds increased as the number of naphthalene units increased
(from 20% to 82%).2f Even in the cases of the oligonaphthalene
C series, the quantum yields were about 50% (Φ320 ) 0.486
(all-(S)-4C), Φ320 ) 0.535 (all-(S)-8C), Φ320 ) 0.467 (all-(S)-
16C), and Φ320 ) 0.445 (all-(S)-32C); Figure SI-3 of Supporting
Information). These results indicate that the quantum yields of
these oligonaphthalenes are affected by the mobility of the
substituent on the side chain.
The purity and separation of diastereomeric 16A and 32A
1
were confirmed using both recycling HPLC (Figure 1) and H
NMR (two sharp single signals corresponding to the methylene
proton in the top and bottom benzyl groups and the phenolic
proton in central hydroxy groups). Figure 2 shows the 1H NMR
spectra of the oligonaphthalenes with a hydroxy group (A and
D series). The signals, which are ascribed to the hydroxy proton,
appeared near 6.0-6.4 ppm, and the sample concentration did
not affect chemical shifts of these signals (Supporting Informa-
3942 J. Org. Chem. Vol. 74, No. 10, 2009

new intrinsic functions of these oligonaphthalenes such as
selective solubilization of carbon nanotubes.
Experimental Section
Synthesis of 16A. To a mixture of CuCl2 (29 mg, 216.6 µmol)
in methanol (1 mL) was added i-propylamine (23 µL, 270.8 µmol)
under argon atmosphere under ice-bath cooling. After 45 min, a
solution of all-(S)-8D (204.8 mg, 108.3 µmol) in dichloromethane
(1 mL) was added, and the reaction mixture was stirred for 5 h at
0 °C to rt. The reaction mixture was poured into the mixed solvent
of 1 M hydrochloric acid solution and CHCl3. The aqueous layer
was extracted with chloroform (twice). The organic layer was
combined, washed with brine, dried over sodium sulfate, and
evaporated to give a residue. The residue was purified by column
chromatography (SiO2 hexane/chloroform/ethyl acetate ) 10:1:1)
to afford to all-(S)-16A (96.6 mg, 47%) and hetero-16A (17.5 mg,
5.4%).
FIGURE 4. Fluorescence spectra of all-(S)-4A, 8A, 16A, and 32A.
Conditions: CH2Cl2, 20 °C, light path length ) 10 mm. λext ) 320 nm.
Fluorescence quantum yield (Φ) excited at 320 nm using a solution of
quinine sulfate in 1 N H2SO4 as a reference standard (Φ ) 0.546) in
parentheses.
In conclusion, the last challenge in constructing optically
active oligonaphthalenes among three different pathways, that
is, a thermodynamic one, was completed. The chirality of the
newly formed axis in the 32mers, which were the upper limit
because of technical isolation or separation problems, could be
unambiguously determined by the CD exciton chirality method.
The corresponding 32mers, which are the highest examples of
oligonaphthalenes, maintained a sufficient solubility against
various kinds of organic solvents, and thus, their properties
should be suitable to contribute to the field of materials
chemistry. Therefore, we plan to shift our attention to developing
Acknowledgment. This study was partly supported by a
Grant-in-Aid for Scientific Research (KAKENHI) (17659004)
and the Japan Securities Scholarship Foundation (JSSF).
Supporting Information Available: Full experimental details
and characterization data of all new compounds, Figures SI 1-4.
This material is available free of charge via the Internet at
http://pubs.acs.org.
JO900463T
J. Org. Chem. Vol. 74, No. 10, 2009 3943