Regio- and stereoselective synthesis of new substituted tetrahydrocarbazoles and carbazoles using Diels-Alder reactions

Article abstract of DOI:10.1080/00397911.2010.544440

Diels-Alder reactions of 3-vinylindoles were carried out with methyl acrylate and N-phenylmaleimide as dienophiles under microwave conditions to furnish unreported tetrahydrocarbazoles regio- and stereoselectively in good yields. Further dehydrogenation r

Full text of DOI:10.1080/00397911.2010.544440

This article was downloaded by: [Dalhousie University]
On: 16 June 2013, At: 03:09
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
Regio- and Stereoselective Synthesis of
New Substituted Tetrahydrocarbazoles
and Carbazoles Using Diels–Alder
Reactions
Dattatray G. Hingane a , Shailesh K. Goswami a , Vedavati Puranik b
& Radhika S. Kusurkar a
a Department of Chemistry, University of Pune, Pune, India
b Centre for Material Characterization, National Chemical
Laboratory, Pune, India
Accepted author version posted online: 17 Nov 2011.Published
online: 27 Feb 2012.
To cite this article: Dattatray G. Hingane , Shailesh K. Goswami , Vedavati Puranik & Radhika S.
Kusurkar (2012): Regio- and Stereoselective Synthesis of New Substituted Tetrahydrocarbazoles and
Carbazoles Using Diels–Alder Reactions, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 42:12, 1786-1795
To link to this article: http://dx.doi.org/10.1080/00397911.2010.544440
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation
that the contents will be complete or accurate or up to date. The accuracy of any
instructions, formulae, and drug doses should be independently verified with primary
sources. The publisher shall not be liable for any loss, actions, claims, proceedings,

demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.

Synthetic Communications1, 42: 1786–1795, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.544440
REGIO- AND STEREOSELECTIVE SYNTHESIS OF NEW
SUBSTITUTED TETRAHYDROCARBAZOLES AND
CARBAZOLES USING DIELS–ALDER REACTIONS
Dattatray G. Hingane,1 Shailesh K. Goswami,1
Vedavati Puranik,2 and Radhika S. Kusurkar1
1Department of Chemistry, University of Pune, Pune, India
2Centre for Material Characterization, National Chemical Laboratory,
Pune, India
GRAPHICAL ABSTRACT
Abstract Diels–Alder reactions of 3-vinylindoles were carried out with methyl acrylate and
N-phenylmaleimide as dienophiles under microwave conditions to furnish unreported tetra-
hydrocarbazoles regio- and stereoselectively in good yields. Further dehydrogenation
resulted in new substituted carbazoles.
Keywords Carbazoles; regio- and stereoselective Diels–Alder reactions; tetrahydrocarba-
zoles
INTRODUCTION
Carbazole and tetrahydrocarbazole ring systems are major artifacts of many
naturally occurring biologically active compounds.[1] There has been strong interest
in carbazole alkaloids from chemists and biologists because of the intriguing struc-
tural features and promising biological activities. In the literature,[1–7] various meth-
ods are available for the synthesis of carbazole alkaloids, including classical methods
such as Fischer–Borsche synthesis and Graebe–Ullmann synthesis as well as meth-
ods based on transition metal–mediated and catalyzed coupling.[1] Electrocyclization
and Diels–Alder reactions of vinylindoles have been extensively used[1,8,9] for
the synthesis of tetrahydrocarbazoles and carbazoles. Recently, microwave
irradiation, a green technique, has been shown[10] to be the most preferred
method for many organic reactions because the reactions are fast, high-yielding,
and stereoselective. We herein report the regio- and stereoselective synthesis of
Received July 5, 2010.
Address correspondence to Radhika S. Kusurkar, Department of Chemistry, University of Pune,
Pune 411 007, India. E-mail: rsk@chem.unipune.ac.in
1786

