Absolute asymmetric photocyclization of triisopropylbenzophenone derivatives in crystals and their morphological changes

Article abstract of DOI:10.1021/jo5000913

Although 4-(2,4,6-triisopropylbenzoyl)benzylbenzamide is an achiral molecule, chiral crystals can form through spontaneous crystallization in a methanol solution. In the M crystal, twofold helical hydrogen-bond chains form in a counterclockwise direction among the molecules along the a axis to generate crystal chirality. The solid-state circular dichroism spectra of the two enantiomorphous crystals as Nujol mulls show a good mirror-image relationship. UV irradiation of the M crystal at >290 nm caused highly enantioselective Norrish type II photocyclization to yield the (R)-cyclobutenol with 94% ee in 100% yield as the sole product, resulting in successful absolute asymmetric synthesis. In contrast, the (S)-cyclobutenol was obtained from the P crystal with 95% ee in 100% yield. The high enantiodifferentiation in the crystalline-state photocyclization is attributed to the shorter distance between the carbonyl oxygen atom and one of the methine ?-hydrogen atoms of the two o-isopropyl groups as well as the smooth transformation with minimum molecular motion because of the similar shapes of the reactant and product molecules. UV irradiation of the platelike crystals resulted in a crack in the direction perpendicular to the long axis (the a axis of the unit cell), likely because the hydrogen-bond chains were broken during the photocyclization.

Full text of DOI:10.1021/jo5000913

Article
pubs.acs.org/joc
Absolute Asymmetric Photocyclization of
Triisopropylbenzophenone Derivatives in Crystals and Their
Morphological Changes
Hideko Koshima,*,† Michitaro Fukano,† Naoko Ojima,† Kohei Johmoto,‡ Hidehiro Uekusa,‡
and Motoo Shiro§
†Department of Materials Science and Biotechnology, Graduate School of Science and Engineering, Ehime University, Matsuyama,
Ehime 790-8577, Japan
‡Department of Chemistry and Materials Science, Tokyo Institute of Technology, 2 Ookayama, Meguro-ku, Tokyo 152-8551, Japan
§Rigaku Corporation, 3-9-12 Matsubara, Akishima, Tokyo 196-8666, Japan
S
* Supporting Information
ABSTRACT: Although 4-(2,4,6-triisopropylbenzoyl)benzyl-
benzamide is an achiral molecule, chiral crystals can form
through spontaneous crystallization in a methanol solution. In
the M crystal, twofold helical hydrogen-bond chains form in a
counterclockwise direction among the molecules along the a axis
to generate crystal chirality. The solid-state circular dichroism
spectra of the two enantiomorphous crystals as Nujol mulls show
a good mirror-image relationship. UV irradiation of the M crystal
at >290 nm caused highly enantioselective Norrish type II
photocyclization to yield the (R)-cyclobutenol with 94% ee in
100% yield as the sole product, resulting in successful absolute asymmetric synthesis. In contrast, the (S)-cyclobutenol was
obtained from the P crystal with 95% ee in 100% yield. The high enantiodifferentiation in the crystalline-state photocyclization is
attributed to the shorter distance between the carbonyl oxygen atom and one of the methine γ-hydrogen atoms of the two o-
isopropyl groups as well as the smooth transformation with minimum molecular motion because of the similar shapes of the
reactant and product molecules. UV irradiation of the platelike crystals resulted in a crack in the direction perpendicular to the
long axis (the a axis of the unit cell), likely because the hydrogen-bond chains were broken during the photocyclization.
We recently achieved diastereospecific photocyclization in
the chiral crystal of an isopropylbenzophenone derivative with
an (S)-phenylethylamide group.13 Our success led us to
construct chiral crystals of isopropylbenzophenone derivatives
substituted with an achiral benzylamide group to identify a
novel chiral crystal. Here we report the highly enantioselective
photocyclization of 4-(2,4,6-triisopropylbenzoyl)benzyl-
benzamide (1) in chiral crystals and the morphological changes
of the single crystals during the photoreaction.
