Solid State Photochemical Reaction of N-(α,β-Unsaturated carbonyl)benzoylformamides

Article abstract of DOI:10.1021/jo9704974

Photochemical reactions of various N-(α,β-unsaturated carbonyl)benzoylformamides both in solution and in a solid state were investigated. Under homogeneous conditions, all acyclic imides underwent photochemical 2 + 2 cycloaddition that resulted in the production of bicyclic oxetanes. N-Isopropyl- and N-benzyl-N-tigloylbenzoylformamides crystallized in a chiral space group, and the photolysis in the solid state yielded corresponding optically-active oxetanes. N-Tigloylbenzoylformanilide underwent cis-trans isomerization to yield a photostationary state (cis/trans = 1.3). Solid state oxetane formation of N-benzyl- and N-(o-tolyl)- and N-(2,6-xylyl)-N-tigloylbenzoylformamides progressed via the crystal-to-crystal pathway which was followed by X-ray powder diffraction. N-Benzyl-N-methacryloylbenzoylformamide crystallized in a chiral space group, and the solid state reaction led to an optically active β-lactam via topochemically-controlled hydrogen abstraction by the alkenyl carbon atom. Photolysis of N-isopropyl-N-methacryloylbenzoylformamide in the solid state led to both oxetane formation and a transformation to azetidine-2,4-dione involving a 1,5- benzoyl shift.

Full text of DOI:10.1021/jo9704974

6298
J . Org. Chem. 1997, 62, 6298-6308
Solid Sta te P h otoch em ica l Rea ction of N-(r,â-Un sa tu r a ted
ca r bon yl)ben zoylfor m a m id es
Masami Sakamoto,*,‡ Masaki Takahashi,† Tsutomu Fujita,† Shoji Watanabe,†
Takehiko Nishio,† Ikuo Iida,† and Hiromu Aoyama§
Department of Applied Chemistry, Faculty of Engineering, Chiba University,
Yayoi-cho, Inage-ku, Chiba 263, J apan, Department of Chemistry, The University of Tsukuba,
Tsukuba, Ibaraki 305, J apan, and Department of Material Chemistry,
Faculty of Textile Science and Technology, Shinshu University, Ueda, Nagano 386, J apan
Received March 18, 1997X
Photochemical reactions of various N-(R,â-unsaturated carbonyl)benzoylformamides both in solution
and in a solid state were investigated. Under homogeneous conditions, all acyclic imides underwent
photochemical 2 + 2 cycloaddition that resulted in the production of bicyclic oxetanes. N-Isopropyl-
and N-benzyl-N-tigloylbenzoylformamides crystallized in a chiral space group, and the photolysis
in the solid state yielded corresponding optically-active oxetanes. N-Tigloylbenzoylformanilide
underwent cis-trans isomerization to yield a photostationary state (cis/trans ) 1.3). Solid state
oxetane formation of N-benzyl- and N-(o-tolyl)- and N-(2,6-xylyl)-N-tigloylbenzoylformamides
progressed via the crystal-to-crystal pathway which was followed by X-ray powder diffraction.
N-Benzyl-N-methacryloylbenzoylformamide crystallized in a chiral space group, and the solid state
reaction led to an optically active â-lactam via topochemically-controlled hydrogen abstraction by
the alkenyl carbon atom. Photolysis of N-isopropyl-N-methacryloylbenzoylformamide in the solid
state led to both oxetane formation and a transformation to azetidine-2,4-dione involving a 1,5-
benzoyl shift.
In tr od u ction
molecular 2 + 2 cycloaddition, several examples of suc-
cessful intramolecular reactions have been reported.12-19
Furthermore, elucidation of the relationship (1) between
conformation of molecules and substituents, (2) between
the space groups and substituents, and (3) between the
arrangement of molecules in the crystal lattice and
photoreactivity may play an important role in the
fields of crystal engineering and organic asymmetric
synthesis.
Another advantage associated with solid state photo-
reaction is that X-ray analysis allows the orientation of
the constituent molecules to be determined prior to
reaction and, in some favorable systems, even after the
reaction has occurred. Schmidt et al. investigated bimo-
lecular reactions in crystals through the crystallographic
Solid state photoreaction has received much attention
both from a mechanistic and synthetic perspective, be-
cause this reaction provides stereoselectivity as well as
enantioselectivity for a wide range of products compared
to reactions that occur in solution due to restriction of
molecular movement imposed by the environment.1-8 In
addition, achiral substrates sometimes adopt a chiral
orientation in the crystal lattice, even in the absence of
any outside influences.9,10 The chirality of such a mol-
ecule in the crystal can be transformed spontaneously
through a solid state photoreaction into the stereocenter
of the product. Therefore, the reactions in the solid phase
may provide a model that will allow determination of
origin of chirality in molecules of living matter.11 As in
the case of the absolute asymmetric synthesis by inter-
(11) Addadi, L.; Lahav, M. Origin of Optically Activity in Nature;
Walker, D. C., Ed.; Elsevier: New York, 1979; Chapter 14.
(12) Sakamoto, M.; Hokari, N.; Takahashi, M.; Fujita, T.; Watanabe,
S.; Iida, I.; Nishio, T. J . Am. Chem. Soc. 1993, 115, 818.
(13) We already reported the absolute oxetane synthesis by the solid
state photoreaction of N-isopropyl-N-tigloylbenzoylformamide in pre-
liminary form: Sakamoto, M.; Takahashi, M.; Fujita, T.; Watanabe,
S.; Iida, I.; Nishio, T.; Aoyama, H. J . Org. Chem. 1993, 58, 3476-3477.
(14) For the absolute synthesis via radical pairs: Sakamoto, M.;
Takahashi, M.; Fujita, T.; Iida, I.; Takehiko, N.; Watanabe, S. J . Org.
Chem. 1995, 60, 4682-4683.
(15) For intramolecular hydrogen abstraction by carbonyl oxygen
or thiocarbonyl sulfur: (a) Evans, S. V.; Garcia-Garibay, M.; Omkaram,
N.; Scheffer, J . R.; Trotter, J .; Wireko, F. J . Am. Chem. Soc. 1986, 108,
5648-5649. (b) Sekine, A.; Hori, K.; Ohashi, Y.; Yagi, M.; Toda, F. J .
Am. Chem. Soc. 1989, 111, 697-700. (c) Sakamoto, M.; Takahashi,
M.; Shimizu, M.; Fujita T.; Takehiko, N.; Iida, I.; Yamaguchi K.;
Watanabe, S. J . Org. Chem. 1995, 60, 7088-7089. (d) Hashizume,
D.; Kogo, H.; Sekine, A.; Ohashi, Y.; Miyamoto, H.; Toda, F. J . Chem.
Soc., Perkin Trans. 2 1996, 61-66.
(16) For solid state di-π-methane rearrangement: (a) Garcia-
Garibay, M.; Scheffer, J . R.; Trotter, J .; Wireko, F. J . Am. Chem. Soc.
1989, 111, 4985-4986. (b) Fu, T. Y.; Liu, Z; Scheffer, J . R.; Trotter, J .
J . Am. Chem. Soc. 1993, 115, 12202-12203. (c) Roughton, A. L.;
Muneer, M.; Demuth, M. J . Am. Chem. Soc. 1993, 115, 2085-2086.
(17) Sakamoto, M.; Takahashi, M.; Yamaguchi, K.; Fujita, T.;
Watanabe, S. J . Am. Chem. Soc. 1996, 118, 8138-8139.
(18) Sakamoto, M.; Takahashi, M.; Kamiya, K.; Yamaguchi, K.;
Fujita, T.; Watanabe, S. J . Am. Chem. Soc. 1996, 118, 10664-10665.
(19) Toda, F.; Tanaka, K. Supramol. Chem. 1994, 3, 87-88.
† Chiba University.
‡ The University of Tsukuba.
§ Shinshu University.
X Abstract published in Advance ACS Abstracts, August 1, 1997.
(1) Scheffer, J . R.; Garcia-Garibay, M.; Nalamasu, O. Organic
Photochemistry; Padwa, A., Ed., Marcel Dekker: New York and Basel,
1987; Vol. 8, pp 249-338.
(2) Ramamurthy, V.; Weiss, R. G.; Hammond, G. S. Advances in
Photochemistry, Vol. 18; Volman, D. H., Hammond, G. S., Neckers, D.
C., Ed.; J ohn Wiley & Sons: New York, 1993; pp 67-234.
(3) Ramamurthy, V.; Venkatesan, K. Chem. Rev. 1987, 87, 433-
481.
