Memory of Chirality Generated by Spontaneous Crystallization
ee) were isolated (Table 2, entry 2). The ee value of the
products was determined by HPLC by using a chiral cel
OJ column. Optically active products were also obtained
from the reaction at 10 to -10 °C (entries 3-5); however,
the ee value is lower than that of the reaction at 20 °C.
Furthermore, according to the decreased temperature,
the enantioselectivity increased (entries 6-9), and the
maximum ee values, 83% ee for 4 and 81% ee for 5, were
obtained when the reaction temperature was -80 °C
(entry 9). There was a solubility problem when diethyl
ether was used, and the reaction in toluene resulted in
lower ee values (entries 10 and 11). When hexane was
used as a solvent, the crystals did not dissolve at all, and
the reaction did not proceed even after 24 h (entry 12).
Therefore, THF is the most prominent solvent for this
asymmetric nucleophilic reaction. Furthermore, the re-
sult of the reaction in hexane solution (entry 12) indicates
that the nucleophilic reaction does not proceed on the
surface of the crystals, but occurred in homogeneous
conditions. It is noteworthy that optically active products
were obtained at 20 °C, and higher optical purity was
observed than in the reaction at 10 to -10 °C (entries
3-5), though the imide 1 racemized in an instant at this
temperature. The ee value of the products is influenced
by the rate of both enantiomerization of the imide 1 and
the reaction with a nucleophile. In the range of 10 to -10
°C, the rate of racemization is superior to the addition of
a nucleophile, and low ee values of products were
obtained. It seems that the nucleophilic reaction of 1
occurs competitively with racemization at 20 °C; there-
fore, higher enantioselective reaction is promoted. These
results are particularly surprising in view of the fact that
optically active materials are obtained by the reaction of
frozen chirality with n-buthyllithium even at 20 °C.
The absolute configuration of neither the imide 1 in
chiral crystal nor frozen chiral conformation could be
determined. When the crystals, which exhibited the (+)-
Cotton effect at 358 nm in the CD spectra (Figure 3), were
irradiated in the solid state, (+)-rotatory oxetane 2 was
obtained. On the other hand, the reaction with n-
butyllithium with the same rotatory crystals gave (-)-4
and (-)-5. As a matter of course, the use of enantiomor-
phic crystals gave (-)-2 by the solid-state photolysis and
(+)-4 and (+)-5 by the nucleophilic reaction with n-
butyllithium in the same chemical and enantiomeric
yields.
In conclusion, we have provided a new asymmetric
synthesis by the use of frozen molecular chirality gener-
ated by spontaneous resolution of achiral materials.
Exp er im en ta l Section
Gen er a l In for m a tion . Melting points are uncorrected. FT-
IR spectra are reported in cm-1. 1H and 13C NMR spectra were
obtained in CDCl3 solutions at 300 MHz. Chemical shifts are
reported in delta (δ) units, parts per million (ppm) relative to
the TMS as internal standard. Both 500-W high-pressure and
250-W ultra-high-pressure mercury lamps were used as ir-
radiation sources.
P r ep a r a tion of N-cycloh exen eca r bon yl-N-(5,6,7,8-tet-
r a h yd r on a p h th a len -1-yl)ben zoylfor m a m id e 1: The asym-
metrically substituted imide 1 was prepared by the conden-
sation reaction of N-(tetrahydronaphthyl)-1-cyclohenenecar-
boamide with benzoylformyl chloride in the presence of tri-
ethylamine according to the procedure reported in the litera-
ture.31 The imide 1 was obtained as colorless prismatic crystals
from hexane-chloroform: HRMS (FAB), calcd for C25H26NO3
(MH+) 388.1913, found 388.1887; mp 161-163 °C; IR (cm-1
,
KBr) 1460, 1668, 1716; 1H NMR (CDCl3) δ 1.22-1.24 (m, 2H),
1.41-1.45 (m, 2H), 1.56-1.86 (m, 6H), 2.07 (s, 2H), 2.61-2.85
(m, 4H), 6.45 (t, 1H, J ) 2.0 Hz), 6.97 (dd, 1H, J ) 2.0 and 9.0
Hz), 7.15-7.19 (m, 2H), 7.48-7.53 (m, 2H), 7.60-7.63 (m, 2H),
8.02-8.05 (m, 2H); 13C NMR (CDCl3) δ 20.8, 21.3, 22.5, 22.6,
24.5, 24.7, 25.2, 29.5, 125.6, 126.1, 128.7, 129.9, 130.3, 132.7,
134.3, 135.3, 135.5, 136.3, 139.2, 140.2, 169.5, 172.7, 186.5.
