Synthesis of angular quinoid heterocycles from 2-(2-nitrovinyl)-1,4- benzoquinone

Article abstract of DOI:10.1021/jo981899u

Reactions of 2-(2-nitrovinyl)-1,4-benzoquinone with furans, indoles, and endocyclic enol ethers form angular fused heterocyclic quinoid ring systems. The reaction proceeds by a formal inverse electron-demand [4 + 2] cycloaddition reaction of the nitrovinylquinone and a double bond of the heterocycle. The initial quinoid cycloadducts can be readily tautomerized to hydroquinoid species, which may be dehydrogenated to fully aromatic quinones. In the case of furans, the tautomerized adducts may be ring-opened to give 6,7-di- or 5,6,7-tri-substituted-1,4-naphthalenediols. In the case of endocyclic enol ethers, formation of benzofuran products competes with [4 + 2] cycloaddition.

Full text of DOI:10.1021/jo981899u

596
J . Org. Chem. 1999, 64, 596-603
Syn th esis of An gu la r Qu in oid Heter ocycles fr om
2-(2-Nitr ovin yl)-1,4-ben zoqu in on e
Wayland E. Noland* and Brant L. Kedrowski
Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455
Received September 18, 1998
Reactions of 2-(2-nitrovinyl)-1,4-benzoquinone with furans, indoles, and endocyclic enol ethers form
angular fused heterocyclic quinoid ring systems. The reaction proceeds by a formal inverse electron-
demand [4 + 2] cycloaddition reaction of the nitrovinylquinone and a double bond of the heterocycle.
The initial quinoid cycloadducts can be readily tautomerized to hydroquinoid species, which may
be dehydrogenated to fully aromatic quinones. In the case of furans, the tautomerized adducts
may be ring-opened to give 6,7-di- or 5,6,7-tri-substituted-1,4-naphthalenediols. In the case of
endocyclic enol ethers, formation of benzofuran products competes with [4 + 2] cycloaddition.
Sch em e 1
In tr od u ction
We have previously studied the formation of benzo[a]-
carbazole-1,4-diones (2) by normal electron demand [4
+ 2] cycloadditions of 3-(2-nitrovinyl)indoles (1) with
benzoquinone (Scheme 1).1 Compounds of this type have
been of recent interest due to their potential DNA
intercalating ability2a-d and significant antitumor activ-
ity.2a,3 We were interested in the possibility of accessing
a more structurally diverse group of analogues (4) by a
different route involving inverse electron-demand [4 +
2] cycloadditions of nitrovinyl-substituted quinones (3)
and electron-rich heterocycles. We were also interested
in developing a general method for synthesizing angular
quinoid heterocycles from nitrovinylquinones.
Nitrovinylquinones are a little-studied class of electron-
deficient molecules with multiple sites and modes po-
tentially available for reaction with electron-rich unsat-
urated species. Some of the possibilities include the
following: (1) inverse electron-demand cycloaddition as
a diene; (2) normal electron-demand cycloaddition as a
dienophile; (3) 1,4- or 1,6-conjugate addition; (4) 1,2-
carbonyl addition; and (5) redox reactions. Testing the
selectivity of these reactive molecules is an intriguing
proposition. Although many substituted variations of
2-(2-nitrovinyl)quinones are possible, we chose to focus
on one of the simplest and most easily obtainable
analogues for this preliminary work, 2-(2-nitrovinyl)-1,4-
benzoquinone (3) itself.
for furans, but examples of furans acting as dienophiles
are known.4a-c Indoles are more common inverse electron-
demand dienophiles, and reactions with a variety of
electron-poor dienes have been reported.5a-m Endocyclic
enol ethers gave a [4 + 2] cycloaddition product in one
case but also formed benzofurans as the preferred reac-
tion pathway. Similar reactivity of the latter type with
benzoquinone and quinone imides has been reported
previously with silyl enol ethers,6 2-(trimethylsiloxy)-
It was found that furans, indoles, and endocyclic enol
ethers, such as dihydropyran, react selectively with 3.
The regiochemistry and stereochemistry of the resulting
products is consistent with a formal inverse electron
demand [4 + 2] cycloaddition, with 3 functioning as the
diene and a double bond of the heterocycle functioning
as the dienophile. This is an unusual reactivity pattern
(4) (a) Raasch, M. S. J . Org. Chem. 1980, 45, 867-870. (b) Ghisal-
berti, E. L.; J efferies, P. R.; Payne, T. G. Tetrahedron 1974, 30, 3099-
3102. (c) Horspool, W. M.; Tedder, J . M.; Din, Z. U. J . Chem. Soc. C
1969, 1694-1697.
(5) (a) Fan, W.; Parikh, M.; Snyder, J . K. Tetrahedron Lett. 1995,
36, 6591-6594. (b) Li, J .; Snyder, J . K. Tetrahedron Lett. 1994, 35,
1485-1488. (c) Benson, S. C.; Li, J .; Snyder, J . K. J . Org. Chem. 1992,
57, 5285-5287. (d) Benson, S. C.; Gross, J . L.; Snyder, J . K. J . Org.
Chem. 1990, 55, 3257-3269. (e) Pinder, U.; Kim, M. Tetrahedron Lett.
1988, 29, 3927-3928. (f) Benson, S. C.; Palabrica, C. A.; Snyder, J . K.
J . Org. Chem. 1987, 52, 4610-4614. (g) Takahashi, M.; Ishida, H.;
Kohmoto, M. Bull. Chem. Soc. J pn. 1976, 49, 1725-1726. (h) Li, J . P.;
Newlander, K. A.; Yellin, T. O. Synthesis 1988, 73-75. (i) Plate, R.;
Hermkens, P. H. H.; Smits, J . M. M.; Ottenheijm, H. C. J . J . Org.
Chem. 1986, 51, 309-314. (j) Plate, R.; Ottenheijm, H. C. J .; Nivard,
R. J . F. J . Org. Chem.1984, 49, 540-543. (k) Gilchrist, T. L.; Lingham,
D. A.; Roberts, T. G. J . Chem. Soc., Chem. Commun. 1979, 1089-1090.
(l) Kraus, R. A.; Bougie, D.; J acobson, R. A.; Su, Y. J . Org. Chem. 1989,
54, 4, 2425-2428. (m) Omote, Y.; Tomotake, A.; Kashima, C. Tetra-
hedron Lett. 1984, 25, 2993-2994.
(1) Noland, W. E.; Konkel, M. J .; Tempesta, M. S.; Cink, R. D.;
Powers, D. M.; Schlemper, E. O.; Barnes, C. L. J . Heterocycl. Chem.
1993, 30, 183-192.
(2) (a) Rogge, M.; Fischer, G.; Pindur, U.; Schollmeyer, D. Monatsh.
Chem. 1996, 127, 97-102. (b) Dra¨ger, M.; Haber, M.; Erfanian-
Abdoust, H.; Pindur, U.; Sattler, K. Monatsh. Chem. 1993, 124, 559-
576. (c) Pindur, U.; Pfeuffer, L.; Eitel, M.; Rogge, M.; Haber, M.
Monatsh. Chem. 1991, 122, 291-298. (d) Hiremath, S. P.; Purohit, M.
G. Indian J . Chem. 1974, 12, 493-495.
(3) Noland, W. E. University of Minnesota, unpublished results from
the National Cancer Institute.
10.1021/jo981899u CCC: $18.00 © 1999 American Chemical Society
Published on Web 12/29/1998

Synthesis of Angular Quinoid Heterocycles
J . Org. Chem., Vol. 64, No. 2, 1999 597
Ta ble 2. Rin g Op en in g of F u r a n Cycloa d d u cts u n d er
Acid ic Con d ition s
Sch em e 2
Ta ble 1. Cycloa d d ition Rea ction s of 3 w ith F u r a n s
R1
R2
reactant
acid
product
yield, %
H
H
CH3
CH3
CH3
H
H
H
H
CH3
H
H
9a
9a
8b
8b
9c
9d
9d
AcOH
TsOH
AcOH
TsOH
TsOHa
AcOH
TsOH
10a
10a
10b
10b
10c
10d
10d
72
26
60
39
79
55
98
CH2OCH3
CH2OCH3
a
This furan cycloadduct failed to yield ring-opened products in
AcOH.
proceeded even further to give 10e. Although all carbons
in 3 are electrophilic, C-3 was predicted to be the most
electrophilic due to simultaneous conjugation with car-
bonyl and nitro groups. The regiochemistry of 8 is as
expected, with bond formation occurring between the
most electron-poor end of the diene (C-3) and the most
electron-rich carbon of the furan (C-5). The stereochem-
istry of the cycloadducts 8 was determined to be endo by
1H NMR coupling constant analysis. No exo products
were detected. This selectivity for the endo transition
state likely results from secondary orbital overlap be-
tween C-1′ and C-2 of the diene and C-3 and C-2 of the
furan. Compounds of type 8 are highly prone to tau-
tomerization and convert to 9 under conditions as mild
as contact with polar solvents. Hence, the quinoid tau-
tomer 8 is often not observed, as it readily converts to
the hydroquinoid tautomer 9. It was sometimes possible
to isolate 8, if it precipitated out of the reaction mixture
before tautomerization could take place. A thoroughly
dried, nonpolar solvent is required for this purpose.
