Synthesis of Optically Active Oligonaphthalenes via Second-Order Asymmetric Transformation

Article abstract of DOI:10.1021/ja038910e

Synthesis of numerous optically active rod-shaped oligo(2,3-dioxyfunctionalized)naphthalenes connected at their 1,4-positions was achieved using oxidative coupling under CuCl₂/α-methylbenzylamine conditions by second-order asymmetric transforma

Full text of DOI:10.1021/ja038910e

Published on Web 12/06/2003
Synthesis of Optically Active Oligonaphthalenes via Second-Order
Asymmetric Transformation
Kazunori Tsubaki,*,† Masaya Miura,† Hiroshi Morikawa,† Hiroyuki Tanaka,† Takeo Kawabata,†
Takumi Furuta,‡ Kiyoshi Tanaka,‡ and Kaoru Fuji§
Institute for Chemical Research, Kyoto UniVersity, Gokasho, Uji, Kyoto, 611-0011, Japan,
School of Pharmaceutical Sciences, UniVersity of Shizuoka, Yada, Shizuoka, 422-8002, Japan, and
Kyoto Pharmaceutical UniVersity, Misasagi, Yamashina, Kyoto 607-8414, Japan
Received October 7, 2003; E-mail: tsubaki@fos.kuicr.kyoto-u.ac.jp
Scheme 1 a
The helical structure is one of the most ordered structures and
packs molecular information into a restricted space. In the field of
supramolecular chemistry, these helical structures have attracted
considerable attention, and various artificial helical molecules have
been synthesized.1 We have focused our attention on optically active
rod-shaped oligo(2,3-dioxyfunctionalized)naphthalenes connected
at their 1,4-positions.2 Important characteristics of these oligonaph-
thalenes include: (1) their frameworks are rigid in the rod direction,
(2) they have chirality and some degree of flexibility around the
axes, and (3) functional groups can be introduced into scaffolding
2,3-dioxy groups. If all axis chiralities could be controlled, then
either R or S, functionalized, optically active helical oligonaphtha-
lenes, which may be applicable in material science, could be
constructed.
There are two reported methods for controlling the axis chirality
when coupling 2-naphthol derivatives, which should be the first
step toward constructing the optically active oligonaphthalenes. One
is the enantioselective oxidative couplings.3 In this reaction, the
axis chirality was directly induced in the coupling step. Furthermore,
an attempt of polymerization of chiral binaphtharene derivatives
as a monomeric unit was also reported.4 On the other hand, an
a Red bonds denote (S)-configuration, and the blue square denotes a newly
formed bond.
Table 1
aminea
isolationb
yield (%)c
de (%)d
alternative synthesis for optically active binaphthols via second-
order asymmetric transformation was reported.5 In this transforma-
tion, epimerization of the axis under amine-copper conditions
together with diastereoselective crystallization occurs.6 Although
this method is effective for synthesizing optically active compounds,
fortuitous conditions are essential. For example, for the self-coupling
of 2-naphthol, high selectivity was reported for R-methylphenyl-
ethylamine (96% ee), whereas â-methylphenylethylamine (8% ee)
or R-methylbenzylamine (8% ee) yielded poor selectivities.5a Herein,
we report the synthesis of optically active naphthalene derivatives
(from tetramer to hexadecamer) via second-order asymmetric
transformations.
entry
substrate
1
2
3
4
5
6
7
1
1
1
1
1
3
5
(RS)-
(R)-
(S)-
(S)-
(S)-
(S)-
(S)-
-
-
PF
P
F
PF
PF
73
69
87
58
15
86
78
12
26
75
93
17
99
79
a Amine ) R-methylbenzylamine. b - ) no precipitation; PF ) without
separating precipitate and filtrate; P ) from precipitate; F ) from filtrate.
c Isolated yield. d Based on the isolated yields of corresponding diastereo-
mers.
First, the reaction conditions were investigated using optically
active dimer 1 as the starting material (Scheme 1 and Table 1,
entries 1-5). Diastereoselectivity was barely observed for the dimer
(17% de, 15% yield). It should be emphasized that the same
diastereomer (S,S,S)-2 was preferentially obtained over (S,R,S)-2
from both the precipitate and the filtrate. These data strongly
suggested that the mechanism of the axis chirality control should
be epimerization of the axis along with diastereoselective crystal-
lization.
Next, applicability of this method to higher naphthalene deriva-
tives (S,S,S)-3 and (S,S,S,S,S,S,S)-5 was investigated (Table 1, en-
tries 6 and 7). The coupling reaction of the tetramer (S,S,S)-3 pro-
ceeded smoothly with a large amount of brown precipitate, and an
extremely high diastereoselectivity was observed ((S,S,S,S,S,S,S)-
4, 85% yield; (S,S,S,R,S,S,S)-4, 0.6% yield; 99% de). For the
coupling of (S,S,S,S,S,S,S)-5, a high diastereoselectivity afforded
hexadecamer ((S,S,S,S,S,S,S,S,S,S,S,S,S,S,S)-6, 70% yield;
(S,S,S,S,S,S,S,R,S,S,S,S,S,S,S)-6, 8% yield; 79% de). To the best of
7
(S)-1 and (R)- or (RS)-R-methylbenzylamine (Table 1, entries 1
and 2). On the other hand, (S)-1 was treated with (S)-R-methyl-
benzylamine to afford a large amount of brown precipitate. After
an acidic workup, (S,S,S)- and (S,R,S)-2 were obtained in 76% and
11% isolated yield, respectively (75% de).8 Moreover, after the
brown precipitate was removed by filtration, the precipitate and
the filtrate were separately purified (entries 4 and 5). An extremely
high diastereoselectivity was observed from the precipitate (93%
de, 58% yield), but a poor selectivity was obtained from the filtrate
† Kyoto University.
‡ University of Shizuoka.
§ Kyoto Pharmaceutical University.
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10.1021/ja038910e CCC: $25.00 © 2003 American Chemical Society