INTRODUCTION
■
Asymmetric synthesis usually requires an external chiral source,
such as a chiral catalyst. In contrast, absolute asymmetric
synthesis using chiral crystals that are spontaneously formed
from achiral molecules does not require an external chiral
source. Since the first report of the absolute asymmetric [2 + 2]
photodimerization of butadiene derivatives in mixed crystals in
1973,1 more than 20 successful examples have been
published.2−6 We also performed the absolute asymmetric
photodecarboxylative condensation of acridine with diphenyl-
acetic acid in chiral cocrystals7 and the absolute asymmetric
photocyclization of isopropylbenzophenone in chiral salt
crystals.8 It is known that achiral molecules spontaneously
form chiral crystals at 8% statistical probability.9 However,
chiral crystallization of achiral molecules cannot be predicted
presently, making it difficult to perform absolute asymmetric
syntheses. Nevertheless, we prepared a number of chiral
cocrystals composed of two different achiral molecules using a
trial-and-error approach.10−12 Consequently, we realized that
chiral crystals could be found in higher probability by learning
and using useful information obtained from the molecular
arrangements of both chiral and achiral crystals of analogous
compounds.
RESULTS AND DISCUSSION
■
Preparation of Chiral Crystals. Three achiral 2,4,6-
triisopropylbenzophenone derivatives with benzylamide groups
at the para, meta, and ortho positions (1−3, respectively) were
synthesized and recrystallized from methanol solutions to yield
single crystals. X-ray crystallographic analyses of 1−3 were
performed. They showed that the crystal of 1 was chiral and
belonged to an orthorhombic system with space group P212121
(Table 1). In contrast, the crystals of 2 and 3 revealed an achiral
nature with orthorhombic systems showing space groups
Received: January 29, 2014
Published: March 16, 2014
© 2014 American Chemical Society
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Pna/21 and Pbcn, respectively. The probability of chiral
crystallization of achiral molecules 1−3 was 33%, considerably
higher than the 8% statistical probability.9
The two enantiomeric crystals of 1 were obtained by
evaporating the methanol solution and were discriminated
using solid-state circular dichroism (CD) spectra as Nujol
mulls, which showed a good mirror-image relationship (Figure
1). The absolute structure of 1 was determined using a half
piece of the single crystal to be in the M form with a high
degree of certainty on the basis of the Flack parameter, χ =
0.01(24), in X-ray crystallographic analyses at 93 K.14 The
crystal maintained the same space group, P212121, but the unit
cell size decreased slightly compared with that at 296 K (Table
1). Another half piece of the M-1 single crystal gave the CD
curve labeled M in Figure 1; the absolute structure of 1 could
be related to the CD spectrum.
Figure 2a shows the ORTEP drawing of molecule 1 in the M-
1 crystal at 296 K. The 4-isopropylphenyl group of 2,4,6-
triisopropylbenzophenone (blue color) and the phenyl ring of
the benzyl group (green color) were disordered with 0.234 and
0.329 occupancy, respectively. Molecule 1 showed a torsional
conformation: the dihedral angle between the triisopropylben-
zene plane and the phenyl plane of triisopropylbenzophenone
was 85.71° (almost perpendicular), and the dihedral angles
between the phenyl plane of triisopropylbenzophenone and the
disordered phenyl plane of the benzyl group were 65.29°
(0.671 occupancy) and 60.13° (0.329 occupancy). In the M-1
crystal, twofold helical hydrogen-bond chains formed in a
counterclockwise (minus, M) direction among the benzophe-
none carbonyl groups and the amide groups through CO···
H−N (2.28 Å) interactions along the a axis (Figure 2b,c). In
contrast, clockwise (plus, P) helical chains alone are arranged in
the P crystal. The helical chains are alternately arranged in
opposite directions with a half translation along the c axis,
which induces the crystal chirality.