(4) Zimmerman, H. E.; Zuraw, M. J . J . Am. Chem. Soc. 1995, 117,
5245-5262.
(5) Cohen, M. D.; Schmidt, G. M. J . Chem. Soc. 1964, 1969.
(6) Venkatesan, K.; Ramamurthy, V. Photochemistry in Organized
and Constrained Media; Ramamurthy, V., Ed.; VCH: New York, 1991;
pp 133-184.
(7) Scheffer, J . R.; Pokkuluri, P. R. Photochemistry in Organized and
Constrained Media; Ramamurthy, V., Ed., VCH: New York, 1991, pp
185-246.
(8) Vaida, M.; Popvitz-Biro, R.; Leiserowitz, L.; Lahav, M. Photo-
chemistry in Organized and Constrained Media; Ramamurthy, V., Ed.,
VCH: New York, 1991, 247-302.
(9) Green B. S., Lahav, M.; Rabinovich, D. Acc. Chem. Res., 1979,
69, 191-197.
(10) Sakamoto, M. Chem. Eur. J . 1997, 3, 684-689.
S0022-3263(97)00497-0 CCC: $14.00 © 1997 American Chemical Society

Photochemical Reaction of Benzoylformamides
J . Org. Chem., Vol. 62, No. 18, 1997 6299
F igu r e 1.
Sch em e 1
F igu r e 2.
mation may be used for photochemical cycloaddition
between benzoyl carbonyl (X) and alkenyl double bonds
(Y). On the other hand, imides with an (E,Z), (Z,E), or
(Z,Z) conformation cannot be used to produce oxetanes.
Since the interconversion takes place in solution, most
acyclic imides can promote oxetane formation, although
the quantum efficiency is affected by the conformer
distribution.
In the solid phase, conformational factors become more
important because interconversion involving dramatic
movement of the substituents cannot usually occur.
Photoreactivity in the solid state cannot be determined
only by the intramolecular parameter. In this case,
although reorientation to permit the reaction to occur and
the fitness of the surrounding crystal lattice are impor-
tant considerations, two principal parameters, distance
and the dihedral angle between the reacting carbonyl and
the alkenyl double bonds, are the most critical for
determining the photochemical reactivity of 2 + 2 cy-
cloaddition.
study of a large number of cinnamic acids. As a result,
they developed an important set of “topochemical rules”
with respect to photochemical reactivity by connecting
the configuration of the product and the crystal structure
of the reactant.20
The details of cyclobutane formation of alkenyl double
bonds, di-π-methane rearrangement,1,16 and the hydrogen
transfer of carbonyl or alkenyl double bonds1,21 have been
studied extensively with respect to the geometric param-
eters of the reacting sites. However, the geometric
parameters of the well-known Paterno-Bu¨chi photocy-
clization (oxetane formation) are hitherto unknown. The
present paper reports the photochemical behavior of
N-(R,â-unsaturated carbonyl)benzoylformamides in the
solid state and presents several remarkable examples of
“absolute” asymmetric syntheses involving 2 + 2 oxetane
formation and hydrogen transfer by the alkenyl carbon
atom.
Cr ysta l Str u ctu r e a n d th e Con for m a tion in th e
Cr ysta llin e Sta te. The photochemical reaction of five
N-tigloylbenzoylformamides 1a -e and five N-meth-
acryloylbenzoylformamides 1f-j was studied both in
solution and in a solid state (Figure 2). All imides ex-
cept 1b were subjected to X-ray single-crystal analysis.29
The crystal data are summarized in Tables 1 and 2.
Figure 3 shows the ORTEP diagram of the imides 1a and
1c-1j.
Table 3 shows the molecular conformation and the
geometrical data of the imides 1. All the imides showed
an either E,E or E,Z conformation. In the E,E conforma-
tion, the reacting carbonyl and the alkenyl double bonds
are assumed to be closely placed. Such imides are
extremely useful for cross-type 2 + 2 cycloaddition. On
the other hand, the E,Z-conformation is disadvantageous
for cycloaddition because of the separation between the
reacting double bonds. All imides maintain almost
planer conformation for the imide plane, the torsional
angles of the imide carbonyls, C1-N-C3-O3 or N-C1-
C2-O2 are within 33° of the sp2 nitrogen atom. The
torsional angles of the alkenyl group against the N-C3-
C4 plane are between 35.9° and 52.4°. Each carbonyl
group of the benzoylformyl group twists in the range of
47.4° to 79.9°. The phenyl ring and carbonyl group of
the benzoyl group are almost planar (absolute value:
3.0-13.3°). On the other hand, the aromatic rings on
the nitrogen atom are nearly orthogonal to the imide
chromophore (absolute value: 61.4-81.2°).
Resu lts a n d Discu ssion
Acyclic imides, N-(R,â-unsaturated carbonyl)benzoyl-
formamides 1, were used in the photochemical study
because they possess a nearly planar imide chromophore
with photochemically reactive alkenyl and benzoyl groups
at both ends of the imide carbonyls. Both chromophores
were placed as close to each other as the appropriate
conformation would allow. Irradiation of the imides 1
under homogeneous conditions results in cross-type 2 +
2 intramolecular cycloaddition between the ketone car-
bonyl and the alkenyl double bonds, the efficiency of
which is dependent on the substituents (Scheme 1).22 One
important factor that determines the reactivity involves
the distribution of the stable conformation of the imides.
Conformations of asymmetric imides are described as
(E,E), (E,Z), (Z,E) and (Z,Z), based on the planar sp2
nitrogen atom (Figure 1). The energy barrier of rotation
around the C()O)sN bond is significantly lower (7-13
kcal/mol) than that of the corresponding amides (17-25
kcal/mol), reflecting the decreased CdN double bond
characteristics of these systems. These conformational
factors may play an important role in the photochemical
reactivity of acyclic imides. Imides in the (E,E) confor-
(20) Schmidt, G. H. J . Pure Appl. Chem. 1971, 27, 647.
(21) Wagner, P. J .; Park, B. Organic Photochemistry; Padwa, A., Ed.,
Marcel Dekker: New York and Basel, 1991; Vol. 11, pp 227-366.
(22) Sakamoto, M.; Aoyama, H.; Omote, Y. J . Chem. Soc., Perkin
Trans. 1 1986, 1759-1762.

6300 J . Org. Chem., Vol. 62, No. 18, 1997
Sakamoto et al.
Ta ble 1. Cr ysta l Da ta for N-(r,â-Un sa tu r a ted ca r bon yl)ben zoylfor m a m id es 1a -e
1a 1c 1d
entry
1e
R1
R2
Me
Pri
C16H19NO3
272.33
monoclinic
P21
Me
Ph
Me
o-tolyl
C20H19NO3
321.4
monoclinic
P21/a
Me
2,6-Me2C6H3
C21H21NO3
335.4
orthorhombic
Pbca
formula
mol weight
crystal system
space group
Z
C19H17NO3
307.35
orthorhombic
Pca21
2
4
4
8
a/Å
b/Å
c/Å
5.933(1)
12.552(1)
10.594(2)
100.35(1)
776.1
9.271(4)
17.533(4)
10.320(5)
90a
13.855(4)
20.352(5)
6.137(2)
102.17(2)
1691.6(8)
1.26
13.543(5)
21.588(4)
12.526(5)
90a
â/deg
V/Å3
1677(2)
1.217
3662(1)
1.217
F
calc/g cm-3
1.16
µ/cm-1
0.8b
6.7c
6.48c
6.54c
F(000)
290
648
679
1424
crystal size/mm
used reflctns
0.4 × 0.15 × 0.20
0.05 × 0.05 × 0.50
0.50 × 0.15 × 0.15
0.30 × 0.30 × 1.00
2024
1480
2453
1817
R
RW
0.052
0.047
0.038
0.021
0.0398
0.0435
0.041
0.035
a
b
The angles of the crystal lattice are defined as â ) 90°. Mo KR radiation was used. c Cu KR radiation was used.
