Tani et al.
FIGURE 3. Most stable conformation of 4.
FIGURE 2. Helicenoid diarylethene 3O/3C.
the sterically and electronically more repulsive substituent with
the other benzothiophene group compared with the methyl group
on the stereogenic center. However, in 1O, although the steric
repulsion worked as well, the electronic repulsion did not seem
to work well because of the larger distance between the oxygen
atoms and the relevant sulfur atom compared with that in 2O.
In this paper, our efforts and success in overcoming the lack of
electronic repulsion in 1O are described.
FIGURE 4. Catalytic asymmetric reduction of 1-acetylnaphthothiophene.
We then designed 5 by shortening the longer wing of 3. In
5, the steric repulsion that the chiral substituent suffers from
the end phenyl group was not so large. The synthetic route of
5O we have carried out is shown in Scheme 2.
Results and Discussion
Although the enantioselective reduction of 1-acetylnaph-
thothiophene with borane catalyzed by (S)-2-methyl-CBS-
oxazaborolidine6 proceeded to give 13 with only 11% ee and
13% chemical yield (Figure 4), reduction of 3-acetylthiophene
with the same reaction conditions successfully yielded the (R)-
3-(1-hydroxyethyl)thiophene (7) in 96.0% ee7 with quantitative
chemical yield. The ee values were determined on their acetates
(8) by chiral HPLC, based on the behavior of the racemic
compounds.
The absolute configuration of the alcohol 7 was determined
to be R, because (S)-2-methyl-CBS-oxazaborolidine catalyzed
borane reduction of arylmethylketones had been known to give
(R)-alcohols.6 In addition, the specific optical rotation value
([R]D) of the alcohol 7 was +20° (ethyl acetate; 6.4 × 10-4
g/mL, 19 °C), the sign of which is the same as those of the
known (R)-alcohols.6 As the enantioselective reduction was done
at the first stage of the whole synthesis, all successive reactions
were done on chiral materials.
Introduction of the formyl group to C-5 of (R)-3-(1-hydroxy-
ethyl)thiophene 7 was done after the protection of the hydroxyl
group with the bulky tert-butyldiphenylsilyl group. Other smaller
protecting groups such as tert-butyldimethylsilyl group gave a
mixture of aldehydes in which a formyl group was introduced
at C-2 or C-5. When the hydroxyl group was protected with a
methoxymethyl group, which had been used in 1 and 2,
introduction of the formyl group occurred on C-2 predominantly
because of the favorable chelation to the C-2 lithium cation by
the MOMO group.
At the last step of the synthesis, introducing trimethylth-
iophene, an unidentified and non-photochromic byproduct was
produced, which was inseparable from 5O by column chroma-
tography. Although the byproduct was produced in a consider-
able amount in THF, it was greatly reduced when the reaction
was carried out in ether.
Molecular Design and Synthesis. To restore the electronic
repulsion between the oxygen atoms on the MOMO group and
the sulfur atom on the other aromatic group, the longer helicene
wing should possess the stereogenic carbon atom with a MOMO
group, and the shorter wing should be a thiophene group (or
another heteroaromatic ring) that is connected to the perfluo-
rocyclopentene at C-3. If the aromatic group is connected to
the perfluorocyclopentene at C-2, the distances between its sulfur
atom and the MOMO oxygen atoms become larger. If a
benzothiophene instead of thiophene is connected to the
perfluorocyclopentene at C-3, the colored form generated by
photocyclization can no longer maintain the helicenoid structure.
Instead, it would take an S-shaped structure. Therefore, the
following structural requirements are inevitable: (1) the longer
wing should possess the methoxymethoxyethyl group, and (2)
the other wing should be a thiophene that is connected to
perfluorocyclopentene at C-3. We first designed 3O (Figure 2),
by taking advantage of the common structure of the longer wing
of 1.2
However, the synthesis of 3O was not successful, despite our
execution of several possible methods as shown in Scheme 1.
The reason why we could not obtain 3O is the sterically severe
situation around the chiral substituent. The phenyl group on the
end of the longer wing of 3O (4) gives severe steric pressure to
the chiral substituent, almost colliding with it. Therefore 4 takes
the conformation shown in Figure 3. In this conformation,
hydrogen, the smallest substituent, is forced to face the phenyl
group, so that the methyl and MOMO groups will come close
to C-2. Similar observations of the conformation of a chiral
auxiliary attached to the terminal of helical oligoamide foldamers
has been described.5 Therefore, the C-C coupling reaction
between the carbanion, generated from 4 and butyllithium, and
perfluorocyclopentene is almost impossible because of the steric
hindrance caused by the methyl and MOMO groups.
In order to get rid of the byproduct, the mixture was irradiated
with 366-nm light in ethyl acetate to produce 5C, and 5C was
(4) (a) Yokoyama, Y.; Shiraishi, H.; Tani, Y.; Yokoyama, Y.; Yamaguchi,
Y. J. Am. Chem. Soc. 2003, 125, 7194. (b) Kose, M.; Shinoura, M.;
Yokoyama, Y.; Yokoyama, Y. J. Org. Chem. 2004, 69, 8403. (c) Yokoyama,
Y. Chem. Eur. J. 2004, 10, 4389.
(5) Dolain, C.; Jiang, H.; Le´ger, J-M.; Guionneau, P.; Huc, I. J. Am.
Chem. Soc. 2005, 127, 12943.
(6) (a) Corey, E. J.; Bakshi, R. K.; Shibata, S. J. Am. Chem. Soc. 1987,
109, 5551. (b) Corey, E. J.; Heral, C. J. Angew. Chem., Int. Ed. 1998, 37,
1986.
(7) See Supporting Information.
1640 J. Org. Chem., Vol. 72, No. 5, 2007