REGIO- AND STEREOSELECTIVE SYNTHESIS OF CARBAZOLES
1787
new substituted tetrahydrocarbazoles and carbazoles using Diels–Alder reactions
with methyl acrylate and N-phenylmaleimide as dienophiles.
RESULTS AND DISCUSSION
Three different 3-vinylindoles 1–3 were used for the presented Diels–Alder
reactions. Indole was first formylated, and the indole-3-aldehyde[11] formed was pro-
tected at the indole nitrogen with a phenylsulfonyl group.[12] Further reactions with
appropriate Wittig reagents furnished dienes 1–3.[13,14] According to 1H NMR data,
diene 2 was obtained as a mixture of E and Z isomers in the ratio of 1:1, while diene
3 was isolated as pure E isomer.
Reactions of Dienes 1–3 with Methyl Acrylate
Treatment of 1-phenylsulfonyl-3-vinylindole 1 with methyl acrylate at reflux
temperature using microwave irradiation furnished a solid. After chromatography,
compound 4a (76%) was isolated as a major product (Scheme 1). The product was
shown to be an endo adduct, and the structure was confirmed by the presence of a
singlet for –COOMe at 3.6 d and a narrow multiplet of an olefinic proton at 5.86
d in 1H NMR. A small amount of the other isomer was also isolated. Further dehy-
drogenation of the cycloadduct 4a, using 2,3-dichloro-5,6-dicyanobenzoquinone
(DDQ), furnished product 5 (68%). The 1H NMR data of 5 differed from its
Scheme 1. Reactions of dienes 1–3 with methyl acrylate.

1788
D. G. HINGANE ET AL.
reported[15] regioisomer. Thus, the reported N-benzenesulfonyl-2-carbomethoxycar-
bazole showed a singlet at 8.88 d for C1H (meta coupling not seen) and a singlet at
3.95 d for –OMe, whereas in N-benzenesulfonyl-1-carbomethoxy carbazole 5
no singlet was observed for aromatic protons, and –OMe was seen at 4.03 as a
singlet. This data confirmed the position of the –COOMe group at C-1 also in the
cycloadduct 4a.
Finally, deprotection of the indole nitrogen in compound 5 using sodium
methoxide furnished 1-carbomethoxy carbazole 6 in 80% yield (Scheme 1).
Treatment of diene 2 (E þ Z) with methyl acrylate furnished two cycloadducts,
7a and 7b, in 68% yield in the ratio 1:1. The isomers were separated by column chro-
1
matography. The structure and stereochemistry of 7a and 7b was determined by H
NMR spectroscopy. Dehydrogenation carried out with 7a and 7b using DDQ in
both cases gave 8, indicating that 7a and 7b are diastereomers (Scheme 1). The struc-
ture of unreported carbazole 8 was confirmed by the presence of two singlets at 7.7
and 8.72 d for C4H and C1H respectively. The formation of two diastereomers 7a
and 7b can be explained by the cis addition in the Diels–Alder reaction on E and
Z isomers respectively. Thus, diene 2 furnished cycloadducts 7a and 7b regio- and
stereoselectively.
In the Diels–Alder reaction of diene 3 with methyl acrylate, an inseparable mix-
ture of cycloadducts 9 was obtained. After dehydrogenation with DDQ, two new
products, 10 and 11, in the ratio of 1:0.04, were produced. Compound 10 showed
two singlets at 8.29 and 8.66 d for C1H and C4H in 1H NMR indicating the position
of –COOMe at C2. This was further supported by x-ray analysis[16] (Fig. 1).
Compound 11 exhibited two meta-coupled (J ¼ 1.65 Hz) doublets at 8.49 and 8.58
d for C2H and C4H respectively, indicating the position of –COOMe at C1.
Figure 1. ORTEP diagram of the compound 10. Ellipsoids are drawn at 50% probability. (Figure is
provided in color online.)

REGIO- AND STEREOSELECTIVE SYNTHESIS OF CARBAZOLES
1789
These results showed that the dienes 1, 2, and 3 furnished ortho adducts
as major products. Formation of these adducts can be explained using frontier
molecular orbital (FMO) theory. Diene 1 has an electron-withdrawing ꢀNSO2Ph
at C1 of the diene unit, giving 4a as ortho adduct to the sulfonamido group. The
electron-donating methoxy group is controlling the formation of the regiochemis-
try of the products 7a and 7b. Diene 3 has two electron-withdrawing groups at 1
and 4 positions. The formation of ortho adduct to –COOEt indicated its stronger
controlling effect.
Reactions of Dienes 1–3 with N-Phenylmaleimide
1-Phenylsulfonyl-3-vinylindole (1) and N-phenylmaleimide (NPMI) were
adsorbed on silica gel and exposed to microwave for 20 min to furnish selectively
one cycloadduct[17,18] 12 (Scheme 2). The same result was observed by carrying
1
out the reaction in the microwave oven using toluene as a solvent. The H NMR
of compound 12 was in agreement with reported data.[18] However, use of microwave
heating improved the yield and minimized the reaction time (74%, 20 min) compared
to the earlier report (60%, 7 h).
Diene 2 (E=Z ¼ 1:1) and NPMI were adsorbed on silica gel and irradiated in a
microwave oven for 20 min to furnish two cycloadducts, 13a and 13b. The major iso-
mer was shown to be 13a, which was identical with the reported[14] cycloadduct
obtained in a similar reaction carried out by the conventional method. In contrast
to that report, the other isomer 13b was also isolated successfully and was character-
1
ized by spectral data. From H NMR, 13a and 13b were shown to be the diastereo-
mers of each other. The isomers 13a and 13b were obtained from the E and Z
isomers of the diene 2 respectively according to cis addition rule in [4 þ 2] cycloaddi-
tion reaction. In an observation, when the irradiation was carried out in toluene,
product 13a precipitated out after 15 min, which indicated that the E isomer was
reacting faster than the Z. When starting diene was used in the ratio E=Z ¼ 1:1,
the product ratio of 13a/13b was 9:1. The change in the ratios of the isomers of start-
ing and product could be attributed to the conversion of Z to E isomer during the
reaction. This was confirmed experimentally by irradiating the mixture of E=Z
Scheme 2. Reactions of dienes 1–3 with N-phenylmaleimide.

