Synthesis of novel polycyclic indole-annulated thiopyranocoumarin derivatives via domino Knoevenagel-hetero-Diels-Alder reaction in aqueous media

Article abstract of DOI:10.1002/hlca.200900324

An efficient synthesis of polycyclic indole derivatives is achieved via domino Knoevenagel - hetero-Diels - Alder reaction of O-acrylated salicylaldehyde derivatives with dihydroindole-2-thiones in H₂O as solvent. The products are formed in goo

Full text of DOI:10.1002/hlca.200900324

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Helvetica Chimica Acta – Vol. 93 (2010)
Synthesis of Novel Polycyclic Indole-Annulated Thiopyranocoumarin
Derivatives via Domino Knoevenagel – Hetero-Diels – Alder Reaction in
Aqueous Media
by Firouz Matloubi Moghaddam*, Mostafa Kiamehr, Salman Taheri, and Zohreh Mirjafary
Laboratory of Organic Synthesis and Natural Products, Department of Chemistry, Sharif University of
Technology, P. O. Box 11155-9516, Tehran, Iran
(phone: þ 98-21-66165309; fax: þ 98-21-66012983; e-mail: matloubi@sharif.edu.)
An efficient synthesis of polycyclic indole derivatives is achieved via domino Knoevenagel – hetero-
Diels – Alder reaction of O-acrylated salicylaldehyde derivatives with dihydroindole-2-thiones in H2O as
solvent. The products are formed in good-to-excellent yields with high regio- and stereoselectivity.
Introduction. – Heterocycles have popularly been utilized as pharmacophores for
preparing drugs [1]. Among them, the indole moiety is frequently encountered in
medicinal chemistry and is considered to be a privileged scaffold [2]. However,
polycyclic annulated indole compounds continue to be of extensive synthetic interest,
partly because there are many biologically active natural products of this type, and also
because the polycyclic frameworks lead to relatively rigid structures that might be
expected to show substantial selectivity in their interactions with enzymes or receptors
[3]. On the other hand, coumarins and their derivatives are very important organic
compounds. They constitute the structural scaffold of several natural products [4].
Their applications range from pharmaceuticals [5], optical brighteners, and laser dyes
[6]. Also coumarins and functionalized coumarins have shown activity as antimicro-
bials and chemotherapeutics [7].
An important objective in organic synthesis is the development of highly efficient
synthetic procedures toward complex molecules. The hetero-Diels – Alder reaction
represents an effective method for the synthesis of heterocyclic compounds, especially
natural products [8]. In recent years, intramolecular hetero-Diels – Alder reactions
have widely been used in numerous reactions because of their economical and
stereocontrolled nature [9]. These reactions allow the formation of two or more rings in
one operation, thus avoiding sequential chemical transformations. However, it is
prerequisite that activating groups have to be built into dienophiles to achieve the
desired reactivity [10].
Recently, domino reactions have been used as highly efficient processes for the
improvement of reaction efficiency [11]. Among these reactions, the domino
Knoevenagel – hetero-Diels – Alder reaction is a very efficient process, especially in
the field of heterocycles and natural products [12].
Tietze et al. extensively described the domino Knoevenagel – hetero-Diels – Alder
reaction (DKHDA) of unsaturated aromatic and aliphatic aldehydes (especially O-
ꢀ 2010 Verlag Helvetica Chimica Acta AG, Zꢁrich

Helvetica Chimica Acta – Vol. 93 (2010)
965
allylated salicylaldehydes) with several 1,3-dicarbonyl compounds [13], and recently
Balalaie and co-workers described this type of reaction with O-propargylated
salicylaldehyde derivatives for synthesis of tetracycles with a pyran ring [14], but
DKHDA reactions of O-acrylated salicylaldehydes are rare [15].
In the context of our general interest in the synthesis of heterocyclic compounds
using thioamides [16], we herein report a new and highly efficient reaction for the
preparation of polycyclic compounds 3a – 3z, which consist of an indole ring (A) and a
dihydrothiopyran ring (B) annulated to a dihydrocoumarin ring (C; Scheme 1).
Scheme 1. One-Pot Synthesis of Polycyclic Indole Derivatives
Results and Discussion. – The O-acrylated salicylaldehyde derivatives 2 were
prepared in high yields and excellent purity via reaction of substituted salicylaldehydes
and (E)-acryloyl chloride derivatives using anhydrous K2CO3 in dry acetone. Our first
experiment showed that no catalyst is required for DKHDA reaction. The effect of
solvent was studied by carrying out the reaction at various solvents such as toluene,
MeCN, and H2O. Hydrolysis of the ester moiety of intermediate 4 (cf. Scheme 2) in
organic solvents led to low yields. Surprisingly, the hydrolysis did not occur in H2O.
However, high yields with short reaction times were observed in refluxing H2O. The
catalyst-free DKHDA reaction of dihydroindole-2-thiones 1 and O-acrylated salicy-
laldehyde derivatives 2 in H2O led to compounds 3a – 3z in good-to-excellent yields.
The reaction is highly stereoselective, leading exclusively to the cis-fused compounds. It
is highly desirable to develop environmentally benign processes that can be conducted
in aqueous media. Furthermore, using H2O as a solvent has advantages, such as low cost
and safety, and it is part of the biosphere [17]. To generalize our method, we used a
series of dihydroindole-2-thione derivatives 1 and O-acrylated salicylaldehyde
derivatives 2 to obtain the corresponding products 3a – 3z in high yields (Table).
The structures of compounds 3a – 3z have been determined by spectroscopic
methods (1H- and 13C-NMR, and DEPT) and elemental analysis. The relative
configurations were determined from the coupling constants of the relevant H-atoms
and NOE experiments. For instance, in compound 3k, Ha and Hb (J ¼ 9.5 Hz) are in
trans-relation, and Hb and Hc (J ¼ 4.5 Hz) are in a cis-arrangement. NOE Measure-
ments on compound 3k confirmed the cis-orientation of Hb and Hc (Fig.). In all the
cases, the relative orientation of the ring junction H-atoms was found to be same.

