Access to indoles via Diels-Alder reactions of 2-vinylpyrroles with maleimides

Article abstract of DOI:10.1002/jhet.198

(Chemical Equation Presented) Variously substituted 2-vinylpyrroles underwent an endo-addition [4+2] cycloaddition reaction with maleimides followed by a spontaneous highly diastereoselective (93-98% de) isomerization to give tetrahydroindoles in moderate to excellent yield. Treatment with activated MnO₂ in refluxing toluene provided the corresponding indoles in moderate to good yield. This highly convergent methodology for formation of indoles is versatile and the starting materials are conveniently prepared.

Full text of DOI:10.1002/jhet.198

1154
Access to Indoles via Diels-Alder Reactions of 2-Vinylpyrroles
with Maleimides
Vol 46
Wayland E. Noland,* Nicholas P. Lanzatella, Lakshmanan Venkatraman,
Nicholas F. Anderson, and Glen C. Gullickson
Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455
*E-mail: nolan001@umn.edu
Additional Supporting Information may be found in the online version of this article.
Received March 2, 2009
DOI 10.1002/jhet.198
Published online 4 November 2009 in Wiley InterScience (www.interscience.wiley.com).
Variously substituted 2-vinylpyrroles underwent an endo-addition [4þ2] cycloaddition reaction with
maleimides followed by a spontaneous highly diastereoselective (93–98% de) isomerization to give tet-
rahydroindoles in moderate to excellent yield. Treatment with activated MnO2 in refluxing toluene pro-
vided the corresponding indoles in moderate to good yield. This highly convergent methodology for
formation of indoles is versatile and the starting materials are conveniently prepared.
J. Heterocyclic Chem., 46, 1154 (2009).
INTRODUCTION
using acidic conditions has the advantage of allowing
the use of 5-unsubstituted 2-vinylpyrroles in Diels-Alder
reactions. In addition, we were interested in effecting ar-
omatization of the resulting tetrahydroindoles to give
indoles. Some studies have been conducted on this route
toward indoles using as the dienophiles carboxyl-substi-
tuted acetylenes [7,8], several acyclic electron-deficient
alkenes [8,9], maleic anhydride and/or N-phenylmalei-
mide with N-benzenesulfonyl-2-vinylpyrrole [9,10] and
methyl 3-nitroacrylate with N-p-toluenesulfonyl-2-vinyl-
pyrroles [11] (neither of which was taken through to the
aromatic indole), tetrachloro- or tetrabromocyclopropene
with N-p-toluenesulfonyl-2-vinylpyrrole [12], N-phenyl-
maleimide with N-methyl- and N-propanoyloxy-2-vinyl-
pyrrole [9], N-H-maleimide with 3-(N-alkyl-2-pyrrolyl)
acrylates [13] and N-alkyl-2-styrylpyrroles [13,14], and
one report using various maleimides with both N-H and
N-alkyl-2-vinylpyrroles [15]. Several of these studies
report biological activity from this class of compounds,
particularly anticancer activity [13–15]. To our knowl-
edge, no prior broad study of the efficacy of the synthe-
sis of indoles via Diels-Alder reactions of 5-unsubsti-
tuted 2-vinylpyrroles with N-substituted maleimides has
been reported. In most of the earlier studies, only N-
alkyl-substituted pyrroles were studied, presumably due
to both the higher reactivity of N-H pyrroles and the for-
mation of Michael-addition products between the adduct
The formation of indole continues to attract much
study [1] because of its frequent occurrence in nature
and its biological activity in both natural [2] and syn-
thetic [3] products. We have reported that 3-vinylindoles
are generated from condensation of indole and ketones,
which then undergo an in situ Diels-Alder reaction with
maleimides to form tetrahydrocarbazoles [4]. We
recently reported the analogous work in which pyrroles
are condensed with cyclic ketones to give 2-vinylpyr-
roles that also undergo in situ Diels-Alder reactions with
maleimides to give the corresponding tetrahydroindoles,
many of which exhibited high levels of in vitro activity
against a variety of human cancer cell lines [5].
Although the in situ Diels-Alder approach toward
indoles is advantageous with its one-pot method, it is
somewhat limited in that acidic conditions are required
to catalyze the condensation, and pyrroles are well
known to form polymers under acidic conditions [6].
Indeed, we battled with the formation of polymeric ma-
terial when using vinylpyrroles for in situ Diels-Alder
reactions and found that to circumvent the problem, the
use of 5-alkyl-substituted pyrroles was essential.
These results inspired us to explore the Diels-Alder
chemistry of separately prepared 2-vinylpyrroles. Prepar-
ing the vinylpyrrole in a separate step via methods not
C
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November 2009 Access to Indoles via Diels-Alder Reactions of 2-Vinylpyrroles with Maleimides
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Scheme 1. Synthesis of 2-vinylpyrroles.
and dienophile when certain N-H-2-vinylpyrroles are
used in Diels-Alder reactions, reported here for the first
time. None of the earlier studies has characterized the
diastereoselective isomerism of the adduct, potentially
valuable for synthetic applications. We report here the
first demonstration of the use of chiral maleimides in
Diels-Alder reactions with 2-vinylpyrroles.
tures, respectively, as determined by 1H NMR, which
were used without further purification for formation of
the Diels-Alder adducts. Vinylpyrrole 3a decomposed or
polymerized [20] rapidly at room temperature (rt) to a
dark viscous liquid before it could be used in any Diels-
Alder reaction.
Although the sodium ethoxide procedure produced the
desired N-H-2-vinylpyrrole 4, it also consistently gave a
1:1 molar ratio of the unwanted and not easily separated
byproduct 2-(1-ethoxyethyl)-pyrrole 7. X-ray crystallog-
raphy proved the structure of 7 (Fig. 1). The isolation of
7 was surprising, considering the lack of mention of this
compound in any literature procedure for synthesis of 4.
Although the mixture of 4 and 7 was used as is for
Herein, we report 38 examples where indoles are con-
veniently available from oxidation of the corresponding
tetrahydroindoles, formed via Diels-Alder reactions of
both N-H and N-alkyl-2-vinylpyrroles with a wide range
of N-substituted maleimides. We also report a highly
diastereoselective isomerism of the Diels-Alder adduct,
and isolation of Michael-addition products between the
adduct and the dienophile with the major product being
the more sterically congested diastereomer. Additionally,
we report an improved synthesis of N-H-2-vinylpyrrole.
RESULTS AND DISCUSSION
Synthesis of starting materials. A Vilsmeier-Haack
formylation [16] was performed on the appropriate pyr-
role (1a and 1b, Scheme 1) to give pyrrole-2-carboxal-
dehydes 2a and 2b. Next, a Wittig reaction was con-
ducted on 2a and 2b or on commercially available 2c
and 2d to form the appropriate vinylpyrrole 3–6
[7a,8,17,18]. Various procedures for the Wittig reaction
were used to synthesize the vinylpyrroles. The common
procedure for the synthesis of 2-vinylpyrroles [18,19]
using sodium ethoxide as the base for formation of the
ylide was used to make methyl-substituted vinylpyrroles
3a–3g. For vinylpyrroles 3b, 3c, 3f, and 3g, this proce-
dure gave ꢀ1:3.9, 2.8:1, 1:1.8, and 1:1.5 E:Z molar mix-
Figure 1. ORTEP representation of the X-ray structure of 2-(1-ethoxy-
ethyl)pyrrole (7).
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Vol 46
Scheme 2. Synthesis of maleimides.
formation of the Diels-Alder adducts, a search for a way
to avoid contamination with this impurity was sought,
which probably comes from an acid-catalyzed addition
of ethoxide to the vinyl group in the expected Markov-
nikov orientation. Eliminating the acidic aqueous so-
dium bisulfite wash from the workup had no effect on
the proportion of 7 formed. Heating the mixture of 4
and 7 in DMSO was attempted with the hope of effect-
ing deethanolysis, which did occur, but with the destruc-
tion of a large amount of the desired 4, probably from
polymerization. It was found that using sodium t-butox-
ide in place of sodium ethoxide completely eliminated
the byproduct and gave a higher efficiency than the so-
dium ethoxide procedure, with a consistent yield of
ꢀ80%, and less need for excess methyltriphenylphos-
phonium bromide and base (1.25 equiv) than was
required for complete conversion using the sodium eth-
oxide procedure (2 equiv).
thanamine (9n) was synthesized by methylation of 9o
by reaction of sodium hydride followed by addition of
methyl iodide [24].
Diels-Alder reactions. Diels-Alder reactions of 2-
vinylpyrroles 3b–3g, 4, and 5a with maleimides 10a–
10f, 10h, 10m, and 10n in chloroform gave adducts 11–
29, 31, and 39–51 (Scheme 3, Table 1). The chiral
adducts 39–51 were not isolated but were taken directly
through to the aromatic indoles 85–97 (Scheme 4). The
reaction solution was refluxed, if necessary, and stopped
when complete, as indicated by TLC. Alternatively, the
Diels-Alder reactions of 2-vinylpyrroles 5 and 6 with
maleimides 10c, 10d, 10g, and 10i–10l were run in
refluxing toluene, giving adducts 30–38. In both proce-
dures, vinylpyrroles 3–6 were used in slight excess (1.1
equiv) to simplify the required chromatographic purifica-
tion procedure, because, while the vinylpyrroles were
always eluted first, unreacted maleimides generally were
eluted very near to the adducts. The unrearranged
adducts were not isolated in any case; instead, the rear-
omatized form of the adducts was obtained. Although
an extensive case-by-case comparison of the efficiency
of the two procedures was not undertaken, adduct 31
was produced in both chloroform (70% yield) and tolu-
ene (41%). Further, comparing the average yield of the
toluene-procedure-derived products 30–38 (38%) to the
average yield of the chloroform-procedure-derived prod-
ucts 12, 14, 15, 17–29, and 31 (73%), the chloroform
procedure gave better yields.
To determine whether the Diels-Alder reactions of 2-
vinylpyroles with maleimides took place with the pre-
dicted endo-addition, vinylpyrroles with predominantly
E or Z stereochemistry were desired. Ethyl- and pentyl-
substituted vinylpyrroles 5a and 5b were made from
aldehyde 2a with the Corey procedure for the Wittig
reaction [21], using methylsulfinyl carbanion as the
base, formed from the reaction of DMSO with sodium
1
hydride. H NMR analysis showed that this procedure
gave 5a [18a] exclusively as the Z isomer and 5b in a
1:9 E:Z mixture. For comparison of the stereochemistry
in the resulting Diels-Alder adducts, (E)-2-(2-ethylvi-
nyl)pyrrole 6 [18a] was synthesized using the Schlosser
modification of the Wittig reaction [22], giving a 40%
yield of an ꢀ12:1 E:Z molar mixture.
To determine whether endo- or exo-addition was pre-
dominant, the orientation of a terminal substituent on
the vinyl group of the pyrrole was studied in the result-
ing isomerized adducts using nuclear Overhauser effect
(NOE) experiments (Fig. 2). For description of the ori-
entation, the diastereomer with the syn 3a-H and 8b-H
protons (Fig. 3) protruding from the a-face and the
fused maleimide protruding from the b-face will always
be used, corresponding to the structures at the top of
Figure 2, this convention is also used throughout the
Experimental.
Maleimides were synthesized by the typical procedure
[23], by reaction of maleic anhydride 8 with the appro-
priate primary amine 9a–9l and 9n–9o, and then heating
the resulting amide-acid in an excess of acetic anhydride
(10 equiv) with sodium acetate (0.5 equiv), giving the
corresponding N-substituted maleimide (10a–10n,
Scheme 2). When the acid from reaction of 8 with (R)-
(ꢁ)-phenylglycinol (9o) was cyclized, the primary alco-
hol group was acetylated, giving acetate 10m. To make
the chiral methyl ether 10n, (R)-2-methoxy-1-phenyle-
2-(2-Methylvinyl)-pyrroles 3b and 3f gave the
expected mixture of 4a-Me and 4b-Me in rearranged
adducts 24–29, expected for either endo- or exo-
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November 2009 Access to Indoles via Diels-Alder Reactions of 2-Vinylpyrroles with Maleimides
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Scheme 3. Diels-Alder reactions of 2-vinylpyrroles.
addition. (Z)-2-Vinylpyrroles 5a and 5b gave adducts
30–37 with exclusively 4a-Et and 4a-n-pentyl substitu-
ents, as shown by H NMR analysis. Correspondingly,
the same face from which the 8b-H and 3a-H protons
protrude (the a-face); thus, the 5-H proton of the rear-
ranged adduct would have the predominant orientation
of a. The predominance of a particular diastereomer
was observed in our earlier work [4,5], and to verify it
occurred here as well, NOE experiments were performed
on the rearranged adducts 22 and 23, which had a
methyl substituent at the 5-postion; compound 21 had
overlapping 1H NMR peaks which prevented accurate
measurement of NOE interactions. The assignment of
the two peaks corresponding to the 4a-H and 4b-H pro-
tons was confirmed by a weak NOE interaction between
the 8ba-H and 4a-H protons, whereas no interaction
between the 8ba-H and 4b-H protons was observed.
Additionally, a much stronger interaction was observed
between the 3aa-H and 4a-H protons than between the
3aa-H and 4b-H protons. A strong NOE interaction
between the 4a-H and 5-H protons occurred, with no
1
adduct 38 from the E-vinylpyrrole 6 had mainly 4b-Me
with ꢀ12:1 ratio of 4b-Et to 4a-Et product. To the
1
extent of H NMR sensitivity, this is strong evidence of
predominantly endo-addition Diels-Alder reactions.
The spontaneous rearrangement of Diels-Alder
adducts to their aromatic counterparts was also observed
in our previous work with in situ Diels-Alder reactions
of 2-vinylpyrrole with maleimides [5]. As noted in that
work, because orbital symmetry considerations forbid
suprafacial 1,3-hydride shifts and antarafacial 1,3-
hydride shifts are geometrically difficult [25], the iso-
merism probably takes place via acid catalysis, a ‘‘for-
mal 1,3-hydride shift’’ [26]. A proton should approach
from the least sterically hindered face of the adduct, the
opposite face from which the maleimide protrudes and
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Vol 46
Table 1
Diels-Alder reactions of 2-vinylpyrroles.
Yield
%
PhMe
reflux t Indole
Yield
a
%
Vinylpyrrole Maleimide
R1
R2
R3
R4
Conditions
Adduct
b
4
4
4
4
4
4
4
10a
10b
10c
10d
10e
10f
10h
10a
10c
10f
10a
10c
10f
10a
10c
10f
10a
10c
10f
10c
10d
10d
10g
10i
N,N-DiMe
Bn
Ph
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
CHCl3, reflux 24 h
CHCl3, rt 24 h
CHCl3, reflux 24 h
CHCl3, rt 24 h
CHCl3, rt 24 h
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
31
32c
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
–
23
24 h
3 h
24 h
3 h
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
–
64
45
67
47
61
64
38
66
71
66
70
72
66
57
61
59
56
62
61
44
53
–
b
–
4-EtPh
4-iPrPh
4-(MeO)Ph
4-(PhO)Ph
N,N-DiMe
Ph
4-(MeO)Ph
N,N-DiMe
Ph
4-(MeO)Ph
N,N-DiMe
Ph
H
49
32
H
H
3 h
24 h
3 h
b
–
CHCl3, reflux 24 h
CHCl3, rt 24 h
H
H
33
89
94
93
86
91
93
57
93
90
67
89
84
36
41
70
31
54
32
35
45
30
41
–
3d
3d
3d
3e
3e
3e
3b
3b
3b
3f
3f
3f
5a
5a
5a
5a
5a
5a
5a
5a
5b
6
Me CHCl3, reflux 24 h
Me CHCl3, reflux 24 h
Me CHCl3, reflux 24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
3 h
H
H
H
Me Me CHCl3, rt 24 h
Me Me CHCl3, rt 24 h
Me Me CHCl3, rt 24 h
H
H
Me
Me
Me
Me
Me
Me
Et
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
H
H
H
H
CHCl3, rt 24 h
CHCl3, rt 24 h
CHCl3, rt 24 h
4-(MeO)Ph
N,N-DiMe
Ph
Me CHCl3, rt 24 h
Me CHCl3, rt 24 h
Me CHCl3, rt 24 h
4-(MeO)Ph
Ph
4-EtPh
H
H
H
H
H
H
H
H
H
H
H
H
PhMe, reflux 24 h
PhMe, reflux 24 h
CHCl3, reflux 24 h
PhMe, reflux 24 h
PhMe, reflux 24 h
PhMe, reflux 24 h
PhMe, reflux 24 h
PhMe, reflux 24 h
PhMe, reflux 24 h
PhMe, reflux 24 h
CHCl3, reflux 24 h
CHCl3, reflux 24 h
Et
Et
4-EtPh
–
4-(AcO)Ph
4-(HO)Ph
4-ClPh
Et
Et
24 h
–
81c
15
d
–
d
–
10j
10k
10l
Et
Et
Et
Pentyl
Et
24 h
24 h
24 h
–
82
83
84
–
33
36
28
–
4-BrPh
4-NO2Ph
Ph
Ph
10c
10c
10m
10m
10m
10m
10m
10m
10n
10n
10n
10n
10n
10n
10n
–
–
–
4
AcOCH2CHPh
AcOCH2CHPh
AcOCH2CHPh
AcOCH2CHPh
AcOCH2CHPh
AcOCH2CHPh
MeOCH2CHPh
MeOCH2CHPh
MeOCH2CHPh
MeOCH2CHPh
MeOCH2CHPh
MeOCH2CHPh
MeOCH2CHPh
H
Me
H
Me
Me
Me
H
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
24 h
85
86
87
88
89
90
91
92
93
94
95
96
97
46
27
44
29
26
21
39
30
26
40
32
29
23
3b
3d
3c
3f
3g
4
3b
3e
3d
3c
3f
3g
–
Me CHCl3, reflux 24 h
CHCl3, reflux 24 h
Me CHCl3, reflux 24 h
Me Me CHCl3, reflux 24 h
–
–
H
–
–
–
H
H
H
H
CHCl3, reflux 24 h
CHCl3, reflux 24 h
Me
H
–
–
Me Me CHCl3, reflux 24 h
H
H
Me
H
Me CHCl3, reflux 24 h
CHCl3, reflux 24 h
Me CHCl3, reflux 24 h
–
–
Me
Me
Me
H
–
Me Me CHCl3, reflux 24 h
–
a Yields for chiral indoles are over two steps.
b Crude yields for adducts 11 (64%), 13 (92%), and 16 (90%) include double-addition type products detected by TLC but not isolated.
c Product was deacetylated to 81 during the reaction or workup.
d Only starting material 33 was recovered, but see note c above.
Scheme 4. Aromatization of Diels-Alder adducts.
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Figure 2. Effect of endo- or exo-addition on the stereochemistry of Diels-Alder adducts.
detectable interaction between the 4a-H proton and the
5-methyl group. Correspondingly, a strong NOE interac-
tion was seen between the 4b-H proton and the 5-methyl
group, whereas no detectable response was observed
between the 4b-H and 5-H protons, showing the
52–59, giving evidence of the same kind of stereochem-
istry as described earlier for the 5b-Me adducts 22 and
23 (Fig. 4).
For minor product 59, an NOE interaction was
observed between the 8ba-H proton and a geminal pro-
ton of the succinimide substituent, an interaction absent
in major product 55. In 55, an interaction between the
8ba-H and 4a-H protons showed a syn-relationship.
Multiple strong interactions were observed in compound
55 between the 4b-H proton and the succinimide pro-
tons, whereas no such interactions were observed with
the 4a-H proton, giving evidence that the succinimide is
attached to the b-face in the major product. In com-
pounds 52–59, the stereochemistry of the succinimidyl
proton at the point of attachment was not determined.
However, coupling constants and NOE interactions
between the geminal protons of the succinimide and the
succinimidyl proton at the point of attachment did allow
determination of a probable syn- or anti-relationship. In
1
5-methyl group to be in the b-orientation. The H NMR
integrations of 21–23 showed between a 13:1 and 54:1
molar ratio of major to minor product, a 93–98% dia-
stereomeric excess. The predominant diastereomers had
the sterically more congested configuration, with the
5-methyl group protruding from the same face as the
maleimide.
The high diastereoselectivity of the formal 1,3-
hydride shift is further evidenced from products 52–59.
These types of products were detected whenever unsub-
stituted vinylpyrrole 4 was used in Diels-Alder reactions
with maleimides, where they were isolated and charac-
terized in four reactions. Compound 56 was not com-
pletely separated from 52, although sufficient purity was
1
1
obtained to accurately report H NMR data. In several
compound 55, the H NMR peaks of the 5a-H proton
cases, these products were detected by TLC but not iso-
lated, although their masses were included in determin-
ing the percent yield; hence, yields for products 11, 13,
and 16 do not reflect the actual isolated yield. NOE
studies of 55 and 59 verified the structure of products
Figure 3. Numbering scheme.
Figure 4. NOE experiments. *Numbers indicate % enhancement.
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Figure 5. Proposed mechanism for the formation of 52–59.
and the proton at the point of succinimide attachment
overlapped too greatly to allow accurate measurement
of NOE interactions.
dominate and would result in products 52–55, with a
smaller amount of hydrogen delivery occurring from the
more sterically occluded face to give minor products
56–59. The presence of the succinimide substituent at
C5 may cause the steric environment of the a-face to be
more similar to the b-face than does a 5-methyl group;
this would explain the 3:1–5:1 ratios of products 52–59
(75–83% de) as contrasted with the higher diastereo-
meric excess observed in 5-methyl products 21–23 (93–
98% de).
Aromatization of Diels-Alder adducts. Diels-Alder
adducts 11–32, 34–36, and 39–51 were dehydrogenated
using activated MnO2, giving the corresponding indoles
60–84 in 15–72% yield and giving chiral indoles 85–97
with 21–46% yield over two steps (Scheme 4, Table 1).
Using manganese sulfate with potassium permanganate
[29] to make the activated MnO2 gave consistent and
moderate-yielding aromatizations. Some restrictions to
this technique apply, as when aromatization of
hydroxyl-adduct 33 was attempted, only starting mate-
rial was obtained. Competition for adsorption on the ox-
ide surface of the activated MnO2 from the phenol
group of 33 may have partially deactivated the reagent.
When MnO2 treatment of acetoxy-adduct 32 was con-
ducted, the hydroxy-indole 81 was the exclusive product
isolated. When oxidation occurs, water can be produced,
but deacetylation appears to be unprecedented under
these oxidative conditions; therefore, the aromatized
When first detected, products 52–59 were assumed to
be the result of ene-reactions between the Diels-Alder
adduct and the maleimide, as there are several reports of
ene-products formed between Diels-Alder adducts and
their corresponding dienophiles [27]. However, after
determining the stereochemistry at C5, it was realized
that an ene reaction could not adequately explain the
formation of both epimers. Although an ene reaction
could justify the formation of minor products 56–59, the
tight transition state required [28] makes the ene reac-
tion an impossible route toward major products 52–55
(Fig. 5). Because the more sterically congested epimers
52–55 were the predominant products, thermodynamic
equilibration of the feasibly ene-reaction-formed 56–59
is also highly unlikely.
In light of the diastereoselective rearrangement at C5
noted in this work and in our earlier in situ Diels-Alder
reaction work [4,5], it was realized that our mechanistic
explanation for formation of the rearranged adducts
could also explain the formation of 52–59. A Michael-
addition of the unrearranged adduct to the maleimide
would result in 5-succinimide-substituted adducts. When
a proton approaches the molecule to cause the formal
1,3-hydride shift, an addition from the least sterically
congested face (the a-face in the Figures) would pre-
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pling constant of about 1.5 Hz [10,30]. In 5-methyl adducts,
the 3aa-H proton was sometimes observed to couple to the 5a-
H proton at 0.6–0.9 Hz. Additionally, in 4-alkyl adducts, the
3aa-H proton was coupled to the 5a-H proton at ꢀ1.0 Hz. For
indoles 60–97, the 8-H proton and the 5-H proton were consis-
tently coupled at about 1.0 Hz [31].
product was more likely deacetylated on silica gel dur-
ing chromatography, giving 81. Aromatization and puri-
fication of chiral adducts 39–44 gave indoles 85–90
with no deacetylation.
Biological activity. While participating in the Devel-
opmental Therapeutics Program at the National Cancer
Institute (NCI), we submitted 11 compounds to the NCI
for a one-dose 60 human tumor cell line prescreen:
compounds 12, 14, 17, 30, 32, 33, 61, 63, 66, and 79.
Of these, two compounds, 63 and 66, were judged by
the NCI to have sufficient activity to justify screening
with 60 human tumor cell lines at five concentrations
with 10-fold dilutions, from 1 ꢂ 10ꢁ4 to 1 ꢂ 10ꢁ8 M.
Both of these compounds were found to have high lev-
els of activity against many of the 60 different cell lines
tested. Compound 63 was most active against non–
small-cell lung cancer HOP-92 and melanoma cell lines
SK-MEL-5 and LOX IMVI with an IC50 of 322, 412,
and 462 ng/mL, respectively. Compound 66 was most
active against breast cancer HS 578T, melanoma
UACC-257, and leukemia RPMI-8226, with an IC50 of
3.5, 34, and 230 ng/mL, respectively.
General methods for the preparation of vinylpyrroles.
