Regioselective photocycloaddition of pyridine derivatives to electron-rich alkenes

Article abstract of DOI:10.1021/jo0266285

Irradiation of a benzene solution of 3-cyano-2,6-dimethoxypyridine in the presence of ethyl vinyl ether (EVE) gave 1:1 photoadducts, 3-cyano -5-ethoxy-2,8-dimethoxy-4,5-dihydroazocine, in good yields, whose structure was established by X-ray single-crystal analysis. The photoadduct was produced via cycloaddition between the C3-C4 position of the pyridine derivatives and an alkene chromophore. On the other hand, 3-cyano -2,6-dimethoxy-4-methylpyridine cycloadds to EVE at the C2-C3 position of the pyridine ring upon irradiation. The difference is explained on the basis of the steric effect.

Full text of DOI:10.1021/jo0266285

Regioselective P h otocycloa d d ition of P yr id in e Der iva tives to
Electr on -Rich Alk en es
Masami Sakamoto,*,† Takeru Sano,† Shohei Fujita,† Masaru Ando,† Kentaro Yamaguchi,‡
Takashi Mino,† and Tsutomu Fujita†
Department of Materials Technology, Faculty of Engineering, Chiba University,
Yayoi-cho, Inage-ku, Chiba 263-8522, J apan, and Chemical Analysis Center, Chiba University,
Yayoi-cho, Inage-ku, Chiba, 263-8522, J apan
sakamotom@faculty.chiba-u.jp
Received October 29, 2002
Irradiation of a benzene solution of 3-cyano-2,6-dimethoxypyridine in the presence of ethyl vinyl
ether (EVE) gave 1:1 photoadducts, 3-cyano-5-ethoxy-2,8-dimethoxy-4,5-dihydroazocine, in good
yields, whose structure was established by X-ray single-crystal analysis. The photoadduct was
produced via cycloaddition between the C3-C4 position of the pyridine derivatives and an alkene
chromophore. On the other hand, 3-cyano-2,6-dimethoxy-4-methylpyridine cycloadds to EVE at
the C2-C3 position of the pyridine ring upon irradiation. The difference is explained on the basis
of the steric effect.
SCHEME 1
In tr od u ction
Photochemical cycloaddition of benzene derivatives
toward several types of alkenes has been extensively
studied, and 2 + 2, 3 + 2, and 4 + 2 cycloadditions were
reported.1-3 The reaction has received much attention
from both mechanistic and synthetic perspectives because
it is also a useful method of synthesizing natural prod-
ucts. On the other hand, while the valence isomerization
of azaaromatic compounds, such as pyridines, was re-
ported three decades ago,4-11 only a few reports for the
photochemical cycloaddition with alkenes are known.12-14
New developments in the ring transformation of het-
eroaromatics will result in useful synthetic methodology
of heterocyclic compounds.15 Recently, we found that
introduction of both electron-donating and -withdrawing
* To whom correspondence should be addressed. Fax: 81+43-290-
3401.
† Department of Materials Technology.
‡ Chemical Analysis Center.
(1) Bryce-Smith, D.; Gilbert, A. Tetrahedron 1976, 32, 1309.
(2) Cornelisse, J . Chem. Rev. 93, 615.
substituents to the pyridine ring shows high reactivity
toward dimerization and addition reaction.
16-20
(3) Wender, P. A.; Siggel, L.; Nuss, J . M. In Organic Photochemistry;
Padwa, A., Ed.; Marcel Dekker: New York, 1989; Vol. 10, pp 357-
473.
(4) Wender P. A.; Sihgh, S. K. Tetrahedron Lett. 1990, 31, 2517.
(5) Baralotto, C.; Chanon, M.; J ulliard, M. J . Org. Chem. 1996, 61,
3576.
(6) Mani, J .; Cho, J .-H.; Astik, R. R.; Stamm, E.; Bigler, P.; Meyer,
V.; Keese, R. Helv. Chim. Acta 1984, 67, 1390.
