Intramolecular Diels-Alder reactions of brominated masked o-benzoquinones. A detour method to synthesize highly functionalized oxatricyclic [m.3.1.0] ring systems from 2-methoxyphenols

Article abstract of DOI:10.1021/jo020316k

Intramolecular Diels-Alder (IMDA) reactions of masked o-benzoquinones (MOBs) 5a-d to 7a-d and 17a-d to 19a-d generated in situ from 2-methoxyphenols 2-4 and 14-16, respectively, in the presence of alkenols 1a-d, resulting in highly functionalized oxatricyclic [m.3.1.0] ring systems are described. The MOBs 5a-d to 7a-d underwent the IMDA reactions to furnish the adducts 8a-d, 10a-d, and 12a-d (direct method) in poor yields with the concomitant formation of considerable amounts of unexpected byproducts 9a-d, 11a-d, and 13a-d, respectively. To avoid the formation of byproducts and to improve the yields of the desired cycloadducts, a detour method comprising sequential bromination of 2-methoxyphenols 2-4, tandem oxidative acetalization-Diels-Alder reaction, and debromination has been developed. The oxidation of bromophenols 14-16 in the presence of alkenols 1a-d produced the corresponding MOBs 17a-d to 19a-d, which underwent cycloaddition to afford the cycloadducts 20a-d to 22a-d, respectively, as sole products in good to high yields in a highly regio- and stereoselective manner. Treatment of the bromoadducts 20a-d to 22a-d with tributylammonium formate-palladium reagent produced the corresponding debrominated products 8a-d, 10a-d, and 12a-d in high to excellent yields. In general, the latter oxatricycles were obtained in higher overall yields via the detour method than those via the direct method.

Full text of DOI:10.1021/jo020316k

In tr a m olecu la r Diels-Ald er Rea ction s of Br om in a ted Ma sk ed
o-Ben zoqu in on es. A Detou r Meth od To Syn th esize High ly
F u n ction a lized Oxa tr icyclic [m .3.1.0] Rin g System s fr om
2-Meth oxyp h en ols
Ken-Ching Lin, Yi-Ling Shen, N. S. Kameswara Rao, and Chun-Chen Liao*
Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan 300
ccliao@mx.nthu.edu.tw
Received May 3, 2002
Intramolecular Diels-Alder (IMDA) reactions of masked o-benzoquinones (MOBs) 5a -d to 7a -d
and 17a -d to 19a -d generated in situ from 2-methoxyphenols 2-4 and 14-16, respectively, in
the presence of alkenols 1a -d , resulting in highly functionalized oxatricyclic [m.3.1.0] ring systems
are described. The MOBs 5a -d to 7a -d underwent the IMDA reactions to furnish the adducts
8a -d , 10a -d , and 12a -d (direct method) in poor yields with the concomitant formation of
considerable amounts of unexpected byproducts 9a -d , 11a -d , and 13a -d , respectively. To avoid
the formation of byproducts and to improve the yields of the desired cycloadducts, a detour method
comprising sequential bromination of 2-methoxyphenols 2-4, tandem oxidative acetalization-
Diels-Alder reaction, and debromination has been developed. The oxidation of bromophenols 14-
16 in the presence of alkenols 1a -d produced the corresponding MOBs 17a -d to 19a -d , which
underwent cycloaddition to afford the cycloadducts 20a -d to 22a -d , respectively, as sole products
in good to high yields in a highly regio- and stereoselective manner. Treatment of the bromoadducts
20a -d to 22a -d with tributylammonium formate-palladium reagent produced the corresponding
debrominated products 8a -d , 10a -d , and 12a -d in high to excellent yields. In general, the latter
oxatricycles were obtained in higher overall yields via the detour method than those via the direct
method.
In tr od u ction
ated in situ by the oxidation of the corresponding
2-methoxyphenols with hypervalent iodine reagents in
MeOH. When MeOH is replaced by an alkenol during
the oxidation of 2-methoxyphenols, thus formed MOBs
bearing an alkene moiety tethered through an acetal
would undergo tandem IMDA reaction under appropriate
reaction conditions to furnish various highly functional-
ized oxatricycles4 that are useful synthons for polysub-
stituted cis-decalins,5 variously fused triquinanes,6 and
bicyclo[4.2.2]decenones.5f Recently, highly functionalized
tricyclic [m.2.2.0] ring systems were achieved via dias-
tereoselective IMDA reactions of MOBs in our laborato-
ries.7 On the other hand, the IMDA adducts can undergo
interesting and useful photochemical reactions, such as
oxadi-π-methane rearrangement8 to provide a variety of
compounds with potential synthetic utility.6b,9 The IMDA
adducts obtained from analogous tandem processes were
employed as advanced intermediates in the formal syn-
thesis of (()-reserpine10 and the total syntheses of a
clerodane diterpenic acid11 and (()-pallescensin B12 in our
laboratories. In addition to our efforts, various IMDA
adducts of MOBs have been employed as key intermedi-
ates in the total syntheses of (()-xestoquinone5d,13 and
(()-halenoquinone.14 Very recently, the synthesis of the
The intramolecular Diels-Alder (IMDA) reaction has
been proved to be a very useful strategy in the regio- and
stereoselective construction of highly substituted bicyclic
and polycyclic ring systems.1 The advantages of an
intramolecular reaction over its intermolecular counter-
part are well documented.2 One important difference is
that the decreased entropic demands in IMDA reactions
often render them to proceed under milder conditions
with higher reaction rates. Second, the reduction in the
degrees of freedom of the unimolecular transition state
often results in superior selectivities when compared to
the intermolecular reactions.
Masked o-benzoquinones (MOBs),3 a highly reactive
class of 6,6-dialkoxycyclohexa-2,4-dienones, can be gener-
(1) For some reviews of intramolecular Diels-Alder reactions, see:
(a) Bear, B. R.; Sparks, S. M.; Shea, K. J . Angew. Chem., Int. Ed. 2001,
40, 820. (b) Craig, D. In Stereoselective Synthesis; Helmchen, G.,
Hoffmann, R. W., Mulzer J ., Schaumann, E., Eds.; Thieme: Stuttgardt,
1996; Vol. E21c, pp 2872-2904. (c) Roush, W. R. In Comprehensive
Organic Synthesis; Trost, B. M., Fleming, I., Paquette, L. A., Eds.;
Pergamon Press: Oxford, 1991; Vol. 5, Chapter 4.4, pp 513-550. (d)
Craig, D. Chem. Soc. Rev. 1987, 187.
(2) (a) Kirby, A. J . Adv. Phys. Org. Chem. 1980, 17, 183. (b) Page,
M. I.; J encks, W. P. Proc. Natl. Acad. Sci. U.S.A. 1971, 68, 1678. (c)
Page, M. I. Chem. Soc. Rev. 1973, 2, 295.
(3) (a) Liao, C.-C., Peddinti, R. K. Acc. Chem. Res. 2002, 35, 856.
(b) Quideau, S.; Pouyse´gu, L. Org. Prep. Proc. Int. 1999, 31, 617. (c)
Liao, C.-C. In Modern Methodology in Organic Synthesis, Sheno, T.,
Ed.; Kodansha: Tokyo, 1992; pp 409-424.
(4) (a) Chu, C.-S.; Lee, T.-H.; Rao, P. D.; Ko, S.; Song, L.-D.; Liao,
C.-C. J . Org. Chem. 1999, 64, 4111. (b) Chu, C.-S.; Lee, T.-H.; Liao,
C.-C. Synlett 1994, 635.
10.1021/jo020316k CCC: $22.00 © 2002 American Chemical Society
Published on Web 10/24/2002
J . Org. Chem. 2002, 67, 8157-8165
8157

Lin et al.
SCHEME 1
to other alkenols such as trans-crotyl alcohol (1b), cin-
namyl alcohol (1c), and homoallyl alcohol (1d ) to produce
IMDA adducts via the in situ generated MOBs 5b-d .
While the MOBs 5b and 5c yielded the expected products
8b and 8c in 44 and 72% yields, respectively, at room
temperature, the MOB 5d could not provide the desired
product 8d .4a On the other hand, the reactions of 2 with
1b-d at 80 °C afforded the cycloadducts 8b, 8c, and 8d
albeit in low yields, along with the side products 9b, 9c,
and 9d via the MOBs 5b-d , respectively (Scheme 1,
Table 1).
To evaluate the effect of electron-donating substituents
present on the C2 and C3 of cyclohexadienone moiety on
these IMDA reactions, 2-methoxy-6-methylphenol (3) and
2-methoxy-5-methylphenol (4) were oxidized in the pres-
ence of alkenols 1a -d . Surprisingly, 2-methoxyphenols
3 and 4 did not provide the corresponding cycloadducts
in the presence of alkenols 1a -d at room temperature.
However, as shown in Table 1, at 80 °C, the MOB 6a
generated from phenol 3 and allyl alcohol (1a ) underwent
cycloaddition to produce the desired adduct 10a in 38%
yield with the concomitant formation of 11a in 19% yield
(entry 9). In addition to these two cycloadducts, two other
minor products, viz. 1,4-benzoquinone 2320 and 4-acetox-
yphenol 24, were also isolated in 3 and 6% yields,
respectively (Scheme 2). The MOBs 6b, 6c, and 6d
exhibited similar reactivity furnishing a total of four
products in each case. On the other hand, the MOBs
7a -d generated at 80 °C from 2-methoxyphenol 4 and
alkenols 1a -d underwent cycloaddition to produce the
desired adducts 12a -d along with the corresponding
8-acetoxy cycloadducts 13a -d , respectively (Table 1).
Thus, the cycloadditions of the MOBs 5a -d to 7a -d were
found to be inefficient and appear to have no synthetic
value, except in the case of MOB 5c, which provided the
desired product 8c in 72% yield (Table 1, entry 5). No
attempt was made to isolate the MOBs 5a -d to 7a -d
since this type of MOBs were known to dimerize when
concentrated.
Plausible reaction pathways leading to the formation
of the products 23, 24, 10d , and 11d from 2-methoxyphe-
nol 3 in the presence of alkenol 1d , for instance, are
depicted in Scheme 2. The initial interaction of 3 with
the oxidant DAIB leads to the intermediate 25, which
subsequently takes part in the reaction through two
possible pathways A and B. In path A, a tandem oxidative
acetalization-IMDA reaction sequence starting from 25
results in the tricyclic derivative 10d . In path B, acetic
acid, generated from the oxidant, reacts with 25 to
provide 4-acetoxy-2,5-cyclohexadienone 26, which aro-
matizes to give the corresponding phenol 24. Subse-
quently, 2-methoxyphenol 24 undergoes DAIB-mediated
oxidative acetalization in the presence of alkenol 1d to
furnish the oxatricyclic derivative 11d via the MOB 27.
