Copper-Catalyzed Indole-Selective C-N Coupling Reaction of Indolyl(2-alkoxy-phenyl)iodonium Imides: Effect of Substituent on Iodoarene as Dummy Ligand

Article abstract of DOI:10.1021/acs.joc.8b02676

A monoalkoxy phenyl group as a dummy ligand on indolyl(aryl)iodonium imides, which is related to the N-I bonding hypervalent iodine(III) compound, for the copper-catalyzed indole-selective C-N coupling reaction was designed to provide 3-bissulfonimido-ind

Full text of DOI:10.1021/acs.joc.8b02676

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Note
Copper-Catalyzed Indole-Selective C–N Coupling
Reaction of Indolyl(2-alkoxy-phenyl)iodonium Imides;
Effect of Substituent on Iodoarene as Dummy Ligand
Kazuhiro Watanabe, and Katsuhiko Moriyama
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02676 • Publication Date (Web): 29 Oct 2018
Downloaded from http://pubs.acs.org on October 30, 2018
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Copper-catalyzed Indole-selective C–N Coupling
Reaction of Indolyl(2-alkoxy-phenyl)iodonium Imides;
Effect of Substituent on Iodoarene as Dummy Ligand
Kazuhiro Watanabe and Katsuhiko Moriyama*
Department of Chemistry, Graduate School of Science, and Molecular Chirality Research Center, Chiba
University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
moriyama@faculty.chiba-u.jp
RECEIVED DATE (to be automatically inserted after your manuscript is accepted if required
according to the journal that you are submitting your paper to)
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Abstract:
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High induction of chemoselectivity
O
N(SO2R’)2
Cu(MeCN)4BF4 (5 mol%)
(R’SO2)2NH (5 mol%)
I
N(SO2R’)2
R
Xylene, 130 ºC
1 h
N
Piv
up to 97% yield
N
R
Piv
High indole selectivity
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A mono-alkoxy phenyl group as a dummy ligand on indolyl(aryl)iodonium imides, which is related to a
N–I bonding hypervalent iodine (III) compound, for the copper-catalyzed indole-selective C–N
coupling reaction was designed to provide 3-bissulfonimido-indole derivatives in high yields. In
particular, use of indolyl(2-butoxylphenyl)iodonium bissulfonimides indicated the high indole
selectivity. Furthermore, this reaction was applied the one-pot synthesis of 3-bissulfonimido-indole
derivatives directly from indoles with bissulfonimides and (diacetoxyiodo)-2-butoxybenzene in
presence of Cu(MeCN)4BF4 catalyst.
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The Journal of Organic Chemistry
Hypervalent iodine compounds have been recognized as organic reagents in lieu of transition metals for
some unique transformations.1 In particular, diaryliodonium salts have been utilized as a highly versatile
electrophilic arylating agent for a variety of nucleophiles.2 Among them, unsymmetrical iodonium salts
are essential for various chemoselective arylations of organic molecules, since the construction of a
bulky aryl group or an electron-rich aryl group on diaryliodonium salt induces chemoselectivity of the
aryl group, leading to electrophilic arylation by a steric bulky substituent on the aryl group or an
electronic property of the aryl group. Actually, the treatment of 2,4,6-trisubstituted phenyl
(aryl)iodonium salt as a dummy ligand arylating reagent resulted in a high chemoselectivity of arylation
with a coupling partner for the transition-metal-catalyzed coupling reaction (Figure 1Aa).3 For
transition-metal-free arylation with diarylidonium salt, the substituted phenyl(aryl)iodonium salt,
including methoxy-substituted phenyl(aryl)iodonium salt, have been extremely useful in providing the
desired arylating product with high chemoselectivity (Figure 1Ab).4 It has been known that the existence
of a steric bulky group at the 2- and 6-positions on iodoarenes is more effective in inducing the high
chemoselectivity of the electrophilic arylation using unsymmetric diaryliodoarene salt (ortho effect).4b,5
However, it is very difficult to access these 2,4,6-trialkyl-substituted phenyl(aryl)iodonium salts in
particular into tailor-made dummy ligands on unsymmetric diaryliodonium salt. We focused on
designing mono-alkoxy iodonium salt as a novel dummy ligand for the chemoselective coupling
reaction of organic molecules (Figure 1B). This strategy has some advantages: 1) the substituent with a
wide variety of functional groups is installed as an alkoxy group on mono-alkoxyiodobenzene from 2-
iodo-phenol; 2) the hypervalent iodine compound containing this dummy ligand is easily prepared and
utilized in various chemoselective coupling reactions; 3) the use of the hypervalent iodine compound
enabled efficient recovery of 2-alkoxyiodobenzene after the reaction.
