Diels-Alder reactions of fused 5-, 6- and 7-membered ring 2-vinylindoles: Synthesis of annulated tetrahydrocarbazoles

Article abstract of DOI:10.1016/j.tet.2017.09.025

Scaffolds of tetrahydrocarbazoles are an important class of biologically active compounds found abundant in nature. In the present investigation, functionalized polycyclic tetrahydrocarbazoles were synthesized using Diels-Alder cycloaddition between fused

Full text of DOI:10.1016/j.tet.2017.09.025

Tetrahedron xxx (2017) 1e6
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Diels-Alder reactions of fused 5-, 6- and 7-membered ring
2
-vinylindoles: Synthesis of annulated tetrahydrocarbazoles
*
Wayland E. Noland , Ryan J. Herzig, Honnaiah Vijay Kumar, Venkata Srinivasarao Narina,
Pavel K. Elkin, Karen I. Valverde, Briana L. Kim
Department of Chemistry, University of Minnesota, Minneapolis, MN, 55455, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 16 August 2017
Received in revised form
Scaffolds of tetrahydrocarbazoles are an important class of biologically active compounds found abun-
dant in nature. In the present investigation, functionalized polycyclic tetrahydrocarbazoles were syn-
thesized using Diels-Alder cycloaddition between fused 5-, 6- and 7-membered ring 2-vinylindoles and
various dienophiles. The dienophiles used were N-phenylmaleimides, 1,4-naphthoquinone, and dimethyl
acetylenedicarboxylate (DMAD). When 1,4-naphthoquinone was used as a dienophile, the 5-membered
ring Diels-Alder adduct was obtained in the oxidized form, but this form was not observed in the case of
12 September 2017
Accepted 13 September 2017
Available online xxx
6
- and 7-membered ring Diels-Alder adducts. The desired product yields ranged from 60e70% and the
Keywords:
Tetrahydrocarbazoles
Diels-Alder
1
structure of final compounds were determined using 1D and 2D NMR analysis. H NMR studies
confirmed excellent diastereoselectivity (>99% de).
2-Vinylindoles
Published by Elsevier Ltd.
1
. Introduction
cycloaddition reaction with suitable dienophiles and 2-vinylindoles
3
4e36
have been reported.
We first published the synthesis of carbazoles through Diels-
Tetrahydrocarbazoles are well-known chemical intermediates
1
37
38
used in the synthesis of many natural alkaloids, hydrogen bond-
sensitive fluorescent probes, luminogenic molecules, and poten-
tial materials for on-board organic hydrogen storage compounds.
Some of the tetrahydrocarbazole derivatives are also found to
exhibit antibacterial, anti-HPV, and cytotoxic activities against
human cancer cells.7 N-Phenylmaleimides, 1,4-naphthoquinones
and DMAD are important intermediates for the synthesis of a va-
riety of biologically active molecules.
-Vinylindoles can undergo various Diels-Alder reactions.
Alder reactions of 3-vinylindoles in 1959 and 1963. Also, we
reported that carbazoles and tetrahydrocarbazoles are obtained
from 3-vinylindoles, which are trapped in situ by Diels-Alder re-
2
3
4
3
9,40
41
actions with maleimides,
maleic anhydride, and maleic acid.
5
6
We are reporting the synthesis of 15 novel polycyclic tetrahy-
drocarbazoles by the [4þ2] cycloaddition Diels-Alder reaction us-
ing fused 5-, 6-, and 7-membered ring 2-vinylindoles with selected
dienophiles (Fig. 1).
8
e25
2
6,27
2
The derivatives of 2-vinylindoles, however, have not received an
equal amount of attention relative to 3-vinylindoles, which can be
2. Results and discussion
2
8
attributed to difficulties surrounding their synthesis. Despite the
difficulty of synthesis, 2-vinylindoles have been used as in-
The preparation of 2-vinylindoles with varying ring sizes (4, 8a,
8b, Schemes 1 and 2) is the appropriate platform to obtain the
2
9
termediates in the formation of Aspidosperma alkaloids.
2-
Vinylindoles have been studied as [4þ2] components in a limited
desired Diels-Alder adducts (Scheme 3). Synthesis of compound 4 is
3
0
42e44
number of Diels-Alder reactions including cycloadditions with
shown in Scheme 1, following the reported procedures.
The
31
tetrazines and synthesis of carbazoles and 1,2 disubstituted car-
synthesis of a fused 5-membered ring 2-vinylindole 4 involves a
tandem-Michael coupling reaction from ethyl indole-2-carboxylate
1 with ethyl acrylate using sodium hydride as a base, giving the
tricyclic ketoester 2. The latter was then hydrolyzed and decar-
boxylated using 6 N HCl, giving 3, followed by Wittig olefination,
giving 4 in 71% yield. In order to detect the presence of side re-
actions coming from 2-vinylindole, proton NMR studies were
bazoles.3
2,33
Recently, structurally unique and functionally
enriched carbazoles and tetrahydrocarbazoles via the [4þ2]
*
Corresponding author.
E-mail address: nolan001@umn.edu (W.E. Noland).
http://dx.doi.org/10.1016/j.tet.2017.09.025
040-4020/Published by Elsevier Ltd.
0
Please cite this article in press as: Noland WE, et al., Diels-Alder reactions of fused 5-, 6- and 7-membered ring 2-vinylindoles: Synthesis of
annulated tetrahydrocarbazoles, Tetrahedron (2017), http://dx.doi.org/10.1016/j.tet.2017.09.025

2
W.E. Noland et al. / Tetrahedron xxx (2017) 1e6
Fig. 1. Synthesis of tetrahydrocarbazole scaffolds via Diels-Alder reactions.
Scheme 1. Synthesis of fused 5-membered ring 2-vinylindole 4.
Scheme 2. Synthesis of fused 6- and 7-membered ring 2-vinylindoles 8a and 8b.
ꢀ
performed. The attempted reaction was run for 24 h at 50 C and
subjected to Wittig olefination, which gave the corresponding
compounds 8a and 8b in 69 and 65% yields.
1
the H NMR spectrum of the crude product showed the same
pattern as prior to the attempted reaction. This gave evidence that 4
did not react with itself or the solvent to form any side products
under the reaction conditions.
