Selective intermolecular photo-[4 + 4]-cycloaddition with 2-pyridone mixtures. 2. Preparation of (1α,2β,5β,6α)-3-butyl-9-methoxy-3,7- diazatricyclo[4.2.2.22,5]dodeca-9,11-diene-4,8-dione

Article abstract of DOI:10.1021/jo981932c

Photochemistry of 2-pyridone mixtures can be selective and thereby lead to useful quantities of [4 + 4] cycloaddition cross products. The selective intermolecular reaction described here employs an excess of 4-methoxy-2- pyridone (6), which does not photodimerize but will undergo [4 + 4] cycloaddition with 2-pyridones without a 4-methoxy group such as N-butyl-2- pyridone 12. Isolated yields of the trans product (1α,2α,5β,6α)-3-butyl- 9-methoxy-3,7-diazatricyclo[4.2.2.2^2,5]dodeca-9,11-diene-4,8-dione (7) are very sensitive to the ratio of the two starting pyridones, and this product has been isolated in yields of up to 51%. This photoreaction produces, in a single step from simple aromatic precursors, a tricyclic product with four stereogenic centers and four distinct functional groups.

Full text of DOI:10.1021/jo981932c

950
J . Org. Chem. 1999, 64, 950-953
Selective In ter m olecu la r P h oto-[4 + 4]-cycloa d d ition w ith
2-P yr id on e Mixtu r es. 2. P r ep a r a tion of (1r,2â,5â,6r)-3-Bu tyl-
9-m eth oxy-3,7-d ia za tr icyclo[4.2.2.22,5]d od eca -9,11-d ien e-4,8-d ion e
Scott McN. Sieburth,* Chao-Hsiung Lin, and David Rucando
Department of Chemistry, State University of New York, Stony Brook, New York 11794-3400
Received September 22, 1998
Photochemistry of 2-pyridone mixtures can be selective and thereby lead to useful quantities of [4
+ 4] cycloaddition cross products. The selective intermolecular reaction described here employs an
excess of 4-methoxy-2-pyridone (6), which does not photodimerize but will undergo [4 + 4]
cycloaddition with 2-pyridones without a 4-methoxy group such as N-butyl-2-pyridone 12. Isolated
yields of the trans product (1R,2â,5â,6R)-3-butyl-9-methoxy-3,7-diazatricyclo[4.2.2.22,5]dodeca-9,-
11-diene-4,8-dione (7) are very sensitive to the ratio of the two starting pyridones, and this product
has been isolated in yields of up to 51%. This photoreaction produces, in a single step from simple
aromatic precursors, a tricyclic product with four stereogenic centers and four distinct functional
groups.
Cycloaddition reactions are regarded as one of the most
powerful synthetic methods because they form multiple
bonds and multiple stereogenic centers in a single step.
This analysis is generally true because cycloaddition
reactions are also closely associated with stereo and
regioselectivity, the classic example being the Diels-
Alder reaction.1 A third, but less frequently discussed,
selectivity is the selection of two reacting species for each
other rather than for themselves. Once again, the Diels-
Alder reaction provides outstanding examples of diene/
dienophile cycloadditions with dimerization at most a
minor diversion. Electronically tuned reaction partners
play a significant role here; an electron rich diene is best
coupled with an electron poor dienophile, and under these
circumstances the highest levels of selectivity are found.
Higher-order cycloadditions2,3 are less well studied;
however, they can and do profit from the same selectivi-
ties. Photocycloaddition of 2-pyridone 2, originally re-
ported by Taylor and Paudler,4 has a native regioselec-
tivity for head-to-tail products and a stereoselectivity
favoring the trans isomers 3 (Figure 1).5 The third
selectivity, however, is missing: nearly all of the known
2-pyridone photocycloadditions are dimerizations, pro-
ducing a symmetric product with a center of inversion.6
In contrast, most potential synthetic targets are asym-
metric, including most natural products. Our studies of
2-pyridone [4 + 4] cycloaddition initially focused on an
intramolecular variation in which two different pyridones
were tethered at the 3- and 6′-positions to reinforce their
F igu r e 1. Presence of a 4-alkoxy group (X ) OR) prevents
photodimerization to 3, but not isomerization to 1 or intramo-
lecular photocycloaddition of 4.