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Figure 1. Design of unsymmetric diaryliodonium salt.
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A) Unsymmetric iodonium salt containing 2,4,6-substituted benzene for
chemoselective arylation
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2
3
a) Transition-metal-catalyzed
coupling reaction
b) Transition-metal-free arylation
R
OMe
4
5
6
R
I
R
I
OTf
OTf
I
I
OTf
OTf
Ar
Ar
OMe
Ar
Ar
R
(R = Me, i-Pr)
(R = H, OMe)
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8
B) A design of 2-alkoxy iodoarene for chemoselective amination (This work)
9
Novel Dummy Ligand for Coupling Reaction
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O
• One substituted iodoarene
• Easy preparation and tailoring of
various indolyl(aryl)iodonium imides
I
N(SO2R’)2
EWG
• Increase chemoselectivity of coupling reaction
by steric hindrance of alkyl group
N
R
On the other hand, 3-amino indoles are very important molecules for nitrogen-containing natural
products and biologically active compounds.6 Therefore, the 3-amination of indoles with amino reagents
was previously developed using ingenious methodologies. For example, electrophilic aminations with
nitro compounds7 and N-[(benzenesulfonyl)oxy]amides8, azidation with azido compounds9, and
transition-metal-free amination with N-fluorobenzenesulfonimide as the amino reagent10 have been
reported; however, these previous methods suffer a narrow scope of available amino reagents or the
need to use an excess amount of transition metal. Suna and co-workers recently developed that 3-
amination of 2-substituted indoles with amines and azide with the copper catalyst via formation of
indolyl(aryl)iodonium tosylate.3c,9b Although we also developed the metal-free 3-amination of indole
derivatives through the preparation of indolyl(aryl)iodonium imides, the reaction of some substituted
indoles had low reactivity (22–57% yield).11 In this context, we report herein a copper-catalyzed indole-
selective and 3-position-selective C–N coupling reaction of indolyl(aryl)iodonium imides.
Various indolyl(aryl)iodonium imides (2) were prepared from N-protected indoles (1) with
bissulfonimides and (diacetoyiodo)arenes on the basis of previously reported reaction condisions
(Scheme 1).11
Scheme 1. Synthesis of indolyl(aryl)iodonium imides (2).
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The Journal of Organic Chemistry
OAc
I
(1.2 equiv.)
I
N(SO2R)2
Piv
1
2
3
R
R
OAc
+
(RSO2)2NH
(1.2 equiv.)
N
MeCN, 40 ºC
R
N
Piv
1
2
4
5
6
7
8
9
First, we investigated the screening of dummy ligand in indolyl(aryl)iodonium bistosylimide (2) for the
C–N coupling reaction using CuI catalyst (Table 1). It is noteworthy that the presence of catalytic
amount of Ts2NH (20 mol%) as an additive increases the reactivity of this reaction.
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Table 1. Screening of dummy ligand on indolyl(aryl)iodonium imides (2).
NTs2
CuI (20 mol%)
Ts2NH (20 mol%)
I
NTs2
Piv
R
+
NTs2
Xylene, 130 ºC
1 h
R
N
N
Piv
2
3a
4
Substrate (2) and Yield (3a/4) (%)
I
NTs2
t-Bu
I
NTs2
Piv
MeO
I NTs2
N
N
N
Piv
Piv
(2aa)
3a/4aa, 21%/74%
(2ab)
3a/4ab, 30%/69%
(2ac)
3a/4ac, 25%/70%
Cl
Cl
OMe
I
OEt
O2N
I
NTs2
Piv
I
NTs2
NTs2
I
NTs2
Piv
N
N
N
N
Piv
Piv
(2ad)
(2ae)
(2af)
(2ag)
3a/4ag, 62%/17%
3a/4ad, 11%/67%
3a/4ae, 30%/64% 3a/4af, 72%/25%
OPh
O
O
O
I
NTs2
Piv
I
NTs2
Piv
I
NTs2
Piv
I
NTs2
Piv
N
N
N
N
(2ah)
3a/4ah, 76%/7%
(2ai)
3a/4ai, 83%/9%
(2aj)
3a/4aj, 77%/15%
(2ak)
3a/4ak, 68%/10%
Treatment of indolyl(phenyl)iodonium imide (2aa) with CuI (20 mol%) and Ts2NH (20 mol%) in
xylene at 130 ºC yielded aniline derivative (4aa) as the major product. 4-Substituted phenyl groups
bearing an electron-donating group and an electron-withdrawing group, and an 3,5-dichloro phenyl
group as a dummy ligand (2ab–2ae) also enabled mainly the aryl-selective C–N coupling reaction to
proceed. When indolyl(2-methoxyphenyl)iodonium imide (2af) was used in this reaction, the 3-amino
indole derivative (3a) was obtained in 75% yield as the major product. It was found that substrates with
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the 2-alkoxy phenyl group exhibit a tendency of indole selectivity for the C–N coupling reaction.
