Absolute asymmetric phthalide synthesis via the solid-state photoreaction of N,N-disubstituted 2-benzoylbenzamides involving a radical pair intermediate [3]

Full text of DOI:10.1021/ja001064c

10210
J. Am. Chem. Soc. 2000, 122, 10210-10211
Scheme 1
Absolute Asymmetric Phthalide Synthesis via the
Solid-State Photoreaction of N,N-Disubstituted
2-Benzoylbenzamides Involving a Radical Pair
Intermediate
Masami Sakamoto,* Norio Sekine, Hiroko Miyoshi,
Takashi Mino, and Tsutomu Fujita
Department of Materials Technology
Faculty of Engineering, Chiba UniVersity
Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
Table 1. Crystal Data for N,N-Dialkyl-2-benzoylbenzamides 3a-c
ReceiVed March 27, 2000
ReVised Manuscript ReceiVed August 3, 2000
Asymmetric generation influenced by a chiral crystalline
environment can be considered as an attractive methodology to
obtain optically active compounds from achiral compounds; this
methodology is recognized as the “absolute” asymmetric
synthesis.1-9 Recently, we reported an example involving the
solid-state photoreaction of S-aryl 2-aroylbenzothioate 1, which
formed chiral crystals, leading to optically active 3-phenyl-3-
(phenylthio)phthalide 2 (Scheme 1).10,11 According to the absolute-
to-absolute correlation study of the X-ray crystal structures before
and after the photoreaction, the product formation can be
rationalized by an unusual pathway involving aryl migration. We
studied the X-ray structural analysis and the solid-state photore-
action of the amide derivatives, N,N-disubstituted 2-benzoylben-
zamides, to explore the generality and utilization of the pathway
for the asymmetric synthesis.
Benzoylbenzamides 3a-c were conveniently prepared by a
condensation reaction from commercially available amines and
the corresponding 2-benzoylbenzoic acids using DCC and DMAP.11
Recrystallization of these amides from the chloroform-hexane
solution afforded colorless prisms in all cases. All crystals were
subjected to X-ray crystallographic analysis to obtain details of
the molecular conformation and the architecture in the crystals.
Table 1 shows the crystal data of amides 3a-c. For all prochiral
amides 3a-c, the constituent molecules adopted orthorhombic
chiral space group P212121 and were frozen in a chiral and helical
conformation in the crystal lattice. A spontaneous optical resolu-
tion occurred during the crystallization process, in which the
molecules were associated and fixed in a chiral fashion. Generally,
the selection of either enantiomorphic form of molecular config-
uration is equally probable. Once enantiomorphic crystals are
formed, a large amount of chiral crystals with the same optical
rotation can be selectively prepared through recrystallization by
seeding the desired crystals.
entry
formula
mol weight
crystal system
space group
3a
3b
3c
C16H15NO2
253.30
orthorhombic
P212121
4
10.420(2)
17.208(4)
7.519(2)
1348.3(6)
1.246
C21H17NO2
315.37
orthorhombic
P212121
4
11.453(6)
18.572(5)
8.107(2)
1724.5(8)
1.213
C22H19NO2
329.39
orthorhombic
P212121
4
19.106(5)
8.019(2)
11.986(3)
1836.3(9)
1.19
Z
a/Å
b/Å
c/Å
V/Å3
F
calc/g cm-3
µ(CuKR)/cm-1 6.614
6.217
664
6.036
696
F(000)
536
crystal size/
mm
used reflctns
R
0.40 × 0.30 × 0.30 × 0.10 × 0.30 × 0.20 ×
0.30 0.10 0.20
1156 837 613
0.032
0.035
0.044
0.044
0.044
0.045
Rw
Table 2. Solid-State Photoreaction of 3 under Various Conditions
conditiona temp
yield (%) ee (%)
entry amide of the solid (°C) conv (%)
of 4
of 4b
1
2
3
4
5
6
7
8
3a
3b
3b
3b
3b
3b
3c
3c
powder
powder
powder
powder
crystal
crystal
powder
powder
15 recovered
0
>99
>99
>99
>99
>99
>99
>99
15
0
100
100
47
56
46
100
25
80
83
87
86
97
42
87
-50
0
-50
15
-50
(1) Addadi, L.; Lahav, M. In Origin of Optical ActiVity in Nature; Walker,
D. C., Ed.; Elsevier: New York, 1979; Chapter 14.
(2) Green, B. S.; Lahav, M.; Rabinovich, D. Acc. Chem. Res. 1979, 12,
191-197.
(3) Sakamoto, M. Chem. Eur. J. 1997, 3, 684-689.