normal head-to-tail regioselectivity.7 As part of this
investigation, we considered the photochemistry of
4-alkoxy-2-pyridone with a 4-unsubstituted-2-pyridone
(4) and elected to investigate this reaction in an unteth-
ered, intermolecular form to ensure that such a cycload-
dition was possible, before undertaking an intramolecular
application with 4.8
The presence of a 4-alkoxy group on the 2-pyridone
perturbs the photochemistry of this molecule. Photo-[4
+ 4] dimerization to give 3a is the major photochemical
pathway for 2-pyridones 2a , except under dilute condi-
tions where unimolecular isomerization to give Dewar
pyridone 1a dominates.9 In contrast, the presence of a
4-alkoxy group (2b) shuts down the [4 + 4] pathway,
leading to 1b as the only observed transformation. This
photochemical behavior was first observed by Schleigh
and De Selms for the natural product ricinine10 and was
* Corresponding author. Voice: 516-632-7851. FAX: 516-632-8882.
ssieburth@sunysb.edu.
(1) Oppolzer, W. In Comprehensive Organic Synthesis; Trost, B. M.,
Fleming, I., Ed.; Pergamon: New York, 1991; Vol. 5; pp 315-399.
(2) Rigby, J . H. Acc. Chem. Res. 1993, 26, 579-585.
(3) Sieburth, S. McN.; Cunard, N. T. Tetrahedron 1996, 52, 6251-
6282.
(4) Taylor, E. C.; Paudler, W. W. Tetrahedron Lett. 1960, 25, 1-3.
(5) Sieburth, S. McN. In Advances in Cycloaddition; Harmata, M.,
Ed.; J AI: Greenwich, CT, Vol. 5, in press.
(6) Photo-[4 + 4]-cycloaddition of 2-pyridones in a mixture with other
1,3-dienes have been reported. In all cases dimerization of the pyridone
competes with cross reaction, and an excess of the other substrate is
used. Triazolo[1,5-a]pyridines: Nagano, T.; Hirobe, M.; Okamoto, T.
Tetrahedron Lett. 1977, 3891-3894. 1,3-Dienes: see ref 22.
(7) Sieburth, S. McN.; Chen, J .-l. J . Am. Chem. Soc. 1991, 113,
8163-8164.
(8) A communication describing initial results has appeared: Sie-
burth, S. McN.; Lin, C.-H. Tetrahedron Lett. 1996, 37, 1141-1144.
(9) Nakamura, Y.; Kato, T.; Morita, Y. J . Chem. Soc., Perkin Trans.
1 1982, 1187-1191.
(10) De Selms, R. C.; Schleigh, W. R. Tetrahedron Lett. 1972, 3563-
3566.
10.1021/jo981932c CCC: $18.00 © 1999 American Chemical Society
Published on Web 01/15/1999

Photo-[4 + 4]-cycloaddition with 2-Pyridone Mixtures. 2
J . Org. Chem., Vol. 64, No. 3, 1999 951
F igu r e 2. Photoproducts from a mixture of 6 and 12.
generalized by Kaneko who employed Dewar pyridones
1b in the synthesis of novel â-lactams.11 While the
reasons that 2b resists photodimerization remain ob-
scure, we needed to know, for the purposes of intramo-
lecular photochemistry with 4, if a 4-alkoxy group would
allow [4 + 4] reactions with other 2-pyridones. The
photochemistry of bis-2-pyridone 4 was studied as a
synthetic route to the anticancer drug paclitaxel12 and
its analogues. Successful photocycloaddition of 4 led to a
[4 + 4] product with one alkene an enol ether.13 The
position of this enol ether methoxy group allows for
introduction of paclitaxel’s A-ring carbons.14
(42% yield overall).17 As with many of our 2-pyridones,18
we found the potassium salt in methanol to be more
selective for N-alkylation, giving an 80% yield of 12.