Ta ble 2. Cr ysta l Da ta for N-(r,â-Un sa tu r a ted ca r bon yl)ben zoylfor m a m id es 1f-j
entry
1f
1g
1h
1i
1j
R1
R2
H
H
Bn
H
Ph
H
H
Pri
2,6-Me2C6H3
C20H19NO3
321.38
monoclinic
P21/c
2,6-Cl2C6H32
C18H13NO3Cl2
362.21
monoclinic
P21/c
formula
mol weight
crystal system
space group
Z
C15H17NO3
259.3
monoclinic
P21/a
C19H17NO3
307.35
monoclinic
P21
C18H15NO3
293.32
monoclinic
P21/c
4
2
4
4
4
a/Å
b/Å
c/Å
10.998(7)
8.852(6)
14.929(8)
101.30(6)
1425(1)
1.208
9.649(5)
8.318(3)
10.216(5)
98.05(2)
811.9
17.627(3)
8.923(2)
10.116(2)
92.41(1)
1589.8(5)
1.23
8.533(3)
11.184(3)
18.845(2)
100.80(2)
1766.5(8)
1.208
8.542(5)
11.063(5)
18.763(6)
102.36(4)
1731(1)
1.389
â/deg
V/Å3
F
calc/g cm-3
1.21
µ/cm-1
6.51a
0.8b
6.466a
6.57a
35.1a
F(000)
552
312
615
680
744
crystal size /mm
used reflctns R
0.50 × 0.50 × 0.50
0.70 × 0.50 × 0.60
0.30 × 0.35 × 0.20
0.50 × 0.30 × 0.70
0.50 × 0.50 × 1.00
1587
2290
2234
2038
2220
R
RW
0.069
0.068
0.041
0.042
0.0554
0.061
0.045
0.039
0.047
0.05
a
b
Cu KR radiation was used.
Mo KR radiation was used.
Deter m in a tion of th e Con for m a tion of (E,E) or
(E,Z) Im id es in th e Cr ysta llin e sta tes. The relation-
ship between the substituents and the conformation of
the imide moiety is rather complex. The intermolecular
interaction due to the crystal packing force is one of the
most important factors in the crystals. A consistent re-
lationship does not appear to exist between the molecular
conformation and the substituents based solely on the
intramolecular interaction. However, the intramolecular
interaction of each chromophore may play an important
role in determining the conformation. Recent work has
suggested the existence of an interaction between the
C-H group and the π-electron system on the basis of the
conformational relationship associated with a series of
compounds that bear an aliphatic group on one side of
the molecule and a phenyl group on another.23 X-ray and
photochemical results indicate that tigloyl derivatives
1a -e except 1c prefer the (E,E) conformation. The
ORTEP diagrams indicate that the CH‚‚‚π interaction
between the â-methyl group and benzoyl phenyl ring
restrains the molecular conformation. As a result, the
distance between the â-methyl hydrogen atom and the
center of phenyl ring is 3.37 Å for 1a , 2.98 Å for 1d , and
3.16 Å for 1e.24
Of the methacryloyl derivatives (1f-j), only the iso-
propyl derivative (1f) crystallized in the (E,E) conforma-
tion. The others crystallized in the (E,Z) conformation.
Intramolecular interaction was not found in the crys-
tal of 1c. On the other hand, the alkenyl group and
phenyl ring were in closer proximity in the N-aryl
derivatives, and therefore this interaction may play an
important role in determining the molecular conforma-
tion; the distance between the alkenyl group and the edge
of the benzene ring was 3.26 Å for 1h , 3.38 Å for 1i, and
2.96 Å for 1j.
P h ot och em ica l R ea ct ion of t h e Im id es 1a -j in
Solu tion . We already reported that irradiation of 1f and
1g in benzene underwent [2 + 2] cyclization to bicyclic
oxetanes 2f and 2g in 96% and 99% yields, respectively.22
Photolysis of other imides in benzene also gave corre-
sponding oxetanes in high yields as shown in Table 4. In
the case of tigloyl derivatives 1a -1e, oxetanes were
obtained as a mixture of two stereoisomers. The ratio of
syn -2/a n ti-2 was 2.1, independent of the substituents on
the nitrogen atom. The stereochemistry was determined
on the basis of NOE experiments. Furtheremore, the
structure was established by X-ray single-crystal analysis
of syn -2a .
(23) Nishio, M; Umezawa, Y.; Hirota, M.; Takeuchi, Y. Tetrahedron
1995, 51, 8665-8701.
(24) J orgensen, W.; Seberance, L. J . Am. Chem. Soc. 1990, 112,
4768-4777.

Photochemical Reaction of Benzoylformamides
J . Org. Chem., Vol. 62, No. 18, 1997 6301
F igu r e 3. ORTEP drawings of the X-ray structures of 1a -1j.
P h ot och em ica l R ea ct ion of Im id es w it h t h e
Tigloyl Gr ou p (1a -e) in th e Solid Sta te. All crystals
are recrystallized from chloroform-hexane solution and
were photolyzed as powders sandwiched between Pyrex

6302 J . Org. Chem., Vol. 62, No. 18, 1997
Ta ble 3. Con for m a tion of Im id es 1 a n d th e Tor sion a l An gles
Sakamoto et al.
1
conformation
C1-N-C3-O3
C3-N-C1-O1
N-C1-C2-O2
N-C3-C4-C5
O2-C2-C6-C7
C1-N-C8-C9
1a
1c
1d
1e
1f
1g
1h
1i
E,E
E,Z
E,E
E,E
E,E
E,Z
E,Z
E,Z
E,Z
150.4
15.5
-178.3
-168.0
172.6
173.6
179.5
168.4
166.4
163.2
160.0
-60.5
72.0
-46.8
50.4
-7.5
3.0
8.6
13.3
-8.4
-9.1
-9.0
3.5
a
62.9
-77.9
98.8
a
155.5
157.9
147.0
-4.0
-8.7
-2.6
-15.0
-54.0
-56.8
-47.4
-76.9
-72.4
-79.9
-55.0
-47.3
-48.2
-35.9
-52.4
-56.3
-46.6
-36.9
a
-69.0
-75.9
-74.0
1j
4.9
a R2
is not an aryl group.
Ta ble 4. P h otolysis of Im id es 1a -j in Ben zen e
entry
yield of 2, % (syn/anti)
1a
1b
1c
1d
1e
1f
1g
1h
1i
100 (2.1)
100 (2.1)
76 (2.1)
100 (2.1)
100 (2.1)
96
99
100
100
100
F igu r e 4. Time course for the photoreaction of cis-1a ([) and
the formation of trans-1a (9), syn-2a (2), and anti-2a (b) in
benzene solution.
1j
glasses on the inside of a polyethylene bag with a 500-W
high-pressure mercury lamp.
Sch em e 2
When the powdered crystals of 1a were photolyzed at
0 °C for 1 h, bicyclic oxetane 2a was obtained as a
mixture of stereoisomers in 84% yield at a ratio of syn -
2a /a n ti-2a ) 3.7. X-ray crystal structural analysis of
1a indicated that the space group is chiral P21 (Table 1).
As expected, the major isomer syn -2a showed optical
activity, [R]20 +34 (c 1.0 in CHCl3), 35% ee (conversion
D
100%), whereas the minor isomer a n ti-2a was obtained
as a racemate. Unfortunately, the crystals melted during
irradiation under these conditions. The solid state pho-
toreaction proceeded, even at -78 °C, yielding the opti-
cally active (+)-syn -2a which showed a higher ee value,
[R]20 +95 (c 1.0 in CHCl3), >99% ee (conversion 100%,
D
chemical yield 89%, syn -2a /a n ti-2a ) 6.7).
racemization which takes place at the defect lattice sites
where a n ti-2a is formed.
To explain how the anti isomer was produced as a
racemate, the time course for consumption of 1a and the
formation of 2a (syn and anti isomers) was studied
(Figure 4). When 1a was irradiated in benzene, the yield
of 2a showed a roughly linear increase from the ini-
tial stage at the expense of 1a . During photolysis,
trans-1a was not detected at all, and both syn -2a and
a n ti-2a were formed constantly at syn -2a /a n ti-2a )
2.1 throughout the reaction, even after all 1a was
consumed. Thus, the photoreaction appears to proceed
via a diradical intermediate (3a ), and the direct cis-trans
isomerization of 1a and the back reaction from 3a to 1a
does not occur, as depicted in Scheme 2. On the basis of
these assumptions, racemic a n ti-2a is obtained as a
result of the solid state photoreaction due to the partial
The absolute configuration of (+)-2a was determined
by an indirect method to be (1R,5R,7R)-1,7-dimethyl-3-
isopropyl-5-phenyl-6-oxa-3-azabicyclo[3.1.1]heptane-2,4-
dione. That of thiocarbonyl derivative (-)-syn -4a ob-
tained by thionation of (+)-syn -2a was determined by
X-ray crystallographic analysis using anomalous scat-
tering method to be (1R,5R,7R)-1,7-dimethyl-3-isopropyl-
5-ph en yl-4-oxo-6-oxa -3-a za bicyclo[3.1.1]h ept a n e-2-
thione (Scheme 3). Direct determination of the absolute
configuration of 1a in the chiral crystal could not be
performed. However, it is reasonably concluded that one
enantiomorph, which yielded (+)-syn -2a by the solid
state photolysis, should be consistent with the M config-
uration shown in Figure 3a and Scheme 3.