1790
D. G. HINGANE ET AL.
isomers in the ratio of 1:1 for 15 min in a microwave oven to get the conversion as
E=Z ¼ 2:1.
Thus, as compared to the earlier report[14] (15 h, 5% of 13a, absence of 13b), the
reaction under microwave irradiation was rapid, and high yielding (20 min, 72% of
13a and 8% of 13b) and furnished unreported diastereomer 13b. It should be noted
that the dimer obtained in the earlier report was not formed in this reaction.
1-Phenylsulfonyl-3-(b-carbethoxyvinyl) indole 3 on reaction with NPMI using
microwave-irradiation furnished cycloadduct 14 with 72% yield. When the micro-
wave irradiation reaction was carried out in toluene, cycloadduct 14 was precipitated
1
out after 20 min. By comparing the H NMR spectrum and by using the analogy
with 13a, the structure of the product 14 was confirmed as a single unreported
diastereomer, which is expected from the starting E isomer of 3.
Surprisingly, in contrast to the dehydrogenation of cycloadducts 4a, 7a, 7b,
and 9, attempts to dehydrogenate the cycloadducts 12, 13a, 13b, and 14 using
DDQ, chloranil, or Pd=C (10%) in different solvents failed to give aromatic pro-
ducts. This could be attributed to the presence of the fused NPMI ring at C1 and
C2 positions.
CONCLUSION
The microwave-assisted Diels–Alder reaction of 3-vinylindoles was shown to
be faster and furnished new cycloadducts stereoselectively and regioselectively in
good yields. The cycloadducts obtained by using methyl acrylate were further dehy-
drogenated to new substituted carbazoles. Reactions using NPMI furnished new
cycloadducts. The formation of major adducts was explained using FMO theory
and the cis addition rule.
EXPERIMENTAL
The Diels–Alder reactions were carried out at reflux temperature of methyl
acrylate at 700 W in a Raga microwave synthesizer. 1H NMR and 13C NMR spectra
were recorded at 300 MHz and 75 MHz respectively on a Varian Mercury instrument
as d values in CDCl3 with reference to tetramethylsilane (TMS) as an internal stan-
dard. Fourier transform infrared (FTIR) spectra were recorded on a Shimadzu 8400
instrument. Mass spectra were recorded on a Shimadzu QP 5050 device. Elemental
analysis was recorded on a Flash E. A. 1112 Thermo instrument.
General Procedure for the Cycloaddition Reaction of Vinylindoles
1–3 with Methyl Acrylate in Microwave Oven
Vinylindole (1–3, 1 mmol) was dissolved in methyl acrylate (5 ml) in a
round-bottomed flask, equipped with a reflux condenser, and exposed to microwave
irradiation. The reaction was monitored by thin-layer chromatography (TLC) after
every 2 min. After completion of the reaction, methyl acrylate was removed using a
rotary evaporator, and the reaction mixture was chromatographed using silica gel
with hexane=ethyl acetate (90:10) as an eluent to furnish the products.