The other minor byproduct p-benzoquinone 23 may arise
from the oxidation of 24 and/or 26 (Scheme 2).
carbocyclic core of CP-263,114 was accomplished by
employing a tandem phenolic oxidation-IMDA sequence
as one of the key steps.15 It is also worth mentioning that
the IMDA reactions of 2-pyrones, homodienes structur-
ally related to MOBs, tethered with unsymmetrically
substituted alkynes and alkenes16 were employed as key
steps in the total syntheses of several alkaloids17 and
physiologically important vitamin D3 analogues.18
We have previously developed an unprecedented meth-
odology4 involving in situ tethering of an alkenol to a
diene system through acetal formation as an efficient
route to furnish a oxatricyclic ring system. Several easily
accessible 2-methoxyphenols were oxidized by (diacetoxy-
iodo)benzene (DAIB) in the presence of alkenols 1a -d
to generate MOBs that underwent IMDA reaction
smoothly to provide highly functionalized oxatricycles in
moderate to high yields. However, the IMDA reactions
of the MOBs derived from the parent 2-methoxyphenol
(guaiacol, 2) were found to be less efficient in this
methodology. To improve the yields of the desired cy-
cloadducts, a detour method that was developed recently
in this laboratory for the intermolecular Diels-Alder
reactions of the MOBs19 is now extended to the intramo-
lecular strategies as well. This protocol comprises se-
quential bromination of 2-methoxyphenols 2-4, tandem
oxidative acetalization-Diels-Alder reaction, and de-
bromination and has been proved quite successful. We
report herein the details of this detour method to
synthesize highly functionalized oxatricycles 8a -d , 10a -
d , and 12a -d .
Resu lts a n d Discu ssion
The IMDA reactions of MOBs 5a -d to 7a -d generated
from the 2-methoxyphenols 2-4 in the presence of
alkenols 1a -d , respectively, are outlined in Scheme 1,
and the results are summarized in Table 1. Initial
investigations are conducted on the MOB 5a that was
generated in situ from guaiacol (2) in the presence of allyl
alcohol (1a ) using DAIB in CH2Cl2. At room temperature,
the MOB 5a underwent intramolecular cycloaddition to
provide the tricyclic compound 8a in 33% yield.4a When
the IMDA reaction was attempted at 80 °C (method A),
the cycloadduct 8a was obtained in 28% yield along with
an unexpected IMDA adduct 9a , bearing acetoxy function
in 18% yield. Subsequently, this reaction was extended
Based on our detour method recently developed in the
case of intermolecular Diels-Alder reactions,19 we envi-
(5) (a) Hsu, P.-Y.; Lee, Y.-C.; Liao, C.-C. Tetrahedron Lett. 1998,
39, 659. (b) Rao, P. D.; Chen, C.-H.; Liao, C.-C. Chem. Commun. 1998,
155. (c) Carlini, R.; Higgs, K. C.; Rodrigo, R., Taylor, N. J . Chem.
Commun. 1998, 65. (d) Carlini, R.; Higgs, K.; Older, C.; Randhawa,
S.; Rodrigo, R. J . Org. Chem. 1997, 62, 2330. (e) Hsiu, P.-Y.; Liao, C.-
C. Chem. Commun. 1997, 1085. (f) Lee, T.-H.; Liao, C.-C.; Liu, W.-C.
Tetrahedron Lett. 1996, 37, 5897.
8158 J . Org. Chem., Vol. 67, No. 23, 2002

Diels-Alder Reactions of Brominated Masked o-Benzoquinones
TABLE 1. In tr a m olecu la r Diels-Ald er Rea ction s of Ma sk ed o-Ben zoqu in on es 5a -d , 6a -d , a n d 7a -d Der ived fr om
2-Meth oxyp h en ols 2, 3, a n d 4, Resp ectively (Dir ect Meth od )a
reaction conditions
products
additionc
after additiond
entry
phenol
alkenol
MOB
time (h)/T (°C)
time (h)/T (°C)
yield (%)
yield (%)
1e
2
2
1a
1a
1b
1b
1c
1c
1d
1d
1a
1b
1c
1d
1a
1b
1c
1d
5a
5a
5b
5b
5c
5c
5d
5d
6a
6b
6c
6d
7a
7b
7c
7d
4/rt
1/80
4/rt
1/80
4/rt
1/80
4/rt
1/80
1/80
1/80
1/80
1/80
1/80
1/80
1/80
1/80
8/rt
1/80
8/rt
1/80
8/rt
1/80
8/rt
1/80
1/80
1/80
1/80
1/80
1/80
1/80
1/80
1/80
8a /33
8a /28
8b/44
8b/25
8c/72
9a /0
9a /18
9b/0
9b/16
9c/0
9c/32
9d /0
9d /10
11a /19
11b/18
11c/10
11d /39
13a /17
13b/10
13c/10
13d /10
3e
4
5e
6
7
8c/38
8d /0
8
8d /17
10a /38
10b/36
10c/21
10d /4
12a /26
12b/26
12c/15
12d /3
9f
3g
4g
10f
11f
12f
13
14
15
16
a
b
Reactions in entries 2, 4, and 6-15 were carried out following method A. Five equivalents of alkenols was used in method A. c Time
d
during which 2-methoxyphenol (2, 3, or 4) was added to a mixture of alkenol 1 and DAIB in toluene. Time for which the reaction
mixture was stirred after the complete addition of 2-methoxyphenol (2, 3, 4) and reaction temperature. e Results in entries 1, 3, and 5
were taken from ref 4a for comparison. f In addition to the products mentioned in the table, 23 and 24 were also isolated during the
g
reactions in entries 9, 10, 11, and 12 in yields of 3, 6; 2, 6; 10, 5; and 3, 6%, respectively. Phenols 3 and 4 did not react with alkenols
1a -d at room temperature.
sioned that the incorporation of a readily removable
bromo substitution at the position-4 of MOBs 5a -d to
7a -d would prevent the formation of the undesired side
products and self-dimerization of MOBs. In fact, the
introduction of a bromine atom has been found useful
earlier in the cases of 2-pyrones where the resultant
brominated pyrones reacted with both electron-poor and
electron-rich dienophiles via normal and inverse-electron-
demand Diels-Alder cycloadditions with good stereocon-
trol.21 Thus, we have examined the IMDA reactions of
MOBs 17a -d to 19a -d obtained from the bromophenols
14-16, respectively, in the presence of the alkenols 1a -d
(Scheme 3 and Table 2). The requisite 4-bromophenols
14-1619a were readily accessed by the bromination (NBS/
AcOH) of the corresponding 2-methoxyphenols using a
modified literature procedure.22 The oxidation of 4-bro-
mophenol 14 with DAIB in CH2Cl2 carried out at 0 °C in
the presence of allyl alcohol reached completion within
10 min to provide MOB 17a . The crude MOB 17a was
subjected to the IMDA reaction by heating in dry toluene
at 80 °C for 12 h (method B). The usual workup followed
by silica gel column chromatography yielded the pure
cycloadduct 20a in 58%. To investigate the generality of
this reaction, it was extended to other alkenols 1b-d to
obtain the corresponding cycloadducts 20b-d in 70, 78,
and 38% yields, respectively. Similarly, the MOBs 18a -d
and 19a -d produced in the analogous manner by the
oxidation of the bromophenols 15 and 16 in the presence
of alkenols 1a -d furnished the expected products 21a -d
and 22a -d , respectively. All the MOBs 17a -d to 19a -d
were generated in situ, and no attempt was made to
isolate them. The 1H NMR (400 MHz) spectra of the crude
reaction mixtures resulted from the IMDA reactions of
the latter MOBs did not show the peaks corresponding
to the isomeric cycloadducts indicating that the cycload-
dition proceeded in a highly regio- and stereoselective
manner.
(6) (a) Hsu, D.-S.; Rao, P. D.; Liao, C.-C. Chem. Commun. 1998,
1795. (b) Hwang, J .-T.; Liao, C.-C. Tetrahedron Lett. 1991, 32, 6583.
(7) Chen, Y.-K.; Peddinti, R. K.; Liao, C.-C. Chem. Commun. 2001,
1340-1341.
(8) (a) Zimmerman, H. E.; Armesto, D. Chem. Rev. 1996, 96, 3065.
(b) Demuth, M. Org. Photochem. 1991, 11, 37. (c) Schaffner, K.;
Demuth, M. In Modern Synthetic Methods; Scheffold, R., Ed.; Springer-
Verlag: Berlin, 1986; Vol. 4, pp 61-88.
(9) Lee, T.-H.; Rao, P. D.; Liao, C.-C. Chem. Commun. 1999, 801.
(10) Chu, C.-S.; Liao, C.-C.; Rao, P. D. Chem. Commun. 1996, 1537.
(11) Lee, T.-H.; Liao, C.-C. Tetrahedron Lett. 1996, 37, 6869.
(12) Liu, W.-C.; Liao, C.-C. Chem. Commun. 1999, 117.
(13) Sutherland, H. S.; Higgs, K. C.; Taylor, N. J .; Rodrigo, R.
Tetrahedron 2001, 57, 309.
(14) Sutherland, H. S.; Souza, F. E. S.; Rodrigo, R. G. A. J . Org.
Chem. 2001, 66, 3639.
(15) Njardarson, J . T.; McDonald, I. M.; Spiegel, D. A.; Inoue, M.;
Wood, J . L. Org. Lett. 2001, 3, 2435.
(16) Afarinkia, K.; Vinader, V.; Nelson, T. D.; Posner, G. H.
Tetrahedron 1992, 48, 9111 and references therein.
(17) (a) Martin, S. F.; Ru¨eger, H.; Williamson, S. A.; Grzejszczak,
S. J . Am. Chem. Soc. 1987, 109, 6124. (b) Ciganek, E. J . Am. Chem.
Soc. 1981, 103, 6261.
(18) Posner, G. H.; Cho, C.-G.; Anjeh, T. E. N.; J ohnson, N.; Horst,
R. L.; Kobayashi, T.; Okano, T.; Tsugawa, N. J . Org. Chem. 1995, 60,
4617.
As evidenced from the yields incorporated in Tables 1
and 2, the IMDA reactions of the MOBs 17a -d to 19a -d
with bromo substitution are more facile than their
corresponding nonbrominated counterparts 5a -d to 7a -
d . This may be due to the bulkiness of the bromine atom
at the 4-position of 4-bromo-2-methoxyphenols that hin-
ders the ipso attack of AcOH to prevent the side reactions
and thus increases the yields of the IMDA reactions of
brominated MOBs 17a -d to 19a -d . Furthermore, the
introduction of a bromine atom at the 4-position retards
the self-dimerization of MOBs as we have observed in
the cases of intermolecular Diels-Alder reactions19 and
(19) (a) Lai, C.-H.; Shen, Y.-L.; Wang, M.-N.; Rao, N. S. K.; Liao,
C.-C. J . Org. Chem. 2002, 67, 6493. (b) Lai, C.-H.; Shen, Y.-L.; Liao,
C.-C. Synlett 1997, 1351.
(20) (a) Ho¨fle, G. Tetrahedron 1976, 32, 1431. (b) Singh, J . M.;
Turner, A. B. J . Chem. Soc., Perkin Trans. 1 1974, 2556.
(21) (a) Cho, C.-G.; Kim, Y.-W.; Lim, Y.-K.; Park, J .-S.; Lee, H.; Koo,
S. J . Org. Chem. 2002, 67, 290. (b) Posner, G. H.; Afarinkia, K.; Dai,
H. Org. Synth. 1995, 73, 231. (c) Afarinkia, K.; Posner, G. H.
Tetrahedron Lett. 1992, 33, 7839.
J . Org. Chem, Vol. 67, No. 23, 2002 8159

Lin et al.