Benzene was used with some success, since the solubility
of most of the initially formed cycloadducts is low in this
solvent. Some furans failed to give cycloaddition products
in benzene, or other more polar solvents such as THF.
In these cases, it was found that the reactions would
proceed in the neat heterocycle. Where comparison was
possible, yields were generally slightly better using the
neat heterocycle instead of benzene as solvent. With
2-substituted furans, reaction with 3 occurs through the
less hindered C-4 and C-5 double bond of the furan as
expected; however, the sterically more hindered 2,5-
dimethylfuran still reacts with 3 in good yield. In the case
of furfuryl alcohol, a ring-opened compound (10e) was
isolated as the major product. This compound likely
arises from an intermediate 9e by a rearrangement
analogous to that reported for cycloadducts of furans with
halogenated thiophene dioxides.4a It is significant to note
that the similar O-methyl ether of furfuryl alcohol does
not ring-open by itself. Although most compounds of types
8 and 9 do not ring-open under the reaction conditions,
they will ring-open to 10 when heated in the presence of
acid (Table 2). Refluxing in AcOH or in CHCl3 with
catalytic TsOH was used with varying degrees of success.
In cases where 8 was converted to 10, it presumably first
tautomerized to 9 and then ring-opened to 10.
R1
R2
solvent
product
yield, %
H
H
H
H
CH3
H
neata
neat
PhH
neatb
neat
9a
87
83
71
74
68
53
38
CH3
CH3
CH3
CH2OCH3
CH2OCH3
CH2OH
8b
8b
8c
9d
8d
10e
H
H
PhH
neata
a
These furans failed to yield cycloaddition products in PhH.
2,5-Dimethylfuran failed to react cleanly in PhH.
b
furan,7a,b enamines,8 and styrenes9 leading to benzofurans
and indoles. Attempted reactions of 3 with pyrroles and
thiophenes gave either no reaction or produced intrac-
table mixtures.
Resu lts a n d Discu ssion
Synthesis of 2-(2-nitrovinyl)-1,4-benzoquinone (3) was
carried out in two steps from commercially available 2,5-
dimethoxybenzaldehyde 5 (Scheme 2), which was con-
verted to 2,5-dimethoxy-â-nitrostyrene (6) by reaction
with nitromethane and NaOH in methanol, followed by
dehydration with HCl.10 Compound 6 was converted to
3 by oxidative demethylation11 using ceric ammonium
nitrate (CAN) in CH3CN/H2O.
Rea ction s w ith F u r a n s. Several readily available
2-substituted furans (7) were selected as reaction part-
ners for 3. Reactions led to products of type 8 (Table 1),
which often react further, producing 9, and in one case
(6) Mukaiyama, T.; Sagawa, Y.; Kobayashi, S. Chem. Lett. 1987,
2169-2172.
(7) (a) Brimble, M. A.; Brimble, M. T.; Gibson, J . J . Chem. Soc.,
Perkin Trans. 1 1989, 179-184. (b) Brimble, M. A.; Duncalf, L. J .; Reid,
D. C. W. Tetrahedron: Asymmetry 1995, 6, 263-269.
(8) Titov, E. A.; Grishchenko, A. S. Chem. Heterocycl. Compd. (Engl.
Transl.) 1972, 8, 789-791.
(9) Engler, T. A.; Iyengar, R. J . Org. Chem. 1998, 63, 1929-1934
and references therein.
(10) Worrall, D. E. in Organic Syntheses, 2nd ed.; Gilman, H., Blatt,
A. H., Eds.; J ohn Wiley and Sons: New York, 1941; Collect. Vol. I, pp
413-415.
(11) J acob, P.; Callery, P. S.; Shulgin, A. T.; Castagnoli, N. J . Org.
Chem. 1976, 41, 3627-3629.
Rea ction s w ith 5,6-F u sed Heter ocycles. Benzo[b]-
furan and several indoles were investigated as dieno-

598 J . Org. Chem., Vol. 64, No. 2, 1999
Noland and Kedrowski
Ta ble 3. Cycloa d d ition Rea ction s of 3 w ith In d oles a n d
Ben zofu r a n
Ta ble 4. Cycloa d d ition Rea ction s of 3 w ith En d ocyclic
En ol Eth er s
n
solvent
product(s)
ratio
yield, %
1
1
2
neat
PhH
neata
16a , 17a
16a , 17a
17b
1:1.7
1:1
85
48
21
R
X
solvent
product(s)
ratio
yield, %
a
This heterocycle failed to yield isolable products in PhH.
H
H
H
Br
OCH3
O
NH
NCH3
NH
NH
neat
PhH
PhH
PhH
PhH
13a
13b, 14b
13c
13d , 14d
13e
14
95
57
33
53
3.6:1
the most electron-rich carbon of the heterocycle (C-3). The
stereochemistry of 16a and 17 was determined by NMR
coupling-constant analysis and confirmed in 16a by X-ray
crystallography.12 Products 17 may be formed by conju-
gate addition of the enol ether to 3, followed by tau-
tomerization to a phenolic nucleophile which can ring-
closeto17.6Compound17aisasubstitutedtetrahydrofurobenzofuran,
10.8:1
philes in inverse electron-demand [4 + 2] cyclization
reactions with 3 (Table 3). Although benzene was used
as the solvent in reactions of indoles with 3, the initial
cycloadducts 12 could not be isolated or detected before
tautomerizing to 13. With benzofuran 11a , both 12a and
the core ring system of the mycotoxins aflatoxin B2 and
13a-j
1
G2
and
dihydro-O-methylsterig-
13a could be detected in the crude product by H NMR;
matocystin.14a,b This methodology might provide a new
racemic route to these molecules.
however, attempts at separation of 12a from 13a resulted
in tautomerization or decomposition of 12a . To simplify
the workup of this reaction, 12a was converted to 13a in
a controlled manner by tautomerization with Et3N. The
regiochemistry of 13 is as expected, with bond formation
occurring between the most electron-poor end of the diene
(C-3) and the most electron-rich carbon of the heterocycle
(C-3). In the cases of indole derivatives 11b and 11d there
was some oxidation of products 13b and 13d by 3 to form
14b and 14d , respectively. Although these were the only
cases where isolable amounts of 14 were formed, the
reduced, hydroquinone form of 3 could be isolated or
detected spectroscopically as a byproduct in all of the
reactions with 5,6-fused heterocycles. This was not
surprising, since electron-deficient quinones such as DDQ
and chloranil are known to be oxidizing agents. Reaction
of 3 with 3-methylindole was attempted to test the steric
limits of these reactions with indoles. In contrast to the
sterically hindered 2,5-dimethylfuran, 3-methylindole
failed to produce detectable cycloaddition products. Only
reduced 3 was detected.
Oxid a tion of Cycloa d d u cts To Give F u lly Ar o-
m a tic Qu in on es. Cycloadducts of types 9 and 13 can
be oxidized to fully aromatic heterocyclic quinones using
activated MnO2 as the dehydrogenating agent (Table 5).
The resulting compounds are analogues of 2. Compounds
of type 14 tended to be rather insoluble in most common
solvents, and this led to problems in isolation and
characterization in some cases. In many cases, 13C NMR
analyses proved impractical due to low solubility. Dehy-
drogenation of the 5-methoxyindole cycloadduct 13e was
attempted, and the product was detected spectroscopi-
cally but was not isolated in pure form.
Con clu sion s
We have found that 2-(2-nitrovinyl)-1,4-benzoquinone
(3) serves as a useful precursor in the synthesis of a
variety of angular-fused quinoid heterocycles. Inverse
Rea ction s w ith En d ocyclic En ol Eth er s. In addi-
tion to aromatic heterocycles, 3 was also found to react
with the endocyclic enol ethers 2,3-dihydrofuran and 3,4-
dihydro-2H-pyran 15 (n ) 1, 2) (Table 4). Cycloadditon
products of type 16 were expected, and this was observed,
with 16a . A new reaction pathway leading to 17, how-
ever, was also functioning and was the preferred pathway
for these heterocycles. This shift in selectivity may be
due to the loss of [4 + 2] transition state stabilizing
secondary orbital overlap in going from aromatic dieno-
philes to endocyclic enol ethers. The regiochemistry of
16a is as expected, with bond formation occurring
between the most electron-poor end of the diene (C-3) and
(12) Young, V. G., X-ray Crystallographic Laboratory, Department
of Chem., University of Minnesota, Minneapolis, MN.
(13) (a) Syntheses reviewed by: Schuda, P. F. Top. Curr. Chem.
1980, 91, 75. (b) Knight, J . A.; Roberts, J . C.; Roffey, P. J . Chem. Soc.