For the initial reaction, a 1:1 solution of 4-methoxy-2-
pyridone and N-butyl-2-pyridone in methanol, both at
0.25 M, was irradiated. The initial concentration of
pyridones was considered to be critical because at con-
centrations below 0.1 M isomerization of 12 to Dewar
pyridone 16 becomes significant.9 In the event, the
mixture of 6 and 12 was irradiated for 72 h with a
standard 450 W medium-pressure mercury lamp fitted
with a Pyrex filter. The resulting mixture of products,
still containing both starting reagents, was concentrated
and separated chromatographically. A pair of products
7 and 8 were identified as the trans and cis isomers of
the desired [4 + 4] cycloaddition between 6 and 12.19 The
identity of the trans cross-product 7 was subsequently
confirmed by X-ray crystallography.8 This result provided
the necessary preliminary support for the intramolecular
photochemistry of 4 that has been reported elsewhere.13
In addition to the two cross products 7 and 8, the two
known dimers 13 and 14 were isolated, as well as the
cyclobutane 15 which presumably results from Cope
rearrangement of the cis [4 + 4] product 14.8,9 The
cyclooctadiene in 14 can only rearrange to one product
15 because of 14’s C2 axis of symmetry. Rearrangement
of cis cross-product 8, which lacks symmetry, leads to two
different cyclobutanes, 9 and 10. We were surprised,
however, to find very little Dewar pyridone 16, derived
from 12, and none from the 4-methoxy-2-pyridone sub-
strate 6 (see Table 1).20
Resu lts a n d Discu ssion
To study the intermolecular reaction of a 2-pyridone
mixture, we elected to use 4-methoxy-2-pyridone 6 and
N-butyl-2-pyridone 12, both of which were available in
a single operation from commercially available reagents
(Figure 2). Pyridone 12 was chosen because its dimers
are known, and its dimerization/isomerization (13 vs 16)
reactivity was found by Nakamura to be identical to
N-methyl-2-pyridone, the simplest N-alkyl-2-pyridone.9
Further, the N-butyl group was anticipated to make the
photoproducts lipophilic and easily handled. To contrast
with 12, an N-unsubstituted 6 was chosen to allow for
its facile separation from the photoreaction mixture by
simple base extraction of this phenol-like substance.
Methoxypyridone 6 was prepared by rearrangement of
4-methoxypyridine N-oxide 5 with refluxing acetic an-
hydride. The resulting 2-acetoxy-4-methoxypyridine was
then directly hydrolyzed by refluxing with methanol.15,16
N-Butyl-2-pyridone 12 has been prepared by alkylation
of the sodium salt of 2-pyridone with bromobutane,
yielding a 6:1 mixture of N- and O-alkylation in ethanol
The major product, trans dimer 13, was favored over
the desired trans cross-product 7 by nearly a factor of 2,
and both were formed in poor yield (22% and 6%,
respectively, based on 12). These yields, combined with
(17) Brower, K. R.; Ernst, R. L.; Chen, J . S. J . Phys. Chem. 1964,
68, 3814-3820.
(11) Katagiri, N.; Sato, M.; Yoneda, N.; Saikawa, S.; Sakamoto, T.;
Muto, M.; Kaneko, C. J . Chem. Soc., Perkin Trans. 1 1986, 1289-1296.
Kaneko, C.; Katagiri, N.; Sato, M.; Muto, M.; Sakamoto, T.; Saikawa,
S.; Naito, T.; Saito, A. J . Chem. Soc., Perkin Trans. 1 1986, 1283-
1288. Kaneko, C.; Shiba, K.; Fujii, H.; Momose, Y. J . Chem. Soc., Chem.
Commun. 1980, 1177-1178.
(12) Taxane Anticancer Agents: Basic Science and Current Status;
Georg, G. I., Chen, T. T., Ojima, I., Vyas, D. M., Eds.; ACS Symposium
Series 583; American Chemical Society: Washington, DC, 1995.
(13) Sieburth, S. McN.; Chen, J .; Ravindran, K.; Chen, J .-l. J . Am.
Chem. Soc. 1996, 118, 10803-10810.
(14) J ianhao Chen, research notes, State University of New York
at Stony Brook.
(15) Shone, R. L.; Coker, V. M.; Moormann, A. E. J . Heterocycl.
Chem. 1975, 12, 389-390.
(16) Fujii, H.; Shiba, K.; Kaneko, C. J . Chem. Soc., Chem. Commun.
1980, 537-538.
(18) Sieburth, S. McN.; Hiel, G.; Lin, C.-H.; Kuan, D. P. J . Org.