SCHEME 2
SCHEME 3
TABLE 2. In tr a m olecu la r Diels-Ald er Rea ction s of
Ma sk ed 4-Br om o-o-ben zoqu in on es 17a -d , 18a -d , a n d
19a -d Der ived fr om 2-Meth oxyp h en ols 14, 15, a n d 16,
Resp ectively (Detou r Meth od )a
overall yield
adduct/ productc/
entry phenol alkenolb MOB yield (%) yield (%) detourd direct
1
2
3
4
5
6
7
8
9
14
15
16
1a
1b
1c
1d
1a
1b
1c
1d
1a
1b
1c
1d
17a
17b
17c
17d
18a
18b
18c
18d
19a
19b
19c
19d
20a /58
20b/70
20c/78
8a /91
8b/96
8c/90
51
65
68
32
56
62
65
48
47
63
65
39
33e
44e
72e
17
38
36
21
4
26
26
15
3
20d /38 8d /88
21a /73
21b/74
21c/79
10a /85
10b/92
10c/91
21d /62 10d /86
22a /60
22b/73
22c/75
12a /80
12b/88
12c/89
10
11
12
22d /46 12d /87
a
Reactions in entries 4-12 were carried out following method
B (MOBs were stirred in toluene at 80 °C for 12 h, see the
b
Experimental Section). Five equivalents of alkenols were used
in method B. c Debrominated products were obtained from method
d
C. Overall yield of three steps: bromination, tandem oxidative
acetalization-Diels-Alder reaction, and debromination. e Results
were taken from ref 4a for comparison.
tained via the direct method in one step in all cases but
one (8c, entry 3). It is especially worth mentioning that
there is 12-fold and 13-fold increase in the overall yields
of the cycloadducts 10d (entry 8) and 12d (entry 12),
respectively, via the detour method.
thus increases the yields of the IMDA reactions of
brominated MOBs. It may also be noted that the adducts
8d , 10d , and 12d (Table 1, entries 7, 8, 12, and 16) and
20d - 22d (Table 2, entries 4, 8, and 12) with one more
carbon (n ) 2) in the tether of their corresponding MOBs
are obtained in relatively lower yields. This is in agree-
ment with our earlier observation in the cases of IMDA
reactions of other MOBs.4a
The cycloadducts 20a -d to 22a -d were then subjected
to debromination using tributylammonium formate-
palladium reagent [Bu3N, HCO2H/Pd(PPh3)2Cl2]19a,23 to
obtain the corresponding debrominated products 8a -d ,
10a -d , and 12a -d in high to excellent yields (Table 2).
Thus, we have achieved the latter cycloadducts via the
detour method in higher overall yields than those ob-
The structures of all the new compounds were estab-
lished by spectroscopic methods including IR, 1H and 13C
NMR, and low- and high-resolution mass. For the major-
ity of the cycloadducts, satisfactory elemental analyses
were obtained. For most of the adducts in both of their
low-resolution and high-resolution mass spectra recorded
in electron impact mode (70 eV), the peaks corresponding
to the molecular ion could not be seen; instead the peaks
corresponding to M+ - 28 were observed indicating the
facile extrusion of CO from the molecular ions. The IR
specta of all the cycloadducts showed strong absorptions
at 1730-1749 cm-1, characteristic of the carbonyl group
adjacent to the R-methoxyl and cyclic ether functionality.4a
The IR spectra of 9a -d , 11a -d , and 13a -d showed
additional absorption at 1746-1764 cm-1 corresponding
to the carbonyl of the enol acetate.
(22) Mitchell, R. H.; Lai, Y.-H.; Williams, R. V. J . Org. Chem. 1979,
44, 4733.
(23) Cacchi, S.; Morera, E.; Ortar, G. Tetrahedron Lett. 1984, 42,
4821.
The regio- and stereochemical assignments of the
unknown cylcoadducts were made by comparing the
8160 J . Org. Chem., Vol. 67, No. 23, 2002

Diels-Alder Reactions of Brominated Masked o-Benzoquinones
CHART 1
20a -d to 22a -d can act as potential substrates for the
syntheses of higher olefins by organometallic coupling
reactions. The evaluation of the synthetic utility of the
bromoadducts 20a -d to 22a -d is underway in our
laboratory.
Exp er im en ta l Section
Gen er a l Meth od s. For general details and instrumenta-
tion, see our previous publication.4a
Gen er a l P r oced u r es for Ta n d em Oxid a tive Aceta liza -
tion -Diels-Ald er Rea ction s. (i) Th e Rea ction s of P h e-
n ols 2-4 w ith Alk en ols 1a -d . Meth od A. To a suspension
of DAIB (1.8 mM, 1.2 equiv) and an alkenol (7.5 mM, 5 equiv)
in toluene (1.2 mL) was added a solution of phenol (2, 3 or 4,
1.5 mM, 1 equiv) in toluene (2 mL) at 80 °C during 1 h using
a syringe pump under nitrogen atmosphere. Stirring was
continued for 1 h at the same temperature. The reaction
mixture was then cooled to rt, washed successively with
saturated NaHCO3 and brine, and extracted with EtOAc. The
combined organic layer was dried over anhydrous MgSO4 and
concentrated, and the residue was purified by silica gel column
chromatography with EtOAc/hexanes as eluent to furnish the
pure cycloadducts (8a -d to 13a -d ).
(ii) Th e Rea ction s of P h en ols 14-16 w ith Alk en ols 1a -
d . Meth od B. To a flask containing a mixture of DAIB (1.2
mM, 1.2 equiv) and an alkenol (5.0 mM, 5 equiv) in dry CH2-
Cl2 (5 mL) was added slowly a solution of phenol (14, 15, or
16, 1.0 mM, 1 equiv) in dry CH2Cl2 (5 mL) at 0 °C under
nitrogen atmosphere. The contents were then stirred for 10
min. The volatiles were removed under reduced pressure, and
the residue was dissolved in dry toluene (10 mL). After being
stirred at 80 °C for 12 h, the reaction mixture was cooled to rt
and concentrated under reduced pressure, and the residue was
purified by silica gel column chromatography using EtOAc/
hexanes as eluent to furnish the pure cycloadduct (20a -d to
22a -d ).
Gen er a l P r oced u r e for th e Debr om in a tion of Cy-
cloa d d u cts. Meth od C.19a,23 To the bromo compound (20a -d
to 22a -d , 0.5 mM) were added successively Bu3N (1.5 mM, 3
equiv), HCO2H (1.0 mM, 2 equiv), and Pd(PPh3)2Cl2 (0.025
mM, 0.05 equiv) in dry DMF (1.0 mL) under nitrogen atmo-
sphere. The contents were then heated at 80 °C for 16 h. The
reaction mixture was cooled to room temperature, diluted with
EtOAc, and worked up as usual. The thus obtained residue
was subjected to silica gel column chromatography (EtOAc/
hexanes) to afford the pure product (8a -d , 10a -d , 12a -d ).
Yields are given Table 2.
coupling patterns and coupling constants of the various
protons with those of the analogous IMDA adducts,
whose regio- and stereochemistries were earlier deter-
mined unambiguously in our laboratories.4a For the
cycloadduct 10b (R1 ) Me, R2 ) H), for instance, the
observed long-range W-type coupling between Hc and Hf
(J ) 1.3 Hz) confirms that the methyl group is oriented
syn to the vinyl bridge and anti to the ether ring,
supporting the assigned regiochemistry, which is further
corroborated by the coupling between Hg and Hi (J ) 3.2
Hz). Similarly, the coupling patterns of Ha-Hg and Hd-
Hf (Chart 1) in cycloadduct 12c (R1 ) H, R2 ) Me) are
diagnostic for the meta regiochemistry (with respect to
the carbonyl function), ruling out the alternate structures
that result from ortho regiochemistry. The proposed
regiochemistry gains additional support by the existence
of Hg-Hi coupling (J ) 3.6 Hz) for the adduct 12c. It may
be noted that there is no coupling between Hg and Hh
for the adducts 10a and 12c presumably due to their
orthogonal relationship. In the remaining cycloadducts
also, the stereochemical assignments were based on the
similar analogy of the coupling patterns.
The structural assignments of 20a -d to 22a -d were
based on the spectroscopic methods and the chemical
transformation into the corresponding debrominated
products 8a -d , 10a -d , and 12a -d . The coupling pat-
(1S*,3R*,6R*,7R*)-3-Met h oxy-4-oxa t r icyclo[4.3.1.03,7]-
dec-8-en -2-on e (8a).4a Following the general procedure (method
A), MOB 5a , generated in situ from phenol 2 and allyl alcohol
(1a ), was reacted and the crude residue was subjected to
column chromatography (EtOAc/hexanes ) 1:2) to afford 8a
(28% yield) as a colorless solid.
I
terns in the H NMR spectra of 20a -d to 22a -d are
analogous to those observed in case of 8a -d , 10a -d , and
12a -d , respectively.
Con clu sion
(1R *,3R *,6R *,7R *,10R *)-3-M e t h o x y -10-m e t h y l-4-
oxa tr icyclo[4.3.1.03,7]d ec-8-en -2-on e (8b).4a Following the
general procedure (method A), MOB 5b generated in situ from
phenol 2 and trans-crotyl alcohol (1b) was reacted and the
crude residue was subjected to column chromatography (EtOAc/
hexanes ) 1:2) to furnish 8b (25% yield) as a colorless liquid.
(1R *,3R *,6R *,7R *,10R *)-3-M e t h o x y -10-p h e n y l-4-
oxa tr icyclo[4.3.1.03,7]d ec-8-en -2-on e (8c).4a Following the
general procedure (method A), MOB 5c generated in situ from
phenol 2 and cinnamyl alcohol (1c) was reacted and the crude
residue was subjected to column chromatography (EtOAc/
hexanes ) 1:3) to afford 8c (38% yield) as a colorless solid:
mp 129-131 °C (from EtOAc-hexanes).
In conclusion, we have developed a new and efficient
detour method comprising sequential bromination of
2-methoxyphenols 2-4, tandem oxidative acetalization-
Diels-Alder reaction, and debromination to synthesize
highly functionalized oxatricyclic [m.3.1.0] ring systems.
The MOBs 17a -d to 19a -d generated in situ from
2-methoxyphenols 14-16, respectively, in the presence
of alkenols 1a -d , underwent highly regio- and stereo-
selective IMDA reactions to furnish exclusively meta,
syn-adducts (with respect to carbonyl group) 20a -d to
22a -d . The introduction of a bromine atom at position-4
of the 2-methoxyphenols served the purpose of achieving
higher overall yields of the oxatricycles 8a -d , 10a -d ,
and 12a -d via the detour method than those obtained
via the direct method. In addition, the vinyl bromides
(1S*,3R*,7S*,8R*)-3-Met h oxy-4-oxa t r icyclo[5.3.1.03,8]-
u n d ec-9-en -2-on e (8d ). Following the general procedure
(method A), MOB 5d generated in situ from phenol 2 and
homoallyl alcohol (1d ) was reacted and the crude residue was
subjected to column chromatography (EtOAc/hexanes ) 1:4)
J . Org. Chem, Vol. 67, No. 23, 2002 8161

Lin et al.
to provide 8d (17% yield) as a colorless solid: IR (film) 2946,
Hz, 1H), 3.80 (d, J ) 8.0 Hz, 1H), 3.51 (s, 3H), 3.31 (ddd, J )
6.0, 4.6, 1.8 Hz, 1H), 2.58-2.53 (m, 1H), 1.78 (dd, J ) 13.2,
10.0 Hz, 1H), 1.63 (d, J ) 13.2 Hz, 1H), 1.30 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 202.6, 136.4, 129.2, 100.7, 74.1, 51.4, 47.2,
42.8, 38.9, 37.3, 16.8; MS (EI, 12 eV) m/z (relative intensity)
166 (M+ - CO, 60), 151 (8), 134 (5), 125 (100), 119 (4), 107
(26), 91 (18), 79 (9), 74 (3), 43 (3); HRMS (EI) calcd for C10H14O2
(M+ - CO) 166.0994, found 166.0998.
