Iodine-catalysed versatile sulfenylation of indoles with thiophenols: controllable synthesis of mono- and bis-arylthioindoles

Article abstract of DOI:10.1016/j.tet.2015.09.070

A versatile method for the synthesis of mono- and bis-arylthioindoles via I₂ catalysed direct oxidative sulfenylation of indoles with thiophenols (especially mercaptobenzoic acids) has been presented. This system features environmental friendliness, easy operation, and mild reaction conditions, and shows a broad functional group tolerance furnishing good to excellent yields.

Full text of DOI:10.1016/j.tet.2015.09.070

Accepted Manuscript
Iodine-Catalysed Versatile Sulfenylation of Indoles with Thiophenols: Controllable
Synthesis of mono- and bis-Arylthioindoles
Hailei Zhang, Xiaoze Bao, Yuming Song, Jingping Qu, Baomin Wang
PII:
S0040-4020(15)30100-9
10.1016/j.tet.2015.09.070
TET 27167
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 4 September 2015
Revised Date: 28 September 2015
Accepted Date: 30 September 2015
Please cite this article as: Zhang H, Bao X, Song Y, Qu J, Wang B, Iodine-Catalysed Versatile
Sulfenylation of Indoles with Thiophenols: Controllable Synthesis of mono- and bis-Arylthioindoles,
Tetrahedron (2015), doi: 10.1016/j.tet.2015.09.070.
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Iodine-Catalysed Versatile Sulfenylation of
Indoles with Thiophenols: Controllable
Synthesis of mono- and bis-Arylthioindoles
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Hailei Zhang, Xiaoze Bao, Yuming Song, Jingping Qu, Baomin Wang*
State Key Laboratory of Fine Chemicals, School of Pharmaceutical Science and Technology, Dalian University
of Technology, Dalian 116024, P. R. China

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Tetrahedron
journal homepage: www.elsevier.com
Iodine-Catalysed Versatile Sulfenylation of Indoles with Thiophenols:
Controllable Synthesis of mono- and bis-Arylthioindoles
Hailei Zhang, Xiaoze Bao, Yuming Song, Jingping Qu, Baomin Wang*
State Key Laboratory of Fine Chemicals, School of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian 116024, P. R. China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A versatile method for the synthesis of mono- and bis-arylthioindoles via I2 catalysed direct
oxidative sulfenylation of indoles with thiophenols (especially mercaptobenzoic acids) has been
presented. This system features environmental friendliness, easy operation, and mild reaction
conditions, and shows a broad functional group tolerance furnishing good to excellent yields.
Available online
2009 Elsevier Ltd. All rights reserved
.
Keywords:
Sulfenylation
Arylthioindole
Iodine Catalysis
Thiophenol
———
Corresponding author: Tel.: +86-411-8498-6190; fax: +86-411-8498-6186; e-mail: bmwang@dlut.edu.cn

2
Tetrahedron
1. Introduction
Table 1. Optimization of reaction conditions for the synthesis
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of 3-(p-tolylthio)-1H-indole 3aba,b
The significance of sulfur-bearing indoles is well reflected in
the myriad constructive and functional building blocks in
medicinal chemistry, materials science and natural products.1
Among a wide range of sulfur-modified indole derivatives
known, the wide spectrum of therapeutic value of numerous
sulfenylated indoles which constitutes a constant source of
fascination, has been recently revealed to have dramatic effects
on bacterial infection, HIV, cardiovascular diseases, cancer,
affective and respiratory disorders, to name but a few,2 since the
discovery of 3-sulfenylindoles that can serve as an orally active
inhibitor of 5-lipoxygenase in 1993.3
Entry
Catalyst
Oxidant
TBHP
TBHP
TBHP
TBHP
TBHP
H2O2
Solvent
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
DMSO
MeOH
H2O
T (oC)
40
Yield (%)b
1
2
NIS
70
73
I2
KI
TBAI
I2
40
3
40
13
On account of the intriguing synthetic value and varying
pronounced bioactivities of these compounds, the synthetic
repertoire has currently enjoyed a resurgence of interest after the
initial studies in 1980s,4 and resulted in the development of two
major synthetic strategies. The first route is achieved by
cyclization reactions of 2-alkynylanilines,5 o-ethenylaryl
4
40
Trace
92
5
60
6
I2
60
78
7
I2
(NH4)2S2O8
DTBP
TBHP
TBHP
TBHP
TBHP
TBHP
60
83
8
I2
60
Trace
81
isocyanides,6
2-(gem-dibromo(chloro)vinyl)
anilines7
or
9
I2
60
phenylhydrazine hydrochloride,8 whereas the other method
involves the direct sulfenylation of a pre-existing indole ring
owing to its nucleophilic nature,9-16 using arylsulfenyl
halides,4a,17b,c diaryl disulfides,9 aryl-N-thioimides,10 aryl thiols,11
arylsulfonyl chlorides,12 sulfonyl hydrazides,13 quinone mono-
O,S-acetals,14 arylsulfonium salts15 and sulfinic acids16 as sources
of the sulfenylating agents. Nevertheless, many of these sulfur-
transfer reagents are either difficult to prepare or air and moisture
sensitive. Moreover, the existing methodologies frequently
require harsh reaction conditions, excess additives and transition
metal catalysts, suffer from a narrow substrate scope, or yield by-
products unfriendly to the environment.
10
11
12c
13
I2
60
63
I2
60
74
I2
MeCN
MeCN
60
71
-
80
-
a
Reaction conditions: indole 1a (0.50 mmol), p-toluenethiol 2b (0.505
mmol), catalyst (10 mol%), oxidant (0.525 mmol), solvent (2.0 mL), open to
air. b Isolated yield. c 5 mol% iodine was used.
reaction system was subsequently assessed; nonetheless, better
yield could not be obtained (Table 1, entries 6-8). Replacement
of MeCN with other common solvents such as DMSO, MeOH
and H2O all decreased the reaction yield to varying degrees
(Table 1, entries 9-11). By screening the catalyst loading, it was
indicated that reducing the loading to 5 mol% gave rise to a much
lower yield (Table 1, entry 12) and no product was formed
without the presence of iodine catalyst (Table 1, entry 13).
Although many methods have been successfully demonstrated
to construct structurally diverse mono-sulfenyl indoles, synthesis
of arylthioindoles having acidic proton functional groups
(peculiarly CO2H) has not been well documented to date.9g,11e
Moreover, methodologies that can accomplish double C–H
sulfenylation in indoles at 2- and 3-positions have remained
elusive. In the context of step- and atom-economy points of view
in industrial and green chemistry, especially the low threshold
residual tolerance of harmful ingredients for pharmaceuticals,
there is a highly urgent demand for organic chemists to explore
alternative sustainable processes for mono- and bis-
arylthioindoles from simple and readily exploitable precursors
under mild reaction conditions. To the best of our knowledge,
there is no report on I2/TBHP catalyzed mono- and bis-
sulfenylation of indoles with thiophenols. Herein, we detail an
efficient and generally applicable methodology for the synthesis
of diversely substituted mono- and bis-arylthioindoles. Unlike the
previously reported sulfenylation of indoles with thiophenols, the
protocol here has an extremely broad substrate scope, simple
reaction conditions, and excellent yields. Notably, in this
transformation, no metal salts, ligands or additives were added
and without exclusion of air and moisture.
With the optimal reaction conditions in hand, a systematic
investigation was conducted to evaluate the generality of the
Scheme 1 Synthesis of monosulfenyl indolesa,b
2. Results and Discussion
To acquire the optimized reaction conditions, the preliminary
investigation was initiated from the model reaction of indole 1a
and p-toluenethiol 2b in the presence of various iodo-containing
catalysts and 1.05 equiv of tert-butyl hydroperoxide (TBHP).
Pleasingly, I2 (10 mol%) exhibited the best performance to
produce the expected product 3ab, 3-(p-tolylthio)-1H-indole, in
72% yield at 40 °C under air (Table 1, entry 2). Increasing the
temperature to 60 °C caused an increase to 92% yield (Table 1,
entry 5). The influence of the stoichiometric oxidant on the
a
Reaction conditions: 1 (0.5 mmol), 2 (0.51 mmol), I2 (0.05 mmol),
TBHP (0.525 mmol), MeCN (2 mL) under air. b Isolated yield.