1966, 1308. (c) Bu¨chi, G.; Foulkes, D. M.; Kurono, M.; Mitchell, G. F.;
Schneider, R. S. J . Am. Chem. Soc. 1967, 89, 6745. (d) Roberts, J . C.;
Sheppard, A. H.; Knight, J . A.; Roffey, P. J . Chem. Soc. 1968, 22. (e)
Bu¨chi, G.; Weinreb, S. M. J . Am. Chem. Soc. 1971, 93, 746. (f)
Castellino, A. J .; Rapoport, H. J . Org. Chem. 1986, 51, 1006. (g) Sloan,
C. P.; Cuevas, J . C.; Quesnelle, C.; Snieckus, V. Tetrahedron Lett. 1988,
29, 4685. (h) Weeratunga, G. Horne, S.; Rodrigo, R. J . Chem. Soc.,
Chem. Commun. 1988, 721. (i) Civitello, E. R.; Rapoport, H. J . Org.
Chem. 1994, 59, 3775. (j) Toshikazu, B.; Shishido, K. Synlett 1997,
33, 665.
(14) For previous syntheses, see: (a) Rance, M. J .; Roberts, J . C.
Tetrahedron Lett. 1969, 277-278. (b) Horne, S.; Rodrigo, R. J . Org.
Chem. 1990, 55, 4520-4522.

Synthesis of Angular Quinoid Heterocycles
J . Org. Chem., Vol. 64, No. 2, 1999 599
Ta ble 5. Deh yd r ogen a tion of Cycloa d d u cts To Give
F u lly Ar om a tic Qu in on es
(200 mL) was poured with rapid stirring into a solution of 6
(20.00 g, 95.6 mmol) in CH3CN (500 mL). The reaction solution
was stirred for 5 min and then washed with brine (100 mL),
and the brine layer was extracted with CH3CN (2 × 100 mL).
The CH3CN fractions were combined and concentrated until
the product began to phase-separate. (It is important that the
solution not be concentrated to dryness, as flash detonations
have occurred under these conditions). The mixture was
partitioned between CHCl3 (500 mL) and H2O (200 mL), and
the resulting aqueous layer was extracted with CHCl3 (200
mL). The CHCl3 fractions were combined, washed with H2O
(100 mL), and dried over anhydrous MgSO4. The CHCl3 was
removed under reduced pressure, and the residual brown solid
was crystallized twice from THF/cyclohexane, giving 3 as
golden yellow needles (7.68 g, 45%): mp 104-106 °C; IR (KBr,
1
cm-1) 3126, 1652, 1522, 1344; H NMR (CDCl3, δ ppm) 8.12
(d, J ) 13.8 Hz, 1 H), 7.62 (d, J ) 13.8 Hz, 1 H), 6.98 (m, 1 H),
6.93-6.84 (m, 2 H); 13C NMR (acetone-d6, δ ppm) 185.4, 183.9,
142.3, 136.1, 135.9, 135.4, 135.1, 129.0; CI HRMS m/z (M+
+
H) calcd 180.0297, found 180.0289. Anal. Calcd for C8H5NO4:
C, 53.64; H, 2.81; N, 7.82. Found: C, 53.81; H, 2.92; N, 7.75.
cis-3a ,9b-Dih yd r o-6,9-d ih yd r oxy-4-n itr on a p h th o[1,2-b]-
fu r a n (9a ). Compound 3 (0.200 g, 1.12 mmol) was dissolved
in furan (7.5 mL) and stirred in the dark for 20 h. The
precipitate that formed was vacuum-filtered and dried under
high vacuum, giving 9a as an orange powder (0.240 g, 87%):
mp 188 °C dec; IR (KBr, cm-1) 3424, 1637, 1490, 1320, 1265;
1H NMR (acetone-d6, δ ppm) 8.92 (s, exchanges with D2O, 1
H), 8.39 (s, exchanges with D2O, 1 H), 8.26 (d, J ) 1.5 Hz, 1
H), 7.02 (d, J ) 9.0 Hz, 1 H), 6.95 (d, J ) 9.0 Hz, 1 H), 6.66 (t,
J ) 2.4 Hz, 1 H), 6.09 (d, J ) 11.1 Hz, 1 H), 5.34 (t, J ) 2.7
Hz, 1 H), 4.39 (m, 1 H); 13C NMR (acetone-d6, δ ppm) 149.6,
149.5, 148.2, 146.6, 123.6, 121.2, 117.7, 117.5, 116.9, 100.3,
76.7, 40.0; CI HRMS m/z (M + NH4+) calcd 265.0824, found
265.0820. Anal. Calcd for C12H9NO5: C, 58.30; H, 3.67; N, 5.67.
Found: C, 58.08; H, 3.80; N, 5.41.
[(()-(3a â,4R,9a R,9bâ)]-3a ,4,9a ,9b-Tetr a h yd r o-2-m eth yl-
4-n itr on a p h th o[1,2-b]fu r a n -6,9-d ion e (8b). A. Rea ction in
Nea t Het er ocycle. Compound 3 (0.200 g, 1.12 mmol) was
dissolved in 2-methylfuran (7.5 mL) and stirred. Within
minutes, a heavy precipitate formed, which was vacuum-
filtered after 30 min and dried under high vacuum, giving 8b
as a pale yellow microcrystalline solid (0.243 g, 83%): mp 120
°C; IR (KBr, cm-1) 2932, 1691, 1670, 1553, 1373, 1304; 1H NMR
(CDCl3, δ ppm) 7.70 (dt, J ) 0.9, 3.0, 3.0 Hz, 1 H), 7.04 (d, J
) 10.8 Hz, 1 H), 6.96 (d, J ) 10.8 Hz, 1 H), 5.70 (dd, J ) 3.3,
9.6 Hz, 1 H), 4.97 (ddd, J ) 2.1, 3.0, 6.6 Hz, 1 H), 4.33 (dq, J
) 1.2, 1.2, 1.2, 2.4 Hz, 1 H), 4.29 (ddddq, J ) 0.9, 1.2, 1.2, 1.2,
2.4, 6.6, 9.6 Hz, 1 H), 3.32 (ddd, J ) 2.4, 3.0, 3.3 Hz, 1 H),
1.65 (t, J ) 1.2 Hz, 3 H); 13C NMR (CDCl3, δ ppm) 192.8, 182.1,
160.4, 142.7, 141.8, 133.8, 131.0, 93.1, 83.0, 79.9, 48.3, 47.7,
13.3; CI HRMS m/z (M+ + H) calcd 262.0715, found 262.0711.
Anal. Calcd for C13H11NO5: C, 59.77; H, 4.24; 5.36 N. Found:
C, 59.62; H, 4.30; N, 5.20.
B. Rea ction in Ben zen e. Compound 3 (0.200 g, 1.12 mmol)
was partially dissolved in benzene (5 mL), and 2-methylfuran
(0.184 g, 2.24 mmol) was added with stirring. After 18 h of
stirring, a precipitate formed, which was filtered and dried
under high vacuum, giving 8b as a pale yellow solid (0.208 g,
71%): mp 119 °C; the mixture melting point with material
from part A showed no depression; the 1H NMR spectrum was
identical with that of the material obtained in part A.
[(()-(3a â,4R,9a R,9b â)]-3a ,4,9a ,9b -Tet r a h yd r o-2,9b -d i-
m eth yl-4-n itr on a p h th o[1,2-b]fu r a n -6,9-d ion e (8c). Com-
pound 3 (0.400 g, 2.24 mmol) was dissolved in 2,5-dimethyl-
furan (10.0 mL) and stirred for 15.5 h, during which time a
yellow precipitate formed. The entire reaction mixture was
poured into hexane (20 mL), with stirring, and more precipi-
tate formed. The precipitate was filtered and dried under high
vacuum, giving 8c as a yellow powder (0.452 g, 74%): mp 104-
106 °C; IR (KBr, cm-1) 2923, 1682, 1542, 1375, 1300; 1H NMR
(CDCl3, δ ppm) 7.64 (ddd, J ) 1.2, 2.7, 3.3 Hz, 1 H), 6.94 (d, J
) 10.5 Hz, 1 H), 6.88 (d, J ) 10.5 Hz, 1 H), 4.97 (ddd, J ) 1.8,
3.3, 6.6 Hz, 1 H), 4.22 (dq, J ) 1.2, 1.2, 1.2, 2.3 Hz, 1 H), 3.84
(dddq, J ) 1.2, 1.5, 1.5, 1.5, 2.3, 6.6 Hz, 1 H), 3.05 (dd, J )
R1
R2
X
product
yield, %
H
18a
18b
18c
14a
14b
14c
14d
53
54
32
58
63
41
33
CH3
CH2OCH3
H
H
H
Br
O
NH
NCH3
NH
electron-demand [4 + 2] cycloaddition reactions with
substituted furans, indoles, and endocyclic enol ethers
proceed with good regioselectivity, and the products can
be transformed further to give fully aromatic ring sys-
tems, or ring-opened in the case of furans. Work is
currently under way analyzing the reactivity of 3 and
other nitrovinylquinones with a wider array of enol
ethers. We are also exploring the prospects of synthesiz-
ing aflatoxin B2 and G2 and dihydro-O-methylsterigma-
tocystin via reactions related to that which produced 17.