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Table. Synthesis of Polycyclic Indole Derivativesa)
Product Yield [%]b) Entry R1 R2 R3
Entry R1 R2 R3
Product Yield [%]b)
1
2
3
4
5
6
7
8
H
H
H
H
H
H
Ph
Ph 5-Br
Ph 3-MeO
Me 3-MeO
H
H
H
3a
3b
3c
3d
3e
3f
3g
3h
3i
88
80
94
94
85
90
80
88
83
74
95
92
83
14
15
16
17
18
19
20
21
22
23
24
25
26
Et Ph 5-Br
Et Ph 3-MeO
Et Ph 5,6-Benzo 3p
Et Me 3-MeO
Et Me 5-Br
3n
3o
85
92
70
87
93
85
92
88
82
65
83
90
85
3q
3r
3s
3t
3u
3v
5-Br
H
H
Et
Ph Ph
H
H
H
Me Ph
Me Ph 3-MeO
Me Ph 5-Br
Me Ph 5,6-Benzo 3j
Me Me 5-Br
Ph Ph 5-Br
Ph Ph 3-MeO
Ph Ph 5,6-Benzo 3w
Ph Me 5-Br
9
10
11
12
13
3k
3l
3m
3x
3y
3z
Me
Et Ph
H
5-Br
H
Ph Me 3-MeO
Ph
H
5-Br
a) All the reactions were carried out in H2O under reflux for 2 h, molar ratio 1/2 1 : 1. b) Isolated product.
Figure. Selected NOE enhancements of 3k
A plausible mechanism for the intramolecular DKHDA reaction to produce
stereoselectively products 3a – 3z is proposed in Scheme 2. Dihydroindole-2-thiones 1
undergo a Knoevenagel condensation with aldehydes 2 in refluxing H2O to afford the
ꢂheterodienesꢃ 4, the stereochemistry of the final Diels – Alder reaction depends on the
ꢂendoꢃ- and ꢂexoꢃ-orientation of the dienophile in the transition state. All efforts to
isolate the intermediates 4 failed. The intermediates 4 may undergo rotation around
single bond to assume the structures 4a, which may then undergo [4 þ 2] cyclization
with ꢂendoꢃ-selectivity to give desired products 3a – 3z.
Conclusions. – We have reported a highly efficient stereoselective method for the
synthesis of novel heteropolycyclic compounds through a DKHDA reaction in aqueous
media. The major advantage of this reaction is the ease of the workup, since the
products can be isolated without chromatography. This reaction also offers other
advantages such as clean reactions, high yields of products, short reaction time, and no
need of a catalyst, which make it a useful and attractive procedure for the synthesis of
pentacyclic indole derivatives. Further studies to extend the scope and synthetic utility
of dihydroindole-2-thiones and dihydroindole-2-ones in DKHDA reactions are in
progress in our laboratory.

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967
Scheme 2. A Plausible Mechanism for the Formation of Compounds 3a – 3z
We would like to acknowledge the Islamic Development Bank (IDB) for granting a loan in 1993 for
purchasing a 500-MHz Bruker NMR spectrometer.
Experimental Part
General. Commercially available materials were purchased from Sigma – Aldrich and Merck, and
were used without any additional purification. TLC: Silica-gel plates 60 F254 (SiO2; Merck). M.p.: Bꢀchi
1
melting point B-540 apparatus; in sealed capillaries; uncorrected. H- and 13C-NMR Spectra: Bruker
(DRX-500 Avance) spectrometer at 500 (1H) and 125 (13C) MHz, in CDCl3 and (D6)DMSO solns., at
ambient temp.; d in ppm rel. to Me4Si as internal standard, J in Hz. Signals of the 13C-NMR spectra
corresponding to CH, CH2, or Me groups are assigned from DEPT. Elemental analysis: Perkin-Elmer
2004 (II) CHN analyzer.
General Procedure for Preparation of the O-Acrylated Salicylaldehyde Derivatives 2. A mixture of a
salicylaldehyde derivative (10 mmol), and acryloyl chloride or its derivative (12 mmol) was stirred in
acetone (10 ml) in the presence of K2CO3 (1.38 – 1.66 g, 10 – 12 mmol) for 8 – 10 h at r.t. After completion
of the reaction (monitored by TLC), ice-cold H2O (50 ml) was added to the mixture with vigorous
stirring to afford a light precipitate that was filtered, washed with H2O, and air-dried.
General Procedure for Domino Knoevenagel-Hetero-Diels – Alder (DKHDA) Reaction (3a – 3z).
Dihydroindole-2-thiones 1 were prepared according to the procedure described in [18]. A mixture of 1
(1 mmol) and an O-acrylated salicylaldehyde derivative 2 (1 mmol) in H2O (8 ml) was refluxed. The
progress of the reaction was monitored by TLC (mini-extraction with AcOEt carried out for TLC). After
completion (2 h), the mixture was cooled, and the solid precipitate was filtered, washed with H2O, air
dried, and recrystallized from EtOH.
(6aR*,7S*,13cS*)-6a,7,9,13c-Tetrahydro-7-phenyl-6H-[1]benzopyrano[4’,3’:4,5]thiopyrano[2,3-
1
b]indol-6-one (3a). Yellow solid. Yield: 168 mg (88%). M.p. 267 – 2688. H-NMR (CDCl3/(D6)DMSO
1:10): 3.39 (dd, J ¼ 8.7, 4.5, HꢀC(6a)); 4.49 – 4.52 (m, HꢀC(7), HꢀC(13c)); 6.83 (t, J ¼ 7.4, 1 H); 6.84 –
6.93 (m, 3 H); 7.08 – 7.18 (m, 9 H); 10.45 (s, NH). 13C-NMR (CDCl3/(D6)DMSO 1:10): 33.14 (CH); 43.46

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(CH); 47.52 (CH); 103.39 (C); 111.09 (CH); 116.95 (CH); 116.97 (CH); 119.94 (CH); 121.16 (CH);
125.10 (CH); 126.18 (C); 128.06 (C); 128.47 (C); 128.70 (CH); 129.08 (CH); 129.17 (CH); 129.24 (CH);
129.76 (CH); 136.84 (C); 137.56 (C); 150.13 (C); 167.44 (C). Anal. calc. for C24H17NO2S (383.46): C 75.17,
H 4.47, N 3.65; found: C 74.92, H 4.42, N 3.68.
(6aR*,7S*,13cS*)-2-Bromo-6a,7,9,13c-tetrahydro-7-phenyl-6H-[1]benzopyrano[4’,3’:4,5]thiopyra-
no[2,3-b]indol-6-one (3b). Pale-yellow solid. Yield: 185 mg (80%). M.p. 245 – 2478. 1H-NMR
((D6)DMSO): 3.81 (dd, J ¼ 8.2, 4.6, HꢀC(6a)); 4.77 (d, J ¼ 8.0, HꢀC(7)); 4.84 (d, J ¼ 4.6, HꢀC(13c));
6.98 (t, J ¼ 7.4, 1 H); 7.06 (t, J ¼ 7.5, 1 H); 7.13 (d, J ¼ 8.6, 1 H); 7.24 (d, J ¼ 7.5, 1 H); 7.31 (d, J ¼ 8.0, 1 H);
7.34 – 7.46 (m, 6 H); 7.55 (d, J ¼ 8.5, 1 H); 11.52 (s, NH). 13C-NMR ((D6)DMSO): 32.53 (CH); 43.28
(CH); 46.09 (CH); 103.22 (C); 111.55 (CH); 117.20 (C); 117.37 (CH); 119.79 (CH); 120.32 (CH); 121.57
(CH); 128.42 (C); 128.52 (C); 129.38 (CH); 129.38 (C); 129.53 (2 CH); 132.35 (CH); 132.53 (CH);
136.96 (C); 138.37 (C); 149.88 (C); 166.83 (C). Anal. calc. for C24H16BrNO2S (462.36): C 62.35, H 3.49, N
3.03; found: C 62.05, H 3.42, N 2.98.