Photochemical Reaction of Benzoylformamides
J . Org. Chem., Vol. 62, No. 18, 1997 6303
Sch em e 3
Ta ble 5. P h otolysis of Im id es 1a -j in th e Solid Sta te
entry
reactn temp (°C)
yield of 2, % (syn/anti)
ee (%)
1a
1a
1b
1b
1c
1d
1e
1f
0
-78
15
-78
0
15
15
0
84 (3.7)
89 (6.7)
100 (60)
100 (60)
0b
35a
99a
91a
91a
100 (27)
100 (20)
68 (31)c
50 (15)d
0f
0
0
0
1g
1h
1i
0
0 (88)e
15
15
15
0f
1j
0f
a
b
ee of syn -2. Only cis-trans isomerization took place and the
ratio of cis-1c/tr a n s-1c was 1.3. c Chemical yield of 5f. Chemi-
d
cal yield of 6g. e ee of 6g. f Starting materials were recovered.
Solid state photolysis of 1b also yielded oxetane 2b,
but the reaction proceeded more stereoselectively than
that of 1a with the ratio of syn/anti ) 60 (Table 5).
Unfortunately, a single crystal could not be obtained from
1b for X-ray single-crystal analysis. However, the crystal-
to-crystal transformation was followed by X-ray powder
diffraction. Figure 5 shows the diffraction patterns which
indicate that the transformation proceeds effectively to
oxetane 2b while retaining a crystal lattice (F-2). After
30 min, all of the starting material changed to oxetane
(F-3). F-4 shows the diffraction pattern that differs from
that of recrystallized oxetane 2b. This indicates that
photolyzed crystals are metastable.
F igu r e 5. X-ray diffraction patterns for the transformation
of 1b to 2b. (F-1) Starting material 1b. (F-2) Irradiated for
5 min. (F-3) Irradiated for 30 min. (F-4) Recrystallized 2b
from CHCl3-hexane.
Whereas the space group of 1b was ambiguous, oxe-
tane syn -2b obtained by solid state photolysis at 15 °C
was optically active, [R]20 ) +57, 91% ee as shown in
D
Table 5. Low-temperature photolysis (-78 °C) produced
similar results in which there was no change in the
ratio of syn -2b/a n ti-2b or the ee value because the
solid state reaction proceeded via the crystal-to-crystal
path, even at room temperature. Enantiomorphic 1b was
also obtained by spontaneous resolution, and both enan-
tiomers were synthesized selectively by the seeding
method.
Solid state photolysis of 1c showed that the crystal
differed remarkably from 1a and 1b with respect to
photochemical behavior. X-ray single-crystal analysis
revealed that the crystal was a orthorhombic achiral
space group Pca21 with an (E,Z) conformation which is
disadvantageous for oxetane formation (Figure 3c). In
this case, oxetane was not obtained but a photostationary
state of cis-1c/tr a n s-1c ) 1.3 was obtained.1,25 Photo-
chemical cis-trans isomerization was also observed in
the benzene solution during the early stage of the
reaction (cis/trans ) 1.4). Since structural modification
resulting from rotation of the C(dO)sN bond from (E,Z)
to (E,E) is allowed in solution, the following two reactions
occur competitively: (a) cis-trans isomerization and (b)
oxetane formation from an (E,E) conformer.
As expected from X-ray analysis, solid state photolysis
of 1d yielded racemic oxetane 2d in a 100% yield (syn/
anti ) 27). Photolysis of 1e also yielded racemic oxetane
2e in the ratio of syn/anti ) 20. In both cases, the crystal-
to-crystal transformations were observed and followed by
X-ray powder diffraction. Figures 6 and 7 show the
diffraction patterns of solid state photolysis of 1d and
1e. These indicate that the transformation progressed
effectively to oxetanes 2d and 2e while retaining a crystal
lattice.
P h otoch em ical Reaction of Im ides with th e Meth -
a cr yloyl gr ou p (1f-j) in th e Solid Sta te. X-ray
crystallographic analysis of 1f revealed that the molec-
ular conformation was (E,E) and the space group was
achiral, P21/a (Table 2, Figure 3f). The molecular con-
formation in the crystal is suitable for oxetane formation.
(25) Kinbara, K.; Saigo, K. Bull. Chem. Soc. J pn. 1996, 69, 779-
784 and references cited therein.

6304 J . Org. Chem., Vol. 62, No. 18, 1997
Sakamoto et al.
F igu r e 7. X-ray diffraction patterns for the transformation
of 1e to 2e. (F-1) Starting material 1e. (F-2) Transition
pattern. (F-3) Irradiated crystals (100% conversion). (F-4)
Recrystallized 2e from CHCl3-hexane.
F igu r e 6. X-ray diffraction patterns for the transformation
of 1d to 2d . (F-1) Starting material 1d . (F-2) Transition
pattern. (F-3) Irradiated crystals (100% conversion). (F-4)
Recrystallized 2d from CHCl3-hexane.
Sch em e 4
When the crystals were irradiated in the solid state, the
corresponding oxetane 2f was obtained as well as an
unexpected product, azetidine-2,4-dione 5f in 68% and
31% yields, respectively (Scheme 4).
The formation of 5f can be explained in terms of
cyclization that results in 1,4-diradical formation by an
R-cleavage reaction that involves a 1,5-benzoyl shift.26
The (E,E) conformation is also preferred for the 1,5-
benzoyl shift. The distance between carbonyl carbon C9
and alkenyl â-carbon C3 was 2.84 Å, which is shorter
than the sum of the van der Waals radii (3.0 Å). Figure
8 shows the correlation between the conversion rates and
chemical yields of 2f and 5f in the solid state photore-
action at 0 °C. The photolysate melts at a conversion
rate of approximately 50%. During this process, the
photolyzed crystals maintained the crystalline phase and
the yields of both 2f and 5f increased as a result of the
increased conversion. After the crystals melt, only ox-
etane was obtained. These results indicate that the
topochemically-allowable solid state photoreaction domi-
nates both the 1,5-benzoyl shift and oxetane formation.
Photochemical reaction of 1g in the solid state showed
a different behavior from that in solution chemistry. In
solution, imide 1g underwent photocyclization which led
to formation of the corresponding oxetane 2g in a 99%
yield. On the other hand, irradiation of the crystals gave
(26) Aoyama, H.; Sakamoto, M.; Omote, Y. J . Chem. Soc., Chem.
Commun. 1982, 119-120.

Photochemical Reaction of Benzoylformamides
J . Org. Chem., Vol. 62, No. 18, 1997 6305
F igu r e 9. Correlation diagram of the conversion of 1g versus
the chemical yields of 2g ([) and 6g (9). (4) ee of 6g.
F igu r e 8. Correlation diagram between the conversion and
the chemical yields of 2f ([) and 5f (9) in the solid state
photolysis at 0 °C.
azetidinone via hydrogen transfer by the alkenyl carbon
atom is a topochemically-controlled process. Further-
more, oxetane 2g was formed in the defect crystal lattice
in which the (E,Z) conformation changed to the energeti-
cally more stable (E,E) conformation. Therefore, racemic
oxetane 2g was obtained during solid state photolysis,
even in the chiral crystal environment. The same
phenomenon was observed during solid state photolysis
of 1a in which racemic a n ti-2a was formed after the
chirality of the crystal was no longer apparent.
Sch em e 5
Scheffer et al. examined the solid state hydrogen
transfer by the alkenyl carbon atom and defined the
important geometrical parameters of the hydrogen trans-
fer reaction.1 In the case of 1g, conformation in the
crystalline state is apparently advantageous for the
formation of azetidinone 6g (Figure 3). The angle
between the Pz orbital of alkenyl carbon C7 and the
benzylic hydrogen atom (H14) was 64.8° (ideal 90°), and
the intramolecular distance between the C7 and the H14
was 2.61 Å which is much shorter than the sum of the
van der Waals radii (2.90 Å).
both 2g and a topochemical product, azetidin-2-one 6g,
in 40% and 20% yields, respectively, at a 66% conversion
rate (Scheme 5). X-ray crystallographic analysis of 1g
shows that the space group of the crystal was chiral, P21
(Table 2), and isolated azetidin-2-one 6g exhibited optical
activity [R]20D ) +112, 88% ee. However, oxetane 2g that
possesses two chiral centers was obtained as a racemate.