C O M M U N I C A T I O N S
Figure 2. (a) UV-visible spectra of all (S)-hexadecamer (dark green), all
(S)-octamer (red), (S,S,S)-tetramer (blue), and (S)-dimer (purple). Solid lines
and dotted lines show pyrene derivatives (7-9, 14, and 15) and methoxy
derivatives (10, 11, and 13), respectively. Conditions: chloroform, 1.0 ×
10-5 M, light path length ) 10 mm, 20 °C. (b) CD spectra of all-(S)-9
(dark green), all-(S)-8 (red), (S,S,S)-7 (blue), (S,R,S)-7 (green), (S)-14
(purple), and (R)-14 (dotted purple). Conditions: chloroform, 1.0 × 10-4
M, light path length ) 1 mm, 25 °C.
Figure 1. Red bonds denote (S)-configuration, and blue squares denote
newly formed bonds.
metric transformation. We believe that this method is practical and
should contribute to the field of material science. Constructing the
effective energy transfer system based on the optically active
oligonaphthalenes is currently underway.
our knowledge, this is the first synthesis of oligonaphthalenes in
which 15 continuous axial bonds were controlled.9
The absolute configuration of the newly formed axis bond was
determined by the following method. During these studies, three
empirical rules have been established. (1) The Rf value on silica
gel TLC of the all-S isomer is larger than that of the one-R
containing isomer. (2) The absolute value of specific rotation of
the all-S isomer is larger than that of the one-R containing isomer.
(3) The amplitude on a CD spectrum of the all-S isomer is larger
than that of the one-R containing isomer. To confirm the above
rules, 4, which was evaluated for (S,S,S,S,S) chirality, was converted
to the all-methoxy derivative 12, and the physical data, including
1H NMR and the [R]D value, were consistent with the physical data
for (S,S,S,S,S,S,S)-12, which was synthesized by an alternative
route.2a Furthermore, because the absolute configuration of the
unknown bond was sandwiched between two free hydroxy groups,
two 4-(2-pyreneyl)-butyric acid was condensed to the scaffolding
hydroxy groups as the exciton part (Figure 1, compounds 7-9).
Figure 2 shows the UV spectra and CD spectra of these compounds.
Comparing the UV spectra of the compounds (7-9 and 14),
methylated samples (10, 11, and 13), and methyl 4-(2-pyreneyl)-
butyrate (15), the absorbance around 350 nm was clearly assigned
to the π-π* transition of the pyrene moiety. Thus, a positive or
negative sense around 350 nm on the CD spectrum should reflect
the absolute configuration of the target axis bond. As shown in
Figure 2b, the absolute configuration of (S,S,S)-7 and (S,S,S,S,S,S,S)-8
was confirmed by comparing them to the control samples, which
indicated a positive sense around 350 nm. Therefore, the absolute
configuration of the major hexadecamer 9 was assigned as
(S,S,S,S,S,S,S,S,S,S,S,S,S,S,S).
Acknowledgment. The authors wish to thank Prof. N. Harada
(Tohoku University) and Dr. A. Nakamura (JST ERATO) for their
useful suggestions and valuable discussions.
Supporting Information Available: Procedures, characterization
data of all compounds, and full CD spectra of key oligomers (PDF).
This material is available free of charge via the Internet at http://
pubs.acs.org.
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In conclusion, the synthesis of numerous optically active
oligonaphthalene derivatives was achieved by second-order asym-
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