Exp er im en ta l Section
Gen er a l Meth od s. Benzene was dried by distillation over
CaH2. Liquid reagents were freshly distilled just prior to use,
except where noted otherwise. Brine refers to saturated
aqueous NaCl solution. Flash chromatography15 was per-
formed with silica gel (E. Merck 60, 230-400 mesh). Melting
points are uncalibrated. H NMR and 13C NMR spectra were
1
recorded at 300 and 75 MHz, respectively. Elemental analyses
were performed at M-H-W Laboratories, Phoenix, AZ.
2,5-Dim eth oxy-â-n itr ostyr en e (6). A solution of 5 (101.5
g, 611 mmol) and CH3NO2 (37.3 g, 611 mmol) in MeOH (600
mL) was cooled to 10 °C in an ice bath. A solution of NaOH
(25.58 g, 640 mmol) in H2O (200 mL) was added dropwise with
stirring at a rate such that the temperature stayed between
10 and 15 °C. The reaction mixture was then immediately
dripped into 5 N HCl (1.5 L), with stirring, and an orange
precipitate formed. The precipitate was vacuum-filtered and
crystallized from i-PrOH/H2O, giving 6 as orange needles
(80.87 g, 63%): mp 119.5-120 °C; IR (KBr, cm-1) 3106, 2841,
1
1621, 1498, 1350, 1253, 1224; H NMR (CDCl3, δ ppm) 8.11
(d, J ) 13.5 Hz, 1 H), 7.85 (d, J ) 13.5 Hz, 1H), 7.01 (dd, J )
3.0, 9.0 Hz, 1 H), 6.95 (d, J ) 3.0 Hz, 1 H), 6.90 (d, J ) 9.0 Hz,
1 H), 3.93 (s, 3 H), 3.83 (s, 3 H); 13C NMR (CDCl3, δ ppm) 150.8,
150.4, 135.2, 132.2, 116.3, 116.0, 113.2, 109.3, 52.9, 52.7; EI
HRMS m/z (M+) calcd 209.0688, found 209.0688. Anal. Calcd
for C10H11NO4: C, 57.41; H, 5.30; N, 6.70. Found: C, 57.50;
H, 5.40; N, 6.79.
2-(2-Nitr ovin yl)-1,4-ben zoqu in on e (3). A solution of ceric
ammonium nitrate (115.20 g, 210.1 mmol) in 3:1 H2O/CH3CN
(15) Still, W. C.; Kahn, M.; Mitra, A. J . Org. Chem. 1978, 43, 2923-
2925.

600 J . Org. Chem., Vol. 64, No. 2, 1999
Noland and Kedrowski
1.8, 2.7 Hz, 1 H), 1.75 (s, 3 H), 1.61 (dd, J ) 1.2, 1.5 Hz, 3 H);
13C NMR (CDCl3, δ ppm) 193.0, 182.6, 159.4, 142.8, 141.2,
133.9, 132.7, 92.0, 88.3, 83.2, 56.7, 51.9, 25.0, 13.4; EI HRMS
m/z (M+) calcd 275.0794, found 275.0794. Anal. Calcd for
C14H13NO5: C, 61.09; H, 4.76; N, 5.09. Found: C, 60.89; H,
5.00; N, 5.04.
247.0481, found 247.0475. Anal. Calcd for C12H9NO5: C, 58.30;
H, 3.67; N, 5.67. Found: C, 58.11; H, 3.79; N, 5.69.
B. Rin g Op en in g w ith TsOH. Compound 9a (0.120 g,
0.495 mmol) was mixed with CHCl3 (12 mL), TsOH‚H2O (1
mg, 0.005 mmol) was added, and the solution was refluxed
with stirring for 90 min. The resulting precipitate was vacuum-
filtered, giving 10a as a red powder (0.031 g, 26%): mp >350
°C; the mixture melting point with material from part A
showed no depression; the 1H NMR spectrum was identical
with that of the material obtained in part A.
cis-3a ,9b-Dih yd r o-6,9-d ih yd r oxy-2-(m eth oxym eth yl)-4-
n itr on a p h th o[1,2-b]fu r a n (9d ). Compound 3 (0.200 g, 1.12
mmol) was dissolved in 2-(methoxymethyl)furan16 (5 mL) and
stirred. After 30 min of stirring, an orange precipitate formed,
and after 18 h, the precipitate was vacuum-filtered and dried
under high vacuum, giving 9d as an orange powder (0.222 g,
68%): mp 167-169 °C; IR (KBr, cm-1) 3412, 1638, 1488, 1322,
1-(5,8-Dih yd r oxy-3-n itr o-2-n a p h th yl)p r op a n on e (10b).
A. Rin g Op en in g w ith AcOH. Compound 8b (0.243 g, 0.930
mmol) was mixed with glacial AcOH (10 mL) and stirred until
all solid dissolved. The solution was allowed to evaporate
overnight, producing an oily dark red solid, which was
triturated with boiling AcOH, giving 10b as a maroon micro-
crystalline solid (0.146 g, 60%): mp 229-233 °C dec; IR (KBr,
1
1299, 1260; H NMR (acetone-d6, δ ppm) 8.89 (bs, 1 H), 8.39
(bs, 1 H), 8.25 (d, J ) 1.5 Hz, 1 H), 7.02 (d, J ) 8.7 Hz, 1 H),
6.94 (d, J ) 8.7 Hz, 1 H), 6.18 (d, J ) 10.5 Hz, 1 H), 5.28 (d,
J ) 2.7 Hz, 1 H), 4.41 (m, 1 H), 3.92 (m, 2 H), 3.29 (s, 3 H); 13
C
1
cm-1) 3422, 3228, 1707, 1603, 1484, 1327; H NMR (acetone-
NMR (DMSO-d6, δ ppm) 157.6, 150.0, 149.4, 146.3, 124.4,
122.0, 118.3, 116.9, 116.6, 98.3, 77.1, 66.5, 58.1, 40.4; EI HRMS
m/z (M+) calcd 291.0743, found 291.0744. Anal. Calcd for
d6, δ ppm) 9.04 (s, 1 H), 8.94 (s, 1 H), 8.81 (s, 1 H), 8.10 (s, 1
H), 6.97 (d, J ) 8.4 Hz, 1 H), 6.89 (d, J ) 8.4 Hz, 1 H), 4.42 (s,
2 H), 2.29 (s, 3 H); 13C NMR (acetone-d6, δ ppm) 203.8, 147.4,
146.7, 145.7, 127.5, 126.9, 125.8, 123.7, 120.6, 112.6, 110.0,
48.4, 29.0; EI HRMS m/z (M+) calcd 261.0637, found 261.0633.
Anal. Calcd for C13H11NO5: C, 59.77; H, 4.24; N, 5.36. Found:
C, 60.00; H, 4.40; N, 5.45.
C
14H13NO6: C, 57.73; H, 4.50; N, 4.81. Found: C, 57.56; H,
4.38; N, 4.61.
[(()-(3a â,4R,9a R,9b â)]-3a ,4,9a ,9b-Tetr a h yd r o-2-(m eth -
oxym et h yl)-4-n it r on a p h t h o[1,2-b]fu r a n -6,9-d ion e (8d ).
Compound 3 (0.200 g, 1.12 mmol) was partially dissolved in
benzene (5 mL), and 2-(methoxymethyl)furan16 (0.250 g, 2.23
mmol) was added with stirring. Stirring was continued for 18
h, during which time a precipitate formed, which was vacuum-
filtered, washed with benzene, and dried, giving 8d as a pale
yellow microcrystalline solid (0.172 g, 53%): mp 134-137 °C;
B. Rin g Op en in g w ith TsOH. Compound 8b (0.132 g,
0.505 mmol) was mixed with CHCl3 (15 mL), TsOH‚H2O (1
mg, 0.005 mmol) was added, and the solution was refluxed
for 2 h, during which time a precipitate formed. The mixture
was concentrated to half its original volume, vacuum-filtered,
and dried, giving 10b as a maroon solid (0.052 g, 39%): mp
228-231 °C dec; the mixture melting point with material from
part A showed no depression; the 1H NMR spectrum was
identical with that of the material obtained in part A.