(6aR*,7S*,13cS*)-6a,7,9,13c-Tetrahydro-4-methoxy-7-phenyl-6H-[1]benzopyrano[4’,3’:4,5]thiopyra-
no[2,3-b]indol-6-one (3c). Yellow solid. Yield: 194 mg (94%). M.p. 253 – 2558. 1H-NMR ((D6)DMSO):
3.75 (dd, J ¼ 7.0, 4.7, HꢀC(6a)); 3.82 (s, MeO); 4.56 (d, J ¼ 4.7, HꢀC(13c)); 4.83 (d, J ¼ 6.7, HꢀC(7));
6.87 (t, J ¼ 7.5, 1 H); 6.92 (d, J ¼ 6.9, 1 H); 7.00 (t, J ¼ 7.5, 1 H); 7.08 – 7.15 (m, 3 H); 7.27 (d, J ¼ 8.0, 1 H);
7.33 – 7.40 (m, 3 H); 7.43 (d, J ¼ 7.0, 2 H); 11.44 (s, NH). 13C-NMR ((D6)DMSO): 32.48 (CH); 43.32
(CH); 46.08 (CH); 56.78 (Me); 103.79 (C); 111.31 (CH); 112.96 (CH); 117.79 (CH); 119.98 (CH); 121.30
(CH); 121.40 (CH); 125.31 (CH); 127.69 (C); 128.08 (C); 128.48 (C); 129.14 (CH); 129.21 (CH); 129.53
(CH); 136.94 (C); 139.26 (C); 139.66 (C); 148.06 (C); 167.26 (C). Anal. calc. for C25H19NO3S (413.49): C
72.62, H 4.63, N 3.39; found: C 72.32, H 4.56, N 3.33.
(6aR*,7R*,13cS*)-6a,7,9,13c-Tetrahydro-4-methoxy-7-methyl-6H-[1]benzopyrano[4’,3’:4,5]thio-
pyrano[2,3-b]indol-6-one (3d). Yellow solid. Yield: 165 mg (94%). M.p. 205 – 2088. 1H-NMR
((D6)DMSO): 1.49 (d, J ¼ 6.7, Me); 3.29 (dd, J ¼ 4.7, 3.7, HꢀC(6a)); 3.72 – 3.75 (m, HꢀC(7)); 3.85 (s,
MeO); 4.77 (d, J ¼ 3.7, HꢀC(13c)); 6.87 (t, J ¼ 7.2, 1 H); 6.98 (d, J ¼ 6.4, 2 H); 7.06 (d, J ¼ 7.7, 1 H); 7.11 –
7.17 (m, 2 H); 7.26 (d, J ¼ 7.8, 1 H); 10.93 (s, NH). 13C-NMR ((D6)DMSO): 21.27 (Me); 32.19 (CH);
34.13 (CH); 45.87 (CH); 56.75 (Me); 103.37 (C); 111.14 (CH); 112.89 (CH); 117.75 (CH); 119.79 (CH);
121.00 (CH); 121.57 (CH); 125.19 (CH); 127.87 (C); 127.98 (C); 128.47 (C); 137.05 (C); 139.84 (C);
148.07 (C); 167.98 (C). Anal. calc. for C20H17NO3S (351.42): C 68.36, H 4.88, N 3.99; found: C 68.51, H
4.82, N 3.93.
(6aR*,13cS*)-2-Bromo-6a,7,9,13c-tetrahydro-6H-[1]benzopyrano[4’,3’:4,5]thiopyrano[2,3-b]indol-
6-one (3e). Light yellow solid. Yield: 164 mg (85%). M.p. 248 – 2508. 1H-NMR ((D6)DMSO): 3.23 – 3.37
(m, 2 HꢀC(7)); 3.58 (m, HꢀC(6a)); 4.86 (d, J ¼ 4.2, HꢀC(13c)); 6.92 (t, J ¼ 7.3, 1 H); 7.01 (t, J ¼ 7.4,
1 H); 7.10 – 7.14 (m, 2 H); 7.26 (d, J ¼ 7.9, 1 H); 7.53 (s, 1 H); 7.54 (d, J ¼ 7.9, 1 H); 11.41 (s, NH). 13C-NMR
((D6)DMSO): 25.22 (CH2); 30.30 (CH); 39.51 (CH); 103.28 (C); 111.33 (CH); 117.10 (C); 117.24 (CH);
119.91 (CH); 120.12 (CH); 121.33 (CH); 127.85 (C); 128.54 (C); 129.56 (C); 132.36 (CH); 132.44 (CH);
136.87 (C); 150.13 (C); 168.51 (C). Anal. calc. for C18H12BrNO2S (386.26): C 55.97, H 3.14, N 3.63; found:
C 56.12, H 3.18, N 3.68.
(6aR*,13cS*)-6a,7,9,13c-Tetrahydro-6H-[1]benzopyrano[4’,3’:4,5]thiopyrano[2,3-b]indol-6-one
(3f). Yellow solid. Yield: 138 mg (90%). M.p. 227 – 2298. 1H-NMR (CDCl3/(D6)DMSO 1:10): 2.88 (dd,
J ¼ 12.4, 2.4, 1 HꢀC(7)); 3.02 (dd, J ¼ 12.4, 10.2, 1 HꢀC(7)); 3.15 – 3.18 (m, HꢀC(6a)); 4.48 (d, J ¼ 4.8,
HꢀC(13c)); 6.74 (t, J ¼ 7.4, 1 H); 6.79 – 6.83 (m, 3 H); 6.99 – 7.06 (m, 4 H); 10.43 (s, NH). 13C-NMR
(CDCl3/(D6)DMSO (10%)): 24.85 (CH2); 32.85 (CH); 40.47 (CH); 103.37 (C); 110.90 (CH); 116.74
(CH); 117.01(CH); 119.80 (CH); 121.03 (CH); 125.17 (CH); 125.87 (C); 126.79 (C); 128.66 (C); 128.94
(CH); 129.58 (CH); 136.70 (C); 150.05 (C); 169.26 (C). Anal. calc. for C18H13NO2S (307.37): C 70.34, H
4.26, N 4.56; found: C 70.04, H 4.31, N 4.51.