Method I. Sodium ethoxide (0.125 mol, 2.5 equiv, made
freshly from sodium (2.87 g, 0.125 mol, 2.5 equiv) and EtOH
followed by evaporation using a rotating evaporator) was sus-
pended with the appropriate alkyltriphenylphosphonium bro-
mide (0.1 mol, 2 equiv) in THF (50 mL) [18,19]. The mixture
was stirred at rt under nitrogen for 3 h. Then, a solution of the
appropriate pyrrole-2-carboxaldehyde 2a or 2b or 2-acetylpyr-
role 2c or 2d (0.05 mol) in THF (20 mL) was added over 1
min, and the mixture was stirred under reflux for 15 h. The
solvent was removed using a rotating evaporator, the residue
was suspended in dichloromethane and filtered, and the filter
cake was washed with dichloromethane (3 ꢂ 50 mL). The fil-
trate was washed with saturated NaHSO3 (50 mL), saturated
Na2CO3 (50 mL), and brine (50 mL), and dried over Na2SO4.
The solvent was removed using a rotating evaporator and the
crude product was vacuum-distilled, giving the appropriate
pure 2-vinylpyrrole (with the exception of 4, see later) at com-
parable 60% yield [18,19]. When method I was used to gener-
ate vinylpyrrole 4, 7 was found to be an unwanted byproduct
in an ꢀ1:1 molar ratio to the desired product. This mixture
was used without further purification in subsequent Diels-Alder
reactions.
CONCLUSIONS
Variously substituted 2-vinylpyrroles undergo endo-
addition Diels-Alder additions with maleimides, fol-
lowed by a highly diastereoselective (93–98% de) rear-
rangement to tetrahydroindoles in moderate to excellent
yield. Treatment with activated MnO2 in refluxing tolu-
ene gives the corresponding indole aromatized products
in moderate to good yield. This highly convergent meth-
odology for formation of indoles is flexible and the
starting materials are conveniently prepared.
Method II. Potassium t-butoxide (14.76 g, 0.132 mol, 1.25
equiv) was added slowly to methyltriphenylphosphonium bro-
mide (46.98 g, 0.132 mol, 1.25 equiv) in THF (100 mL) at
0ꢃC. Formation of the bright yellow color characteristic of the
ylide was observed immediately. The mixture was stirred at rt
under nitrogen for 30 min and then cooled to 0ꢃC. A solution
of the pyrrole 2a (10.00 g, 0.105 mmol) in THF (20 mL) was
added over 5 min, with stirring, and refluxed for 30 min until
TLC analysis indicated the reaction was complete. The mixture
was allowed to cool to rt and filtered. The filter cake was
washed with diethyl ether (4 ꢂ 25 mL). The filtrate was
washed with saturated NaHSO3 (50 mL), saturated Na2CO3
(50 mL), and brine (50 mL), and dried over anhydrous
Na2SO4. The solvents were removed using a rotating evapora-
tor and the residue was vacuum-distilled, giving 4 as a color-
EXPERIMENTAL
General. Solvents and reagents were purchased and used as
received. Flash chromatography was performed using 230–450
mesh silica gel. TLC analyses were performed on plastic-
backed plates precoated with 0.2-mm silica with F254 indica-
tor. Infrared spectra were recorded on a 4000 FTIR spectrome-
ter; only the most intense and/or diagnostic peaks are reported.
High-resolution mass spectra were recorded with a time-of-
flight instrument using electrospray ionization with PEG as an
internal calibrant. For NMR spectra, chemical shifts (d) were
referenced to the solvent. 13C NMR spectra were proton
decoupled. Melting points are uncalibrated. Elemental analyses
were performed by M-H-W Laboratories, Phoenix, AZ. Petro-
leum ether refers to the fraction boiling at 35–60ꢃC.
1H NMR analysis. In the 1H NMR spectra of adducts 11–
38, the 8ba-H proton often appears as a doublet of doublet of
doublets in 5-unsubstituted adducts; COSY experiments indi-
cate that the 8ba-H proton is coupled not only to the 3aa-H
proton but also to the 5-bond-distant 5-H protons with a cou-
1
less liquid (7.66 g, 78%). The H and 13C NMR data matched
the values in the literature [18,19].
For Diels-Alder reactions, vinylpyrroles 5a and 5b were
synthesized using Corey’s procedure for the Wittig reaction
[21], and method I was used to synthesize vinylpyrroles 3a–g.
However, for purposes of characterization 3a–c, 3e–f, and 5b
were synthesized using method II.
2-(2-Propenyl)-1H-pyrrole (3a). Method II with 2c (3.16 g,
0.029 mol) and distillation at 37ꢃC/0.04 mm Hg gave 3a (436
1
mg, 14%) as a white waxy solid [17a]: mp 71–73ꢃC; H NMR
(300 MHz, CDCl3, d) 8.32 (bs, 1H, 1-H), 6.82 (ddd, J ¼ 2.8,
2.8, 1.4 Hz, 1H, 5-H), 6.37 (dddd, J ¼ 3.1, 3.1, 1.7, 1.3 Hz,
1H, 3-H), 6.32 (dddd, J ¼ 3.3, 2.6, 2.6, 0.9 Hz, 1H, 4-H),
5.09–5.11 (m, 1H, 10-H cis to pyrrole), 4.91–4.93 (m, 1H, 10-H
trans to pyrrole), 2.17 (ddd, J ¼ 1.6, 0.8, 0.8 Hz, 3H, 30-H);
13C NMR (75 MHz, CDCl3, d) 135.1, 133.2, 118.8, 109.5,
107.0, 105.7, 20.8; IR (thin film, cmꢁ1) 3450(bs), 3400(s),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1162
W. E. Noland, N. P. Lanzatella, L. Venkatraman, N. F. Anderson, and G. C. Gullickson
Vol 46
2969(s), 2925(m), 2840(w), 1634(m), 1597(m), 1557(w),
1499(w), 1470(m), 1403(m), 1235(m), 1110(w), 1035(m);
HRMS m/z (M þ Hþ) calcd. for C7H9N: 108.0808, found
108.0815.
10maj-H), 6.20–6.23 (m, 1H, 50min-H), 6.06–6.19 (m, 1H,
20min-H), 5.76–5.88 (m, 1H, 20maj-H), 3.69 (s, 3H, 1min-
CH3), 3.69 (s, 3H, 1maj-CH3), 2.04–2.08 (m, 3H, 30maj-H),
1.98–2.02 (m, 3H, 20maj-H); 13C NMR (75 MHz, CDCl3, d)
132.4, 130.4, 124.3, 124.1, 122.24, 122.16, 120.1, 118.6,
109.6, 107.8, 107.6, 105.3, 34.1, 18.9, 15.3; IR (thin film,
cmꢁ1) 3103(m), 3018(m), 2967(s), 2937(s), 2917(s), 2860(m),
1698(w), 1640(w), 1479(s), 1450(m), 1412(m), 1376(m),
1356(w), 1342(w), 1302(m), 1292(s), 1241(w), 1228(w),
1089(m), 1064(w), 1033(w), 998(w), 832(w), 781(m), 649(s),
2-(1-Propenyl)-1H-pyrrole (3b). Method II with 2a (2.66 g,
0.028 mol) and distillation at 35.5ꢃC/0.05 mm Hg gave 3b
(2.32 g, 77%) as a white solid [17b,18a]: 1.0:3.9 E:Z; mp 27–
1
28ꢃC; H NMR (300 MHz, CDCl3, d) 8.10 (bs, 1H, 1-H), 6.82
(ddd, J ¼ 2.6, 2.6, 1.4 Hz, 1H, 5maj-H), 6.74 (ddd, J ¼ 2.7,
2.7, 1.4 Hz, 1H, 5min-H), 6.22–6.42 (m, 3H, 3-H, 4-H, 10-H),
5.80–5.93 (m, 1H, 20min-H), 5.61–5.74 (m, 1H, 20maj-H),
2.03–2.07 (m, 3H, 30maj-H), 1.93–1.97 (m, 3H, 30min-H); 13C
NMR (75 MHz, CDCl3, d) 130.4, 122.2, 121.8, 120.9, 120.4,
118.0, 117.8, 109.6, 109.4, 109.0, 106.6, 18.5, 15.2; IR (thin
film, cmꢁ1) 3469(s), 3396(bs), 3107(w), 3024(m), 2963(m),
2950(m), 2935(m), 2857(w), 1642(m), 1603(w), 1546(w),
1459(m), 1409(w), 1366(m), 1294(w), 1278(w), 1216(w),
1118(m), 1098(m), 1032(m), 957(w), 800(s); HRMS m/z (M þ
Hþ) calcd. 108.0808, found 108.0802. Anal. Calcd. for
C7H9N: C, 78.46; H, 8.47; N, 13.07. Found: C, 78.28; H, 8.66;
N, 12.94.
2-(2-But-2-enyl)-1H-pyrrole (3c). Method II with 2c (3.16
g, 0.029 mol) and distillation at 43ꢃC/0.04 mm Hg gave 3c
(922 mg, 26%) as a colorless liquid: 2.8:1.0 E:Z; 1H NMR
(300 MHz, CDCl3, d) 8.32 (bs, 1H, 1-H), 6.87 (ddd, J ¼ 2.4,
2.4, 2.4 Hz, 1H, 5maj-H), 6.77 (ddd, J ¼ 2.2, 2.2, 2.2 Hz, 1H,
5min-H), 6.36–6.40 (m, 2H, 3maj-H, 4maj-H), 6.27–6.31 (m,
2H, 3min-H, 4min-H), 5.67–5.76 (m, 1H, 30min-H), 5.50–5.59
(m, 1H, 30maj-H), 2.12–2.15 (m, 3H, 10maj-H), 2.05–2.07 (m,
3H, 10min-H), 1.97–2.01 (m, 3H, 40maj-H), 1.86–1.90 (m, 3H,
40min-H); 13C NMR (75 MHz, CDCl3, d) 134.9, 132.4, 127.6,
126.9, 119.5, 117.8, 117.5, 116.0, 109.1, 109.0, 108.4, 105.2,
23.1, 15.4, 14.4, 13.7; IR (thin film, cmꢁ1) 3481(s), 3419(bm),
2973(m), 2922(m), 2862(m), 1643(w), 1551(w), 1452(m),
1403(m), 1378(m), 1353(w), 1119(m), 1090(m), 1068(w),
1036(m), 806(m), 791(m); HRMS m/z (M þ Hþ) calcd.
122.0964, found 122.0965. Anal. Calcd. for C8H11N: C, 79.29;
H, 9.15; N, 11.56. Found: C, 79.22; H, 8.96; N, 11.33.
N-Methyl-2-(2-propenyl)-1H-pyrrole (3e). Method II with
2d (3.57 g, 0.029 mol) and distillation at 31.5ꢃC/0.04 mm Hg
gave 3e (1.62 g, 46%) as a colorless liquid [7a,17c,17e,17f]:
1H NMR (300 MHz, CDCl3, d) 6.77 (ddd, J ¼ 2.7, 1.4, 1.4
Hz, 1H, 5-H), 6.37 (ddd, J ¼ 3.7, 1.9, 1.9 Hz, 1H, 3-H), 6.30
(ddd, J ¼ 3.8, 2.7, 1.8 Hz, 1H, 4-H), 5.26 (dq, J ¼ 3.0, 1.5
Hz, 1H, 10-H cis to pyrrole), 5.17 (dq, J ¼ 3.0, 1.5 Hz, 1H, 10-
H trans to pyrrole), 3.85 (d, J ¼ 1.2 Hz, 3H, 1-CH3), 2.28
(dddd, J ¼ 1.7, 1.7, 1.0, 0.9 Hz, 3H, 30-H); 13C NMR (75
MHz, CDCl3, d) 135.9, 134.7, 124.7, 111.6, 108.8, 107.3,
36.3, 24.1; IR (thin film, cmꢁ1) 3104(m), 2974(s), 2952(s),
2921(s), 2881(m), 2806(w), 2726(w), 1794(w), 1701(w),
1626(s), 1478(s), 1449(m), 1434(s), 1413(m), 1374(m),
1363(m), 1313(s), 1260(m), 1224(w), 1094(m), 1062(w),
997(w), 789(m), 605(m); HRMS m/z (M þ Hþ) calcd.
122.0964, found 122.0959. Anal. Calcd. for C8H11N: C, 79.29;
H, 9.15; N, 11.56. Found: C, 79.54; H, 8.92; N, 11.54.
608(s); HRMS m/z (M
122.0956. Anal. Calcd. for C8H11N: C, 79.29; H, 9.15; N,
11.56. Found: C, 79.50; H, 8.93; N, 11.80.
þ
Hþ) calcd. 122.0964, found
2-(2-But-2-enyl)-N-methyl-1H-pyrrole (3g). Method II with
2d (3.50 g, 0.032 mol) and distillation at 31.5ꢃC/0.04 mm Hg
gave 3g (1.01 g, 23%) as a colorless liquid: 1.0:1.5 E:Z; 1H
NMR (300 MHz, CDCl3, d) 6.70 (ddd, J ¼ 2.7, 1.8, 1.8 Hz,
1H, 5maj-H), 6.64 (ddd, J ¼ 2.7, 2.0, 2.0 Hz, 1H, 5min-H),
6.24 (ddd, J ¼ 3.5, 2.4, 2.4 Hz, 1H, 3maj-H), 6.18 (ddd, J ¼
3.6, 2.4, 2.4 Hz, 1H, 3min-H), 6.10 (dddd, J ¼ 3.9, 3.9, 2.0,
2.0 Hz, 1H, 4min-H), 6.02 (dddd, J ¼ 3.8, 3.8, 2.0, 2.0 Hz,
1H, 4maj-H), 5.74–5.84 (m, 1H, 30maj-H), 5.60–5.69 (m, 1H,
30min-H), 3.68 (d, J ¼ 2.1 Hz, 3H, 1min-CH3), 3.57 (d, J ¼
1.8 Hz, 3H, 1maj-CH3), 2.04–2.06 (m, 3H, 10-H), 1.85–1.90
(m, 3H, 40min-H), 1.59–1.64 (m, 3H, 40maj-H); 13C NMR (75
MHz, CDCl3, d) 137.7, 133.6, 129.1, 128.1, 126.3, 124.1,
122.7, 121.4, 107.4, 107.1, 106.8, 33.3, 34.0, 25.5, 17.3, 15.5,
14.2; IR (thin film, cmꢁ1
) 3106(m), 3026(m), 2943(m),
2918(m), 2884(m), 2857(w), 2810(w), 1703(w), 1638(m),
1484(s), 1451(m), 1367(w), 1305(s), 1261(w), 1228(w),
1091(m), 1058(w), 1009(w), 954(m), 789(m), 648(s), 605(m);
HRMS m/z (M þ Hþ) calcd. for C9H13N: 136.1121, found
136.1124.
2-Ethenyl-1H-pyrrole (4). Method II with 2a (10.00 g,
0.105 mol) and distillation at 30ꢃC/0.04 mm Hg gave 4 (7.66
g, 78%) as a colorless liquid [18,19]; the 1H and 13C NMR
data matched the literature values [18,19]. Anal. Calcd. for
C6H7N: C, 77.38; H, 7.58; N, 15.04. Found: C, 77.17; H, 7.67;
N, 14.83.
2-(1-Heptenyl)-1H-pyrrole (5b). Method II with 2a (2.91 g,
0.031 mol) and distillation at 68ꢃC/0.04 mm Hg gave 5b (4.40
g, 81%) as a colorless liquid: 1.0:9.0 E:Z; 1H NMR (300
MHz, CDCl3, d) 8.10 (bs, 1H, 1-H), 6.81 (ddd, J ¼ 2.3, 2.3,
1.7 Hz, 1H, 5maj-H), 6.74 (ddd, J ¼ 2.6, 2.6, 1.4 Hz, 1H,
5min-H), 6.21–6.37 (m, 3H, 3-H, 4-H, 10-H), 5.85 (ddd, J ¼
16.1, 7.0, 7.0 Hz, 1H, 20min-H), 5.53 (ddd, J ¼ 12.8, 6.8, 5.8
Hz, 1H, 20maj-H), 2.45 (ddt, J ¼ 7.3, 7.2, 1.8 Hz, 2H, 30maj-
H), 2.25 (dt, J ¼ 7.2, 7.1, 1.5 Hz, 2H, 30min-H), 1.34–1.65
(m, 6H, 40-H, 50-H, 60-H), 1.01 (t, J ¼ 7.2 Hz, 3H, 70-H); 13C
NMR (75 MHz, CDCl3, d) 134.0, 133.7, 130.3, 128.9, 128.8,
128.7, 128.6, 126.3, 120.5, 119.0, 117.8, 117.7, 109.6, 109.4,
108.9, 106.7, 32.9, 31.8, 31.5, 29.4, 29.4, 22.7, 14.2; IR (thin
film, cmꢁ1) 3469(s), 3392(bs), 3105(m), 3014(m), 2957(s),
2926(s), 2857(s), 1712(w), 1639(m), 1545(w), 1460(m),
1434(m), 1412(m), 1379(m), 1293(w), 1280(w), 1212(w),
1182(w), 1118(m), 1095(m), 1033(m), 955(m), 799(m),
949(m); HRMS m/z (M þ Hþ) calcd. 164.1434, found
164.1434. Anal. Calcd. for C11H17N: C, 80.93; H, 10.50; N,
8.58. Found: C, 81.07; H, 10.32; N, 8.74.
N-Methyl-2-(1-propenyl)-1H-pyrrole (3f). Method II with
2b (3.50 g, 0.032 mol) and distillation at 32.5ꢃC/0.04 mm Hg
gave 3f (2.66 g, 68%) as a colorless liquid [17d,17g,17i]:
1.0:1.8 E:Z; 1H NMR (300 MHz, CDCl3, d) 6.72 (ddd, J ¼
2.9, 1.5, 1.5 Hz, 1H, 5maj-H), 6.66 (ddd, J ¼ 2.4, 2.0, 2.0 Hz,
1H, 5min-H), 6.36–6.44 (m, 2H, 3-H, 4-H), 6.29–6.32 (m, 1H,
2-(1-Ethoxyethyl)-N-methyl-1H-pyrrole (7). A 1:1 molar
mixture of 4 and 7, prepared using method I, was left in a
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2009 Access to Indoles via Diels-Alder Reactions of 2-Vinylpyrroles with Maleimides
1163
refrigerator for 6 months, giving large colorless crystals of 7.
The crystals were removed and the liquid 4 was washed off
using ice-cold petroleum ether, giving colorless crystals: mp
826(m), 696(s); HRMS m/z (M þ Naþ) calcd. for C13H13NO3:
254.0783, found 254.0783.
General method for Diels-Alder reactions. A mixture of
the vinylpyrrole (0.0050 mol, 1.1 equiv) and the maleimide
(0.0045 mol) (1) in chloroform (20 mL) was stirred at rt for
24 h and, if TLC analysis indicated maleimide remaining, the
mixture was also refluxed for 24 h (method A) or (2) in tolu-
ene (20 mL) was refluxed for 24 h (method B). The solvent
was removed using a rotating evaporator. The crude adduct
was purified with flash chromatography or MPLC with ethyl
acetate/hexanes as eluent, except in the case of chiral adducts,
which were used without further purification in the next step.
General method for the dehydrogenation of Diels-Alder
adducts. A mixture of the adduct (3.76 mmol) and activated
MnO2 [29] (18.8 mmol, 5 equiv) in toluene (30 mL) was
refluxed for 2–3 h until the reaction was complete, as indicated
by TLC (method C), or refluxed for 24 h (method D). For
dehydrogenation of chiral adducts, the crude Diels-Alder reac-
tion product was placed in toluene (30 mL) along with acti-
vated MnO2 (5 equiv) and refluxed for 24 h (method E). The
mixture was cooled to rt and filtered through a fine glass frit.
The insoluble manganese salts were washed with several por-
tions of dichloromethane until the washings ran clear (5 ꢂ 20
mL), and the combined organic filtrate and washings were
evaporated to dryness using a rotating evaporator. Flash chro-
matography or MPLC with ethyl acetate/hexanes as eluent pro-
vided the desired product in good yields.
1
26.5–28.5ꢃC; H NMR (300 MHz, CDCl3, d) 8.39 (bs, 1H, 1-
H), 6.78 (ddd, J ¼ 2.6, 2.6, 1.6 Hz, 1H, 5-H), 6.16 (ddd, J ¼
3.3, 2.7, 2.5 Hz, 1H, 4-H), 6.08 (ddd, J ¼ 3.5, 2.6, 1.5 Hz,
1H, 3-H), 4.55 (q, J ¼ 6.6 Hz, 1H, 10-H), 3.44 (dq, J ¼ 12.0,
7.0 Hz, 1H, OCH2CH3), 3.40 (dq, overlapped, J ¼ 11.7, 7.0
Hz, 1H, OCH2CH3), 1.51 (d, J ¼ 6.6 Hz, 3H, 20-H), 1.19 (dd,
J ¼ 6.9, 7.2 Hz, 3H, OCH2CH3); 13C NMR (75 MHz, CDCl3,
d) 133.7 (C2), 117.5 (C5), 107.9 (C4), 106.0 (C3), 71.1 (C10),
63.4 (OCH2CH3), 21.7 (C20), 15.5 (OCH2CH3); IR (film,
cmꢁ1
)
3464(m), 3322(w), 3054(m), 2980(m), 2933(w),
2873(w), 1446(w), 1422(w), 1373(w), 1325(w), 1266(s),
1151(w), 1086(m), 1028(w), 1006(w), 896(w), 796(w), 739(s),
707(s). X-ray data for 7 in CIF format are available in the
Supporting Information.
General method for the synthesis of chiral
maleimides. The primary amine (0.070 mol) dissolved in a
large excess of diethyl ether (100 mL) was added over 20 min
using a dropping funnel to a 2-L flask containing maleic anhy-
dride (6.85 g, 0.070 mol, 1 equiv) dissolved in diethyl ether
(500 mL) [23]. Throughout the addition, the mixture turned
into a thick off-white suspension. The suspension was concen-
trated to half-volume, cooled in the freezer, and vacuum-fil-
tered, giving the crude acid as a thick paste. Acetic anhydride
(300 mL) and sodium acetate (2.87 g, 0.035 mol, 0.5 equiv)
were added to the crude acid and the mixture was heated to
100ꢃC in a boiling water bath for 2 h. The mixture was then
cooled to rt, diluted with water (200 mL), and portions of
NaHCO3 were added slowly with vigorous stirring until the
acetic acid was nearly neutralized. The solution was extracted
with ether (3 ꢂ 200 mL), and the organic extracts were
washed with saturated NaHCO3 until neutral, then washed
with water (100 mL) and brine (100 mL), and dried over anhy-
drous Na2SO4. The solvent was removed using a rotating
evaporator and the product was purified using flash chromatog-
raphy on silica gel using ethyl acetate/hexanes to give the pure
chiral maleimide in moderate yield (ꢀ50%).
2-Dimethylamino-3aa,4,5,8ba-tetrahydro-2H,6H-pyrrolo[3,
4-e]indole-1,3-dione (11). Method A with vinylpyrrole 4 and
maleimide 10a gave 11 (597 mg, 64% crude yield, including
contamination from double-addition type products, detected by
TLC; the crude adduct was recrystallized from methylene
chloride/petroleum ether, giving the pure compound, but the
isolated yield is not available) as a light-brown powder: mp
1
56–57ꢃC; H NMR (300 MHz, CDCl3, d) 8.02 (bs, 1H, 6-H),
6.68 (dd, J ¼ 2.7, 2.7 Hz, 1H, 7-H), 6.37 (dd, J ¼ 2.9, 2.9 Hz,
1H, 8-H), 3.89 (ddd, J ¼ 8.1, 1.4, 1.4 Hz, 1H, 8ba-H), 3.18
(ddd, J ¼ 7.8, 5.4, 5.4 Hz, 1H, 3aa-H), 2.84 (s, 6H, N(CH3)2),
2.57–2.65 (m, 2H, 5a-H and 5b-H), 2.34 (dddd, J ¼ 13.6, 5.1,
5.1, 5.1 Hz, 1H, 4b-H), 2.00 (dddd, J ¼ 13.7, 8.6, 6.3, 5.1 Hz,
1H, 4a-H); 13C NMR (75 MHz, CDCl3, d) 177.6, 176.7,
127.1, 117.2, 109.9, 107.7, 44.0, 38.8, 38.7, 22.2, 19.5; IR
(film, cmꢁ1) 3361(bs), 2930(m), 1777(w), 1711(s), 1448(w),
1369(m), 1200(m), 1147(m), 719(w); HRMS m/z (M þ Naþ)
calcd. 256.1057, found 256.1057. Anal. Calcd. for
C12H15N3O2: C, 61.79; H, 6.48; N, 18.01. Found: C, 61.59; H,
6.32; N, 17.90.
(1)-(R)-2-(2,5-Dioxo-1H-pyrrol-1-yl)-2-phenylethyl acetate
(10m). The general method gave 10m (8.167 g, 45%) as a
light-red oil: [a]23 þ1.7 (c 10.0, CHCl3); 1H NMR (300
D
MHz, CDCl3, d) 7.43–7.46 (m, 2H, Ph), 7.33–7.40 (m, 3H,
Ph), 6.71 (s, 2H, vinyl-H), 5.43 (dd, J ¼ 10.5, 5.4 Hz, 1H, 20-
H), 4.99 (dd, J ¼ 11.1, 10.5 Hz, 1H, 10-H), 4.71 (dd, J ¼
11.1, 5.4 Hz, 1H, 10-H), 2.04 (s, 3H, OAc); 13C NMR (75
MHz, CDCl3, d) 170.7, 170.6, 135.9, 134.3, 128.9, 128.6,
128.0, 62.4, 53.6, 20.8; IR (film, cmꢁ1) 3465(m), 3101(m),
2950(w), 1743(s), 1713(s), 1399(s), 1370(s), 1232(s), 1163(m),
1043(m), 828(m), 696(s); HRMS m/z (M þ Naþ) calcd. for
C14H13NO4: 282.0738, found 282.0740.