(4) Evans, S. V.; Garcia-Garibay, M.; Omkaram, N.; Scheffer, J. R.; Trotter,
J.; Wireko, F. J. Am. Chem. Soc. 1986, 108, 5648-5650.
(5) Sekine, A.; Hori, K.; Ohashi, Y.; Yagi, M.; Toda, F. J. Am. Chem.
Soc. 1989, 111, 697-699.
a Powder was prepared by grinding the crystals. b ee value was
determined by HPLC using Chiral Cell OJ column.
All of the solid-state photolyses were done under an atmosphere
of deoxygenated and dried argon. Solid samples placed in the
bottom of the test tube were cooled in a cooling apparatus and
were irradiated by Pyrex-filtered light transmitted by using a
flexible light guide from a 250-W ultra-high-pressure mercury
lamp. When the powdered 3a was irradiated at 15 °C, the solid
remained unchanged for 10 h; however, it gradually changed to
amorphous on prolonged irradiation. At this point, no isolable
photoproduct was obtained, and the unchanged starting amide was
verified by IR and NMR spectroscopy (Table 2, entry 1). On the
other hand, photolysis of powdered 3b at 15 °C for 2 h gave a
quantitative amount of 3-(N-methylanilino)-3-phenylphthalide 4b,
(6) Roughton, A. L.; Muneer, M.; Demuth, M. J. Am. Chem. Soc. 1993,
115, 2085-2087.
(7) Scheffer, J. R.; Garcia-Garibay, M.; Nalamasu, O. In Organic Photo-
chemistry; Padwa, A., Ed.; Marcel Dekker: New York and Basel, 1987; Vol.
8, pp 249-338.
(8) Gamlin, J. N.; Jones, R.; Leibovitch, M.; Patrick, B.; Scheffer, J. R.;
Trotter, J. Acc. Chem. Res. 1996, 29, 203-209.
(9) Venkatesan, K.; Ramamurthy, V. In Photochemistry in Organized and
Constrained Media; Ramamurthy, V., Ed.; VCH: New York, 1991; pp 133-
184.
(10) Sakamoto, M.; Takahashi, M.; Moriizumi, S.; Yamaguchi, K.; Fujita,
T.; Watanabe, S. J. Am. Chem. Soc. 1996, 118, 8138-8139.
(11) Takahashi, M.; Sekine, N.; Fujita, T.; Watanabe, S.; Yamaguchi, K.;
Sakamoto, M. J. Am. Chem. Soc. 1998, 120, 12770-12776.
10.1021/ja001064c CCC: $19.00 © 2000 American Chemical Society
Published on Web 10/03/2000

Communications to the Editor
J. Am. Chem. Soc., Vol. 122, No. 41, 2000 10211
Table 3. Geometrical Parameters for the Reaction Pathway
Scheme 2
torsional angle (deg)
distance
a
b
c
d
amide
CdOamide
CdObenzoyl
dCC
dCN
3a
3b
3c
66
63
65
38
26
31
2.80
2.74
2.74
3.77
3.87
3.88
a CdOamide is defined as the torsional angle for C4-C3-C2-O1.
b CdObenzoyl is defined as the torsional angle for C3-C4-C5-O6.c dCC
d
is the distance between C2 and O6. dCN is the distance between C5
and N7.
reaction mechanism as 3c; however, the pathway could not be
definitively proved.
the structure of which was determined on the basis of spectral
data. As expected, the asymmetric induction in 4b was confirmed
X-ray structural analysis indicates that the crystal of 3c is also
chiral, in the space group P212121 (Table 1). When powdered 3c
was irradiated at 15 °C until the conversion reached 100%, the
photoproduct 4c-B showed an optical activity of 42% ee (Table
2, entry 7). Furthermore, a higher ee value for 4c-B (87% ee)
was obtained by the reaction at -50 °C (entry 8).
by observation of its optical rotation, the [R]20 value of which
D
was 21° (c )1.0 in CHCl3) (Table 2, entry 2). The ee value was
determined by HPLC using a chiral cell OJ column (Daicel
Chemical Ind.). As a result of the suppression of the reaction
conversion yield and by decreasing the reaction temperature to
-50 °C, the enantiomeric purity rose to 87% ee (entries 3 and
4). Furthermore, irradiation of single crystals of 3b gave 97% ee
of 4b when the reaction conversion reached 46% (entries 5 and
6).
It has been generally argued that solid-state reactions proceed
with minimum atomic or molecular movement.14-16 Therefore,
the reactivities are mainly influenced by atomic arrangement
represented by distances and angles between the reaction centers.