Under the reaction conditions, compound 2 gave only the keto
form, but compounds 6a and 6b were in a keto-enol tautomeric
mixture. We have observed an approximately 1:1 keto-enol ratio
for 6a and 6b, whereas previous literature reported 1:3 keto-enol
Scheme 2 shows the synthetic route to obtain the key in-
4
3
termediates 8a and 8b, by following the literature procedures with
ratios for 6a. The coexistence of both the keto and enol tauto-
mild variations.4
4,45
Compound
1
reacted with ethyl 4-
mers was determined by H NMR studies. Compound 6a in CD
solution showed a narrow singlet at 12.2 ppm and two triplets for
CH protons, centered at 1.37 and 1.30 ppm. For 6b there was also a
1
2 2
Cl
bromobutyrate or ethyl 4-bromopentanoate in the presence of
sodium hydride to give the open indole diesters 5a and 5b, These
were isolated and cyclized using potassium tert-butoxide in tetra-
hydrofuran (THF) giving indole esters 6a and 6b. Hydrolysis and
decarboxylation using either acidic or basic conditions gave the
desired ketones 7a and 7b in 80e94% yield. These were then
3
narrow singlet at 12.9 ppm and two triplets for CH
centered at 1.36 and 1.26 ppm.
3
protons,
With the synthesis of a set of 2-vinylindoles with an additional
ring annulated onto C2 and N of the indole scaffolds, compounds 4,
Please cite this article in press as: Noland WE, et al., Diels-Alder reactions of fused 5-, 6- and 7-membered ring 2-vinylindoles: Synthesis of
annulated tetrahydrocarbazoles, Tetrahedron (2017), http://dx.doi.org/10.1016/j.tet.2017.09.025

W.E. Noland et al. / Tetrahedron xxx (2017) 1e6
3
Scheme 3. Diels-Alder reactions of fused 5-, 6-, and 7-membered ring 2-vinylindoles and selected dienophiles. *For compound 13a.
8
a, and 8b, undergo Diels-Alder reactions with dienophiles, such as
spectroscopy (COSY), and heteronuclear multiple bond correlation
(HMBC). 1D gradient NOE experiments were performed on three
tetrahydrocarbazoles (9c, 10a, and 10b, one of each fused ring size).
unsubstituted and substituted N-phenylmaleimides, 1,4-
naphthoquinone, and DMAD, giving fused tetrahydrocarbazoles
9
a-13c (Scheme 3) in good yields (60e70%) with excellent dia-
The NOE enhancements of H
ating H . These interactions were consistent with syn stereochem-
istry of H , H , and H (Fig. 2).
We suspect similar stereochemistry for the other Diels-Alder
i m
and H were observed when irradi-
stereoselectivity (>99% de). N-Arylmaleimides with electron
donating or withdrawing groups all worked well under the reaction
conditions without undergoing any side reactions. In the case of
l
i
m
l
1
1,4-naphthoquinone, the reaction gave Diels-Alder adducts; how-
adducts and at least 99% diastereoselectivity was observed by
NMR for all Diels-Alder products.
H
ever, unlike the other dienophiles, the 5-memberend ring 2-
vinylindole gave the oxidized form of the Diels-Alder product 13a
in a 31% yield. This oxidation is presumed due to the higher steric
strain of the smaller ring size. An attempted Diels-Alder reaction
with 1,4-benzoquinone, a highly reactive dienophile, and 4 gave no
expected Diels-Alder adduct. The reaction was allowed to run for
3. Conclusion
A strategy for the construction of functionalized novel tetrahy-
drocarbazoles via DielseAlder reaction using 5-, 6- and 7-
membered ring 2-vinylindoles with various dienophiles is re-
ported. The synthetic routes to obtain annulated tetrahy-
drocarbazoles are versatile, and the starting materials are easily
prepared. All the Diels-Alder products yields range from 60-70%. A
5-membered ring Diels-Alder adduct was obtained in the oxidized
form in 31% yield when 1,4-naphthoquinone was used as a dien-
ophile. The structures of the compounds were elucidated, including
the relative stereochemistry by 1D and 2D NMR experiments.
ꢀ
1
120 h at 50 C but the crude H NMR spectrum showed only the
diene starting material and what appeared to be a polymerized
form of 1,4-benzoquinone.
Rearranged Diels-Alder adducts were obtained with five-, six-,
and seven-membered ring 2-vinylindoles. The unrearranged Diels-
Alder adducts were not obtained, probably because subsequent
facile isomerization of the double bond into the five-membered
ring of the indole gave the more stable aromatized tetrahy-
drocarbazoles (Scheme 3). The five, six and seven-membered Diels-
Alder intermediates were probably protonated on the exo face by
residual acid, followed by aromatization.
The structures of tetrahydrocarbazoles 9e11 a-c were eluci-
dated using 1D and 2D NMR techniques such as H NMR, C NMR,
heteronuclear single quantum coherence (HSQC), correlation
4. Experimental
4
6
4.1. General information
1
13
All reagents and solvents were purchased and used without
further purification. The procedures for the synthesis and the
spectra of the known starting materials 2, 3, 4, 5a, 5b, 6a, 6b, 7a, 7b,
and 8a are provided in the supplementary information. Com-
pounds 4, 8a, and 8b were purified using activated neutral alumina,
and other compounds were purified using silica gel (particle size
2
30e450 mesh) with column chromatography using reagent grade
ꢀ
ethyl acetate and hexanes (bp 68 C) as the eluents. All reactions
were monitored by thin-layer chromatography (TLC) on 0.2 mm
f
silica gel plates using F254 fluorescence indicator. All R values were
determined using an EtOAc:hexane solution. The melting points
recorded are uncalibrated and uncorrected. Elemental analyses
were performed by M-H-W Laboratories, Phoenix, AZ. or Atlantic
Fig. 2. General stereochemistry of the tetrahydrocarbazoles.