2-Benzyl-3aa,4,5,8ba-tetrahydro-2H,6H-pyrrolo[3,4-e]indole-
1,3-dione (12). Method A with vinylpyrrole 4 and maleimide
1
10b gave 12 (258 mg, 23%) as a colorless oil; H NMR (300
MHz, CDCl3, d) 7.98 (bs, 1H, 6-H), 7.24–7.29 (m, 5H, Ph),
6.68 (dd, J ¼ 2.7, 2.7 Hz, 1H, 7-H), 6.37 (dd, J ¼ 2.7, 2.7 Hz,
1H, 8-H), 4.64 (AA0 d, J ¼ 14.4 Hz, 1H, Bn), 4.58 (AA0 d,
J ¼ 14.1 Hz, 1H, Bn), 3.98 (ddd, J ¼ 8.1, 1.2, 1.2 Hz, 1H,
8ba-H), 3.24 (ddd, J ¼ 7.8, 5.1, 5.1 Hz, 1H, 3aa-H), 2.61
(dddd, J ¼ 16.0, 5.3, 5.3, 0.9 Hz, 1H, 5b-H), 2.51 (dddd, J ¼
15.4, 9.9, 5.4, 0.9 Hz, 1H, 5a-H), 2.37 (dddd, J ¼ 13.5, 4.8,
4.8, 4.8, 1H, 4b-H), 1.99 (dddd, J ¼ 13.7, 9.8, 5.5, 5.3 Hz,
1H, 4a-H); 13C NMR (75 MHz, CDCl3, d) 179.0, 178.0,
136.0, 128.7, 128.4, 127.8, 127.2, 117.2, 110.4, 107.6, 42.3,
40.4, 40.1, 22.2, 19.6; IR (KBr, cmꢁ1) 3450s, 3100w, 2924m,
(1)-(R)-1-(2-Methoxy-1-phenylethyl)-1H-pyrrole-2,5-dione
(10n). The general method gave 10n (7.608 g, 47%) as white
1
crystals: mp 55–56ꢃC; [a]23 þ22.5 (c 1.0, CHCl3); H NMR
D
(300 MHz, CDCl3, d) 7.41–7.45 (m, 2H, Ph), 7.30–7.38 (m,
3H, Ph), 6.68 (s, 2H, vinyl-H), 5.38 (dd, J ¼ 10.5, 5.4 Hz, 1H,
10-H), 4.46 (dd, J ¼ 11.2, 11.2 Hz, 1H, 20-H), 3.82 (dd, J ¼
10.9, 5.4 Hz, 1H, 20-H), 3.39 (s, 3H, OCH3); 13C NMR (75
MHz, CDCl3, d) 171.0, 137.0, 134.2, 128.8, 128.3, 128.0,
70.8, 58.8, 54.3; IR (film, cmꢁ1) 3460(bm), 3095(m), 2915(m),
2810(w), 1706(s), 1400(m), 1368(m), 1154(w), 1110(m),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1164
W. E. Noland, N. P. Lanzatella, L. Venkatraman, N. F. Anderson, and G. C. Gullickson
Vol 46
2980w, 1701s; HRMS m/z (M þ Naþ) calcd. 303.1105, found
303.1093. Anal. Calcd. for C17H16N2O2: C, 72.84; H, 5.75; N,
9.99. Found: C, 72.92; H, 5.75; N, 9.43.
3444(m), 3353(bs), 3105(w), 2959(m), 2931(m), 2863(w),
1773(w), 1704(s), 1513(m), 1463(w), 1428(w), 1381(m),
1347(w), 1280(w), 1194(m), 1177(m), 1152(m), 1093(w),
1067(w), 1051(w), 721(m); HRMS m/z (M þ Naþ) calcd.
331.1418, found 331.1410. Anal. Calcd. for C19H20N2O3: C,
74.00; H, 6.54; N, 9.08. Found: C, 74.00; H, 6.51; N, 9.16.
2-(4-Methoxyphenyl)-3aa,4,5,8ba-tetrahydro-2H,6H-pyrrolo
[3,4-e]indole-1,3-dione (16). Method A with vinylpyrrole 4
and maleimide 10f gave 16 (1.067 g, 90% crude yield, includ-
ing contamination from double-addition type products,
detected by TLC; the crude adduct was recrystallized from
methylene chloride/petroleum ether, giving the pure com-
pound, but the isolated yield is not available) as a white pow-
2-Phenyl-3aa,4,5,8ba-tetrahydro-2H,6H-pyrrolo[3,4-e]indole-
1,3-dione (13). Method A with vinylpyrrole 4 and maleimide
10c gave 13 (980 mg, 92% crude yield, including contamina-
tion from double-addition type products, detected by TLC; the
crude adduct was recrystallized from methylene chloride/petro-
leum ether, giving the pure compound, but the isolated yield is
not available) as a light-brown powder: mp 155–156ꢃC; 1H
NMR (300 MHz, CDCl3, d) 7.95 (bs, 1H, 6-H), 7.41–7.47 (m,
2H, Ph), 7.33–7.39 (m, 1H, Ph), 7.23–7.28 (m, 2H, Ph), 6.70
(dd, J ¼ 2.9, 2.9 Hz, 1H, 7-H), 6.41 (dd, J ¼ 2.6, 2.6 Hz, 1H,
8-H), 4.15 (ddd, J ¼ 8.1, 1.4, 1.4 Hz, 1H, 8ba-H), 3.45 (ddd,
J ¼ 8.1, 5.0, 5.0 Hz, 1H, 3aa-H), 2.63–2.67 (m, 2H, 5a-H and
5b-H), 2.53 (dddd, J ¼ 13.6, 4.5, 4.5, 4.5 Hz, 1H, 4b-H), 2.06
(dddd, J ¼ 13.4, 8.3, 7.6, 5.2 Hz, 1H, 4a-H); 13C NMR (75
MHz, CDCl3, d) 178.3, 177.3, 132.1, 129.1, 128.4, 127.3,
126.4, 117.3, 110.2, 107.7, 40.5, 40.4, 22.0, 19.4; IR (film,
1
der: mp 187–188ꢃC; H NMR (300 MHz, CDCl3, d) 7.94 (bs,
1H, 6-H), 7.17 (d, J ¼ 9.0 Hz, 2H, Ph), 6.94 (d, J ¼ 9.0 Hz,
2H, Ph), 6.70 (dd, J ¼ 2.7, 2.7 Hz, 1H, 7-H), 6.41 (dd, J ¼
2.9, 2.9 Hz, 1H, 8-H), 4.15 (ddd, J ¼ 8.1, 1.4, 1.4 Hz, 1H,
8ba-H), 3.82 (s, 3H, OCH3), 3.45 (ddd, J ¼ 7.8, 5.0, 5.0 Hz,
1H, 3aa-H), 2.63–2.67 (m, 2H, 5a-H and 5b-H), 2.53 (dddd, J
¼ 13.5, 4.5, 4.5, 4.5 Hz, 1H, 4b-H), 2.06 (dddd, J ¼ 13.7, 8.0,
7.7, 5.2 Hz, 1H, 4a-H); 13C NMR (75 MHz, CDCl3, d) 178.5,
177.5, 159.3, 127.7, 127.2, 124.8, 117.2, 114.4, 110.4, 107.7,
55.6, 40.5, 40.3, 22.0, 19.4; IR (film, cmꢁ1) 3378(bm),
2931(w), 2842(w), 1776(w), 1704(s), 1608(w), 1513(s),
1466(w), 1441(w), 1389(m), 1300(w), 1251(m), 1168(m),
1030(w), 729(w); HRMS m/z (M þ Naþ) calcd. 319.1054,
found 319.1056. Anal. Calcd. for C17H16N2O3: C, 68.91; H,
5.44; N, 9.45. Found: C, 68.86; H, 5.61; N, 9.28.
cmꢁ1
)
3374(bs), 2857(m), 1775(w), 1707(s), 1596(w),
1498(m), 1383(m), 1177(m), 1064(m), 793(m), 723(m);
HRMS m/z (M þ Naþ) calcd. 289.0948, found 289.0947.
Anal. Calcd. for C16H14N2O2: C, 72.16; H, 5.30; N, 10.52.
Found: C, 71.96; H, 5.43; N, 10.57.
2-(4-Ethylphenyl)-3aa,4,5,8ba-tetrahydro-2H,6H-pyrrolo[3,
4-e]indole-1,3-dione (14). Method A with vinylpyrrole 4 and
maleimide 10d gave 14 (577 mg, 49%) as a white powder: mp
144–146ꢃC; 1H NMR (300 MHz, CDCl3, d) 7.93 (bs, 1H, 6-
H), 7.26 (d, J ¼ 8.9, 2H, Ph), 7.15 (d, J ¼ 8.4 Hz, 2H, Ph),
6.70 (dd, J ¼ 2.6, 2.6 Hz, 1H, 7-H), 6.41 (dd, J ¼ 2.7, 2.7 Hz,
1H, 8-H), 4.13 (ddd, J ¼ 7.8, 1.4, 1.4 Hz, 1H, 8ba-H), 3.43
(ddd, J ¼ 8.1, 5.0, 5.0 Hz, 1H, 3aa-H), 2.63–2.71 (m, 2H, 5a-
H and 5b-H), 2.66 (q, overlapped, J ¼ 7.6 Hz, 2H, CH2CH3),
2.52 (dddd, J ¼ 13.7, 4.6, 4.6, 4.6 Hz, 1H, 4b-H), 2.06 (dddd,
J ¼ 13.4, 8.4, 7.3, 5.1 Hz, 1H, 4a-H), 1.23 (t, J ¼ 7.7 Hz, 3H,
CH2CH3); 13C NMR (75 MHz, CDCl3, d) 178.7, 177.7, 144.7,
129.6, 128.6, 127.3, 126.4, 117.3, 110.1, 107.4, 40.6, 40.4,
28.7, 22.1, 19.4, 15.6; IR (KBr, cmꢁ1) 3340(bs), 3030(w),
2970(m), 2940(m), 2860(w), 1780(m), 1700(s), 1600(w),
1510(m), 1445(w), 1395(s), 1360(w), 1310(w), 1295(w),
1205(m), 1195(m), 1170(m), 850(w), 815(w), 785(m), 720(m),
695(m); HRMS m/z (M þ Naþ) calcd. 317.1261, found
317.1262. Anal. Calcd. for C18H18N2O2: C, 73.45; H, 6.16; N,
9.52. Found: C, 73.60; H, 6.26; N, 9.36.
2-(4-Phenoxyphenyl)-3aa,4,5,8ba-tetrahydro-2H,6H-pyrrolo
[3,4-e]indole-1,3-dione (17). Method A with vinylpyrrole 4
and maleimide 10h gave 17 (473 mg, 33%) as a light-yellow
1
powder: mp 200–202ꢃC; H NMR (300 MHz, CDCl3, d) 7.93
(bs, 1H, 6-H), 7.33–7.39 (m, 2H, Ph), 7.21 (d, J ¼ 9.0 Hz, 2H,
Ph), 7.12–7.17 (m, 1H, Ph), 7.01–7.06 (m, 2H, Ph), 7.03 (d,
overlapped, J ¼ 9.0 Hz, 2H, Ph), 6.70 (dd, J ¼ 2.7, 2.7 Hz,
1H, 7-H), 6.41 (dd, J ¼ 2.7, 2.7 Hz, 1H, 8-H), 4.14 (ddd, J ¼
8.1, 1.4, 1.4 Hz, 1H, 8ba-H), 3.44 (ddd, J ¼ 7.8, 4.9, 4.9 Hz,
1H, 3aa-H), 2.63–2.67 (m, 2H, 5a-H and 5b-H), 2.53 (dddd, J
¼ 13.4, 4.6, 4.6, 4.6 Hz, 1H, 4b-H), 2.06 (dddd, J ¼ 13.6, 8.5,
1
7.3, 5.1 Hz, 1H, 4a-H); H NMR (300 MHz, DMSO-d6) 10.60
(bs, 1H, 6-H), 7.39–7.44 (m, 2H, Ph), 7.15–7.20 (m, 1H, Ph),
7.19 (d, overlapped, J ¼ 8.7 Hz, 2H, Ph), 7.03–7.07 (m, 2H,
Ph), 7.05 (d, overlapped, J ¼ 8.7 Hz, 2H, Ph), 6.59 (dd, J ¼
2.6, 2.6 Hz, 1H, 7-H), 6.04 (dd, J ¼ 2.4, 2.4 Hz, 1H, 8-H),
4.02 (d, J ¼ 8.1 Hz, 1H, 8ba-H), 3.51 (ddd, J ¼ 8.1, 5.2, 5.2
Hz, 1H, 3aa-H), 2.58 (ddd, J ¼ 15.5, 4.7, 4.7 Hz, 1H, 5b-H),
2.43 (ddd, 15.2, 10.0, 4.9 Hz, 1H, 5a-H), 2.23 (dddd, J ¼
13.5, 4.8, 4.8, 4.8 Hz, 1H, 4b-H), 1.88 (dddd, J ¼ 13.6, 10.1,
5.2, 5.2 Hz, 1H, 4a-H); 13C NMR (75 MHz, DMSO-d6, d)
178.9, 177.8, 156.9, 156.6, 130.8, 129.1, 127.9, 127.3, 124.5,
119.7, 118.9, 117.1, 110.0, 106.8, 22.5, 21.3, 19.5, 18.2; IR
(KBr, cmꢁ1) 3387(bs), 3104(w), 2960(w), 2934(w), 2854(w),
1771(w), 1702(s), 1588(m), 1506(m), 1487(m), 1430(w),
1390(m), 1352(w), 1285(w), 1244(s), 1199(m), 1179(m),
1155(m), 1093(w), 1069(w), 876(w), 723(m); HRMS m/z (M
þ Naþ) calcd. 381.1210, found 381.1202. Anal. Calcd. for
C22H18N2O3: C, 73.73; H, 5.06; N, 7.82. Found: C, 73.95; H,
5.03; N, 7.71.
2-(4-Isopropylphenyl)-3aa,4,5,8ba-tetrahydro-2H,6H-pyrrolo
[3,4-e]indole-1,3-dione (15). Method A with vinylpyrrole 4
and maleimide 10e gave 15 (395 mg, 32%) as a light-orange
1
powder: mp 188–190ꢃC; H NMR (300 MHz, CDCl3, d) 7.93
(bs, 1H, 6-H), 7.29 (d, J ¼ 8.4 Hz, 2H, Ph), 7.16 (d, J ¼ 8.7
Hz, 2H, Ph), 6.70 (dd, J ¼ 2.6, 2.6 Hz, 1H, 7-H), 6.41 (dd, J
¼ 2.6, 2.6 Hz, 1H, 8-H), 4.13 (ddd, J ¼ 8.1, 1.4, 1.4 Hz, 1H,
8ba-H), 3.44 (ddd, J ¼ 8.1, 5.0, 5.0 Hz, 1H, 3aa-H), 2.92
(septet, J ¼ 6.9 Hz, 1H, CH(CH3)2), 2.65 (m, 2H, 5a-H and
5b-H), 2.52 (dddd, J ¼ 13.7, 4.6, 4.6, 4.6 Hz, 1H, 4b-H), 2.06
(dddd, J ¼ 13.5, 8.3, 7.4, 5.1 Hz, 1H, 4a-H), 1.24 (d, J ¼ 6.9
Hz, 6H, CH(CH3)2); 13C NMR (75 MHz, CDCl3, d) 178.6,
177.5, 149.2, 129.6, 127.2 (two peaks overlapped), 117.2,
110.2, 107.6, 40.5, 40.4, 34.0, 24.0, 22.0, 19.4; 13C NMR (75
MHz, DMSO-d6, d) 179.0, 177.8, 148.9, 130.7, 127.2 (three
peaks overlapped), 117.1, 110.0, 106.8, ꢀ40 (two peaks
2-Dimethylamino-6-methyl-3aa,4,5,8ba-tetrahydro-2H,6H-
pyrrolo[3,4-e]indole-1,3-dione (18). Method A with vinylpyr-
role 3d and maleimide 10a gave 18 (880 mg, 89%) as a dark-
obscured by DMSO), 33.7, 24.3, 22.5, 19.5; IR (KBr, cmꢁ1
)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2009 Access to Indoles via Diels-Alder Reactions of 2-Vinylpyrroles with Maleimides
1165
brown oil: 1H NMR (300 MHz, CDCl3, d) 6.54 (d, J ¼ 2.7
Hz, 1H, 7-H), 6.28 (d, J ¼ 2.7 Hz, 1H, 8-H), 3.87 (ddd, J ¼
8.1, 1.4, 1.4 Hz, 1H, 8ba-H), 3.50 (s, 3H, 6-CH3), 3.15 (ddd, J
¼ 8.1, 5.3, 5.3 Hz, 1H, 3aa-H), 2.85 (s, 6H, N(CH3)2), 2.58
(dddd, J ¼ 16.1, 5.6, 5.6, 1.2 Hz, 1H, 5b-H), 2.48 (dddd, J ¼
15.5, 9.5, 5.6, 1.2 Hz, 1H, 5a-H), 2.34 (dddd, J ¼ 13.4, 5.3,
5.3, 5.3 Hz, 1H, 4b-H), 1.99 (dddd, J ¼ 13.5, 9.1, 5.5, 5.5 Hz,
1H, 4a-H); 13C NMR (75 MHz, CDCl3, d) 177.5, 176.6,
128.1, 121.5, 110.1, 106.5, 44.0, 38.9, 38.6, 33.2, 22.1, 18.2;
36.8, 33.0, 28.8, 25.3, 22.0; IR (film, cmꢁ1) 2962(s), 1777(m),
1711(s), 1500(w), 1446(w), 1369(m), 1293(w), 1189(m),
1149(m), 1046(w); HRMS m/z (M þ Naþ) calcd. 284.1370,
found 284.1373. Anal. Calcd. for C14H19N3O2: C, 64.35; H,
7.33; N, 16.08. Found: C, 64.15; H, 7.12; N, 16.18.
5b,6-Dimethyl-2-phenyl-3aa,4,5a,8ba-tetrahydro-2H,6H-
pyrrolo[3,4-e]indole-1,3-dione (22). Method A with vinyl-
pyrrole 3e and maleimide 10c with reflux gave 22 (1.071 g,
91%) as a light-yellow cream-colored powder: mp 239–240ꢃC;
1
IR (film, cmꢁ1
) 3105(w), 3054(w), 2931(m), 2891(m),
maj/min ¼ 54:1; H NMR (300 MHz, CDCl3, d) 7.42–7.48 (m,
2H, Ph), 7.33–7.39 (m, 1H, Ph), 7.25–7.29 (m, 2H, Ph), 6.58
(d, J ¼ 3.0 Hz, 1H, 7-H), 6.32 (d, J ¼ 2.7 Hz, 1H, 8-H), 4.16
(d, J ¼ 8.7 Hz, 1H, 8ba-H), 3.55 (s, 3H, 6-CH3), 3.39 (ddd, J
¼ 8.8, 6.7, 2.2 Hz, 1H, 3aa-H), 3.08 (ddq, J ¼ 6.6, 6.6, 2.4 Hz,
1H, 5a-H), 2.62 (ddd, J ¼ 14.1, 2.1, 2.1 Hz, 1H, 4b-H), 2.16
(ddd, J ¼ 14.0, 6.3, 6.3 Hz, 1H, 4a-H), 1.19 (d, J ¼ 6.9 Hz,
3H, 5b-CH3); 13C NMR (75 MHz, CDCl3, d) 179.5, 177.3,
132.6, 132.3, 129.1, 128.4, 126.4, 122.0, 109.5, 106.5, 40.0,
38.6, 33.1, 29.0, 25.4, 22.2; IR (film, cmꢁ1) 2960(m), 2956(m),
1775(w), 1711(s), 1595(w), 1499(m), 1453(w), 1380(m),
1348(m), 1293(w), 1270(w), 1175(m), 1157(m), 1062(w),
741(w), 728(w), 717(w), 691(m); HRMS m/z (M þ Naþ) calcd.
317.1261, found 317.1253. Anal. Calcd. for C18H18N2O2: C,
73.45; H, 6.16; N, 9.52. Found: C, 73.55; H, 6.31; N, 9.51.
2-(4-Methoxyphenyl)-5b,6-dimethyl-3aa,4,5a,8ba-tetrahydro-
1777(m), 1716(s), 1497(m), 1446(m), 1364(s), 1270(w),
1248(w), 1181(m), 1145(m), 1053(w), 714(m); HRMS m/z (M
þ Naþ) calcd. 270.1214, found 270.1221. Anal. Calcd. for
C13H17N3O2: C, 63.14; H, 6.93; N, 16.99. Found: C, 62.94; H,
7.07; N, 16.76.
6-Methyl-2-phenyl-3aa,4,5,8ba-tetrahydro-2H,6H-pyrrolo
[3,4-e]indole-1,3-dione (19). Method A with vinylpyrrole 3d
and maleimide 10c gave 19 (1.054 g, 94%) as a light-brown
1
powder: mp 169–170ꢃC; H NMR (300 MHz, CDCl3, d) 7.38–
7.47 (m, 2H, Ph), 7.32–7.38 (m, 1H, Ph), 7.24–7.29 (m, 2H,
Ph), 6.57 (d, J ¼ 2.7, 2.7 Hz, 1H, 7-H), 6.33 (d, J ¼ 2.7, 2.7
Hz, 1H, 8-H), 4.13 (ddd, J ¼ 8.4, 1.4, 1.4 Hz, 1H, 8ba-H),
3.52 (s, 3H, 6-CH3), 3.43 (ddd, J ¼ 8.1, 4.5, 4.4 Hz, 1H, 3aa-
H), 2.50–2.68 (m, 3H, 4b-H, 5a-H and 5b-H), 2.05 (dddd, J ¼
15.4, 12.5, 6.2, 5.0 Hz, 1H, 4a-H); 13C NMR (75 MHz, CDCl3,
d) 178.2, 177.2, 132.2, 129.0, 128.3, 128.2, 126.4, 121.6,
2H,6H-pyrrolo[3,4-e]indole-1,3-dione (23). Method
A with
110.6, 106.5, 40.6, 40.4, 33.2, 21.7, 18.2; IR (film, cmꢁ1
)
vinylpyrrole 3e and maleimide 10f with reflux gave 23 (1.207
g, 93%) as a white powder: mp 190–191ꢃC; maj/min ¼ 37:1;
1H NMR (300 MHz, CDCl3, d) 7.18 (d, J ¼ 9.3 Hz, 2H, Ph),
6.95 (d, J ¼ 9.3 Hz, 2H, Ph), 6.57 (d, J ¼ 3.0 Hz, 1H, 7-H),
6.32 (d, J ¼ 2.7 Hz, 1H, 8-H), 4.15 (dd, J ¼ 8.7, 0.6 Hz, 1H,
8ba-H), 3.82 (s, 3H, OCH3), 3.55 (s, 3H, 6-CH3), 3.37 (ddd, J
¼ 8.9, 6.8, 2.3 Hz, 1H, 3aa-H), 3.07 (dddq, J ¼ 6.9, 5.7, 2.1,
0.6 Hz, 1H, 5a-H), 2.61 (ddd, J ¼ 14.1, 2.1, 2.1 Hz, 1H, 4b-
H), 2.15 (ddd, J ¼ 14.1, 6.9, 5.7 Hz, 1H, 4a-H), 1.17 (d, J ¼
6.9 Hz, 3H, 5b-CH3); 13C NMR (75 MHz, CDCl3, d) 179.7,
177.5, 159.4, 132.6, 127.7, 125.0, 122.0, 114.5, 109.6, 106.5,
3060(w), 2931(m), 2849(w), 1777(w), 1711(s), 1596(w),
1498(m), 1455(w), 1380(m), 1290(w), 1269(w), 1173(m),
1150(m), 718(m), 692(m); HRMS m/z (M þ Naþ) calcd.
303.1105, found 303.1109. Anal. Calcd. for C17H16N2O2: C,
72.84; H, 5.75; N, 9.99. Found: C, 72.60; H, 5.67; N, 9.81.
2-(4-Methoxyphenyl)-6-methyl-3aa,4,5,8ba-tetrahydro-2H,
6H-pyrrolo[3,4-e]indole-1,3-dione (20). Method
vinylpyrrole 3d and maleimide 10f gave 20 (1.154 g, 93%) as
A
with
1
a cream-colored powder: mp 161–162ꢃC; H NMR (300 MHz,
CDCl3, d) 7.17 (d, J ¼ 9.0 Hz, 2H, Ph), 6.94 (d, J ¼ 9.0 Hz,
2H, Ph), 6.57 (d, J ¼ 2.7 Hz, 1H, 7-H), 6.33 (d, J ¼ 2.7 Hz,
1H, 8-H), 4.11 (ddd, J ¼ 8.4, 2.0, 2.0 Hz, 1H, 8ba-H), 3.82 (s,
3H, OCH3), 3.52 (s, 3H, 6-CH3), 3.40 (ddd, J ¼ 7.8, 4.7, 4.7
Hz, 1H, 3aa-H), 2.49–2.68 (m, 3H, 4b-H, 5a-H and 5b-H),
2.05 (dddd, J ¼ 16.5, 7.6, 6.0, 4.5 Hz, 1H, 4a-H); 13C NMR
(75 MHz, CDCl3, d) 178.5, 177.5, 159.3, 128.2, 127.6, 124.9,
121.5, 114.3, 110.6, 106.5, 55.6, 40.5, 40.4, 33.2, 21.8, 18.2;
IR (film, cmꢁ1) 2934(w), 2841(w), 1776(w), 1709(s), 1609(w),
1513(s), 1442(w), 1386(m), 1300(w), 1250(m), 1171(m),
1151(w), 1030(w); HRMS m/z (M þ Naþ) calcd. 333.1210,
found 333.1222. Anal. Calcd. for C18H18N2O3: C, 69.66; H,
5.85; N, 9.03. Found: C, 69.89; H, 6.00; N, 8.90.