1
1736 cm-1; H NMR (400 MHz, CDCl3) δ 6.37 (ddd, J ) 8.0,
6.8, 1.6 Hz, 1H), 6.20 (ddd, J ) 8.0, 6.4, 1.6 Hz, 1H), 3.90
(apparent dd, J ) 12.4, 5.6 Hz, 1H), 3.61 (ddd, J ) 13.2, 13.2,
2.8 Hz, 1H), 3.41 (s, 3H), 3.13 (m, 1H), 2.74-2.71 (m, 1H), 2.26
(m, 1H), 1.96-1.88 (m, 1H), 1.65 (ddd, J ) 13.6, 3.2, 3.2 Hz,
1H), 1.55 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 207.5, 134.0,
128.2, 93.2, 60.7, 50.9, 48.2, 43.2, 30.1, 29.1, 27.6; MS (EI, 70
eV) m/z (relative intensity) 166 (M+ - CO, 100), 138 (29), 113
(14), 107 (17), 91 (24) 79 (76); HRMS (EI) calcd for C11H14O3
(M+) 194.0943, found 194.0940.
(1S *,3R *,6R *,7S *)-3-Me t h o x y -2-o x o -4-o x a t r ic y c lo -
[4.3.1.03,7]d ec-8-en -8-yl a ceta te (9a ): colorless solid obtained
in 18% yield; mp 79-80 °C (from CH2Cl2-hexanes); IR (film)
2969, 1764, 1742 cm-1; 1H NMR (400 MHz, CDCl3) δ 5.88 (dd,
J ) 7.6, 3.0 Hz, 1H), 4.10 (dd, J ) 8.2, 3.6 Hz, 1H), 3.77 (d, J
) 8.2 Hz, 1H), 3.51 (s, 3H), 3.21 (dd, J ) 4.4, 3.0 Hz, 1H), 3.15
(ddd, J ) 7.6, 2.8, 2.8 Hz, 1H), 2.80-2.76 (m, 1H), 2.16 (s, 3H),
1.96-1.82 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 200.2, 168.5,
149.2, 111.7, 99.7, 73.4, 51.2, 46.4, 43.7, 35.5, 31.3, 20.7; MS
(EI, 70 eV) m/z (relative intensity) 238 (M+, 6), 210 (13), 209
(49), 193 (17), 167 (41) 99 (100); HRMS (EI) calcd for C12H14O5
(M+) 238.0841, found 238.0846.
(1R *,3R *,6R *,7R *,10R *)-3-Me t h oxy-1,10-d im e t h yl-4-
oxa tr icyclo[4.3.1.03,7]d ec-8-en -2-on e (10b). Following the
general procedure (method A), MOB 6b generated in situ from
phenol 3 and trans-crotyl alcohol (1b) was reacted and the
crude residue was subjected to column chromatography (EtOAc/
hexanes ) 1:3) to afford 10b (36% yield) as a colorless liquid:
1
IR (film) 2971, 1739 cm-1; H NMR (400 MHz, CDCl3) δ 6.21
(dd, J ) 8.1, 6.5 Hz, 1H), 5.78 (ddd, J ) 8.1, 1.3, 1.3 Hz, 1H),
4.11 (dd, J ) 8.0, 3.2 Hz, 1H), 3.80 (d, J ) 8.0 Hz, 1H), 3.51
(s, 3H), 3.25 (ddd, J ) 6.5, 4.7, 1.3 Hz, 1H), 2.04 (ddd, J ) 4.7,
3.2, 1.3 Hz, 1H), 1.80 (apparent m, ddq, J ) 7.1, 1.3, 1.3 Hz,
1H), 1.27 (s, 3H), 0.95 (d, J ) 7.1 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 203.2, 133.3, 128.6, 100.0, 73.7, 51.4, 51.3, 46.4, 42.3,
16.6, 15.1; MS (EI, 70 eV) m/z (relative intensity) 180 (M+
-
CO, 100), 165 (15), 151 (6), 125 (16), 105 (14), 91 (27), 77 (22),
65 (15), 39 (23), 27 (11); HRMS (EI) calcd for C11H16O2 (M+
CO) 180.1151, found 180.1167.
-
(1S*,3R*,6R*,7S*,10R*)-3-Meth oxy-10-m eth yl-2-oxo-4-
oxa tr icyclo[4.3.1.03,7]d ec-8-en -8-yl a ceta te (9b): colorless
solid (16% yield); mp 87-89 °C (from CH2Cl2-hexanes); IR
(1R*,3R*,6S*,7R*,10S*)-3-Meth oxy-1-m eth yl-10-p h en yl-
4-oxa tr icyclo[4.3.1.03,7]d ec-8-en -2-on e (10c). Following the
general procedure (method A), MOB 6c generated in situ from
phenol 3 and cinnamyl alcohol (1c) was reacted and the crude
residue was subjected to column chromatography (EtOAc/
hexanes ) 1:3) to furnish 10c (21% yield) as a colorless solid:
mp 136-137 °C (from EtOAc-hexanes); IR (film) 2973, 1740
(film) 2975, 1763, 1739 cm-1 1H NMR (400 MHz, CDCl3) δ
;
5.71 (dd, J ) 7.4, 2.6 Hz, 1H), 4.08 (dd, J ) 8.0, 3.2 Hz, 1H),
3.80 (d, J ) 8.0 Hz, 1H), 3.51 (s, 3H), 3.16 (dd, J ) 4.0, 2.6
Hz, 1H), 3.02 (dd, J ) 7.4, 3.2 Hz, 1H), 2.28-2.26 (m, 1H),
2.16 (s, 4H), 1.03 (d, J ) 8.0 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 200.6, 168.8, 148.7, 109.1, 99.1, 73.5, 51.5, 50.9, 46.9,
44.4, 37.3, 28.8, 18.5; MS (EI, 70 eV) m/z (relative intensity)
252 (M+, 3), 224 (5), 181 (16), 165 (14), 151 (10) 57 (100); HRMS
(EI) calcd for C12H14O5 (M+) 252.0998, found 252.0988.
1
cm-1; H NMR (400 MHz, CDCl3) δ 7.19-7.09 (m, 5H), 6.21
(dd, J ) 8.1, 6.6 Hz, 1H), 5.74 (dd, J ) 8.1, 1.6 Hz, 1H), 4.20
(dd, J ) 8.1, 3.4 Hz, 1H), 3.95 (d, J ) 8.1 Hz, 1H), 3.57 (s,
3H), 3.51-3.48 (m, 1H), 2.88 (dd, J ) 1.7, 1.7 Hz, 1H), 2.82
(apparent m, ddd, J ) 4.4, 3.4, 1.7 Hz, 1H), 1.08 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 202.0, 141.6, 133.4, 129.9, 129.3,
128.1, 127.1, 100.2, 72.3, 52.9, 52.2, 51.6, 48.5, 43.4, 15.7; MS
(EI, 70 eV) m/z (relative intensity) 242 (M+ - CO, 23), 183
(28), 167 (29), 143 (30), 125 (95), 115 (41), 100 (43), 91 (100),
77 (36), 65 (30); HRMS (EI) calcd for C17H18O3 (M+) 270.1256,
found 270.1262. Anal. Calcd for C17H18O3: C, 75.52, H, 6.72.
Found: C, 75.44, H, 6.68.
(1R*,3R*,6R*,7S*,10R*)-3-Meth oxy-2-oxo-10-p h en yl-2-
oxo-4-oxa tr icyclo[4.3.1.03,7]d ec-8-en -8-yl a ceta te (9c): col-
orless needles (32% yield); mp 109-110 °C (from CH2Cl2-
hexanes); IR (film) 2975, 1746 cm-1 1H NMR (400 MHz,
;
CDCl3) δ 7.27-7.25 (m, 5H), 5.52 (dd, J ) 7.4, 2.8 Hz, 1H),
4.20 (dd, J ) 8.4, 3.2 Hz, 1H), 3.93 (d, J ) 8.4 Hz, 1H), 3.56
(s, 3H), 3.41 (dd, J ) 4.0, 2.8 Hz, 1H), 3.35 (dd, J ) 2.8, 2.8
Hz, 1H), 3.26 (dd, J ) 7.4, 2.8 Hz, 1H), 3.16-3.14 (m, 1H),
2.24 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 199.7, 169.2, 150.0,
141.2, 128.4, 128.3, 127.0, 108.9, 99.3, 74.0, 52.4, 51.8, 47.7,
47.6, 44.8, 20.8; MS (EI, 70 eV) m/z (relative intensity) 286
(M+ - CO, 28), 244 (38), 243 (38), 144 (45), 115 (51) 99 (100);
HRMS (EI) calcd for C17H18O4 (M+ - CO) 286.1205, found
286.1203.
(1S*,3R*,7S*,8R*)-3-Met h oxy-1-m et h yl-4-oxa t r icyclo-
[5.3.1.03,8]u n d ec-9-en -2-on e (10d ). Following the general
procedure (method A), MOB 6d generated in situ from phenol
3 and homoallyl alcohol (1d ) was reacted and the crude residue
was subjected to column chromatography (EtOAc/hexanes )
1:4) to furnish 10d (4% yield) as a colorless liquid: IR (film)
(1S *,3R *,7S *,8S *)-3-Me t h o x y -2-o x o -4-o x a t r ic y c lo -
[5.3.1.03,8]u n d ec-9-en -9-yl a ceta te (9d ): colorless solid (10%
yield); mp 128-129 °C (from CH2Cl2-hexanes); IR (film) 2976,
1
2944, 1730 cm-1; H NMR (400 MHz, CDCl3) δ 6.40 (dd, J )
8.3, 6.5 Hz, 1H), 5.91 (ddd, J ) 8.3, 1.6, 0.8 Hz, 1H), 3.94-
3.92 (m, 1H), 3.60 (ddd, J ) 13.2, 12.7, 2.9 Hz, 1H), 3.43 (s,
3H), 2.73 (ddd, J ) 6.5, 3.5, 1.5 Hz, 1H), 2.37-2.31 (m, 1H),
1.97-1.88 (m, 1H), 1.83 (dd, J ) 13.5, 11.6 Hz, 1H), 1.56-
1
1757, 1730 cm-1; H NMR (400 MHz, CDCl3) δ 5.76 (dd, J )
7.0, 6.4, 2.6 Hz, 1H), 3.89 (dddd, J ) 12.8, 5.6, 1.2, 1.2 Hz,
1H), 3.56 (ddd, J ) 12.8, 12.8, 2.4 Hz, 1H), 3.44 (s, 3H), 3.12
(ddd, J ) 7.4, 3.0, 2.6 Hz, 1H), 2.74-2.69 (m, 1H), 2.61 (dd, J
) 2.8, 2.6 Hz, 1H), 2.17 (s, 3H), 2.06 (ddd, J ) 13.6, 11.6, 2.6
Hz, 1H), 1.91 (dddd, J ) 13.6, 9.6, 5.6, 3.6 Hz, 1H), 1.64 (ddd,
J ) 13.6, 3.2, 3.0 Hz, 1H), 1.52-1.57 (m, 1H); 13C NMR (125
MHz, CDCl3) δ 206.6, 168.9, 153.4, 109.8, 92.9, 60.7, 51.3, 47.6,
46.6, 29.7, 29.6, 27.7, 20.8; MS (EI, 70 eV) m/z (relative
intensity) 252 (M+, 2), 224 (5), 181 (17), 165 (21), 125 (18) 99
(100); HRMS (EI) calcd for C12H16O4 (M+ - CO) 224.1049,
found 224.1039.