Figure 1. Solid-state CD spectra of the enantiomorphous M-1 and P-1
crystals as Nujol mulls.
solid-state CD spectra (Figure 1). UV irradiation of the
pulverized crystals of M-1 with a high-pressure mercury lamp
through Pyrex (>290 nm) under argon at 15 °C for 24 h caused
highly enantioselective photocyclization to yield chiral cyclo-
butenol 4 as the sole product in 100% chemical yield (Scheme
1). The enantiomeric excess was determined to be 94% ee on
the basis of high-performance liquid chromatography (HPLC)
using a chiral column.
The absolute configuration of product 4 was determined as
follows (Scheme 2). We previously reported that 4-(2,4,6-
triisopropylbenzoyl)benzoic acid (5) undergoes enantioselec-
tive photocyclization in the three-component cocrystal with L-
prolinol and water via a single-crystal-to-single-crystal trans-
formation to yield the R-form cyclobutenol (R)-6 with 30% ee
as the sole product.15 At this time, we performed the same
photoreaction of the cocrystal and obtained (R)-6 with 15% ee.
Cyclobutenol (R)-6 was then transformed into the benzylamide
derivative (R)-4 through a reaction with benzylamine in the
presence of BOP and triethylamine. Chiral HPLC analysis
revealed the first peak (retention time, 11.6 min) and second
peak (retention time, 24.3 min) corresponding to (S)-4 and
(R)-4, respectively, and the enantiomeric excess of (R)-4 was
determined to be 12% ee (Scheme 2). Consequently, the
reaction of M-1 crystals yielded the R-form cyclobutenol (R)-4
with 94% ee. UV irradiation of the opposite-handed P-1 crystals
yielded (S)-4 alone in 100% chemical yield with 95% ee. In
contrast, solution photolysis of 1 in acetonitrile yielded a
racemic mixture of (R)- and (S)-4 in 65% chemical yield.
Figure 3 shows the possible reaction paths in the M-1 crystal.
Photoirradiation of the M-1 crystal at >290 nm with a high-
pressure mercury lamp through Pyrex causes n,π* excitation of
Solid-State Photoreaction. Both enantiomorphous crys-
tals of 1 for the solid-state photoreaction were prepared by
seeding on a large scale and differentiated on the basis of their
Table 1. Selected Crystal Data
1
M-1
2
3
rac-4
T (K)
296
93
296
296
296
crystal system
space group
a (Å)
orthorhombic
P212121 (No. 19)
9.340(3)
11.0137(10)
25.4582(11)
90.0
orthorhombic
P212121 (No. 19)
9.30070(17)
10.82862(17)
24.9809(7)
90.0
orthorhombic
Pna/21 (No. 33)
26.203(3)
8.9809(9)
11.0665(11)
90.0
orthorhombic
Pbcn (No. 60)
34.511(3)
8.6859(8)
18.3438(17)
90.0
monoclinic
C2/c (No. 15)
34.467(4)
16.0663(18)
9.5149(10)
93.017(7)
5261.6(11)
8
b (Å)
c (Å)
β (deg)
V (Å3)
Z
2618.8(9)
4
2515.91(9)
4
2604.2(5)
4
5498.7(9)
8
D (g cm−3
)
1.120
1.166
1.126
1.067
1.115
Flack parameter
−
0.01(24)
−
−
−
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Figure 2. (a) ORTEP drawing of molecule 1 in the M-1 crystal at 296 K; the thermal ellipsoids are plotted at the 25% probability level. The 4-
isopropyl group (blue color) and the phenyl ring (green color) are disordered with 0.234 and 0.329 occupancy, respectively. (b, c) Molecular
arrangements on (b) the (100) face and (c) the (011) face. Counterclockwise twofold helical hydrogen-bond chains (blue dotted lines) form along
̅
the a axis. The hydrogen atoms in (b) and (c) have been omitted for clarity, and the disordered 4-isopropyl group and the phenyl ring have also been
omitted.