REGIO- AND STEREOSELECTIVE SYNTHESIS OF CARBAZOLES
1791
General Procedure for Dehydrogenation of Cycloadducts
Tetrahydrocarbazoles (4a, 7a, 7b, and 9, 1 mmol) were dissolved in 10 ml dry
benzene. To the well-stirred and ice-cooled solution, DDQ (2.5 mmol) was added
in 3–4 lots. Addition of DDQ gave a green color to the solution, which vanished
immediately. After complete addition of DDQ, the green color persisted. The reac-
tion mixture was refluxed for 6 h, and the reaction was monitored by TLC. After
completion of reaction, the reaction mixture was filtered and washed with benzene,
and the solvent was removed using a rotary evaporator. The oily mixture obtained
was chromatographed using silica gel with hexane=ethyl acetate (95:5) as an eluent
to get the product.
Procedure for Deprotection of Carbazole 5
To a freshly prepared sodium methoxide solution (0.1 g sodium in 10 ml dry
methanol), compound 5 (0.2 g) was added, and the reaction mixture was refluxed
for 5 h. The reaction was monitored by TLC. After completion of reaction, it was
neutralized with dilute HCl and extracted with dichloromethane (DCM). The solvent
was removed using a rotary evaporator. The solid product was chromatographed
using silica gel with hexane=ethyl acetate (95:5) as an eluent to furnish carbazole 6.
General Procedure for the Cycloaddition Reaction of Vinylindoles
with NPMI in Microwave Oven
Vinylindole (1–3, 1 mmol) and NPMI (1.1 mmol) were adsorbed on silica gel.
The mixture was exposed to microwave radiation. The reaction was monitored by
TLC every 2 min. The reaction was complete in 20 min of microwave irradiation.
The reaction mixture was purified by column chromatography using silica gel with
hexane=ethyl acetate (90:10) as an eluent to furnish the products.
Selected Data
1
Compound 4a. Yield: 76%; mp 115–116 ꢁC; H NMR (300 MHz, CDCl3): d
2.05 (m, 1H, C2Ha), 2.30 (m, 3H, C3H2 & C2Hb), 3.60 (s, 3H, ꢀOCH3), 3.81 (nm,
1H, J ¼ 3.6 Hz, C1Hb), 4.39 (t, 1H, J ¼ 3.3 Hz, C9aHb), 5.86 (d, 1H, J ¼ 3.3 Hz,
C4H), 6.99 (t, 1H, J ¼ 3 Hz, ArH), 7.18–7.26 (m, 2H, ArH), 7.41–7.56 (m, 3H,
ArH), 7.72–7.80 (m, 3H, ArH); 13C NMR (75 MHz, CDCl3): d 22.58, 23.92, 41.65,
51.60, 63.68, 115.28, 116.42, 120.22, 123.94, 127.46, 128.94, 129.19, 133.26, 133.87,
135.34, 136.05, 143.04, 171.44; IR (Nujol): v 1730, 1640 cmꢀ1; MS: m=z 369 (Mþ).
Anal. calcd. for C20H19NO4S: C, 65.05; H, 5.14; N, 3.79%. Found: C, 65.22; H,
5.10; N, 3.68%.
1
Compound 5. Yield: 68%; mp 124–126 ꢁC; H NMR (300 MHz, CDCl3): d
4.03 (s, 3H, ꢀCOOCH3), 7.08 (t, J ¼ 8.3 Hz, 2H, C3H & C6H), 7.20 (dd, J ¼ 8.5,
1.2 Hz, 2H, ArH), 7.29 (m, 2H, ArH), 7.43 (m, 2H ArH), 7.7 (d, J ¼ 7.6 Hz, 1H,
ArH), 7.83 (dd, J ¼ 7.6, 0.9 Hz, 1H, C2H), 7.90 (d, J ¼ 7.9 Hz, 1H, C5H), 8.12 (d,
J ¼ 8.2 Hz, 1H, C4H); 13C NMR (75 MHz, CDCl3): d 52.4, 118.04, 119.8, 122.7,
124.54, 125.26, 126.27, 126.57, 127.63, 128.13, 128.56, 129.01, 130.09, 133.43,