Scheme 3 2,3-Bis-sulfenylation of indoles a,b
facile transformation. As outlined in Scheme 1, a vast variety of
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aryl- and heteroarylthiols smoothly underwent sulfenylation with
indoles to generate structurally diverse thioethers in high yields
with extremely high regioselectivity (Scheme 1, 3a-j). In
addition, sulfenylation reaction using benzyl mercaptan
successfully took place under present catalytic conditions
(Scheme 1, 3ak). Indoles bearing functional groups such as
alkoxyl, halide and ester all displayed satisfactory tolerance to
the protocol and provided corresponding products with good to
excellent yields (Scheme 1, 3da-3ga). Furthermore, we were
delighted to disclose that high yields were also obtained from 7-
aza, 2- and 3-substituted indoles (Scheme 1, 3ia-3la).
In the existing literature, very few synthetic pathways
enabling the preparation of the sulfenylindoles using
mercaptobenzoic acids as sulfur-transfer reagents were found
because of the strong electron-withdrawing feature of carboxy
group.9g,11e Within this scenario, the optimized reaction
conditions prompted us to validate a further useful application by
reacting two sorts of mercaptobenzoic acids with various indoles
to furnish the corresponding arylthioindoles. By comparing with
previously reported results,9g,11e it could be easily discerned that
the new method not only considerably reduced the reaction time
and temperature, but above all markedly increased the yield of
the products. In particular, under our experimental conditions,
methyl indole-4-carboxylate and 3-methylindole smoothly went
through sulfenylation to afford the relevant derivatives in good
yields (Scheme 2, 3gg, 3kg). Among the mercaptobenzoic acids
tested, 4-mercaptobenzoic acid 2h which exhibited worse
reactivity compared with 3dg could be explained mainly by
taking into account the formation of different active species of
mercaptobenzoic acids proposed by Li.11e
a
Reaction conditions: 1 (0.5 mmol), 2 (1.05 mmol), I2 (0.25 mmol),
TBHP (1.05 mmol), MeCN (2 mL) under air. b Isolated yield.
kinds and loadings of oxidants and iodine-containing catalysts.
Ultimately, 0.5 equiv of I2 and 2.1 equiv of TBHP were found to
be optimum for the maximum yield (83%) of 2,3-bis-
sulfenylindole 4ab (Scheme 3). As illustrated by Scheme 3, it is
noteworthy that both electron-withdrawing and electron-donating
groups were introduced into the 2,3-sulfenylation products by
employing various indoles and thiols bearing such groups on the
aromatic ring to give the respective 2,3-bis-sulfenyl indoles in
moderate to high yields.
Previously, the synthesis of 2,3-bis-sulfenyl indoles had been
attained by Hamel et al utilizing aryl sulfenyl chlorides and
diaryl disulfides as the sulfur source.17 To the best of our
knowledge, there is no report in the literature on the synthesis of
2,3-bis-sulfenyl indoles under mild reaction conditions and using
readily available thiols as yet. Additionally, the sulfenylation
reaction generally took place at the C-3 position of the indole
ring owing to its electron-rich nature. However, the C-2 position
of the indole ring may also be the reaction site of choice when the
C-3 position was occupied by the sulfenylation. To testify our
hypothesis, indole 1a (1.0 equiv) and p-toluenethiol 2b (2.1 equiv)
were selected as the starting materials in the presence of different
Based on the above experimental results and formerly
published similar examples,9d,17c a plausible reaction mechanism
for mono- and bis-sulfenylation of indoles is depicted in Scheme
4. Firstly, RSH reacts with I2 to form an electrophilic species RSI
A, which can provide the electrophile RS+ and react with indole
moiety to produce intermediate B. Deprotonation of B gives the
desired monosulfenyl indole and HI. Then the second
sulfenylation of indole occurs predominantly, if not completely,
by initial addition at the 3-position of the indole ring, leading to a
3,3-disubstituted indolenine intermediate C, followed by
Scheme 4 Proposed mechanism
Scheme 2 Scope of mercaptobenzoic acidsa,b
a Reaction conditions: 1 (5.5 mmol), 2 (5.0 mmol), I2 (0.5 mmol), TBHP
(5.25 mmol), MeCN (20 mL) under air. b Isolated yield.