(7) Zang, C.; Bourgin, D.; Keese, R. Tetrahedron 1991, 47, 3059.
(8) Wender P. A.; Dore, T. M. Tetrahedron Lett. 1996, 37, 6787.
(9) Pavlik, J . W.; Kebede, N.; Thompson, M.; Day, A. C.; Barltrop,
J . A. J . Am. Chem. Soc. 1999, 121, 5666.
(10) Wilzbach, K. E.; Rausch, D. J . J . Am. Chem. Soc. 1970, 92, 2178.
(11) J oussot-Dubien, J .; Houdard, J . Tetrahedron Lett. 1967, 4389.
(12) Lablache-Combier, A.CRC Handbook of Organic Photochemistry
and Photobiology; CRC Press: Boca Raton, 1995; Vol. 82, p 1063 and
references therein.
Previously, we reported the photocycloaddition of
2-alkoxy-3-cyanopyridine 1 with methacrylonitrile lead-
ing to cyclobutane, and ultimately, bicyclic azate 2 and
aminoketone 3 were obtained as shown in Scheme 1.13
Herein we found that the photoreaction of pyridine
(15) Konishi, G.; Chiyonobu, K.; Sugimoto, A.; Mizuno, K. Tetrahe-
dron Lett. 1997, 38, 5313.
(16) Sakamoto, M.; Mino, T.; Fujita, T. Synth. Org. Chem. 2002, 60,
837.
(17) Sakamoto, M.; Tadao, Y.; Mino, T.; Yamaguchi, K.; Fujita, T.
J . Am. Chem. Soc. 2000, 122, 8141.
(18) Sakamoto, M.; Yagi, T.; Fujita, S.; Mino, T.; Fujita, T. J . Org.
Chem. 2002, 67, 1843.
(13) Barlow, M. G.; Brown, D. E.; Haszeldine, R. N. J . Chem. Soc.,
Chem. Commun. 1977, 669.
(14) Sakamoto, M.; Sano, T.; Takahashi, M.; Yamaguchi, K.; Fujita,
T.; Watanabe, S. Chem. Commun. 1996, 1349.
(19) Sakamoto, M.; Yagi, T.; Fujita, S.; Ando. M.; Mino, T.; Yamagi-
chi K.; Fujita, T. Tetrahedron Lett. 2002, 43, 6103.
(20) Sakamoto, M.; Kimura, M.; Fujita, T.; Nishio, T.; Iida, I.;
Watanabe, S. J . Am. Chem. Soc. 1991, 113, 5859.
10.1021/jo0266285 CCC: $25.00 © 2003 American Chemical Society
Published on Web 01/24/2003
J . Org. Chem. 2003, 68, 1447-1450
1447

Sakamoto et al.
TABLE 1. P h otor ea ction of 4 in th e P r esen ce of
Electr on -Rich Alk en esa
entry
4
R1
alkene
conv (%)
yields of 7 (%)
1
2
3
4
a
b
c
a
Me
Et
i-Pr
Me
5
5
5
6
95
96
93
64
83
70
70
60b
F IGURE 1. All UV spectra were measured at a concentration
of 1.0 × 10-4 mol L-1 in C6H12: (a) UV spectrum of 4a ; (b) UV
spectrum of 8; (c) UV spectrum of the adduct 7a ; (d) UV
spectrum of 9; (e) UV spectrum of EVE 5.
a
A benzene solution of 0.02 M of pyridine derivatives 4 and
1.0 M of alkenes was irradiated with a high-pressure mercury
lamp for 6 h. Compound 7d .
SCHEME 2
b
derivatives with electron-rich alkenes effected effective
and regioselective cycloaddition leading to new hetero-
cycles.