1-(5,8-Dih yd r oxy-1-m e t h yl-3-n it r o-2-n a p h t h yl)p r o-
p a n on e (10c). Compound 9c (0.134 g, 0.487 mmol) was mixed
with CHCl3 (12 mL), and the mixture was heated to reflux,
with stirring, until the solid dissolved. Next, TsOH‚H2O (1 mg,
0.005 mmol) was added, and the solution was refluxed for 90
min more, during which time a color change from orange to
red occurred and a precipitate formed. The mixture was
concentrated to half its original volume and cooled, and the
solid was vacuum-filtered and vacuum-dried, giving 10c as a
1
IR (KBr, cm-1) 3065, 2879, 1688, 1667, 1622, 1546, 1371; H
NMR (CDCl3, δ ppm) 7.71 (dt, J ) 1.2, 3.0, 3.0 Hz, 1 H), 7.04
(d, J ) 10.8 Hz, 1 H), 6.95 (d, J ) 10.8 Hz, 1 H), 5.77 (dd, J )
3.3, 9.9 Hz, 1 H), 5.01 (ddd, J ) 2.1, 3.0, 7.2 Hz, 1 H), 4.66 (dt,
J ) 1.2, 1.2, 2.4 Hz, 1 H), 4.36 (ddddt, J ) 1.2, 1.5, 1.5, 2.4,
7.2, 9.9 Hz, 1 H), 3.78 (dd, J ) 1.2, 1.5 Hz, 2 H), 3.33 (ddd, J
) 2.1, 3.0, 3.3 Hz, 1 H), 3.25 (s, 3 H); 13C NMR (CDCl3, δ ppm)
192.2, 181.7, 159.7, 142.5, 141.7, 133.4, 131.2, 95.7, 82.5, 80.3,
66.2, 58.3, 48.1, 47.0; FAB HRMS m/z (M + H+) calcd 292.0821,
found 292.0834. Anal. Calcd for C14H13NO6: C, 57.73; H, 4.50;
N, 4.81. Found: C, 57.59; H, 4.53; N, 4.62.
1-(5,8-Dih yd r oxy-3-n it r o-2-n a p h t h yl)-3-h yd r oxyp r o-
p a n on e (10e). Compound 3 (0.200 g, 1.12 mmol) was dissolved
in furfuryl alcohol (5 mL) and stirred for 18 h, during which
time a fine precipitate formed. The reaction mixture was
poured into benzene (15 mL), with stirring, causing more
precipitate to form. The precipitate was filtered and vacuum-
dried, giving 10e as an orange solid (0.118 g, 38%): mp 245
°C dec; IR (KBr, cm-1) 3348, 3186, 1715, 1604, 1335, 1303; 1H
NMR (DMSO-d6, δ ppm) 10.07 (s, exchanges with D2O, 1 H),
9.83 (s, exchanges with D2O, 1 H), 8.80 (s, 1 H), 8.03 (s, 1 H),
6.94 (d, J ) 8.4 Hz, 1 H), 6.84 (d, J ) 8.4 Hz, 1 H), 5.36 (t,
exchanges with D2O, J ) 6.0 Hz, 1 H), 4.36 (s, 2 H), 4.24 (d, J
) 6.0 Hz, 2 H); 13C NMR (DMSO-d6, δ ppm) 208.0, 147.4, 146.2,
145.6, 128.0, 126.7, 125.1, 123.4, 121.0, 113.4, 110.5, 67.9, 44.1;
CI HRMS m/z (M + NH4+) calcd 295.0930, found 295.0930.
Anal. Calcd for C13H11NO6: C, 56.32; H, 4.00; N, 5.05. Found:
C, 56.55; H, 4.32; N, 4.85.
2-(5,8-Dih yd r oxy-3-n itr o-2-n a p h th yl)eth a n a l (10a ). A.
Rin g Op en in g w ith AcOH. Compound 9a (0.264 g, 1.07
mmol) was mixed with glacial acetic acid (25 mL) and refluxed
for 20 min with stirring. Acetic acid was removed under
reduced pressure, and the residual solid was recrystallized
from EtOH/H2O, giving 10a as a dark red microcrystalline
solid (0.189 g, 72%): mp >350 °C; IR (KBr, cm-1) 3396, 3324,
2860, 1710, 1632, 1603, 1481; 1H NMR (acetone-d6, δ ppm)
10.07 (s, 1 H), 9.06 (s, exchanges with D2O, 1 H), 8.96 (s, 1 H),
8.84 (s, exchanges with D2O, 1 H), 8.17 (s, 1 H), 6.99 (d, J )
8.3 Hz, 1 H), 6.91 (d, J ) 8.3 Hz, 1 H), 4.38 (s, 2 H); 13C NMR
(acetone-d6, δ ppm) 198.0, 147.3, 146.5, 145.6, 127.6, 126.7,
123.8, 123.5, 120.7, 112.6, 110.0, 48.5; EI HRMS m/z (M+) calcd
maroon powder (0.106 g, 79%): mp 186-189 °C; IR (KBr, cm-1
)
3418, 3340, 1708, 1618, 1506, 1329; 1H NMR (acetone-d6, δ
ppm) 8.94 (s, 1 H), 8.68 (s, 1 H), 8.64 (s, 1 H), 6.97 (d, J ) 8.4
Hz, 1 H), 6.87 (d, J ) 8.4 Hz, 1 H), 4.22 (s, 2 H), 2.89 (s, 3 H),
2.32 (s, 3 H); 13C NMR (acetone-d6, δ ppm) 203.3, 148.1, 147.9,
147.1, 138.1, 126.1, 124.0, 123.6, 117.3, 114.1, 109.6, 43.4, 28.8,
18.6; EI HRMS m/z (M+) calcd 275.0794, found 275.0792; Anal.
Calcd for C14H13NO5: C, 61.09; H, 4.76; N, 5.09. Found: C,
61.18; H, 5.00; N, 4.87.
1-(5,8-Dih yd r oxy-3-n it r o-2-n a p h t h yl)-3-m et h oxyp r o-
p a n on e (10d ). A. Rin g Op en in g w ith AcOH. Compound 9d
(0.164 g, 0.563 mmol) was mixed with glacial AcOH (25 mL)
and refluxed for 1 h, with stirring. The AcOH was removed
under reduced pressure, and the residual dark red solid was
crystallized from EtOH/H2O, giving 10d as maroon needles
(0.090 g, 55%): mp 210-212 °C; IR (KBr, cm-1) 3367, 3291,
2968, 1717, 1604, 1490, 1331, 1298; 1H NMR (acetone-d6, δ
ppm) 9.06 (s, 1 H), 8.96 (s, 1 H), 8.83 (s, 1 H), 8.13 (s, 1 H),
6.98 (d, J ) 8.1 Hz, 1 H), 6.89 (d, J ) 8.1 Hz, 1 H), 4.43 (s, 2
H), 4.24 (s, 2H), 3.44 (s, 3H); 13C NMR (acetone-d6, δ ppm)
204.6, 147.3, 146.4, 145.6, 127.7, 126.7, 125.0, 123.5, 120.6,
112.5, 109.9, 77.1, 58.5, 44.3; EI HRMS m/z (M+) calcd
291.0743, found 291.0741. Anal. Calcd for C14H13NO6: C,
57.73; H, 4.50; N, 4.81. Found: C, 57.78; H, 4.76; N, 4.73.
B. Rin g Op en in g w ith TsOH. Compound 9d (0.050 g,
0.017 mmol) was mixed with CHCl3 (5 mL) and heated to
reflux, with stirring. Next, TsOH‚H2O (1 mg, 0.005 mmol) was
added, and the solution was refluxed for 90 min more, during
which time a color change from orange to red occurred and a
precipitate formed. The mixture was concentrated to half its
original volume and cooled, and the solid was vacuum-filtered
and vacuum-dried, giving 10d as a red powder (0.049 g, 98%):
(16) Prepared from furfuryl alcohol, KOH, benzyltriethylammonium
chloride, and MeI, in ether, stirred for 2 days, 60%.

Synthesis of Angular Quinoid Heterocycles
J . Org. Chem., Vol. 64, No. 2, 1999 601
mp 210-212 °C; the mixture melting point with material from
part A showed no depression; the 1H NMR spectrum was
identical with that of the material obtained in part A.
reduced pressure, giving a red oil. Addition of CH2Cl2 (5 mL)
caused 13c to precipitate as a red microcrystalline solid (0.197
g, 57%): mp 195-196 °C dec; IR (KBr, cm-1) 3484, 3388, 1632,
1483, 1320, 1267; 1H NMR (acetone-d6, δ ppm) 8.70 (bs, 1 H),
8.43 (bs, 1 H), 8.04 (d, J ) 0.6 Hz, 1 H), 7.10 (dt, J ) 1.2, 1.2,
7.8 Hz, 1 H), 7.08-7.02 (m, 1 H), 7.00 (d, J ) 8.7 Hz, 1 H),
6.76 (d, J ) 8.7 Hz, 1 H), 6.629 (dt, J ) 0.9, 7.5, 7.5 Hz, 1H),
6.625 (dd, J ) 0.9, 7.8 Hz, 1H), 5.40 (d, J ) 10.5 Hz, 1H), 5.22
(dd, J ) 0.6, 10.5 Hz, 1H), 3.07 (s, 3H); 13C NMR (acetone-d6,
δ ppm) 151.6, 149.7, 148.0, 146.7, 132.7, 128.1, 125.7, 125.1,
122.5, 120.8, 119.2, 115.9, 115.0, 110.5, 63.0, 41.9, 38.7; EI
HRMS m/z (M+) calcd 310.0953, found 310.0943. Anal. Calcd
for C17H14N2O4: C, 65.80; H, 4.55; N, 9.03. Found: C, 65.80;
H, 4.70; N, 8.86.