The mechanism associated with the transformation of
1g to 6g can be reasonably explained in terms of
hydrogen abstraction by the alkenyl carbon leading to a
1,4-biradical (Scheme 5).27,28 The ORTEP diagram shows
that the conformation of the imide chromophore was
(E,Z), which is disadvantageous for oxetane formation
(Figure 3). Formation of 2g requires structural modifica-
tion from an (E,Z) to (E,E) conformation, which is
impossible to perform in the crystalline state. Figure 9
shows the time course for the chemical yields of both 2g
and 6g and that of the ee value for 6g versus the
conversion of 1g. At the early stage of the reaction,
azetidinone 6g was formed preferentially. As the conver-
sion rate increased, formation of oxetane 2g became
accelerated. Throughout the reaction, the ee value of the
resultant azetidinone ranges from 85% to 88% within the
acceptable experimental error whereas that of oxetane
was zero. On the basis of these results, the formation of
Photolysis of imides 1h -j in benzene solution yielded
the corresponding oxetanes in quantitative amounts.
However, crystals of the imides were nonreactive to
photolysis. This poor reactivity may be explained on the
basis of the molecular conformation in the solid state
(Figures 3h-j). X-ray crystallographic analysis of 1h , 1i,
and 1j revealed that all the crystals are members of the
monoclinic space group P21/c and the conformation was
(E,Z) which is disadvantageous for oxetane formation.
Rela tion sh ip betw een th e Con for m a tion of th e
Im id es a n d P h ot or ea ct ivit y. Table 6 shows the
relationship between the molecular conformation and the
geometric parameters of the reacting carbonyl and alk-
enyl double bonds for oxetane formation. In the (E,E)
conformation, the double bonds are maintained in close
proximity, such that the distance between the reacting
carbonyl oxygen and alkenyl carbon is 2.8-3.1 Å and that
between carbonyl carbon and the alkenyl carbon is 2.8-
3.0 Å. In this case, the double bonds are almost parallel
(dihedral angle < 23°). In the (E,Z) conformation, the
molecules are unreactive to oxetane formation, and the
distance between carbonyl oxygen and alkenyl carbon is
4.5-4.8 Å, which is considerably longer than the sum of
the van der Waals radii (3.22 Å). Furthermore, the
reacting carbonyl carbon and alkenyl carbon atoms
exceed the sum of the van der Waals radii (3.4 Å) by a
considerable margin. Photochemical reactivity was pri-
marily influenced by the conformation of the imide
chromophore.
(27) Aoyama, H.; Hasegawa, T.; Okazaki, M. J . Chem. Soc., Perkin
Trans. 1 1979, 263-268.
(28) Sakamoto, M.; Kimura, M.; Shimoto, T.; Fujita, T.; Watanabe,
S. J . Chem. Soc., Chem. Commun. 1990, 1214-1215.
(29) The author has deposited atomic coordinates for structures
1a ,c-j, syn-2a , and syn-4a with the Cambridge Crystallographic Data
Centre. The coordinates can be obtained, on request, from the Director,
Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge,
CB2 1EZ, UK.

6306 J . Org. Chem., Vol. 62, No. 18, 1997
Sakamoto et al.
Ta ble 6. Geom etr ica l P a r a m eter for th e Oxeta n e
F or m a tion
N-Ben zyl-N-tigloylben zoylfor m a m id e (1b) was obtained
as a colorless powder: yield 80%; mp 44-45 °C; IR (cm-1, KBr)
1660, 1640, 1710; UV (nm, CH3CN) 257 (ꢀ 7000), 346 (ꢀ 40);
1H NMR (CDCl3) δ 0.98 (qd, J ) 1.0 and 6.6 Hz, 3H), 1.62
(brs, 3H), 5.06 (s, 2H), 5.82 (dq, J ) 1.0 and 6.6 Hz, 1H), 7.2-
7.6 (m, 8H), 7.9-8.0 (m, 2H); 13C NMR (CDCl3) δ 12.7 (q), 46.9
(t), 127.7 (d), 128.3 (d), 128.6 (d), 128.8 (d), 129.5 (d), 134.4
(d), 136.4 (s), 136.5 (d), 132.8 (s), 137.0 (s), 169.1 (s), 173.8 (s),
185.9 (s). Anal. Calcd for C20H19O3N: C, 74.73; H, 5.96; N,
4.36. Found: C, 74.65; H, 6.02; N, 4.32.
distance between
dihedral angle
reacting atoms
of CdO
1
conformation
C‚‚‚Ob
C‚‚‚Cc
and CdCd
1a
1b
1c
1d
1e
1f
1g
1h
1i
E,E
E,Ea
E,Z
E,E
E,E
E,E
E,Z
E,Z
E,Z
E,Z
2.98
2.99
22.9
3.79
2.68
2.98
2.78
4.71
4.50
4.47
4.54
4.75
2.70
2.98
2.84
5.28
4.91
5.19
5.18
36.0
23.3
23.4
20.6
31.7
33.6
34.3
41.0
N-Tigloylben zoylfor m a n ilid e (1c) was obtained as a
colorless prismatic crystal: yield 78%; mp 91-92 °C; IR (cm-1
,
KBr) 1670, 1690; UV (nm, CH3CN) 250 (ꢀ 15 100), 350 (ꢀ 90);
1H NMR (CDCl3) δ 1.46 (qd, J ) 1.0 and 6.9 Hz, 3H), 1.62
(brs, 3H), 6.40 (dq, J ) 1.0, 6.9 Hz, 1H), 7.2-7.7 (m, 7H), 8.0-
8.1 (m, 2H); 13C NMR (CDCl3) δ 12.7 (q), 13.9 (q), 127.6 (d),
128.5 (d), 128.7 (d), 129.3 (s), 129.5 (d), 129.8 (d), 132.8 (s),
139.6 (d), 132.9 (s), 134.2 (d), 169.6 (s), 173.9 (s), 187.2 (s).
Anal. Calcd for C19H17O3N: C, 74.20; H, 5.57; N, 4.56.
Found: C, 74.20; H, 5.36; N, 4.48.
1j
a
The conformation was speculated from the experimental
b
results. Distance between the reacting alkenyl â-carbon and the
benzoyl carbonyl oxygen atoms. c Distance between the reacting
d
alkenyl R-carbon and the benzoyl carbonyl carbon atoms. Di-
hedral angle of the reacting double bond.
N-Tigloylben zoyl-o-m et h ylfor m a n ilid e (1d ) was ob-
tained as a colorless prismatic crystal: yield 72%; mp 77-78
°C; IR (cm-1, KBr) 1640, 1670, 1710; UV (nm, CH3CN) 210 (ꢀ
Con clu sion
1
24 800), 251 (ꢀ 12 300), 336 (ꢀ 170); H NMR (CDCl3) δ 1.38
(qd, J ) 1.0 and 6.8 Hz, 3H), 1.62 (brs, 3H), 2.31 (s, 3H), 6.31
(dq, J ) 1.0 and 6.8 Hz, 1H), 7.1-7.7 (m, 7H), 8.0-8.1 (m,
2H); 13C NMR (CDCl3) δ 12.7 (q), 13.7 (q), 17.7 (s), 127.0 (d),
128.3 (d), 128.8 (d), 129.1 (d), 129.7 (d), 131.5 (d), 132.8 (s),
133.5 (s), 134.2 (d), 135.6 (s), 136.1 (s), 138.2 (d), 169.6 (s),
173.6 (s), 186.8 (s). Anal. Calcd for C20H19O3N: C, 74.58; H,
5.92; N, 4.35. Found: C, 74.75; H, 5.96; N, 4.36.
N-Tigloylben zoyl-2,6-d im eth ylfor m a n ilid e (1e) was ob-
tained as a colorless prismatic crystal: yield 75%; mp 106-
107 °C; IR (cm-1, KBr) 1670, 1715; UV (nm, CH3CN) 254 (ꢀ
11 600), 339 (ꢀ 130); 1H NMR (CDCl3) δ 1.28 (qd, J ) 1.3 and
6.9 Hz, 3H), 1.65 (d, J ) 1.3 Hz, 3H), 2.29 (s, 6H), 6.24 (dq, J
) 1.3, 6.9 Hz, 1H), 7.1-7.7 (m, 6H), 7.9-8.1 (m, 2H); 13C NMR
(CDCl3) δ 12.8 (q), 13.5 (q), 18.1 (s), 128.8 (d), 128.9 (d), 129.1
(d), 129.6 (d), 132.9 (s), 134.2 (d), 136.2 (s), 137.1 (d), 169.8
(s), 173.0 (s), 186.5 (s). Anal. Calcd for C21H21O3N: C, 75.19;
H, 6.31; N, 4.18. Found: C, 75.04; H, 6.29; N, 4.13.