(6aR*,7S*,13cS*)-6a,7,9,13c-Tetrahydro-9-methyl-7-phenyl-6H-[1]benzopyrano[4’,3’:4,5]thiopyra-
1
no[2,3-b]indol-6-one (3g). Yellow solid. Yield: 154 mg (80%). M.p. 247 – 2508. H-NMR (CDCl3): 3.57
(dd, J ¼ 8.7, 4.5, HꢀC(6a)); 3.66 (s, MeN); 4.71 – 4.73 (m, HꢀC(7), HꢀC(13c)); 7.08 – 7.12 (m, 3 H); 7.20
(t, J ¼ 7.6, 1 H); 7.27 (d, J ¼ 7.8, 1 H); 7.31 (d, J ¼ 7.9, 2 H); 7.33 – 7.38 (m, 6 H). 13C-NMR (CDCl3): 30.43
(Me); 33.47 (CH); 43.79 (CH); 47.45 (CH); 103.11 (C); 108.96 (CH); 117.13 (CH); 117.47 (CH); 120.38
(CH); 121.37 (CH); 125.26 (CH); 126.26 (C); 128.46 (C); 128.82 (CH); 129.41 (3 CH); 129.88 (CH);

Helvetica Chimica Acta – Vol. 93 (2010)
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130.61 (C); 137.39 (C); 137.80 (C); 150.29 (C); 167.54 (C). Anal. calc. for C25H19NO2S (397.49): C 75.54, H
4.82, N 3.52; found: C 75.31, H 4.86, N 3.44.
(6aR*,7S*,13cS*)-6a,7,9,13c-Tetrahydro-4-methoxy-9-methyl-7-phenyl-6H-[1]benzopyrano[4’,3’:4,5]-
1
thiopyrano[2,3-b]indol-6-one (3h). Light yellow solid. Yield: 188 mg (88%). M.p. 259 – 2618. H-NMR
((D6)DMSO): 3.64 (s, MeN); 3.76 (dd, J ¼ 5.7, 4.4, HꢀC(6a)); 3.82 (s, MeO); 4.60 (d, J ¼ 4.4,
HꢀC(13c)); 4.87 (d, J ¼ 5.7, HꢀC(7)); 6.91 – 6.95 (m, 2 H); 7.09 – 7.14 (m, 3 H); 7.19 (d, J ¼ 7.4, 1 H);
7.36 – 7.44 (m, 6 H). 13C-NMR ((D6)DMSO): 30.68 (Me); 32.62 (CH); 43.43 (CH); 45.84 (CH); 56.80
(Me); 103.34 (C); 109.84 (CH); 113.02 (CH); 117.92 (CH); 120.27 (CH); 121.30 (CH); 121.40 (CH);
125.37 (CH); 127.59 (C); 128.12 (C); 129.23 (2 CH); 129.56 (CH); 130.25 (C); 137.78 (C); 138.92 (C);
139.60 (C); 148.06 (C); 167.18 (C). Anal. calc. for C26H21NO3S (427.51): C 73.04, H 4.95, N 3.28; found: C
72.83, H 4.88, N 3.34.
(6aR*,7S*,13cS*)-2-Bromo-6a,7,9,13c-tetrahydro-9-methyl-7-phenyl-6H-[1]benzopyrano[4’,3’:4,5]-
thiopyrano[2,3-b]indol-6-one (3i). Yellow solid. Yield: 197 mg (83%). M.p. 260 – 2638. 1H-NMR
(CDCl3): 3.60 (dd, J ¼ 9.0, 4.4, HꢀC(6a)); 3.71 (s, MeN); 4.72 (d, J ¼ 9.0, HꢀC(7)); 4.75 (d, J ¼ 3.8,
HꢀC(13c)); 7.02 (d, J ¼ 8.6, 1 H); 7.18 (t, J ¼ 7.4, 1 H); 7.26 (t, J ¼ 7.6, 1 H); 7.36 – 7.42 (m, 8 H); 7.48 (dd,
J ¼ 8.6, 2.1, 1 H). 13C-NMR (CDCl3): 30.47 (Me); 33.52 (CH); 43.78 (CH); 47.13 (CH); 102.20 (C);
109.11 (CH); 117.17 (CH); 118.05 (C); 119.09 (CH); 120.71 (CH); 121.58 (CH); 128.23 (C); 128.56 (C);
128.78 (CH); 129.49 (CH); 129.60 (CH); 130.81 (C); 132.51 (CH); 132.56 (CH); 136.96 (C); 137.85 (C);
149.37 (C); 166.81 (C). Anal. calc. for C25H18BrNO2S (476.38): C 63.03, H 3.81, N 2.94; found: C 63.32, H
3.75, N 2.98.
(4aR*,5S*,11cS*)-4a,5,7,11c-Tetrahydro-7-methyl-5-phenyl-4H-naphtho[1’’,2’’:5’,6’]pyrano[4’,3’:4,5]-
1
thiopyrano[2,3-b]indol-4-one (3j). Light brown solid. Yield: 164 mg (74%). M.p. 204 – 2078. H-NMR
((D6)DMSO): 3.69 (s, MeN); 3.91 (dd, J ¼ 3.9, 2.0, HꢀC(4a)); 4.70 (d, J ¼ 3.9, HꢀC(5)); 5.39 (d, J ¼ 2.0,
HꢀC(11c)); 5.83 (d, J ¼ 8.0, 1 H); 6.38 (t, J ¼ 7.4, 1 H); 6.87 (t, J ¼ 7.4, 1 H); 7.32 – 7.38 (m, 3 H); 7.43 (t,
J ¼ 7.2, 2 H); 7.54 – 7.58 (m, 3 H); 7.63 (t, J ¼ 7.4, 1 H); 7.97 (d, J ¼ 8.4, 1 H); 8.02 (d, J ¼ 8.8, 1 H); 8.07 (d,
J ¼ 8.0, 1 H). 13C-NMR ((D6)DMSO): 27.31 (CH); 30.78 (Me); 43.34 (CH); 45.27 (CH); 102.93 (C);
109.71 (CH); 117.55 (CH); 118.17 (CH); 119.79 (CH); 120.03 (C); 120.84 (CH); 123.72 (CH); 126.31
(CH); 126.93 (C); 128.72 (2 CH); 128.95 (CH); 129.58 (CH); 129.98 (CH); 130.62 (CH); 130.90 (C);
131.13 (C); 132.28 (C); 137.71 (C); 141.67 (C); 149.55 (C); 168.09 (C). Anal. calc. for C29H21NO2S
(447.55): C 77.83, H 4.73, N 3.13; found: C 77.01, H 4.61, N 3.19.