1792
D. G. HINGANE ET AL.
135.15, 136.85, 140.16, 169.46; IR: v 1738 cmꢀ1; MS: m=z 365 (Mþ). Anal. calcd. for
C20H15NO4S: C, 65.75; H, 4.10; N, 3.84%. Found: C, 65.68; H, 4.12; N, 3.72%.
1
Compound 6. Yield: 80%, mp 143–144 ꢁC; H NMR (300 MHz, CDCl3): d
4.01 (s, 3H COOCH3), 7.22–7.54 (dd, J ¼ 8, 1.3 Hz, 4H, ArH), 8.07–8.34, m, 3H,
ArH), 9.89 (bs, 1H > N-H exchangeable with D2O); 13C NMR (75 MHz, CDCl3):
d 51.06, 110.69, 117.25, 118.75, 119.15, 121.15, 123.55, 124.31, 125.42, 126.39,
138.57, 139.02, 140.20, 166.32; IR (Nujol): v 1738 cmꢀ1; MS: m=z 225 (Mþ). Anal.
calcd. for C14H11NO2: C, 74.76; H, 4.88; N, 6.22%. Found: C, 74.65; H, 4.70; N,
6.34%.
1
Compound 7a. Yield: 36%; mp 122–124 ꢁC; H NMR (300 MHz, CDCl3): d
2.06 (dd, J ¼ 12.8, 12.37 Hz, 1H, C1H), 2.78 (dd, J ¼ 12.8, 2.4 Hz, 1H, C1H), 2.98 (dd,
J ¼ 12.37, 2.4 Hz, 1H, C2Hb), 3.38 (s, 3H, ꢀOCH3), 3.78 (s, 3H, –COOCH3), 4.10
(d, J ¼ 9.7, 1H, C9aHb), 4.2 (bs, 1H, C3Hb), 6.06 (d, J ¼ 2.8 Hz, 1H, C4H), 7.00 (t,
J ¼ 7 Hz, 1H, ArH), 7.28 (m, 4H, ArH), 7.42 (t, J ¼ 7 Hz, 1H, ArH), 7.78 (m, 3H,
ArH); 13C NMR (75 MHz, CDCl3): d 26.49, 44.56, 51.95, 57.70, 63.98, 73.46,
114.42, 115.38, 120.92, 124.05, 126.29, 127.51, 129.00, 130.24, 133.39, 136.11,
138.98, 144.39, 171.69; IR (Nujol): v 1738 cmꢀ1; MS: m=z 399 (Mþ). Anal. calcd.
for C21H21NO5S: C, 63.16; H, 5.26; N, 3.50%. Found: C, 63.24; H, 5.43; N, 3.72%.
1
Compound 7b. Yield: 32%; mp 126–128 ꢁC; H NMR (300 MHz, CDCl3): d
2.04 (m, 1H, C1H), 3.02 (bs, 1H, C2Hb), 3.06 (dd, J ¼ 16.8, 2.75 Hz, 1H, C1H), 3.42
(s, 3H –OCH3) 3.78 (s, 3H –COOCH3), 4.16 (t, J ¼ 2.5 Hz, 1H, C9aHb), 4.2 (bs, 1H,
C3Ha), 5.92 (d, J ¼ 2.5 Hz, 1H, C4H), 6.98 (t, J ¼ 7.4 Hz, 1H, ArH), 7.26 (m, 2H,
ArH), 7.45 (m, 3H, ArH), 7.80 (m, 3H, ArH); 13C NMR (75 MHz, CDCl3): d
27.48, 41.91, 52.25, 57.23, 60.52, 74.50, 115.26, 115.46, 120.96, 124.18, 126.30,
127.65, 128.90, 130.12, 133.44, 135.39, 138.45, 144.31, 173.68; IR (Nujol): v
1730 cmꢀ1; MS: 399 (Mþ). Anal. calcd. for C21H21NO5S: C, 63.16; H, 5.26; N,
3.50%. Found: C, 63.31; H, 5.10; N, 3.34%.
1
Compound 8. Yield 76% from 7a and 72% from 7b, mp 158–160 ꢁC; H
NMR (300 MHz, CDCl3): d 3.96 (s, 6H –OCH3 and –COOCH3), 7.2–7.4 (m, 5H,
ArH), 7.5 (t, J ¼ 7.8 Hz, 1H, ArH), 7.7 (s, 1H, C4H), 7.74 (d, J ¼ 7.7 Hz, 1H,
ArH), 7.85 (d, J ¼ 7.7 Hz, 1H, ArH), 8.28 (d, J ¼ 8.2 Hz, 1H, C5H), 8.72 (s, 1H,
C1H, ArH); 13C NMR (75 MHz, CDCl3): d 52.36, 56.44, 102.39, 115.39, 118.26,
119.60, 120.46, 124.06, 125.58, 126.31, 128.50, 128.92, 130.44, 131.34, 133.74,
137.11, 139.58, 156.24, 166.24; MS: 395 (Mþ). Anal. calcd. for C21H17NO5S: C,
63.80; H, 4.30; N, 3.54%. Found: C, 63.62; H, 4.41; N, 3.42%.
1
Compound 10. Yield: 72%; mp 135–137 ꢁC; H NMR (300 MHz, CDCl3): d
1.40 (t, J ¼ 7.2 Hz, 3H, ꢀCOOCH2CH3), 3.99 (s, 3H, ꢀCOOCH3), 4.42 (q, 7.2 Hz,
2H, ꢀCOOCH2CH3), 7.30 (m, 3H, ArH), 7.43 (t, J ¼ 8 Hz, 1H, ArH), 7.56 (t,
J ¼ 7.7 Hz, 1H, ArH), 7.81 (d, J ¼ 8 Hz, 2H, ArH), 7.92 (d, J ¼ 7.7 Hz, 1H, ArH),
8.29 (s, 1H, C1H), 8.30 (d, J ¼ 6.3 Hz, 1H, C5H), 8.66 (s, 1H, C4H); 13C NMR
(75 MHz, CDCl3): d 14.12, 52.77, 61.72, 114.79, 115.20, 120.57, 121.12, 124.32,
124.63, 126.18, 127.42, 127.62, 128.67, 129.08, 131.10, 134.06, 137.09, 138.73,
138.96, 166.94, 167.86; IR (Nujol): v 1738 cmꢀ1; MS: m=z 437 (Mþ). Anal. calcd.
for C23H19NO6S: C, 63.16; H, 4.35; N, 3.20%. Found: C, 63.28; H, 4.16; N, 3.32%.