Photolysis of the ten N-(R,â-unsaturated carbonyl)ben-
zoylformamides yielded cross-type oxetanes under ho-
mogeneous conditions. In contrast, irradiation of these
compounds in the solid state resulted in a considerably
different photochemical behavior in which the molecular
conformation in the crystalline phase reflected the pho-
toreactivity and photoproducts. New topochemically-
controlled reactions observed during azetidine-2,4-dione
formation and hydrogen abstraction by the alkenyl
carbon atom are reactions that can only be observed in
the solid state. Three of the ten achiral imides yielded
chiral crystals by spontaneous resolution. The solid state
photolysis yielded optically active compounds. These
reactions provide two examples of absolute asymmetric
synthesis, oxetane formation by intramolecular 2 + 2
cycloaddition and â-lactam synthesis from the hydrogen
abstraction by an alkenyl carbon atom.
N-Meth a cr yloylben zoylfor m a n ilid e (1h ) was obtained
as a colorless prismatic crystal: yield 72%; mp 101-102 °C;
IR (cm-1, KBr) 1675, 1700, 1710; UV (nm, CH3CN) 252 (ꢀ
1
15 500), 336 (ꢀ 170); H NMR (CDCl3) δ 1.77 (d, J ) 1.3 Hz,
Exp er im en ta l Section
3H), 5.42 (d, J ) 1.3 Hz, 1H), 5.58 (brs, 1H), 7.2-7.7 (m, 8H),
7.9-8.1 (m, 2H); 13C NMR (CDCl3) δ 18.7 (q), 126.4 (t,), 127.7
(d), 128.8 (d), 129.6 (d), 129.8 (d), 132.8 (s), 134.3 (d), 136.6
(s), 139.1 (s), 169.8 (s), 173.1 (s), 187.2 (s). Anal. Calcd for
C18H15O3N: C, 73.79; H, 5.12; N, 4.78. Found: C, 73.63; H,
5.03; N, 4.72.
Gen er a l. NMR spectra were recorded on CDCl3 solutions
on a J EOL FX-270, GSX-400, and GSX-500 operating at 270,
400, or 500 MHz are referenced to 0 ppm relative to TMS as
internal standard. Elemental analyses were made using a
Perkin-Elmer-240 instrument. IR spectra were recorded on
J ASCO IR-420 or FT/IR-230 spectrometers as KBr disks,
unless otherwise noted. Optical rotations were determined on
a J ASCO DIP-370 polarimeter operating at the sodium D line
in CHCl3 solution at the concentration of c ) 1.0.
Gen er a l P r oced u r e for th e P r ep a r a tion of N-(r,â-
Un sa t u r a t ed ca r b on yl)b en zoylfor m a m id es 1a -j. All
N-(R,â-unsaturated carbonyl)benzoylformamides 1a -j were
prepared by the condensation of benzoylformyl chloride and
corresponding R,â-unsaturated amides in the presence of
triethylamine according to the literature.22 The structures of
the imides 1a -e, 1h , and 1j were determined on the basis of
spectral data. Those of imides 1f, 1g, and 1i, were confirmed
by the comparison of the spectral data cited in the literature.
N-Met h a cr yloylb en zoyl-2,6-d ich lor ofor m a n ilid e (1j)
was obtained as a colorless prismatic crystal: yield 70%; mp
125-126 °C; IR (cm-1, KBr) 1680, 1690, 1720; UV (nm,
CH3CN) 252 (ꢀ 14 500); 1H NMR (CDCl3) δ 1.90 (d, J ) 1.3
Hz, 3H), 5.37 (d, J ) 1.3 Hz, 1H), 5.58 (br s, 1H), 7.2-7.7
(m, 6H), 7.9-8.1 (m, 2H); 13C NMR (CDCl3) δ 18.8 (q), 124.0
(t), 128.8 (d), 129.1 (d), 129.7 (d), 130.8 (d), 132.8 (s), 133.0
(s), 135.0 (s), 168.6 (s), 171.6 (s), 185.8 (s). Anal. Calcd for
C18H13O3NCl2: C, 59.83; H, 3.63; N, 3.88. Found: C, 59.91;
H, 3.67; N, 3.79.
Gen er a l P r oced u r e for th e P h otoch em ica l Rea ction
in Ben zen e. A benzene solution of imides 1a -1j (0.02 M/L)
was purged with deoxygenated and dried argon for 15 min
prior to photolysis and irradiation with a 500-W high-pressure
mercury lamp through a Pyrex filter. After irradiation, the
photolysate was chromatographed using Merk kieseigel 60
with benzene as the eluent. Crystalline products were recrys-
tallized from a chloroform-hexane mixture.
N-Isop r op yl-N-tigloylben zoylfor m a m id e (1a ) was ob-
tained as a colorless needle crystal: yield 75%; mp 65-66 °C;
IR (cm-1, KBr) 1650, 1710; UV (nm, CH3CN) 256 (ꢀ 11 600),
1
351 (ꢀ 140); H NMR (CDCl3) δ 1.05 (qd, J ) 0.7 and 6.8 Hz,
3H), 1.47 (d, J ) 7.0 Hz, 6H), 1.60 (brs, 3H), 4.78 (sept, J )
7.0 Hz, 1H), 6.03 (dq, J ) 0.7 and 6.8 Hz, 1H), 7.4-7.7 (m,
3H), 7.9-8.0 (m, 2H); 13C NMR (CDCl3) δ 12.5 (q), 13.0 (q),
19.6 (q), 48.2 (d), 128.7 (d), 129.6 (d), 132.9 (s), 134.2 (d), 137.5
(d), 138.3 (s), 168.8 (s), 174.4 (s), 186.4 (s). Anal. Calcd for
C16H19O3N: C, 70.31; H, 7.01; N, 5.12. Found: C, 70.50; H,
6.98; N, 5.04.
Gen er a l P r oced u r e for th e P h otoch em ica l Rea ction
in th e Solid Sta te. All of the solid state photolyses were done
under an atmosphere of deoxygenated and dried nitrogen.
Solid samples were irradiated as powders sandwiched between
Pyrex glasses on the inside of polyethylene bags and were fixed
outside of an emersion well apparatus and cooled during the
photolysis in either a water bath (15 °C) or an ice-water bath

Photochemical Reaction of Benzoylformamides
J . Org. Chem., Vol. 62, No. 18, 1997 6307
(at 0 °C). Sandwiched glasses incorporated into Pyrex tubes
were used for the solid state photolysis at -78 °C with a dry
ice/methanol bath. After irradiation, the photolysate was
treated in the same way as the photoreaction in solution.
Ir r a d ia t ion of N-Isop r op yl-N-t igloylb en zoylfor m a -
m id e (1a .) After irradiation of a benzene solution (0.02 M)
at 100% conversion, one fraction was isolated as an oil in a
100% yield by column chromatography on silica gel. An 1H
NMR spectrum revealed that it was composed of a mixture of
two stereoisomers (2.1:1). Each stereoisomer was separated
by preparative HPLC using Capcell Pak C18 (Shiseido) with
MeCN/H2O ) 4:1 as eluent. The enantiomeric purity was
determined by 1H NMR spectroscopy employing 0.3 equiv of
Eu(hfc)3 (Aldrich).
syn -1,7-Dim et h yl-3-isop r op yl-5-p h en yl-6-oxa -3-a za b i-
cyclo[3.1.1]h ep ta n e-2,4-d ion e (syn -2a ) (major isomer): mp
112-113 °C; IR (cm-1, KBr) 1685, 1745; UV (nm, CH3CN) 257
(ꢀ 550); 1H NMR (CDCl3) δ 1.05 (d, J ) 7.0 Hz, 3H), 1.45 (d, J
) 7.0 Hz, 3H), 1.46 (d, J ) 7.0 Hz, 3H), 1.50 (s, 3H), 3.15 (q,
J ) 7.0 Hz, 1H), 4.82 (sept, J ) 7.0 Hz, 1H), 7.2-7.5 (m, 5H);
13C NMR (CDCl3) δ 10.4 (q), 14.5 (q), 19.3 (q), 44.0 (d), 51.6
(d), 84.6 (s), 87.2 (s), 125.9 (d), 127.9 (d), 128.2 (d), 132.4 (s),
172.6 (s), 174.1 (s). Anal. Calcd for C16H19O3N: C, 70.31; H,
7.01; N, 5.12. Found C, 70.35; H, 6.81; N, 5.09.