4
Tetrahedron
chromatography was performed on silica gel (100~200 mesh).
Scheme 5 Gram-scale reaction
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1
All H NMR and 19F NMR spectra were recorded on a Bruker
Avance Ⅱ 400 MHz and Bruker Avance Ⅲ 471 MHz
respectively, 13C NMR spectra were recorded on a Bruker
AvanceⅡ 101 MHz or Bruker Avance Ⅲ 126 MHz. CDCl3 and
DMSO-d6 were used for NMR spectroscopy, using singlet, d =
doublet, t = triplet, m = multiplet or unresolved, br = broad
singlet, dd = doublet doublet, coupling constants in Hz,
integration). Data for 13C NMR and 19F NMR are reported in
terms of chemical shift (δ, ppm). HRMS (ESI) was determined
by a HRMS/MS instrument (LTQ Orbitrap XL TM).
Scheme 6 Transformation of the products
4.2. Experimental procedure for mono- and bis-sulfenylation of
indoles
A mixture of indole 1 (0.5 mmol), thiol 2 (0.505 mmol) and
TBHP (0.51 mmol) were dissolved in MeCN (2.0 mL) at 60 ℃ in
a flask, then iodine (0.10 mmol, 10 mol%) was added. The
reaction proceeded under an air atmosphere for 0.5-1.0 h until
complete consumption of starting material as monitored by TLC.
The reaction mixture was quenched by the addition of saturated
aq Na2S2O3 (5 mL) and then extracted with EtOAc (2 × 10 mL).
The combined organic layer was separated, dried (MgSO4),
filtered and concentrated under vacuum and the crude product
was purified by column chromatography using petroleum
ether/ethyl acetate as eluent to provide the product 3.
migration of one of the sulfide groups to the 2-position, as has
been suggested by Préville.17c In the end, I2 is regenerated by the
oxidation of TBHP with the formation of water and tert-butanol.
To demonstrate the practical applicability of the mono- and
bis-sulfenylating process on a much larger scale, a gram-scale
synthesis of 3aa and 4aa was subjected to the protocol. To our
delight, with a lower catalyst loading (5 mol% instead of 10
mol% in Scheme 1), the reaction still proceeded smoothly, albeit
expectedly slower, and the mono-sulfenylating product 3aa was
isolated in 86% yield, which is only marginally lower than that of
the 0.5 mmol scale reaction (Scheme 5). Besides, the gram-scale
synthesis of 4aa was conducted with maintained efficiency and
2-indolyl sulfide 5 was acquired via the selective desulfenylation
of 4aa, using trifluoroacetic acid in the presence of 2-
mercaptobenzoic acid as trapping agent (Scheme 6).17b Finally,
the single mixed indole 2,3-bis(sulfides) 6, which was a knotty
problem by one-pot reaction, was synthesized in high yield under
our developed experimental conditions (Scheme 6).
4.2.1. 3-(Phenylthio)-1H-indole (3aa)9 c
1
White solid, yield 90%; H NMR (400 MHz, CDCl3) δ 8.28
(brs, 1H), 7.61 (d, J = 8.0 Hz, 1H), 7.42-7.38 (m, 2H), 7.27-7.21
(m, 1H), 7.17-7.09 (m, 5H), 7.06-7.02 (m, 1H); 13C NMR (126
MHz, CDCl3,): δ 139.3, 136.5, 130.7, 129.1, 128.7, 125.9, 124.8,
123.1, 121.0, 119.7, 111.6, 102.9.
4.2.2. 3-( p-Tolylthio)-1H-indole (3ab)9 c
1
White solid, yield 92%; H NMR (400 MHz, CDCl3) δ 8.11
(brs, 1H), 7.60 (d, J = 8.0 Hz, 1H), 7.32–7.30 (m, 2H), 7.24–7.20
(m, 1H), 7.15–7.11 (m, 1H), 7.01 (d, J = 8.0 Hz, 2H), 6.94 (d, J =
8.0 Hz, 2H), 2.21 (s, 3H); 13 C NMR (126 MHz, CDCl3) δ 136.5,
135.6, 134.8, 130.6, 129.6, 129.2, 126.4, 123.1, 120.9, 119.7,
111.7, 103.3, 20.9.
3. Conclusion
4.2.3. 3-(3-Methoxyphenylthio)-1H-indole (3ac)1 8 a
In summary, a simple and versatile oxidative system for the
selective and controllable sulfenylation of indoles to the
corresponding mono- and bis-sulfenylindoles in the presence of
catalytic amounts of iodine using thiols as sulfenylation reagent
in MeCN under mild conditions has been developed. In
comparison with reported protocols, the present procedure not
only can perform without metal and removal of moisture and air,
but also has the superiority of short reaction time and high yields.
Moreover, both diversely substituted indoles and thiols,
peculiarly with acidic protons, like hydroxyl and carboxylic acid
groups can be tolerated commendably. Last but not the least, the
current study paves the way for the synthesis of 2,3-bis-sulfenyl
indoles with the addition of a catalytic amount of iodine, making
use of thiols as the sulfur source.
1
White solid, yield 93%; H NMR (400 MHz, CDCl3) δ 8.29
(brs, 1H), 7.60 (d, J = 8.0 Hz, 1H), 7.33-7.31 (m, 2H), 7.24-7.18
(m, 1H), 7.15–7.12 (m, 1H), 7.07-7.03 (m, 1H), 6.70-6.66 (m,
2H), 6.60-6.57 (m, 1H), 3.64 (s, 3H); 13C NMR (126 MHz,
CDCl3) δ 159.9, 140.9, 136.5, 130.9, 129.7, 129.1, 123.1, 121.0,
119.6, 118.4, 111.8, 111.7, 110.4, 102.4, 55.2.
4.2.4. 3-(4-hydroxyphenylthio)-1H-indole (3ad)1 7 d
1
Off-white solid, yield 78%; H NMR (400 MHz, DMSO-d6) δ
11.55 (s, 1H), 9.37 (s, 1H), 7.71 (s, 1H), 7.48 (d, J = 8.0 Hz, 2H),
7.16 (m, 1H), 7.04 (d, J = 6.8 Hz, 3H), 6.67 (d, J = 6.8 Hz, 2H);
13C NMR (126 MHz, DMSO-d6) δ 155.7, 136.6, 131.4, 129.0,
128.7, 127.0, 122.0, 119.9, 118.5, 116.0, 112.2, 102.3.
4.2.5. 3-(4-Fluorophenylthio)-1H-indole (3ae)1 1 f
1
4. Experimental section
White solid, yield 86%; H NMR (400 MHz, CDCl3) δ 8.24
(brs, 1H), 7.59 (d, J = 8.0 Hz, 1H), 7.39–7.35 (m, 2H), 7.26–7.22
(m, 1H), 7.19–7.13 (m, 1H), 7.09–7.04 (m, 2H), 6.85–6.81 (m,
2H); 19F NMR (470 MHz, CDCl3) δ -118.10; 13C NMR (126
4.1. General experimental details
Unless otherwise noted, all reagents and chemicals (AR grade)
were purchased from commercial suppliers and used without
further purification. Petroleum ether (PE) refers to the fraction
boiling in the 60-90 ℃ range. Unless otherwise noted, all
reactions were carried out under air in oven-dried glassware with
magnetic stirring. The progress of the reactions was monitored by
TLC (silica gel, Polygram SILG/UV 254 plates). Column
1
MHz, CDCl3) δ 160.9 (d, JC-F = 243 Hz), 136.5, 134.0, 130.5,
3
128.9, 128.0 (d, JC-F = 7.1 Hz), 123.2, 121.0, 119.6, 115.8 (d,
2JC-F = 22 Hz), 111.7, 103.4.
1 1 f
4.2.6. 3-(4-Bromophenylthio)-1H-indole (3af)
1
White solid, yield 92%; H NMR (400 MHz, CDCl3) δ 8.30
(brs, 1H), 7.56 (d, J = 7.6 Hz, 1H), 7.40-7.38 (m, 2H), 7.28-7.22