1.50 (m, 1H), 1.42 (dd, J ) 13.5, 3.0 Hz, 1H), 1.24 (s, 3H); 13
C
NMR (100 MHz, CDCl3) δ 208.3, 133.9, 133.8, 93.6, 60.8, 51.0,
49.5, 42.3, 37.4, 30.3, 29.3, 17.0; MS (EI, 70 eV) m/z (relative
intensity) 180 (M+ - CO, 65), 165 (18), 152 (14), 137 (23), 120
(20), 105 (28), 93 (100), 87 (20), 79 (22), 59 (12); HRMS (EI)
calcd for C11H16O2 (M+ - CO) 180.1151, found 180.1140.
(1S *,3R *,6R *,7S *)-3-M e t h o x y -1-m e t h y l -2 -o x o -4 -
oxa tr icyclo[4.3.1.03,7]d ec-8-en -8-yl a ceta te (11a ): colorless
solid (19% yield); mp 78-80 °C (from EtOAc-hexanes); IR
(1S*,3R*,6R*,7R*)-3-Met h oxy-1-m et h yl-4-oxa t r icyclo-
[4.3.1.03,7]d ec-8-en -2-on e (10a ). Following the general pro-
cedure (method A), MOB 6a generated in situ from phenol 3
and allyl alcohol (1a ) was reacted and the crude residue was
subjected to column chromatography (EtOAc/hexanes ) 1:3)
to give 10a (38% yield) as a colorless liquid: IR (film) 2975,
1749 cm-1; 1H NMR (400 MHz, CDCl3) δ 6.20 (dd, J ) 8.2, 6.4
Hz, 1H), 5.97 (dd, J ) 8.2, 1.7 Hz, 1H), 4.13 (dd, J ) 8.0, 3.6
(film) 2969, 1764, 1742 cm-1 1H NMR (400 MHz, CDCl3) δ
;
5.57 (d, J ) 2.8 Hz, 1H), 4.13 (dd, J ) 8.0, 3.6 Hz 1H), 3.80 (d,
J ) 8.0 Hz, 1H), 3.53 (s, 3H), 3.23 (dd, J ) 4.4, 2.8 Hz, 1H),
2.85 (apparent m, ddd, J ) 10.0, 4.4, 3.6 Hz, 1H), 2.18 (s, 3H),
1.94 (dd, J ) 13.2, 10.0 Hz, 1H), 1.64 (d, J ) 13.2 Hz, 1H),
1.31 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 201.5, 168.7, 149.1,
117.0, 100.3, 74.0, 51.7, 46.8, 45.9, 39.4, 37.3, 20.9, 17.1; MS
(EI, 12 eV) m/z (relative intensity) 224 (M+ - CO, 12), 181
8162 J . Org. Chem., Vol. 67, No. 23, 2002

Diels-Alder Reactions of Brominated Masked o-Benzoquinones
(33), 165 (16), 150 (17), 141 (19), 123 (17), 108 (11), 99 (100),
79 (11), 65 (5); HRMS (EI) calcd for C12H16O4 (M+ - CO)
224.1048, found 224.1040. Anal. Calcd for C12H16O4: C, 61.90,
H, 6.39. Found: C, 61.93, H, 6.40.
δ 5.83 (ddq, J ) 6.7, 1.6, 1.4 Hz, 1H), 4.09 (dd, J ) 8.0, 3.2
Hz, 1H), 3.80 (d, J ) 8.0 Hz, 1H), 3.49 (s, 3H), 3.19 (dd, J )
6.7, 4.4 Hz, 1H), 2.85 (dd, J ) 3.6, 1.4 Hz, 1H), 2.24-2.17 (m,
1H), 1.95-1.93 (apparent m, ddd, J ) 4.4, 3.2, 1.2 Hz, 1H),
1.86 (d, J ) 1.6, 3H), 0.97 (d, J ) 7.2 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 201.4, 137.4, 120.7, 100.0, 73.8, 58.3, 51.2, 44.2,
42.3, 36.7, 21.7, 18.4; MS (EI, 70 eV) m/z (relative intensity)
180 (M+ - CO, 45), 165 (5), 125 (47), 121 (100), 105 (63), 91
(58), 77 (38), 65 (19), 55 (19), 43 (74); HRMS (EI) calcd for
C11H16O2 (M+ - CO) 180.1150, found 180.1152.
(1R*,3R*,6R*,7S*,10R*)-3-Meth oxy-1,10-dim eth yl-2-oxo-
4-oxa tr icyclo[4.3.1.03,7]d ec-8-en -8-yl a ceta te (11b): color-
less liquid (18% yield); IR (film) 2942, 1763, 1739 cm-1 1H
;
NMR (400 MHz, CDCl3) δ 5.39 (dd, J ) 2.8, 0.8 Hz, 1H), 4.12
(dd, J ) 8.0, 3.3 Hz, 1H), 3.81 (d, J ) 8.0 Hz, 1H), 3.54 (s,
3H), 3.16 (dd, J ) 4.4, 2.8 Hz, 1H), 2.37-2.34 (m, 1H), 2.19 (s,
3H), 1.80 (apparent m, ddq, J ) 7.0, 1.3, 0.8 Hz, 1H), 1.28 (s,
3H), 1.04 (d, J ) 7.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ
202.1, 168.7, 148.4, 114.0, 99.6, 73.5, 51.7, 50.2, 46.6, 46.4, 43.2,
20.7, 16.3, 15.4; MS (EI, 70 eV) m/z (relative intensity) 238
(M+ - CO, 58), 196 (39), 195 (79), 181 (29), 179 (22), 141 (19),
99 (100), 96 (20), 71 (18), 43 (84); HRMS (EI) calcd for C13H18O4
(M+ - CO) 238.1205, found 238.1214.
(1S*,3R*,6R*,7R*,10R*)-3-Meth oxy-9-m eth yl-10-p h en -
yl-4-oxa tr icyclo[4.3.1.03,7]d ec-8-en -2-on e (12c). Following
the general procedure (method A), MOB 7c generated in situ
from phenol 4 and cinnamyl alcohol (1c) was reacted and the
crude residue was subjected to column chromatography (EtOAc/
hexanes ) 1:4) to afford 12c (15% yield) as a colorless solid:
mp 118-119 °C (from EtOAc-hexanes); IR (film) 2961, 1744
1
cm-1; H NMR (400 MHz, CDCl3) δ 7.30-7.11 (m, 5H), 6.00
(1R*,3R*,6R*,7S*,10R*)-3-Meth oxy-1-m eth yl-2-oxo-10-
p h en yl-4-oxa tr icyclo[4.3.1.03,7]d ec-8-en -8-yl a ceta te (11c):
colorless solid (10% yield); mp 122-124 °C (from MeOH); IR
(ddq, J ) 6.7, 1.8, 1.6 Hz, 1H), 4.21 (dd, J ) 8.1, 3.4 Hz, 1H),
3.94 (d, J ) 8.1 Hz, 1H), 3.56 (s, 3H), 3.42 (dd, J ) 6.7, 4.4
Hz, 1H), 3.38 (dd, J ) 2.4, 2.3 Hz, 1H), 3.06-3.05 (m, 1H),
2.82-2.80 (m, 1H), 1.44 (d, J ) 1.6 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 200.5, 141.6, 137.3, 128.4, 127.8, 126.9, 121.9,
100.3, 74.2, 59.7, 51.4, 47.0, 44.0, 42.8, 21.4; MS (EI, 70 eV)
m/z (relative intensity) 242 (M+ - CO, 88), 183 (100), 167 (42),
141 (30), 125 (52), 115 (31), 105 (21), 91 (78), 77 (28), 59 (20);
HRMS (EI) calcd for C16H18O2 (M+ - CO) 242.1307, found
242.1368. Anal. Calcd for C17H18O3: C, 75.52, H, 6.72. Found:
C, 75.59, H, 6.76.
1
(film) 2975, 1746 cm-1; H NMR (400 MHz, CDCl3) δ 7.37-
7.23 (m, 5H), 5.26 (d, J ) 2.6 Hz, 1H), 4.19 (dd, J ) 8.2, 3.1
Hz, 1H), 3.94 (d, J ) 8.2 Hz, 1H), 3.59 (s, 3H), 3.42 (dd, J )
4.2, 2.6 Hz, 1H), 3.15 (apparent m, ddd, J ) 4.2, 3.1, 1.7 Hz,
1H), 2.86 (d, J ) 1.70 Hz, 1H), 2.27 (s, 3H), 1.07 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 201.1, 169.2, 149.7, 140.8, 129.4,
128.1, 127.2, 113.9, 99.7, 74.1, 53.6, 51.8, 51.0, 48.4, 47.0, 20.9,
16.0; MS (EI, 70 eV) m/z (relative intensity) 300 (M+ - CO,
4), 257 (7), 167 (13), 158 (22), 141 (15), 115 (33), 99 (100), 91
(26), 77 (14), 69 (16); HRMS (EI) calcd for C19H20O5 (M+)
328.1311, found 328.1315. Anal. Calcd for C19H20O5: C, 69.48,
H, 6.14. Found: C, 69.52, H, 6.19.