X-r a y Cr ysta llogr a p h ic An a lysis of N-(1-cycloh exen -
ecar bon yl)-N-(5,6,7,8-tetr ah ydr on aph th alen -1-yl)ben zoyl-
for m a m id e 1: Colorless prismatic crystals from hexane-
chloroform, orthorhombic space group P212121, a ) 12.774(3)
Å, b ) 21.130(5) Å, c ) 7.766(3) Å, V ) 2096.1(1) Å3, Z ) 4, F
) 1.227 g/cm3, µ(CuKR) ) 6.391 cm-1. The structure was solved
by the direct method of full-matrix least-squares, where the
final R and Rw were 0.041 and 0.045 for 1035 reflections.
Gen er a l p r oced u r e for th e p h otoch em ica l r ea ction in
th e solid sta te: The solid-state photolysis was done under
an atmosphere of dried argon. When the solid samples were
irradiated as powders in a Pyrex tube for 1 h, bicyclic oxetanes
(2, 3) were obtained quantitatively in a 2:3 ratio of 95:5. The
major isomer 2 could be isolated by column chromatography
on silica gel, and the optical purity was determined by HPLC
by using a chiral cel-OJ column as >99% ee, whereas the minor
isomer 3 could not be isolated on the pure form. Irradiation of
the crystals exhibiting the (+)-Cotton effect at 358 nm gave
optically active 2 showing (+)-specific rotation rotatory at the
RD line. Irradiation of the enantiomorphic crystal gave (-)-2
in >99% ee.
Ra cem ic 5-p h en yl-3-(5,6,7,8-tetr a h yd r on a p h th a len -1-
yl)-11-oxa -3-a za t r icyclo[4.4.1.1,501,6]u n d e ca n e -2,4-d i-
on es (2 and 3) were obtained quantitatively in the 2:3 ratio
of 75:25, when a benzene solution of 1 was irradiated in an
argon atmosphere. Oxetane 2 was obtained as colorless
prismatic crystals from hexane-chloroform: HRMS (FAB),
calcd for C25H26NO3 (MH+) 388.1881, found 388.1905; mp 165-
A mechanistic approach for the asymmetric synthesis
cannot be devised without the absolute configuration of
both the starting imide 1 and the products; however, the
presumed asymmetric induction is outlined as follows.
Imide 1 is achiral because the enantiomerization occurs
at room temperature, and afforded chiral crystals by
spontaneous crystallization. The enantiomeric pure bulk
of crystals was obtained without seeding; however, the
crystals in each batch have a fifty-fifty chance for the
absolute configuration of (R)- or (S)-1. Desired crystals
could be easily prepared by the seeding method. When
enantiomorphic crystals of (R)-1 were dissolved in a low-
temperature solvent, the rotation axis of N-(TENAP) was
restricted, and the frozen molecular chirality was re-
tained as the same configuration in the crystal lattice.
Nucleophiles can react from the uncrowded face by
keeping away the cyclohexenecarbonyl group to give
optically active products.
1
166 °C; IR (cm-1, KBr) 1706, 1754; H NMR (CDCl3) δ 1.50-
1.79 (m, 10H), 2.03-2.13 (m, 2H), 2.43-2.52 (m, 2H), 2.79 (br
s, 2H), 3.40 (t, J ) 9.0 Hz, 1H), 6.7-7.0 (m, 1H), 7.1-7.25 (m,
2H), 7.3-7.45 (m, 5H);13C NMR (CDCl3) δ 20.3, 21.7, 22.9, 23.0,
24.3, 24.5, 26.0, 29.9, 51.0, 83.5, 88.8, 126.0, 126.3, 126.4, 128.4,
128.8, 130.8, 132.0, 133.6, 135.6, 139.5, 172.3, 173.8.
Th e d ia ster eom er ic oxeta n e 3 was obtained as colorless
prismatic crystals from hexane-chloroform: HRMS (FAB),
calcd for C25H26NO3 (MH+) 388.1881, found 388.1905; mp 165-
1
170 °C; IR (cm-1, KBr) 1707, 1753; H NMR (CDCl3) δ 1.5-
1.8 (m, 10H), 2.0-2.1 (m, 2H), 2.54 (br s, 2H), 2.83 (br s, 2H),
3.38 (t, J ) 9.0 Hz, 1H), 6.9-7.0 (m, 1H), 7.1-7.25 (m, 2H),
7.3-7.45 (m, 5H);13C NMR (CDCl3) δ 20.3, 21.7, 22.90, 22.98,
24.4, 24.8, 26.0, 29.9, 51.0, 83.5, 88.8, 126.2, 126.3, 126.6, 128.4,
128.7, 130.9, 132.1, 133.6, 135.4, 139.2, 172.0, 173.6.
J . Org. Chem, Vol. 68, No. 3, 2003 945