Scheme 1. Solid-State Photoreaction of the Enantiomorphous M-1 and P-1 Crystals
Scheme 2. Enantioselective Photocyclization through Single-Crystal-to-Single-Crystal Transformation and Determination of the
Absolute Configuration of Product 4
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Figure 4. Drawings of cavities for the o-isopropyl groups and the
carbonyl group in the M-1 crystal to produce the enantiomers (a) (R)-
4 and (b) (S)-4.
Figure 3. Possible reaction paths for enantioselective photocyclization:
(a) reactant molecule 1 in the M-1 crystal; (b, c) product molecules
(b) (R)-4 and (c) (S)-4 coexisting in the racemic crystal rac-4
obtained by solution photolysis of 1. The disordered isopropyl and
phenyl groups in the molecules of 1, (R)-4, and (S)-4 have been
omitted for clarity.
recrystallization from 2-propanol solution of the racemic
mixture of (R)-4 and (S)-4 obtained from the solution
photolysis of 1. Crystallographic analysis of rac-4 was successful
(Table 1). The reaction path in the M-1 crystal is discussed on
the basis of the most stable conformation of (R)- and (S)-4
molecules in the racemic rac-4 crystal.
the carbonyl oxygen atom (O1) of molecule 1 (Figure 3a). The
excited O1 atom can release the methine hydrogen atoms of
two o-isopropyl groups (H7 and H13) to produce the (R)- and
(S)-ketyl radicals (·C16), respectively, and the corresponding
methine radicals (·C7 and ·C13). The radicals approach each
other and finally couple to produce (R)- and (S)-cyclobutenol
[i.e., the enantiomeric products (R)-4 and (S)-4, respectively].
However, (R)-4 was obtained with high enantioselectivity (94%
ee) through the crystalline-state photocyclization. Hence, the
geometrical parameters for the two possible γ-hydrogen atom
abstractions were compared: the O1−C16−C1−C2 and O1−
C16−C1−C6 torsion angles are −80.92° and 100.05°,
respectively, and the O1 atom is tilted toward the C7 by
9.6°. Thus, the O1···H7 distance (2.65 Å) is shorter than the
O1···H13 distance (2.99 Å) by 0.34 Å, leading to abstraction of
H7 with higher priority than H13, yielding (R)-cyclobutenol
(R)-4 with higher enantioselectivity than (S)-4.16 However, it is
not clear why very high enantiodifferentiation of (R)-4 (94%
ee) results from the shorter distance of hydrogen abstraction.
As a matter of course, the o-isopropyl groups and the
carbonyl group of the reactant M-1 move upon the occurrence
of hydrogen abstraction by the excited carbonyl oxygen, and
thus, a larger surrounding space is advantageous. The
surrounding area, a cavity, is defined as a space limited by a
concave surface of the spheres of inter- and intramolecular
atoms in the neighborhood.17 The cavity size of 3.8 Å required
to yield (R)-4 is larger than that to yield (S)-4 (2.7 Å),
supporting the preferential enantioselective formation of (R)-4
from the M-1 crystal (Figure 4).
The molecular conformation of (R)-4 in the rac-4 crystal
(Figure 3b) is similar to that of reactant 1 in the M-1 crystal
(Figure 3a). This suggests that the transformation from
molecule 1 to (R)-4 should proceed smoothly upon UV
irradiation because of the minimum motion within the helical
chains in the M-1 crystal. In contrast, the molecular
conformation of (S)-4 in the rac-4 crystal (Figure 3c) differs
significantly from that of molecule 1 in the M-1 crystal because
the phenyl ring of the benzylamide group is twisted to the
opposite side. Hence, a large motion would be required to turn
the phenyl ring to the opposite side and produce the (S)-4
molecule in the M-1 crystal. However, it would be difficult to
achieve such a large molecular motion within the restricted
crystal lattice. This may also explain why (S)-4 is rarely
produced but (R)-4 shows very high enantioselectivity (94%
ee).
We observed morphological changes of the microcrystals of 1
during photocyclization using a CCD microscope. Figure 5a
shows a piece of the platelike microcrystal before irradiation.
The top surface is the (011) face, and the long axis is the a axis.