REGIO- AND STEREOSELECTIVE SYNTHESIS OF CARBAZOLES
1793
1
Compound 11. Yield 3%; mp 140–142 ꢁC; H NMR (300 MHz, CDCl3): d
1.45 (t, J ¼ 7.2 Hz, 3H, ꢀCOOCH2CH3), 4.03 (s, 3H, ꢀCOOCH3), 4.46 (q,
J ¼ 7.2 Hz, 2H, ꢀCOOCH2CH3), 7.12 (t, J ¼ 8.2 Hz, 1H, ArH), 7.27 (m, 5H,
ArH), 7.45 (t, J ¼ 7.4 Hz, 1H, ArH), 7.8 (d, J ¼ 7.4 Hz, 1H, ArH), 8.1 (d, J ¼ 7.9 Hz,
1H, C5H), 8.49 (d, J ¼ 1.65 Hz, 1H, C2H), 8.58 (d, J ¼ 1.65 Hz, 1H, C4H); 13C NMR
(75 MHz, CDCl3): d 14.46, 52.78, 61.62, 117.90, 120.22, 124.04, 124.28, 125.51,
126.63, 127.02, 127.47, 128.24, 128.40, 129.66, 130.20, 133.70, 135.50, 139.53,
140.52, 165.35, 167.75; MS: 437 (Mþ). Anal. calcd. for C23H19NO6S: C, 63.16; H,
4.35; N, 3.20%. Found: C, 63.35; H, 4.18; N, 3.42%.
1
Compound 12. Yield 74%; mp 162–163 ꢁC; H NMR (300 MHz, CDCl3): d
2.28 (ddd, J ¼ 15.6, 7.42, 3.5 Hz, 1H, C4H), 3.12 (dd, J ¼ 15.6, 7.7 Hz, 1H, C4H),
3.36 (dd, J ¼ 7.7, 7.42 Hz, 1H, C3aHb), 4.22 (dd, J ¼ 8.8, 6.8 Hz, 1H, C10bHb), 4.64
(dd, J ¼ 6.8, 3.58 Hz, 1H, C10aHb), 6.14 (m, 1H, C5H), 6.95–7.92 (m, 14 H, ArH);
13C NMR (75 MHz, CDCl3): d 23.84, 35.74, 42.09, 59.97, 112.30, 112.96, 119.35,
122.31, 124.75, 124.89, 125.43, 126.65, 127.07, 127.66, 128.15, 130.25, 132.10,
134.64, 134.86, 142.12, 171.90, 176.35. Anal. calcd. for C26H20N2O4S: C, 68.42; H,
4.38; N, 6.14%. Found: C, 68.28; H, 4.42; N, 6.32%.
Compound 13a. Yield: 72%; mp 230–232 ꢁC; 1H NMR (300 MHz, CDCl3): d
3.66 (s, 3H, ꢀOCH3), 3.71 (dd, J ¼ 8.3, 7.7 Hz, 1H, C3aHb), 4.12 (ddd, J ¼ 7.7, 3,
1.9 Hz, 1H, C4Hb), 4.17 (dd, J ¼ 8.5, 6.1 Hz, 1H, C10bHb), 4.59 (m, 1H, C10aHb),
6.12 (dd, J ¼ 3 Hz, 1H, C5H), 6.99–7.92 (m, 14H, ArH); 13C NMR (75 MHz, CDCl3):
d 37.72, 37.98, 41.75, 56.18, 59.48, 113.28, 115.38, 119.92, 122.59, 124.42, 125.12,
125.66, 126.80, 127.24, 127.84, 128.88, 130.44, 132.26, 133.32, 135.14, 143.18,
171.28, 171.46. MS: m=z 486 (Mþ).
1
Compound 13b. Yield: 8%; mp 176–178 ꢁC; H NMR (300 MHz, CDCl3): d
3.34 (s, 3H, ꢀOCH3), 3.67 (dd, J ¼ 8.5, 2.2 Hz, 1H, C3aHb), 4.27 (dd, J ¼ 8.5,
7.4 Hz, 1H, C10bHb), 4.66 (dd, J ¼ 5.7, 2.2 Hz, 1H, C4Ha), 5.22 (dd, J ¼ 7.4,
3.3 Hz, 1H, C10aHb), 6.25 (dd, J ¼ 5.7, 3.3 Hz, 1H, C5H), 6.98–7.94 (m, 14 H,
ArH); 13C NMR (75 MHz, CDCl3): d 41.70, 44.05, 56.66, 60.54, 73.76, 112.40,
115.49, 121.47, 123.91, 125.89, 126.09, 127.28, 128.39, 128.78, 129.04, 131.29,
131.46, 133.40, 136.82, 141.77, 144.96, 172.55, 174.80; MS: 486 (Mþ). Anal. calcd.
for C27H22N2O5S: C, 66.66; H, 4.52; N, 5.76%. Found: C, 66.50; H, 4.62; N,
5.88%.
1
Compound 14. Yield: 72%; mp 205–207 ꢁC; H NMR (300 MHz, CDCl3): d
1.35 (t, J ¼ 7.14 Hz, 3H, ꢀCOOCH2CH3), 3.22 (brs, 1H, C3aHb), 3.95 (dd, J ¼ 9,
5.3 Hz, 1H, C10bHb), 4.27 (ddd, J ¼ 8.8, 3.6, 2.6 Hz, 1H, C4Hb), 4.34 (q, J ¼ 7.14 Hz,
2H, ꢀCOOCH2CH3), 4.6 (ddd, J ¼ 7.42, 5.3, 2.6 Hz, 1H, C10aHb), 6.62 (dd, J ¼ 7.42,
3.6 Hz, 1H, C5H), 6.62–7.90 (m, 14 H, ArH); 13C NMR (75 MHz, CDCl3): d 14.16,
40.44, 41.88, 42.70, 61.66, 61.94, 112.18, 115.28, 121.20, 124.12, 125.64, 126.06,
127.12, 128.32 128.70, 129.14, 130.60, 131.14, 133.50, 136.48, 136.76, 144.48,
169.58, 171.86, 174.84; MS: m=z 528 (Mþ). Anal. calcd. for C29H24N2O6S: C,
65.90; H, 4.54; N, 5.30%. Found: C, 65.72; H, 4.70; N, 5.14%.