Chem. 1994, 59, 80-87. See ref 28.
(19) The first reaction of a 2-pyridone mixture using 4-methoxy-2-
pyridone was performed with N-methyl-2-pyridone; however, only
qualitative data not directly comparable to that presented here was
obtained. See: K. Ravindran, Ph.D. Thesis, SUNY at Stony Brook,
1994.
(20) Absence of significant amounts of 17 may be due to the
dominance of the pyridone 12 chromophore (see Figure 3). Alterna-
tively, absence of 17 could be caused by our use of a medium-pressure
mercury lamp, with its limited spectral output, rather than a high-
pressure mercury lamp11 with its relatively homogeneous spectral
dispersion. See Horspool, W. M. In Synthetic Organic Photochemistry;
Horspool, W. M., Ed.; Plenum: New York, 1984; pp 489-509. Murov,
S. L.; Carmichael, I.; Hug, G. L. Handbook of Photochemistry; Marcel
Dekker: New York, 1993.

952 J . Org. Chem., Vol. 64, No. 3, 1999
Lin and Rucando
Ta ble 1.
Pyrex filter used for most 2-pyridone photochemistry
blocks wavelengths below 290 nm, and therefore under
the reaction conditions nearly all of the light is absorbed
by 12. It is clear from the data in Figure 3 that a high
relative concentration of 6 would be compatible with
photoexcitation of 12. In view of the instability of the cis
isomers 8 and 14, further experimentation with these
mixtures concentrated on the isolated yields of the trans
[4 + 4] products 7 and 13, the Dewar pyridones 16 and
17, and the percent recovery of starting 2-pyridones 6
and 12.
The effect of altering the ratio of 6 to 12 was dramatic
(Table 1). Because intermolecular photoreactions of 2-py-
ridones can be very concentration dependent, the overall
2-pyridone concentration was held at 0.5 M. Changing
the ratio from 1:1 (entry 1) to 4:1 (entry 2) led to the
complete conversion of N-butyl-2-pyridone 12 into pho-
toproducts after 72 h whereas the 1:1 ratio (entry 1) led
to less than 50% conversion. Further, the ratio of trans
cross-product 7 to trans dimer 13 was reversed, to favor
the former by a factor of 7, and the isolated yield of 7
increased from 6% to 42%. The yield of Dewar pyridone
16 remained low, and the unreacted 6 was recovered in
high yield. Increasing the ratio to 7:1 continued these
trends, with a 51% yield of 7 and less than 10% yield of
13. The reaction time was found to be shorter as well,
with pyridone 12 consumed within 48 h.
At the highest ratio of 6:12 tested, 9:1 (entry 4), the
ratio of products 7 and 13 reach their highest level, with
nearly 95% of the trans isomers occurring as the cross-
product 7. With a ratio of 9:1, however, some limitations
become apparent. After 72 h, some N-butyl-2-pyridone
12 remains, and Dewar pyridone 17 appears for the first
time. Both of these observations are consistent with the
excess of 6 overwhelming the ability of 12 to compete for
photons. For this pair of reactants, therefore, the ratio
of 7:1 (entry 3) is close to ideal.
F igu r e 3. UV spectra of 6 and 12 in methanol.
the low conversion after 72 h and the complex mixture
of products overall, did not bode well for this intermo-
lecular reaction. Notably, however, the unreacted 6 was
recovered in high yield (Table 1, entry 1).
Despite these disappointing initial results, the ability
to generate a richly functionalized photoproduct 7 from
simple aromatic substrates 6 and 12 was intriguing, and
the high recovery of unreacted 6 suggested the possibility
that the reaction outcome could be altered by changing
the starting stoichiometry. Like other reactions involving
two similar species where one is self-reactive,21 increasing
the relative concentration of the unreactive partner (6)
was expected to enhance the yield of cross-product 7. The
photochemical nature of this reaction, however, requires
that the appropriate chromophore be accessible. Our
working assumption, that the excited state of 12 is
responsible for the photochemistry, is based in part on
the ability of simple 2-pyridones to undergo [4 + 4]
photocycloaddition with 1,3-dienes under conditions where
only the pyridones are capable of absorbing light.22 The
UV spectra of 6 and 12 are illustrated in Figure 3.