̅
UV irradiation of the microcrystal for 1 h resulted in a crack in
the direction perpendicular to the long axis (Figure 5b). The
Solid-state reactions generally proceed with minimum
molecular motion in the crystal lattice because the molecules
are arranged at close positions in three-dimensional regularity
and thus the motion is very restricted. In contrast, the
molecules are arranged with the most stable conformation in
the crystal from solution. Thus, the molecular conformation of
a product in a solid-state reaction often differs from that of a
product crystallized from solution. Nevertheless, it is mean-
ingful that the reaction path is discussed on the basis of the
most stable conformation of the molecules in the product
crystal. At this time, enantiomorphous crystals of (R)-4 did not
form by recrystallization from solution of the photoproducts
from the solid-state photoreaction of the M-1 crystals.
However, racemic crystals of rac-4 were obtained by
Figure 5. (a, b) Morphological changes of a microcrystal of 1 (a)
before and (b) after UV irradiation for 1 h. The scale bar is 100 μm. (c,
d) Morphological changes of a bulk crystal of 1 (c) before and (d)
after UV irradiation for 15 h. The scale bar is 1.0 mm.
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bulk single crystal of 1 also cracked in the direction
perpendicular to the long axis after UV irradiation for 15 h
(Figure 5c,d). In the reactant crystal of 1, twofold helical
hydrogen-bond chains form among the benzophenone carbonyl
groups and the amide groups through CO···H−N
interactions along the a axis (Figure 2b,c), which is the long
axis of the platelike crystal (Figure 5). When the benzophenone
CO group of molecule 1 is transformed into the cyclo-
butenol O−H group of product molecule 4 by the Norrish type
II hydrogen abstraction followed by cyclization upon UV
irradiation, the hydrogen-bond chains along the a axis
inevitably break.
The reaction process could be traced by the changes in the
Fourier-transform infrared (FT-IR) spectrum. The 1640 cm−1
band of the stretching vibration of the benzophenone CO
group in molecule 1 decreased as a result of the change to the
cyclobutenol O−H group in product molecule 4 with
increasing UV irradiation time (Figure 6a). The 1247 cm−1
molecular shapes of the reactant and the product. The platelike
single crystals cracked upon UV irradiation in the direction
perpendicular to the long axis, likely because of breaking of the
hydrogen-bond chains in the reactant crystals during photo-
cyclization.
EXPERIMENTAL SECTION
■
General Information. All melting points are uncorrected. 1H
NMR and 13C NMR spectra were recorded using a 400 MHz NMR
instrument. Chemical shifts are reported in parts per million relative to
tetramethylsilane. IR spectra were recorded on an FT-IR instrument,
and samples were analyzed as films with KBr. The solvents were of
analytical grade.
4-(2,4,6-Triisopropylbenzoyl)benzylbenzamide (1). 2,4,6-Trii-
sopropyl-4′-carboxybenzophenone (0.401 g, 1.14 mmol) and benzyl-
amine (0.379 g, 3.54 mmol) were dissolved in chloroform (10 mL)
and THF (10 mL), and triethylamine (4.0 mL, 28 mmol) and BOP
(1.073 g, 2.43 mmol) were added. The solution was stirred at room
temperature for 15 h, and the solvent was evaporated under vacuum.
The crude product was purified via silica gel column chromatography
(hexane/ethyl acetate, 10:1) to afford 1 (0.333 g, 0.75 mmol, 66%
1
yield) as a white powder. Mp 206.3−207.2 °C; H NMR (400 MHz,
CDCl3) δ 7.90−7.83 (m, 4H), 7.37−7.31 (m, 5H), 7.06 (s, 2H), 6.41
(bs, 1H), 4.66 (d, J = 5.6 Hz, 2H), 2.94 (septet, J = 6.8 Hz, 1H), 2.56
(septet, J = 6.8 Hz, 2H), 1.30 (d, J = 6.8 Hz, 6H), 1.16 (d, J = 6.8 Hz,
6H), 1.04 (d, J = 6.8 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 200.5,
166.5, 150.1, 145.0, 140.3, 138.6, 137.8, 134.5, 129.7, 128.9, 128.0,
127.8, 127.3, 121.1, 96.1, 44.3, 34.4, 31.1, 24.9, 24.0, 23.4; IR (cm−1)
3426, 3033, 2960, 2929, 2869, 1658, 1604, 1531, 1494, 1458, 1385,
1361, 1319, 1281, 1139, 948, 922, 876, 732. Anal. Calcd for
C30H35NO2: C, 81.59; H, 7.99; N, 3.17. Found: C, 81.38; H, 7.73;
N, 3.14.