1794
D. G. HINGANE ET AL.
Crystallographic Data of Compound 10
Single crystals of the compound were grown by slow evaporation of the com-
pound in methanol. A colorless crystal of approximate size 0.42 ꢂ 0.28 ꢂ 0.03 mm,
was used for data collection on Bruker Smart Apex CCD diffractometer using Mo
Ka radiation C23 H19 N O6 S, M ¼ 437.45. Crystals belong to monoclinic space
ꢁ
˚
group P21=c, a ¼ 11.8641(7), b ¼ 14.7655(9), c ¼ 13.0207(8) A, b ¼ 115.425(1) ,
3
[19]
˚
V ¼ 2060.0(2) A , Z ¼ 4. SHELX-97 (ShelxTL)
was used for structure solution
and full matrix least squares refinement on F2. Hydrogen atoms were included in
the refinement as per the riding model.
ACKNOWLEDGMENTS
We are grateful to M. S. Wadia for helpful discussions, A. P. Gadgil for IR
spectra, J. P. Chaudhari for NMR spectra, and Mr. Shishupal for GC-MS. D. G.
H. is thankful to the University Grants Commission for FIP.
REFERENCES
1. Knolker, H. J.; Reddy, K. R. Isolation and synthesis of biologically active carbazole
alkaloids. Chem. Rev. 2002, 102, 4303–4427.
2. Saxton, J. E. Recent progress in the chemistry of the monoterpenoid indole alkaloids. Nat.
Prod. Rep. 1997, 14, 559–590.
3. Bonjoch, J.; Sole, D. Synthesis of strychnine. Chem. Rev. 2000, 100, 3455–3482.
4. Abbiati, G.; Canevari, V.; Facoetti, D.; Rossi, E. Diels–Alder reactions of 2-vinylindoles
=
with open-chain C C dienophiles. Eur. J. Org. Chem. 2007, 517–525.
5. Siripurapu, U.; Kolanos, R.; Dukat, M.; Roth, B. L.; Glennon, R. A. Binding of
methoxy-substituted N1-benzenesulfonylindole analogs at human 5-HT6 serotonin
receptors. Bioorg. Med. Chem. Lett. 2006, 16, 3793–3796.
6. Fabio, R. D.; Giovannini, R.; Bertani, B.; Borriello, M.; Bozzoli, A.; Donati, D.; Falchi,
A.; Ghirlanda, D.; Leslie, C. P.; Pecunioso, A.; Rumboldt, G.; Spada, S. Synthesis and
SAR of substituted tetrahydrocarbazole derivatives as new NPY-1 antagonists. Bioorg.
Med. Chem. Lett. 2006, 16, 1749–1752.
7. Hesse, M. Alkaloids, Nature Curse or Blessing? Wiley-VCH: New York, 2002.
8. Pindur, U.; Pfeuffer, L. [4 þ 2]-Cycloaddition to 4-demethoxycarbazomycin. Heterocycles
1987, 26, 325–327.
9. Kusurkar, R. S.; Patil, U. G. Synthesis of carbazoles via Diels–Alder reaction of 3-viny-
lindoles. Indian J. Chem. 1986, 25B, 1038–1041.
10. Caddick, S.; Fitzmaurice, R. Microwave enhanced synthesis. Tetrahedron 2009, 65,
3325–3355.
11. Smith, G. F. Indoles, part I: The formylation of indole and some reactions of 3-formylin-
dole. J. Chem. Soc. 1954, 3842–3846.
12. Hibino, S.; Sugino, E.; Yamochi, T.; Kuwata, M.; Hashimoto, H.; Sato, K.; Karasawa, Y.
Syntheses and sleeping-time-prolonging effect of nitramarine and related compounds.
Chem. Pharm. Bull. 1987, 35, 2261–2265.
13. Pindur, U.; Pfeuffer, L. Wittig-Olefinierung zu neuen donor-und akzeptor-substituierten 3
Vinyl indolen: Optimierte Syntheseverfahren. Monatsh. Chem. 1989, 120, 157–162.