Substitution of the 2-pyridone with a 4-methoxy group
shifts the absorption maximum from the ca. 300 nm
typical for simple pyridones, to below 280 nm, and also
attenuates the extinction coefficient by one-third. The
Con clu sion s
With this simple model system, we have found that
4-methoxy-2-pyridones (6) can be effectively used in [4
+ 4] cycloaddition reactions with 2-pyridones lacking the
4-alkoxy substituent (12). The modest level of cross
reactivity for 6 requires that an excess be used to limit
the competing dimerization of 12; however, the unreacted
4-methoxy-2-pyridone can be recovered in high yield and
recycled. It is possible that other 2-pyridone mixtures will
have optimum initial ratios other than 7:1, and further
studies are in progress. The four distinct functional
(21) Classic examples include the cross-aldol reaction (Heathcock,
C. H. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I.,
Ed.; Pergamon: New York, 1991; Vol. 2; pp 133-179) and cross-Claisen
condensation (Davis, B. R.; Garratt, P. J . In Comprehensive Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: New York, 1991;
Vol. 2; pp 795-863).
(22) Kanaoka, Y.; Ikeda, K.; Sato, E. Heterocycles 1984, 21, 645. Sato,
E.; Ikeda, Y.; Kanaoka, Y. Liebigs Ann. Chem. 1989, 781-788. Sato,
E.; Ikeda, Y.; Kanaoka, Y. Heterocycles 1989, 28, 117-120.

Photo-[4 + 4]-cycloaddition with 2-Pyridone Mixtures. 2
J . Org. Chem., Vol. 64, No. 3, 1999 953
177.1, 174.7. 160.7, 133.9, 133.1, 98.0, 55.9, 55.8, 55.7, 52.8,
groups in cross-product 7, alkene, enol ether, secondary
amide, and tertiary amide allows for selective function-
alization of this product (see following paper in this issue)
and rapid synthesis of complex cyclooctanoid products
from readily available materials.
48.1, 45.3, 30.0, 19.9, 13.8. IR (CH2Cl2) 3420, 1688, 1658 cm-1
.
Exact mass (FAB) m/z calcd for C15H21N203: 277.1552, found:
277.1553. Anal. Calcd for C15H20N203: C, 65.19; H, 7.30; N,
10.14. Found: C, 65.11; H, 7.29; N, 10.09.
(1R,2R,5R,6R)-3-Bu t yl-9-m e t h oxy-3,7-d ia za t r icyclo-
[4.2.2.22,5]d od eca -9,11-d ien e-4,8-d ion e (8): Rf ) 0.4 (1:9
2-propanol/acetonitrile). 1H NMR (CDCl3) δ 6.85 (d, 1H), 6.28-
6.18 (m, 2H), 4.96 (dd, 1H, J ) 7.2, 2 Hz), 4.29-4.16 (m, 2H),
3.93-3.81 (m, 1H), 3.69-3.52 (m, 1H), 3.52 (s, 3H), 3.34 (d,
1H, J ) 10 Hz), 2.90-2.79 (m, 1H), 1.89-1.18 (m, 4H), 0.87
(t, 3H, J ) 7.2 Hz). 13C NMR (CDCl3) δ 174.6, 173.8, 163.5,
134.4, 130.0, 95.4, 56.9, 55.7, 55.3, 52.7, 48.4, 45.7, 29.3, 19.9,
13.8.
