Reaction-phase-selective inter- and intramolecular photochemical reaction of 2-pyridone derivatives

Article abstract of DOI:10.1021/ol036138e

Phase-selective photochemical reaction of 2-pyridone derivatives was examined. Irradiation of 1 in benzene mainly gave rearrangement products 2. However, intermolecular [4 + 4] photocycloaddition proceeded quantitatively in the solid state, affording phot

Full text of DOI:10.1021/ol036138e

ORGANIC
LETTERS
2004
Vol. 6, No. 5
683-685
Reaction-Phase-Selective Inter- and
Intramolecular Photochemical Reaction
of 2-Pyridone Derivatives
,†
Shigeo Kohmoto,* Takao Noguchi,† Hyuma Masu,† Keiki Kishikawa,†
Makoto Yamamoto,† and Kentaro Yamaguchi‡
Department of Materials Technology, Faculty of Engineering and Chemical Analysis
Center, Chiba UniVersity, 1-33, Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
kohmoto@faculty.chiba-u.jp
Received November 1, 2003
ABSTRACT
Phase-selective photochemical reaction of 2-pyridone derivatives was examined. Irradiation of 1 in benzene mainly gave rearrangement products
2. However, intermolecular [4 + 4] photocycloaddition proceeded quantitatively in the solid state, affording photodimers 3. An effective π−π
stacking and dipole−dipole interaction between two pyridone moieties might play important roles in an effective arrangement of 1 for
photodimerization in their crystal structures.
Irradiation of 2-pyridone derivatives is widely known to
undergo [4 + 4] photocycloaddition to produce cyclooc-
tanoids, which is one of the efficient and direct methods to
prepare eight-membered carbocyclic rings.1 An intramolecu-
lar version of this photocycloaddition is applicable to natural
product synthesis. A typical example is the synthesis of the
carbocyclic skeleton of Taxol.2 Although many reports have
described the photochemical reaction of 2-pyridones since
1960,3 there is no example of an efficient and quantitative
intermolecular [4 + 4] photocycloaddition of them because
the intermolecular reaction is strongly concentration depend-
ent in the solution phase.4 In many cases, intramolecular 1,4-
electrocyclization5 was observed together with intermolecular
[4 + 4] cycloaddition. To develop an efficient route to
intermolecular [4 + 4] photocycloaddition of 2-pyridone
derivatives, we considered their solid-state photochemical
reaction. It is well-known that photochemical conversion
proceeds under topochemical control in the solid state.6
However, only a few examples of solid-state photoreaction
of 2-pyridones have been reported. Moreover, even in those
examples, intramolecular 1,4-electrocyclization leading to the
corresponding â-lactam has been dominantly described
instead of [4 + 4] photodimerization.7 These facts challenged
us to study the reaction-mode-selective photochemistry8 of
2-pyridones, in which a selection of a reaction phase, either
(4) (a) Nakamura, Y.; Kato, T.; Morita, Y. J. Chem. Soc., Perkin Trans.
1 1982, 1187. (b) Matsushima, R.; Terada, K. J. Chem. Soc., Perkin Trans.
2 1985, 1445.
(5) Corey, E. J.; Streith, J. J. Am. Chem. Soc. 1964, 86, 950.
(6) Ramamuthy, V.; Venkatesan, K. Chem. ReV. 1987, 87, 433.
(7) (a) Kuzuya, M.; Noguchi, A.; Yokota, N.; Okuda, T.; Toda, F.;
Tanaka, K. Nippon Kagaku Kaishi 1986, 1746. (b) Toda, F.; Tanaka, K.
Tetrahedron Lett. 1988, 29, 4299. (c) Wu, L. C.; Cheer, C. J.; Olovsson,
G.; Scheffer, J. R.; Trotter, J. Tetrahedron Lett. 1997, 38, 3135. (d) Tanaka,
K.; Fujiwara, T.; Urbanczyk-Lipkowska, Z. Org. Lett. 2002, 4, 3255.
† Department of Materials Technology.
‡ Chemical Analysis Center.
(1) (a) Ayer, W. A.; Hayatsu, R.; de Mayo, P.; Reid, S. T.; Stothers, J.
B.; Tetrahedron Lett. 1961, 18, 648. (b) Slomp, G.; Mackellar, F. A.;
Paquette, L. A. J. Am. Chem. Soc. 1961, 83, 4472.
(2) (a) Sieburth, S. McN.; Chen, J.; Ravindran, K.; Chen, J. J. Am. Chem.
Soc. 1996, 118, 10803. (b) Lee, Y.; McGee, K. F., Jr.; Chen, J.; Rucando,
D.; Sieburth, S. McN. J. Org. Chem. 2000, 65, 6676.
(3) Taylor, E. C.; Paulder, W. W. Tetrahedron Lett. 1960, 25, 1.
10.1021/ol036138e CCC: $27.50 © 2004 American Chemical Society
Published on Web 01/29/2004