cis-10-Br om o-6a ,11b -d ih yd r o-1,4-d ih yd r oxy-6-n it r o-
7H-ben zo[c]ca r ba zole a n d 10-Br om o-6-n itr o-7H-ben zo-
[c]ca r ba zole-1,4-d ion e (13d a n d 14d ). 5-Bromoindole (0.438
g, 2.23 mmol) was dissolved in benzene (5 mL), and compound
3 (0.200 g, 1.12 mmol) was added with stirring. After 18 h of
stirring, a black precipitate developed, which was vacuum-
filtered and washed with benzene (5 mL) and then triturated
with boiling H2O (5 mL). The solid mixture was extracted with
acetone (5 mL) and filtered. The solid was recrystallized from
acetone, giving 14d as dark red needles (0.010 g, 7%): mp
350-351 °C; IR (KBr, cm-1) 3287, 1717, 1654, 1598, 1472,
1334; 1H NMR (acetone-d6, δ ppm) 12.29 (s, 1 H), 9.64 (d, J )
1.5 Hz, 1 H), 9.05 (s, 1 H), 7.91 (d, J ) 8.1 Hz, 1 H), 7.84 (dd,
J ) 1.8, 8.4 Hz, 1 H), 7.29 (d, J ) 10.2 Hz, 1 H), 7.21 (d, J )
10.2 Hz, 1 H); 13C NMR, too insoluble; EI HRMS m/z (M+) calcd
369.9589, found 369.9590. Anal. Calcd for C16H7BrN2O4: C,
51.78; H, 1.90; N, 7.55. Found: C, 51.32; H, 1.48; N, 7.40.
The filtrate from the acetone extraction was concentrated
under vacuum, giving a dark red oil, which was precipitated
as a dark red solid by addition of CH2Cl2 (5 mL). This solid
was redissolved in a minimum amount of acetone and purified
by flash chromatography, giving 13d as a red oil. Addition of
CH2Cl2 (5 mL) caused precipitation of 13d as a red powder
(0.109 g, 26%): mp 180-185 °C dec; IR (KBr, cm-1) 3395, 1698,
1490, 1262; 1H NMR (acetone-d6, δ ppm) 8.92 (s, 1 H), 8.54 (s,
1 H), 8.23 (d, J ) 0.9 Hz, 1 H), 7.09 (d, J ) 8.7 Hz, 1 H), 7.08
(ddd, J ) 1.2, 2.1, 8.4 Hz, 1 H), 7.05-7.02 (m, 1 H), 6.82 (d, J
) 9.0 Hz, 1 H), 6.64 (d, J ) 8.4 Hz, 1 H), 5.79 (bs, 1 H), 5.44
(ddd, J ) 0.9, 2.8, 10.5 Hz, 1 H), 5.22 (dt, J ) 0.9, 0.9, 10.8
Hz, 1 H); 13C NMR (acetone-d6, δ ppm) 150.3, 148.8, 147.5,
145.5, 133.3, 130.4, 127.2, 127.1, 121.7, 121.6, 115.8, 115.5,
110.6, 108.7, 57.2, 41.5; EI HRMS m/z (M+) calcd 373.9902,
found 373.9892. Anal. Calcd for C16H11BrN2O4: C, 51.22; H,
2.96; N, 7.47. Found: C, 51.41; H, 2.84; 7.40.
cis-6a,11b-Dih ydr o-1,4-dih ydr oxy-6-n itr oben zo[b]n aph -
th o[1,2-d ]fu r a n (13a ). Compound 3 (0.550 g, 3.07 mmol) was
dissolved in benzo[b]furan (5.5 mL, used as received from
Aldrich Chemical Co.) and stirred for 72 h in the dark. A black
precipitate formed, and the mixture was poured into hexane
(20 mL), with stirring, using another portion of hexane (20
mL) to aid in the transfer. The resulting solid was vacuum-
filtered, dissolved in THF (27.5 mL), and cooled to 0 °C under
N2, and 10% Et3N/THF (1 drop) was added with stirring,
causing a color change from red to darker red. After 1 h of
stirring at 0 °C, the THF was evaporated in a stream of N2,
and the residual dark red solid was purified by flash chroma-
tography, eluting successively with 2:1 and 1:1 hexane/EtOAc.
Band 2 was concentrated under reduced pressure, giving a red
oil, which was recrystallized from EtOH/H2O, giving 13a as
red needles (0.131 g, 14%): mp 188-190 °C; IR (KBr, cm-1
)
3504, 3358, 1638, 1492, 1476, 1269; 1H NMR (acetone-d6, δ
ppm) 8.91 (bs, 1H), 8.58 (bs, 1 H), 8.21 (d, J ) 1.5 Hz, 1 H),
7.50 (bd, J ) 7.5, w1/2 ) 2.8 Hz, 1 H), 7.18 (dt, J ) 1.5, 7.5, 7.5
Hz, 1 H), 7.05 (d, J ) 8.7 Hz, 1 H), 6.96 (d, J ) 8.7 Hz, 1 H),
6.89 (dt, J ) 1.2, 7.5, 7.5 Hz, 1 H), 6.80 (bd, J ) 7.5 Hz, w1/2
) 2.2 Hz, 1 H), 6.37 (d, J ) 9.3 Hz, 1 H), 5.03 (d, J ) 9.3 Hz,
w1/2 ) 3.3 Hz, 1 H); 13C NMR (acetone-d6, δ ppm) 159.1, 149.6,
149.4, 146.0, 129.0, 126.9, 125.9, 124.4, 121.3, 120.9, 117.9,
117.0, 116.6, 109.4, 78.4, 40.3; EI HRMS m/z (M+) calcd
297.0637, found 297.0635. Anal. Calcd for C16H11NO5: C,
64.65; H, 3.73; N, 4.71. Found: C, 64.46; H, 3.90; N, 4.58.
cis-6a ,11b-Dih yd r o-1,4-d ih yd r oxy-6-n itr o-7H-ben zo[c]-
ca r b a zole a n d 6-Nit r o-7H -b en zo[c]ca r b a zole-1,4-d ion e
(13b a n d 14b). Indole (0.261 g, 2.23 mmol) was dissolved in
benzene (5 mL), and compound 3 (0.200 g, 1.12 mmol) was
added with stirring; after 18 h, a brown precipitate formed.
After the mixture was kept for 24 h, an orange paste
developed, which was vacuum-filtered with the aid of benzene
(10 mL). The solid was purified by flash chromatography,
eluting successively with 2:1 and 1:1 hexane/EtOAc, giving two
orange colored bands.
The solvent was removed from band 1 under reduced
pressure, giving 14b as an orange powder (0.047 g, 43%): mp
294-296 °C; IR (KBr, cm-1) 1661, 1590, 1334; 1H NMR
(DMSO-d6, δ ppm) 12.77 (s, 1 H), 9.16 (bd, J ) 8.4 Hz, w1/2
)
2.4 Hz, 1H), 8.74 (s, 1 H), 7.83 (dt, J ) 0.9, 0.9, 8.4 Hz, 1 H),
7.63 (ddd, J ) 1.2, 7.2, 8.4 Hz, 1 H), 7.36 (ddd, J ) 1.2, 7.2,
8.4 Hz, 1 H), 7.20 (d, J ) 10.2 Hz, 1 H), 7.14 (d, J ) 10.2 Hz,
1 H); 13C NMR, too insoluble; EI HRMS m/z (M+) calcd
292.0484, found 292.0500. Anal. Calcd for C16H8N2O4: C,
65.75; H, 2.76; N, 9.59. Found: C, 66.02; H, 2.80; N, 9.41.