Exp er im en ta l Section
4-Meth oxy-2-p yr id on e (6).15 A solution of 4-methoxypy-
ridine N-oxide 5 (2.3 g, 18 mmol) in acetic anhydride (75 mL)
was heated to reflux for 6 h. The solvent was removed in vacuo,
and the intermediate 2-acetoxy-4-methoxypyridine was dis-
tilled using a kugelrohr (75 °C, 0.05 mmHg). The product was
dissolved in methanol/water (1:1, 20 mL) and stirred at room
temperature for 1 h. The solvent was removed in vacuo, and
the residue was recrystallized from acetonitrile to give 6 as
colorless flakes (1.3 g, 57%). Rf ) 0.44 (9:l methylene chloride/
methanol). λmax ) 278 (3700). 1H NMR (CDCl3) δ 12.9 (br, 1H),
7.22 (d, 1H, J ) 7.2 Hz), 5.98 (dd, 1H, J ) 2.4, 7.3 Hz), 5.88
(d, 1H, J ) 2.4 Hz), 3.78 (s, 3H). 13C NMR (CDCl3) δ 169.8,
(1R,2â,5â,6R)-3,7-Dib u t yl-3,7-d ia za t r icyclo[4.2.2.22,5]-
d od eca -9,11-d ien e-4,8-d ion e (13):9 Rf ) 0.17 (1:1 hexane/
ethyl acetate). 1H NMR (CDCl3) δ 6.60 (dd, 2H, d ) 1.6, 6.8
Hz), 6.15 (dd, 2H, J ) 1.2, 8.2 Hz). 4.08-4.01 (m, 2H), 3.83-
3.71 (m, 2H), 3.60-3.52 (m, 2H), 2.49-2.38 (m, 2H), 1.57-
1.37 (m, 4H), 1.32-1.17 (m, 4H), 0.89 (t, 6H, J ) 7.2 Hz). 13C
NMR (CDCl3) δ 174.2, 134.9, 130.4, 56.0, 50.7, 47.1, 29.6, 20.0,
167.4, 134.6, 101.3, 97.0, 55.4. IR (CH2Cl2) 1646 cm-1
.
13.7. IR (CH2Cl2) 1649 cm-1
.
N-Bu tyl-2-p yr id on e (12).17 A slurry of 2-hydroxypyridine
(20 g, 0.21 mol), 1-bromobutane (45 mL, 0.4 mol), K2CO3 (29
g, 0.21 mol), and KI (20 mg) in methanol (200 mL) was heated
to reflux for 12 h. The slurry was cooled, and the solid was
removed by filtration. The filtrate was partitioned between
water (100 mL) and CH2Cl2 (100 mL), and the aqueous phase
was extracted with CH2Cl2 (3 × 50 mL). The combined organics
were dried over Na2SO4 and concentrated to give a light brown
oil. Distillation (115 °C, 0.3 mmHg) gave 12 as a colorless oil
(25.4 g, 80%). Rf ) 0.38 (3:2 ethyl acetate/hexane). λmax ) 302
(1R,2R,5R,6R)-3,7-Dib u t yl-3,7-d ia za t r icyclo[4.2.2.22,5]-
d od eca -9,11-d ien e-4,8-d ion e (14):9 Rf ) 0.3 (1:1 hexane/ethyl
acetate). 1H NMR (CDCl3) δ 6.24-6.16 (m, 4H), 4.23-4.16 (m,
2H), 3.90-3.79 (m, 2H), 3.65-3.57 (m. 2H); 2.94-2.82 (m, 2H),
1.50-1.35 (m, 4H), 1.34-1.15 (m, 4H). 0.87 (t, 6H, J ) 7.3
Hz). 13C NMR (CDCl3) δ 173.0, 133.9, 132.0, 58.1, 52.4, 49.6,
45.9, 29.5, 19.9, 13.8.
4b ,7,8a ,8b -Tet r a h yd r o-1,7-d ib u t yl-(4a R,4b R,8a R,8b R)-
cyclobu ta [1,2-b:4,3-c′]dip yr id in e-2,8-(1H,4aH)-d ion e (15):9
1
Rf ) 0.43 (1:1 hexane/ethyl acetate). H NMR (CDCl3) δ 6.41
1
(5,600). H NMR (CDCl3) δ 7.21 (m, 2H), 6.46 (d, 1H, J ) 8.8
(d, 1H, J ) 10.0 Hz), 6.01 (d, 1H, J ) 8.0 Hz), 5.80 (d, 1H, J
) 9.7 Hz), 4.76 (dd, 1H, J ) 5.7, 8.0 Hz), 4.50 (t, 1H, J ) 8.7
Hz), 3.98 (m, 1H), 3.62-3.40 (m, 3H), 3.35 (m, 1H), 3.13
(pentet, 1H, J ) 7.1 Hz), 2.85 (pentet, 1H, J ) 7.1 Hz), 1.7-
1.2 (m, 8H), 1.05-0.80 (m, 6H). 13C NMR (CDCl3) δ 165.4,
162.6, 137.3, 131.5, 125.6, 99.7, 54.6, 46.9, 45.0, 44.3, 41.9, 34.6,
30.0, 29.5, 20.2, 20.0, 13.9, 13.6.