The twist around the C-C bonds defined by benzoyl and amide
against the central phenyl ring may be the most important factor
for the formation of the helical and chiral structures. The X-ray
structural studies revealed that all amides 3a-c tend to have
almost the same molecular conformation (Table 3). Remarkably,
the amide carbonyl is inclined to strongly twist against the central
phenyl ring (63-66°), and the twisted angle formed by the
benzoyl carbonyl is small (26-38°). Table 3 also lists interatomic
distances responsible for the photochemical events via radical
cyclization. The dCC value is the distance between the amide
carbonyl carbon and the benzoyl oxygen atoms, which are placed
close to each other, and is much less than the sum of van der
Waals radii (3.22 Å), ranging from 2.74 to 2.80 Å. Although the
dCN value, defined as the distance between the benzoyl carbon
and amino nitrogen atoms, was slightly longer (3.77-3.88 Å)
than the sum of van der Waals radii (3.25 Å), the subsequent
recombination of the amino radical with the phthalide radical
might occur since some conformational changes enhanced by
initial cyclization would allow the reaction centers to be located
close to each other. These atomic arrangements in the crystal
lattices satisfy the effective radical cyclization followed by
recombination between the phthalide and amino radical pair.
Although all amides offered almost the same molecular confor-
mation, N,N-dimethyl derivative 3a was inert toward the photo-
cylization. It is generally understood that the cleavage of the
C(dO)sN bond of aliphatic amides is an unfavorable process
owing to the difference in stabilities of the amino radicals.17,18
In conclusion, the solid-state photoreaction of N,N-disubstituted
2-benzoylbenzamides promoted intramolecular cyclization to
phthalides via a radical pair intermediate, in which the “absolute”
asymmetric conversion into the prochiral starting materials in the
chiral crystalline environment was performed with good enantio-
selectivity.
In regard to the mechanism of the solid-state photoreactions,
there are two possible pathways from the starting amides to
phthalides (Scheme 2). Path A involves phenyl migration, the
same as in the mechanism of thioester derivatives 1 as shown in
Scheme 1. The other path, B, is initiated by homolytic cleavage
of the C(dO)sN bond to generate a radical pair intermediate.
The radical mechanism has been confirmed in the photo-Fries
rearrangement of aromatic amides.12 To answer the question of
the reaction mechanism involved, regiochemical correlation was
examined using a methyl probe (R3 ) Me) on the central aryl
ring in the starting material. The findings based on the methyl
probe between the starting material and the final product provide
straightforward proof for the determination of the pathway since
the position of this substituent in the product can represent the
reaction course as shown in Scheme 2. Different regiochemical
isomers, 4-A or 4-B, should be obtained from each reaction
pathway.
When the crystal of 3c was irradiated at 15 °C for 1 h, a single
regioisomer of 4c was obtained quantitatively (Table 2, entry 7).
Direct establishment of the regiochemistry was not performed;
however, the structure could be determined as 4c-B on the basis
of the fact that 3-hydroxy-6-methyl-3-phenylphthalide was ob-
tained by hydrolysis of 4c with aqueous potassium hydroxide.13
As is apparent from the regiochemical correlation, reaction
pathway B was indispensable for the rationalization of the product
formation since path A would lead to another regioisomer, 4c-A
(Scheme 2). Apparently, the reaction of 3b also involves the same
(12) Reviews for amides: Bellus, D. AdV. Photochem. 1973, 8, 109.
(13) When the photoproduct 4c was hydrolyzed with aqueous potassium
hydroxide, 3-hydroxy-6-methyl-3-phenylphthalide was isolated. This material
was also obtained by the same treatment of 3c or 4-methyl-2-benzoylbenzoic
acid.
(14) Zimmerman, H. E.; Zuraw, M. J. J. Am. Chem. Soc. 1989, 111, 2358
and 7974.
(15) Zimmerman, H. E.; Zhu, Z. J. Am. Chem. Soc. 1995, 117, 5245-
Supporting Information Available: X-ray structural information on
3a-c (PDF, CIF). This material is available free of charge via the Internet
at http://pubs.acs.org.
5262.
(16) Choi, T.; Peterfy, K.; Khan, S. I.; Garcia-Garibay, M. A. J. Am. Chem.
Soc. 1996, 118, 12477-12478.
(17) Mazzocchi, P. H.; Thomas, J. J. Am. Chem. Soc. 1972, 94, 8281.
(18) Mazzocchi, P. H.; Thomas, J.; Danisi, F. J. Org. Chem. 1979, 44, 50.
JA001064C