Exchanging the alkoxyl group on a dummy ligand improved the indole selectivity for this reaction, and
indolyl(2-butoxyphenyl)iodonium imide (2ai) produced the desired product (3a) in 83% yield as the
best result. Other 2-substituted phenyl groups (2ag–2ak) slightly reduced the yield of 3a. By contrast,
the indolyl(aryl)iodonium imide bearing 2,4,6-trimethyl phenyl group was synthesized from
(diacetoxy)-2,4,6-trimethyliodobenzene with N-pivaloyl indole and Ts2NH in a lower yield than that of
indolyl(o-alkoxyphenyl)iodonium imide (51% 1H-NMR yield of indolyl(2,4,6-trimethyl
phenyl)iodonium imide)12 by the protocol in Scheme 1, and could not prepared. Moreover, copper
catalysts and solvents were screened for the C–N coupling reaction of 2ai (Table 2), and xylene was
proven to be the optimum solvent for the reaction (Entries 1–7). For the screening of copper catalysts,
Cu(OAc)2 and Cu(MeCN)4BF4 were more suitable than other copper catalysts for the C–N coupling
reaction (Entries 8–15). The reaction in the absence of copper catalyst and Ts2NH as additive decreased
the yield of 3a (Entries 16 and 17). The use of Cu(MeCN)4BF4 allowed the copper load to be reduced
from 20 to 5 mol% (with 5 mol% Ts2NH) without decreasing the yield of 3a (Entries 18 and 19). In
addition, 2-butoxy-iodobenzene was recovered to 82% by column chromatography after the reaction
(Entry 19). The C–N coupling reaction of 2ai on the 1 mmol scale also gave 3a in high yield (92%
yield) (Entry 20).
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Table 2. Screening of Cu catalyst for C–N coupling reaction.
O
NTs2
“Cu” (x mol%)
Ts2NH (y mol%)
I
NTs2
Piv
Xylene, 130 ºC
1 h
N
N
Piv
2ai
3a
Entry Cu catalyst
(x mol%)
y
Solvent
Temp. Yield
(ºC)
130
(%)
83
1
2
CuI (20)
CuI (20)
20 Xylene
20 MeCN
reflux trace
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The Journal of Organic Chemistry
3
CuI (20)
CuI (20)
CuI (20)
CuI (20)
CuI (20)
CuCl (20)
CuBr (20)
20 ClCH2CH2Cl reflux 70
1
2
3
4
5
6
7
8
4
20 THF
reflux 65
5
20 DMF
130
130
42
18
6
20 DMSO
20 Toluene
20 Xylene
20 Xylene
7
reflux 82
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130
130
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78
95
89
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58
92
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Cu(OAc)2 (20) 20 Xylene
Cu(OBz)2 (20) 20 Xylene
CuCl2 (20)
20 Xylene
20 Xylene
Cu(OTf)2 (20)
Cu(MeCN)2BF4 20 Xylene
(20)
15
16
17
CuOAc (20)
-
20 Xylene
20 Xylene
130
130
130
88
5
Cu(MeCN)2BF4
(20)
0
Xylene
81
18
19
Cu(OAc)2 (5)
5
5
Xylene
Xylene
130
130
86
Cu(MeCN)2BF4
(5)
93
(82)a
20b
Cu(MeCN)2BF4
(5)
5
Xylene
130
92
a
b
Number in parentheses indicates degree of recovery of 2-butoxy-iodobenzene. Reaction on 1 mmol
scale.