REGIO- AND STEREOSELECTIVE SYNTHESIS OF CARBAZOLES
1795
14. Pfeuffer, L.; Pindur, U. Diels–Alder-Reaktionen von 20-substituierten 3-Vinyl-1H-indolen
zu neuen anellierten Indol-und Carbazol-Derivaten. Helv. Chim. Acta 1987, 70, 1419–
1428.
15. Pindur, U.; Kim, M. H.; Rogge, M.; Massa, W.; Moliniert, M. New Diels–Alder reactions
of (E=Z)-20-methoxy-substituted 3-vinylindoles with carbo- and heterodienophiles: Regio-
and stereoselective access to [b] annelated indoles and functionalized or [a] annelated
carbazoles. J. Org. Chem. 1992, 57, 910–915.
16. Cambridge Crystallographic Data Centre, 758883.
17. Srinivasan, P. C.; Saroja, B. Synthesis and [4 þ 2]-cycloadditions of N-phenylsulfonyl-3-
vinylindole. Synthesis 1986, 9, 748–749.
18. Pindur, U.; Pfeuffer, L. New reactions of 3-vinyl- and 3-(2-propenyl) indoles with N-
phenylmaleimide: [4 þ 2] Cycloaddition, ene reaction, and dimerization. Helv. Chim. Acta
1988, 71, 467–471.
19. Sheldrick, G. M. SHELX-97 Program for Crystal Structure Solution and Refinement;
University of Gottingen: Gottingen, Germany, 1997.