55.6, 39.9, 38.5, 33.1, 29.0, 25.4, 22.2; IR (film, cmꢁ1
)
2964(m), 1777(w), 1709(s), 1610(w), 1513(s), 1386(m),
1299(w), 1250(m), 1196(m), 1030(w); HRMS m/z (M þ Naþ)
calcd. 347.1367, found 347.1367. Anal. Calcd. for
C19H20N2O3: C, 70.35; H, 6.21; N, 8.64. Found: C, 70.20; H,
6.37; N, 8.44.
2-Dimethylamino-4-methyl-3aa,4,5,8ba-tetrahydro-2H,6H-
pyrrolo[3,4-e]indole-1,3-dione (24). Method A with vinylpyr-
role 3b and maleimide 10a with reflux gave 24 (564 mg, 57%)
as a brown powder: mp 117–118ꢃC; maj/min ¼ 1.4:1.0; 1H
NMR (300 MHz, CDCl3, d) 7.94 (bs, 1H, 6-H), 6.66–6.69 (m,
1H, 7-H), 6.35–6.66 (m, 1H, 8-H), 3.83–3.87 (m, 1H, 8ba-H),
3.12 (ddd, J ¼ 7.8, 4.4, 0.9 Hz, 1H, 3aamin-H), 2.83–2.88 (m,
1H, 3aamaj-H), 2.85 (s, overlapped by 3aamaj-H, 6H,
N(CH3)2maj), 2.84 (s, overlapped by 3aamaj-H, 6H,
N(CH3)2min), 2.32–2.78 (m, 3H, 4-H and 5-H ꢂ 2), 1.34 (d, J
¼ 6.9 Hz, 3H, 4bmin-CH3), 1.56 (d, J ¼ 6.9 Hz, 3H, 4amaj-
CH3); 13C NMR (75 MHz, CDCl3, d) 177.2, 176.6, 125.7,
117.2, 109.0, 107.5, 45.1, 44.0, 37.9, 28.2, 27.4, 19.5; IR
(film, cmꢁ1) 3321(bm), 2960(m), 1776(w), 1710(s), 1448(w),
1367(m), 1199(m), 1145(m), 1063(w), 719(w); HRMS m/z
(M þ Naþ) calcd. 270.1214, found 270.1217. Anal. Calcd.
for C13H17N3O2: C, 63.14; H, 6.93; N, 16.99. Found: C,
63.40; H, 7.10; N, 16.88.
2-Dimethylamino-5b,6-dimethyl-3aa,4,5a,8ba-tetrahydro-2H,
6H-pyrrolo[3,4-e]indole-1,3-dione (21). Method A with vinyl-
pyrrole 3e and maleimide 10a with reflux gave 21 (899 mg,
86%) as a light-orange powder: mp 100–101ꢃC; maj/min ¼
1
13:1; H NMR (300 MHz, CDCl3, d) 6.55 (d, J ¼ 2.7 Hz, 1H,
7-H), 6.28 (d, J ¼ 2.7 Hz, 1H, 8-H), 3.92 (dd, J ¼ 9.0, 0.6
Hz, 1H, 8ba-H), 3.53 (s, 3H, 6-CH3), 3.14 (ddd, J ¼ 8.9, 7.0,
2.3 Hz, 1H, 3aa-H), 3.02 (dddq, J ¼ 7.2, 5.7, 2.1, 0.6 Hz, 1H,
5a-H), 2.87 (s, 6H, N(CH3)2), 2.50 (ddd, J ¼ 14.1, 2.1, 2.1
Hz, 1H, 4b-H), 2.04 (ddd, J ¼ 14.1, 7.2, 5.7 Hz, 1H, 4a-H),
1.11 (d, J ¼ 7.2 Hz, 3H, 5b-CH3); 13C NMR (75 MHz,
CDCl3, d) 178.7, 176.6, 132.5, 121.9, 109.2, 106.5, 43.7, 38.3,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1166
W. E. Noland, N. P. Lanzatella, L. Venkatraman, N. F. Anderson, and G. C. Gullickson
Vol 46
NMR (300 MHz, CDCl3, d) 7.20–7.46 (m, 5H, Ph), 6.57 (d, J
¼ 2.7 Hz, 1H, 7min-H), 6.55 (d, J ¼ 2.7 Hz, 1H, 7maj-H),
6.32 (d, J ¼ 2.7 Hz, 1H, 8min-H), 6.30 (d, J ¼ 2.7 Hz, 1H,
8maj-H), 4.07–4.13 (m, 1H, 8ba-H), 3.51 (s, 3H, 6-CH3), 3.36
(ddd, J ¼ 7.4, 3.8, 1.0 Hz, 1H, 3amaj-H), 3.12 (ddd, J ¼ 8.0,
4.8, 0.9 Hz, 1H, 3amin-H), 2.32–2.83 (m, 3H, 4-H and 5-H ꢂ
2), 1.52 (d, J ¼ 6.9 Hz, 3H, 4amaj-CH3), 1.23 (d, J ¼ 6.9 Hz,
3H, 4bmin-CH3); 13C NMR (75 MHz, CDCl3, d) 177.3, 177.0,
132.1, 129.0, 128.4, 128.2, 126.4, 121.6, 110.7, 106.4, 45.5,
4-Methyl-2-phenyl-3aa,4,5,8ba-tetrahydro-2H,6H-pyrrolo
[3,4-e]indole-1,3-dione (25). Method A with vinylpyrrole 3b
and maleimide 10c with reflux gave 25 (1.043 g, 93%) as a
1
cream-colored powder: mp 208–209ꢃC; maj/min ¼ 2.0:1.0; H
NMR (300 MHz, CDCl3, d) 7.90 (bs, 1H, 6-H), 7.21–7.46 (m,
5H, Ph), 6.68–6.71 (m, 1H, 7-H), 6.39–6.41 (m, 1H, 8-H),
4.11 (d, J ¼ 7.8 Hz, 1H, 8bamin-H), 4.10 (d, overlapped by
8bamin-H, J ¼ 7.5 Hz, 1H, 8bamaj-H), 3.38 (dd, J ¼ 7.7, 4.1
Hz, 1H, 3aamin-H), 3.14 (ddd, J ¼ 8.0, 5.0, 0.9 Hz, 1H,
3aamaj-H), 2.39–2.86 (m, 3H, 4-H and 5-H ꢂ 2), 1.47 (d, J ¼
6.9 Hz, 3H, 4bmin-CH3), 1.21 (d, J ¼ 6.9 Hz, 3H, 4amaj-
CH3); 13C NMR (75 MHz, DMSO-d6, d) 178.3, 177.5, 133.0,
129.4, 128.6, 127.4, 125.8, 117.2, 109.0, 106.8, 46.7, 41.3,
28.6, 27.5, 19.9; IR (film, cmꢁ1) 3367(bs), 3050(m), 2990(m),
2900(m), 1776(w), 1693(s), 1591(w), 1495(w), 1453(w),
1386(m), 1177(m), 1164(m), 1065(w), 786(w), 769(w),
741(w); HRMS m/z (M þ Naþ) calcd. 303.1105, found
303.1103. Anal. Calcd. for C17H16N2O2: C, 72.84; H, 5.75; N,
9.99. Found: C, 72.61; H, 5.59; N, 9.96.
42.0, 33.2, 30.0, 26.4, 18.7; IR (film, cmꢁ1
) 3060(m),
3030(m), 2929(m), 1775(w), 1710(s), 1597(w), 1498(m),
1453(w), 1377(m), 1174(m), 1142(m), 691(w); HRMS m/z (M
þ Naþ) calcd. 317.1261, found 317.1268. Anal. Calcd. for
C18H18N2O2: C, 73.45; H, 6.16; N, 9.52. Found: C, 73.51; H,
5.98; N, 9.54.
2-(4-Methoxyphenyl)-4,6-dimethyl-3aa,4,5,8ba-tetrahydro-
2H,6H-pyrrolo[3,4-e]indole-1,3-dione (29). Method A with
vinylpyrrole 3f and maleimide 10f with reflux gave 29 (1.090
g, 84%) as a light-brown powder: mp 126–127ꢃC; maj/min ¼
2.4:1.0; 1H NMR (300 MHz, CDCl3, d) 7.10–7.19 (m, 2H,
Ph), 6.90–7.00 (m, 2H, Ph), 6.57 (d, J ¼ 2.7 Hz, 1H, 7min-H),
6.55 (d, J ¼ 3.0, 1H, 7maj-H), 6.32 (d, J ¼ 3.0 Hz, 1H, 8min-
H), 6.30 (d, J ¼ 3.0 Hz, 1H, 8maj-H), 4.05–4.10 (m, 1H, 8ba-
H), 3.82 (s, 3H, OCH3), 3.51 (s, 3H 6-CH3), 3.33 (ddd, J ¼
7.6, 3.8, 1.1 Hz, 1H, 3amaj-H), 3.09 (ddd, J ¼ 7.9, 4.6, 0.8,
1H, 3aamin-H), 2.32–2.81 (m, 3H, 4-H and 5-H ꢂ 2), 1.51 (d,
J ¼ 6.9 Hz, 3H, 4amaj-CH3), 1.22 (d, J ¼ 7.2 Hz, 1H,
4bmin-CH3); 13C NMR (75 MHz, CDCl3, d) 177.6, 177.3,
159.2, 128.4, 127.7, 124.8, 121.5, 114.3, 110.8, 106.4, 55.6,
45.4, 41.8, 33.2, 30.0, 26.5, 18.6; IR (film, cmꢁ1) 2950(m),
2931(m), 2839(m), 1770(w), 1708(s), 1610(w), 1513(s),
1442(w), 1384(m), 1300(w), 1250(m), 1168(m), 1143(w),
1031(w), 704(w); HRMS m/z (M þ Naþ) calcd. 347.1367,
found 347.1362. Anal. Calcd. for C19H20N2O3: C, 70.35; H,
6.21; N, 8.64. Found: C, 70.51; H, 6.40; N, 8.79.
2-(4-Methoxyphenyl)-4-methyl-3aa,4,5,8ba-tetrahydro-2H,
6H-pyrrolo[3,4-e]indole-1,3-dione (26). Method
vinylpyrrole 3b and maleimide 10f with reflux gave 26 (1.117
A
with
g, 90%) as a cream-colored powder: mp 163–164ꢃC; maj/min
1
¼ 1.3:1.0; H NMR (300 MHz, CDCl3, d) 7.91 (bs, 1H, 6-H),
7.10–7.19 (m, 4H, Ph), 6.68–6.71 (m, 1H, 7-H), 6.38–6.41 (m,
1H, 8-H), 4.05–4.11 (m, 1H, 8ba-H), 3.82 (s, 3H, OCH3), 3.36
(ddd, J ¼ 7.5, 4.2, 0.6 Hz, 1H, 3aamin-H), 3.11 (ddd, J ¼ 8.0,
4.5, 0.9 Hz, 1H, 3aamaj-H), 2.37–2.86 (m, 3H, 4-H and 5-H
ꢂ 2), 1.45 (d, J ¼ 6.9 Hz, 1H, 4bmin-CH3), 1.21 (d, J ¼ 7.2
Hz, 1H, 4amaj-CH3); 13C NMR (75 MHz, CDCl3, d) 178.1,
177.5, 159.3, 127.7, 125.7, 124.7, 117.3, 114.4, 109.3, 107.5,
55.6, 46.8, 39.4, 28.0, 27.2, 19.6; IR (film, cmꢁ1) 3370(bs),
2930(m), 2870(m), 1767(w), 1703(s), 1609(w), 1513(s),
1442(w), 1389(m), 1300(w), 1251(m), 1192(m), 1166(m),
1028(w), 721(w); HRMS m/z (M þ Naþ) calcd. 333.1210,
found 333.1216. Anal. Calcd. for C18H18N2O3: C, 69.66; H,
5.85; N, 9.03. Found: C, 69.45; H, 6.00; N, 8.83.
4a-Ethyl-2-phenyl-3aa,4b,5,8ba-tetrahydro-2H,6H-pyrrolo
[3,4-e]indole-1,3-dione (30). Method B with vinylpyrrole 5a
and maleimide 10c gave 30 (424 mg, 36%) as a white powder:
2-Dimethylamino-4,6-dimethyl-3aa,4,5,8ba-tetrahydro-2H,
1
mp 203–204ꢃC; H NMR (500 MHz, CDCl3, d) 7.93 (bs, 1H,
6H-pyrrolo[3,4-e]indole-1,3-dione (27). Method
vinylpyrrole 3f and maleimide 10a with reflux gave 27 (700
A
with
6-H), 7.40–7.44 (m, 2H, Ph), 7.32–7.36 (m, 1H, Ph), 7.22–
7.27 (m, 2H, Ph), 6.66 (dd, J ¼ 2.8, 2.8 Hz, 1H, 7-H), 6.35
(dd, J ¼ 2.5, 2.5 Hz, 1H, 8-H), 4.05 (ddd, J ¼ 7.5, 1.4, 1.4
Hz, 1H, 8ba-H), 3.28 (ddd, J ¼ 7.5, 4.0, 0.9 Hz, 1H, 3aa-H),
2.77 (ddd, J ¼ 15.8, 5.3, 1.7 Hz, 1H, 5b-H), 2.61 (m, 1H, 4b-
H), 2.51 (dd, J ¼ 15.8, 2.5 Hz, 1H, 5a-H, see 3aa-H and 8ba-
H), 1.56 (ddq, J ¼ 14.1, 8.0, 7.3 Hz, 1H, 4a-CH2CH3), 1.44
(ddq, J ¼ 14.4, 7.5, 7.3 Hz, 1H, 4a-CH2CH3), 1.00 (dd, J ¼
mg, 67%) as a cream-colored powder: mp 85–86ꢃC; maj/min
1
¼ 1.2:1.0; H NMR (300 MHz, CDCl3, d) 6.55 (d, J ¼ 2.7 Hz,
1H, 7min-H), 6.52 (d, J ¼ 2.7 Hz, 1H, 7maj-H), 6.28 (d, J ¼
2.7 Hz, 1H, 8min-H), 6.26 (d, J ¼ 2.7 Hz, 1H, 8maj-H), 3.85
(ddd, J ¼ 7.5, 1.4, 1.4 Hz, 1H, 8bamaj-H), 3.80–3.84 (m, over-
lapped by 8bamaj-H, 1H, 8bamin-H), 3.09 (ddd, J ¼ 7.6, 4.1,
0.6 Hz, 1H, 3aamaj-H), 2.81–2.86 (m, 1H, 3aamin-H), 2.85 (s,
overlapped by 3aamin-H, 6H, N(CH3)2min), 2.83 (s, over-
lapped by 3aamin-H, 6H, N(CH3)2maj), 2.27–2.70 (m, 3H, 4-H
and 5-H ꢂ 2), 1.40 (d, J ¼ 6.6 Hz, 3H, 4bmaj-CH3), 1.18 (d, J
¼ 6.6 Hz, 4amaj-CH3); 13C NMR (75 MHz, CDCl3, d) 176.8,
176.5, 128.0, 121.4, 110.2, 106.3, 44.0, 43.5, 39.9, 33.1, 29.9,
26.5, 18.2; IR (film, cmꢁ1) 2956(m), 2893(m), 1776(m),
1713(s), 1500(w), 1448(m), 1365(m), 1196(m), 1181(m),
1144(m), 706(w), 662(w); HRMS m/z (M þ Naþ) calcd.
284.1370, found 284.1370. Anal. Calcd. for C14H19N3O2: C,
64.35; H, 7.33; N, 16.08. Found: C, 64.30; H, 7.51; N, 16.11.
4,6-Dimethyl-2-phenyl-3aa,4,5,8ba-tetrahydro-2H,6H-pyr-
rolo[3,4-e]indole-1,3-dione (28). Method A with vinylpyrrole
3f and maleimide 10c with reflux gave 28 (1.048 g, 89%) as a
light-brown powder: mp 178–179ꢃC; maj/min ¼ 2.4:1.0; 1H
1
7.3, 7.3 Hz, 3H, 4a-CH2CH3); H NMR (300 MHz, DMSO-d6,
d) 10.57 (bs, 1H, 6-H), 7.35–7.48 (m, 3H, Ph), 7.17–7.18 (m,
2H, Ph), 6.59 (dd, J ¼ 2.6, 2.6 Hz, 1H, 7-H), 6.02 (dd, J ¼
2.6, 2.6 Hz, 1H, 8-H), 3.98 (d, J ¼ 7.8 Hz, 1H, 8ba-H), 3.41
(ddd, J ¼ 8.1, 4.2, 0.9 Hz, 1H, 3aa-H), 2.60 (dd, J ¼ 15.9, 5.1
Hz, 1H, 5b-H), 2.45 (dd, J ¼ 15.6, 3.6 Hz, 1H, 5a-H), 2.32–
2.40 (m, 1H, 4b-H), 1.47 (ddq, J ¼ 14.2, 7.5, 6.8 Hz, 1H, 4a-
CH2CH3), 1.32 (ddq, J ¼ 14.3, 7.7, 7.5 Hz, 1H, 4a-CH2CH3),
0.93 (dd, J ¼ 7.5, 7.5 Hz, 3H, 4a-CH2CH3); 13C NMR (75
MHz, CDCl3, d) 178.1, 177.3, 132.1, 129.0, 128.3, 126.4,
125.6, 117.2, 109.6, 107.6, 45.2, 39.3, 33.9, 25.6, 23.8, 12.1;
13C NMR (75 MHz, DMSO-d6, d) 178.6, 177.7, 132.9, 129.4,
128.6, 127.3, 125.5, 117.2, 109.2, 106.7, 44.8, ꢀ40 (obscured
by DMSO), 34.4, 25.6, 24.1, 12.3; IR (KBr, cmꢁ1) 3346(bs),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2009 Access to Indoles via Diels-Alder Reactions of 2-Vinylpyrroles with Maleimides
1167
3064(w), 2962(m), 2962(m), 2925(m), 2875(m), 2859(m),
1771(m), 1699(s), 1599(w), 1499(m), 1459(w), 1390(m),
1308(w), 1287(w), 1187(s), 1150(m), 1083(w), 1065(w),
743(m), 731(m), 689(m); HRMS m/z (M þ Naþ) calcd.
317.1261, found 317.1263. Anal. Calcd. for C18H18N2O2: C,
73.45; H, 6.16; N, 9.52. Found: C, 73.60; H, 6.08; N, 9.71.
4a-Ethyl-2-(4-ethylphenyl)-3aa,4b,5,8ba-tetrahydro-2H,6H-
pyrrolo[3,4-e]indole-1,3-dione (31). Method A with vinylpyr-
role 5a and maleimide 10d gave 31 (903 mg, 70%), method B
with vinylpyrrole 5a and maleimide 10d gave 31 (529 mg,
41%), as a light-orange powder: mp 247–248ꢃC; 1H NMR
(300 MHz, CDCl3, d) 7.93 (bs, 1H, 6-H), 7.25 (d, J ¼ 8.1 Hz,
2H, Ph), 7.14 (d, J ¼ 8.4 Hz, 2H, Ph), 6.67 (dd, J ¼ 2.6, 2.6
Hz, 1H, 7-H), 6.36 (dd, J ¼ 2.7, 2.7, 1H, 8-H), 4.05 (ddd, J ¼
7.8, 1.2, 1.2 Hz, 1H, 8ba-H), 3.28 (ddd, J ¼ 7.8, 3.9, 0.9 Hz,
1H, 3aa-H), 2.78 (ddd, J ¼ 15.3, 5.4, 0.9 Hz, 1H, 5b-H), 2.66
(q, J ¼ 7.6 Hz, 2H, PhCH2CH3), 2.58–2.64 (m, overlapped by
PhCH2CH3, 1H, 4b-H), 2.52 (dd, J ¼ 15.6, 3.0 Hz, 1H, 5a-H,
see 3aa-H and 8ba-H), 1.56 (ddq, J ¼ 13.8, 7.5, 6.9 Hz, 1H,
4a-CH2CH3), 1.44 (ddq, J ¼ 14.3, 7.4, 7.2 Hz, 1H, 4a-
CH2CH3), 1.23 (t, J ¼ 7.7 Hz, 3H, PhCH2CH3), 1.00 (dd, J ¼
7.7 Hz, 3H, 4a-CH2CH3); 13C NMR (75 MHz, CDCl3, d)
178.3, 177.5, 144.6, 129.6, 128.5, 126.3, 125.6, 117.1, 109.7,
107.6, 45.2, 39.3, 34.0, 28.6, 25.6, 23.8, 15.5, 12.1; IR (KBr,
H2O, J ¼ 4.2, 7.8 Hz, 1H, 3aa-H), 2.57 (dd, J ¼ 16.2, 4.8 Hz,
1H, 5b-H), 2.44 (dd, J ¼ 15.6, 3.3 Hz, 1H, 5a-H), 2.33–2.39
(m, 1H, 4b-H), 1.45 (ddq, J ¼ 13.8, 7.5, 7.2 Hz, 1H, 4a-
CH2CH3), 1.27 (ddq, J ¼ 14.1, 7.7, 7.5 Hz, 1H, 4a-CH2CH3),
0.91 (dd, J ¼ 7.5, 7.5 Hz, 3H, 4a-CH2CH3); 13C NMR (75
MHz, DMSO-d6, d) 178.9, 178.0, 157.6, 128.6, 125.5, 124.0,
117.1, 115.8, 109.4, 106.7, 44.6, ꢀ40 (obscured by DMSO),
34.4, 25.6, 24.1, 12.3; IR (KBr, cmꢁ1) 3467(m), 3374(bm),
2965(w), 2927(w), 2877(w), 1767(w), 1696(s), 1601(w),
1518(m), 1447(w), 1398(m), 1274(w), 1198(m), 1165(m),
1105(w), 1065(w), 1021(w), 837(w), 776(w), 725(m), 708(m);
HRMS m/z (M þ Naþ) calcd. 333.1210, found 333.1205.
Anal. Calcd. for C18H18N2O3: C, 69.66; H, 5.85; N, 9.03.
Found: C, 69.49; H, 6.05; N, 9.20.
2-(4-Chlorophenyl)-4a-ethyl-3aa,4b,5,8ba-tetrahydro-2H,
6H-pyrrolo[3,4-e]indole-1,3-dione (34). Method
vinylpyrrole 5a and maleimide 10j gave 34 (421 mg, 32%) as
B
with
1
a white powder: mp 197–198ꢃC; H NMR (300 MHz, CDCl3,
d) 7.88 (bs, 1H, 6-H), 7.40 (d, J ¼ 9.0 Hz, 2H, Ph), 7.22 (d, J
¼ 9.0 Hz, 2H, Ph), 6.69 (dd, J ¼ 2.9, 2.9 Hz, 1H, 7-H), 6.36
(d, J ¼ 2.7, 2.7 Hz, 1H, 8-H), 4.06 (ddd, J ¼ 8.1, 1.4, 1.4 Hz,
1H, 8ba-H), 3.29 (ddd, J ¼ 7.8, 3.6, 1.0 Hz, 1H, 3aa-H), 2.78
(ddd, J ¼ 15.3, 5.4, 1.5 Hz, 1H, 5b-H), 2.58–2.65 (m, 1H, 4b-
H), 2.53 (dd, J ¼ 16.0, 2.6 Hz, 1H, 5a-H, see 3aa-H and 8ba-
H), 1.54 (ddq, overlapped by H2O, J ¼ 14.5, 1.2, 7.2 Hz, 1H,
4a-CH2CH3), 1.44 (ddq, J ¼ 14.5, 7.2, 7.2 Hz, 1H, 4a-
CH2CH3), 1.28 (dd, J ¼ 7.2, 7.2 Hz, 3H, 4a-CH2CH3); 13C
NMR (75 MHz, CDCl3, d) 177.8, 177.0, 134.0, 130.6, 129.2,
127.6, 125.6, 117.3, 109.4, 107.6, 45.1, 39.3, 33.9, 25.6, 23.8,
12.1; IR (KBr, cmꢁ1) 3370(s), 3342(s), 3095(w), 2969(m),
2925(m), 2877(m), 2856(m), 1769(m), 1698(s), 1600(w),
1495(m), 1463(w), 1445(w), 1390(m), 1358(m), 1308(w),
1274(w), 1183(s), 1149(m), 1090(m), 1066(w), 1017(w),
768(m), 715(m); HRMS m/z (M þ Naþ) calcd. 351.0872,
found 351.0871. Anal. Calcd. for C18H17ClN2O2: C, 65.75; H,
5.21; N, 8.52. Found: C, 65.58; H, 5.09; N, 8.69.
cmꢁ1
)
3342(bs), 2960(m), 2929(w), 2872(w), 1768(m),
1697(s), 1514(m), 1461(w), 1444(w), 1392(m), 1306(w),
1289(w), 1190(s), 1151(m), 834(w), 772(m), 723(m), 702(m);
HRMS m/z (M þ Naþ) calcd. 345.1574, found 345.1575.
Anal. Calcd. for C20H22N2O2: C, 74.51; H, 6.88; N, 8.69.
Found: C, 74.48; H, 6.96; N, 8.68.