Please cite this article in press as: Noland WE, et al., Diels-Alder reactions of fused 5-, 6- and 7-membered ring 2-vinylindoles: Synthesis of
annulated tetrahydrocarbazoles, Tetrahedron (2017), http://dx.doi.org/10.1016/j.tet.2017.09.025

4
W.E. Noland et al. / Tetrahedron xxx (2017) 1e6
Microlab, Inc., Norcross, GA. High-resolution mass spectra were
recorded using ESI/TOF or EI-GC/QTOF. NMR spectra were recorded
on a Bruker 500 MHz, Bruker 400 MHz, or a Varian 300 MHz in-
strument. Chemical shifts of H NMR spectra are given in parts per
million and the coupling constant J was measured in Hz. The signals
4.3.2. rac-(7aR,8aR,11aR)-10-(4-Bromophenyl)-7,7a,8,8a,10,11a-
hexahydro-6H-dipyrrolo[3,4-c:1 ,2 ,3 -lm]carbazole-9,11-dione
(10a)
0
0
0
1
ꢀ
Yield (0.539 g, 64%) as an off-white solid: mp 270e272.5 C;
¼ 0.56 (1:1); IR (neat, NaCl) max 3046, 2926, 2854, 1711, 1490,
1448, 1375, 1298, 1167 cm ; H NMR (400 MHz, CD Cl 8.00 (d,
R
f
y
ꢂ1
1
from the CH
the reference peaks in the H NMR and C NMR spectra, respec-
tively. The signals from the CHCl in the solvent CDCl , 7.24 and
7.23 ppm, are set as the reference peaks in the H NMR and
2
Cl
2
in the solvent CD
2
Cl
2
, 5.32 and 54.0 ppm, are set as
2
2
) d
1
13
J ¼ 7.4 Hz, 1H), 7.62e7.59 (m, 2H), 7.26 (d, J ¼ 7.7 Hz, 1H), 7.22e7.19
(m, 2H), 7.15e7.07 (m, 2H), 4.45 (dd, J ¼ 8.0, 1.9 Hz, 1H), 4.25 (td,
J ¼ 10.2, 6.2 Hz, 1H), 4.07 (t, J ¼ 9.8 Hz, 1H), 3.57 (ddd, J ¼ 13.0, 8.0,
5.2 Hz, 1H), 3.37e3.28 (m, 1H), 2.89 (quintet, J ¼ 6.5 Hz, 1H), 2.79
(dt, J ¼ 12.4, 5.2 Hz, 1H), 2.18 (dq, J ¼ 12.5, 9.5 Hz, 1H), 1.33e1.24
3
3
1
13
7
C
NMR spectra, respectively. The following abbreviations were used
to describe the multiplicities: s ¼ singlet, d ¼ doublet, t ¼ triplet,
q ¼ quartet, m ¼ multiplet, dd ¼ doublet of doublets, ddd ¼ doublet
of doublets of doublets, dt ¼ doublet of triplets, td ¼ triplet of
doublets, dq ¼ doublet of quartets.
13
2 2
(quartet like, 1H) ppm; C NMR (100 MHz, CD Cl ) d 177.7, 175.5,
150.5, 137.1, 132.7, 131.9, 130.8, 128.8, 122.6, 122.2, 121.4, 119.9, 110.6,
98.3, 46.6, 44.3, 41.5, 38.5, 34.1, 31.9 ppm; HRMS (ESIþ) calcd. for
þ
C
C
22
H
H
17BrN
17BrN
2
O
O
2
Na [M þ Na] : 443.0366. found: 443.0354; For
4
.2. Procedure for synthesis of compound 8b43
22
2
2
(421.29) Calcd. C 62.72, H 4.07, N 6.65, Br 18.97;
Found C 62.66, H 4.11, N 6.66, Br 18.82.
n-BuLi (2.5 M, 8.8 mL, 22.0 mmol, 1.1 eq) was added to a well-
stirred suspension of methyltriphenylphosphonium bromide
4.3.3. rac-(7aR,8aR,11aR)-10-(4-Methoxyphenyl)-7,7a,8,8a,10,11a-
hexahydro-6H-dipyrrolo[3,4-c:1 ,2 ,3 -lm]carbazole-9,11-dione
ꢀ
0
0
0
(
7.86 g, 22.0 mmol, 1.1 eq) in anhydrous THF (75 mL) at 0 C, under
N
2
. After 30 min a solution of 7b (20.0 mmol, 1 eq) in anhydrous
(11a)
ꢀ
THF (75 mL) was added dropwise, and the reaction was stirred at
0
Yield (0.447 g, 60%) as an off-white solid: mp 230e232 C;
¼ 0.45 (1:1); IR (neat, NaCl) max 3051, 2980, 2955, 2931, 2853,
2834,1709,1641,1609,1513,1448,1383,1301,1285,1247,1178,1122,
ꢀ
C for 2 h. The reaction was quenched with water (50 mL),
R
f
y
extracted with DCM (4 ꢁ 40 mL) and concentrated under vacuum.
ꢂ1
1
Purification by column chromatography gave compound 8b.
2 2
1035 cm ; H NMR (400 MHz, CD Cl ) d 8.04e8.02 (m,1H), 7.27 (d,
J ¼ 7.4 Hz 1H), 7.20e7.16 (m, 2H), 7.14e7.08 (m, 2H), 7.01e6.97 (m,
2H), 4.41 (dd, J ¼ 7.9, 1.9 Hz, 1H), 4.24 (td, J ¼ 10.1, 6.2 Hz, 1H), 4.06
(t, J ¼ 9.9 Hz, 1H), 3.83 (s, 3H), 3.53 (ddd, J ¼ 12.9, 7.9, 5.2 Hz, 1H),
3.34e3.26 (m, 1H), 2.87 (quintet, J ¼ 6.5 Hz, 1H), 2.78 (dt, J ¼ 12.4,
4
(
.2.1. 10-Methylene-7,8,9,10-tetrahydro-6H-azepino[1,2-a]indole
8b)
Colorless oil/semi-solid (2.56 g, 65%); R
NaCl) max 3048, 2973, 2925, 2829, 1458, 1411, 1378, 1365, 1321,
310,1271,1228,1164 cm ; H NMR (400 MHz, CD
m, 1H), 7.33e7.31 (m, 1H), 7.21e7.16 (m, 1H), 7.09e7.05 (m, 1H),
f
¼ 0.69 (1:4); IR (neat,
Cl 7.57e7.55
y
5.2 Hz, 1H), 2.18 (dq, J ¼ 12.5, 9.5 Hz, 1H), 1.28 (quartet like, 1H)
ꢂ1
1
13
1
(
2
2
)
d
ppm; C NMR (100 MHz, CD
2
Cl
2
)
d
178.3, 176.1, 160.0, 150.5, 137.1,
130.9, 128.5, 125.4, 122.3, 121.3, 119.8, 114.8, 110.6, 98.6, 56.0, 46.5,
6
4
(
.50 (d, J ¼ 0.7 Hz, 1H), 5.38 (d, J ¼ 2.3 Hz, 1H), 5.20e5.19 (m, 1H),
44.2, 41.4, 38.5, 34.2, 31.9 ppm; HRMS (ESIþ) calcd. for
þ
.15e4.13 (m, 2H), 2.58e2.55 (m, 2H), 2.01e1.96 (m, 2H), 1.94e1.88
C
C
23
H
H
20
N
N
2
O
O
3
Na [M
þ
Na] : 395.1366. found: 395.1367; For
m, 2H) ppm; 13C NMR (100 MHz, CD
Cl
2
)
d
144.7, 143.2, 138.4,
(372.42) Calcd. C 74.18, H 5.41, N 7.52; Found C 73.88, H
2
23
20
2
3
1
2
28.4, 121.8, 120.8, 119.8, 116.2, 109.7, 100.8, 45.7, 36.7, 30.2,
5.41, N 7.40.
þ
H15N [M ]: 197.1199. found:
9.5 ppm; HRMS (EI) calcd. for C14
15N (197.28) Calcd. C 85.24, H 7.66, N 7.10; Found
C 84.94, H 7.56, N 7.01.