(6aR*,7R*,13cS*)-2-Bromo-6a,7,9,13c-tetrahydro-7,9-dimethyl-6H-[1]benzopyrano[4’,3’:4,5]thio-
1
pyrano[2,3-b]indol-6-one (3k). Yellow solid. Yield: 219 mg (95%). M.p. 245 – 2478. H-NMR (CDCl3):
1.56 (d, J ¼ 6.1, Me); 3.18 (dd, J ¼ 9.5, 4.5, HꢀC(6a)); 3.59 – 3.63 (m, HꢀC(7)); 3.68 (s, MeN); 4.82 (d,
J ¼ 4.3, HꢀC(13c)); 7.01 (d, J ¼ 8.6, 1 H); 7.18 (t, J ¼ 7.4, 1 H); 7.24 (t, J ¼ 7.6, 1 H); 7.31 – 7.35 (m, 2 H);
7.40 – 7.44 (m, 2 H). 13C-NMR (CDCl3): 19.59 (Me); 30.41 (Me); 33.42 (CH); 33.45 (CH); 47.16 (CH);
102.00 (C); 109.04 (CH); 116.92 (CH); 118.14 (C); 119.01 (CH); 120.64 (CH); 121.46 (CH); 128.33 (C);
128.66 (C); 130.55 (C); 132.25 (CH); 132.27 (CH); 137.85 (C); 149.17 (C); 167.69 (C). Anal. calc. for
C20H16BrNO2S (414.32): C 57.98, H 3.89, N 3.38; found: C 57.58, H 3.74, N 3.31.
(6aR*,13cS*)-2-Bromo-6a,7,9,13c-tetrahydro-9-methyl-6H-[1]benzopyrano[4’,3’:4,5]thiopyrano[2,3-
b]indol-6-one (3l). Light yellow solid. Yield: 184 mg (92%). M.p. 255 – 2578. 1H-NMR (CDCl3): 3.21 (dd,
J ¼ 12.5, 2.4, 1 HꢀC(7)); 3.28 (dd, J ¼ 12.4, 10.7, HꢀC(7)); 3.41 – 3.45 (m, HꢀC(6a)); 3.70 (s, MeN); 4.80
(d, J ¼ 4.6, HꢀC(13c)); 7.01 (d, J ¼ 8.6, 1 H); 7.18 (t, J ¼ 7.2, 1 H); 7.24 (t, J ¼ 7.2, 1 H); 7.33 (s, 1 H); 7.34
(d, J ¼ 8.0, 1 H); 7.41 (d, J ¼ 7.8, 1 H); 7.44 (dd, J ¼ 8.5, 2.0, 1 H). 13C-NMR ((D6)DMSO): 25.28 (CH2);
30.59 (Me); 33.36 (CH); 39.35 (CH); 102.82 (C); 109.84 (CH); 117.14 (C); 117.36 (CH); 119.91 (CH);
120.38 (CH); 121.30 (CH); 128.16 (C); 129.42 (C); 130.09 (C); 132.36 (CH); 132.44 (CH); 137.69 (C);
150.05 (C); 168.40 (C). Anal. calc. for C19H14BrNO2S (400.29): C 57.01, H 3.53, N 3.50; found: C 56.64, H
3.35, N 3.43.
(6aR*,7S*,13cS*)-9-Ethyl-6a,7,9,13c-tetrahydro-7-phenyl-6H-[1]benzopyrano[4’,3’:4,5]thiopyra-
no[2,3-b]indol-6-one (3m). White solid. Yield: 170 mg (83%). M.p. 253 – 2568. 1H-NMR (CDCl3): 1.39 (t,
J ¼ 7.2, Me); 3.60 (dd, J ¼ 8.9, 4.5, HꢀC(6a)); 4.08 – 4.14 (m, CH2N); 4.70 (d, J ¼ 8.9, HꢀC(7)); 4.75 (d,
J ¼ 4.2, HꢀC(13c)); 7.09 (t, J ¼ 6.8, 3 H); 7.18 (t, J ¼ 7.4, 1 H); 7.27 – 7.38 (m, 9 H). 13C-NMR (CDCl3):
15.35 (Me); 33.55 (CH); 39.26 (CH2); 43.76 (CH); 47.50 (CH); 103.16 (C); 109.04 (CH); 117.28 (CH);
117.54 (CH); 120.30 (CH); 121.30 (CH); 125.26 (CH); 126.26 (C); 128.72 (C); 128.82 (CH); 129.41

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Helvetica Chimica Acta – Vol. 93 (2010)
(2 CH); 129.44 (CH); 129.69 (C); 129.88 (CH); 136.72 (C); 137.27 (C); 150.26 (C); 167.52 (C). Anal. calc.
for C26H21NO2S (411.52): C 75.89, H 5.14, N 3.40; found: C 75.59, H 5.03, N 3.48.
(6aR*,7S*,13cS*)-2-Bromo-9-ethyl-6a,7,9,13c-tetrahydro-7-phenyl-6H-[1]benzopyrano[4’,3’:4,5]-
1
thiopyrano[2,3-b]indol-6-one (3n). Light yellow solid. Yield: 208 mg (85%). M.p. 267 – 2708. H-NMR
(CDCl3): 1.45 (t, J ¼ 7.2, Me); 3.63 (dd, J ¼ 9.1, 4.4, HꢀC(6a)); 4.14 – 4.20 (m, CH2N); 4.70 (d, J ¼ 9.1,
HꢀC(7)); 4.78 (d, J ¼ 4.1, HꢀC(13c)); 7.02 (d, J ¼ 8.6, 1 H); 7.18 (t, J ¼ 7.8, 1 H); 7.24 (t, J ¼ 7.3, 1 H);
7.38 – 7.42 (m, 8 H); 7.48 (dd, J ¼ 8.6, 2.3, 1 H). 13C-NMR (CDCl3): 15.35 (Me); 33.61 (CH); 39.33 (CH2);
43.76 (CH); 47.18 (CH); 102.22 (C); 109.16 (CH); 117.23 (CH); 118.05 (C); 119.06 (CH); 120.62 (CH);
121.51 (CH); 128.48 (C); 128.53 (C); 128.79 (CH); 129.47 (CH); 129.59 (CH); 129.90 (C); 132.49 (CH);
132.55 (CH); 136.79 (C); 137.34 (C); 149.36 (C); 166.80 (C). Anal. calc. for C26H20BrNO2S (490.41): C
63.68, H 4.11, N 2.86; found: C 64.05, H 4.04, N 2.91.