4-(4a-Ethyl-1,3-dioxo-3aa,4b,5,8ba-tetrahydro-2H,6H-pyr-
rolo[3,4-e]indol-2-yl)phenyl acetate (32). Method B with
vinylpyrrole 5a and maleimide 10g gave 32 (437 mg, 31%) as
1
a cream-colored powder: mp 218–219ꢃC; H NMR (300 MHz,
CDCl3, d) 7.93 (bs, 1H, 6-H), 7.29 (d, J ¼ 9.3 Hz, 2H, Ph),
7.16 (d, J ¼ 9.0 Hz, 2H, Ph), 6.67 (dd, J ¼ 2.7, 2.7 Hz, 1H,
7-H), 6.35 (dd, J ¼ 2.7, 2.7 Hz, 1H, 8-H), 4.06 (ddd, J ¼ 7.8,
1.4, 1.4 Hz, 1H, 8ba-H), 3.29 (ddd, J ¼ 7.7, 3.9, 0.9 Hz, 1H,
3aa-H), 2.78 (ddd, J ¼ 14.4, 5.4, 1.2 Hz, 1H, 5b-H), 2.58–
2.65 (m, 1H, 4b-H), 2.52 (dd, J ¼ 15.8, 3.2 Hz, 1H, 5a-H, see
3aa-H and 8ba-H), 2.29 (s, 3H, Ac), 1.56 (ddq, J ¼ 14.4, 7.5,
7.4 Hz, 1H, 4a-CH2CH3), 1.47 (ddq, J ¼ 14.7, 7.4, 7.2 Hz,
1H, 4a-CH2CH3), 1.01 (dd, J ¼ 7.4, 7.4 Hz, 3H, 4a-CH2CH3);
13C NMR (75 MHz, CDCl3, d) 177.9, 177.1, 169.2, 150.1,
129.5, 127.4, 125.6, 122.2, 117.2, 109.5, 107.5, 45.1, 39.3,
2-(4-Bromophenyl)-4a-ethyl-3aa,4b,5,8ba-tetrahydro-2H,
6H-pyrrolo[3,4-e]indole-1,3-dione (35). Method
vinylpyrrole 5a and maleimide 10k gave 35 (523 mg, 35%) as
B
with
1
a cream-colored powder: mp 193–194ꢃC; H NMR (300 MHz,
CDCl3, d) 7.88 (bs, 1H, 6-H), 7.55 (d, J ¼ 8.7 Hz, 2H, Ph),
7.16 (d, J ¼ 8.7 Hz, 2H, Ph), 6.69 (dd, J ¼ 2.6, 2.6 Hz, 1H,
7-H), 6.35 (dd, J ¼ 2.7, 2.7 Hz, 1H, 8-H), 4.06 (ddd, J ¼ 7.5,
1.2, 1.2 Hz, 1H, 8ba-H), 3.29 (ddd, J ¼ 7.8, 3.6, 0.9 Hz, 1H,
3aa-H), 2.78 (ddd, J ¼ 15.6, 5.4, 1.8 Hz, 1H, 5b-H), 2.59–
2.65 (m, 1H, 4b-H), 2.53 (dd, J ¼ 16.5, 2.1 Hz, 1H, 5a-H, see
3aa-H and 8ba-H), 1.53 (ddq, overlapped by H2O, J ¼ 14.0,
7.5, 7.5 Hz, 1H, 4a-CH2CH3), 1.44 (ddq, J ¼ 14.0, 7.5, 7.5
Hz, 1H, 4a-CH2CH3), 1.01 (dd, J ¼ 7.4, 7.4 Hz, 3H, 4a-
CH2CH3); 13C NMR (75 MHz, CDCl3, d) 177.8, 176.9, 132.2,
131.1, 127.9, 125.6, 122.0, 117.3, 109.4, 107.6, 45.2, 39.3,
33.9, 25.6, 23.8, 12.1; IR (KBr, cmꢁ1) 3364(s), 3341(s),
3092(w), 2963(m), 2924(m), 2875(m), 2860(m), 1771(w),
1699(s), 1599(w), 1492(m), 1463(w), 1444(w), 1389(m),
1358(w), 1307(w), 1274(w), 1184(s), 1148(m), 1069(m),
1015(m), 935(w), 829(w), 783(w), 767(m), 714(m); HRMS m/
z (M þ Naþ) calcd. 395.0366, found 395.0363. Anal. Calcd.
for C18H17BrN2O2: C, 57.92; H, 4.59; N, 7.51. Found: C,
57.71; H, 4.54; N, 7.59.
33.9, 25.6, 23.8, 21.2, 12.1; IR (KBr, cmꢁ1
) 3359(bs),
3114(w), 3081(w), 2964(m), 2926(m), 2876(m), 2855(w),
1767(m), 1699(s), 1601(w), 1510(m), 1464(w), 1441(w),
1392(s), 1372(m), 1199(s), 1150(m), 1105(w), 1084(w),
1016(w), 938(w), 911(w), 849(w), 773(m), 719(m), 706(m);
HRMS m/z (M þ Naþ) calcd. 375.1316, found 375.1317.
Anal. Calcd. for C20H20N2O4: C, 68.17; H, 5.72; N, 7.95.
Found: C, 67.89; H, 5.53; N, 7.90.
4a-Ethyl-2-(4-hydroxyphenyl)-3aa,4b,5,8ba-tetrahydro-2H,
6H-pyrrolo[3,4-e]indole-1,3-dione (33). Method
B
with
vinylpyrrole 5a and maleimide 10i gave 33 (670 mg, 54%) as
1
a cream-colored powder: mp 238–239ꢃC; H NMR (300 MHz,
DMSO-d6, d) 10.54 (bs, 1H, 6-H), 9.70 (s, 1H, OH), 6.92 (d, J
¼ 9.0 Hz, 2H, Ph), 6.78 (d, J ¼ 8.7 Hz, 2H, Ph), 6.57 (dd, J
¼ 2.6, 2.6 Hz, 1H, 7-H), 6.01 (dd, J ¼ 2.4, 2.4 Hz, 1H, 8-H),
3.93 (d, J ¼ 7.8 Hz, 1H, 8ba-H), 3.35 (dd, overlapped by
4a-Ethyl-2-(4-nitrophenyl)-3aa,4b,5,8ba-tetrahydro-2H,6H-
pyrrolo[3,4-e]indole-1,3-dione (36). Method B with vinylpyrrole
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1168
W. E. Noland, N. P. Lanzatella, L. Venkatraman, N. F. Anderson, and G. C. Gullickson
Vol 46
5a and maleimide 10l gave 36 (611 mg, 45%) as a cream-col-
1
2-Benzyl-5b-(1-benzyl-2,5-dioxopyrrolidin-3-yl)-3aa,4,5a,8ba-
tetrahydro-2H,6H-pyrrolo[3,4-e]indole-1,3-dione (52). Method
A with vinylpyrrole 4 and maleimide 10b gave 52 (421 mg,
ored powder: mp 145–146ꢃC; H NMR (300 MHz, CDCl3, d)
8.29 (d, J ¼ 9.0 Hz, 2H, Ph), 7.92 (bs, 1H, 6-H), 7.57 (d, J ¼
9.3 Hz, 2H, Ph), 6.71 (dd, J ¼ 2.9, 2.9 Hz, 1H, 7-H), 6.35
(dd, J ¼ 2.7, 2.7 Hz, 1H, 8-H), 4.11 (ddd, J ¼ 7.9, 1.4, 1.4
Hz, 1H, 8ba-H), 3.34 (ddd, J ¼ 7.7, 3.8, 0.9 Hz, 1H, 3aa-H),
2.80 (ddd, J ¼ 15.6, 5.3, 1.7 Hz, 1H, 5b-H), 2.61–2.70 (m,
1H, 4b-H), 2.56 (dd, J ¼ 15.8, 2.9 Hz, 1H, 5a-H, see 3aa-H
and 8ba-H), 1.39–1.63 (m, 2H, 4-CH2CH3), 1.02 (dd, J ¼ 7.2,
7.2 Hz, 3H, 4-CH2CH3); 13C NMR (75 MHz, CDCl3, d)
177.3, 176.4, 146.7, 137.8, 126.7, 125.6, 124.3, 117.5, 109.1,
1
45%) as a light-brown powder: mp 212–213ꢃC; H NMR (300
MHz, CDCl3, d) 10.58 (bs, 1H, 6-H), 7.32–7.42 (m, 5H, Ph),
7.18–7.26 (m, 5H, Ph), 6.76 (dd, J ¼ 2.6, 2.6 Hz, 1H, 7-H),
6.34 (dd, J ¼ 2.7, 2.7 Hz, 1H, 8-H), 4.74 (AA0 d, J ¼ 14.1
Hz, 1H, Bn), 4.69 (AA0 d, J ¼ 13.8 Hz, 1H, Bn), 4.59 (AA0 d,
J ¼ 14.4 Hz, 1H, Bn), 4.52 (AA0 d, J ¼ 14.4 Hz, 1H, Bn),
4.02 (dd, J ¼ 7.8, 1.2 Hz, 1H, 8ba-H), 3.32 (ddd, J ¼ 7.9,
4.7, 3.5 Hz, 1H, 3aa-H), 3.01 (ddd, J ¼ 9.4, 9.4, 6.1 Hz, 1H,
10-H), 2.93 (dd, overlapped by 10-H, J ¼ 17.3, 9.6 Hz, 1H, 20-
H), 2.83–2.95 (m, overlapped by 20-H, 1H, 5a-H), 2.77 (dd,
overlapped by 5a-H, J ¼ 17.0, 5.6 Hz, 1H, 20-H), 2.54 (ddd, J
¼ 13.3, 3.8, 3.8 Hz, 1H, 4b-H), 1.58 (ddd, J ¼ 13.3, 11.5, 4.9
Hz, 1H, 4a-H); 13C NMR (75 MHz, CDCl3, d) 180.0, 178.2,
177.7, 174.7, 135.8, 135.3, 129.0, 128.9, 128.7, 128.4, 128.3,
127.9, 127.3, 118.3, 111.8, 107.2, 44.6, 42.9, 42.3, 40.1, 40.0,
33.0, 31.5, 26.6; IR (KBr, cmꢁ1) 3446(w), 3329(bs), 3062(w),
3033(w), 2924(m), 2854(w), 1772(m), 1702(s), 1586(w),
1495(w), 1453(w), 1433(m), 1398(s), 1341(m), 1314(m),
1292(w), 1167(s), 1119(w), 1083(w), 714(m), 696(m); HRMS
m/z (M þ Naþ) calcd. 490.1738, found 490.1745. Anal. Calcd.
for C28H25N3O4: C, 71.93; H, 5.39; N, 8.99. Found: C, 71.97;
H, 5.44; N, 8.70.
107.5, 45.2, 39.3, 33.8, 25.5, 23.8, 12.1; IR (KBr, cmꢁ1
)
3375(bm), 3115(w), 2960(m), 2929(w), 2873(w), 1771(w),
1704(s), 1611(w), 1598(w), 1519(m), 1499(m), 1460(w),
1384(m), 1348(m), 1297(w), 1193(m), 1170(m), 1147(m),
1105(w), 1067(w), 1019(w), 851(w), 782(w), 743(m), 717(m);
HRMS m/z (M þ Naþ) calcd. for C18H17N3O4: 362.1112,
found 362.1114.
4a-n-Pentyl-2-phenyl-3aa,4b,5,8ba-tetrahydro-2H,6H-pyr-
rolo[3,4-e]indole-1,3-dione (37). Method B with vinylpyrrole
5b and maleimide 10c gave 37 (404 mg, 30%) as a light-brown
1
powder: mp 208–209ꢃC; H NMR (300 MHz, CDCl3, d) 7.90
(bs, 1H, 6-H), 7.40–7.46 (m, 2H, Ph), 7.32–7.37 (m, 1H, Ph),
7.22–7.27 (m, 2H, Ph), 6.68 (dd, J ¼ 2.7, 2.7 Hz, 1H, 7-H), 6.37
(dd, J ¼ 2.7, 2.7 Hz, 1H, 8-H), 4.07 (d, J ¼ 7.8 Hz, 1H, 8ba-H),
3.28 (ddd, J ¼ 8.0, 3.0, 0.9 Hz, 1H, 3aa-H), 2.79 (ddd, J ¼ 15.5,
5.2, 1.1 Hz, 1H, 5b-H), 2.67–2.75 (m, 1H, 4b-H), 2.50 (dd, J ¼
15.3, 2.0 Hz, 1H, 5a-H, see 3aa-H), 1.25–1.52 (m, 8H, 4a-
(CH2)4CH3), 0.90 (t, J ¼ 6.9 Hz, 3H, 4a-(CH2)4CH3); 13C NMR
(75 MHz, CDCl3, d) 178.0, 177.3, 132.1, 129.0, 128.3, 126.4,
125.6, 117.2, 109.6, 107.6, 45.4, 39.3, 32.7, 32.2, 31.8, 27.3,
24.3, 22.7, 14.1; IR (KBr, cmꢁ1) 3361(bs), 3066(w), 2953(m),
2926(s), 2855(m), 1766(w), 1708(s), 1598(w), 1497(m),
1457(w), 1380(s), 1291(w), 1187(m), 1150(w), 1090(w),
1072(w), 742(w); HRMS m/z (M þ Naþ) calcd. 359.1731,
found 359.1734. Anal. Calcd. for C21H24N2O2: C, 74.97; H,
7.19; N, 8.33. Found: C, 74.72; H, 6.93; N, 8.22.
2-(4-Ethylphenyl)-5b-(1-(4-ethylphenyl)-2,5-dioxopyrrolidin-
3-yl)-3aa,4,5a,8ba-tetrahydro-2H,6H-pyrrolo[3,4-e]indole-1,3-
dione (53). Method A with vinylpyrrole 4 and maleimide 10d
gave 53 (228 mg, 23%) as a light-brown powder: mp 173–
174ꢃC; 1H NMR (300 MHz, CDCl3, d) 10.52 (bs, 1H, 6-H),
7.35 (d, J ¼ 8.4 Hz, 2H, Ph), 7.25 (d, J ¼ 8.4 Hz, 2H, Ph),
7.20 (d, J ¼ 8.4 Hz, 2H, Ph), 7.12 (d, J ¼ 8.4 Hz, 2H, Ph),
6.75 (dd, J ¼ 2.9, 2.9 Hz, 1H, 7-H), 6.39 (dd, J ¼ 2.7, 2.7 Hz,
1H, 8-H), 4.19 (dd, J ¼ 8.1, 1.2 Hz, 1H, 8ba-H), 3.57 (ddd, J
¼ 8.0, 4.7, 3.4 Hz, 1H, 3aa-H), 3.24 (ddd, J ¼ 9.1, 9.1, 6.2
Hz, 1H, 10-H), 3.13–3.23 (m, overlapped by 10-H, 1H, 5a-H),
3.11 (dd, overlapped by 5a-H, J ¼ 17.7, 8.7 Hz, 1H, 20-H),
2.98 (dd, J ¼ 17.7, 6.6 Hz, 1H, 20-H), 2.73 (ddd, J ¼ 12.9,
3.6, 3.6 Hz, 1H, 4b-H), 2.72 (q, overlapped by 4b-H, J ¼7.6
Hz, 2H, CH2CH3), 2.66 (q, overlapped by CH2CH3, J ¼ 7.7
Hz, 2H, CH2CH3), 1.75 (ddd, J ¼ 13.2, 10.8, 4.8 Hz, 1H, 4a-
H), 1.28 (t, J ¼ 7.1 Hz, 3H, CH2CH3), 1.23 (t, J ¼ 7.2 Hz,
3H, CH2CH3); 13C NMR (75 MHz, CDCl3, d) 179.7, 177.7,
177.1, 174.2, 145.6, 144.8, 129.4, 129.0, 128.9, 128.6, 127.3,
126.4, 126.2, 118.4, 111.8, 107.3, 44.8, 40.4, 40.2, 33.2, 31.6,
4b-Ethyl-2-phenyl-3aa,4a,5,8ba-tetrahydro-2H,6H-pyrrolo
[3,4-e]indole-1,3-dione (38). Method B with vinylpyrrole 6
and maleimide 10c gave 38 (483 mg, 41%) as a cream-colored
powder: mp 182–183ꢃC; maj/min ¼ 12:1; 1H NMR (300
MHz, CDCl3, d) 7.89 (bs, 1H, 6-H), 7.41 (dd, J ¼ 7.8, 7.8 Hz,
2H, Ph), 7.32–7.38 (m, 1H, Ph), 7.20 (d, J ¼ 7.5 Hz, 2H, Ph),
6.67 (dd, J ¼ 2.5, 2.5 Hz, 1H, 7-H), 6.36 (dd, J ¼ 2.8, 2.8 Hz,
1H, 8-H), 4.11 (ddd, J ¼ 7.5, 1.3, 1.3 Hz, 1H, 8ba-H), 3.46
(ddd, J ¼ 7.3, 3.8, 0.9 Hz, 1H, 3aa-H), 2.74 (dd, J ¼ 15.8, 4.3
Hz, 1H, 5a-H, see 3aa-H and 8ba-H), 2.51 (ddd, J ¼ 15.0,
11.0, 1.5 Hz, 1H, 5b-H), 2.08–2.15 (m, 1H, 4a-H), 2.05 (ddq,
overlapped by 4a-H, J ¼ 13.1, 7.5, 7.5 Hz, 1H, 4b-CH2CH3),
1.95 (ddq, J ¼ 13.1, 7.5, 7.5 Hz, 1H, 4b-CH2CH3), 1.07 (dd, J
¼ 7.5, 7.5 Hz, 3H, 4b-CH2CH3); 13C NMR (75 MHz, CDCl3,
d) 177.25, 177.20, 132.0, 129.0, 128.3, 127.5, 126.5, 117.4,
111.0, 107.4, 44.1, 42.0, 37.3, 25.5, 25.2, 12.6; IR (KBr,
28.7, 28.6, 26.6, 15.5, 15.4; IR (KBr, cmꢁ1
) 3353(bs),
3122(w), 3103(w), 3038(w), 2964(m), 2930(m), 2872(w),
1777(m), 1711(s), 1580(w), 1514(m), 1485(w), 1459(w),
1440(w), 1390(s), 1294(w), 1282(w), 1179(s), 1117(m),
1064(w), 832(m), 797(w), 768(w), 731(m); HRMS m/z (M þ
Naþ) calcd. 518.2051, found 518.2069. Anal. Calcd. for
C30H29N3O4: C, 72.71; H, 5.90; N, 8.48. Found: C, 73.00; H,
6.19; N, 8.34.
cmꢁ1
)
3369(bs), 3112(w), 3053(m), 2958(m), 2925(m),
2-(4-Isopropylphenyl)-5b-(1-(4-isopropylphenyl)-2,5-diox-
opyrrolidin-3-yl)-3aa,4,5a,8ba-tetrahydro-2H,6H-pyrrolo[3,4-e]
indole-1,3-dione (54). Method A with vinylpyrrole 4 and mal-
eimide 10e gave 54 (304 mg, 29%) as a light-brown powder:
2895(m), 2871(m), 2840(w), 1768(m), 1706(w), 1595(m),
1553(w), 1497(m), 1455(m), 1384(s), 1316(w), 1294(m),
1268(w), 1194(s), 1153(m), 1137(m), 1089(w), 1059(m),
1026(w), 994(w), 910(w), 817(w), 719(s); HRMS m/z (M þ
Naþ) calcd. 317.1261, found 317.1262. Anal. Calcd. for
C18H18N2O2: C, 73.45; H, 6.16; N, 9.52. Found: C, 73.21; H,
6.13; N, 9.72.
1
mp 148–150ꢃC; H NMR (300 MHz, CDCl3, d) 10.45 (bs, 1H,
6-H), 7.37 (d, J ¼ 8.4 Hz, 2H, Ph), 7.27 (d, J ¼ 8.7 Hz, 2H,
Ph), 7.20 (d, J ¼ 8.4 Hz, 2H, Ph), 7.13 (d, J ¼ 8.4 Hz, 2H,
Ph), 6.70 (dd, J ¼ 2.4, 2.4 Hz, 1H, 7-H), 6.38 (dd, J ¼ 2.7,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2009 Access to Indoles via Diels-Alder Reactions of 2-Vinylpyrroles with Maleimides
1169
2.7 Hz, 1H, 8-H), 4.17 (d, J ¼ 7.8 Hz, 1H, 8ba), 3.56 (ddd, J
¼ 7.7, 4.0, 4.0 Hz, 1H, 3aa), 3.24 (ddd, J ¼ 8.8, 8.8, 6.1 Hz,
1H, 10-H), 2.85–3.25 (m, overlapped by 10-H, 5H, 20-H ꢂ 2
and 5a-H and CH(CH3)2 ꢂ 2), 2.69 (ddd, J ¼ 13.4, 3.8, 3.8
Hz, 1H, 4b-H), 1.72 (ddd, J ¼ 13.0, 10.7, 4.3 Hz, 1H, 4a-H),
1.29 (d, J ¼ 6.9 Hz, 6H, CH(CH3)2), 1.24 (d, J ¼ 6.9 Hz, 6H,
CH(CH3)2); 13C NMR (75 MHz, CDCl3, d) 179.7, 177.8,
177.2, 174.4, 150.1, 149.3, 129.4, 129.0, 127.6, 127.3, 127.2,
126.4, 126.1, 118.4, 111.8, 107.3, 44.6, 40.4, 40.2, 35.04,
34.97, 33.1, 31.5, 26.4, 24.0; IR (KBr, cmꢁ1) 3354(bs),
3039(w), 2960(s), 2928(m), 2871(m), 1779(m), 1708(s),
1574(w), 1514(m), 1461(m), 1385(s), 1281(w), 1168(s),
1114(m), 1059(m), 831(m), 732(m), 693(m), 659(m); HRMS
m/z (M þ Naþ) calcd. 546.2364, found 546.2377. Anal. Calcd.
for C32H33N3O4: C, 73.40; H, 6.35; N, 8.02. Found: C, 73.18;
H, 6.52; N, 8.04.
1773(m), 1702(s), 1585(w), 1495(w), 1455(w), 1432(m),
1397(m), 1341(m), 1314(w), 1166(m), 1083(w), 1065(w),
723(w), 699(m); HRMS m/z (M þ Naþ) calcd. 490.1738,
found 490.1739. Anal. Calcd. for C28H25N3O4: C, 71.93; H,
5.39; N, 8.99. Found: C, 71.87; H, 5.52; N, 8.73.
2-(4-Ethylphenyl)-5a-(1-(4-ethylphenyl)-2,5-dioxopyrrolidin-
3-yl)-3aa,4,5b,8ba-tetrahydro-2H,6H-pyrrolo[3,4-e]indole-1,3-
dione (57). Method A with vinylpyrrole 4 and maleimide 10d
gave 57 (50 mg, 5%) as a cream-colored powder: mp 252–
254ꢃC; 1H NMR (300 MHz, CDCl3, d) 7.96 (bs, 1H, 6-H),
7.34 (d, J ¼ 8.4 Hz, 2H, Ph), 7.29 (d, J ¼ 8.7 Hz, 2H, Ph),
7.16 (d, J ¼ 8.4 Hz, 2H, Ph), 7.15 (d, overlapped, J ¼ 8.4 Hz,
2H, Ph), 6.71 (dd, J ¼ 2.7, 2.7 Hz, 1H, 7-H), 6.48 (dd, J ¼
2.7, 2.7 Hz, 1H, 8-H), 4.14 (d, J ¼ 8.1 Hz, 1H, 8ba-H), 3.92
(ddd, J ¼ 5.9, 5.9, 3.3 Hz, 1H, 5b-H), 3.40 (ddd, J ¼ 9.2, 6.8,
3.3 Hz, 1H, 10-H), 3.39 (ddd, overlapped by 10-H, J ¼ 9.6,
7.9, 5.3 Hz, 1H, 3aa-H), 2.95 (dd, J ¼ 17.6, 9.2 Hz, 1H, 20-H
syn to 10-H), 2.71 (q, J ¼ 7.7 Hz, 2H, CH2CH3), 2.68 (q, over-
lapped by CH2CH3, J ¼ 7.5 Hz, 2H, CH2CH3), 2.52 (dd, J ¼
17.6, 6.8 Hz, 1H, 20-H anti to 10-H), 2.42 (ddd, J ¼ 13.9, 9.2,
5.9 Hz, 1H, 4b-H), 2.21 (ddd, J ¼ 13.7, 5.7, 5.7 Hz, 1H, 4a-
H), 1.27 (t, J ¼ 7.6 Hz, 3H, CH2CH3), 1.25 (t, overlapped by
CH2CH3, J ¼ 7.6 Hz, 3H, CH2CH3); 13C NMR (75 MHz,
CDCl3, d) 179.1, 177.9, 176.1, 174.9, 145.5, 144.9, 129.3,
129.1, 129.0, 128.7, 126.23, 126.18, 124.6, 119.4, 113.5,
108.4, 45.4, 39.8, 38.9, 31.3, 30.3, 28.7, 28.4, 15.5; IR (KBr,
2-(4-Phenoxyphenyl)-5b-(1-(4-phenoxyphenyl)-2,5-dioxo-
pyrrolidin-3-yl)-3aa,4,5a,8ba-tetrahydro-2H,6H-pyrrolo[3,4-e]
indole-1,3-dione (55). Method A with vinylpyrrole 4 and mal-
eimide 10h gave 55 (474 mg, 38%) as a cream-colored pow-
1
der: mp 133–135ꢃC; H NMR (300 MHz, CDCl3, d) 10.51 (bs,
1H, 6-H), 7.33–7.42 (m, 4H, Ph), 7.01–7.26 (m, 14H, Ph),
6.76 (dd, J ¼ 2.6, 2.6 Hz, 1H, 7-H), 6.39 (dd, J ¼ 2.6, 2.6 Hz,
1H, 8-H), 4.20 (dd, J ¼ 7.8, 1.4 Hz, 1H, 8ba-H), 3.58 (ddd, J
¼ 8.0, 4.7, 3.3 Hz, 1H, 3aa-H), 3.13–3.26 (m, 1H, 5a-H), 3.25
(ddd, overlapped by 5a-H, J ¼ 9.2, 9.2, 6.2 Hz, 1H, 10-H),
3.14 (dd, overlapped by 5a-H, J ¼ 17.7, 8.7 Hz, 1H, 20-H),
3.00 (dd, J ¼ 17.9, 6.5 Hz, 1H, 20-H), 2.74 (ddd, J ¼ 13.3,
4.3, 3.5 Hz, 1H, 4b-H), 1.76 (ddd, J ¼ 13.1, 11.0, 4.9 Hz, 1H,
4a-H); 13C NMR (75 MHz, CDCl3, d) 179.7, 177.7, 177.1,
174.2, 158.2, 157.3, 156.5, 156.2, 130.1, 130.0, 128.0, 127.8,
127.3, 126.6, 125.9, 124.3, 124.0, 119.9, 119.5, 118.8, 118.5,
111.8, 107.4, 44.7, 40.4, 40.2, 33.2, 31.6, 26.5; IR (KBr,
cmꢁ1
)
3462(w), 3364(bs), 3037(w), 2965(m), 2929(m),
2871(w), 1776(m), 1705(s), 1514(m), 1488(w), 1458(w),
1386(s), 1354(m), 1313(w), 1301(w), 1223(w), 1163(s),
1190(s), 1110(w), 1100(w), 1083(w), 770(m), 720(m); HRMS
m/z (M þ Naþ) calcd. 518.2051, found 518.2059. Anal. Calcd.
for C30H29N3O4: C, 72.71; H, 5.90; N, 8.48. Found: C, 72.99;
H, 5.93; N, 8.70.
cmꢁ1
)
3346(bs), 3061(m), 2922(m), 1778(m), 1718(s),
2-(4-Isopropylphenyl)-5a-(1-(4-isopropylphenyl)-2,5-dioxo-
pyrrolidin-3-yl)-3aa,4,5b,8ba-tetrahydro-2H,6H-pyrrolo[3,4-e]
indole-1,3-dione (58). Method A with vinylpyrrole 4 and mal-
eimide 10e gave 58 (84 mg, 8%) as a cream-colored powder:
1588(m), 1506(s), 1487(s), 1388(m), 1286(m), 1244(s),
1196(m), 1113(m), 1067(m), 1017(w), 875(m), 845(m),
770(m), 695(m); HRMS m/z (M þ Naþ) calcd. 646.1949,
found 646.1951. Anal. Calcd. for C38H29N3O6: C, 73.18; H,
4.69; N, 6.74. Found: C, 73.40; H, 4.87; N, 6.61.