197.1199; For C14
H
4.3.4. Dimethyl rac-1,2,2a,3-tetrahydropyrrolo[3,2,1-jk]carbazole-
4,5-dicarboxylate (12a)
ꢀ
Yield (0.436 g, 70%) as yellow crystals: mp 172.5e173 C;
¼ 0.60 (1:1); IR (neat, NaCl) max 3051, 2949, 2885, 1733, 1698,
4
.3. Procedure for synthesis of Diels-Alder adducts
R
f
y
1623, 1564, 1537, 1446, 1434, 1389, 1328, 1270, 1238, 1196, 1171,
ꢂ1
1
A solution of diene (2.0 mmol,1 eq), dienophile (2.0 mmol,1 eq),
1146, 1124, 1096, 1067, 1046 cm
; H NMR (400 MHz, CD Cl )
2 2
ꢀ
and toluene (6.0 mL) was stirred at 50 C under N
2
for 24 h (120 h
d 7.37e7.35 (m,1H), 7.27e7.25 (m,1H), 7.16e7.09 (m, 2H), 4.26e4.16
for 13a). The reaction was allowed to cool to rt and the solvent was
removed under vacuum. Products 12a, 12b, 12c, 13a, and 13c were
purified by column chromatography. All products were then
(m, 2H), 3.97 (s, 3H), 3.75 (s, 3H), 3.58 (dq, J ¼ 16.3, 8.8 Hz, 1H), 3.25
(dd, J ¼ 16.5, 8.7 Hz, 1H), 3.00e2.93 (m, 1H), 2.42e2.33 (m, 2H)
13
2 2
ppm; C NMR (100 MHz, CD Cl ) d 169.8, 167.7, 154.8, 139.7, 136.6,
ꢀ
recrystallized using a DCM and petroleum ether (bp 60 C) system.
128.6, 121.7, 121.5, 119.1, 118.4, 111.5, 101.4, 52.8, 52.2, 48.2, 39.6,
þ
3
2.5, 30.8 ppm; HRMS (ESIþ) calcd. for C18
334.1050. found: 334.1050; For C18 17NO
5.50, N 4.50; Found C 69.17, H 5.46, N 4.46.
H
17NO
4
Na [M þ Na] :
4
6
.3.1. rac-(7aR,8aR,11aR)-10-Phenyl-7,7a,8,8a,10,11a-hexahydro-
H
4
(311.34) Calcd. C 69.44, H
0
0
0
H-dipyrrolo[3,4-c:1 ,2 ,3 -lm]carbazole-9,11-dione (9a)
ꢀ
Yield (0.452 g, 66%) as a white solid: mp 262e264 C; R
1:1); IR (neat, NaCl) max 3045, 2948, 2891, 2854, 1774, 1713, 1640,
596, 1497, 1450, 1380, 1336, 1314, 1299, 1288, 1269, 1232, 1183,
f
¼ 0.65
(
1
y
4.3.5. rac-6,7,7a,8-Tetrahydronaphtho[2,3-c]pyrrolo[1,2,3-lm]
carbazole-9,14-dione (13a)
ꢂ1
1
ꢀ
1
7
(
4
150 cm
.50e7.47 (m, 2H), 7.43e7.40 (m, 1H), 7.29e7.27 (m, 3H), 7.16e7.07
m, 2H), 4.44 (dd, J ¼ 8.0, 2.0 Hz, 1H), 4.25 (td, J ¼ 10.1, 6.2 Hz, 1H),
.07 (t, J ¼ 9.5 Hz,1H), 3.56 (ddd, J ¼ 12.9, 8.0, 5.2 Hz,1H), 3.36e3.28
;
H NMR (400 MHz, CD
2
Cl
2
)
d
8.03e8.01 (m, 1H),
Yield (0.202 g, 31%) as purple crystals: mp 258e260 C; R
f
¼ 0.49
(1:4); IR (neat, NaCl)
1611, 1592, 1582, 1562, 1505, 1443, 1342, 1325, 1290, 1259 cm ; H
NMR (400 MHz, CD Cl 8.38e8.36 (m, 1H), 8.19e8.17 (m, 1H),
ymax 3424, 2924, 2853, 2360, 2343, 1659, 1634,
ꢂ1
1
2
2
) d
(
2
m, 1H), 2.88 (quintet, J ¼ 6.5 Hz, 1H), 2.79 (dt, J ¼ 12.4, 5.2 Hz, 1H),
8.10e8.08 (m, 1H), 7.76e7.70 (m, 2H), 7.32e7.30 (m, 1H), 7.24e7.17
(m, 2H), 4.33e4.29 (m, 2H), 3.83 (dd, J ¼ 16.9, 8.3 Hz,1H), 3.68e3.58
(m, 1H), 3.12e3.05 (m, 1H), 2.56e2.45 (m, 1H), 2.43e2.35 (m, 1H)
13
.19 (dq, J ¼ 12.6, 9.5 Hz, 1H), 1.35e1.26 (quartet like, 1H) ppm;
Cl 178.1, 175.9, 150.5, 137.1, 132.8, 130.9,
29.5, 129.0, 127.3, 122.3, 121.4, 119.8, 110.6, 98.5, 46.5, 44.3, 41.4,
C
NMR (100 MHz, CD
1
3
2
2
) d
13
2 2
ppm; C NMR (100 MHz, CD Cl ) d 185.3, 184.0, 157.3, 143.1, 137.3,
8.5, 34.1, 31.9 ppm; HRMS (ESIþ) calcd. for C22
H
18
N
2
O
2
Na [M þ
135.2, 134.0, 133.5, 133.1, 132.5, 130.0, 126.5, 126.4, 123.8, 122.3,
þ
Na] : 365.1260. found: 365.1260; For C22
18
H N
2
O
2
(342.40) Calcd. C
122.0, 111.1, 101.4, 48.0, 39.2, 31.0, 29.8 ppm; HRMS (ESIþ) calcd. for
þ
7
7.17, H 5.30, N 8.18; Found C 76.88, H 5.18, N 8.16.
C
22
H15NO
2
Na [M
þ
Na] : 348.0995. found: 348.0995; For
Please cite this article in press as: Noland WE, et al., Diels-Alder reactions of fused 5-, 6- and 7-membered ring 2-vinylindoles: Synthesis of
annulated tetrahydrocarbazoles, Tetrahedron (2017), http://dx.doi.org/10.1016/j.tet.2017.09.025

W.E. Noland et al. / Tetrahedron xxx (2017) 1e6
5
C
22
H
15NO
2
(325.37) Calcd. C 81.21, H 4.65, N 4.30; Found C 80.94, H
4.3.10. rac-(8aR,9aS,15aS)-7,8,8a,9,9a,15a-Hexahydro-6H-naphtho
[2,3-c]pyrido[1,2,3-lm]carbazole-10,15-dione (13b)
Yield (0.451 g, 66%) as green crystals: mp 178e180 C; R
(1:2); IR (neat, NaCl)
1293, 1244, 1194, 1003 cm
8.14e8.12 (m, 1H), 8.08e8.05 (m, 1H), 7.82e7.77 (m, 2H), 7.52 (d,
4
.55, N 4.29.