To explore the range of applicable substrates for the copper-catalyzed indole-selective C–N coupling
reaction, various indolyl(2-butoxyphenyl)iodonium imides (2) were examined under the optimum
conditions (Table 2, Entry 19) (Scheme 2). The use of substrates bearing other sulfonyl groups (2bi–2ei)
instead of the tosyl group resulted in the corresponding product (3b–3e) in 75–82% yield. Treatment of
substituted indole derivatives (2bf–2es) other than 4-bromo indole derivatives (2qs) also led to the 3-
amino indole derivatives (3b–3e) in high yields (75–97%). The indole selectivity of 2qs was reduced for
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amination into the 2-butoxy phenyl moiety by the steric hindrance of the 4-bromo group on an indole
skeleton. Other N-protected indole derivatives (2ti and 2ui) in place of N-pivaloyl indole were also
competent substrates for forming 3-amino indole derivatives (3t and 3u) in high yields (84% and 81%).
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3
4
5
6
7
8
9
Scheme 2. Cu-catalyzed C–N coupling of indolyl(2-butoxyphenyl)iodonium imides (2i).
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O
N(SO2R’)2
Cu(MeCN)4BF4 (5 mol%)
(R’SO2)2NH (5 mol%)
I
N(SO2R’)2
Piv
R
Xylene, 130 ºC
1 h
N
Piv
N
R
3
2i
Product (3) and Yield (%)
N(SO2Ph)2
NTsMs
N(SO2n-Pr)2
N(SO2Bn)2
N
N
N
N
Piv
3b, 80%
Piv
Piv
Piv
3e,a 75%
3c, 82%
3d, 77%
NTs2
F
NTs2
NTs2
NTs2
Cl
Br
N
N
N
N
Piv
Piv
3g, 93%
Piv
Piv
3f, 93%
3h, 91%
3i, 91%
NTs2
NTs2
NTs2
NTs2
MeO
PivO
MeO2C
NC
N
N
N
N
Piv
Piv
Piv
Piv
3j, 92%
3k, 93%
3l, 84%
3m, 97%
O
Br
NTs2
NTs2
NTs2
NTs2
N
N
N
O
N
Cl
N
Piv
Piv
Piv
Piv
3p, 94%
3q, 40%
3n, 75%
3o, 95%
NTs2
NTs2
NTs2
NTs2
Cl
Cl
N
N
N
N
Piv
Piv
Bz
Ts
3u, 81%
3r,b 77%
3s, 93%
3t, 84%
a For 2 h. b At 100 ºC.
The proposed reaction mechanism of the copper-catalyzed C–N coupling reaction of indolyl(2-
butoxyphenyl)iodonium imides (2i) is depicted in Scheme 3. We suggest the activation of 2i by copper
catalyst on the basis of the previous reports of copper-catalyzed coupling reactions with
diaryliodoonium salts.3a–d,9b This C–N coupling reaction promotes the generation of a Cu(III) active
species (A) upon the oxidative addition of Cu(I) catalyst into 2i. The presence of 2-butoxy group on the
dummy ligand of 2i induces high indole selectivity by a steric effect but an electoric effect for the
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The Journal of Organic Chemistry
oxidative addition step. Consequently, it is possible that copper catalyst slightly improves the reactivity
of the C–N coupling reaction by exchanging the ligand to the bissulfonimide group (Table 2, Entry 7 vs
10). Subsequently, the reductive elimination of A results in the desired product (3) and the regeneration
of the Cu(I) species. In addition, the reaction with Cu(II) catalyst also progressed via generation of the
Cu(I) species, which is reduced from Cu(II) by indole derivatives.3a
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Scheme 3. Plausible reaction mechanism.
O
CuIN(SO2R’)2
I
N(SO2R’)2
Piv
(R’SO2)2NH
N
R
CuI
2i
L
CuIII
O
N(SO2R’)2
N(SO2R’)2
I
R
N
R
N
Piv
Piv
A
3
Next, we attempted one-pot synthesis of 3-amino indole derivatives (3) from indoles (1) with Ts2NH
through the copper-catalyzed C–N coupling reaction (Scheme 4). Treatment of N-pivaloyl indole (1a)
with Ts2NH (1.6 equiv.) and (diacetoxyiodo)-2-butoxybenzene (1.2 equiv.) in MeCN at 40 ºC for 7 h,
followed by the addition of Cu(MeCN)4BF4 (5 mol%) in xylene at 130 ºC for 1 h produced the desired
product (3a) in 78% yield. The use of various functional-group-substituted indoles (1j, 1h, 1l, 1o, 1p, 1r,
and 1s) also produced the corresponding 3-amino indole derivatives (3j, 3h, 3l, 3o, 3p, 3r, and 3s) in
54–79% yields, respectively.