(6aR*,7S*,13cS*)-9-Ethyl-6a,7,9,13c-tetrahydro-4-methoxy-7-phenyl-6H-[1]benzopyrano[4’,3’:4,5]-
1
thiopyrano[2,3-b]indol-6-one (3o). Light yellow solid. Yield: 203 mg (92%). M.p. 268 – 2708. H-NMR
((D6)DMSO): 1.26 (t, J ¼ 7.0, Me); 3.79 (dd, J ¼ 6.8, 4.8, HꢀC(6a)); 3.82 (s, MeO); 4.08 – 4.18 (m,
CH2N); 4.61 (d, J ¼ 4.8, HꢀC(13c)); 4.88 (d, J ¼ 6.9, HꢀC(7)); 6.89 – 6.94 (m, 2 H); 7.06 – 7.14 (m, 3 H);
7.19 (d, J ¼ 7.7, 1 H); 7.36 – 7.40 (m, 3 H); 7.43 – 7.47 (m, 3 H). 13C-NMR ((D6)DMSO): 15.58 (Me); 32.64
(CH); 39.12 (CH2); 43.38 (CH); 45.86 (CH); 56.80 (Me); 103.56 (C); 109.82 (CH); 113.02 (CH); 118.05
(CH); 120.24 (CH); 121.32 (CH); 121.40 (CH); 125.37 (CH); 127.59 (C); 128.39 (C); 129.23 (2 CH);
129.56 (CH); 129.56 (C); 136.70 (C); 138.94 (C); 139.60 (C); 148.06 (C); 167.16 (C). Anal. calc. for
C27H23NO3S (441.54): C 73.45, H 5.25, N 3.17; found: C 73.05, H 5.25, N 3.11.
(4aR*,5S*,11cS*)-7-Ethyl-4a,5,7,11c-tetrahydro-5-phenyl-4H-naphtho[1’’,2’’:5’,6’]pyrano[4’,3’:4,5]-
1
thiopyrano[2,3-b]indol-4-one (3p). Light brown solid. Yield: 161 mg (70%). M.p. 211 – 2148. H-NMR
((D6)DMSO): 1.29 (t, J ¼ 6.9, Me); 3.91 (dd, J ¼ 4.3, 2.0, HꢀC(4a)); 4.15 – 4.21 (m, CH2N); 4.70 (d, J ¼
4.3, HꢀC(5)); 5.39 (d, J ¼ 2.0, HꢀC(11c)); 5.83 (d, J ¼ 8.1, 1 H); 6.38 (t, J ¼ 7.6, 1 H); 6.87 (t, J ¼ 7.6,
1 H); 7.34 – 7.38 (m, 3 H); 7.43 (t, J ¼ 7.4, 2 H); 7.54 – 7.58 (m, 3 H); 7.63 (t, J ¼ 7.5, 1 H); 7.97 (d, J ¼ 8.3,
1 H); 8.02 (d, J ¼ 8.8, 1 H); 8.07 (d, J ¼ 8.0, 1 H). 13C-NMR ((D6)DMSO): 15.48 (Me); 27.35 (CH); 39.13
(CH2); 43.28 (CH); 45.37 (CH); 103.18 (C); 109.67 (CH); 117.72 (CH); 118.17 (CH); 119.76 (CH);
120.06 (C); 120.88 (CH); 123.79 (CH); 126.31 (CH); 127.20 (C); 128.72 (2 CH); 128.92 (CH); 129.61
(CH); 129.89 (C); 129.96 (CH); 130.62 (CH); 131.13 (C); 132.28 (C); 136.62 (C); 141.67 (C); 149.55 (C);
168.07 (C). Anal. calc. for C30H23NO2S (461.57): C 78.07, H 5.02, N 3.03; found: C 78.27, H 5.06, N, 3.05.
(6aR*,7R*,13cS*)-9-Ethyl-6a,7,9,13c-tetrahydro-4-methoxy-7-methyl-6H-[1]benzopyrano[4’,3’:4,5]-
thiopyrano[2,3-b]indol-6-one (3q). Yellow solid. Yield: 165 mg (87%). M.p. 173 – 1768. 1H-NMR
((D6)DMSO): 1.21 (t, J ¼ 7.0, Me); 1.47 (d, J ¼ 6.9, Me); 3.40 (dd, J ¼ 5.7, 5.6, HꢀC(6a)); 3.79 – 3.81 (m,
4 H); 4.03 – 4.09 (m, CH2N); 4.78 (d, J ¼ 4.6, HꢀC(13c)); 6.88 (t, J ¼ 7.8, 1 H); 7.01 – 7.09 (m, 3 H); 7.13 –
7.19 (m, 2 H); 7.40 (d, J ¼ 8.1, 1 H). 13C-NMR ((D6)DMSO): 15.48 (Me); 21.34 (Me); 32.19 (CH); 34.31
(CH); 38.94 (CH2); 45.54 (CH); 56.66 (Me); 103.07 (C); 109.62 (CH); 112.78 (CH); 118.05 (CH); 120.03
(CH); 121.03 (CH); 121.55 (CH); 125.26 (CH); 127.82 (C); 128.29 (C); 129.07(C); 136.69 (C); 139.69
(C); 148.02 (C); 167.93 (C). Anal. calc. for C22H21NO3S (379.47): C 69.63, H 5.58, N 3.69; found: C 69.25,
H 5.55, N 3.74.
(6aR*,7S*,13cS*)-2-Bromo-9-ethyl-6a,7,9,13c-tetrahydro-7-methyl-6H-[1]benzopyrano[4’,3’:4,5]-
thiopyrano[2,3-b]indol-6-one (3r). Pale-yellow solid. Yield: 200 mg (93%). M.p. 238 – 2408. 1H-NMR
(CDCl3): 1.43 (t, J ¼ 7.2, Me); 1.56 (d, J ¼ 6.8, Me); 3.19 (dd, J ¼ 9.6, 4.6, HꢀC(6a)); 3.58 – 3.62 (m,
HꢀC(7)); 4.08 – 4.19 (m, CH2N); 4.84 (d, J ¼ 4.4, HꢀC(11c)); 7.01 (d, J ¼ 8.6, 1 H); 7.18 (t, J ¼ 7.4, 1 H);
7.24 (t, J ¼ 7.5, 1 H); 7.31 (s, 1 H); 7.37 (d, J ¼ 8.1, 1 H); 7.41 – 7.44 (m, 2 H). 13C-NMR (CDCl3): 15.33
(Me); 19.52 (Me); 33.39 (CH); 33.49 (CH); 39.26 (CH2); 47.24 (CH); 102.04 (C); 109.11 (CH); 117.00
(CH); 118.14 (C); 118.99 (CH); 120.56 (CH); 121.40 (CH); 128.58 (C); 128.66 (C); 129.64 (C); 132.26
(2 CH); 136.79 (C); 149.17 (C); 167.69 (C). Anal. calc. for C21H18BrNO2S (428.34): C 58.89, H 4.24, N
3.27; found: C 58.63, H 4.18, N 3.21.