3-(2,4,6-Triisopropylbenzoyl)benzylbenzamide (2). 2,4,6-Trii-
sopropyl-3′-carboxybenzophenone (0.400 g, 1.13 mmol) and benzyl-
amine (0.368 g, 3.43 mmol) were dissolved in chloroform (10 mL)
and THF (10 mL), and triethylamine (4.0 mL, 28 mmol) and BOP
(1.073 g, 2.43 mmol) were added. The solution was stirred at room
temperature for 15 h, and the solvent was evaporated under vacuum.
The crude product was purified via silica gel column chromatography
(hexane:/ethyl acetate, 10:1) to afford 2 (0.400 g, 0.91 mmol, 80%
Figure 6. (a) Changes in the IR spectra and (b) conversion of the
photocyclization of 1 in the microcrystals under UV irradiation.
band corresponding to interactions among the CO
stretching, N−H bending, and C−N stretching of the amide
in reactant molecule 1 also decreased upon UV irradiation. The
amide group is not involved in the photocylization reaction, but
the CO···H−N hydrogen bond chains along the a axis break
as a result of the change from the benzophenone CO group
to the cyclobutenol O−H group as the reaction proceeds. The
1247 cm−1 band is susceptible to the change in the crystalline
environment due to the reaction, and thus, its strength
decreases with increasing UV irradiation time. The conversion
of the photocyclization, based on the intensity changes in the
absorption at 1247 cm−1, showed an almost linear relationship
with irradiation time (Figure 6b). With UV irradiation for 1 h,
around 80% of the hydrogen-bond chains along the long axis of
the crystals were estimated to be broken. This may explain why
the crystals cracked in the direction perpendicular to the long
axis during photocyclization.
1
yield) as a white powder. Mp 147.5−149.8 °C; H NMR (400 MHz,
CDCl3) δ 8.36 (s, 1H), 8.11 (d, J = 7.8 Hz, 1H), 7.78 (d, J = 7.8 Hz,
1H), 7.51 (t, J = 7.8 Hz, 1H), 7.31−7.38 (m, 5H), 7.06 (s, 2H), 6.52
(bs, 1H), 4.66 (d, J = 5.6 Hz, 2H), 2.93 (septet, J = 6.8 Hz, 1H), 2.56
(septet, J = 6.8 Hz, 2H), 1.29 (d, J = 6.8 Hz, 6H), 1.16 (d, J = 6.8 Hz,
6H), 1.05 (d, J = 6.8 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 200.6,
166.3, 150.1, 145.0, 138.3, 137.8, 135.1, 134.3, 133.3, 132.6, 129.1,
128.9, 128.0, 127.8, 126.0, 121.2, 96.1, 44.3, 34.4, 31.2, 24.9, 24.0, 23.4;
IR (cm−1) 3421, 2958, 1678, 1658, 1599, 1534, 1460, 1426, 1385,
1362, 1322, 1249, 1185, 1106, 954, 875, 731. Anal. Calcd for
C30H35NO2: C, 81.59; H, 7.99; N, 3.17. Found: C, 81.46; H, 7.74; N,
3.08.