Resu lts a n d Discu ssion
When a benzene solution of 2-alkoxy-3-cyanopyridine
1 was irradiated in the presence of ethyl vinyl ether
(EVE), the 1H NMR spectrum of the photolysate indicated
the formation of some adducts; however, the adducts were
too unstable to isolate. An attempted isolation of adducts
by chromatography resulted in the formation of an
intractable mixture. On the other hand, irradiation of a
benzene solution of 2,6-dimethoxy-3-cyanopyridine 4a
(0.02 M) in the presence of EVE 5 (1.0 M) gave a 1:1
adduct, 5-ethoxy-2,8-dimethoxy-4,5-dihydroazocine-3-car-
bonitrile 7a , in 83% yield (Table 1, entry 1). Photolysis
of other nicotinates 4b-c under the same conditions also
gave the corresponding adducts 7b-c in good yields
(Table 1, entries 2 and 3). No other photoproducts, such
as another type of adduct, transpositional isomer, or
pyridine dimers, were isolated.16,19 The adducts 7 were
stable under usual conditions and were easily isolated
by chromatography on silica gel and recrystallization
from a mixture of chloroform and hexane.
Next we tried the photoreaction of pyridine derivative
8, which possesses another methyl group at the 4-position
of 4a (Scheme 2). When 8 was irradiated with EVE, a
different type of adduct 9, 6-cyano-4-ethoxy-1,3-dimethoxy-
7-methyl-2-azabicyclo[4.2.0]octa-2,7-diene, was obtained
in 61% yield at 52% conversion.
The structure was determined on the basis of spectral
data. The mass spectroscopy (FAB) showed a molecular
ion peak at 251 (MH+), which supported that the product
was a 1:1 adduct of 9 and EVE. The IR spectrum
exhibited an absorption at 1655 cm-1 derived from the
1
CdN bond. The H and 13C NMR spectra also strongly
suggest a bicyclic structure. The 1H NMR spectrum
showed new peaks at δ 1.88 (d, J ) 1.7 Hz, 3H, 7-CH3),
2.11 (m, 1H, 5-CH), 2.33 (m, 1H, 5-CH), 3.57 (m, 1H,
4-CH), 6.04 (s, 1H, 8-CH) accompanied by peaks derived
from the alkoxy group. The 13C NMR also showed new
peaks at δ 11.9 (q, 7-CH3), 31.9 (t, 5-C), 47.8 (s, 6-C),
68.6 (d, 4-C), 87.9 (s, 1-C), 119.2 (s, CN), 134.4 (d, 8-C),
145.7 (s, 7-C), 163.3 (s, 3-C). The assignment was made
using the COSY sequence. Finally, the bicyclic structure
of 9 was also established by X-ray structural analysis.
Figure 1 shows the UV spectra of pyridine 4a and EVE
5 at the concentration of each 1.0 × 10-4 mol L-1 in
cyclohexane. EVE has no absorption band above 250 nm.
Since a high-pressure mercury lamp with a Pyrex filter
was used as the irradiation source, light quantum of the
313 nm line was absorbed by the pyridine 4a (ꢀ 110 at
313 nm). The production of 7a was not quenched by
addition of 2,5-dimethylhexadiene (triplet quencher), and
also the reaction was not sensitized by a triplet sensitizer
such as 3-methoxyacetophenone. These results indicate
that the photoaddition proceeds from the singlet-excited
state of pyridine 4a .
The structure was determined on the basis of spectral
data. For example, mass spectroscopy (FAB) of 7a showed
a molecular ion peak at 237 (MH+), which supported that
the product was a 1:1 adduct of 4a and EVE 5. Further-
1
more, the H and 13C NMR spectra strongly suggest the
structure of the adduct 7a . The 1H NMR spectrum
(CDCl3) showed new protons at δ 2.19 (m, 1H, 4-CH), 2.40
(m, 1H, 4-CH), 4.07 (m, 1H, 5-CH), 5.83 (d, J ) 13.2 Hz,
1H, 7-CH), 6.21 (dd, J ) 3.7, 13.2 Hz, 1H, 6-CH) in
addition to the alkoxy protons. The 13C NMR also showed
peaks at δ 29.2 (t, 4-C), 69.9 (s, 7-C), 77.0 (d, 3-C), 117.3
(d, 7-C), 139.7 (d, 6-C), 161.0 (s, 8-C), 166.4 (s, 2-C),
ascribed to the azocine rings. The assignment was made
using the COSY sequence.