1
mp 280–282ꢃC; H NMR (300 MHz, CDCl3, d) 7.94 (bs, 1H,
6-H), 7.37 (d, J ¼ 8.1 Hz, 2H, Ph), 7.31 (d, J ¼ 8.4 Hz, 2H,
Ph), 7.17 (d, J ¼ 8.7 Hz, 2H, Ph), 7.16 (d, J ¼ 8.4 Hz, 2H,
Ph), 6.71 (dd, J ¼ 2.9, 2.9 Hz, 1H, 7-H), 6.48 (dd, J ¼ 2.6,
2.6 Hz, 1H, 8-H), 4.14 (d, J ¼ 8.4 Hz, 1H, 8ba-H), 3.93 (ddd,
J ¼ 5.6, 5.6, 3.2 Hz, 1H, 5b-H), 3.40 (ddd, J ¼ 9.2, 6.6, 3.3
Hz, 1H, 10-H), 3.40 (ddd, overlapped, J ¼ 9.3, 8.0, 5.6 Hz,
1H, 3a-H), 2.97 (septet, J ¼ 7.0 Hz, 1H, CH(CH3)2), 2.95 (dd,
overlapped by CH(CH3)2 ꢂ 2, J ¼ 17.6, 9.2 Hz, 1H, 20-H syn
to 10-H), 2.94 (dd, overlapped by CH(CH3)2 and 20-H, J ¼ 6.9
Hz, 1H, CH(CH3)2), 2.53 (dd, J ¼ 17.9, 6.8 Hz, 1H, 20-H anti
to 10-H), 2.43 (ddd, J ¼ 14.0, 9.0, 5.9 Hz, 1H, 4b-H), 2.21
(ddd, J ¼ 14.0, 5.8, 5.8 Hz, 1H, 4a-H), 1.28 (d, J ¼ 7.2 Hz,
6H, CH(CH3)2), 1.26 (d, overlapped by CH(CH3)2, J ¼ 7.2
Hz, 6H, CH(CH3)2); 13C NMR (75 MHz, CDCl3, d) 179.1,
177.9, 176.1, 175.0, 150.0, 149.5, 129.3, 129.1, 127.6, 127.3,
126.2, 126.1, 124.6, 119.4, 113.5, 108.4, 45.4, 39.8, 38.9, 34.0,
31.3, 30.3, 28.4, 24.0; IR (KBr, cmꢁ1) 3365(bs), 3038(w),
2961(s), 2927(m), 2899(m), 1776(m), 1708(s), 1514(m),
1460(w), 1387(s), 1355(m), 1306(w), 1187(s), 1160(s),
1105(m), 1085(w), 1055(m), 832(m), 727(m); HRMS m/z (M
þ Naþ) calcd. 546.2364, found 546.2373. Anal. Calcd. for
C32H33N3O4: C, 73.40; H, 6.35; N, 8.02. Found: C, 73.22; H,
6.51; N, 7.96.
2-Benzyl-5a-(1-benzyl-2,5-dioxopyrrolidin-3-yl)-3aa,4,5b,8ba-
tetrahydro-2H,6H-pyrrolo[3,4-e]indole-1,3-dione (56) and 2-ben-
zyl-5b-(1-benzyl-2,5-dioxopyrrolidin-3-yl)-3aa,4,5a,8ba-tetrahy-
dro-2H,6H-pyrrolo[3,4-e]indole-1,3-dione (52). Method A with
vinylpyrrole 4 and maleimide 10b followed by fractional
recrystallizations from CH2Cl2/petroleum ether gave 56 (168
mg, 18%) as a light-brown powder, with a maximum purity of
56:52 in a 5:1 molar ratio, mass calculated from 1H NMR,
spectroscopic data for 56 only reported: mp 86–91ꢃC; 1H
NMR (300 MHz, CDCl3, d) 7.36–7.41 (m, 4H, Ph), 7.27–7.28
(m, 6H, Ph), 7.02 (bs, 1H, 6-H), 6.24 (dd, J ¼ 2.6, 2.6 Hz,
1H, 7-H), 6.15 (dd, J ¼ 2.7, 2.7 Hz, 1H, 8-H), 4.79 (AA0 d, J
¼ 13.8 Hz, 1H, Bn), 4.62 (AA0 d, J ¼ 13.8 Hz, 1H, Bn), 4.61
(AA0 d, overlapped, J ¼ 14.1 Hz, 1H, Bn), 4.54 (AA0 d, J ¼
14.1 Hz, 1H, Bn), 3.89 (dd, J ¼ 7.8, 0.6 Hz, 1H, 8ba-H), 3.63
(dddd, J ¼ 7.5, 5.4, 3.3, 0.8 Hz, 1H, 5b-H), 3.17 (ddd, J ¼
8.0, 8.0, 5.6 Hz, 1H, 3aa-H), 3.13 (ddd, overlapped by 5b-H, J
¼ 8.9, 5.8, 3.1 Hz, 1H, 10-H), 2.74 (dd, J ¼ 18.0, 9.3 Hz, 1H,
20-H syn to 10-H), 2.26 (ddd, J ¼ 13.5, 7.8, 5.7 Hz, 1H, 4b-H),
2.22 (dd, overlapped by 4b-H, J ¼ 18.0, 5.7 Hz, 1H, 20-H anti
to 10-H), 1.88 (ddd, J ¼ 13.6, 7.7, 5.8 Hz, 1H, 4a-H); IR
(KBr, cmꢁ1) 3382(bm), 3063(w), 3033(m), 2922(s), 2853(m),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1170
W. E. Noland, N. P. Lanzatella, L. Venkatraman, N. F. Anderson, and G. C. Gullickson
Vol 46
(bs, 1H, 6-H), 7.94 (dd, J ¼ 8.4, 0.9 Hz, 1H, 5-H), 7.82 (dd, J
¼ 2.9, 2.9 Hz, 1H, 7-H), 7.68 (d, J ¼ 8.4 Hz, 1H, 4-H), 7.55–
7.60 (m, 4H, Ph), 7.40–7.44 (m, 1H, Ph), 7.01 (ddd, J ¼ 3.2,
2.1, 0.9 Hz, 1H, 8-H); 13C NMR (75 MHz, DMSO-d6, d)
168.9, 168.6, 141.3, 132.9, 132.5, 129.3, 128.1, 127.8, 124.1,
123.1, 123.0, 117.5, 115.8, 100.5; IR (film, cmꢁ1) 3288(bs),
2953(m), 2870(m), 1753(m), 1696(s), 1620(w), 1590(w),
1495(w), 1490(w), 1365(m), 1265(w), 1227(w), 1153(w),
1061(w), 753(m); HRMS m/z (M þ Naþ) calcd. 285.0635,
found 285.0641. Anal. Calcd. for C16H10N2O2: C, 73.27; H,
3.84; N, 10.68. Found: C, 73.00; H, 3.73; N, 10.82.
2-(4-Phenoxyphenyl)-5a-(1-(4-phenoxyphenyl)-2,5-dioxopyr-
rolidin-3-yl)-3aa,4,5b,8ba-tetrahydro-2H,6H-pyrrolo[3,4-e]indole-
1,3-dione (59). Method A with vinylpyrrole 4 and maleimide
10h gave 59 (100 mg, 8%) as a white powder: mp 267–
268ꢃC; 1H NMR (300 MHz, CDCl3, d) 7.94 (bs, 1H, 6-H),
7.34–7.43 (m, 4H, Ph), 7.03–7.24 (m, 14H, Ph), 6.72 (dd, J ¼
2.9, 2.9 Hz, 1H, 7-H), 6.48 (dd, J ¼ 2.7, 2.7 Hz, 1H, 8-H),
4.15 (d, J ¼ 8.1 Hz, 1H, 8ba-H), 3.93 (ddd, J ¼ 5.6, 5.6, 3.4
Hz, 1H, 5b-H), 3.41 (ddd, J ¼ 9.0, 6.6, 3.3 Hz, 1H, 10-H),
3.41 (ddd, overlapped by 10-H, J ¼ 9.1, 7.8, 5.9 Hz, 1H, 3aa-
H), 2.96 (dd, J ¼ 17.7, 9.0 Hz, 1H, 20-H syn to 10-H), 2.53
(dd, 17.7, 6.6 Hz, 1H, 20-H anti to 10-H), 2.43 (ddd, J ¼ 14.2,
8.6, 5.6 Hz, 1H, 4b-H), 2.21 (ddd, J ¼ 14.0, 5.9, 5.9 Hz, 1H,
4a-H); 13C NMR (75 MHz, DMSO-d6, d) 179.0, 178.2, 177.2,
176.1, 157.1, 156.60, 156.59, 130.8, 129.4, 128.0, 127.9,
127.2, 124.6, 119.75, 119.69, 118.9, 118.4, 111.5, 107.2, 43.4,
ꢀ40 (obscured by DMSO), 38.4, 33.2, 32.7, 28.5; 13C NMR
(75 MHz, CDCl3, d) 179.01, 178.95, 177.8, 174.8, 157.6,
154.6, 152.8, 130.1, 130.0, 127.82, 127.78, 126.2, 126.0,
124.6, 124.3, 124.0, 119.8, 119.6, 119.4, 118.8, 113.5, 108.4,
45.4, 39.7, 38.9, 31.3, 30.3, 28.3; IR (KBr, cmꢁ1) 3358(bs),
3053(w), 2994(W), 2950(w), 2915(m), 2856(w), 1770(m),
1711(s), 1589(m), 1506(m), 1489(m), 1456(w), 1386(m),
1350(w), 1294(w), 1244(s), 1193(m), 1155(m), 1102(m),
1072(m), 1019(w), 880(w), 800(w), 760(m), 730(m), 699(m);
HRMS m/z (M þ Naþ) calcd. 646.1949, found 646.1958.
Anal. Calcd. for C38H29N3O6: C, 73.18; H, 4.69; N, 6.74.
Found: C, 72.96; H, 4.80; N, 6.58.
2-(4-Ethylphenyl)-2H,6H-pyrrolo[3,4-e]indole-1,3-dione (63).
Method C with adduct 14 gave 63 (51 mg, 47%) as a yellow
1
powder: mp 172–173ꢃC; H NMR (300 MHz, CDCl3, d) 8.82
(bs, 1H, 6-H), 7.76 (d, J ¼ 8.4 Hz, 1H, 4-H), 7.71 (dd, J ¼
8.1, 0.9 Hz, 1H, 5-H), 7.52 (dd, J ¼ 3.3, 2.4 Hz, 1H, 7-H),
7.40 (d, J ¼ 8.7 Hz, 2H, Ph), 7.34 (d, J ¼ 8.7 Hz, 2H, Ph),
7.13 (ddd, J ¼ 3.1, 2.0, 0.8 Hz, 1H, 8-H), 2.72 (q, J ¼ 7.7 Hz,
2H, CH2CH3), 1.29 (t, J ¼ 7.7 Hz, 3H, CH2CH3); 13C NMR
(75 MHz, DMSO-d6, d) 169.1, 168.7, 143.9, 141.3, 132.6,
130.4, 128.7, 127.8, 124.2, 123.1, 123.0, 117.5, 115.8, 100.4,
28.4, 16.2; IR (KBr, cmꢁ1) 3417(bs), 3319(w), 2963(w),
2929(w), 1760(m), 1706(s), 1629(w), 1592(w), 1517(m),
1460(w), 1426(w), 1380(s), 1366(s), 1274(w), 1228(w),
1088(m), 1068(w), 823(w), 800(w), 759(m), 745(m); HRMS
m/z (M þ Naþ) calcd. 313.0948, found 313.0942. Anal. Calcd.
for C18H14N2O2: C, 74.47; H, 4.86; N, 9.65. Found: C, 74.35;
H, 4.94; N, 9.51.
2-(4-Isopropylphenyl)-2H,6H-pyrrolo[3,4-e]indole-1,3-dione
(64). Method C with adduct 15 gave 64 (70 mg, 61%) as yel-
2-Dimethylamino-2H,6H-pyrrolo[3,4-e]indole-1,3-dione (60).
Method D with adduct 11 gave 60 (55 mg, 64%) as orange
crystals: mp 237–238ꢃC; 1H NMR (300 MHz, DMSO-d6, d)
11.89 (bs, 1H, 6-H), 7.79 (m, 2H, 4-H and 5-H), 7.49 (dd, J ¼
8.1, 1.2 Hz, 1H, 7-H), 6.79 (ddd, J ¼ 2.1, 2.1, 0.9 Hz, 1H, 8-
H), 2.89 (s, 6H, N(CH3)2); 13C NMR (75 MHz, DMSO-d6, d)
168.6, 168.4, 141.3, 132.5, 122.8, 122.5, 121.3, 117.3, 115.4,
100.2, 45.0; IR (film, cmꢁ1) 3251(bs), 2940(m), 2870(m),
1756(m), 1704(s), 1448(m), 1440(w), 1357(m), 1274(w),
1142(w), 1104(m), 740(m); HRMS m/z (M þ Naþ) calcd.
252.0744, found 252.0748. Anal. Calcd. for C12H11N3O2: C,
62.87; H, 4.84; N, 18.33. Found: C, 62.68; H, 4.81; N, 18.17.
2-Benzyl-2H,6H-pyrrolo[3,4-e]indole-1,3-dione (61). Method
C with adduct 12 gave 61 (47 mg, 45%) as a yellow powder:
1
low needle-like crystals: mp 178–179ꢃC; H NMR (300 MHz,
CDCl3, d) 8.68 (bs, 1H, 6-H), 7.78 (d, J ¼ 8.4 Hz, 1H, 4-H),
7.73 (dd, J ¼ 8.1, 0.9 Hz, 1H, 5-H), 7.55 (dd, J ¼ 2.4, 0.9 Hz,
1H, 7-H), 7.41 (d, J ¼ 8.4 Hz, 2H, Ph), 7.37 (d, J ¼ 8.4 Hz,
2H, Ph), 7.15 (ddd, J ¼ 3.1, 2.0, 1.0 Hz, 1H, 8-H), 2.98 (sep-
tet, J ¼ 6.9 Hz, 1H, CH(CH3)2), 1.30 (d, J ¼ 6.9 Hz, 6H,
CH(CH3)2); 13C NMR (75 MHz, DMSO-d6, d) 169.1, 168.7,
148.4, 141.3, 132.6, 130.5, 127.8, 127.2, 124.2, 123.1, 123.0,
117.6, 115.8, 108.5, 100.5, 39.2, 24.4; IR (KBr, cmꢁ1
)
3419(s), 2960(m), 2925(s), 2855(m), 1758(m), 1711(s),
1516(w), 1457(w), 1427(w), 1378(m), 1367(m), 1315(w),
1274(m), 1227(w), 1155(w), 1120(m), 1070(w), 714(w);
HRMS m/z (M þ Naþ) calcd. 327.1105, found 327.1113.
Anal. Calcd. for C19H16N2O2: C, 74.98; H, 5.30; N, 9.20.
Found: C, 74.71; H, 5.12; N, 9.07.
1
mp 195–196ꢃC; H NMR (300 MHz, DMSO-d6, d) 11.99 (bs,
1H, 6-H), 7.81 (dd, J ¼ 8.1, 1.1 Hz, 1H, 5-H), 7.79–7.81 (m,
overlapped by 4-H, 1H, 7-H), 7.56 (d, J ¼ 8.1 Hz, 1H, 4-H),
7.23–7.37 (m, 5H, Ph), 6.81 (ddd, J ¼ 3.0, 2.0, 0.9 Hz, 1H, 8-
H), 4.76 (s, 2H, Bn); 13C NMR (75 MHz, CDCl3, d) 169.7,
169.4, 140.4, 137.2, 129.7, 128.7, 128.6, 127.7, 125.2, 124.0,
123.2, 116.4, 115.8, 102.1, 41.4; 13C NMR (75 MHz, DMSO-
d6, d) 169.7, 169.4, 141.3, 137.8, 132.6, 129.1, 127.8 (two
peaks overlapped), 124.3, 123.0, 115.2, 113.8, 100.3, ꢀ40
(obscured by DMSO); IR (KBr, cmꢁ1) 3275(bs), 3108(w),
3057(w), 3035(w), 2941(w), 1756(m), 1687(s), 1590(w),
1508(w), 1492(w), 1455(w), 1433(m), 1398(m), 1368(m),
1340(m), 1272(w), 1062(m), 764(w), 745(m), 675(m); HRMS
m/z (M þ Naþ) calcd. 299.0792, found 299.0794. Anal. Calcd.
for C17H12N2O2: C, 73.90; H, 4.38; N, 10.14. Found: C,
73.63; H, 4.28; N, 9.90.
2-(4-Methoxyphenyl)-2H,6H-pyrrolo[3,4-e]indole-1,3-dione
(65). Method D with adduct 16 gave 65 (70 mg, 64%) as
1
brown crystals: mp 220–221ꢃC; H NMR (300 MHz, acetone-
d6, d) 11.12 (bs, 1H, 6-H), 7.93 (dd, J ¼ 8.1, 0.9 Hz, 1H, 5-
H), 7.81 (dd, J ¼ 2.9, 2.9 Hz, 1H, 7-H), 7.66 (d, J ¼ 8.1 Hz,
1H, 4-H), 7.44 (d, J ¼ 9.0 Hz, 2H, Ph), 7.09 (d, J ¼ 9.0 Hz,
2H, Ph), 6.98–7.02 (m, 1H, 8-H), 3.89 (s, 3H, OCH3); 13C
NMR (75 MHz, acetone-d6, d) 168.7, 168.4, 159.0, 141.2,
131.2, 128.5, 125.6, 124.6, 123.4, 123.2, 116.8, 115.4, 114.0,
100.7, 55.0; IR (film, cmꢁ1) 3300(bs), 2920(m), 2810(m),
1758(w), 1706(s), 1517(m), 1441(w), 1369(m), 1250(m),
1155(w), 1117(w), 743(m); HRMS m/z (M þ Naþ) calcd.
315.0741, found 315.0743. Anal. Calcd. for C17H12N2O3: C,
69.86; H, 4.14; N, 9.58. Found: C, 69.67; H, 4.10; N, 9.39.
2-(4-Phenoxyphenyl)-2H,6H-pyrrolo[3,4-e]indole-1,3-dione
(66). Method C with adduct 17 gave 66 (51 mg, 38%) as
2-Phenyl-2H,6H-pyrrolo[3,4-e]indole-1,3-dione (62). Method
D with adduct 13 gave 62 (66 mg, 67%) as bright-yellow crys-
1
tals: mp 265–266ꢃC; H NMR (300 MHz, acetone-d6, d) 11.16
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2009 Access to Indoles via Diels-Alder Reactions of 2-Vinylpyrroles with Maleimides
1171
bright yellow crystals: mp 193–194ꢃC; 1H NMR (300 MHz,
CDCl3, d) 8.72 (bs, 1H, 6-H), 7.78 (d, J ¼ 8.4 Hz, 1H, 4-H),
7.73 (dd, J ¼ 8.4, 0.8 Hz, 1H, 5-H), 7.56 (dd, J ¼ 3.2, 2.6 Hz,
1H, 7-H), 7.36–7.48 (m, 4H, Ph), 7.08–7.19 (m, 6H, 8-H, Ph);
13C NMR (75 MHz, DMSO-d6, d) 169.0, 168.7, 156.8, 156.6,
141.3, 132.6, 130.7, 129.6, 127.9, 124.4, 124.2, 123.1, 123.0,
119.6, 119.0, 117.6, 115.8, 100.5; IR (KBr, cmꢁ1) 3316(bm),
3065(w), 1764(m), 1703(s), 1629(w), 1588(w), 1506(m),
1487(m), 1460(w), 1433(w), 1383(m), 1370(m), 1241(s),
1151(m), 1105(m), 1089(m), 1070(m), 1005(w), 870(w),
822(w), 744(m), 691(m); HRMS m/z (M þ Naþ) calcd.
377.0897, found 377.0883. Anal. Calcd. for C22H14N2O3: C,
74.57; H, 3.98; N, 7.91. Found: C, 74.44; H, 3.93; N, 7.54.
2-Dimethylamino-6-methyl-2H,6H-pyrrolo[3,4-e]indole-1,3-
dione (67). Method D with adduct 18 gave 67 (60 mg, 66%)
as yellow crystals: mp 201–202ꢃC; 1H NMR (300 MHz, ace-
tone-d6, d) 7.84 (d, J ¼ 8.4 Hz, 1H, 4-H), 7.67 (d, J ¼ 3.3 Hz,
1H, 7-H), 7.57 (dd, J ¼ 8.1, 0.6 Hz, 1H, 5-H), 6.88 (dd, J ¼
3.0, 0.6 Hz, 1H, 8-H), 3.99 (s, 3H, 6-CH3), 2.99 (s, 6H,
N(CH3)2); 13C NMR (75 MHz, CDCl3, d) 168.8, 168.5, 141.2,
134.6, 123.5, 122.7, 122.0, 115.8, 114.2, 100.7, 45.2, 33.4; IR
(film, cmꢁ1) 3102(m), 2969(m), 2877(m), 2854(w), 1763(m),
1706(s), 1509(w), 1498(w), 1375(w), 1357(m), 1296(w),
1168(w), 1092(w), 1023(w); HRMS m/z (M þ Naþ) calcd.
266.0901, found 266.0892. Anal. Calcd. for C13H13N3O2: C,
64.19; H, 5.39; N, 17.27. Found: C, 64.46; H, 5.30; N, 17.27.
6-Methyl-2-phenyl-2H,6H-pyrrolo[3,4-e]indole-1,3-dione (68).
Method D with adduct 19 gave 68 (74 mg, 71%) as bright or-
ange-yellow crystals: mp 214–215ꢃC; 1H NMR (300 MHz,
CD2Cl2, d) 7.76 (d, J ¼ 8.4 Hz, 1H, 4-H), 7.71 (dd, J ¼ 8.4,
0.6 Hz, 1H, 5-H), 7.41–7.58 (m, 6H, 7-H and Ph), 7.03 (dd, J
¼ 3.9, 0.7 Hz, 1H, 8-H), 3.93 (s, 3H, 6-CH3); 13C NMR (75
MHz, CD2Cl2, d) 168.8, 168.3, 141.3, 134.9, 132.6, 129.0,
127.8, 127.6, 126.9, 124.3, 123.6, 115.7, 114.6, 100.4, 33.5; IR
(film, cmꢁ1) 3125(m), 2900(w), 1759(m), 1710(s), 1595(m),
1512(m), 1490(m), 1453(w), 1377(s), 1361(s), 1294(m),
1223(w), 1171(w), 1094(w), 1063(w), 744(m); HRMS m/z (M
þ Naþ) calcd. 299.0792, found 299.0792. Anal. Calcd. for
C17H12N2O2: C, 73.90; H, 4.38; N, 10.14. Found: C, 73.71; H,
4.28; N, 10.14.
DMSO-d6, d) 168.5, 168.3, 139.6, 137.8, 129.0, 124.1, 122.8,
119.6, 117.4, 99.2, 45.0, 37.3, 20.1; IR (film, cmꢁ1) 3120(m),
2998(m), 2963(m), 2875(m), 2815(m), 1757(s), 1709(s),
1596(w), 1517(m), 1477(w), 1448(m), 1348(s), 1321(m),
1188(w), 1172(m), 1105(w), 1015(w), 760(m), 740(m); HRMS
m/z (M þ Naþ) calcd. 280.1057, found 280.1055. Anal. Calcd.
for C14H15N3O2: C, 65.35; H, 5.88; N, 16.33. Found: C,
65.55; H, 5.99; N, 16.50.