(1S*,3R*,7S*,8R*)-3-Meth oxy-10-m eth yl-4-oxa tr icyclo-
[5.3.1.03,8]u n d ec-9-en -2-on e (12d ). Following the general
procedure (method A), MOB 7d generated in situ from phenol
4 and homoallyl alcohol (1d ) was reacted and the crude residue
was subjected to column chromatography (EtOAc/hexanes )
1:4) to provide 12d (3% yield) as a colorless liquid; IR (film)
2948, 1732 cm-1; 1H NMR (400 MHz, CDCl3) δ 6.00 (ddq, J )
6.7, 2.1, 1.6 Hz, 1H), 3.94-3.89 (m, 1H), 3.63 (ddd, J ) 13.2,
12.7, 2.9 Hz, 1H), 3.43 (s, 3H), 2.94 (apparent q, ddd, J ) 2.8,
2.4, 2.1 Hz, 1H), 2.64 (dd, J ) 6.7, 3.8 Hz, 1H), 2.24-2.30 (m,
1H), 1.99-1.93 (m, 2H), 1.84 (d, J ) 1.6 Hz, 3H), 1.65 (ddd, J
) 13.6, 3.1, 2.8 Hz, 1H), 1.54-1.52 (m, 1H); 13C NMR (100
MHz, CDCl3) δ 207.6, 137.7, 126.6, 93.8, 60.8, 54.1, 51.1, 43.2,
30.6, 28.9, 28.8, 19.8; MS (EI, 70 eV) m/z (relative intensity)
180 (M+ - CO, 36), 152 (16), 137 (7), 121 (14), 105 (18), 93
(100), 77 (38), 65 (16), 59 (20), 43 (36); HRMS (EI) calcd for
(1 S *,3 R *,7 S *,8 S *)-3 -M e t h o x y -1 -m e t h y l -2 -o x o -4 -
oxa tr icyclo[5.3.1.03,8]u n d ec-9-en -9-yl a ceta te (11d ): color-
less solid (39% yield); mp 122-123 °C (from EtOAc-hexanes);
IR (film) 2976, 1757, 1730 cm-1; 1H NMR (400 MHz, CDCl3) δ
5.49 (d, J ) 2.6 Hz, 1H), 3.94-3.89 (m, J ) 12.8, 5.7, 1.5, 1.2
Hz, 1H), 3.55 (ddd, J ) 13.1, 12.8, 2.8 Hz, 1H), 3.47 (s, 3H),
2.81-2.75 (m, 1H), 2.63 (dd, J ) 3.6, 2.6 Hz, 1H), 2.19 (s, 3H),
1.99 (dd, J ) 13.6, 11.6 Hz, 1H), 1.96-1.81 (m, 1H), 1.51-
1.55 (m, 1H), 1.42 (dd, J ) 13.6, 3.6 Hz, 1H), 1.25 (s, 3H); 13
C
NMR (100 MHz, CDCl3) δ 207.4, 168.8, 153.2, 114.9, 93.3, 60.7,
51.3, 48.4, 47.4, 32.9, 29.8, 29.1, 20.8, 17.3; MS (EI, 70 eV)
m/z (relative intensity) 238 (M+ - CO, 6), 195 (27), 179 (45),
135 (14), 113 (80), 91 (12), 81 (22), 65 (5), 53 (23), 43 (100);
HRMS (EI) calcd for C13H18O4 (M+ - CO) 238.1205, found
238.1207. Anal. Calcd for C14H18O5: C, 63.13, H, 6.82. Found:
C, 63.10, H, 6.78.
C
11H16O2 (M+ - CO) 180.1150, found 180.1145.
(1S *,3R *,6R *,7S *)-3-M e t h o x y -9-m e t h y l -2 -o x o -4 -
oxa tr icyclo[4.3.1.03,7]d ec-8-en -8-yl a ceta te (13a ): colorless
solid (17% yield); mp 107-108 °C (from EtOAc-hexanes); IR
(film) 2951, 1743 cm-1; 1H NMR (400 MHz, CDCl3) δ 4.11 (dd,
J ) 8.0, 3.2 Hz, 1H), 3.78 (d, J ) 8.0 Hz, 1H), 3.52 (s, 3H),
3.19 (d, J ) 4.4 Hz, 1H), 2.99 (dd, J ) 3.3, 2.0 Hz, 1H), 2.86-
2.81 (m, 1H), 2.21 (s, 3H), 1.97 (ddd, J ) 13.3, 9.9, 2.1 Hz,
1H), 1.85 (ddd, J ) 13.3, 3.3, 1.5 Hz, 1H), 1.73 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 200.2, 169.0, 142.2, 122.0, 100.3,
73.6, 51.5, 50.1, 46.6, 36.6, 31.2, 20.4, 13.5; MS (EI, 70 eV)
m/z (relative intensity) 224 (M+ - CO, 16), 181 (45), 165 (26),
122 (17), 99 (90), 93 (16), 82 (13), 71 (13), 53 (13), 43 (100);
HRMS (EI) calcd for C12H16O4 (M+ - CO) 224.1048, found
224.1043. Anal. Calcd for C13H16O5: C, 61.90; H, 6.39. Found:
C, 61.85; H, 6.37.
(1S*,3R*,6R*,7R*)-3-Met h oxy-9-m et h yl-4-oxa t r icyclo-
[4.3.1.03,7]d ec-8-en -2-on e (12a ). Following the general pro-
cedure (method A), MOB 7a generated in situ from phenol 4
and allyl alcohol (1a ) was reacted and the crude residue was
subjected to column chromatography (EtOAc/hexanes ) 1:4)
to furnish 12a (26% yield) as a colorless solid: mp 107-108
°C (from EtOAc-hexanes); IR (film) 2959, 1742 cm-1; 1H NMR
(400 MHz, CDCl3) δ 5.80 (ddq, J ) 6.5, 1.7, 1.6 Hz, 1H), 4.11
(dd, J ) 8.0, 3.2 Hz, 1H), 3.79 (d, J ) 8.0 Hz, 1H), 3.51 (s,
3H), 3.24 (dd, J ) 6.5, 4.6 Hz, 1H), 2.97 (ddd, J ) 3.1, 1.8, 1.7
Hz, 1H), 2.50-2.46 (m, 1H), 1.86 (d, J ) 1.6 Hz, 3H), 1.85 (dd,
J ) 6.0, 1.8 Hz, 1H), 1.84 (dd, J ) 6.0, 3.1 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ 201.4, 140.4, 121.7, 100.7, 73.9, 51.2, 51.1,
42.4, 36.3, 30.7, 19.9; MS (EI, 70 eV) m/z (relative intensity)
166 (M+ - CO, 59), 125 (81), 107 (73), 91 (100), 79 (70), 77
(32), 65 (22), 59 (11), 51 (16), 39 (34); HRMS (EI) calcd for
(1S*,3R*,6R*,7S*,10R*)-3-Meth oxy-9,10-dim eth yl-2-oxo-
4-oxa tr icyclo[4.3.1.03,7]d ec-8-en -8-yl a ceta te (13b): color-
less solid (10% yield); IR (film) 2963, 1746, 1731 cm-1; 1H NMR
(400 MHz, CDCl3) δ 4.09 (dd, J ) 8.0, 3.2 Hz, 1H), 3.81 (d, J
) 8.0 Hz, 1H), 3.52 (s, 3H), 3.13 (d, J ) 4.4 Hz, 1H), 2.85 (d,
J ) 2.8 Hz, 1H), 2.33-2.30 (m, 2H), 2.21 (s, 3H), 1.73 (s, 3H),
1.06 (d, J ) 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 200.3,
170.0, 141.2, 119.1, 99.6, 73.5, 57.1, 51.4, 46.4, 44.4, 37.4, 20.4,
C
10H14O2 (M+ - CO) 166.0994, found 166.0997.
(1S *,3R *,6R *,7R *,10R *)-3-Me t h oxy-9,10-d im e t h yl-4-
oxa tr icyclo[4.3.1.03,7]d ec-8-en -2-on e (12b). Following the
general procedure (method A), MOB 7b generated in situ from
phenol 4 and trans-crotyl alcohol (1b) was reacted and the
crude residue was subjected to column chromatography (EtOAc/
hexanes ) 2:7) to furnish 12b (26% yield) as a colorless
liquid: IR (film) 2966, 1741 cm-1; 1H NMR (400 MHz, CDCl3)
18.1, 15.2; MS (EI, 70 eV) m/z (relative intensity) 238 (M+
CO, 21), 195 (56), 179 (45), 163 (17), 136 (24), 121 (18), 107
(28), 99 (94), 67 (15), 43 (100); HRMS (EI) calcd for C13H18O4
-
J . Org. Chem, Vol. 67, No. 23, 2002 8163

Lin et al.
(M+ - CO) 238.1205, found 238.1192. Anal. Calcd for
(dd, J ) 3.2, 8.2 Hz, 1H), 6.16 (dd, J ) 2.4, 7.2 Hz, 1H), 7.32-
7.24 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 198.6, 141.1, 128.7,
128.0, 127.3, 126.7, 120.4, 99.8, 73.5, 55.6, 53.3, 51.9, 47.4, 45.0;
C
13H16O5: C, 61.90; H, 6.39. Found: C, 61.85; H, 6.37.
(1S*,3R*,6R*,7S*,10R*)-3-Meth oxy-9-m eth yl-2-oxo-10-
MS (EI, 70 eV) m/z (relative intensity) 308 (65), 306 (M+
-
p h en yl-4-oxa tr icyclo[4.3.1.03,7]d ec-8-en -8-yl a ceta te (13c):
colorless solid (10% yield); IR (film) 2978, 1746 cm-1; 1H NMR
(400 MHz, CDCl3) δ 7.35-7.20 (m, 5H), 4.21 (dd, J ) 8.1, 3.0
Hz, 1H), 3.93 (d, J ) 8.1 Hz, 1H), 3.58 (s, 3H), 3.40 (d, J ) 4.4
Hz, 1H), 3.37 (dd, J ) 2.8, 1.0 Hz, 1H), 3.19-3.21 (m, 1H),
3.03 (d, J ) 2.8 Hz, 1H), 2.28 (s, 3H), 1.34 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 199.5, 169.5, 142.6, 141.1, 128.5, 128.0,
126.9, 118.7, 99.7, 74.1, 58.9, 51.8, 48.0, 47.2, 49.6, 20.6, 14.8;
MS (EI, 70 eV) m/z (relative intensity) 300 (M+ - CO, 72),
257 (100), 241 (77), 225 (47), 197 (53), 158 (94), 128 (56), 115
CO, 62), 249 (11), 247 (11), 191 (19), 189 (19), 168 (93), 167
(100), 153 (21), 152 (26); HRMS (EI) calcd for C16H15O379Br
(M+) 334.0205, found 334.0223.
(1S*,3R*,7S*,8R*)-9-Br om o-3-m et h oxy-4-oxa t r icyclo-
[5.3.1.03,8]u n d ec-9-en -2-on e (20d ). Following the general
procedure (method B), MOB 17d generated in situ from phenol
14 and homoallyl alcohol (1d ) was reacted and the crude
residue was subjected to column chromatography (EtOAc/
hexanes ) 1:4) to provide 20d (38% yield) as a noncrystalliz-
(69), 99 (100), 91 (55); HRMS (EI) calcd for C18H20O4 (M+
CO) 300.1362, found 300.1350.