Scheme 1
Scheme 2
solution or solid state, can control a mode of reaction. Such
a control, a choice of specific reaction out of some possible
reactions from the same starting material, is attractive not
only from synthetic viewpoints but also from a mechanistic
understanding. However, successful examples of this kind
of control are very limited. Photochemical reaction of 2,4-
cyclohexadienones is an example in which the mode of
reaction can be controlled by the irradiation wavelength or
the solvent polarity of the reaction media.9 Herein we report
the novel reaction mode control in photochemical reaction
of 2-pyridone derivatives.
To carry out [4 + 4] photodimerization effectively in the
solid state, we designed phenyl ether derivatives 1a-d. These
derivatives were prepared by Williamson ether synthesis from
3-chloromethyl-2-pyridone10 and 4-alkoxyphenols. The phen-
yl rings are expected to assist crystal packing through an
intermolecular aromatic interaction such as face-to-face or
edge-to-face stacking.11 In addition to this, the 2-pyridone
moiety also contributes to an efficient stacking for [4 + 4]
dimerization via bimolecular dipole-dipole interaction.4b
Prior to the solid-state reaction of 1, their photoreaction in
solution was examined.
Irradiation was conducted externally with a 450W high-
pressure mercury lamp through a Pyrex filter. A benzene
solution of 1a-d at 0.3 or 0.03 M was irradiated at 0 °C for
8 h under an argon atmosphere. After evaporation of solvent,
the reaction mixture was chromatographed on silica gel with
ethyl acetate-hexane (2:1) as an eluent. A photo-[1,3]
migration of pyridone methylene group, relatively well-
known for benzyl phenyl ethers,12 gave 2a-d in an isolated
yield of 30∼40% (Scheme 1). No concentration dependency
was observed for product ratios in this photolysis.
In contrast to the photolysis in solution, an alteration of
the mode of photochemical reaction occurred in solid-state
photolysis. Irradiation of 1a, 1c, and 1d in the solid state at
0 °C for 20 h resulted in a quantitative formation of the [4
+ 4] cycloadducts 3a, 3c, and 3d, respectively (Scheme 2).
The syn-anti configuration of photodimers could be deter-
mined from a coupling pattern of bridgehead protons in their
1H NMR spectra. Syn isomers should show a ddd coupling
pattern for their bridgehead protons, whereas dd should be
the characteristic coupling pattern for those of anti isomers.
The bridgehead protons of photodimers 3a, 3c, and 3d
showed a dd (J ) 7.0 and 1.2∼1.5 Hz) coupling pattern that
confirmed their stereochemistry to be anti. More specifically,
the stereochemistry of four possible [4 + 4] photodimers
(trans-anti, trans-syn, cis-anti, and cis-syn)4a derived from
2-pyridones can be defined from their Nuclear Overhauser
Effects (NOEs).13 Photodimers 3 were confirmed to have a
trans-anti configuration on the basis of NOEs observed
between N-methyl protons and the olefinic proton distant
from the bridgehead proton and between the bridgehead
proton and one of the geminal protons of phenoxymethyl
group (Scheme 2). Since the photodimers were thermally
unstable, their mass spectra (FAB) did not show the
corresponding molecular peaks. Instead, the m/z correspond-
ing to 1 was observed. The quantitative retro [4 + 4]
cycloaddition presumably took place. Therefore, the struc-
tures of photodimers were confirmed by carrying out their
reduction by hydrogenation in ethyl acetate. The reduced
photodimers 4a, 4c, and 4d showed the exact mass spectra
for them. The formation of cycloadducts implies that there
is a close overlapping between the two pyridone rings in
their crystal structures. However, irradiation of 1b in the solid
state gave 2b in 9% yield. In this case, no preference to
photodimerization was observed even in the solid state.
To elucidate solid-state photochemical behavior, we
examined the single-crystal X-ray structures of 1a14 and 1b15
(Figure 1). In the crystal structure of 1a, an efficient face-
(8) (a) Kohmoto, S.; Miyaji, Y.; Tsuruoka, M.; Kishikawa, K.; Yama-
moto, M.; Yamada, K. J. Chem. Soc., Perkin Trans. 1 2001, 2082. (b)
Ihmels, H.; Schneider, M.; Waidelich, M. Org. Lett. 2002, 4, 3247. (c)
Zimmerman, H. E.; Sereda, G. A. J. Org. Chem. 2003, 68, 283.
(9) Uppili, S.; Ramamurthy, V. Org. Lett. 2002, 4, 87.
(10) Sieburth, S. McN.; McGee, K. F., Jr.; Zhang, F.; Chen, Y. J. Org.
Chem. 2000, 65, 1972.
(11) (a) Tsuzuki, S.; Honda, K.; Uchimaru, T.; Miyaji, M.; Tanabe, K.
J. Am. Chem. Soc. 2002, 124, 104. (b) Sinnokrot, M. O.; Valeev, E. F.;
Sherrill, C. D. J. Am. Chem. Soc. 2002, 124, 10887.
(13) Sieburth, S. McN.; Hiel, G.; Lin, C.-H.; Kuan, D. P.J. Org. Chem.
1994, 59, 80.
(14) Crystal data for 1a: C13H13NO2, Mw ) 215.25, colorless prism,
orthorhombic Pbca, a ) 10.759(2), b ) 8.835(2), c ) 23.277(5) Å V )
2212.6(8) Å3, Z ) 8, Dcalc ) 1.292 g/cm3, λ(Mo KR) ) 0.71069 Å, µ )
0.088 mm-1, R ) 0.049, Rw ) 0.075, T ) 100 K.
(15) Crystal data for 1b: C17H21NO3, Mw ) 287.36, colorless prism,
monoclinic P21/n, a ) 13.007(1), b ) 11.100(1), c ) 13.003(1) Å, â)
56.808(5)°, V ) 1571.0(3) Å3, Z ) 4, Dcalc ) 1.215 g/cm3, λ(CuKR) )
1.54178 Å, µ ) 0.670 mm-1, R ) 0.060, Rw ) 0.072, T ) 298 K.
(12) Kelly, D. P.; Pinhey, J. T.; Rigby, R. D. G. Tetrahedron Lett. 1966,
5953.
684
Org. Lett., Vol. 6, No. 5, 2004