5,6-Dimethyl-2-phenyl-2H,6H-pyrrolo[3,4-e]indole-1,3-dione
(71). Method D with adduct 22 gave 71 (79 mg, 72%) as
bright orange-yellow crystals: mp 225–226ꢃC; 1H NMR (300
MHz, CDCl3, d) 7.48–7.53 (m, 4H, Ph), 7.45 (s, 1H, 4-H),
7.38–7.41 (m, 1H, Ph), 7.24 (d, J ¼ 3.0 Hz, 1H, 7-H), 7.01 (d,
J ¼ 3.0 Hz, 1H, 8-H), 4.16 (s, 3H, 6-CH3), 2.91 (s, 3H, 5-
CH3); 13C NMR (75 MHz, DMSO-d6, d) 168.8, 168.4, 139.7,
138.0, 132.9, 129.4, 129.3, 128.0, 127.7, 124.6, 124.4, 121.3,
117.9, 99.5, 37.3, 20.1; IR (film, cmꢁ1) 3120(m), 2940(m),
1752(m), 1706(s), 1596(w), 1517(w), 1501(m), 1453(w),
1405(w), 1376(m), 1356(m), 1321(w), 1226(w), 1102(w),
753(m); HRMS m/z (M þ Naþ) calcd. 313.0948, found
313.0945. Anal. Calcd. for C18H14N2O2: C, 74.47; H, 4.86; N,
9.65. Found: C, 74.70; H, 4.63; N, 9.80.
2-(4-Methoxyphenyl)-5,6-dimethyl-2H,6H-pyrrolo[3,4-e]indole-
1,3-dione (72). Method D with adduct 23 gave 72 (79 mg,
66%) as bright-red crystals: mp 229-230ꢃC; 1H NMR (300
MHz, CD2Cl2, d) 7.43 (s, 1H, 4-H), 7.36 (d, J ¼ 9.0 Hz, 2H,
Ph), 7.31 (d, J ¼ 3.0 Hz, 1H, 7-H), 7.05 (d, J ¼ 9.0 Hz, 2H,
Ph), 6.97 (d, J ¼ 3.0 Hz, 1H, 8-H), 4.17 (s, 3H, 6-CH3), 3.88
(s, 3H, OCH3), 2.94 (s, 3H, 5-CH3); 13C NMR (75 MHz,
DMSO-d6, d) 169.1, 168.7, 159.0, 139.6, 137.92, 137.87,
129.2, 125.4, 124.6, 124.4, 121.1, 117.8, 114.6, 99.5, 55.9,
37.3, 20.1; IR (film, cmꢁ1) 3104(m), 2938(m), 2844(m),
1751(m), 1698(s), 1512(s), 1461(m), 1384(m), 1356(m),
1327(w), 1299(w), 1249(m), 1171(m), 1090(w), 1074(w),
1031(w), 802(w); HRMS m/z (M þ Naþ) calcd. 343.1054,
found 343.1069. Anal. Calcd. for C19H16N2O3: C, 71.24; H,
5.03; N, 8.74. Found: C, 71.62; H, 5.10; N, 8.55.
2-Dimethylamino-4-methyl-2H,6H-pyrrolo[3,4-e]indole-1,3-
dione (73). Method D with adduct 24 gave 73 (52 mg, 57%)
as yellow crystals: mp 255–256ꢃC; 1H NMR (300 MHz,
CDCl3, d) 8.70 (bs, 1H, 6-H), 7.41–7.45 (m, 2H, 5-H and 7-
H), 7.03 (ddd, J ¼ 3.2, 2.0, 1.1 Hz, 1H, 8-H), 3.07 (s, 6H,
N(CH3)2), 2.77 (d, J ¼ 0.9 Hz, 3H, 4-CH3); 13C NMR (75
MHz, DMSO-d6, d) 169.2, 168.1, 141.3, 131.8, 129.3, 121.6,
2-(4-Methoxyphenyl)-6-methyl-2H,6H-pyrrolo[3,4-e]indole-
1,3-dione (69). Method D with adduct 20 gave 69 (76 mg,
1
66%) as bright-yellow crystals: mp 236–237ꢃC; H NMR (300
MHz, CD2Cl2, d) 7.75 (d, J ¼ 8.4 Hz, 1H, 4-H), 7.70 (dd, J ¼
8.4, 0.6 Hz, 1H, 5-H), 7.44 (d, J ¼ 3.3 Hz, 1H, 7-H), 7.38 (d,
J ¼ 9.0 Hz, 2H, Ph), 7.06 (d, J ¼ 9.0 Hz, 2H, Ph), 7.01 (dd, J
¼ 3.3, 0.7 Hz, 1H, 8-H), 3.93 (s, 3H, OCH3), 3.89 (s, 3H, 6-
CH3); 13C NMR (75 MHz, DMSO-d6, d) 169.1, 168.7, 159.1,
141.4, 136.6, 129.2, 125.4, 124.2, 123.3, 123.2, 115.9, 115.6,
114.6, 99.8, 55.9, 33.6; IR (film, cmꢁ1) 3125(w), 2988(m),
2870(w), 1753(m), 1709(s), 1509(s), 1388(m), 1366(w),
1352(w), 1299(m), 1249(s), 1170(w), 1092(w), 806(w),
704(m); HRMS m/z (M þ Naþ) calcd. 329.0897, found
329.0908. Anal. Calcd. for C18H14N2O3: C, 70.58; H, 4.61; N,
9.15. Found: C, 70.40; H, 4.59; N, 9.01.
121.5, 119.5, 118.3, 100.0, 44.9, 18.2; IR (film, cmꢁ1
)
3250(bs), 2995(m), 2880(m), 2871(m), 1748(m), 1697(s),
1446(m), 1402(w), 1390(w), 1350(m), 1101(w), 762(m);
HRMS m/z (M þ Naþ) calcd. 266.0901, found 266.0907.
Anal. Calcd. for C13H13N3O2: C, 64.19; H, 5.39; N, 17.27.
Found: C, 63.96; H, 5.34; N, 17.08.
4-Methyl-2-phenyl-2H,6H-pyrrolo[3,4-e]indole-1,3-dione (74).
Method D with adduct 25 gave 74 (63 mg, 61%) as yellow
crystals: mp 305-306ꢃC; 1H NMR (300 MHz, acetone-d6, d)
10.93 (bs, 1H, 6-H), 7.72 (dd, J ¼ 2.9, 2.9 Hz, 1H, 7-H), 7.67
(dq, J ¼ 0.9, 0.9 Hz, 1H, 5-H), 7.50–7.60 (m, 4H, Ph), 7.40–
7.50 (m, 1H, Ph), 6.94 (ddd, J ¼ 3.6, 2.1, 0.9 Hz, 1H, 8-H),
2.77 (d, J ¼ 0.6 Hz, 3H, 4-CH3); 13C NMR (75 MHz, DMSO-
d6, d) 169.0, 168.4, 141.4, 132.9, 131.9, 129.7, 129.3, 128.0,
2-Dimethylamino-5,6-dimethyl-2H,6H-pyrrolo[3,4-e]indole-
1,3-dione (70). Method D with adduct 21 gave 70 (68 mg,
1
70%) as bright-yellow crystals: mp 226–227ꢃC; H NMR (300
MHz, CDCl3, d) 7.33 (s, 1H, 4-H), 7.21 (d, J ¼ 3.3 Hz, 1H,
7-H), 6.95 (d, J ¼ 3.0 Hz, 1H, 8-H), 4.13 (s, 3H, 6-CH3), 3.05
(s, 6H, N(CH3)2), 2.87 (s, 3H, 5-CH3); 13C NMR (75 MHz,
127.9, 123.2, 121.9, 121.2, 118.5, 100.3, 18.4; IR (film, cmꢁ1
)
3288(bs), 2900(m), 2880(m), 1764(w), 1752(m), 1693(s),
1640(w), 1496(m), 1392(m), 1368(m), 1167(w), 763(m);
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1172
W. E. Noland, N. P. Lanzatella, L. Venkatraman, N. F. Anderson, and G. C. Gullickson
Vol 46
HRMS m/z (M þ Naþ) calcd. 299.0792, found 299.0785.
Anal. Calcd. for C17H12N2O2: C, 73.90; H, 4.38; N, 10.14.
Found: C, 73.71; H, 4.54; N, 9.86.
4-Ethyl-2-phenyl-2H,6H-pyrrolo[3,4-e]indole-1,3-dione (79).
Method D with adduct 30 gave 79 (48 mg, 44%) as light-
1
brown crystals: mp 261–262ꢃC; H NMR (300 MHz, DMSO-
2-(4-Methoxyphenyl)-4-methyl-2H,6H-pyrrolo[3,4-e]indole-
1,3-dione (75). Method D with adduct 26 gave 75 (68 mg,
d6, d) 11.85 (bs, 1H, 6-H), 7.81 (ddd, J ¼ 2.0, 1.0, 1.0 Hz,
1H, 8-H), 7.75 (dd, J ¼ 3.0, 3.0 Hz, 1H, 7-H), 7.64 (d, J ¼
0.9 Hz, 1H, 5-H), 7.39–7.55 (m, 5H, Ph), 3.15 (q, J ¼ 7.5 Hz,
2H, 4-CH2CH3), 1.28 (t, J ¼ 7.4 Hz, 3H, 4-CH2CH3); 13C
NMR (75 MHz, DMSO-d6, d) 169.1, 168.4, 141.6, 136.5,
132.9, 132.1, 129.3, 128.1, 128.0, 123.5, 122.0, 120.7, 117.2,
1
59%) as yellow crystals: mp 207–208ꢃC; H NMR (300 MHz,
acetone-d6, d) 10.91 (bs, 1H, 6-H), 7.71 (dd, J ¼ 3.0, 2.6 Hz,
1H, 7-H), 7.66 (dq, J ¼ 0.9, 0.9 Hz, 1H, 5-H), 7.43 (d, J ¼
9.3 Hz, 2H, Ph), 7.08 (d, J ¼ 9.0 Hz, 2H, Ph), 6.94 (ddd, J ¼
3.2, 2.0, 0.9 Hz, 1H, 8-H), 3.89 (s, 3H, OCH3), 2.76 (d, J ¼
0.9 Hz, 3H, 4-CH3); 13C NMR (75 MHz, DMSO-d6, d) 169.6,
168.6, 159.0, 141.4, 131.7, 129.6, 129.3, 125.5, 123.2, 121.9,
100.3, 24.9, 16.1; IR (KBr, cmꢁ1
) 3300(bs), 2970(m),
1763(m), 1683(s), 1637(m), 1592(w), 1496(m), 1456(w),
1368(s), 1163(w), 1101(w), 1062(w), 848(w), 760(m); HRMS
m/z (M þ Naþ) calcd. 313.0948, found 313.0945. Anal. Calcd.
for C18H14N2O2: C, 74.47; H, 4.86; N, 9.65. Found: C, 74.61;
H, 4.88; N, 9.48.
121.2, 118.4, 114.5, 100.3, 55.8, 18.4; IR (film, cmꢁ1
)
3331(bs), 2989(m), 2810(m), 1756(m), 1702(s), 1518(m),
1400(m), 1301(w), 1256(m), 1168(w), 1117(w), 760(m);
HRMS m/z (M þ Naþ) calcd. 329.0897, found 329.0905.
Anal. Calcd. for C18H14N2O3: C, 70.58; H, 4.86; N, 8.98.
Found: C, 70.77; H, 4.86; N, 8.98.
4-Ethyl-2-(4-ethylphenyl)-2H,6H-pyrrolo[3,4-e]indole-1,3-
dione (80). Method C with adduct 31 gave 80 (63 mg, 53%)
as orange crystals: mp 238–239ꢃC; 1H NMR (300 MHz,
DMSO-d6, d) 11.83 (bs, 1H, 6-H), 7.73 (dd, J ¼ 2.4, 0.9 Hz,
1H, 7-H), 7.63 (d, J ¼ 0.6 Hz, 1H, 5-H), 7.36–7.39 (m, 4H,
Ph), 6.80 (ddd, J ¼ 2.9, 1.7, 1.0 Hz, 1H, 8-H), 3.14 (q, J ¼
7.4 Hz, 2H, 4-CH2CH3), 2.67 (q, J ¼ 7.6 Hz, 2H, PhCH2CH3),
1.27 (t, J ¼ 7.5 Hz, 3H, 4-CH2CH3), 1.23 (t, J ¼ 7.7, 3H,
PhCH2CH3); 13C NMR (75 MHz, DMSO-d6, d) 169.3, 168.5,
143.7, 141.5, 136.4, 132.1, 130.4, 128.6, 127.9, 123.5, 121.9,
2-Dimethylamino-4,6-dimethyl-2H,6H-pyrrolo[3,4-e]indole-
1,3-dione (76). Method D with adduct 27 gave 76 (54 mg,
56%) as light-yellow crystals: mp 179–180ꢃC; 1H NMR (300
MHz, CDCl3, d) 7.31 (dq, J ¼ 1.0, 0.9 Hz, 1H, 5-H), 7.25 (d,
J ¼ 3.3 Hz, 1H, 7-H), 6.95 (dd, J ¼ 3.3, 0.9 Hz, 1H, 8-H),
3.84 (s, 3H, 6-CH3), 3.07 (s, 6H, N(CH3)2), 2.78 (d, J ¼ 0.9
Hz, 3H, 4-CH3); 13C NMR (75 MHz, CDCl3, d) 169.4, 168.3,
141.3, 134.0, 130.3, 122.3, 122.2, 119.8, 115.6, 100.5, 45.1,
33.3, 18.5; IR (film, cmꢁ1) 3125(m), 3100(m), 2945(m),
3877(m), 3851(m), 1759(m), 1704(s), 1632(w), 1513(m),
1470(w), 1446(w), 1403(w), 1375(m), 1353(m), 1294(w),
1099(m), 758(w); HRMS m/z (M þ Naþ) calcd. 280.1057,
found 280.1057. Anal. Calcd. for C14H15N3O2: C, 65.35; H,
5.88; N, 16.33. Found: C, 65.11; H, 5.71; N, 16.38.
120.7, 117.1, 100.3, 28.4, 24.9, 16.2, 16.1; IR (KBr, cmꢁ1
)
3307(bs), 2964(m), 2929(w), 2871(w), 1757(m), 1696(s),
1633(w), 1514(m), 1458(m), 1368(s), 1294(m), 1167(m),
1117(w), 1095(m), 1066(w), 832(w), 764(m), 726(w); HRMS
m/z (M þ Naþ) calcd. 341.1261, found 341.1260. Anal. Calcd.
for C20H18N2O2: C, 75.45; H, 5.70; N, 8.80. Found: C, 75.70;
H, 5.58; N, 8.20.
4,6-Dimethyl-2-phenyl-2H,6H-pyrrolo[3,4-e]indole-1,3-dione
(77). Method D with adduct 28 gave 77 (68 mg, 62%) as bright
orange-yellow crystals: mp 181–182ꢃC; 1H NMR (300 MHz,
CDCl3, d) 7.45–7.55 (m, 4H, Ph), 7.35–7.41 (m, 2H, 5-H and
Ph), 7.28 (d, J ¼ 3.0 Hz, 1H, 7-H), 6.99 (d, J ¼ 2.7, 0.9 Hz, 1H,
4-Ethyl-2-(4-hydroxyphenyl)-2H,6H-pyrrolo[3,4-e]indole-1,3-
dione (81). Method D with adduct 32 gave 81 (17 mg, 15%)
as yellow crystals: mp 265–267ꢃC; 1H NMR (500 MHz,
DMSO-d6, d) 11.80 (bs, 1H, 6-H), 9.69 (bs, 1H, Ph-OH),
7.69–7.74 (m, 1H, 5-H), 7.58–7.62 (m, 1H, 7-H), 7.18 (d, J ¼
7.5 Hz, 2H, Ph), 6.85 (d, J ¼ 8.0 Hz, 2H, Ph), 6.75–6.79 (m,
1H, 8-H), 3.11 (q, J ¼ 7.3 Hz, 2H, 4-CH2CH3), 1.25 (t, J ¼
7.3 Hz, 3H, 4-CH2CH3); 13C NMR (75 MHz, DMSO-d6, d)
169.6, 168.8, 157.4, 141.5, 136.3, 132.0, 129.5, 123.8, 123.5,
8-H), 3.85 (s, 3H, 6-CH3), 2.84 (d, J ¼ 0.9 Hz, 3H, 4-CH3); 13
C
NMR (75 MHz, CDCl3, d) 169.3, 168.3, 141.4, 134.1, 132.4,
130.6, 129.0, 127.5, 126.7, 123.9, 122.5, 121.4, 115.8, 100.7,
33.3, 18.6; IR (film, cmꢁ1) 3120(m), 2900(m), 2860(m),
1754(m), 1710(S), 1595(w), 1492(m), 1375(s), 1357(s),
1294(w), 1168(w); HRMS m/z (M þ Naþ) calcd. 313.0948,
found 313.0951. Anal. Calcd. for C18H14N2O2: C, 74.47; H,
4.86; N, 9.65. Found: C, 74.28; H, 4.61; N, 9.60.
121.9, 120.7, 117.0, 115.8, 100.2, 24.9, 16.1; IR (KBr, cmꢁ1
)
3464(m), 3311(bs), 3115(w), 2966(m), 2926(m), 1751(m),
1683(s), 1636(w), 1597(w), 1515(s), 1455(w), 1379(s),
1295(w), 1269(m), 1206(m), 1162(m), 1114(m), 1087(w),
834(w), 765(w); HRMS m/z (M
C18H14N2O3: 329.0897, found 329.0906.
þ
Naþ) calcd. for
2-(4-Methoxyphenyl)-4,6-dimethyl-2H,6H-pyrrolo[3,4-e]indole-
1,3-dione (78). Method D with adduct 29 gave 78 (73 mg,
1
61%) as bright-yellow crystals: mp 243–244ꢃC; H NMR (300
2-(4-Chlorophenyl)-4-ethyl-2H,6H-pyrrolo[3,4-e]indole-1,3-
dione (82). Method D with adduct 34 gave 82 (40 mg, 33%)
as yellow crystals: mp 219–220ꢃC; 1H NMR (300 MHz,
CDCl3, d) 8.56 (bs, 1H, 6-H), 7.53 (app. s, 1H, 5-H), 7.47–
7.49 (m, 5H, 7-H and Ph), 7.09 (app. dd, J ¼ 2.3, 2.3 Hz, 1H,
8-H), 3.25 (q, J ¼ 7.6 Hz, 2H, 4-CH2CH3), 1.36 (t, J ¼ 7.7
MHz, CD2Cl2, d) 7.43 (dq, J ¼ 0.9, 0.9 Hz, 1H, 5-H), 7.37–
7.40 (m, 3H, 7-H and Ph), 7.06 (d, J ¼ 9.0 Hz, 2H, Ph), 6.95
(dd, J ¼ 3.0, 0.9 Hz, 1H, 8-H), 3.89 (s, 3H, 6-CH3 or OCH3),
3.87 (s, 3H, 6-CH3 or OCH3), 2.83 (d, J ¼ 0.9 Hz, 3H, 4-
CH3); 13C NMR (75 MHz, DMSO-d6, d) 169.6, 168.5, 159.1,
141.5, 136.0, 129.6, 129.3, 125.4, 123.5, 122.1, 121.3, 117.0,
114.6, 99.6, 55.9, 33.5, 18.5; IR (film, cmꢁ1) 3120(m),
2999(m), 2940(w), 2860(w), 1751(m), 1706(s), 1632(w),
1612(w), 1510(s), 1480(w), 1438(w), 1402(m), 1382(m),
1362(w), 1345(m), 1290(m), 1244(s), 1167(m), 1113(w),
1089(w), 1028(w); HRMS m/z (M þ Naþ) calcd. 343.1054,
found 343.1064. Anal. Calcd. for C19H16N2O3: C, 71.24; H,
5.03; N, 8.74. Found: C, 71.41; H, 4.87; N, 8.54.
1
Hz, 3H, 4-CH2CH3); H NMR (300 MHz, DMSO-d6, d) 11.86
(bs, 1H, 6-H), 7.64 (d, J ¼ 0.9 Hz, 1H, 5-H), 7.59 (d, J ¼ 9.0
Hz, 2H, Ph), 7.50 (d, J ¼ 9.0 Hz, 2H, Ph), 7.49 (dd, J ¼ 3.1,
2.6 Hz, 1H, 7-H), 6.80 (ddd, J ¼ 3.0, 1.8, 1.1 Hz, 1H, 8-H),
3.14 (q, J ¼ 7.4 Hz, 2H, 4-CH2CH3), 1.27 (t, J ¼ 7.5 Hz, 3H,
4-CH2CH3); 13C NMR (75 MHz, DMSO-d6, d) 168.9, 168.1,
141.6, 136.5, 132.4, 132.2, 131.8, 129.6, 129.3, 123.4, 122.0,
120.7, 117.2, 100.3, 24.9, 16.0; IR (KBr, cmꢁ1) 3308(bs),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2009 Access to Indoles via Diels-Alder Reactions of 2-Vinylpyrroles with Maleimides
1173
3105(w), 2968(m), 2933(w), 2880(w), 1762(m), 1707(s),
1635(w), 1495(m), 1459(w), 1409(m), 1376(s), 1313(w),
1295(m), 1241(w), 1209(w), 1167(w), 1109(w), 1092(m),
1066(w), 1016(w), 852(w), 830(m), 807(m), 781(m), 753(m),
717(w); HRMS m/z (M þ Naþ) calcd. for C18H13ClN2O2:
347.0559, found 347.0557.
1041(w), 750(m), 699(m); HRMS m/z (M þ Naþ) calcd.
371.1003, found 371.1009. Anal. Calcd. for C20H16N2O4: C,
68.96; H, 4.63; N, 8.04. Found: C, 68.80; H, 4.62; N, 8.00.
(R)-2-(4-Methyl-1,3-dioxo-2H,6H-pyrrolo[3,4-e]indol-2-yl)-
2-phenylethyl acetate (86). Method A with vinylpyrrole 3b
and maleimide 10m gave adduct 40, which with method E
gave 86 (391 mg, 27%) as light-yellow crystals: mp 158–
159ꢃC; 1H NMR (300 MHz, CD2Cl2, d) 8.85 (bs, 1H, 6-H),
7.55–7.59 (m, 2H, Ph), 7.33–7.46 (m, 5H, 5-H, 7-H and Ph),
6.95 (ddd, J ¼ 3.1, 2.1, 1.0 Hz, 1H, 8-H), 5.65 (dd, J ¼ 9.6,
6.0 Hz, 1H, 20-H), 5.16 (dd, J ¼ 11.1, 9.6 Hz, 1H, 10-H), 4.86
(dd, J ¼ 6.0, 11.1 Hz, 1H, 10-H), 2.73 (d, J ¼ 0.9 Hz, 3H, 4-
CH3), 2.01 (s, 3H, Ac); 13C NMR (75 MHz, CDCl3, d) 171.2,
170.4, 169.6, 140.8, 137.0, 130.7, 129.7, 128.9, 128.4, 128.2,
123.6, 121.9, 121.7, 117.6, 101.5, 63.1, 53.0, 21.0, 18.3; IR
(film, cmꢁ1) 3370(bs), 1747(m), 1696(s), 1637(m), 1457(w),
1391(m), 1350(m), 1238(m), 1043(w), 767(m), 738(w),
700(m); HRMS m/z (M þ Naþ) calcd. 385.1160, found
385.1161. Anal. Calcd. for C21H18N2O4: C, 69.60; H, 5.01; N,
7.73. Found: C, 69.51; H, 4.98; N, 7.52.
2-(4-Bromophenyl)-4-ethyl-2H,6H-pyrrolo[3,4-e]indole-1,3-
dione (83). Method D with adduct 35 gave 83 (50 mg, 36%)
as yellow crystals: mp 246–247ꢃC; 1H NMR (300 MHz,
CDCl3, d) 8.53 (bs, 1H, 6-H), 7.63 (d, J ¼ 9.0 Hz, 2H, Ph),
7.53 (d, J ¼ 0.9 Hz, 1H, 5-H), 7.48 (dd, J ¼ 3.3, 2.4 Hz, 1H,
7-H), 7.42 (d, J ¼ 9.0 Hz, 2H, Ph), 7.10 (ddd, J ¼ 3.2, 2.2,
0.9 Hz, 1H, 8-H), 3.25 (q, J ¼ 7.4 Hz, 2H, 4-CH2CH3), 1.37
1
(t, J ¼ 7.7 Hz, 3H, 4-CH2CH3); H NMR (300 MHz, DMSO-
d6, d) 11.86 (bs, 1H, 6-H), 7.75 (dd, J ¼ 2.7 Hz, 1H, 7-H),
7.72 (d, J ¼ 8.7 Hz, 2H, Ph), 7.65 (d, J ¼ 0.9 Hz, 1H, 5-H),
7.44 (d, J ¼ 8.7 Hz, 2H, Ph), 6.80 (ddd, J ¼ 3.0, 2.0, 0.9 Hz,
1H, 8-H), 3.14 (q, J ¼ 7.5 Hz, 2H, 4-CH2CH3), 1.27 (t, J ¼
7.5 Hz, 3H, 4-CH2CH3); 13C NMR (75 MHz, DMSO-d6, d)
168.8, 168.1, 141.6, 136.5, 132.2, 129.9, 123.4, 122.0, 120.9,
120.69, 120.65, 117.2, 105.0, 100.3, 24.9, 16.1; IR (KBr,
(1)-(R)-2-(6-Methyl-1,3-dioxo-2H,6H-pyrrolo[3,4-e]indol-
2-yl)-2-phenylethyl acetate (87). Method A with vinylpyrrole
3d and maleimide 10m gave adduct 41, which with method E
gave 87 (638 mg, 44%) as light-brown crystals: mp 52–53ꢃC;
cmꢁ1
)
3307(bs), 3100(w), 3082(w), 2966(m), 2878(w),
1763(m), 1707(s), 1637(m), 1493(m), 1460(w), 1367(s),
1314(w), 1298(w), 1243(w), 1209(w), 1167(w), 1122(w),
1108(w), 1090(w), 1074(m), 1012(w), 980(w), 820(m),
790(m), 740(m); HRMS m/z (M þ Naþ) calcd. 391.0053,
found 391.0044. Anal. Calcd. for C18H13BrN2O2: C, 58.56; H,
3.55; N, 7.59. Found: C, 58.59; H, 3.41; N, 7.46.