Hz), 6.08 (t, 1H, J ) 6.7 Hz), 3.85 (t, 2H, J ) 7.5 Hz), 1.65 (m,
2H), 1.29 (m, 2H), 0.86 (t, 3H, 7.1 Hz). 13C NMR (CDCl3) δ
162.5, 139.2, 137.6, 120.9, 105.8, 49.5, 31.2, 19.8, 13.7. IR (CH2-
Cl2) 1660, 1585, 1538 cm-1
.
In ter m olecu la r P h otocycloa d d ition . A stream of dry
nitrogen was passed through a solution of 6 (454 mg, 3.62
mmol) and 12 (77 mg, 0.51 mmol) in methanol (8.3 mL) in a
Pyrex test tube for several minutes, and the test tube was then
sealed with a septum and fitted with a nitrogen balloon. This
tube was taped to the side of a water-cooled quartz cooling
jacket surrounding a 450 W medium-pressure mercury lamp
inside of a Pyrex filter and irradiated for a total of 72 h. The
methanol was removed in vacuo, and the residue was taken
up in acetonitrile. On standing, 4-methoxy-2-pyridone (6)
crystallized from solution. The mother liquor was concentrated
and chromatographed. A gradient of hexane and ethyl acetate
(1:1 hexane/ethyl acetate to 100% ethyl acetate) led to the
isolation of Dewar pyridone 16, trans dimer 13, and cis dimer
14. Changing the solvent to 1:9 2-propanol/acetonitrile gave
trans cross-product 7, cis cross-product 8, and residual 4-meth-
oxy-2-pyridone (6).
(1R,2â,5â,6R)-3-Bu t yl-9-m e t h oxy-3,7-d ia za t r icyclo-
[4.2.2.22,5]d od eca -9,11-d ien e-4,8-d ion e (7): Rf ) 0.25 (1:9
2-propanol/acetonitrile). mp 179 °C. 1H NMR (CDCl3) δ 6.85
(br, 1H), 6.58 (dd, 1H, J ) 7.3, 7.3 Hz), 6.16 (dd, 1H, J ) 7.3,
7.3 Hz), 5.34 (dd, 1H, J ) 2.1, 7.2 Hz), 4.18-4.12 (m, 2H),
3.85-3.74 (m, 1H), 3.60-3.51 (m, 1H), 3.51 (s, 3H), 3.38 (d,
1H, J ) 10.1 Hz), 2.68-2.57 (m, 1H), 1.91-1.35 (m, 2H), 1.30-
1.18 (m, 2H), 0.87 (t, 3H, J ) 7.2 Hz). 13C NMR (CDCl3) δ
2-Bu tyl-2-a za bicyclo[2.2.0]h ex-5-en -3-on e (16):9 Rf
)
0.70 (3:2 hexane/ethyl acetate). 1H NMR (CDCl3) δ 6.55 (m,
2H), 4.30 (s, 1H), 4.10 (s, 1H), 3.20 (m, 1H), 3.05 (m, 1H), 1.45
(m, 2H), 1.35 (m, 2H), 0.90 (t, 3H, J ) 7.2 Hz). 13C NMR
(CDCl3) δ 170.0, 141.1, 140.4, 57.5, 54.0, 43.0, 29.5, 20.1, 13.7.
IR (neat) 1737, 1505 cm-1
.
5-Meth oxy-2-a za bicyclo[2.2.0]h ex-5-en -3-on e (17):16 1
H
NMR (CDCl3) δ 6.07 (br, 1H), 5.05 (s, 1H), 4.25 (m, 2H), 3.67
(s, 3H).
Ack n ow led gm en t. This work was supported by the
National Institutes of Health (GM45214). NMR spec-
trometers used in this study were purchased with
funding from the National Science Foundation (CHE-
9413510).
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra for
6-8, 12-17, COSY spectra for 7, 8, 13, 14, and HETCOR
spectra for 13 (14 pages). This material is available free of
charge via the Internet at http://pubs.acs.org.
J O981932C