(m, 3H), 7.18-7.14 (m, 1H), 6.93 (d, J = 8.0 Hz, 2H); 13C NMR
(126 MHz, CDCl3) δ 138.6, 136.5, 131.7, 130.8, 128.8, 127.5,
(126 MHz, DMSO-d6) δ 167.6, 155.0, 146.5, 133.7, 132.2, 130.3,
129.8, 127.5, 124.9, 113.8, 113.0, 100.2, 97.8, 55.7.
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123.3, 121.1, 119.5, 118.4, 111.8, 102.3.
4.2.15. 5-Bromo-3-(phenylthio)-1H-indole (3ea)9 c
1
4.2.7. 3-[(2-Carboxyphenyl)thio] -1H-indole
White solid, yield 88%; H NMR (400 MHz, DMSO-d6) δ
(3ag)9 g
11.97 (brs, 1H), 7.89 (s, 1H), 7.57-7.52 (m, 2H), 7.34 (d, J = 8.0
Hz, 1H), 7.23-7.20 (m, 2H), 7.10-7.06 (m, 3H) 13C NMR (126
MHz, DMSO-d6) δ 138.7, 135.5, 134.1, 130.6, 128.9, 125.4,
125.0, 124.8, 120.4, 114.5, 113.0, 99.3.
Light brown solid, yield 79%; 1H NMR (400 MHz, DMSO-d6)
δ 13.18 (brs, 1H), 11.77 (s, 1H), 7.98 (d, J = 7.2 Hz, 1H), 7.79 (d,
J = 2.4 Hz, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.38 (d, J = 8.0 Hz,
1H), 7.24-7.20 (m, 2H), 7.14-7.07 (m, 2H), 6.75 (d, J = 8.0 Hz,
1H); 13C NMR (126 MHz, DMSO-d6) δ 167.5, 143.8, 137.0,
132.7, 132.0, 131.0, 128.7, 126.7, 125.6, 123.7, 122.2, 120.2,
118.3, 112.4, 100.0.
4.2.16. 5-Bromo-3-[(2-Carboxyphenyl)thio] -1H-
indole (3eg)9 g
1
Yellow solid, yield 78%; H NMR (400 MHz, DMSO-d6) δ
13.22 (brs, 1H), 12.00 (s, 1H), 8.00 (d, J = 7.2 Hz, 1H), 7.88 (s,
1H), 7.55 (d, J = 8.4 Hz, 1H), 7.49 (s, 1H), 7.35 (d, J = 8.0 Hz,
1H), 7.30-7.26 (m, 1H), 7.18-7.15 (m, 1H), 6.72 (d, J = 8.0 Hz,
1H); 13C NMR (126 MHz, DMSO-d6) δ 167.4, 143.2 135.7,
134.3, 132.2, 131.1, 130.7, 126.7, 125.5, 124.8, 123.9, 120.4,
114.6, 113.0, 99.9.
4.2.8. 3-(Pyridin-2-ylthio)-1H-indole (3ai)1 8 b
1
Pale-yellow solid, yield 90%; H NMR (400 MHz, CDCl3) δ
9.70 (brs, 1H), 8.36-8.34 (m, 1H), 7.59 (d, J = 8.0 Hz, 1H), 7.41-
7.37 (m, 2H), 7.33-7.29 (m, 1H), 7.24-7.20 (m, 1H), 7.16-7.12
(m, 1H), 6.94-6.90 (m, 1H), 6.80 (d, J = 8.0 Hz, 1H); 13C NMR
(126 MHz, CDCl3) δ 162.9, 148.9, 136.9, 131.7, 128.9, 123.0,
120.9, 120.2, 119.5, 119.3, 112.1, 100.2.
4.2.17. 6-Fluoro-3-[(2-Carboxyphenyl)thio] -1H-
indole (3fg)9 g
4.2.9. 3-(Benzothiazole-2-ylthio)-1H-indol (3aj)1 8 c
Light purple solid, yield 56%; 1H NMR (400 MHz, DMSO-d6)
δ 13.20 (brs, 1H), 11.83 (s, 1H), 7.98 (d, J = 8.8 Hz, 1H), 7.80 (d,
J = 2.4 Hz, 1H), 7.38-7.32 (m, 2H), 7.27-7.23 (m, 1H), 7.16-7.12
(m, 1H), 6.98-6.93 (m, 1H), 6.74 (d, J = 8.0 Hz, 1H); 13C NMR
1
White solid, yield 94%; H NMR (400 MHz, DMSO-d6) δ
12.13 (brs, 1H), 8.08 (d, J = 2.8 Hz, 1H), 7.86 (d, J = 8.0 Hz, 1H),
7.79 (d, J = 8.0 Hz, 1H), 7.67-7.62 (m, 2H), 7.43-7.39 (m, 1H),
7.31-7.24 (m, 2H), 7.21-7.17 (m, 1H); 13C NMR (126 MHz,
DMSO-d6) δ 173.3, 154.2, 136.8, 135.0, 133.8, 128.0, 126.1,
123.9, 122.6, 121.5, 121.1, 120.8, 118.1, 112.7, 97.3.
1
(126 MHz, DMSO-d6) δ 167.5, 159.3 (d, JC-F = 236 Hz), 143.4,
136.9, 133.4, 132.1, 131.0, 126.7, 125.6, 125.3, 123.8, 119.5,
108.8, 108.6, 100.5, 98.6, 98.4.
9 c
4.2.18. Methyl 1-methyl-3-(Phenylthio)-1H-indole-
4-carboxylate (3ga)
4.2.10. 3-(Benzylthio)-1H-indole (3ak)
1
Yellow solid, yield 64%; H NMR (400 MHz, CDCl3) δ 8.02
Light yellow liquid, yield 88%; 1H NMR (400 MHz, CDCl3) δ
9.33 (brs, 1H), 7.46-7.42 (m, 2H), 7.34 (d, J = 2.8 Hz, 1H), 7.22-
7.17 (m, 1H), 7.12-7.08 (m, 2H), 7.02-6.97 (m, 3H), 3.58 (s, 3H);
13C NMR (126 MHz, CDCl3) δ 169.8, 140.2, 137.7, 134.1, 128.6,