ꢀ
f
¼ 0.54
4.3.6. rac-(8aR,9aS,12aR)-11-Phenyl-6,7,8,8a,9,9a,11,12a-
ymax 3049, 2939, 2854, 1684, 1592, 1460, 1339,
ꢂ1
1
octahydropyrido[1,2,3-lm]pyrrolo[3,4-c]carbazole-10,12-dione (9b)
;
2 2
H NMR (400 MHz, CD Cl )
ꢀ
Yield (0.478 g, 67%) as a white solid: mp 232e234 C; R
f
¼ 0.42
d
(
1:2); IR (neat, NaCl)
y
max 3471, 3047, 2942, 2852, 1777, 1714, 1596,
J ¼ 7.7 Hz, 1H), 7.32 (d, J ¼ 7.9 Hz, 1H), 7.21e7.11 (m, 2H), 4.54 (d,
J ¼ 6.0 Hz, 1H), 4.30 (dd, J ¼ 11.5, 5.2 Hz, 1H), 3.71 (td, J ¼ 11.9,
5.5 Hz, 1H), 3.56 (ddd, J ¼ 12.7, 6.1, 2.4 Hz, 1H), 3.08e3.00 (m, 1H),
2.28e2.02 (m, 4H), 1.68e1.59 (quartet like, 1H), 1.27 (dq, J ¼ 12.6,
ꢂ1
1
1497, 1456, 1378, 1309, 1269, 1222, 1181, 1126, 1083, 1015 cm ; H
NMR (400 MHz, CD
2
Cl
2
)
d
8.03 (d, J ¼ 7.8 Hz, 1H), 7.53e7.15 (m, 8H),
4
8
2
.36e4.28 (m, 2H), 3.70 (td, J ¼ 11.9, 4.9 Hz, 1H), 3.43 (ddd, J ¼ 13.0,
13
.0, 5.2 Hz, 1H), 2.95e2.89 (m, 1H), 2.57 (dt, J ¼ 12.6, 4.6 Hz 1H),
.29e2.08 (m, 3H), 1.58 (q, J ¼ 12.4 Hz 1H), 1.37e1.27 (m, 1H) ppm;
2 2
3.1 Hz) ppm; C NMR (100 MHz, CD Cl ) d 199.3,196.8,138.5,138.3,
136.1, 135.1, 134.7, 134.4, 129.3, 127.50, 127.48, 121.4, 120.2, 120.1,
1
3
C NMR (100 MHz, CD
2
Cl
2
)
d
178.5, 176.4, 138.7, 137.9, 132.9, 129.5,
109.8, 104.2, 51.1, 46.6, 43.1, 35.4, 33.8, 27.7, 24.1 ppm; HRMS (ESIþ)
þ
128.9, 127.8, 127.3, 121.6, 121.4, 120.3, 109.5, 100.8, 42.8, 41.9, 40.6,
calcd. for C23
19NO
H19NO
2
Na [M þ Na] : 364.1308. found: 364.1300; For
3
3.2, 32.2, 27.9, 23.7 ppm; HRMS (ESIþ) calcd. for C23
H
20
N
2
O
2
Na
C
23
H
2
(341.41) Calcd. C 80.92, H 5.61, N 4.10; Found C 81.05, H
þ
[M þ Na] : 379.1417. found: 379.1413; For C23
20 2 2
H N O (356.42)
5.60, N 3.92.
Calcd. C 77.51, H 5.66, N 7.86; Found C 77.26, H 5.52, N 7.73.
4.3.11. rac-(9aR,10aS,13aR)-12-Phenyl-6,7,8,9,9a,10,10a,12-
4
6
.3.7. rac-(8aR,9aS,12aR)-11-(4-Bromophenyl)-
,7,8,8a,9,9a,11,12a-octahydropyrido[1,2,3-lm]pyrrolo[3,4-c]
octahydroazepino[1,2,3-lm]pyrrolo[3,4-c]carbazole-11,13-dione (9c)
ꢀ
Yield (0.504 g, 68%) as a white solid: mp 221e222 C; R
f
¼ 0.71
carbazole-10,12-dione (10b)
Yield (0.557 g, 64%) as a pinkish white solid: mp 247e250 C;
¼ 0.48 (1:2); IR (neat, NaCl) max 2941, 2856, 1714, 1489, 1460,
375, 1177 cm ; H NMR (500 MHz, CD Cl
7.99 (d, J ¼ 7.8 Hz,
H), 7.62 (d, J ¼ 8.6 Hz, 2H), 7.30e7.12 (m, 5H), 4.37 (d, J ¼ 8.1 Hz,
H), 4.30 (dd, J ¼ 11.9, 5.6 Hz, 1H), 3.70 (td, J ¼ 11.9, 4.9 Hz, 1H), 3.44
(1:1); IR (neat, NaCl)
1378, 1319, 1270, 1190, 1171, 1016 cm ; H NMR (500 MHz, CD
ymax 2924, 2852, 1778, 1713, 1597, 1498, 1465,
ꢀ
ꢂ1 1
2
2
Cl )
R
1
1
1
f
y
d
7.93 (d, J ¼ 7.9 Hz, 1H), 7.48e7.45 (m, 2H), 7.41e7.37 (m, 1H), 7.32
ꢂ1
1
2
2
)
d
(d, J ¼ 8.3 Hz, 1H), 7.28e7.26 (m, 2H), 7.21e7.18 (m, 1H), 7.12e7.09
(m, 1H), 4.52 (dd, J ¼ 14.4, 5.4 Hz, 1H), 4.40 (dd, J ¼ 7.9, 1.4 Hz, 1H),
3.83 (dd, J ¼ 14.1,11.6 Hz,1H), 3.43 (td, J ¼ 7.9, 5.6 Hz,1H), 3.07e3.02
(m, 1H), 2.45 (dt, J ¼ 13.8, 5.8 Hz, 1H), 2.18 (ddd, J ¼ 14.1, 7.9, 6.3 Hz,
(
4
ddd, J ¼ 13.2, 8.1, 5.3 Hz, 1H), 2.96e2.92 (m, 1H), 2.56 (dt, J ¼ 12.6,
.6 Hz, 1H), 2.29e2.26 (m, 1H), 2.19e2.09 (m, 2H), 1.56 (q,
1H), 2.13e2.04 (m, 3H), 1.78e1.69 (m, 1H), 1.57e1.49 (m, 1H),
13
13
J ¼ 12.5 Hz,1H),1.36e1.28 (m,1H) ppm; C NMR (125 MHz, CD
2
Cl
2
)
1.42e1.34 (m, 1H) ppm; C NMR (125 MHz, CD
2
Cl
2
)
d
178.8, 176.4,
d
178.2, 176.1, 138.7, 137.9, 132.7, 132.0, 128.8, 127.8, 122.6, 121.7,
142.1, 137.5, 133.0, 129.5, 128.9, 127.14, 127.11, 121.9, 120.8, 119.8,
1
21.4, 120.4, 109.6, 100.6, 42.9, 41.9, 40.7, 33.2, 32.3, 27.9, 23.8 ppm;
109.3, 102.3, 45.6, 40.9, 40.8, 36.5, 34.2, 31.9, 30.8, 29.7 ppm; HRMS
þ
þ
HRMS (ESIþ) calcd. for C23
H
19BrN
19BrN
2
O
2
Na [M þ Na] : 457.0522.