Finally, the azocine structure of 7a was unequivocally
established by X-ray structural analysis.
The adduct 9 has no absorption above 250 nm, and the
azocine derivatives 7a absorbs 313 nm line. It seems that
azocine 7 is also able to transform to a bicyclic compound;
however, the product is unstable and easily reverts to 7.
Therefore, 7 was apparently inert toward photolysis and
was obtained in good chemical yields (Table 1).
Irradiation of 4a in the presence of 2-methoxypropene
6 also gave azocine derivative 7d (entry 4); however, the
chemical yield slightly decreased (Table 1, entry 4). It
seems that the steric hindrance caused by induction of
one methyl group affected the addition reaction.
1448 J . Org. Chem., Vol. 68, No. 4, 2003

Photocycloaddition of Pyridine Derivatives to Electron-Rich Alkenes
F IGURE 3. Left: energetically minimum conformation of the
exo isomer. Right: energetically minimum conformation of the
endo isomer.
formation of biradical intermediate 10, which subse-
quently cyclizes to cyclobutane derivative 11. However,
cyclobutane-fused azacyclohexadiene is unstable and
easily opens the cyclobutane ring leading to azocine
derivative 7.
F IGURE 2. Estimated energies and coefficients of pyridine
4a (singlet excited state) and the ground state of ethyl vinyl
ether obtained from the PM3 Hamiltonian contained within
the MOPAC program.
On the other hand, the introduction of a methyl group
at the 4-position of the pyridine ring (R4 ) Me) prevents
the following bond formation at the C-4 position of the
biradical intermediate 10 because of the steric repulsion
between the alkoxy group and the methyl group at the
C-4 position. Ultimately, the biradical recombines at the
C-2 position to give cyclobutane 12, which also easily
opens the cyclobutane ring to yield azatriene 13. The
triene absorbs light quantum to effect the electrocycliza-
tion reaction and gives bicyclic cyclobutene 9. To deter-
mine the proposed mechanism, the reaction was followed
by 1H NMR spectroscopy. A deuterated benzene solution
containing 0.02 M of pyridine 4a or 8 with 1.0 M of EVE
was irradiated; however, the intermediates proposed in
Scheme 3 were not detected, and the spectra assignable
to the final photoproduct 7a and 9 were exhibited.
There are two possible ways of electrocyclization from
azatriene 13 to 2-azabicyclo[4.2.0]octa-2,7-diene 9. Only
one isomer was isolated from the photoreaction of 8 with
EVE. The result was supported by computational calcu-
lations using the PM3 method with Mac-Spartan. The
energetically more favorable exo isomer of 9 is 1.1 kcal
mol-1 more stable than the endo isomer of 9 (Figure 3).
In conclusion, we have found a new example of the
photochemical addition reaction of a pyridine ring with
electro-rich alkenes leading to 1:1 cycloadducts. This
reaction proceeds in a highly controlled regioselective
manner and also provides a synthesis of new nitrogen-
containing heterocycles.
SCHEME 3
The regioselectivity and stereoselectivity in many
singlet photoadditions can be explained by orbital inter-
actions.21,22 Frontier-MO calculations by the PM3 method
help to explain the photocycloaddition.23 The orbital
surfaces of the H-SOMO and L-SOMO of 4a were
obtained from the PM3 Hamiltonian contained within the
MOPAC program as shown in Figure 2. The ∆∆E value
(2.84304 eV) between the L-SOMO of the excited state
of the pyridine derivative and the HOMO of EVE is
smaller than the value (4.55826 eV) between the H-SO-
MO of the excited state of the pyridine derivative and
the HOMO of EVE. The coefficient value at the C-3
position of 4a is bigger than those at other positions, and
interaction between the C-3 position of 4a and the C-2
position of EVE is suggested.