the networks of edge-to-face aromatic interaction between
the two phenyl rings and between the pyridone and phenyl
rings are confirmed in the packing structure. The distances
between the two (centroid-to-centroid) are 5.26 Å (phenyl-
phenyl) and 4.94 Å (pyridone-phenyl), respectively, and the
tilt angle is ca. 100°. These are typical values for the edge-
to-face geometry.18 Due to these intermolecular interactions,
the pyridone and phenyl moieties in 1a are located orthogo-
nally to each other, which assists the molecular orientation
in the crystal packing on the whole. As a result, the
intermolecular interactions play a dominant role in solid-
state [4 + 4] cycloaddition. In contrast, the molecular
orientation of 1b in its crystal structure is far from ideal for
[4 + 4] cycloaddition because the pyridone ring forms a
π-stacked structure intermolecularly with the phenyl ring.
The centroid-to-centroid distance between the two rings is
3.59 Å. The molecular arrangement of 1b in the crystal seems
to be affected by the length of alkyl chain in addition to this
π-π stacking. The C4 alkyl chain adopts a pseudo-gauche
conformation at its terminal, and disorder is observed there.
In summary, we have demonstrated the novel reaction-
phase-selective photochemical reaction of 2-pyridone deriva-
tives in which [4 + 4] photocycloaddition proceeded
exclusively in the solid state, while photorearrangement
occurred in solution.
Figure 1. Bimolecular association in the crystal structures of 1a
and 1b.
to-face π-π stacking operates between two pyridone rings.
The distances between the two sets of two carbon atoms to
be reacted are 3.8 Å (C1-C3 and C2-C4). This value is
within the range of Schmidt’s rule (4.2 Å) for [2 + 2]
photocycloaddition16 and our previous observation for aro-
matic [4 + 4] photocycloaddition (4.5 Å).17 The torsional
angle between the two pyridone rings (C1-C2-C4-C3) is
0°. As a result, the two pyridone rings are overlapped well
in a parallel manner. In addition, this bimolecular association
preorganizes the two pyridone moieties to the trans-anti
orientation due to the dipole-dipole interaction. Furthermore,
Supporting Information Available: Experimental pro-
cedures and spectral data of 1a-d, 2a-d, 3a, 3c, 3d, 4a,
4c, and 4d; X-ray structural information for 1a and 1b in
CIF format. This material is available free of charge via the
Internet at http://pubs.acs.org.
OL036138E
(16) Schmidt, G. M.; Pure Appl. Chem. 1971, 27, 647.
(17) Kohmoto, S.; Ono, Y.; Masu, H.; Yamaguchi, K.; Kishikawa, K.;
Yamamoto, M. Org. Lett. 2001, 3, 4153.
(18) Grossel, M. C.; Cheetham, A. K.; Hope, D. A. O.; Weston, S. C. J.
Org. Chem. 1993, 58, 6654 and references therein.
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