(ESIþ) calcd. for C24
H
22
N
2
O
2
Na [M þ Na] : 393.1573. found:
found: 457.0533; For C23
H
2
O
2
(435.31) Calcd. C 63.46, H 4.40,
393.1572; For C24
H
22
N
2
O
2
(370.45) Calcd. C 77.81, H 5.99, N 7.56;
N 6.44, Br 18.36; Found C 63.23, H 4.28, N 6.24, Br 18.13.
Found C 77.83, H 6.17, N 7.56.
4
6
.3.8. rac-(8aR,9aS,12aR)-11-(4-Methoxyphenyl)-
,7,8,8a,9,9a,11,12a-octahydropyrido[1,2,3-lm]pyrrolo[3,4-c]
4.3.12. rac-(9aR,10aS,13aR)-12-(4-Bromophenyl)-
6,7,8,9,9a,10,10a,12-octahydroazepino[1,2,3-lm]pyrrolo[3,4-c]
carbazole-11,13-dione (10c)
carbazole-10,12-dione (11b)
Yield (0.479 g, 62%) as a white solid: mp 246e248 C; R
1:2); IR (neat, NaCl) max 3048, 2937, 2853, 1711, 1610, 1512, 1460,
ꢀ
ꢀ
f
¼ 0.29
Cl
Yield (0.584 g, 65%) as an off-white solid: mp 237.5e238.5 C;
¼ 0.69 (1:1); IR (neat, NaCl) max 2924, 2851, 1715, 1489, 1465,
1378, 1319, 1190, 1164, 1070, 1013 cm ; H NMR (400 MHz, CD
(
y
R
f
y
ꢂ1
1
ꢂ1 1
1384, 1301, 1248, 1180, 1155, 1031 cm ; H NMR (400 MHz, CD
2
2
)
2 2
Cl )
d
8.03 (d, J ¼ 7.0 Hz, 1H), 7.32e7.16 (m, 5H), 7.01e6.99 (m, 2H), 4.33
d
7.90 (d, J ¼ 7.8 Hz, 1H), 7.60e7.56 (m, 2H), 7.31 (d, J ¼ 8.3 Hz, 1H),
(
1
d, J ¼ 7.3 Hz, 2H), 3.84 (s, 3H), 3.72e3.70 (m, 1H), 3.42e3.40 (m,
7.21e7.16 (m, 3H), 7.11e7.07 (m, 1H), 4.51 (dd, J ¼ 14.4, 5.3 Hz, 1H),
4.40 (dd, J ¼ 7.9, 1.4 Hz, 1H), 3.83 (dd, J ¼ 14.2, 11.4 Hz, 1H), 3.42 (td,
J ¼ 7.8, 5.6 Hz, 1H), 3.07e3.01 (m, 1H), 2.44 (dt, J ¼ 13.8, 5.8 Hz, 1H),
2.17 (ddd, J ¼ 13.9, 7.8, 6.2 Hz, 1H), 2.12e2.02 (m, 3H), 1.78e1.68 (m,
H), 2.91 (s, 1H), 2.57e2.54 (m, 1H), 2.25e2.15 (m, 3H), 1.61e1.52
13
(
m, 1H), 1.36e1.30 (m, 1H) ppm; C NMR (100 MHz, CD
2 2
Cl )
d
178.8, 176.7, 160.0, 138.7, 137.9, 128.4, 127.8, 125.5, 121.6, 121.4,
13
1
2
4
20.3, 114.8, 109.5, 100.9, 56.0, 42.8, 41.8, 40.5, 33.2, 32.2, 27.9,
1H), 1.56e1.46 (m, 1H), 1.40e1.33 (m, 1H) ppm; C NMR (100 MHz,
þ
3.7 ppm; HRMS (ESIþ) calcd. for C24
H
22
N
2
O
3
Na [M þ Na] :
2 2
CD Cl ) d 178.5, 176.0, 142.1, 137.5, 132.6, 132.0, 128.6, 127.0, 122.4,
122.0, 120.7, 119.8, 109.4, 102.0, 45.6, 40.8, 40.7, 36.5, 34.1, 31.7, 30.8,
09.1523. found: 409.1517; For C24
22
H N
2
O
3
(386.45) Calcd. C 74.59,
þ
H 5.74, N 7.25; Found C 74.37, H 5.73, N 7.00.
29.6 ppm; HRMS (ESIþ) calcd. for C24
H
21BrN
2
O
2
Na [M þ Na] :
4
71.0679. found: 471.0690; For C24 21BrN
H
2
O
2
(449.35) Calcd. C
4
.3.9. Dimethyl rac-1H,2,3,3a,4-tetrahydropyrido[3,2,1-jk]
carbazole-5,6-dicarboxylate (12b)
Yield (0.443 g, 68%) as yellow crystals: mp 134.5e136 C;
¼ 0.31 (1:2); IR (neat, NaCl) max 3052, 2948, 2861, 1734, 1695,
591, 1529, 1501, 1478, 1456, 1434, 1395, 1355, 1316, 1300, 1251,
64.15, H 4.71, N 6.23; Found C 63.91, H 4.66, N 5.99.