Exp er im en ta l Section
Melting points are uncorrected. FT-IR spectra are reported
in cm-1 1H and 13C NMR spectra were obtained in CDCl3
.
solutions at 300 MHz. Chemical shifts are reported in delta
(δ) units, parts per million (ppm) relative to the TMS as
internal standard. Eikosya 500-W and 1000-W high-pressure
mercury lamps were used as the irradiation source.
P r ep a r a tion of 3-Cya n o-2,6-d ia lk oxyp yr id in es 4a -c
a n d 3-Cya n o-2,6-d ia lk oxy-4-m eth ylp yr id in es 8. The py-
ridines were prepared by alkylation of 3-cyano-2,6-dihydroxy-
pyridine or 3-cyano-2,6-dihydroxy-4-methylpyridine.24-27 For
Scheme 3 shows a plausible mechanism for the forma-
tion of 7 and 9. When R3 is a hydrogen atom, C-C bond-
formation between the C3-position of the pyridine ring
and the C2 postion of EVE proceeds and results in
(21) Yang, N. C.; Gan, H.; Kim. S. S.; Masnovi, J . M. Tetrahedron
Lett. 1990, 31, 3825.
(22) Somekawa, K.; Okuhira, H.; Sendayama, M.; Suishu, T.; Shimo,
T. J . Org. Chem. 1992, 57, 5708.
(23) Stewart, J . J . P. J . Comput. Chem. 1989, 10, 221.
(24) Hopkins, G. C.; J onak, J . P.; Minnemeyer, H. J .; Tieckelmann,
H. J . Org. Chem. 1967, 32, 4040.
(25) Chung, N. M.; Tiechelmann, H. J . Org. Chem. 1970, 35, 2517.
J . Org. Chem, Vol. 68, No. 4, 2003 1449

Sakamoto et al.
example, the synthesis of 4a is exemplified next. To 50 mL of
benzene were added 3-cyano-2,6-dihydroxypyridine (25 mmol),
silver carbonate (18 mmol), and methyl iodide (50 mmol), and
the mixture was warmed at 50 °C for 24 h in the dark.
Precipitated silver salts were filtered off through a Celite (545)
column. After removal of the solvent in vacuo, the residual
mixture was subjected to chromatography on silica gel. A
colorless solid of 4a was recrystallized from the chloroform-
hexane mixture. Other pyridines 4b,c and 8 were synthesized
in the same manner.
3-Cya n o-2,6-d im eth oxyp yr id in e 4a : mp 87-88 °C; UV
(C6H12) 243 (ꢀ 12 600), 290 (11 800), 294 (11 100); IR (CHCl3)
2230 cm-1; 1H NMR (CDCl3) δ 3.98 (s, 3H, OCH3), 4.05 (s, 3H,
OCH3), 6.37 (d, J ) 8.2 Hz, 1H, 5-CH), 7.70 (d, J ) 8.2 Hz,
1H, 4-CH); 13C NMR (CDCl3) δ 54.0, 54.2, 86.7, 102.7, 116.0,
144.1, 164.7, 165.6; MS (FAB) 165 (MH+). Anal. Calcd for
C8H8N2O2: C, 58.53; H, 4.91; N, 17.06. Found: C, 58.48; H,
4.86; N, 17.01.
29.2, 54.5, 55.1, 64.9, 69.9, 77.0, 117.3, 119.9, 139.7, 161.0,
166.4; HR-MS (FAB) calcd 237.1239 for C12H17N2O3 (MH+),
found m/z 237.1234.