-
able brown color solid: IR (film) 2945, 1737 cm-1 1H NMR
;
(400 MHz, CDCl3) δ 6.35 (dd, J ) 6.8, 2.4 Hz, 1H), 3.92-3.88
(m, 1H), 3.58 (ddd, J ) 12.8, 12.8, 2.8 Hz, 1H), 3.46 (s, 3H),
3.16 (ddd, J ) 6.8, 3.2, 3.2 Hz, 1H), 2.98 (dd, J ) 3.2, 2.4 Hz,
1H), 2.53 (dt, J ) 11.6, 3.2 Hz, 1H), 2.02 (ddd, J ) 14.0, 11.6,
2.8 Hz, 1H), 1.88-1.97 (m, 1H), 1.66 (ddd, J ) 13.6, 3.2, 3.2
Hz, 1H), 1.56 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 205.4,
127.3, 123.8, 93.3, 60.7, 53.0, 51.5, 50.1, 29.8, 29.1, 28.5; MS
(EI, 70 eV) m/z (relative intensity) 246 (96), 244 (M+ - CO,
100), 165 (20), 159 (22), 157 (22), 133 (15), 105 (36); HRMS
(1S *,3R *,7S *,8S *)-3-M e t h o x y -10-m e t h y l-2-o x o -4-
oxa tr icyclo[5.3.1.03,8]u n d ec-9-en -9-yl a ceta te (13d ): color-
less solid (10% yield); mp 91-92 °C (from EtOAc-hexanes);
IR (film) 2949, 1749 cm-1; 1H NMR (400 MHz, CDCl3) δ 3.93-
3.88 (m, 1H), 3.58 (ddd, J ) 13.2, 12.8, 2.8 Hz, 1H), 3.46 (s,
3H), 2.94 (dd, J ) 3.0, 2.8 Hz, 1H), 2.82-2.76 (m, 1H), 2.58
(d, J ) 3.6 Hz, 1H), 2.21 (s, 3H), 2.10 (ddd, J ) 13.7, 11.3, 2.8
Hz, 1H), 1.96-1.87 (m, 1H), 1.71 (s, 3H), 1.65 (dd, J ) 13.7,
3.3 Hz, 1H), 1.58-1.52 (m, 1H); 13C NMR (100 MHz, CDCl3) δ
206.8, 169.0, 146.6, 119.5, 93.6, 60.7, 53.1, 51.3, 47.4, 30.1, 29.6,
28.7, 20.4, 13.3; MS (EI, 70 eV) m/z (relative intensity) 238
(M+ - CO, 14), 195 (51), 179 (74), 163 (12), 135 (17), 113 (75),
107 (25), 81 (25), 53 (3), 43 (100); HRMS (EI) calcd for C13H18O4
(M+ - CO) 238.1205, found 238.1200. Anal. Calcd for
(EI) calcd for
244.0087.
C
10H13O279Br (M+ - CO) 244.0028, found
(1S *,3R *,6R *,7S *)-8-Br om o-3-m e t h oxy-1-m e t h yl-4-
oxa tr icyclo[4.3.1.03,7]d ec-8-en -2-on e (21a ). Following the
general procedure (method B), MOB 18a generated in situ
from phenol 15 and allyl alcohol (1a ) was reacted and the crude
residue was subjected to column chromatography (EtOAc/
hexanes ) 2:7) to furnish 21a (73% yield) as a colorless solid:
mp 99-100 °C (from EtOAc-hexanes); IR (film) 2973, 1749
C
14H18O5: C, 63.13; H, 6.82. Found: C, 63.12; H, 6.78.
(1S*,3R*,6R*,7R*)-8-Br om o-3-m et h oxy-4-oxa t r icyclo-
[4.3.1.03,7]d ec-8-en -2-on e (20a ). Following the general pro-
cedure (method B), MOB 17a generated in situ from phenol
14 and allyl alcohol (1a ) was reacted and the crude residue
was subjected to column chromatography (EtOAc/hexanes )
1:3) to furnish 20a (58% yield) as a light brown color gran-
ules: mp 108-109 °C (from EtOAc-hexanes); IR (film) 2944,
1747 cm-1; 1H NMR (400 MHz, CDCl3) δ 4.12 (dd, J ) 8.0, 3.2
Hz, 1H), 3.77 (d, J ) 8.0 Hz, 1H), 3.53 (s, 3H), 3.52 (m, 1H),
3.20 (ddd, J ) 7.2, 2.8, 2.8 Hz, 1H), 2.72 (m, 1H), 1.89 (m,
2H); 13C NMR (100 MHz, CDCl3) δ 199.3, 129.3, 119.9, 100.1,
73.1, 52.4, 51.6, 47.4, 35.7, 30.7; MS (EI, 70 eV) m/z (relative
intensity) 232 (47), 230 (M+ - CO, 48), 191 (74), 189 (78), 171
(11), 151 (14), 119 (19), 92 (48), 91 (100); HRMS (EI) calcd for
1
cm-1; H NMR (400 MHz, CDCl3) δ 6.11 (d, J ) 2.0 Hz, 1H),
4.12 (dd, J ) 8.0, 3.6 Hz, 1H), 3.78 (d, J ) 8.0 Hz, 1H), 3.51
(s, 3H), 3.50 (dd, J ) 4.4, 2.0 Hz, 1H), 2.77 (ddd, J ) 10.4, 4.4,
3.6 Hz, 1H), 1.88 (dd, J ) 13.2, 10.4 Hz, 1H), 1.64 (d, J ) 4.4,
2.0 Hz, 1H), 1.29 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 200.5,
134.4, 100.5, 119.3, 73.5, 51.9, 51.6, 49.5, 38.5, 37.2, 16.8; MS
(EI, 70 eV) m/z (relative intensity) 272 (M+, 2), 246 (59), 244
(59), 203 (100), 165 (30), 133 (27), 105 (80), 91 (64), 77 (64), 39
(20); HRMS (EI) calcd for C10H1379BrO2 (M+ - CO) 244.0098,
found 244.0099; C10H1381BrO2 246.0079, found 246.0078. Anal.
Calcd for C11H13BrO3 : C, 48.37, H, 4.80. Found: C, 48.68, H,
4.96.
C
10H11O379Br (M+) 257.9892, found 257.9940.
(1R*,3R*,6R*,7R*,10R*)-8-Br om o-3-m eth oxy-1,10-d im -
eth yl-4-oxa tr icyclo[4.3.1.03,7]d ec-8-en -2-on e (21b). Follow-
ing the general procedure (method B), MOB 18b generated in
situ from phenol 15 and trans-crotyl alcohol (1b) was reacted
and the crude residue was subjected to column chromatogra-
phy (EtOAc/hexanes ) 1:4) to provide 21b (74% yield) as a
colorless solid: mp 100-101 °C (from EtOAc-hexanes); IR
(1S*,3R*,6R*,7S*,10R*)-8-Br om o-3-m eth oxy-10-m eth yl-
4-oxa tr icyclo[4.3.1.03,7]d ec-8-en -2-on e (20b). Following the
general procedure (method B), MOB 17b generated in situ
from phenol 14 and trans-crotyl alcohol (1b) was reacted and
the crude residue was subjected to column chromatography
(EtOAc/hexanes ) 1:3) to furnish 20b (70% yield) as a colorless
crystals: mp 119-122 °C (from EtOAc-hexanes); IR (film)
1
(film) 2968, 1744 cm-1; H NMR (400 MHz, CDCl3) δ 5.97 (d,
1
2967, 1747 cm-1; H NMR (400 MHz, CDCl3) δ 6.34 (dd, J )
J ) 2.8 Hz, 1H), 4.10 (dd, J ) 8.0, 3.6 Hz, 1H), 3.78 (d, J )
8.0 Hz, 1H), 3.52 (s, 3H), 3.45 (dd, J ) 4.8, 2.8 Hz, 1H), 2.25
(ddd, J ) 4.8, 3.6, 1.6 Hz, 1H), 1.79 (q, J ) 1.6, 7.4 Hz, 1H),
1.25 (s, 3H), 0.98 (d, J ) 7.2 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 201.0, 131.6, 118.4, 99.8, 73.0, 53.6, 51.5, 51.2, 46.1,
42.3, 16.6, 15.0; MS (EI, 70 eV) m/z (relative intensity) 286
7.2, 2.4 Hz, 1H), 4.09 (dd, J ) 8.0, 3.2 Hz, 1H), 3.79 (d, J )
8.0 Hz, 1H), 3.51 (s, 3H), 3.48 (dd, J ) 4.4, 2.2 Hz, 1H), 3.06
(dd, J ) 7.2, 2.8 Hz, 1H), 2.20-2.18 (m, 2H), 1.00 (d, J ) 7.2
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 199.4, 126.7, 119.1,
99.3, 73.1, 54.4, 52.4, 51.6, 44.5, 36.9, 18.8; MS (EI, 70 eV)
m/z (relative intensity) 246 (69), 244 (M+ - CO, 71), 191 (57),
189 (57), 187 (21), 184 (24), 165 (24), 133 (20), 106 (83), 105
(100); HRMS (EI) calcd for C10H13O279Br (M+ - CO) 244.0099,
found 244.0087.
(M+, 100), 258 (83), 203 (60), 200 (33), 170 (8), 146 (13), 119
79
(48), 105 (42), 63 (11), 53 (7); HRMS (EI) calcd for C11H15
-
BrO2 (M+ - CO) 258.0255, found 258.0256. Anal. Calcd for
C
12H15BrO3: C, 50.19, H, 5.26. Found: C, 50.15, H, 5.29.
(1R*,3R*,6R*,7R*,10R*)-8-Br om o-3-m et h oxy-10-p h en -
yl-4-oxa tr icyclo[4.3.1.03,7]d ec-8-en -2-on e (20c). Following
the general procedure (method B), MOB 17c generated in situ
from phenol 14 and cinnamyl alcohol (1c) was reacted and the
crude residue was subjected to column chromatography (EtOAc/
hexanes ) 1:4) to give 20c (78% yield) as colorless needles:
mp 139-141 °C (from EtOAc-hexanes); IR (film) 2973, 1749
(1R*,3R*,6R*,7R*,10R*)-8-Br om o-3-m eth oxy-1-m eth yl-
10-p h en yl-4-oxa t r icyclo[4.3.1.03,7]d ec-8-en -2-on e (21c).
Following the general procedure (method B), MOB 18c gener-
ated in situ from phenol 15 and cinnamyl alcohol (1c) was
reacted and the crude residue was subjected to column
chromatography (EtOAc/hexanes ) 1:5) to afford 21c (79%
yield) as a colorless solid: mp 161-162 °C (from EtOAc-
cm-1; H NMR (400 MHz, CDCl3) δ 3.00 (m, 1H), 3.31 (dd, J
hexanes); IR (film) 2973, 1744 cm-1 1H NMR (400 MHz,
;
1
) 3.2, 7.2 Hz, 1H), 3.36 (dd, J ) 2.0, 2.0 Hz, 1H), 3.58 (s, 3H),
3.69 (dd, J ) 2.4, 4.4 Hz, 1H), 3.94 (d, J ) 8.2 Hz, 1H), 4.21
CDCl3) δ 7.29-7.01 (m, 5H), 5.86 (d, J ) 2.8 Hz, 1H), 4.18
(dd, J ) 8.0, 3.2 Hz, 1H), 3.93 (d, J ) 8.0 Hz, 1H), 3.58 (s,
8164 J . Org. Chem., Vol. 67, No. 23, 2002

Diels-Alder Reactions of Brominated Masked o-Benzoquinones
3H), 3.67 (dd, J ) 4.6, 2.8 Hz, 1H), 3.00 (ddd, J ) 4.6, 3.2, 2.0
Hz, 1H), 2.85 (d, J ) 2.0 Hz, 1H), 1.06 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 199.9, 140.5, 131.7, 128.9, 128.4, 128.3, 127.3,
119.9, 100.0, 73.6, 54.4, 53.1, 52.4, 51.7, 48.3, 15.7; MS (EI,
70 eV) m/z (relative intensity) 348 (M+, 2), 322 (42), 320 (43),
241 (18), 205 (42), 181 (100), 165 (67), 152 (23), 115 (33), 91
(39); HRMS (EI) calcd for C16H1779BrO2, (M+ - CO) 320.0411,
phy (EtOAc/hexanes ) 1:5) to provide 22c (75% yield) as a
colorless solid: mp 127-128 °C (from EtOAc-hexanes); IR
1
(film) 2963, 1747 cm-1; H NMR (400 MHz, CDCl3) δ 7.30-
7.03 (m, 5H), 4.20 (dd, J ) 8.4, 3.2 Hz, 1H), 3.92 (d, J ) 8.4
Hz, 1H), 3.69 (d, J ) 4.4 Hz, 1H), 3.57 (s, 3H), 3.36 (dd, J )
2.0, 2.0 Hz, 1H), 3.18 (d, J ) 2.0 Hz, 1H), 3.01 (m, 1H), 1.43
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 198.3, 140.7, 133.8,
128.7, 127.5, 127.1, 114.0, 100.2, 73.4, 61.0, 52.6, 51.6, 47.5,
44.1, 20.7; MS (EI, 70 eV) m/z (relative intensity) 348 (M+,
72), 322 (98), 320 (100), 261 (7), 203 (80), 181 (28), 165 (42),
141 (10), 115 (20), 63 (10); HRMS (EI) calcd for C16H1779BrO2
(M+ - CO) 320.0411, found 320.0412; calcd for C16H1781BrO2
322.0392, found 322.0392. Anal. Calcd for C17H17BrO3: C,
58.47; H, 4.91. Found: C, 58.31; H, 4.99.
found 320.0412; calcd for
C
16H1781BrO2, 322.0392, found
322.0392. Anal. Calcd for C17H17BrO3: C, 58.47; H, 4.91.
Found: C, 58.34; H, 4.91.