NMR (CDCl3) δ 1.01 (d, J ) 7.2 Hz, 3H), 1.59 (s, 3H,), 3.50 (q,
J )7.2 Hz, 1H), 4.97 (s, 2H), 7.1-7.5 (m, 10H); 13C NMR
(CDCl3) δ 9.86 (q), 18.7 (q), 42.2 (t), 56.3 (d), 86.6 (s), 88.6 (s),
125.0 (d), 128.4 (d), 128.8 (d), 129.2 (d), 130.5 (d), 134.5 (d),
135.8 (s), 136.3 (s), 171.3 (s), 172.3 (s).
tr a n s-N-Tigloylben zoylfor m an ilide (tr a n s-1c): 1H NMR
(CDCl3) δ 1.70 (s, 3H), 1.75 (d, J ) 7.3 Hz, 3H), 5.48 (q, J )
7.3 Hz, 1H), 7.2-7.5 (m, 8H), 7.6-7.7 (m, 2H); 13C NMR
(CDCl3) δ 12.8 (q), 13.9 (q), 127.6 (d), 127.7 (d), 128.4 (d), 128.7
(d), 129.5 (d), 129.6 (d), 129.8 (d), 131.8 (s), 134.1 (s), 134.2
(s), 139.6 (s), 169.2 (s), 172.0 (s), 173.5 (s).
syn -1,7-Dim e t h yl-3,5-d ip h e n yl-6-oxa -3-a za b icyclo-
[3.1.1]h ep ta n e-2,4-d ion e (syn -2c) (major isomer): mp 159-
160 °C; IR (cm-1
, KBr) 1700, 1760; UV (nm, CH3CN)
251 (ꢀ 1000); 1H NMR (CDCl3) δ 1.11 (d, J ) 6.9 Hz, 3H), 1.58
(s, 3H), 3.43 (q, J ) 6.9 Hz, 1H), 7.2-7.6 (m, 10H); 13C
NMR (CDCl3) δ 10.5 (q), 14.6 (q), 51.5 (d), 84.9 (s), 87.4 (s),
125.1 (d), 128.1 (d), 128.3 (d), 128.4 (d), 128.8 (d), 129.2 (d),
132.5 (s), 135.7 (s), 172.0 (s), 173.5 (s). Anal. Calcd for
C19H17O3N: C, 74.20; H, 5.57; N, 4.56. Found: C, 73.98; H,
5.61; N, 4.51.
a n t i-1,7-Dim e t h yl-3,5-d ip h e n yl-6-oxa -3-a za b icyclo-
[3.1.1]h ep ta n e-2,4-d ion e (a n ti-2c) (minor isomer): 1H NMR
(CDCl3) δ 1.37 (d, J ) 6.9 Hz, 3H), 1.68 (s, 3H), 3.62 (q, J )
6.9 Hz, 1H), 7.2-7.6 (m, 10H); 13C NMR (CDCl3) δ 10.4 (q),
18.9 (q), 55.9 (d), 86.9 (s), 88.8 (s), 126.0 (d), 127.9 (d), 128.2
(d), 128.8 (d), 128.9 (d), 129.2 (d), 132.0 (s), 132.7 (s), 170.9
(s), 172.0 (s).
syn -1,7-Dim et h yl-5-d ip h en yl-6-oxa -3-(o-t olyl)-3-a za -
bicyclo[3.1.1]h ep ta n e-2,4-d ion e (syn -2d ) (Ma jor Isom er ).
This material was composed of two rotamers owing to the
rotation of o-tolyl group and the ratio was 1.9:1: mp 164-165
°C; IR (cm-1, KBr) 1690, 1750; UV (nm, CH3CN) 255 (ꢀ 3000),
285 (ꢀ 810); 1H NMR (CDCl3) δ 1.12 and 1.13 (each d, J )
6.9 Hz, total 3H), 1.58 (d, J ) 1.0 Hz, 3H), 2.23 (s, 3H),
3.45 (dq, J ) 1.0 and 6.9 Hz, 1H), 7.1-7.5 (m, 9H); 13C NMR
(CDCl3) δ 10.5 (q), 14.6 (q), 17.2, 17.6 (q), 51.6 and 51.7 (each
d), 85.0 and 85.1 (each s), 87.5 (s), 126.0 (d), 126.8 (d), 127.1
(d), 127.9 (d), 128.4 (d), 128.6 (d), 129.3 (d), 129.4 (d), 131.0
(d), 131.1 (d), 131.7 (s), 131.8 (s), 132.0 (s), 136.1 (s), 136.3 (s),
171.7 and 171.8 (each s), 173.3 and 173.5 (each s). Anal. Calcd
X-r a y cr yst a llogr a p h ic a n a lysis of syn -1,7-d im et h yl-
3-isop r op yl-5-p h en yl-6-oxa -3-a za b icyclo[3.1.1]h ep t a n e-
2,4-d ion e (syn -2a ): colorless prismatic crystals from hexane-
chloroform, space group P21, a ) 10.195(2) Å, b ) 7.231 (4) Å,
c ) 10.860(2) Å, â ) 112.05(1)°, V ) 742.0(4) Å3, Z ) 2, F )
1.219 g/cm3, µ(Cu KR) ) 6.85 cm-1; R ) 0.040, RW ) 0.034 for
2350 reflections.
Syn th esis a n d th e Deter m in a tion of th e Absolu te
Con figu r a tion of syn -1,7-Dim eth yl-3-isop r op yl-5-p h en yl-
4-oxo-6-oxa -3-a za bicyclo[3.1.1]h ep ta n e-2-th ion e (syn -4a ).
A toluene solution of optically pure syn-(+)-2a , which was
obtained by recrystallization of 95% ee of 2a , and 0.5 equiv of
Lawesson’s reagent was refluxed for 2 h. Toluene was
removed in vacuo, and the residual mixture was subjected to
silica gel column chromatography using benzene as eluent.
syn-(-)-1,7-Dimethyl-3-isopropyl-5-phenyl-4-oxo-6-oxa-3-
azabicyclo[3.1.1]heptane-2-thione (syn-4a ) was isolated in 90%
yield and recrystallized from a chloroform-hexane mixture:
for C20
H19O3N: C, 74.58; H, 5.92; N, 4.35. Found: C, 74.68;
)
H, 5.94; N, 4.34.
slightly yellow prismatic crystals, space group P21, a
10.976(4) Å, b ) 7.241(2) Å, c ) 10.407(4) Å, â ) 111.25(1)°, V
) 770.9(4) Å3, Z ) 2, F ) 1.25 g/cm3, µ(Cu KR) ) 1.54 cm-1; R
) 0.0665, RW ) 0.0796 for 1722 reflections. The structure was
solved by the direct method and refined by the method of full-
matrix least-squares. The absolute configuration was deter-
mined through refinement of Roger’s parameter, whose value
was 1.074, as (1R,5R,7R)-4a : mp 84-85 °C; IR (cm-1, KBr)
1730; UV (nm, CH3CN) 285 (ꢀ 17 800); 1H NMR (CDCl3) δ 1.05
(d, J ) 7.0 Hz, 3H), 1.48 (d, J ) 7.0 Hz, 3H), 1.50 (d, J ) 7.0
Hz, 3H), 1.68 (s, 3H), 3.11 (q, J ) 7.0 Hz, 1H), 5.66 (sept, J )
7.0 Hz, 1H) , 7.2-7.5 (m, 5H); 13C NMR (CDCl3) δ 11.1 (q),
18.3 (q), 19.1 and 19.7 (q), 50.7 (d), 52.5 (d), 86.8 (s), 88.8 (s),
126.0 (d), 127.9 (d), 128.3 (d), 132.2 (s), 169.9 (s), 211.1 (s).
a n ti-1,7-Dim et h yl-3-isop r op yl-5-p h en yl-6-oxa -3-a za -
bicyclo[3.1.1]h ep ta n e-2,4-d ion e (a n ti-2a ) (minor isomer):
1H NMR (CDCl3) δ 1.19 (d, J ) 7.0 Hz, 3H), 1.46 (d, J ) 7.0
Hz, 3H), 1.47 (d, J ) 7.0 Hz, 3H), 1.59 (s, 3H), 3.47 (q, J )
7.0 Hz, 1H), 4.82 (sept, J ) 7.0 Hz, 1H), 7.2-7.5 (m, 5H); 13C
NMR (CDCl3) 10.1 (q), 18.8 (q), 19.5 (q), 44.3 (d), 55.8 (d), 86.6
(s), 88.6 (s), 125.1 (d), 128.3 (d), 128.6 (d), 136.1 (s), 171.5 (s),
172.6 (s).
a n ti-1,7-Dim et h yl-5-d ip h en yl-3-(o-t olyl)-6-oxa -3-a za -
bicyclo[3.1.1]h ep ta n e-2,4-d ion e (a n ti-2d ) (Min or Isom er ).