X-r a y Cr ysta llogr a p h ic An a lysis of 7a . The cage product
7a gave colorless prismatic crystals of C12H16N2O3: monoclinic
space group P-1, a ) 7.320(4) Å, b ) 9.327(5) Å, c ) 10.009(5)
Å, R ) 95.736(7)°, â ) 107.392(5)°, γ ) 94.547(7)°, V ) 644.4-
(5) Å3, Z ) 2, F ) 1.217 g/cm3, µ(Mo KR) ) 0.88 cm-1. The
structure was solved by the direct method and refined by the
full-matrix least-squares method, where the final R and Rw
were 0.080 and 0.086 for 1267 reflections.
3-Cya n o-2,5,8-tr ieth oxy-4,5-d ih yd r oa zocin e 7b: yellow-
ish oil; IR (CHCl3) 1580, 1620, 2170, 2950 cm-1 1H NMR
;
(CDCl3) δ 1.24 (m, 6H, OCH2CH3), 1.35 (m, 3H, OCH2CH3),
2.15 (m, 1H, 4-CH), 2.40 (m, 1H, 4-CH), 3.57 (m, 1H, 5-OCH),
3.68 (m, 1H, 5-OCH), 3.98 (m, 2H, 2-OCH2), 4.06 (m, 1H,
5-CH), 4.26 (m, 2H, 8-OCH2), 5.82 (d, J ) 13.2 Hz, 1H, 7-CH),
6.19 (dd, J ) 3.7, 13.2 Hz, 1H, 6-CH); 13C NMR (CDCl3) δ 14.0,
15.1, 15.5, 29.1, 63.4, 63.8, 64.9, 70.0, 77.4, 117.6, 120.1, 139.2,
160.3, 166.3; HR-MS (FAB) calcd 265.1552 for C14H21N2O3
(MH+), found m/z 265.1545.
3-Cya n o-2,6-d ieth oxyp yr id in e 4b: mp 40-41 °C; UV
(C6H12) 244 (ꢀ 12 200), 291 (11 200), 295 (10 700); IR (CHCl3)
2230 cm-1 1H NMR (CDCl3) δ 1.40 (t, J ) 7.0 Hz, 3H,
;
7-Cyan o-5-eth oxy-2,8-diisopr opoxy-1-azacycloocta-1,3,7-
OCH2CH3), 1.43 (t, J ) 7.1 Hz, 3H, OCH2CH3), 4.38 (q, J )
7.0 Hz, 2H, OCH2), 4.46 (q, J ) 7.1 Hz, 2H, OCH2), 6.31 (d, J
) 8.3 Hz, 1H, 5-CH), 7.68 (d, J ) 8.3 Hz, 1H, 4-CH); 13C NMR
(CDCl3) δ 14.3, 14.4, 62.7, 63.1, 86.6, 102.7, 116.3, 144.2, 164.4,
165.2; MS (FAB) 193 (MH+). Anal. Calcd for C10H12N2O2: C,
62.48; H, 6.29; N, 14.57. Found: C, 62.65; H, 6.35; N, 14.75.
3-Cya n o-2,6-d iisop r op oxyp yr id in e 4c: mp 58-60 °C; UV
(C6H12) 245 (ꢀ 14 000), 293 (12 300), 297 (11 600); IR (CHCl3)
tr ien e 7c: yellowish oil; IR (CHCl3) 1580, 1620, 2170 cm-1
;
1H NMR (CDCl3) δ 1.24 (t, J ) 7.0 Hz, 3H, OCH2CH3), 1.33
(d, J ) 6.2 Hz, 12H, C(CH3)2), 2.19 (m, 1H, 4-CH), 2.37 (m,
1H, 4-CH), 3.52 (m, 1H, 5-OCH), 3.69 (m, 1H, 5-OCH), 4.06
(m, 1H, 5-CH), 4.54 (sep, J ) 6.2 Hz, 1H, 2-OCH), 5.15 (sep,
J ) 6.2 Hz, 1H, 8-OCH), 5.78 (d, J ) 13.2 Hz, 1H, 7-CH), 6.16
(dd, J ) 3.7, 13.2 Hz, 1H, 6-CH); 13C NMR (CDCl3) δ 15.3,
21.4, 22.2, 29.0, 64.6, 70.4, 70.6, 70.9, 73.1, 117.8, 120.0, 138.5,
159.5, 165.8; HR-MS (FAB) calcd 293.1865 for C16H25N2O3
(MH+), found m/z 293.1862.