The solvent was removed from band 2 under reduced
pressure, and the residual solid was crystallized from acetone/
H2O, giving 13b as maroon needles (0.171 g, 52%): mp 190
°C dec; IR (KBr, cm-1) 3407, 1634, 1489, 1275; 1H NMR
(acetone-d6, δ ppm) 8.80 (bs, 1 H), 8.49 (bs, 1 H), 8.21 (d, J )
2.4 Hz, 1 H), 7.07 (d, J ) 8.7 Hz, 1 H), 6.96-6.90 (m, 2 H),
6.79 (d, J ) 9.0 Hz, 1 H), 6.68 (d, J ) 7.8 Hz, 1 H), 6.52 (dt, J
) 0.9, 7.5, 7.5 Hz, 1 H), 5.56 (bs, 1 H), 5.38 (dd, J ) 2.4, 10.5
Hz, 1 H), 5.17 (d, J ) 10.5 Hz, 1 H); 13C NMR (acetone-d6, δ
ppm) 150.0, 149.4, 147.7, 146.0, 130.3, 127.7, 127.2, 124.3,
122.5, 121.4, 117.9, 115.9, 115.1, 108.9, 57.0, 41.6; EI HRMS
m/z (M+) calcd 296.0797, found 296.0794. Anal. Calcd for
cis-6a ,11b-Dih yd r o-1,4-d ih yd r oxy-10-m eth oxy-6-n itr o-
7H-ben zo[c]ca r ba zole (13e). 5-Methoxyindole18 (0.329 g,
2.23 mmol) was dissolved in benzene (5 mL), and compound 3
(0.200 g, 1.12 mmol) was added with stirring. After 18 h of
stirring, a dark precipitate developed, which was vacuum-
filtered and purified by flash chromatography, eluting succes-
sively with 2:1 and 1:1 hexane/EtOAc. The second band was
concentrated under reduced pressure, giving a red oil. CH2Cl2
(5 mL) was added to the oil with stirring, precipitating 13e as
a red powder (0.192 g, 53%): mp 211-212 °C dec; IR (KBr,
1
cm-1) 3398, 2943, 1636, 1490, 1323, 1274; H NMR (acetone-
d6, δ ppm) 8.83 (s, exchanges with D2O, 1 H), 8.43 (s, exchanges
with D2O, 1 H), 8.20 (s, 1 H), 7.07 (d, J ) 8.7 Hz, 1 H), 6.79 (d,
J ) 8.7 Hz, 1 H), 6.63-6.53 (m, 3 H), 5.36 (d, J ) 9.9 Hz, 1
H), 5.23 (s, exchanges with D2O, 1 H), 5.15 (d, J ) 9.9 Hz, 1
H), 3.89 (s, 3 H); 13C NMR (DMSO-d6, δ ppm) 152.7, 150.4,
147.5, 146.1, 143.5, 132.6, 127.4, 122.3, 122.2, 115.7, 115.5,
112.5, 111.7, 109.9, 56.9, 55.9, 42.0; EI HRMS m/z (M+) calcd
326.0903, found 326.0905. Anal. Calcd for C17H14N2O5: C,
62.57; H, 4.32; N, 8.58. Found: C, 62.66; H, 4.52; N, 8.39.
cis-1,2,3a,9b-Tetr ah ydr o-6,9-dih ydr oxy-4-n itr on aph th o-
[2,1-b]fu r a n a n d cis-2,3,3a ,8a -Tetr a h yd r o-5-h yd r oxy-4-(2-
n it r ovin yl)fu r o[2,3-d ]b en zo[b]fu r a n (16a a n d 17a ). A.
C
16H12N2O4: C, 64.86; H, 4.08; N, 9.46. Found: C, 65.06; H,
4.26; N, 9.22.
cis-6a ,11b-Dih yd r o-1,4-d ih yd r oxy-7-m eth yl-6-n itr o-7H-
ben zo[c]ca r ba zole (13c). 1-Methylindole17 (0.293 g, 2.23
mmol) was dissolved in benzene (5 mL), and compound 3 (0.200
g, 1.12 mmol) was added, with stirring. After 18 h of stirring,
a yellow-brown precipitate formed, which was vacuum-filtered
and purified by flash chromatography, eluting with 1:1 hexane/
EtOAc. The solvent was removed from the second band under
(17) Heaney, H.; Ley, S. V. In Organic Syntheses; Noland, W. E.,
Ed.; J ohn Wiley and Sons: New York, 1988; Collect. Vol. VI, pp 104-
105.
(18) Batcho, A. D.; Leimgruber, W. In Organic Syntheses; Freeman,
J . P., Ed.; J ohn Wiley and Sons: New York, 1990; Collect. Vol. VII, pp
34-41.

602 J . Org. Chem., Vol. 64, No. 2, 1999
Noland and Kedrowski
Rea ction in Nea t Heter ocycle. Compound 3 (0.200 g, 1.12
mmol) was dissolved in 2,3-dihydrofuran (7.5 mL), with
stirring. An orange precipitate developed after 2 h, and the
mixture was kept for an additional 16 h. The dihydrofuran
was removed under reduced pressure, and the residual solid
was separated by flash chromatography, eluting successively
with 3:2 and 1:1 hexane/EtOAc, giving two major orange
colored bands.
The solvent containing the second band was removed under
reduced pressure, giving 16a as an orange-red powder (0.086
g, 31%): mp 216 °C dec; IR (KBr, cm-1) 3491, 3276, 1640, 1490,
1266; 1H NMR (300 MHz, DMSO-d6, δ ppm) 9.88 (bs, 1 H),
9.25 (bs, 1 H), 8.10 (d, J ) 1.8 Hz, 1 H), 6.86 (d, J ) 8.7 Hz,
1 H), 6.67 (d, J ) 8.7 Hz, 1 H), 5.28 (d, J ) 9.9 Hz, 1 H), 3.85
(dt, J ) 8.4, 8.4, 9.9 Hz, 1 H), 3.67-3.52 (m, 2 H), 2.63 (dddd,
J ) 4.5, 6.0, 8.4, 12.6 Hz, 1 H), 1.73 (dq, J ) 7.5, 7.5, 7.5, 12.3
Hz, 1 H); 13C NMR (DMSO-d6, δ ppm) 150.3, 147.6, 144.6,
127.0, 125.2, 121.5, 115.1, 114.9, 71.5, 64.8, 38.7, 35.8; EI
HRMS m/z (M+) calcd 249.0637, found 249.0634. Anal. Calcd
for C12H11NO5: C, 57.83; H, 4.45; N, 5.62. Found: C, 57.72;
H, 4.61; N, 5.62.
The solvent containing the first band was removed under
reduced pressure, giving 17a as a yellow powder (0.151 g,
54%): mp 222-223 °C dec; IR (KBr, cm-1) 3258, 2884, 1514,
1496, 1338, 1247; 1H NMR (acetone-d6, δ ppm) 9.45 (bs, 1 H),
8.20 (d, J ) 13.5 Hz, 1 H), 8.14 (d, J ) 13.5 Hz, 1H), 6.89 (d,
J ) 8.7 Hz, 1 H), 6.81 (d, J ) 8.7 Hz, 1 H), 6.40 (d, J ) 5.7 Hz,
1 H), 4.41 (dd, J ) 6.0, 9.0 Hz, 1 H), 4.10 (ddd, J ) 0.9, 7.8,
8.7 Hz, 1 H), 3.61 (ddd, J ) 5.1, 8.7, 12.0 Hz, 1 H), 2.48 (ddt,
J ) 7.8, 9.3, 12.0, 12.0 Hz, 1 H), 2.13-2.04 (m, 1 H); 13C NMR
(DMSO-d6, δ ppm) 154.0, 152.2, 139.4, 133.0, 130.3, 116.3,
114.0, 113.9, 111.7, 67.0, 46.5, 33.1; EI HRMS m/z (M+) calcd
249.0637, found 249.0634. Anal. Calcd for C12H11NO5: C,
57.83; H, 4.45; N, 5.62. Found: C, 57.84; H, 4.38; N, 5.44.
of Celite. The Celite was washed with CH2Cl2, unless otherwise
specified, until the washings were colorless. The filtrate and
washings were combined, and the solvents removed under
reduced pressure, giving 18 or 13.
4-Nitr on a p h th o[1,2-b]fu r a n -6,9-d ion e (18a ). Compound
18a was obtained as a yellow powder (0.105 g, 53%): mp 200-
201 °C; IR (KBr, cm-1) 3159, 1676, 1603, 1515, 1302; 1H NMR
(CDCl3, δ ppm) 8.93 (s, 1 H), 8.23 (d, J ) 2.4 Hz, 1 H), 7.68 (d,
J ) 1.8 Hz, 1 H), 7.15 (d, J ) 10.5 Hz, 1 H), 7.10 (d, J ) 10.5
Hz, 1 H); 13C NMR (DMSO-d6, δ ppm) 183.5, 183.0, 156.0,
152.8, 142.6, 140.0, 138.7, 129.1, 128.4, 120.7, 117.1, 107.3;
EI HRMS m/z (M+) calcd 243.0168, found 243.0173. Anal.
Calcd for C12H5NO5: C, 59.27; H, 2.07; N, 5.76. Found: C,
59.30; H, 1.99; N, 5.79.
2-Meth yl-4-n itr on a p h th o[1,2-b]fu r a n -6,9-d ion e (18b).
Compound 8b (0.630 g, 2.41 mmol) was converted to 9b in situ
by dissolving in benzene (160 mL), adding 10% Et3N/THF (1
drop), and stirring for 5 min. The general procedure was then
followed, giving 18b as yellow needles (0.335 g, 54%): mp 201-
202 °C dec; IR (KBr, cm-1) 3101, 1673, 1584, 1530, 1335, 1299;
1H NMR (acetone-d6, δ ppm) 8.76 (s, 1 H), 7.34 (q, J ) 1.2 Hz,
1 H), 7.18 (d, J ) 10.5 Hz, 1 H), 7.12 (d, J ) 10.5 Hz, 1 H),
2.72 (d, J ) 1.2 Hz, 3 H); 13C NMR (DMSO-d6, δ ppm) 183.6,
183.2, 167.6, 152.8, 141.4, 140.0, 138.9, 131.0, 127.3, 119.7,
117.1, 104.1, 15.0; EI HRMS m/z (M+) calcd 257.0324, found
257.0319. Anal. Calcd for C13H7NO5: C, 60.71; H, 2.74; N, 5.45.
Found: C, 60.67; H, 2.73; N, 5.22.