(6aR*,13cS*)-9-Ethyl-6a,7,9,13c-tetrahydro-6H-[1]benzopyrano[4’,3’:4,5]thiopyrano[2,3-b]indol-6-
one (3s). Yellow solid. Yield: 142 mg (85%). M.p. 231 – 2338. 1H-NMR (CDCl3): 1.37 (t, J ¼ 7.2, Me); 3.16
(dd, J ¼ 11.9, 2.0, 1 HꢀC(7)); 3.28 (dd, J ¼ 12.3, 10.8, HꢀC(7)); 3.41 – 3.44 (m, HꢀC(6a)); 4.04 – 4.14 (m,
CH2N); 4.78 (d, J ¼ 4.8, HꢀC(11c)); 7.06 (t, J ¼ 7.5, 1 H); 7.10 (t, J ¼ 8.1, 2 H); 714 – 7.22 (m, 2 H); 7.28 –
7.32 (m, 2 H); 7.39 (d, J ¼ 7.8, 1 H). 13C-NMR ((D6)DMSO): 15.30 (Me); 24.98 (CH2); 32.90 (CH); 39.18

Helvetica Chimica Acta – Vol. 93 (2010)
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(CH2); 40.64 (CH); 103.21 (C); 108.95 (CH); 117.32 (CH); 117.36 (CH); 120.27 (CH); 121.30 (CH);
125.47 (CH); 125.89 (C); 128.38 (C); 129.02 (C); 129.14 (CH); 129.76 (CH); 136.64 (C); 150.15 (C);
169.62 (C). Anal. calc. for C20H17NO2S (335.42): C 71.62, H 5.11, N 4.18; found: C 71.15, H 5.04, N 4.16.
(6aR*,7S*,13cS*)-6a,7,9,13c-Tetrahydro-7,9-diphenyl-6H-[1]benzopyrano[4’,3’:4,5]thiopyrano[2,3-
b]indol-6-one (3t). White solid. Yield: 211 mg (92%). M.p. 250 – 2528. 1H-NMR (CDCl3): 3.67 (dd, J ¼
9.4, 4.5, HꢀC(6a)); 4.63 (d, J ¼ 9.4, HꢀC(7)); 4.87 (d, J ¼ 4.2, HꢀC(11c)); 7.11 – 7.17 (m, 4 H); 7.24 – 7.27
(m, 1 H); 7.32 – 7.35 (m, 7 H); 7.42 – 7.57 (m, 6 H). 13C-NMR (CDCl3): 33.74 (CH); 44.03 (CH); 47.46
(CH); 104.91 (C); 110.27 (CH); 117.33 (CH); 117.48 (CH); 121.23 (CH); 122.07 (CH); 125.35 (CH);
126.06 (C); 127.60 (CH); 128.76 (CH); 128.88 (CH); 128.97 (C); 129.34 (CH); 129.45 (CH); 129.49
(CH); 129.85 (CH); 129.85 (C); 130.08 (CH); 131.07 (C); 136.84 (C); 138.22 (C); 150.23 (C); 167.41 (C).
Anal. calc. for C30H21NO2S (459.56): C 78.41, H 4.61, N 3.05; found: C 77.95, H 4.72, N 3.15.
(6aR*,7S*,13cS*)-2-Bromo-6a,7,9,13c-tetrahydro-7,9-diphenyl-6H-[1]benzopyrano[4’,3’:4,5]thio-
1
pyrano[2,3-b]indol-6-one (3u). Yellow solid. Yield: 237 mg (88%). M.p. 228 – 2308. H-NMR (CDCl3):
3.70 (dd, J ¼ 9.5, 4.4, HꢀC(6a)); 4.63 (d, J ¼ 9.5, HꢀC(7)); 4.90 (d, J ¼ 3.6, HꢀC(13c)); 7.05 (d, J ¼ 8.5,
1 H); 7.21 – 7.26 (m, 2 H); 7.31 – 7.38 (m, 6 H); 7.49 – 7.51 (m, 4 H); 7.55 – 7.60 (m, 4 H). 13C-NMR
(CDCl3): 33.80 (CH); 44.03 (CH); 47.14 (CH); 103.98 (C); 110.41 (CH); 117.15 (CH); 118.16 (C); 119.12
(CH); 121.55 (CH); 122.30 (CH); 127.62 (CH); 128.34 (C); 128.71 (C); 128.86 (2 CH); 129.41 (CH);
129.60 (CH); 130.13 (CH); 131.29 (C); 132.53 (CH); 132.61 (CH); 136.45 (C); 136.74 (C); 138.29 (C);
149.33 (C); 166.68 (C). Anal. calc. for C30H20BrNO2S (538.45): C 66.92, H 3.74, N 2.60; found: C 66.55, H
3.66, N 2.60.
(6aR*,7S*,13cS*)-6a,7,9,13c-Tetrahydro-4-methoxy-7,9-diphenyl-6H-[1]benzopyrano[4’,3’:4,5]thio-
pyrano[2,3-b]indol-6-one (3v). White solid. Yield: 201 mg (82%). M.p. 262 – 2658. 1H-NMR
((D6)DMSO): 3.82 – 3.84 (m, 4 H); 4.76 – 4.80 (m, 2 H); 6.93 (d, J ¼ 6.5, 1 H); 7.02 – 7.17 (m, 5 H);
7.31 – 7.38 (m, 4 H); 7.42 (d, J ¼ 6.8, 2 H); 7.50 (d, J ¼ 7.6, 3 H); 7.60 (t, J ¼ 7.6, 2 H). 13C-NMR
((D6)DMSO): 32.84 (CH); 43.69 (CH); 45.92 (CH); 56.83 (Me); 105.49 (C); 110.18 (CH); 113.07 (CH);
118.28 (CH); 121.26 (CH); 121.32 (CH); 122.32 (CH); 125.49 (CH); 127.37 (C); 127.76 (2 CH); 128.81
(C); 129.29 (2 CH); 129.52 (CH); 130.37 (C); 130.50 (C); 130.74 (CH); 136.71 (C); 137.98 (C); 139.53
(C); 148.11 (C); 166.96 (C). Anal. calc. for C31H23NO3S (489.58): C 76.05, H 4.73, N 2.86; found: C 75.65,
H 4.62, N 2.92.