125.6, 125.4, 125.2, 124.7, 122.1, 122.0, 115.4, 101.7, 52.0;
HRMS (ESI) Calcd. for C16H14NO2S ([M+H]+) 284.0740, Found
284.0739.
(brs, 1H), 7.70 (d, J = 7.6 Hz, 1H), 7.31 (d, J = 7.6 Hz, 1H), 7.24-
7.15 (m, 5H), 7.08-7.05 (m, 2H), 6.95 (d, J = 2.4 Hz, 1H), 3.85 (s,
2H); 13C NMR (101 MHz, CDCl3) δ 139.1, 136.2, 129.9, 129.3,
129.0, 128.3, 126.8, 122.7, 120.5, 119.3, 111.5, 105.3, 41.0.
4.2.11. 4-Methyl-3-[(2-Carboxyphenyl)thio] -1H-
9 g
indole (3cg)
1
White solid, yield 86%; H NMR (400 MHz, DMSO-d6) δ
4.2.19. Methyl 1-methyl-3-[(2-
11.74 (s, 1H), 8.01 (d, J = 6.8 Hz, 1H), 7.71 (s, 1H), 7.41 (d, J =
8.0 Hz, 1H), 7.26-7.24 (m, 1H), 7.14-7.07 (m, 2H), 6.84-6.79 (m,
2H), 2.49 (s, 3H); 13C NMR (126 MHz, DMSO-d6) δ 168.0,
146.5, 138.0, 133.6, 132.6, 131.4, 130.7, 127.2, 126.9, 126.4,
124.0, 122.7, 122.1, 110.8, 100.7, 18.4.
Carboxyphenyl)thio] -1H-indole-4-carboxylate (3gg)
1
Light yellow solid, yield 65%, mp: 233.7-235.5 °C; H NMR
(400 MHz, DMSO-d6) δ 13.09 (brs, 1H), 12.13 (brs, 1H), 7.95 (d,
J = 7.6 Hz, 1H), 7.89 (s, 1H), 7.74 (d, J = 7.6 Hz, 1H), 7.34-7.23
(m, 3H), 7.14-7.10 (m, 1H), 6.77 (d, J = 8.0 Hz, 1H), 3.33 (s, 3H);
13C NMR (126 MHz, DMSO-d6) δ 168.6, 167.5, 145.0, 137.9,
135.8, 131.8, 130.6, 126.2, 126.0, 125.1, 124.8, 123.4, 121.4,
121.0, 115.5, 99.8, 50.9; HRMS (ESI) Calcd. for C17H14NO4S
([M+H]+) 328.0638, Found 328.0649.
9 c
4.2.12. 3-(5-Methoxyphenylthio)-1H-indole (3da)
1
White solid, yield 80%; H NMR (400 MHz, DMSO-d6) δ
11.63 (brs, 1H), 7.75 (d, J = 2.4 Hz, 1H), 7.47 (d, J = 8.8 Hz, 1H)
7.20-7.16 (m, 2H), 7.08-7.02 (m, 3H), 6.94 (d, J = 2.4 Hz, 1H),
6.90-6.87 (dd, J = 8.8 Hz, J = 2.4 Hz, 1H), 3.69 (s, 3H); 13C
NMR (126 MHz, DMSO-d6) δ 154.4, 139.4, 132.9, 131.7, 129.6,
128.8, 125.2, 124.6, 113.2, 112.3, 99.9, 98.9, 55.2.
4.2.20. 2-Methyl-3-(phenylthio)-1H-indole (3ia)9 c
1
White solid, Yield 94%; H NMR (400 MHz, CDCl3) δ 7.86
(brs, 1H), 7.53 (d, J = 6 Hz, 1H), 7.18-6.95 (m, 8H), 2.31 (s, 3H);
13C NMR (126 MHz, CDCl3) δ 141.5, 139.5, 135.6, 130.4, 128.9,
125.7, 124.80, 122.3, 120.9, 119.0, 111.0, 99.2.
4.2.13. 5-Methoxyl-3-[(4-Carboxyphenyl)thio] -1H-
9 g
indole (3dg)
1
White solid, yield 81%; H NMR (400 MHz, DMSO-d6) δ
4.2.21. 2-Methyl-3-[(2-Carboxyphenyl)thio] -1H-
13.14 (brs, 1H), 11.63 (brs, 1H), 7.98 (d, J = 7.2 Hz, 1H), 7.72 (s,
1H), 7.47 (d, J = 8.8 Hz, 1H), 7.28-7.24 (m, 1H), 7.15-7.11 (m,
1H), 6.89-6.84 (m, 2H), 6.77 (d, J = 8.0 Hz, 1H), 3.70 (s, 3H);
13C NMR (126 MHz, DMSO-d6) δ 172.8, 159.6, 149.1, 138.3,
137.3, 137.1, 136.2, 134.8, 131.9, 130.8, 128.9, 118.5, 117.6,
105.0, 104.7, 60.5.
indole (3ig)
1
Light yellow solid, yield 91%, mp: 190.5-191.9 °C; H NMR
(400 MHz, DMSO-d6) δ 13.18 (brs, 1H), 11.71 (s, 1H), 8.00 (d, J
= 7.6 Hz, 1H), 7.47 (d, J = 8 Hz, 1H), 7.32 (d, J = 7.6 Hz, 1H),
7.23-7.19 (m, 1H), 7.16-7.09 (m, 2H), 7.05-7.01 (m, 1H), 6.67 (d,
J = 8 Hz, 1H), 2.47 (s, 3H); 13C NMR (126 MHz, DMSO-d6) δ
167.6, 143.5, 142.3, 135.9, 132.0, 131.1, 129.7, 126.9, 125.2,
123.6, 121.4, 119.9, 117.6, 111.3, 96.9, 11.6; HRMS (ESI) Calcd.
for C16H14NO2S ([M+H]+) 284.0740, Found 284.0742.
4.2.14. 5-Methoxyl -3-[(4-Carboxyphenyl)thio] -1H-
9 g
indole (3dh)
Light yellow solid, yield 57%; 1H NMR (400 MHz, DMSO-d6)
δ 12.84 (brs, 1H), 11.74 (brs, 1H), 7.87-7.82 (m, 3H), 7.51 (d, J =
8.0 Hz, 1H), 7.15 (s, 2H), 6.93 (s, 2H), 3.73 (s, 3H); 13C NMR