ꢀ
4.3.13. rac-(9aR,10aS,13aR)-12-(4-Methoxyphenyl)-
6,7,8,9,9a,10,10a,12-octahydroazepino[1,2,3-lm]pyrrolo[3,4-c]
carbazole-11,13-dione (11c)
R
1
f
y
ꢂ1
1
ꢀ
1
205,1144,1089,1058,1044,1016 cm ; H NMR (400 MHz, CD
7.37e7.34 (m, 1H), 7.32e7.30 (m, 1H), 7.21e7.12 (m, 2H), 4.24 (dd,
J ¼ 12.2, 5.5 Hz, 1H), 3.97 (s, 3H), 3.82 (td, J ¼ 12.1, 4.8 Hz, 1H), 3.76
s, 3H), 3.14e3.03 (m, 2H), 2.34e2.22 (m, 3H), 2.13e2.01 (m, 1H),
2
Cl
2
)
Yield (0.505 g, 63%) as a white solid: mp 232e233 C; R
f
¼ 0.59
d
(1:1); IR (neat, NaCl) ymax 2924, 2852, 1711, 1513, 1465, 1382, 1300,
1249, 1170, 1030 cm ; 1H NMR (400 MHz, CD
ꢂ1
2 2
Cl ) d 7.91 (d,
(
J ¼ 7.8 Hz, 1H), 7.32 (d, J ¼ 8.3 Hz, 1H), 7.21e7.14 (m, 3H), 7.12e7.08
(m, 1H), 6.98e6.95 (m, 2H), 4.51 (dd, J ¼ 14.3, 5.2 Hz, 1H), 4.38 (dd,
J ¼ 7.9, 1.3 Hz, 1H), 3.86e3.80 (m, 4H), 3.40 (td, J ¼ 8.0, 5.6 Hz, 1H),
13
1.54e1.44 (m, 1H) ppm; C NMR (100 MHz, CD
2 2
Cl ) d 170.0, 167.5,
143.5, 139.4, 138.0, 124.6, 122.1, 122.0, 118.4, 115.7, 110.4, 105.5, 52.8,
5
C
2.2, 42.4, 31.8, 30.9, 27.0, 23.8 ppm; HRMS (ESIþ) calcd. for
3.06e3.01 (m, 1H), 2.44 (dt, J ¼ 13.8, 5.8 Hz, 1H), 2.19e2.02 (m, 4H),
þ
13
19
H
19NO
4
Na [M þ Na] : 348.1206. found: 348.1217; For C19
H19NO
4
1.78e1.68 (m, 1H), 1.56e1.47 (m, 1H), 1.41e1.31 (m, 1H) ppm;
C
(
325.36) Calcd. C 70.14, H 5.89, N 4.31; Found C 70.21, H 6.01, N 4.40.
2 2
NMR (100 MHz, CD Cl ) d 179.1, 176.6, 159.9, 142.1, 137.4, 128.3,
Please cite this article in press as: Noland WE, et al., Diels-Alder reactions of fused 5-, 6- and 7-membered ring 2-vinylindoles: Synthesis of
annulated tetrahydrocarbazoles, Tetrahedron (2017), http://dx.doi.org/10.1016/j.tet.2017.09.025

6
W.E. Noland et al. / Tetrahedron xxx (2017) 1e6
1
4
C
C
5
27.1, 125.5, 121.9, 120.7, 119.7, 114.7, 109.3, 102.3, 56.0, 45.6, 40.8,
References
0.6, 36.5, 34.1, 31.9, 30.8, 29.6 ppm; HRMS (ESIþ) calcd. for
þ
1. Kn o€ lker HJ, Reddy KR. Chem Rev. 2002;102:4303e4427.
25
H
H
24
N
N
2
O
O
3
Na [M
þ
Na] : 423.1679. found: 423.1679; For
2
3
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25
24
2
3
(400.48) Calcd. C 74.98, H 6.04, N 7.00; Found C 75.19, H
.90, N 6.88.
4. Sotoodeh F, Smith K. J Ind Eng Chem Res. 2010;49:1018e1026.
5
6
7
. Mohamed NA, El-Serwy WS, Abd El-Karim SS, Awad GEA, Elseginy SA. Res Chem
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4
.3.14. Dimethyl rac-1,2,3,4,4a,5-hexahydroazepino[3,2,1-jk]
carbazole-6,7-dicarboxylate (12c)
Yield (0.468 g, 69%) as yellow crystals: mp 160.0e162.0 C;
¼ 0.39 (1:2); IR (neat, NaCl) max 2946, 2926, 2853, 1736, 1697,
601,1517,1461,1430,1393,1334,1300,1286,1260,1230,1214,1198,
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8. Burtoloso AB, Garcia AL, Miranda KC, Correia CD. Synlett. 2006;18:3145e3149.
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9
R
1
f
y
1
1
0. Howard-Jones AR, Walsh CT. J Am Chem Soc. 2006;128:12289e12298.
1. Peifer C, Stoiber T, Unger E, et al. J Med Chem. 2006;49:1271e1281.
ꢂ1
1
1
d
156, 1139, 1118, 1076 1062, 1023 cm ; H NMR (400 MHz, CD
7.37e7.33 (m, 2H), 7.22e7.18 (m, 1H), 7.15e7.11 (m, 1H), 4.45 (dd,
J ¼ 14.2, 5.7 Hz, 1H), 3.98 (s, 3H), 3.86 (dd, J ¼ 14.1, 11.0 Hz, 1H), 3.77
s, 3H), 3.22e3.15 (m, 1H), 3.09e3.02 (m, 1H), 2.63 (dd, J ¼ 17.0,
0.7 Hz, 1H), 2.08e2.05 (m, 2H), 1.96e1.93 (m, 1H), 1.74e1.59 (m,
2
Cl
2
)
12. Trapp J, Jochum A, Meier R, et al. J Med Chem. 2006;49:7307e7316.
13. Routier S, Merour J, Dias N, et al. J Med Chem. 2006;49:789e799.
1
4. Ehrlich A, Barnett VA, Chen HC, Schoenberg M. Biochim Biophys Acta.
995;1232:13e20.
5. Verma RP. Med Chem. 2006;6:489e499.
1
(
1
1
3
16. Tuyun AF, Bayrak N, Yildirim H, Onul N, Kara EM, Celik BO. J Chem. 2015:1e8.
17. Lawrence HR, Kazi A, Luo Y, et al. Bioorg Med Chem. 2010;18:5576e5592.
H) ppm; 1 C NMR (100 MHz, CD
3
2 2
Cl ) d 170.1, 167.2, 147.4, 138.4,
1
1
8. Ryu C-K, Kim D-H. Arch Pharm Res. 1992;15:263e268.
9. Tandon VK, Maurya HK, Mishra NN, Shukla PK. Eur J Med Chem. 2009;44:
3130e3137.
138.3, 124.2, 122.4, 121.7, 118.5, 113.9, 110.5, 107.0, 52.8, 52.2, 45.9,
3
C
C
6
5.3, 34.4, 32.2, 29.4, 28.6 ppm; HRMS (ESIþ) calcd. for
þ
20. Inbaraj JJ, Chignell CF. Chem Res Toxicol. 2004;17:55e62.
1. Zhivetyeva SI, Zakharova OD, Ovchinnikova LP, et al. J Fluor Chem. 2016;192:
8e77.