(4aR*,5S*,11cS*)-4a,5,7,11c-Tetrahydro-5,7-diphenyl-4H-naphtho[1’’,2’’:5’,6’]pyrano[4’,3’:4,5]thio-
pyrano[2,3-b]indol-4-one (3w). Light brown solid. Yield: 165 mg (65%). M.p. 241 – 2448. 1H-NMR
((D6)DMSO): 3.96 (dd, J ¼ 4.5, 2.2, HꢀC(4a)); 4.76 (d, J ¼ 4.5, HꢀC(5)); 4.31 (d, J ¼ 2.2, HꢀC(11c));
5.90 (d, J ¼ 8.1, 1 H); 6.46 (t, J ¼ 7.5, 1 H); 6.84 (t, J ¼ 7.6, 1 H); 7.00 (d, J ¼ 8.2, 1 H); 7.34 – 7.38 (m, 2 H);
7.43 (t, J ¼ 7.4, 2 H); 7.54 – 7.56 (m, 6 H); 7.64 – 7.67 (m, 3 H); 8.01 (d, J ¼ 8.4, 1 H); 8.06 (d, J ¼ 8.9, 1 H);
8.10 (d, J ¼ 8.0, 1 H). 13C-NMR ((D6)DMSO): 27.35 (CH); 43.55 (CH); 45.43 (CH); 104.83 (C); 110.01
(CH); 117.91 (CH); 118.21 (CH); 119.79 (C); 120.72 (CH); 121.78 (CH); 123.76 (CH); 126.38 (CH);
128.29 (CH); 128.56 (C); 128.69 (CH); 128.84 (CH); 128.98 (CH); 129.61 (2 CH); 130.02 (CH); 130.82
(2 CH); 131.07 (C); 131.30 (C); 132.32 (C); 136.69 (C); 138.09 (C); 141.59 (C); 149.67 (C); 167.41 (C).
Anal. calc. for C34H23NO2S (509.62): C 80.13, H 4.55, N 2.75; found: C 79.07, H 4.48, N 2.71.
(6aR*,7S*,13cS*)-2-Bromo-6a,7,9,13c-tetrahydro-7-methyl-9-phenyl-6H-[1]benzopyrano[4’,3’:4,5]-
1
thiopyrano[2,3-b]indol-6-one (3x). Pale-yellow solid. Yield: 198 mg (83%). M.p. 231 – 2348. H-NMR
(CDCl3): 1.50 (d, J ¼ 6.8, Me); 3.24 (dd, J ¼ 9.8, 4.5, HꢀC(6a)); 3.53 – 3.56 (m, HꢀC(7)); 4.42 (d, J ¼ 4.1,
HꢀC(13c)); 7.04 (d, J ¼ 8.5, 1 H); 7.19 – 7.25 (m, 2 H); 7.29 (d, J ¼ 8.0, 1 H); 7.40 (s, 1 H); 7.45 – 7.54 (m,
5 H); 7.60 (t, J ¼ 7.6, 2 H). 13C-NMR (CDCl3): 19.30 (Me); 33.52 (CH); 33.61 (CH); 47.28 (CH); 103.83
(C); 110.34 (CH); 116.95 (CH); 118.21 (C); 119.07 (CH); 121.48 (CH); 122.19 (CH); 127.61 (CH);
128.42 (C); 128.78 (C); 128.84 (CH); 130.10 (CH); 130.95 (C); 132.24 (CH); 132.35 (CH); 136.83 (C);
138.31 (C); 149.19 (C); 167.61 (C). Anal. calc. for C25H18BrNO2S (476.38): C 63.03, H 3.81, N 2.94; found:
C 62.45, H 3.71, N 2.90.
(6aR*,7S*,13cS*)-6a,7,9,13c-Tetrahydro-4-methoxy-7-methyl-9-phenyl-6H-[1]benzopyrano[4’,3’:4,5]-
thiopyrano[2,3-b]indol-6-one (3y). Yellow solid. Yield: 192 mg (90%). M.p. 214 – 2168. 1H-NMR
((D6)DMSO): 1.42 (d, J ¼ 6.8, Me); 3.41 (dd, J ¼ 6.1, 5.2, HꢀC(6a)); 3.68 – 3.71 (m, HꢀC(7)); 3.83 (s,
MeO); 4.91 (d, J ¼ 4.5, HꢀC(11c)); 6.98 (t, J ¼ 7.3, 1 H); 7.03 (t, J ¼ 7.4, 1 H); 7.07 – 7.11 (m, 3 H); 7.19 (t,
J ¼ 7.9, 1 H); 7.27 (d, J ¼ 7.6, 1 H); 7.44 (d, J ¼ 7.7, 2 H); 7.52 (t, J ¼ 7.3, 1 H); 7.60 (t, J ¼ 7.6, 2 H). 13C-NMR

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Helvetica Chimica Acta – Vol. 93 (2010)
((D6)DMSO): 21.01 (Me); 32.31 (CH); 34.41 (CH); 45.69 (CH); 56.71 (Me); 105.01 (C); 110.03 (CH);
112.88 (CH); 118.29 (CH); 121.12 (CH); 121.45 (CH); 122.06 (CH); 125.44 (CH); 127.57 (C); 127.84
(CH); 128.67 (C); 129.27 (CH); 130.35 (C); 130.71 (CH); 136.78 (C); 138.01 (C); 139.64 (C); 148.07 (C);
167.85 (C). Anal. calc. for C26H21NO3S (427.51): C 73.05, H 4.95, N 3.28; found: C 72.57, H 4.91, N 3.17.
(6aR*,13cS*)-2-Bromo-6a,7,9,13c-tetrahydro-9-phenyl-6H-[1]benzopyrano[4’,3’:4,5]thiopyrano[2,3-
b]indol-6-one (3z). Yellow solid. Yield: 196 mg (85%). M.p. 231 – 2348. 1H-NMR (CDCl3): 3.14 (d, J ¼
11.0, 1 HꢀC(7)); 3.24 (dd, J ¼ 12.3, 11.2, 1 HꢀC(7)); 3.47 – 3.50 (m, HꢀC(6a)); 4.88 (d, J ¼ 4.4,
HꢀC(13c)); 7.04 (d, J ¼ 8.5, 1 H); 7.19 – 7.29 (m, 3 H); 7.44 – 7.56 (m, 6 H); 7.60 (t, J ¼ 7.5, 2 H). 13C-NMR
(CDCl3): 25.15 (CH2); 32.90 (CH); 40.35 (CH); 103.99 (C); 110.29 (CH); 116.95 (CH); 118.34 (C);
119.25 (CH); 121.48 (CH); 122.28 (CH); 127.67 (CH); 127.92 (C); 128.89 (CH); 128.90 (C); 129.92 (C);
130.11 (CH); 132.38 (CH); 132.35 (CH); 136.45 (C); 136.74 (C); 149.27 (C); 168.87 (C). Anal. calc. for
C24H16BrNO2S (462.36): C 62.35, H 3.49, N 3.03; found: C 61.92, H 3.40, N 3.07.
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[4] R. D. H. Murray, Prog. Chem. Org. Nat. Prod. 2002, 83, 1 – 673; R. D. H. Murray, J. Mendez, S. A.
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Received September 6, 2009