6
Tetrahedron
1
113.5, -117.3; 13C NMR (126 MHz, CDCl3) δ 162.4 (d, JC-F
=
4.2.22. Ethyl 3-(phenylthio)-1H-indole-2-
ACCEPTED MANUSCRIPT
carboxylate (3ja)9 f
1
249.5 Hz), 161.2 (d, JC-F = 244,4 Hz), 136.8, 133.8, 132.9 (d,
3JC-F = 3.8 Hz), 132.3 (d, JC-F = 8,8 Hz), 129.9, 129.1 (d, JC-F
=
2
3
1
White solid, yield 88%; H NMR (400 MHz, DMSO-d6) δ
12.44 (brs, 1H), 7.61 (d, J = 8.4 Hz, 1H), 7.51 (d, J = 8.0 Hz, 1H),
7.37-7.33 (m, 1H), 7.23-7.20 (m, 2H), 7.15-7.08 (m, 4H), 4.37-
4.31 (m, 2H), 1.28-1.24 (m, 3H); 13C NMR (126 MHz, DMSO-d6)
δ 160.4, 137.9, 136.3, 129.3, 129.2, 128.8, 126.4, 125.4, 125.1,
121.1, 120.3, 113.2, 107.4, 60.7, 14.0.
2
3.8 Hz), 128.8 (d, JC-F = 7.6 Hz), 124.1, 121.5, 119.8, 116.7,
116.5, 115.9, 115.8, 111.3, 109.5; HRMS (ESI) Calcd. for
C20H14F2NS2 ([M+H]+) 370.0530, Found 370.0519.
4.2.30. 2,3-bis[(4-bromophenyl)thio]-1H-indole
(4af)
4.2.23. 3-Methyl-2-(phenylthio)-1H-indole (3ka)1 8 b
Colorless oil, yield 84%; 1H NMR (400 MHz, CDCl3) δ 8.36
(brs, 1H), 7.55 (d, J = 7.6 Hz, 1H), 7.31-7.23 (m, 4H), 7.21-7.14
(m, 3H), 7.01 (d, J = 8.4 Hz, 2H), 6.89 (d, J = 8.4 Hz, 2H); 13C
NMR (126 MHz, CDCl3) δ 138.6, 136.6, 131.7, 130.8, 128.8,
127.5, 123.3, 121.1, 119.5, 118.4, 111.8, 102.3; HRMS (ESI)
Calcd. for C20H12Br2NS2 ([M-H]-) 489.8757, Found 489.8750.
4.2.31. 2,3-bis(phenylthio)-1-benzyl-indole (4ba)
1
White solid, yield 86%; H NMR (400 MHz, CDCl3) δ 7.66
(brs, 1H), 7.54 (d, J = 8.4 Hz, 1H), 7.19-7.15 (m, 1H), 7.12-7.07
(m, 4H), 7.04-7.00 (m, 1H), 6.98-6.95 (m, 2H), 2.34 (s, 3H); 13
C
NMR (126 MHz, CDCl3) δ 137.5, 137.1, 129.3, 128.7, 126.7,
125.89, 123.7, 121.7, 120.1, 119.9, 119.7, 111.2, 9.7.
4.2.24. 3-Methyl-2-[(2-Carboxyphenyl)thio] -1H-
indole (3kg)
1
Colorless oil, Yield 89%; H NMR (400 MHz, CDCl3) δ
9 g
7.66 (d, J = 8.0 Hz, 1H), 7.25-7.05 (m, 11H), 7.03-6.96 (m, 5H),
6.94-6.92 (m, 2H), 5.46 (s, 2H); 13C NMR (101 MHz, CDCl3) δ
138.4, 138.4, 137.2, 135.7, 134.6, 129.6, 129.2, 128.9, 128.8,
128.0, 127.6, 126.8, 126.6, 126.5, 125.3, 124.5, 121.5, 120.7,
112.4, 111.3, 48.5; HRMS (ESI) Calcd. for C27H22NS2 ([M+H]+)
424.1188, Found 424.1175.
1
Light yellow solid, yield 77%; H NMR (400 MHz, DMSO-
d6) δ 13.34 (brs, 1H), 11.37 (s, 1H), 8.02 (d, J = 7.6 Hz, 1H), 7.60
(d, J = 8.0 Hz, 1H), 7.39-7.32 (m, 2H), 7.23-7.18 (m, 2H), 7.10-
7.06 (m, 1H), 6.56 (d, J = 8.0 Hz, 1H), 2.32 (s, 3H); 13C NMR
(126 MHz, DMSO-d6) δ 167.4, 141.8, 137.3, 132.7, 131.2, 127.8,
126.7, 125.7, 124.5, 122.8, 121.4, 119.1, 118.8, 118.4, 111.3,
9.04.
4.2.32. 2,3-bis(phenylthio)-5-methoxy-1H-indole
(4da)
1
Colorless oil, Yield 80%; H NMR (400 MHz, CDCl3) δ
4.2.25. 3-(Phenylthio)-1H-pyrrolo[2,3-b]pyridine
(3la)9 f
8.32 (brs, 1H), 7.21-7.16 (m, 5H), 7.15-7.08 (m, 5H), 7.05-7.00
(m, 2H), 6.89-6.86 (m, 1H), 3.73 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ 155.3, 138.2, 134.6, 133.8, 131.9, 130.9, 129.5, 129.4,
128.8, 127.2, 126.4, 125.1, 114.6, 112.2, 108.6, 101.0, 55.8;
HRMS (ESI) Calcd. for C21H18NOS2 ([M+H]+) 364.0824, Found
364.0813.
1
Light yellow solid, yield 86%; H NMR (400 MHz, DMSO-
d6) δ 12.35 (brs, 1H), 8.35-8.30 (m, 1H), 7.97 (s, 1H), 7.83-7.70
(m, 1H), 7.22-7.07 (m, 6H); 13C NMR (126 MHz, DMSO-d6) δ
148.9, 148.0, 143.7, 143.7, 138.6, 133.2, 130.4, 128.9, 128.0,
126.7, 125.6, 125.0, 122.0, 121.0, 116.5, 116.4, 98.7.
4.2.33. 2,3-bis(phenylthio)-5-bromo-1H-indole
(4ea)
1 7 d
4.2.26. 2,3-bis(phenylthio)-1H-indole (4aa)
1
1
Colorless oil, yield 80%; H NMR (400 MHz, CDCl3) δ 8.25
Colorless oil, yield 78%; H NMR (400 MHz, DMSO-d6) δ
12.49 (brs, 1H), 7.57-7.04 (m, 13H); 13C NMR (126 MHz,
DMSO-d6) δ 137.5, 136.2, 134.7, 130.9, 129.4, 129.0, 128.3,
126.8, 126.1, 125.9, 125.3, 120.8, 114.3, 113.5, 106.9; HRMS
(ESI) Calcd. for C21H18NOS2 ([M+H]+) 411.9824, Found
411.9813.
(brs, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.26-7.16 (m, 7H), 7.14-7.08
(m, 5H), 7.04-7.01 (m, 1H); 13C NMR (126 MHz, CDCl3) δ
138.1, 136.9, 134.5, 133.6, 130.0, 129.7, 129.5, 128.8, 127.3,
126.7, 125.2, 124.0, 121.3, 120.0, 111.3, 109.3.
4.2.27. 2,3-bis[(4-methylphenyl)thio]-1H-indole
(4ab)
4.2.34. 2,3-bis(phenylthio)-6-fluoro-1H-indole (4fa)
1
Colorless oil, Yield 64%; H NMR (400 MHz, CDCl3) δ
1
Colorless oil, yield 83%; H NMR (400 MHz, CDCl3) δ 8.13
8.29 (brs, 1H), 7.47-7.44 (m, 1H), 7.25-7.14 (m, 5H), 7.12-7.02
(m, 5H), 6.95- 6.92 (m, 1H), 6.90-6.85 (m, 1H); 19F NMR (470
MHz, CDCl3) δ -117.7; 13C NMR (126 MHz, CDCl3) δ 160..9 (d,
(brs, 1H), 7.56 (d, J = 8.0 Hz, 1H), 7.20-7.15 (m, 4H), 7.11-7.07
(m, 1H), 7.02 (d, J = 7.6 Hz, 4H), 6.92 (d, J = 7.6 Hz, 2H), 2.27
(s, 3H), 2.21 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 137.8, 136.8,
135.0, 134.6, 130.7, 130.3, 130.2, 129.6, 127.0, 123.6, 121.2,
119.8, 111.1, 108.5, 21.2, 21.0; HRMS (ESI) Calcd. for
C22H20NS2 ([M+H]+) 362.1032, Found 362.1018.
1JC-F = 241 Hz), 137.8, 136.97, 136.8, 134.4, 133.6 (d, JC-F = 3.8
3
Hz), 129.6, 129.5, 128.9, 127.4, 126.9, 126.4, 125.4, 121.0 (d,
2JC-F = 10.0 Hz), 110.3, 110.1, 109.9, 97.9, 97.7; HRMS (ESI)
Calcd. for C20H15FNS2 ([M+H]+) 352.0624, Found 352.0619.
4.2.35. Methyl 1-methyl-2,3-bis(phenylthio)-5-
bromo-1H-indole-4-carboxylate (4ga)
4.2.28. 2,3-bis[(3-methoxyphenyl)thio]-1H-indole
(4ac)
Light yellow solid, yield 73%, mp: 230.1-231.9 °C; 1H
NMR (400 MHz, DMSO-d6) δ 12.58 (brs, 1H), 7.65-7.63 (m,
1H), 7.32-7.29 (m, 4H), 7.25-7.20 (m, 3H), 7.18-7.15 (m, 2H),
7.06-7.02 (m, 1H), 6.95 (d, J = 7.6 Hz, 1H), 3.50 (s, 3H); 13C
NMR (126 MHz, DMSO-d6) δ 168.4, 139.1, 138.1, 136.6, 134.4,
129.4, 128.6, 128.5, 126.9, 125.5, 125.1, 124.6, 122.5, 121.1,
114.9, 105.6, 51.5; HRMS (ESI) Calcd. for C22H18NO2S2
([M+H]+) 392.0773, Found 392.0768.
1
Colorless oil, yield 74%; H NMR (400 MHz, CDCl3) δ 8.42
(brs, 1H), 7.58 (d, J = 8.0 Hz, 1H), 7.26-7.19 (m, 2H), 7.15-7.09
(m, 2H), 7.05-7.01 (m, 1H), 6.82-6.77 (m, 2H), 6.72-6.66 (m,
3H), 6.59-6.57 (m, 1H), 3.65 (s, 3H), 3.63 (s, 3H); 13C NMR (126
MHz, CDCl3) δ 160.2, 159.9, 139.6, 137.0, 135.6, 133.5, 130.2,
130.0, 129.6, 124.0, 121.9, 121.3, 119.9, 118.9, 115.0, 113.2,
112.1, 111.3, 110.8, 109.0, 55.3, 55.2; HRMS (ESI) Calcd. for
C22H20NO2S2 ([M+H]+) 394.0930, Found 394.0925.
4.2.36. 2-(Phenylthio)-1H-indole (5)1 7 a
4.2.29. 2,3-bis[(4-fluorophenyl)thio]-1H-indole
(4ae)
1
White solid, yield 93%; H NMR (400 MHz, CDCl3) δ 7.83
(brs, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.19-7.13 (m, 4H), 7.11-7.06
(m, 4H), 6.81 (s, 1H); 13C NMR (126 MHz, CDCl3) δ 137.8,
136.9, 129.3, 128.6, 127.6, 126.4, 125.3, 123.4, 120.9, 120.5,
111.7, 111.1.
1
Colorless oil, yield 70%; H NMR (400 MHz, CDCl3) δ 8.30
(brs, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.30 (d, J = 8.0 Hz, 1H), 7.26-
7.22 (m, 3H), 7.17-7.13 (m, 1H), 7.09-7.05 (m, 2H), 6.94, 6.9-
6.90 (m, 2H), 6.85-6.81 (m, 2H); 19F NMR (470 MHz, CDCl3) δ -