2-(2,4,6-Triisopropylbenzoyl)benzylbenzamide (3). 2,4,6-Trii-
sopropyl-2′-carboxybenzophenone (0.400 g, 1.13 mmol) and benzyl-
amine (0.365 g, 3.43 mmol) were dissolved in chloroform (10 mL)
and THF (10 mL), and triethylamine (4.0 mL, 28 mmol) and BOP
(1.072 g, 2.40 mmol) were added. The solution was stirred at room
temperature for 15 h, and the solvent was evaporated under vacuum.
The crude product was purified via silica gel column chromatography
(hexane/ethyl acetate, 10:1) to afford 3 (0.293 g, 0.91 mmol, 59%
CONCLUSIONS
■
Absolute asymmetric photocyclization of 4-(2,4,6-triisopropyl-
benzoyl)benzylbenzamide was achieved in the crystalline state.
Irradiation of the M crystal caused highly enantioselective
Norrish type II photocyclization to yield the (R)-cyclobutenol
with 94% ee in 100% yield as the sole product. The high
enantiodifferentiation in the solid-state photocyclization is
attributed to the shorter distance between the carbonyl oxygen
atom and one of the methine γ-hydrogen atoms of the two o-
isopropyl groups as well as the smooth transformation with
minimum molecular motion as a result of the very similar
1
yield) as a white powder. Mp 116.2−118.0 °C; H NMR (400 MHz,
CDCl3) δ 7.56−7.52 (m, 2H), 7.48 (d, J = 7.2 Hz, 2H), 7.41−7.30 (m,
5H), 7.06 (s, 2H), 6.13 (bs, 1H), 4.74 (d, J = 5.6 Hz, 2H), 2.93
(septet, J = 6.8 Hz, 1H), 2.76 (septet, J = 6.8 Hz, 2H), 1.29 (d, J = 6.8
Hz, 6H), 1.10 (bs, 12H); 13C NMR (100 MHz, CDCl3) δ 200.4,
170.0, 150.1, 145.5, 138.2, 137.5, 136.7, 134.9, 132.7, 132.0, 129.3,
128.7, 128.2, 127.5, 121.1, 96.1, 44.4, 34.4, 30.9, 24.0; IR (cm−1) 3248,
3065, 2961, 2868, 1678, 1635, 1601, 1553, 1459, 1383, 1362, 1291,
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1250, 1157, 947, 919, 879, 746. Anal. Calcd for C30H35NO2: C, 81.59;
H, 7.99; N, 3.17. Found: C, 81.70; H, 7.69; N, 3.18.
ACKNOWLEDGMENTS
■
This work was supported by Grants-in-Aid for Scientific
Research (B) (22350063) and Challenging Exploratory
Research (23655129) from the Japan Society for the
Promotion of Science.
Photoreaction of the M-1 and P-1 Crystals. Pulverized M-1
crystals (0.200 g, 0.45 mmol) were placed between two Pyrex plates
and irradiated with a 400 W high-pressure mercury lamp under argon
at 15 °C for 24 h to yield cyclobutenol 4 (0.200 g, 0.45 mmol, 100%
yield) as the sole product. Mp 158.2−159.3 °C; 1H NMR (400 MHz,
CDCl3) δ 7.73 (d, J = 8.4 Hz, 2H), 7.37−7.30 (m, 5H), 7.06 (s, 2H),
6.89 (s, 1H), 6.36 (bs, 1H), 4.66 (d, J = 5.6 Hz, 2H), 2.92 (septet, J =
6.8 Hz, 1H), 2.83 (septet, J = 6.8 Hz, 1H), 1.45 (s, 3H), 1.28 (d, J =
6.8 Hz, 6H), 1.19 (d, J = 6.8 Hz, 3H), 1.15 (d, J = 6.8 Hz, 3H), 0.80 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 167.3, 152.8, 151.7, 146.5,
145.1, 139.5, 138.2, 133.0, 128.8, 128.0, 127.6, 127.0, 126.4, 124.2,
116.2, 96.1, 85.6, 54.8, 44.1, 35.0, 30.5, 24.6, 24.4, 24.3, 24.1, 22.8; IR
(cm−1) 3423, 2959, 1651, 1528, 1496, 1458, 1362, 1283, 1194, 1060,
917, 872, 751. Anal. Calcd for C30H35NO2: C, 81.59; H, 7.99; N, 3.17.