22. Yuk DY, Ryu CK, Hong JT, et al. Biochem Pharmacol. 2000;60:1001e1008.
20
H
21NO
21NO
4
Na [M
þ
Na] : 362.1363. found: 362.1364; For
2
20
H
4
(339.39) Calcd. C 70.78, H 6.24, N 4.13; Found C 70.88, H
6
.19, N 4.15.
2
2
3. Salmon-Chemin L, Buisine E, Yardley V, et al. J Med Chem. 2001;44:548e565.
4. Yavari I, Hossaini Z, Sabbaghan M, Ghazanfarpour-Darjani M. Tetrahedron.
2
007;63:9423e9428.
5. (a) Nair V, Devipriya S, Eringathodi S. Tetrahedron Lett. 2007;48:3667e3670;
b) Nair V, Vidya N, Biju AT, Deepthi A, Abhilash KG, Suresh E. Tetrahedron.
2006;62:10136e10140.
26. Eitel M, Pindur U. J Org Chem. 1990;55:5369.
7. (a) Arai T, Tsuchida A, Miyazaki T, Awata A. Org Lett. 2017;19:758e761;
4
.3.15. rac-(9aR-10aS,16aS)-6,7,8,9,9a,10,10a,16a-
2
Octahydroazepino[1,2,3-lm]naphtho[2,3-c]carbazole-11,16-dione
(
(
13c)
Yield (0.448 g, 63%) as brownish crystals: mp 188e189.5 C;
¼ 0.59 (1:2); IR (neat, NaCl) max 3051, 2924, 2851, 1688, 1593,
ꢀ
2
R
1
f
y
(
(
b) Wang XF, Chen JR, Cao YJ, Cheng HG, Xiao WJ. Org Lett. 2010;12:1140;
c) Bergonzini G, Gramigna L, Mazzanti A, Fochi M, Bernardi L, Ricci A. Chem
467, 1445, 1428, 1380, 1363, 1318, 1292, 1245, 1216, 1188, 1168,
ꢂ1
1
1016, 1006 cm ; H NMR (400 MHz, CD
2
Cl
2
)
d
8.14e8.08 (m, 2H),
Commun. 2010;46:327;
(
(
(
d) Tan F, Li F, Zhang XX, et al. Tetrahedron. 2011;67:446;
e) Tan F, Xiao C, Cheng HG, Wu W, Ding KR, Xiao WJ. Chem Asian J. 2012;7:493;
f) Pirovano V, Dell'Acqua M, Facoetti D, et al. Eur J Org Chem. 2013;2013:6267;
7
.82e7.79 (m, 2H), 7.47 (d, J ¼ 7.8 Hz, 1H), 7.34 (d, J ¼ 8.3 Hz, 1H),
7.19 (t, J ¼ 7.6 Hz, 1H), 7.08 (t, J ¼ 7.4 Hz, 1H), 4.58 (dd, J ¼ 14.3,
4
.2 Hz, 1H), 4.51 (d, J ¼ 5.4 Hz, 1H), 3.76 (dd, J ¼ 14.2, 11.3 Hz, 1H),
.39 (ddd, J ¼ 13.0, 5.4, 2.6 Hz, 1H), 3.12e3.05 (m, 1H), 2.32 (dd,
(g) Tian X, Hofmann N, Melchiorre P. Angew Chem Int Ed. 2014;53:2997;
(h) Talukdar R, Tiwari DP, Saha A, Ghorai MK. Org Lett. 2014;16:3954;
(i) Wang Y, Tu MS, Yin L, Sun M, Shi F. J Org Chem. 2015;80:3223;
(j) Wang L, Guo W, Zhang XX, Xia XD, Xiao WJ. Org Lett. 2012;14:740.
3
J ¼ 12.9, 5.9 Hz, 1H), 2.16e2.12 (m, 2H), 1.91 (d, J ¼ 13.7 Hz, 1H),
1
3
1
.76e1.64 (m, 3H), 1.30 (q, J ¼ 12.2 Hz,1H) ppm; C NMR (100 MHz,
CD Cl 199.5, 197.3, 141.4, 137.3, 135.9, 135.0, 134.8, 134.4, 127.9,
27.6, 127.4, 121.6, 119.6, 119.2, 109.4, 106.2, 50.4, 47.0, 46.1, 36.9,
28. Pindur U. Chimia. 1985;39:264.
2
9. (a) Kuehne ME, Podhorez DE, Mulamba T, Bornmann WG. J Org Chem. 1987;52:
47e353;
b) Kuehne ME, Bornmann WG, Earley WG, Marko I. J Org Chem. 1986;51:
2
2
) d
3
(
1
3
6.2, 35.7, 31.1, 29.9 ppm; HRMS (ESIþ) calcd. for C24
H
21NO
2
Na
2913e2927.
0. Pindur U. Heterocycles. 1988;27:1253e1268.
þ
3
3
3
3
3
[
M þ Na] : 378.1465. found: 378.1462; For C24
H21NO (355.44)
2
1. Pindur U, Kim MH. Tetrahedron Lett. 1988;29:3927e3928.
2. Pindur U, Eitel M. Helv Chim Acta. 1988;71:1060e1064.
3. Bergman J, Pelcman B. Tetrahedron. 1988;44:5215e5228.
4. Mosa Mohamed YA, Inagaki F, Takahashi R, Mukai C. Tetrahedron. 2011;67:
5133e5141.
Calcd. C 81.10, H 5.96, N 3.94; Found C 80.88, H 5.84, N 3.96.
Acknowledgements
3
3
3
3
5. Laronze M, Sapi J. Tetrahedron Lett. 2002;43:7925e7928.
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The authors thank the Wayland E. Noland Research Fellowship
Fund at the University of Minnesota Foundation for generous
financial support of this project. We are grateful to Dr. Kenneth J.
Tritch and to all referees for constructive suggestions.
39. Noland WE, Wann SR. J Org Chem. 1979;44:4402e4410.
4
4
0. Noland WE, Walhstrom MJ, Konkel MJ, et al. J Heterocycl Chem. 1993;30:81e91.
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4
4
4
4
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Appendix A. Supplementary data
6. Chen CB, Wang XF, Cao YJ, Cheng HG, Xiao WJ.
532e3535.
J Org Chem. 2009;74:
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2017.09.025.
3
Please cite this article in press as: Noland WE, et al., Diels-Alder reactions of fused 5-, 6- and 7-membered ring 2-vinylindoles: Synthesis of
annulated tetrahydrocarbazoles, Tetrahedron (2017), http://dx.doi.org/10.1016/j.tet.2017.09.025