1993, 36, 1291; (b) Hutchinson, J. H.; Riendeau, D.; Brideau, C.;
4.2.37.
indole (6)
2-(phenylthio)-3-(pyridin-2-yAlthCioC)-E1PHT- ED MANUSCRIPT
Chan, C.; Delorme, D.; Denis, D.; Falgueyret, J.-P.; Fortin, R.;
Guay, J.; Hamel, P.; Jones, T. R.; Macdonald, D.; McFarlane, C.
S.; Piechuta, H.; Scheigetz, J.; Tagari, P.; Therien, M.; Girard, Y.
J. Med. Chem. 1993, 36, 2771.
1
White solid, yield 90%, mp: 161.8-162.6 °C; H NMR (400
MHz, DMSO-d6) δ 12.44 (brs, 1H), 8.35 (s, 1H), 7.56 (d, J = 7.6
Hz, 1H), 7.50 (d, J = 7.2 Hz, 1H), 7.43-7.39 (m, 1H), 7.28-7.24
(m, 5H), 7.15 (d, J = 6.4 Hz, 2H), 6.99 (m, 1H), 6.70 (d, J = 8.0
Hz, 1H); 13C NMR (126 MHz, DMSO) δ 161.4, 149.7, 138.2,
137.3, 135.9, 133.4, 129.8, 129.7, 128.4, 127.0, 124.1, 121.4,
120.2, 119.8, 119.4, 112.8, 106.9; HRMS (ESI) Calcd. for
C19H15N2S2 ([M+H]+) 335.0671, Found 335.0667.
4. (a) Raban, M.; Chern, L.-J. J. Org. Chem. 1980, 45, 1688; (b)
Saulnier, M. G.; Gribble, G. W. J. Org. Chem. 1980, 47, 757.
5. (a) Guo, Y.-J.; Tang, R.-Y.; Li, J.-H.; Zhong, P.; Zhang, X.-G.
Adv. Synth. Catal. 2009, 351, 2615; (b) Chen, Y.; Cho, C.-H.;
Larock, R. C. Org. Lett. 2009, 11, 173; (c) Li, Z.; Hong, L.; Liu,
R.; Shen, J.; Zhou, X. Tetrahedron Lett. 2011, 52, 1343; (d) Han,
D.; Li, Z.; Fan, R. Org. Lett. 2014, 16, 6508.
6. Mitamura, T.; Iwata, K.; Ogawa, A. J. Org. Chem. 2011, 76, 3880.
7. (a) Liu, J.; Li, P.; Chen, W.; Wang, L. Chem. Commun. 2012, 48,
10052; (b) Xia, Z.; Wang, K.; Zheng, J.; Ma, Z.; Jiang, Z.; Wang,
X.; Lv, X. Org. Biomol. Chem. 2012, 10, 1602.
Acknowledgments
8. Chitra, S.; Paul, N.; Muthusubramanian, S.; Manisankar, P. RSC
Adv. 2012, 2, 1432.
We thank the National Natural Science Foundation of China
(Nos. 21076035, 20972022), the Program for New Century
Excellent Talents in University (NCET-11-0053), the
Fundamental Research Funds of the Central Universities
(DUT13ZD202) for support of this work.
9. (a) Browder, C. C.; Mitchell, M. O.; Smith, R. L.; el-Stdayman, G.
Tetrahedron Lett. 1993, 34, 6245; (b) Li, Z.; Hong, J.; Zhou, X.
Tetrahedron 2011, 67, 3690; (c) Ge, W.; Wei, Y. Synthesis 2012,
44, 934; (d) Ge, W.; Wei, Y. Green Chem. 2012, 14, 2066; (e)
Huang, D.; Chen, J.; Dan, W.; Ding, J.; Liu, M.; Wu, H. Adv.
Synth. Catal. 2012, 354, 2123; (f) Sang, P.; Chen, Z.; Zou, J.;
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Adv. 2014, 4, 1241; (g) Chen, S.-Q.; Wang, Q.-M.; Xu, P.-C.; Ge,
S.-P.; Zhong, P.; Zhang, X.-H. Phosphorus, Sulfur, and Silicon
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ACCEPTED MANUSCRIPT
Supporting Information
Iodine-Catalyzed Versatile Sulfenylation of Indoles with Thiophenols: Controllable
Synthesis of mono- and bis-Arylthioindoles
Hailei Zhang, Xiaoze Bao, Yuming Song, Jingping Qu, Baomin Wang*
State Key Laboratory of Fine Chemicals, School of Pharmaceutical Science and Technology, Dalian University of
Technology, 2 Linggong Road, Dalian 116024, P. R. China bmwang@dlut.edu.cn
Table of Contents
1H and 13C NMR spectra………………………. 2