Found: C, 81.70; H, 8.21; N, 3.12. The absolute configuration of the
product 4 was confirmed to be R (see the details of the determination
method in the Results and Discussion). The enantiomeric excess was
determined to be 94% ee by HPLC using a chiral column (Daicel,
Chiralpak AD) and hexane/2-propanol with monitoring at 210 nm.
Solution Photolysis of 1. A solution of 1 (2.21 g, 5.00 mmol) in
acetonitrile (100 mL) was internally irradiated with a 100 W high-
pressure mercury lamp at room temperature for 55 h under bubbling
of argon. The solvent was evaporated from the irradiated solution, and
the residue was submitted to silica gel column chromatography
(hexane/ethyl acetate, 10:1) to yield racemic 4 (1.44 g, 3.25 mmol,
65% yield) as the sole product and remaining starting material 1
(0.751 g, 1.70 mmol, 66% conversion). Data for rac-4: mp 171.2−
172.3 °C (from hexane and 2-propanol); 1H NMR (400 MHz,
CDCl3) δ 7.73 (d, J = 8.4 Hz, 2H), 7.37−7.30 (m, 5H), 7.06 (s, 2H),
6.89 (s, 1H), 6.36 (bs, 1H), 4.66 (d, J = 5.6 Hz, 2H), 2.92 (septet, J =
6.8 Hz, 1H), 2.83 (septet, J = 6.8 Hz, 1H), 1.45 (s, 3H), 1.28 (d, J =
6.8 Hz, 6H), 1.19 (d, J = 6.8 Hz, 3H), 1.15 (d, J = 6.8 Hz, 3H), 0.80 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 167.3, 152.8, 151.7, 146.4,
145.1, 139.4, 138.2, 133.0, 128.8, 128.0, 127.6, 127.0, 126.4, 124.2,
116.2, 96.1, 85.6, 54.8, 44.1, 35.0, 30.5, 24.6, 24.4, 24.2, 24.1, 22.8; IR
(cm−1) 3423, 2959, 1651, 1528, 1496, 1458, 1362, 1283, 1194, 1060,
917, 872, 751. Anal. Calcd for C30H35NO2: C, 81.59; H, 7.99; N, 3.17.
Found: C, 81.75; H, 8.19; N, 3.10.
REFERENCES
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X-ray Crystallograhic Analysis. X-ray crystallographic analysis
was performed on an X-ray diffractometer using a two-dimensional
imaging plate area detector (Rigaku RAXIS-RAPID) with Cu Kα
radiation (λ = 1.54187 Å). All of the crystallographic calculations were
performed using crystallographic software (Rigaku CrystalStructure
3.8 and 4.0).18 Structures were determined using direct methods and
expanded using Fourier techniques. The non-hydrogen atoms were
refined anisotropically, and the hydrogen atoms were not refined.
Hydrogen atoms attached to carbon atoms were located in the
calculated positions. The absolute structure of 1 was determined from
the Flack parameter.14 The crystal data are summarized in Table 1.
The data in CIF format have been deposited at the Cambridge
Crystallographic Data Centre with deposition numbers CCDC 973507
(1), CCDC 973508 (M-1), CCDC 973509 (2), CCDC 973510 (3),
and CCDC 973511 (rac-4).
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Tokyo, 2005.
ASSOCIATED CONTENT
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S
* Supporting Information
1H and 13C NMR spectra for 1−4 and labeled ORTEP
diagrams and CIFs for 1, M-1, 2, 3, and rac-4. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*Tel: +81-89-927-8523. Fax: +81-89-927-8523. E-mail:
koshima.hideko.mk@ehime-u.ac.jp.
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Notes
The authors declare no competing financial interest.
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dx.doi.org/10.1021/jo5000913 | J. Org. Chem. 2014, 79, 3088−3093