[a]23 þ3.6 (c 2.0, CHCl3); 1H NMR (300 MHz, CDCl3, d)
D
7.66 (dd, J ¼ 8.4, 0.6 Hz, 1H, 5-H), 7.57–7.61 (m, 2H, Ph),
7.58 (d, overlapped, J ¼ 8.4 Hz, 1H, 4-H), 7.28–7.40 (m, 4H,
7-H, Ph), 6.98 (d, J ¼ 3.0 Hz, 1H, 8-H), 5.65 (dd, J ¼ 10.2,
5.7 Hz, 1H, 20-H), 5.16 (dd, J ¼ 10.5, 10.5 Hz, 1H, 10-H),
4.87 (dd, J ¼ 10.7, 5.7 Hz, 1H, 10-H), 3.89 (s, 3H, 6-CH3),
2.01 (s, 3H, Ac); 13C NMR (75 MHz, CDCl3, d) 170.8, 169.9,
169.5, 141.1, 136.8, 134.6, 128.8, 128.4, 128.2, 124.2, 123.6,
123.5, 115.7, 114.1, 100.1, 62.8, 53.3, 33.4, 20.9; IR (film,
cmꢁ1) 3447(bs), 3108(w), 3063(w), 2950(w), 1741(s), 1703(s),
1626(w), 1511(m), 1457(m), 1352(s), 1295(m), 1232(s),
1042(m), 749(s), 701(s); HRMS m/z (M þ Naþ) calcd.
385.1160, found 385.1166. Anal. Calcd. for C21H18N2O4: C,
69.60; H, 5.01; N, 7.93. Found: C, 69.75; H, 4.89; N, 7.93.
(1)-(R)-2-(5,6-Dimethyl-1,3-dioxo-2H,6H-pyrrolo[3,4-e]indol-
2-yl)-2-phenylethyl acetate (88). Method A with vinylpyrrole
3c and maleimide 10m gave adduct 42, which with method E
gave 88 (437 mg, 29%) as yellow crystals: mp 125–126ꢃC;
4-Ethyl-2-(4-nitrophenyl)-2H,6H-pyrrolo[3,4-e]indole-1,3-
dione (84). Method D with adduct 36 gave 84 (35 mg, 28%)
1
as light-orange crystals: mp 296–297ꢃC; H NMR (300 MHz,
DMSO-d6, d) 11.90 (bs, 1H, 6-H), 8.39 (d, J ¼ 9.3 Hz, 1H,
Ph), 7.83 (d, J ¼ 9.3 Hz, 2H, Ph), 7.77 (dd, J ¼ 2.9, 2.9 Hz,
1H, 7-H), 7.68 (d, J ¼ 0.6 Hz, 1H, 5-H), 6.84 (ddd, J ¼ 3.2,
2.0, 1.1 Hz, 1H, 8-H), 3.16 (q, J ¼ 7.4 Hz, 2H, 4-CH2CH3),
1.29 (t, J ¼ 7.5 Hz, 3H, 4-CH2CH3); 13C NMR (75 MHz,
DMSO-d6, d) 168.4, 167.7, 146.1, 141.7, 138.9, 136.7, 132.4,
127.9, 124.6, 123.4, 122.1, 120.6, 117.6, 100.4, 25.0, 16.1; IR
(KBr, cmꢁ1) 3378(bs), 3120(w), 2970(w), 2933(w), 2879(w),
1765(m), 1718(s), 1631(w), 1591(m), 1516(m), 1498(m),
1471(w), 1411(w), 1376(m), 1318(s), 1213(m), 1185(m),
1165(w), 1718(s), 1631(w), 1591(m), 1516(m), 1498(m),
1471(m), 1411(w), 1376(m), 1318(s), 1213(m), 1185(m),
1165(m), 1110(m), 1086(m), 1051(m), 851(m), 781(m),
750(m); HRMS m/z (M þ Naþ) calcd. 358.0799, found
358.0800. Anal. Calcd. for C18H13N3O4: C, 64.47; H, 3.91; N,
12.53. Found: C, 64.10; H, 4.25; N, 12.16.
[a]23 þ3.9 (c 2.0, CHCl3); 1H NMR (300 MHz, CDCl3, d)
D
7.56–7.59 (m, 2H, Ph), 7.27–7.41 (m, 4H, 4-H and Ph), 7.20
(d, J ¼ 3.3 Hz, 1H, 7-H), 6.94 (d, J ¼ 3.0 Hz, 1H, 8-H), 5.60
(dd, J ¼ 9.9, 5.4 Hz, 1H, 20-H), 5.14 (dd, J ¼ 11.1, 10.2 Hz,
1H, 10-H), 4.85 (dd, J ¼ 11.1, 5.4 Hz, 1H, 10-H), 4.13 (s, 3H,
6-CH3), 2.87 (s, 3H, 5-CH3), 2.00 (s, 3H, Ac); 13C NMR (75
MHz, CDCl3, d) 170.8, 169.9, 169.6, 139.6, 136.9, 136.0,
128.8, 128.3, 128.2, 127.6, 124.8, 124.7, 121.9, 118.2, 100.5,
(1)-(R)-2-(1,3-Dioxo-2H,6H-pyrrolo[3,4-e]indol-2-yl)-2-phe-
nylethyl acetate (85). Method A with vinylpyrrole 4 and mal-
eimide 10m gave adduct 39, which with method E gave 85
(641 mg, 46%) as dark-yellow crystals: mp 62–63ꢃC; [a]23
62.9, 53.2, 37.3, 20.9, 20.4; IR (film, cmꢁ1
) 3440(bs),
D
þ2.1 (c 1.0, CHCl3); 1H NMR (300 MHz, CD2Cl2, d) 8.88
(bs, 1H, 6-H), 7.74 (dd, J ¼ 8.1, 0.9 Hz, 1H, 5-H), 7.64 (d, J
¼ 8.1 Hz, 1H, 4-H), 7.56–7.61 (m, 3H, 7-H and Ph), 7.31–
7.42 (m, 3H, Ph), 7.04 (ddd, J ¼ 3.2, 2.0, 1.1 Hz, 1H, 8-H),
5.63 (dd, J ¼ 9.9, 5.7 Hz, 1H, 20-H), 5.13 (dd, J ¼ 11.1, 9.9
Hz, 1H, 10-H), 4.83 (dd, J ¼ 11.1, 5.7 Hz, 1H, 10-H), 2.02 (s,
3H, Ac); 13C NMR (75 MHz, CDCl3, d) 171.2, 170.2, 169.8,
140.9, 136.7, 130.5, 128.9, 128.5, 128.1, 124.5, 123.4, 123.2,
116.4, 116.1, 101.5, 63.0, 53.2, 21.0; IR (film, cmꢁ1) 3360(bs),
1749(m), 1698(s), 1629(w), 1458(w), 1350(s), 1236(m),
1742(m), 1701(s), 1518(w), 1496(w), 1367(m), 1347(s),
1232(m), 1089(w), 762(w), 750(w), 731(w), 701(w); HRMS
m/z (M þ Naþ) calcd. 399.1316, found 399.1328. Anal. Calcd.
for C22H20N2O4: C, 70.20; H, 5.36; N, 7.44. Found: C, 70.08;
H, 5.39; N, 7.29.
(1)-(R)-2-(4,6-Dimethyl-1,3-dioxo-2H,6H-pyrrolo[3,4-e]indol-
2-yl)-2-phenylethyl acetate (89). Method A with vinylpyrrole 3f
and maleimide 10m gave adduct 43, which with method E
gave 89 (391 mg, 26%) as brownish-orange crystals: mp 163–
164ꢃC; [a]23 þ5.9 (c 5.0, CHCl3); 1H NMR (300 MHz,
D
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1174
W. E. Noland, N. P. Lanzatella, L. Venkatraman, N. F. Anderson, and G. C. Gullickson
Vol 46
CDCl3, d) 7.57–7.60 (m, 2H, Ph), 7.27–7.40 (m, 4H, 5-H and
Ph), 7.25 (d, J ¼ 3.0 Hz, 1H, 7-H), 6.98 (d, J ¼ 3.0 Hz, 1H,
8-H), 5.63 (dd, J ¼ 10.2, 5.7 Hz, 1H, 20-H), 5.15 (dd, J ¼
11.1, 10.2 Hz, 1H, 10-H), 4.88 (dd, J ¼ 11.1, 5.7 Hz, 1H, 10-
H), 3.81 (s, 3H, 6-CH3), 2.77 (s, 3H, 4-CH3), 2.02 (s, 3H, Ac);
13C NMR (75 MHz, CDCl3, d) 170.8, 170.4, 169.4, 141.2,
137.0, 134.0, 130.2, 128.8, 128.6, 128.3, 123.8, 122.2, 121.4,
58.7, 53.3, 18.0; IR (film, cmꢁ1) 3413(bs), 1749(w), 1694(s),
1636(m), 1456(w), 1394(w), 1350(m), 766(w), 699(w); HRMS
m/z (M þ Naþ) calcd. for C20H18N2O3: 357.1210, found
357.1211.
(1)-(R)-2-(2-Methoxy-1-phenylethyl)-4,5-dimethyl-2H,6H-
pyrrolo[3,4-e]indole-1,3-dione (93). Method A with vinylpyr-
role 3e and maleimide 10n gave adduct 47, which with
115.5, 100.3, 62.9, 53.0, 33.2, 21.0, 18.4; IR (film, cmꢁ1
)
method E gave 93 (362 mg, 26%) as light-yellow crystals: mp
1
177–178ꢃC; [a]23 þ17.6 (c 0.8, CHCl3); H NMR (300 MHz,
3440(bm), 2925(w), 1746(s), 1698(s), 1510(w), 1381(m),
1350(s), 1291(w), 1233(m), 1041(w), 763(w), 701(w); HRMS
m/z (M þ Naþ) calcd. 399.1316, found 399.1301. Anal. Calcd.
for C22H20N2O4: C, 70.20; H, 5.36; N, 7.44. Found: C, 70.31;
H, 5.49; N, 7.36.
D
CD2Cl2 d) 8.67 (bs, 1H, 6-H), 7.53–7.60 (m, 2H, Ph), 7.28–
7.41 (m, 4H, 7-H, Ph), 6.87 (d, J ¼ 3.0, 1.8 Hz, 1H, 8-H),
5.59 (dd, J ¼ 9.9, 5.7 Hz, 1H, 10-H), 4.60 (dd, J ¼ 9.9, 9.9
Hz, 1H, 20-H), 4.02 (dd, 9.9, 5.5 Hz, 1H, 20-H), 3.47 (s, 3H,
OCH3), 2.67 (s, 3H, 4-CH3), 2.45 (s, 3H, 5-CH3); 13C NMR
(75 MHz, CD2Cl2, d) 170.9, 169.3, 139.9, 138.0, 129.0, 128.6,
128.1, 128.0, 127.9, 125.4, 121.9, 120.9, 120.5, 101.6, 71.5,
58.8, 53.9, 13.2, 13.1; IR (film, cmꢁ1) 3430(bs), 2900(w),
1747(m), 1693(s), 1650(m), 1394(m), 1352(m), 1092(w),
767(m), 732(m), 699(m); HRMS m/z (M þ Naþ) calcd.
371.1367, found 371.1351. Anal. Calcd. for C21H20N2O3: C,
72.40; H, 5.79; N, 8.04. Found: C, 72.22; H, 5.74; N, 7.88.
(1)-(R)-2-(2-Methoxy-1-phenylethyl)-6-methyl-2H,6H-pyr-
rolo[3,4-e]indole-1,3-dione (94). Method A with vinylpyrrole
3d and maleimide 10n gave adduct 48, which with method E
gave 94 (535 mg, 40%) as light-yellow crystals: mp 123–
(1)-(R)-2-(4,5,6-Trimethyl-1,3-dioxo-2H,6H-pyrrolo[3,4-e]
indol-2-yl)-2-phenylethyl acetate (90). Method A with vinyl-
pyrrole 3g and maleimide 10m gave adduct 44, which with
method E gave 90 (328 mg, 21%) as yellow crystals: mp 197–
198ꢃC; [a]23 þ4.1 (c 2.5, CHCl3); 1H NMR (300 MHz,
D
CDCl3, d) 7.55–7.59 (m, 2H, Ph), 7.28–7.40 (m, 3H, Ph), 7.14
(d, J ¼ 2.7 Hz, 1H, 7-H), 6.92 (d, J ¼ 3.0 Hz, 1H, 8-H), 5.62
(dd, J ¼ 9.9, 5.7 Hz, 1H, 20-H), 5.14 (dd, J ¼ 10.7, 9.9 Hz,
1H, 10-H), 4.88 (dd, J ¼ 11.1, 5.7 Hz, 1H, 10-H), 4.12 (s, 3H,
6-CH3), 2.75 (s, 3H, 4-CH3 or 5-CH3), 2.74 (s, 3H, 4-CH3 or
5-CH3), 2.01 (s, 3H, Ac); 13C NMR (75 MHz, CDCl3, d)
170.8, 169.3, 140.0, 137.1, 136.4, 129.4, 128.8, 128.3, 128.2,
126.8, 123.4, 122.0, 121.3, 116.5, 100.0, 62.9, 53.2, 38.0, 25.8,
14.5, 13.8; IR (film, cmꢁ1) 3451(bs), 1746(m), 1697(s),
1498(w), 1455(w), 1387(m), 1344(m), 1309(w), 1231(m),
1039(w), 806(w), 766(m), 730(w); HRMS m/z (M þ Naþ)
calcd. 413.1473, found 413.1456. Anal. Calcd. for
C23H22N2O4: C, 70.75; H, 5.68; N, 7.17. Found: C, 70.82; H,
5.65; N, 6.96.
124ꢃC; [a]23 þ30.4 (c 5.0, CHCl3); 1H NMR (300 MHz,
D
CD2Cl2, d) 7.59–7.62 (m, 2H, 4-H, 5-H), 7.54–7.58 (m, 2H,
Ph), 7.28–7.52 (m, 4H, 7-H and Ph), 6.94 (dd, J ¼ 3.3, 0.9
Hz, 1H, 8-H), 5.58 (dd, J ¼ 9.9, 6.3 Hz, 1H, 10-H), 4.52 (dd, J
¼ 9.6, 9.6 Hz, 1H, 20-H), 4.02 (dd, J ¼ 9.9, 6.0 Hz, 1H, 20-H),
3.89 (s, 3H, 6-CH3), 3.41 (s, 3H, OCH3); 13C NMR (75 MHz,
CDCl3, d) 170.2, 169.8, 141.0, 137.7, 134.4, 128.7, 128.3,
128.1, 124.5, 123.9, 123.5, 115.7, 113.9, 100.6, 71.4, 58.9,
53.9, 33.4; IR (film, cmꢁ1) 3443(bs), 2905(m), 2800(w),
1755(m), 1702(s), 1511(m), 1458(w), 1385(m), 1353(s),
1295(w), 1114(m), 1090(w), 748(s), 700(m); HRMS m/z (M þ
Naþ) calcd. 357.1210, found 357.1200. Anal. Calcd. for
C20H18N2O3: C, 71.84; H, 5.43; N, 8.38. Found: C, 71.61; H,
5.32; N, 8.41.
(1)-(R)-2-(2-Methoxy-1-phenylethyl)-2H,6H-pyrrolo[3,4-e]
indole-1,3-dione (91). Method A with vinylpyrrole 4 and mal-
eimide 10n gave adduct 45, which with method E gave 91
(500 mg, 39%) as light-yellow crystals: mp 63–64ꢃC; [a]23
D
þ27.0 (c 5.0, CHCl3); 1H NMR (300 MHz, CDCl3, d) 8.75
(bs, 1H, 6-H), 7.55–7.60 (m, 4H, 4-H and 5-H and Ph), 7.28–
7.43 (m, 4H, 7-H and Ph), 6.98 (dd, J ¼ 3.3, 1.8 Hz, 1H, 8-
H), 5.63 (dd, J ¼ 10.2, 5.7 Hz, 1H, 10-H), 4.69 (dd, J ¼ 10.2,
10.2 Hz, 1H, 20-H), 4.01 (dd, J ¼ 10.2, 5.7 Hz, 1H, 20-H),
3.47 (s, 3H, OCH3); 13C NMR (75 MHz, CDCl3, d) 170.4,
169.9, 140.6, 137.5, 130.3, 128.9, 128.4, 128.2, 124.0, 123.1,
(1)-(R)-2-(2-Methoxy-1-phenylethyl)-5,6-dimethyl-2H,6H-
pyrrolo[3,4-e]indole-1,3-dione (95). Method A with vinylpyr-
role 3c and maleimide 10n gave adduct 49, which with
method E gave 95 (446 mg, 32%) as orangish-yellow crystals:
mp 157–158ꢃC; [a]23 þ30.2 (c 5.0, CHCl3); 1H NMR (300
122.8, 115.9, 115.8, 101.5, 71.4, 58.9, 53.8; IR (film, cmꢁ1
)
D
MHz, CD2Cl2, d) 7.53–7.58 (m, 2H, Ph), 7.27–7.39 (m, 4H, 4-
H, Ph), 7.25 (d, J ¼ 3.3 Hz, 1H, 7-H), 6.89 (d, J ¼ 3.3 Hz,
1H, 8-H), 5.54 (dd, J ¼ 9.6, 5.7 Hz, 1H, 10-H), 4.49 (dd, J ¼
9.6, 9.6 Hz, 1H, 20-H), 4.12 (s, 3H, 6-CH3), 4.02 (dd, J ¼ 9.6,
6.0 Hz, 1H, 20-H), 3.40 (s, 3H, OCH3), 2.88 (s, 3H, 5-CH3);
13C NMR (75 MHz, CD2Cl2, d) 170.0, 169.6, 139.4, 138.1,
136.0, 128.6, 128.2, 127.9, 127.7, 124.8, 124.4, 121.8, 117.6,
99.9, 71.3, 58.6, 53.6, 37.1, 20.0; IR (film, cmꢁ1) 3440(bs),
2999(w), 2933(w), 2805(w), 1750(m), 1696(s), 1518(w),
1495(w), 1404(w), 1347(s), 1116(m), 1092(w), 760(w),
750(w), 730(w), 701(m), 661(m); HRMS m/z (M þ Naþ)
calcd. 371.1367, found 371.1372. Anal. Calcd. for
C21H20N2O3: C, 72.40; H, 5.79; N, 8.04. Found: C, 72.56; H,
5.93; N, 7.96.
3402(bs), 1754(m), 1699(s), 1610(m), 1458(w), 1393(w),
1353(s), 1109(w), 750(m), 700(m); HRMS m/z (M þ Naþ)
calcd. 343.1054, found 343.1045. Anal. Calcd. for
C19H16N2O3: C, 71.24; H, 5.03; N, 8.74. Found: C, 71.46; H,
5.14; N, 8.82.
(1)-(R)-2-(2-Methoxy-1-phenylethyl)-4-methyl-2H,6H-pyr-
rolo[3,4-e]indole-1,3-dione (92). Method A with vinylpyrrole
3b and maleimide 10n gave adduct 46, which with method E
gave 92 (401 mg, 30%) as dark-yellow crystals: mp 139–
140ꢃC; [a]23 þ14.9 (c 2.3, CHCl3); 1H NMR (300 MHz,
D
CDCl3, d) 8.68 (bs, 1H, 6-H), 7.57–7.60 (m, 2H, Ph), 7.28–
7.40 (m, 5H, 5-H and 7-H and Ph), 6.79–6.81 (m, 1H, 8-H),
5.62 (dd, J ¼ 10.2, 5.7 Hz, 1H, 10-H), 4.77 (dd, J ¼ 10.2, 10.2
Hz, 1H, 20-H), 4.00 (dd, J ¼ 10.2, 5.4 Hz, 1H, 20-H), 3.52 (s,
3H, OCH3), 2.65 (d, J ¼ 0.9 Hz, 3H, 4-CH3); 13C NMR (75
MHz, CD2Cl2, d) 170.4, 169.6, 140.5, 137.9, 130.3, 129.5,
128.7, 128.6, 128.2, 128.1, 123.3, 121.3, 117.2, 101.1, 71.4,
(1)-(R)-2-(2-Methoxy-1-phenylethyl)-4,6-dimethyl-2H,6H-
pyrrolo[3,4-e]indole-1,3-dione (96). Method A with vinylpyr-
role 3f and maleimide 10n gave adduct 50, which with method
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2009 Access to Indoles via Diels-Alder Reactions of 2-Vinylpyrroles with Maleimides
1175
E gave 96 (404 mg, 29%) as yellow crystals: mp 132–133ꢃC;
301; (c) Salmon, M.; Kanazawa, K. K.; Diaz, A. F.; Krounbi, M. J
Polym Sci Polym Lett Ed 1982, 20, 187; (d) Lamb, B. S.; Koviac, P.
J Polym Sci Polym Lett Ed 1980, 18, 1759; (e) Potts, H. A.; Smith,
G. F. J Chem Soc 1957, 4018.
1
[a]23 þ30.2 (c 5.0, CHCl3); H NMR (300 MHz, CD2Cl2, d)
D
7.54–7.58 (m, 2H, Ph), 7.30–7.40 (m, 5H, 5-H and 7-H and Ph),
6.88 (dd, J ¼ 3.0, 0.9 Hz, 1H, 8-H), 5.57 (dd, J ¼ 9.3, 6.0 Hz,
1H, 10-H), 4.53 (dd, J ¼ 9.9, 9.9 Hz, 1H, 20-H), 4.04 (dd, J ¼
9.9, 6.3 Hz, 1H, 20-H), 3.82 (s, 3H, 6-CH3), 3.42 (s, 3H, OCH3),
2.77 (d, J ¼ 0.9 Hz, 3H, 4-CH3); 13C NMR (75 MHz, CDCl3, d)
170.6, 169.6, 141.0, 138.0, 133.7, 129.8, 128.8, 128.4, 128.1,
123.7, 122.0, 121.3, 115.2, 100.1, 71.4, 58.9, 53.7, 33.0, 18.3;
IR (film, cmꢁ1) 3442(bs), 2915(w), 2790(w), 1749(m), 1697(s),
1636(m), 1508(w), 1350(m), 1291(w), 1104(w), 762(m),
700(m); HRMS m/z (M þ Naþ) calcd. 371.1367, found
371.1381. Anal. Calcd. for C21H20N2O3: C, 72.40; H, 5.79; N,
8.04. Found: C, 72.30; H, 5.81; N, 7.84.
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(1)-(R)-2-(2-Methoxy-1-phenylethyl)-4,5,6-trimethyl-2H,6H-
pyrrolo[3,4-e]indole-1,3-dione (97). Method A with vinylpyr-
role 3g and maleimide 10n gave adduct 51, which with
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method E gave 97 (333 mg, 23%) as dark-orange crystals: mp
1
164–165ꢃC; [a]23 þ26.5 (c 0.4, CHCl3); H NMR (300 MHz,
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D
CD2Cl2, d) 7.52–7.58 (m, 2H, Ph), 7.28–7.40 (m, 3H, Ph),
7.17 (d, J ¼ 3.0 Hz, 1H, 7-H), 6.86 (d, J ¼ 3.3 Hz, 1H, 8-H),
5.56 (dd, J ¼ 9.6, 6.0 Hz, 1H, 10-H), 4.50 (dd, J ¼ 9.6, 9.6
Hz, 1H, 20-H), 4.10 (s, 3H, 6-CH3), 4.04 (dd, J ¼ 9.9, 6.0 Hz,
1H, 20-H), 3.42 (s, 3H, OCH3), 2.73 (s, 3H, 4-CH3 or 5-CH3),
2.72 (s, 3H, 4-CH3 or 5-CH3); 13C NMR (75 MHz, CD2Cl2, d)
170.9, 169.4, 139.9, 138.2, 136.4, 129.2, 128.5, 128.1, 127.8,
126.9, 123.2, 122.0, 121.3, 99.5, 71.4, 58.6, 53.3, 37.9, 14.3,
13.4; IR (film, cmꢁ1) 3450(bs), 2932(w), 1748(m), 1695(s),
1519(w), 1496(w), 1395(m), 1345(m), 1309(w), 1112(w),
765(m), 731(m), 700(m); HRMS m/z (M þ Naþ) calcd. for
C22H22N2O3: 385.1523, found 385.1518.
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ples given, only two products are 2-H indoles, both of which are 3-Me
indoles and only one of which has an N-H.
1H and 13C NMR spectra for compounds 3a-3c, 3e-3g, 5b,
7, 10m, 10n, 11-38, 53-97, the 1H NMR spectrum for com-
pound 52, biological activity data for compounds 63 and 66,
and X-ray data for 7 in CIF format. This material is available
online free of charge (see Supporting Information).
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Acknowledgment. N.P.L, L.V., N.F.A, and G.C.G. thank the
Wayland E. Noland Research Fund for generous financial support
of this project.
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