(1S *,3R *,7S *,8R *)-9-Br om o-3-m e t h oxy-1-m e t h yl-4-
oxa tr icyclo[5.3.1.03,8]u n d ec-9-en -2-on e (21d ). Following the
general procedure (method B), MOB 18d generated in situ
from phenol 15 and homoallyl alcohol (1d ) was reacted and
the crude residue was subjected to column chromatography
(EtOAc/hexanes ) 1:6) to furnish 21d (62% yield) as a colorless
solid: mp 90-91 °C (from EtOAc-hexanes); IR (film) 2968,
(1S *,3R *,7S *,8R *)-9-Br om o-3-m e t h oxy-10-m e t h yl-4-
oxa tr icyclo[5.3.1.03,8]u n d ec-9-en -2-on e (22d ). Following the
general procedure (method B), MOB 19d generated in situ
from phenol 16 and homoallyl alcohol (1d ) was reacted and
the crude residue was subjected to column chromatography
(EtOAc/hexanes ) 1:6) to afford 22d (46% yield) as a colorless
solid: mp 90-91 °C (from EtOAc-hexanes); IR (film) 2945,
1
1730 cm-1; H NMR (400 MHz, CDCl3) δ 6.05 (d, J ) 2.4 Hz,
1H), 3.91-3.89 (m, 1H), 3.54 (ddd, J ) 12.8, 12.8, 3.2 Hz, 1H),
2.97 (dd, J ) 3.6, 2.4 Hz, 1H), 3.46 (s, 3H), 2.58 (m, 1H), 1.56-
1.51 (m, 2H), 1.51-1.56 (m, 1H), 1.42 (dd, J ) 13.6, 3.2 Hz,
1H), 1.22 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 206.3, 132.5,
123.2, 93.7, 60.7, 52.7, 52.0, 51.3, 37.0, 29.9, 29.8, 17.0; MS
(EI, 70 eV) m/z (relative intensity) 286 (M+, 19), 258 (100),
243 (9), 227 (36), 207 (18), 179 (15), 147 (47), 119 (98), 105
(37), 89 (100); HRMS (EI) calcd for C11H1579BrO2 (M+ - CO)
258.0255, found 258.0256. Anal. Calcd for C12H15BrO3 : C,
50.19; H, 5.26. Found: C, 49.98; H, 5.28.
1
1733 cm-1; H NMR (400 MHz, CDCl3) δ 3.92-3.87 (m, 1H),
3.59 (ddd, J ) 13.8, 12.8, 2.8 Hz, 1H), 3.46 (s, 3H), 3.09 (dd, J
) 3.0, 2.8 Hz, 1H), 2.97 (d, J ) 3.6 Hz, 1H), 2.53 (m, 1H), 2.01
(ddd, J ) 13.6, 11.4, 2.8 Hz, 1H), 1.98-1.87 (m, 1H), 1.86 (s,
3H), 1.65 (ddd, J ) 13.6, 3.2, 3.0 Hz, 1H), 1.59-1.54 (m, 1H);
13C NMR (100 MHz, CDCl3) δ 205.7, 134.2, 117.8, 93.8, 60.6,
55.2, 52.5, 51.4, 29.9, 29.1, 28.7, 19.1; MS (EI, 70 eV) m/z
(relative intensity) 286 (M+, 45), 260 (92), 258 (100), 229 (30),
227 (42), 174 (5), 147 (12), 119 (23), 105 (18), 63 (10); HRMS
(1S *,3R *,6R *,7R *)-8-Br om o-3-m e t h oxy-9-m e t h yl-4-
oxa t r icyclo[4.3.1.03,7]d ec-8-en -2-on e (22a ). Following the
general procedure (method B), MOB 19a generated in situ
from phenol 16 and allyl alcohol (1a ) was reacted and the crude
residue was subjected to column chromatography (EtOAc/
hexanes ) 1:3) to furnish 22a (60% yield) as a colorless solid:
mp 128-129 °C (from EtOAc-hexanes); IR (film) 2889, 1739
(EI) calcd for
258.0255. Anal. Calcd for C11H13BrO3
Found: C, 50.14; H, 5.29.
C
11H1579BrO2 (M+ - CO) 258.0255, found
: C, 50.19; H, 5.26.
2-Meth oxy-6-m eth yl-1,4-ben zoqu in on e (23):20 colorless
liquid; IR (film) 1678, 1651 cm-1; 1H NMR (400 MHz, CDCl3)
δ 6.54 (apparent m, dq, J ) 2.4, 1.6 Hz, 1H), 5.88 (d, J ) 2.4
Hz, 1H), 3.82 (s, 3H), 2.07 (d, J ) 1.6 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 187.4, 182.4, 158.8, 143.6, 133.8, 107.3, 56.2,
15.5; MS (EI, 70 eV) m/z (relative intensity) 152 (M+, 59), 137
(12), 124 (83), 109 (32), 96 (20), 81 (14), 69 (100), 66 (31), 53
(32), 43 (22); HRMS (EI) calcd for C8H8O3 (M+) 152.0473, found
152.0474. Anal. Calcd for C8H8O3: C, 63.14, H, 5.30. Found:
C, 63.09, H, 5.29.
1
cm-1; H NMR (400 MHz, CDCl3) δ 4.10 (dd, J ) 8.0, 3.2 Hz,
1H), 3.76 (d, J ) 8.0 Hz, 1H), 3.52 (d, J ) 4.0 Hz, 1H), 3.50 (s,
3H), 3.12 (dd, J ) 3.2, 2.4 Hz, 1H), 2.71 (m, 1H), 1.87 (m, 5H);
13C NMR (100 MHz, CDCl3) δ 199.1, 136.6, 113.8, 100.6, 73.3,
52.5, 52.1, 51.4, 36.3, 30.6, 19.4; MS (EI, 70 eV) m/z (relative
intensity) 272 (M+, 85), 246 (88), 244 (95), 229 (12), 205 (90),
203 (100), 133 (12), 105 (72), 91 (30), 63 (10); HRMS (EI) calcd
for C10H1379BrO2 (M+ - CO) 244.0098, found 244.0099; calcd
for C10H1381BrO2 246.0079, found 246.0078. Anal. Calcd for
4-Hyd r oxy-3-m eth oxy-5-m eth ylp h en yl a ceta te (24): col-
1
orless liquid; IR (film) 3466, 2946, 1755 cm-1; H NMR (400
C
11H13BrO3: C, 48.37; H, 4.80. Found: C, 48.38; H, 4.84.
(1S*,3R*,6R*,7R*,10R*)-8-Br om o-3-m eth oxy-9,10-d im -
MHz, CDCl3) δ 6.48 (s, 2H), 5.58 (br, 1H), 3.85 (s, 3H), 2.27 (s,
3H), 2.24 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.1, 146.1,
142.7, 141.4, 124.0, 115.4, 102.5, 56.0, 21.0, 15.4; MS (EI, 70
eV) m/z (relative intensity) 196 (M+, 16), 154 (100), 139 (51),
111 (30); HRMS (EI) calcd for C8H10O2 (M+) 196.0735, found
196.0733.
eth yl-4-oxa tr icyclo[4.3.1.03,7]d ec-8-en -2-on e (22b). Follow-
ing the general procedure (method B), MOB 19b generated in
situ from phenol 16 and trans-crotyl alcohol (1b) was reacted
and the crude residue was subjected to column chromatogra-
phy (EtOAc/hexanes ) 1:4) to afford 22b (73% yield) as a
colorless solid: mp 88-89 °C (from EtOAc-hexanes); IR (film)
1
2962, 1749 cm-1; H NMR (400 MHz, CDCl3) δ 4.07 (dd, J )
Ack n ow led gm en t. We gratefully acknowledge the
financial support from the National Science Council
(NSC) of the Republic of China. N.S.K.R. thanks the
Ministry of Education for a postdoctoral fellowship
under the Program for Promoting Academic Excellence
of Universities, 89-B-FA-04-1-4. We thank Dr. R. K.
Peddinti for helpful discussions.
8.0, 2.8 Hz, 1H), 3.78 (d, J ) 8.0 Hz, 1H), 3.50 (s, 3H), 3.47 (d,
J ) 4.4 Hz, 1H), 2.98 (d, J ) 2.8 Hz, 1H), 2.19 (m, 2H), 1.88
(s, 3H), 0.96 (d, J ) 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3)
δ 199.2, 133.9, 112.6, 99.9, 73.2, 59.5, 51.8, 51.5, 44.2, 37.0,
21.1, 18.6; MS (EI, 70 eV) m/z (relative intensity) 286 (M+,
100), 260 (87), 258 (95), 203 (75), 179 (5), 146 (10), 119 (62),
105 (51), 91 (12), 63 (10); HRMS (EI) calcd for C11H1579BrO2
(M+ - CO) 258.0255, found 258.0255; calcd for C11H1581BrO2
260.0236, found 260.0235. Anal. Calcd for C12H15BrO3: C,
50.19; H, 5.26. Found: C, 50.01; H, 5.33.
Su p p or tin g In for m a tion Ava ila ble: Copies of 1H and 13C
NMR and DEPT spectra for compounds 8d , 10a -d , 12a -d ,
and 20-22(a -d ) and a table of selected coupling constant
values for the cycloadducts. This material is available free of
charge via the Internet at http://pubs.acs.org.
(1S*,3R*,6R*,7R*,10R*)-8-Br om o-3-m eth oxy-9-m eth yl-
10-ph en yl-4-oxatr icyclo[4.3.1.03,7]dec-8-en -2-on e (22c). Fol-
lowing the general procedure (method B), MOB 19c generated
in situ from phenol 16 and cinnamyl alcohol (1c) was reacted
and the crude residue was subjected to column chromatogra-
J O020316K
J . Org. Chem, Vol. 67, No. 23, 2002 8165