2730 J . Org. Chem., Vol. 65, No. 9, 2000
Toda et al.
however, the inclusion compound of prochiral (-)-6 and
4 exhibited a rather strong CD spectrum, suggesting that
this spectrum originates primarily from 4 (Figure 3).
Thus, the prochiral compound exhibits chirality when
frozen in a chiral conformation in the solid state. This
result is expected on the basis of our X-ray crystal
structural analysis.
The mixing of powdered 6 and 4 gave the inclusion
complex in a quantitative yield. Irradiation for 20 h with
stirring of a suspension of this powdered 1:1 complex of
6 and 4 in water containing hexadecylmethylammonium
bromide as a surfactant gave (-)-5 in 87% ee in 15%
yield.
Other phenylglyoxylamides, for example, diethylphen-
ylglyoxylamide, did not form inclusion complexes with 6
by either recrystallization or mixing methods.
In conclusion, we have successfully performed highly
enantioselective photocyclization of amides (1, 4) to
â-lactams (2, 5) using host-guest interaction in chiral
crystals.
F igu r e 2. Molecular packing of 8 with a hydrogen-bonding
network: O2‚‚‚O6 ) 2.664(6) Å, O1‚‚‚O4i ) 3.171(6) Å,
O4‚‚‚O2ii ) 2.914(5) Å, and O3‚‚‚O1ii ) 3.003(5) Å. Symmetry
codes: (i) x + 1, y, z; (ii) x - 1, y, z.
Exp er im en ta l Section
of 162°. The host is conformationally rigid with the two
hydroxyl groups at each acetylenic moiety located on the
same side of the molecular framework. Because of the
bulky chlorine atoms at the ortho position of the phenyl
rings, the torsion angles of O1-C13-C1-C2 and O4-
C24-C2-C26 are 172.0 and 176.7°, respectively. There
are short Cortho-H‚‚‚O(hydroxyl) contacts at both o-
chlorophenyl rings [C6-H6‚‚‚O1 ) 2.741(7) Å and C30-
H30‚‚‚O4 ) 2.744(7) Å].
Gen er a l Meth od s. The preparation of inclusion compounds
of 1 and 4 with the hosts was achieved by recrystallization
from toluene or ether. The host:guest ratio of each inclusion
compound was determined by elemental analysis. Irradiation
of the inclusion compounds as water suspensions at room
temperature was performed through a Pyrex filter using a
100-W high-pressure Hg lamp. IR spectra were measured with
a J ASCO FT/IR-350 IR spectrometer, using Nujol mulls. 1H
NMR spectra were recorded in CDCl3 on a J EOL J NM-LA300
(300 MHz) spectrometer. [R]D values were measured with a
J ASCO DIP-1000S digital polarimeter. Optical purities were
determined by HPLC using a hexane/2-propanol (9:1) solvent
(flow rate ) 1.0 mL/min), unless otherwise stated, and a
column (0.46 cm × 25 cm) containing the chiral solid phase
Chiralcel OC or OD, which is commercially available from
Daicel Chemical Industries, Ltd., Himeji, J apan.
The conformation of the guest molecule can be de-
scribed by the dihedral angle between the best-fit plane
through the phenyl ring, including also the adjacent Cd
O atoms, and the plane through the atoms of the amide
group (C44, C45, C46, N1, and O6); the value is 65.1°.
The conformation is also greatly influenced by four
C-H‚‚‚O interactions ranging from 2.716(9) to 3.075(9)
Å. The short Cl6‚‚‚C38 (guest) distance of 3.714(8) Å
indicates a rather tight packing between guest and host.
Surely the most interesting feature in this crystal
structure is the hydrogen-bond network illustrated in
Figure 2. The molecules are linked by intermolecular
chains of O-H‚‚‚O along the a axis. Each oxygen atom
of each hydroxyl group in the host is included in this
pattern simultaneously as donor and as acceptor, with
the exception of the O3 atom which acts only as a donor.
Also forming an integral part of this hydrogen-bonded
chain is the guest molecule, which is capable of pre-
organizing its conformation to occupy a well-defined
chiral environment provided by the host molecule. In a
figurative way, we can speak about chiral polymeric
chains being formed by hydrogen bonding. It is interest-
ing that the benzoyl carbonyl O5 oxygen atom of the
guest molecule is not included in the previously described
hydrogen-bonding arrangement.
The enantioselectivity of 4 is controlled by the confor-
mation about the O5dC43-C44dO6 bonds. The observed
torsion angle is 113.9(8)°, and in the absence of a mirror-
symmetry-related molecule, a single enantiomer of 5 is
thus formed in the subsequent photoreaction.
The chiral arrangement of the prochiral molecule 4 in
the inclusion complex of 6 and 4 also was clarified by
the measurement of CD spectra in the solid state.8,9 The
chiral host molecule (-)-6 showed neither strong absorp-
tion nor CD peaks in the 400-200 nm region. In contrast,
P r ep a r a tion of 1. The compounds 1a -d were prepared by
the reported method.1
P r ep a r a tion of In clu sion Com p ou n d s of 3 a n d 1. When
a solution of 3c (3.8 g, 7.6 mmol) and 1a (1.2 g, 3.8 mmol) in
toluene (20 mL) was kept at room temperature for 12 h, a 2:1
inclusion compound of 3c and 1a was obtained as colorless
needles (2.6 g, 52% yield, mp is not clear). IR (Nujol) νmax
:
3330, 1690, 1645, 1630 cm-1. Anal. Calcd for C89H89NO10: C,
80.22; H, 6.73; N, 1.05. Found: C, 80.52; H, 6.89; N, 1.02. By
the same procedure, the inclusion compounds of 3 and 1 were
prepared (Table 1).
P h otocycliza tion of 1 to 2. A suspension of a powdered
1:1 inclusion compound of 3c with 1a (2.6 g, 3.2 mmol) in water
(120 mL) containing hexadecyltrimethylammonium bromide
(0.04 g) as a surfactant was irradiated with stirring for 8 h.
The reaction product was filtered, dried, and chromatographed
on silica gel using AcOEt/hexane (1:4) as the eluent to give
(-)-2a in 97% ee as a colorless oil (0.27 g, 26% yield). [R]D -48
(c 0.6, MeOH). By the same procedure, inclusion compounds
of 3 and 1 gave optically active 2, in the yields and optical
purities shown in Table 1. Products 2a -d 1 are known com-
pounds.
P r ep a r a tion of (-)-tr a n s-1,4-Bis[3-(o-ch lor op h en yl)-3-
h yd r oxy-3-p h en ylp r op -1-yn yl]-2,3,5,6-tetr a ch lor o-2,5-cy-
(7) Eu(hfc)3 is available from Aldrich Chemical Company, Inc.,
Milwaukee, WI. The methylene proton signal of the benzyl group of
2b and its (-)- and (+)-enantiomers appeared at δ 4.18 and 4.78,
respectively, in CDCl3 in the presence of 0.1 molar equiv of Eu(hfc)3.
(8) Toda, F.; Miyamoto, H.; Kikuchi, S.; Kuroda, R.; Nagami, F. J .
Am. Chem. Soc. 1996, 118, 11315.
(9) Toda, F.; Miyamoto, H.; Kanemoto, K.; Tanaka, K.; Takahashi,
Y.; Takenaka, Y. J . Org. Chem. 1999, 64, 2096.
Toda, Fumio