2230 cm-1 1H NMR (CDCl3) δ 1.36 (d, J ) 6.3 Hz, 6H,
;
C(CH3)2), 1.40 (d, J ) 6.3 Hz, 6H, C(CH3)2), 5.25 (sep, J ) 6.3
Hz, 1H, OCH), 5.30 (sep, J ) 6.3 Hz, 1H, OCH), 6.26 (d, J )
8.4 Hz, 1H, 5-CH), 7.66 (d, J ) 8.4 Hz, 1H, 4-CH); 13C NMR
(CDCl3) δ 21.9, 69.7, 70.3, 86.6, 103.0, 116.4, 144.2, 164.0,
164.8; MS (FAB) 221 (MH+). Anal. Calcd for C12H16N2O2: C,
65.43; H, 7.32; N, 12.71. Found: C, 65.29; H, 7.11; N, 12.64.
3-Cya n o-2,6-d im eth oxy-4-m eth ylp yr id in e 8: mp 106-
107 °C; UV (C6H12) 245 (ꢀ 11 100), 290 (11 000); IR (CHCl3)
2220 cm-1; 1H NMR (CDCl3) δ 2.42 (s, 3H, 4-CH3), 3.95 (s, 3H,
OCH3), 4.02 (s, 3H, OCH3), 6.23 (s, 1H, 5-CH); 13C NMR
(CDCl3) δ 20.1, 53.1, 54.2, 88.0, 103.2, 115.4, 155.7, 165.2,
165.2; MS (FAB) 179 (MH+). Anal. Calcd for C9H10N2O2: C,
60.66; H, 5.66; N, 15.72. Found: C, 60.56; H, 5.57; N, 15.65.
Gen er a l P r oced u r e for th e P h otoch em ica l Rea ction
of P yr id in e Der iva tives 4 a n d 8 in th e P r esen ce of
Electr on -Rich Alk en es. Twenty milliliters of a benzene
solution containing 0.02 M of pyridine derivative 4 or 8 and
1.0 M of alkene in a test tube was deaerated by bubbling argon
and was irradiated by Pyrex-filtered light with a 1000-W high-
pressure mercury lamp at 15-20 °C. In the case of pyridine
4, the solution was irradiated for 6 h, and phototolysis of
pyridine 8 needed 2 h. After irradiation, the solvent was
removed in vacuo, and the residual mixture was subjected to
chromatography on silica gel (eluant: mixture of n-hexane and
ethyl acetate). The crystalline photoproducts were recrystal-
lized from a mixture of chloroform and hexane. The structure
of the photoproducts was determined on the basis of the
spectral data. Furthermore, the structures of 7a and 9 were
established by X-ray crystallographic analysis.
3-Cya n o-2,5,8-t r im e t h oxy-5-m e t h yl-4,5-d ih yd r oa zo-
cin e 7d : mp 93-94 °C; IR (KBr) 1650, 1690, 2410, 3160 cm-1
;
1H NMR (CDCl3) δ 1.41 (s, 3H, 5-CH3), 2.06 (d, J ) 14.6 Hz,
1H, 4-CH), 2.39 (d, J ) 14.6 Hz, 1H, 4-CH), 3.19 (s, 3H,
5-OCH3), 3.70 (s, 3H, 2-OCH3), 3.90 (s, 3H, 8-OCH3), 5.89 (br,
2H, 6-CH and 7-CH); 13C NMR (CDCl3) δ 26.8, 32.8, 49.6, 54.3,
54.7, 69.3, 78.5, 117.5, 119.8, 142.2, 160.8, 165.9; HR-MS (FAB)
calcd. 237.1239 for C12H17N2O3 (MH+), found m/z 237.1235.