2-(Meth oxym eth yl)-4-n itr on a p h th o[1,2-b]fu r a n -6,9-d i-
on e (18c). The reaction mixture was refluxed for 30 min.
Washing of the Celite filter was accomplished with benzene
and CHCl3 successively. Evaporation under reduced pressure
gave a yellow oil, which precipitated 18c upon addition of
MeOH. Recrystallization from MeOH gave 18c as golden
needles (0.035 g, 32%): mp 121-122 °C; IR (KBr, cm-1) 3064,
B. Rea ction in Ben zen e. Compound 3 (0.200 g, 1.12 mmol)
was partially dissolved in benzene (5 mL), and 2,3-dihydro-
furan (0.086 g, 1.23 mmol) was added with stirring. After 18
h of stirring, an orange precipitate formed. The solvent was
removed under reduced pressure, and the residual solid was
separated as in part A. Compound 16a was obtained as an
orange-red powder (0.066 g, 24%): mp 215 °C dec; the mixture
melting point with 16a from part A showed no depression; the
1H NMR spectrum was identical with that of the material
obtained in part A. Compound 17a was obtained as a dark
yellow solid, which was crystallized from THF/cyclohexane,
giving 17a as a yellow powder (0.066 g, 24%): mp 222-223
°C dec; the mixture melting point with 17a from part A showed
1
1676, 1606, 1522, 1340, 1306; H NMR (CDCl3, δ ppm) 8.90
(s, 1 H), 7.57 (t, J ) 0.6 Hz, 1 H), 7.12 (d, J ) 10.5 Hz, 1 H),
7.05 (d, J ) 10.5 Hz, 1 H), 4.77 (d, J ) 0.6 Hz, 2 H), 3.56 (s,
3 H); 13C NMR (CDCl3, δ ppm) 182.7, 182.6, 165.1, 153.1, 142.5,
139.1, 138.6, 130.2, 127.9, 119.8, 118.0, 105.0, 67.0, 59.4; EI
HRMS m/z (M+) calcd 287.0430, found 287.0424. Anal. Calcd
for C14H9NO6: C, 58.54; H, 3.16; N, 4.88. Found: C, 58.55; H,
3.10; N, 4.69.
6-Nit r ob en zo[b]n a p h t h o[1,2-d ]fu r a n -1,4-d ion e (14a ).
The reaction mixture was refluxed for 2.5 h. Compound 14a
was obtained as a yellow solid, which was triturated with
CH2Cl2, giving 14a as a yellow powder (0.021 g, 58%): mp
261-263 °C; IR (KBr, cm-1) 3084, 1676, 1618, 1531, 1302,
1
no depression; the H NMR spectrum was identical with that
1
1273; H NMR (CDCl3, δ ppm) 8.87 (s, 1 H), 8.63 (ddd, J )
of the material obtained in part A.
0.6, 1.2, 8.1 Hz, 1 H), 7.87 (ddd, J ) 0.9, 1.2, 8.7 Hz, 1 H),
7.76 (ddd, J ) 1.5, 7.2, 8.3 Hz, 1 H), 7.56 (ddd, J ) 1.2, 7.2,
8.2 Hz, 1 H), 7.16 (d, J ) 10.2 Hz, 1 H), 7.11 (d, J ) 10.2 Hz,
1 H); 13C NMR, too insoluble; EI HRMS m/z (M+) calcd
293.0324, found 293.0338. Anal. Calcd for C16H7NO5: C, 65.54;
H, 2.41; N, 4.78. Found: C, 65.61; H, 2.24; N, 4.68.
cis-3,4,4a ,9a -Tet r a h yd r o-6-h yd r oxy-5-(2-n it r ovin yl)-
2H-p yr a n o[2,3-b]ben zofu r a n (17b). Compound 3 (0.200 g,
1.12 mmol) was dissolved in 3,4-dihydro-2H-pyran (7.5 mL),
and the solution was refluxed for 2 h with stirring. Unreacted
3,4-dihydro-2H-pyran was removed under reduced pressure,
leaving a dark red glass. The glass was dissolved in
a
6-Nitr o-7H-ben zo[c]ca r ba zole-1,4-d ion e (14b). The reac-
tion mixture was refluxed for 3 h. Washing of the Celite filter
was accomplished with CH2Cl2 and acetone successively. After
evaporation, the residual solid was crystallized from acetone,
giving 14b as red needles (0.056 g, 63%): mp 296-297 °C;
the mixture melting point with 14b prepared previously
showed no depression; the 1H NMR spectrum was identical
with that of 14b prepared previously.
minimum amount of CH2Cl2 and eluted through a short plug
of silica gel. The CH2Cl2 solvent was removed under reduced
pressure, giving a red glass. Addition of benzene (3 mL) caused
17b to separate as yellow needles (0.061 g, 21%): mp 198-
199 °C; IR (KBr, cm-1) 3334, 3152, 2933, 1495, 1442, 1341; 1H
NMR (acetone-d6, δ ppm) 9.46 (bs, 1 H), 8.18 (d, J ) 13.5 Hz,
1 H), 8.01 (d, J ) 13.5 Hz, 1 H), 6.85 (d, J ) 8.7 Hz, 1 H), 6.82
(d, J ) 8.7 Hz, 1 H), 5.87 (d, J ) 6.0 Hz, 1 H), 3.84 (dd, J )
3.6, 8.1 Hz, 2H), 3.55 (dt, J ) 6.6, 6.6, 9.6 Hz, 1 H), 2.27-2.15
(m, 1 H), 1.83-1.38 (m, 3 H); 13C NMR (acetone-d6, δ ppm)
152.4, 150.1, 139.6, 134.9, 132.1, 115.0, 114.1, 113.9, 104.8,
61.1, 37.3, 25.9, 21.0; EI HRMS m/z (M+) calcd 263.0794, found
263.0783. Anal. Calcd for C13H13NO5: C, 59.31; H, 4.98; N,
5.32. Found: C, 59.35; H, 5.10; N, 5.29.
7-Meth yl-6-n itr o-7H-ben zo[c]ca r ba zole-1,4-d ion e (14c).
The reaction mixture was refluxed for 3 h. Washing of the
Celite filter was accomplished with acetone. After evaporation,
the residual solid was crystallized from acetone, giving 14c
as maroon needles (0.060 g, 41%): mp 256-258 °C; IR (KBr,
1
cm-1) 3073, 1656, 1585, 1514, 1342; H NMR (CDCl3, δ ppm)
9.42 (ddd, J ) 0.6, 0.9, 8.4 Hz, 1 H), 8.65 (s, 1H), 7.73 (ddd, J
) 1.2, 7.2, 8.4 Hz, 1 H), 7.56 (ddd, J ) 1.2, 1.2, 8.4 Hz, 1 H),
7.47 (ddd, J ) 1.2, 7.2, 8.4 Hz, 1 H), 7.12 (d, J ) 10.2 Hz, 1
H), 7.05 (d, J ) 10.2 Hz, 1 H), 3.84 (s, 3H); 13C NMR, too
insoluble; EI HRMS m/z (M+) calcd 306.0641, found 306.0642.
Gen er a l P r oced u r e Deh yd r ogen a tion of 9 a n d 13 to
18 a n d 14. Compound 9 or 13 was mixed with activated MnO2
(10 equiv) and benzene and refluxed for 2 h with stirring, using
a Dean-Stark trap to remove H2O. The mixture was then
cooled to room temperature and vacuum-filtered through a bed

Synthesis of Angular Quinoid Heterocycles
J . Org. Chem., Vol. 64, No. 2, 1999 603
Anal. Calcd for C17H10N2O4: C, 66.67; H, 3.29; N, 9.15.
Found: C, 66.73; H, 3.28; N, 9.22.
Ack n ow led gm en t. We thank the Wayland E. No-
land Research Fellowship Fund for support of this work.
10-Br om o-6-n itr o-7H-ben zo[c]car bazole-1,4-dion e (14d).
The reaction mixture was refluxed for 3 h. Washing of the
Celite filter was accomplished with acetone. After evaporation,
the residual solid was crystallized from acetone, giving 14d
as red needles (0.049 g, 33%): mp 350-351 °C; the mixture
melting point with 14d prepared previously showed no depres-
sion; the 1H NMR spectrum was identical to that of 14d
prepared previously.
Su p p or tin g In for m a tion Ava ila ble: X-ray crystallo-
graphic data for 16a ; detailed coupling constant analyses for
8b-d (37 pages). This material is contained in libraries on
microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
J O981899U