2
Tetrahedron
ACCEPTED MANUSCRIPT
1H and 13C NMR spectra
1H NMR of 3aa
13C NMR of 3aa

ACCEPTED MANUSCRIPT
1H NMR of 3ab
13C NMR of 3ab

4
Tetrahedron
ACCEPTED MANUSCRIPT
1H NMR of 3ac
13C NMR of 3ac

1H NMR of 3ad
ACCEPTED MANUSCRIPT
13C NMR of 3ad

6
Tetrahedron
ACCEPTED MANUSCRIPT
1H NMR of 3ae
13C NMR of 3ae

ACCEPTED MANUSCRIPT
1H NMR of 3af
13C NMR of 3af

8
Tetrahedron
ACCEPTED MANUSCRIPT
1H NMR of 3ag
13C NMR of 3ag

ACCEPTED MANUSCRIPT
1H NMR of 3ai
13C NMR of 3ai

10
Tetrahedron
ACCEPTED MANUSCRIPT
1H NMR of 3aj
13C NMR of 3aj

1H NMR of 3ak
ACCEPTED MANUSCRIPT
13C NMR of 3ak

12
Tetrahedron
ACCEPTED MANUSCRIPT
1H NMR of 3cg
13C NMR of 3cg

ACCEPTED MANUSCRIPT
1H NMR of 3da
13C NMR of 3da

14
Tetrahedron
ACCEPTED MANUSCRIPT
1H NMR of 3dg
13C NMR of 3dg

ACCEPTED MANUSCRIPT
1H NMR of 3dh
13C NMR of 3dh

16
Tetrahedron
ACCEPTED MANUSCRIPT
1H NMR of 3ea
13C NMR of 3ea

ACCEPTED MANUSCRIPT
1H NMR of 3eg
13C NMR of 3eg

18
Tetrahedron
ACCEPTED MANUSCRIPT
1H NMR of 3fg
13C NMR of 3fg

ACCEPTED MANUSCRIPT
1H NMR of 3ga
13C NMR of 3ga

20
Tetrahedron
ACCEPTED MANUSCRIPT
1H NMR of 3gg
13C NMR of 3gg

ACCEPTED MANUSCRIPT
1H NMR of 3ia
13C NMR of 3ia