6-Cyan o-4-eth oxy-1,3-dim eth oxy-7-m eth yl-2-azabicyclo-
[4.2.0]octa -2,7-d ien e 9: mp 81-82 °C; UV (C6H12) 201 (ꢀ
7400); IR (KBr) 1655, 2250, 2970 cm-1; 1H NMR (CDCl3) δ 1.24
(m, 3H, OCH2CH3), 1.88 (d, J ) 1.5 Hz, 3H, 7-CH3), 2.11 (dd,
J ) 10.7, 13.5 Hz, 1H, 5-CH), 2.33 (dd, J ) 5.2, 13.5 Hz, 1H,
5-CH), 3.48 (s, 3H, 1-OCH3), 3.57 (dd, J ) 5.2, 13.5 Hz, 1H,
4-CH), 3.58 (m, 1H, 4-OCH), 3.76 (m, 1H, 4-OCH), 3.78 (s, 3H,
3-OCH3), 6.04 (d, J ) 1.5 Hz, 1H, 8-CH); 13C NMR (CDCl3) δ
11.9, 15.1, 31.9, 47.8, 52.0, 53.2, 66.8, 68.6, 87.9, 119.2, 134.4,
145.7, 163.3; HR-MS (FAB) calcd 251.1396 for C13H19N2O3
(MH+), found m/z 251.1387.
X-r a y Cr ysta llogr a p h ic An a lysis of 9. The adduct 9 gave
colorless prismatic crystals of C13H18N2O3: monoclinic space
group P21/n, a ) 10.184(1) Å, b ) 11.459(1) Å, c ) 11.709(1)
Å, â ) 93.629(9)°, V ) 1363.8(3) Å3, Z ) 4, F ) 1.219 g/cm3,
µ(Cu KR) ) 0.717 cm-1. The structure was solved by the direct
method and refined by the full-matrix least-squares method,
where the final R and Rw were 0.072 and 0.081 for 2747
reflections.
3-Cyan o-5-eth oxy-2,8-dim eth oxy-4,5-dih ydr oazocin e 7a:
mp 127-128 °C; UV (C6H12) 211 (ꢀ 9400), 308 (2400); IR
(CHCl3) 1590, 1620, 2170, 2960 cm-1; 1H NMR (CDCl3) δ 1.24
(t, J ) 7.0 Hz, 3H, OCH2CH3), 2.19 (m, 1H, 4-CH), 2.40 (m,
1H, 4-CH), 3.55 (dq, J ) 1.8, 7.0 Hz, 1H, OCH), 3.68 (s, 3H,
2-OCH3), 3.71 (dq, J ) 1.8, 7.0 Hz, 1H, OCH), 3.86 (s, 3H,
8-OCH3), 4.07 (m, 1H, 5-CH), 5.83 (d, J ) 13.2 Hz, 1H, 7-CH),
6.21 (dd, J ) 3.7, 13.2 Hz, 1H, 6-CH); 13C NMR (CDCl3) δ 15.5,
Ack n ow led gm en t. This work was supported by a
Grant-in-Aid for Scientific Research on Priority Area
(417) from the Ministry of Education, Culture, Sports,
Science and Technology (MEXT) of the J apanese Gov-
ernment.
Su p p or tin g In for m a tion Ava ila ble: Two X-ray crystal-
lographic files (CIF) and ORTEP drawings for 7a and 9. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(26) Mariella, R. P.; Stansfield, R. J . Am. Chem. Soc. 1951, 73, 1368.
(27) Organic Synthesis; J ohn Wiley & Sons: New York, 1976,
Collect. Vol. 4, p 210.
J O0266285
1450 J . Org. Chem., Vol. 68, No. 4, 2003