This material was composed of two rotamers owing to the
rotation of o-tolyl group and the ratio was 1.9:1: 1H NMR
(CDCl3) δ 1.40 and 1.44 (each d, J ) 7.0 Hz, 3H), 1.69 (s, 3H),
2.19 and 2.31 (each s, 3H), 3.62 (q, J ) 6.9 Hz, 1H), 7.1-
7.5 (m, 9H); 13C NMR (CDCl3) δ 10.4 and 10.8 (each q),
18.6 (q), 18.9 (q), 55.8 and 56.0 (each d), 87.0 and 87.2 (each
s), 88.9 (s), 125.1 (d), 126.7 (d), 128.3 (d), 128.6 (d), 128.8 (d),
129.4 (d), 131.2 (d), 131.6 (s), 135.7 (s), 136.2 (s), 170.8 (s),
171.8 (s).
syn -1,7-Dim et h yl-5-p h en yl-3-(2,6-xylyl)-6-oxa -3-a za -
bicyclo[3.1.1]h ep ta n e-2,4-d ion e (syn -2e) (major isomer):
mp 197-198 °C; IR (cm-1, KBr) 1690, 1750; UV (nm, CH3CN)
1
263 (ꢀ 890); H NMR (CDCl3) δ 1.13 (d, J ) 6.9 Hz, 3H), 1.59
(s, 3H), 2.14 (s, 3H), 2.21 (s, 3H), 3.47 (q, J ) 6.9 Hz, 1H),
7.1-7.5 (m, 8H); 13C NMR (CDCl3) δ 10.5 (q), 14.6 (q), 17.3,
(q), 17.8 (q), 51.5 (d), 85.3 (s), 87.7 (s), 126.0 (d), 127.9 (d), 128.4
(d), 128.6 (d), 129.1 (d), 132.0 (s), 136.0 (s), 136.2 (s), 171.4 (s),
173.0 (s). Anal. Calcd for C21H21O3N: C, 75.19; H, 6.31; N,
4.18. Found: C, 75.16; H, 6.24; N, 4.12.
syn -3-Be n zyl-1,7-d im e t h yl-5-p h e n yl-6-oxa -3-a za b i-
cyclo[3.1.1]h ep ta n e-2,4- d ion e (syn -2b) (major isomer): mp
112-113 °C; IR (cm-1, KBr) 1700, 1755; UV (nm, CH3CN) 257
a n ti-1,7-Dim et h yl-5-p h en yl-3-(2,6-xylyl)-6-oxa -3-a za -
bicyclo[3.1.1]h ep ta n e-2,4-d ion e (a n ti-2e) (minor isomer):
1H NMR (CDCl3) δ 1.46 (d, J ) 7.0 Hz, 3H), 1.69 (s, 3H), 2.17,
2.29 (s, 3H), 3.66 (q, 7.0 Hz, 1H), 7.1-7.5 (m, 8H); 13C NMR
(CDCl3) δ 10.7 (q), 17.6 (q), 19.1 (q), 19.7 (q), 55.7 (d), 87.5 (s),
89.2 (sO), 127.1 (d), 128.3 (d), 128.7 (d), 129.4 (s), 131.1(s),
131.2 (d), 135.7 (s), 136.2 (s), 171.0 (s), 173.1 (s).
3-(Ben zoylm eth yl)-1-isop r op yl-3-m eth yla zetid in e-2,4-
d ion e (5f): mp 79-80 °C; IR (cm-1, KBr) 1680, 1720; UV (nm,
CH3CN) 244 (ꢀ 12 400), 280 (ꢀ 12 900); 1H NMR (CDCl3) δ 1.49
(d, J ) 6.8 Hz, 6H), 1.49 (s, 3H), 3.38 (s, 2H), 3.98 (sept, J )
6.8 Hz, 1H), 7.2-7.7 (m, 3H), 7.8-8.0 (m, 2H); 13C NMR
1
(ꢀ 730); H NMR (CDCl3) δ 1.03 (d, J ) 7.2 Hz, 3H), 1.51 (s,
3H), 3.17 (q, J ) 7.2 Hz, 1H), 4.94 (s, 2H), 7.1-7.5 (m, 10H);
13C NMR (CDCl3) δ 10.4 (q), 14.5 (q), 42.4 (t), 51.7 (d), 84.6
(s), 87.2 (s), 125.9 (d), 127.7 (d), 127.9 (d), 128.3 (d), 128.5 (d),
128.7 (d), 132.2 (s), 136.4 (s), 172.3 (s), 173.8 (s). Anal. Calcd
for C20H19O3N: C, 74.73; H, 5.96; N, 4.36. Found: C, 74.80;
H, 5.87; N, 4.37.
a n t i-3-Be n zyl-1,7-d im e t h yl-5-p h e n yl-6-oxa -3-a za b i-
cyclo[3.1.1]h ep ta n e-2,4-d ion e (a n ti-2b) (minor isomer): 1H

6308 J . Org. Chem., Vol. 62, No. 18, 1997
Sakamoto et al.
(CDCl3) δ 18.3 (q), 20.1 (q), 39.9 (t), 44.5 (d), 60.8 (s), 128.0
(d), 128.6 (d), 133.6 (d), 135.6 (s), 173.7 (s), 195.9 (s). Anal.
Calcd for C15H17O3N: C, 69.47; H, 6.61; N, 5.40. Found: C,
69.30; H, 6.60; N, 5.35.
UV (nm, CH3CN) 253 (ꢀ 970); 1H NMR (CDCl3) δ 1.72 (s, 3H),
3.29 and 3.41 (ABq, J ) 9.7 Hz, 2H), 7.2-7.5 (m, 10H); 13C
NMR (CDCl3) δ 19.0 (q), 46.9 (t), 81.7 (s), 83.5 (s), 124.3 (d),
127.2 (d), 127.3 (d), 127.9 (d), 128.2 (d), 131.5 (s), 134.5 (s),
170.8 (s), 171.7 (s). Anal. Calcd for C18H15O3N: C, 73.79; H,
5.12; N, 4.78. Found: C, 73.55; H, 5.07; N, 4.66.
1-(Ben zoylfor m yl)-3,3-d im et h yl-4-p h en yla zet id in -2-
on e (6g): mp 118-119 °C; IR (cm-1, KBr) 1690, 1800; UV
1
(nm, CH3CN) 238 (ꢀ 5600), 251 (ꢀ 6400); H NMR (CDCl3) δ
3-(2,6-Dich lor op h en yl)-1-m et h yl-6-oxa -5-d ip h en yl-3-
a za bicyclo[3.1.1]-h ep ta n e-2,4-d ion e (2j): mp 150-151 °C;
IR (cm-1, KBr) 1720, 1770; UV (nm, CH3CN) 263 (ꢀ 770), 278
(ꢀ 520); 1H NMR (CDCl3) δ 1.76 (s, 3H), 3.46 (br, 2H), 7.3-7.5
(m, 8H); 13C NMR (CDCl3) δ 19.8 (q), 47.7 (t), 83.0 (s), 84.8
(s), 125.4 (d), 128.4 (d), 128.8 (d), 129.0 (d), 131.0 (d), 135.0
(s), 135.2 (s), 135.3 (s), 170.0 (s), 171.0 (s). Anal. Calcd for
C18H13O3NCl2: C, 59.83; H, 3.63; N, 3.88. Found: C, 59.75;
H, 3.58; N, 3.94.
0.85 (s, 3H), 1.54 (s, 3H), 5.03 (s, 1H), 7.2-7.7 (m, 8H), 7.9-
8.0 (m, 2H); 13C NMR (CDCl3) δ 17.8 (q), 23.0 (q), 56.7 (s), 65.4
(d), 125.9 (d), 128.4 (d), 128.8 (d), 129.0 (d), 129.9 (d), 131.9
(s), 134.1 (s), 135.1 (d), 163.2 (s), 170.7 (s), 188.0 (s). Anal.
Calcd for C19H17O3N: C, 74.25; H, 5.57; N, 4.55. Found: C,
73.95; H, 5.64; N, 4.53. The enantiomeric excess was deter-
mined by 1H-NMR spectroscopy employing 0.5 equiv of Eu-
(hfc)3.
1-Meth yl-6-oxa-3,5-diph en yl-3-azabicyclo[3.1.1]h eptan e-
2,4-d ion e (2h ): mp 121-122 °C; IR (cm-1, KBr) 1710, 1760;
J O9704974