Scheme 4. One-pot synthesis of 3-amino indole derivatives (3) from indoles (1).
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O
1
I(OAc)2
NTs2
2
3
4
5
6
7
Cu(MeCN)4BF4
(5 mol%)
(1.2 equiv.)
+
Ts2NH
N
Xylene, 130 ºC
1 h
MeCN, 40 ºC
7 h
R
N
(1.6 equiv.)
Piv
R
Piv
1
3
Product (3) and Yield (%)
NTs2
MeO
NTs2
Cl
NTs2
NTs2
MeO2C
8
N
N
N
N
9
Piv
3a, 78%
(81%)a
Piv
Piv
Piv
3j, 79%
3h, 75%
3l,b 55%
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NTs2
NTs2
NTs2
NTs2
Cl
Cl
N
N
N
N
Cl
Piv
3o,b 68%
Piv
3p, 69%
Piv
3r,c 69%
Piv
3s, 54%
a Reaction on 1 mmol scale. b For 24 h (for 1st step). c At 100 ºC (2nd step).
To realize the transformation of 3-amino indole derivatives (3), the deprotection of the tosyl group on
3a using TBAF was carried out.12 Intriguingly, the reaction of 3a with 3.0 equiv. of TBAF caused the
deprotection of the pivaloyl group and the rearrangement of the tosyl group to obtain 2-tosyl-3-
sulfonamido-indole (5) in 70% yield (Scheme 5). The structure of 5 was determined by X-ray crystal-
structure analysis.13
Scheme 5. Derivatization of 3-aminoindole derivatives (3a).
O
O
N
S
NHTs
Ts
NTs2
TBAF (3.0 equiv.)
O
S
THF, rt
24 h
N
N
N
H
Piv
O
5 (70%)
3a
In conclusion, we designed mono-substituted phenyl groups as dummy ligands on
indolyl(aryl)iodonium imide (2) for the copper-catalyzed indole-selective C–N coupling reaction. This
process proceeds through C–N bond formation between nucleophilic indoles and nucleophilic amides to
provide various 3-amino indole derivatives (3). Furthermore, this reaction was applied in the one-pot
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synthesis of 3 from indoles (1). The design of unsymmetric diaryliodonium-like salt containing novel
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dummy ligands and its use in transition-metal-catalyzed transformation are under way in our laboratory.
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Experimental Section
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General Procedure
1H NMR spectra were measured on a JEOL ECS-500 (500 MHz) spectrometer at ambient temperature.
Data were recorded as follows: chemical shift in ppm from internal tetramethylsilane on the δ scale,
multiplicity (s = singlet; d = doublet; t = triplet; q = quartet; sep = septet; m = multiplet; br = broad),
coupling constant (Hz), integration, and assignment. 13C NMR spectra were measured on a JEOL ECS-
500 (125 MHz) spectrometer. Chemical shifts were recorded in ppm from the solvent resonance
employed as the internal standard (deuterochloroform at 77.0 ppm). High-resolution mass spectra were
recorded by Thermo Fisher Scientific Exactive Orbitrap mass spectrometers. Infrared (IR) spectra were
recorded on a JASCO FT/IR 4100 spectrometer. Single crystal X-ray diffraction data were collected at
173K on a Bruker SMART APEX II ultra CCD diffractometer with Cu Kα (λ = 1.54178) radiation and
graphite monochromator. For thin-layer chromatography (TLC) analysis throughout this work, Merck
precoated TLC plates (silica gel 60GF254 0.25 mm) were used. The products were purified by neutral
column chromatography on silica gel (Kanto Chemical Co., Inc. silica gel 60N, Prod. No. 37560-84;
Merck silica gel 60, Prod. No. 1.09385.9929). Visualization was accomplished by UV light (254 nm),
anisaldehyde, KMnO4, and phosphomolybdic acid. In experiments that required dry solvents such as
CH2Cl2, MeCN, CHCl3, and THF were distilled in prior to use.
Procedure for Cu-catalyzed C–N Coupling Reaction of Indolyl(2-butoxyphenyl)iodonium Imides
(2i) (Table 2; Entry 19, and Scheme 2).
A solution of N-pivaloyl indolyl(2-butoxyphenyl)iodonium bis(tosyl)imide (2ai) (160.2 mg, 0.20 mmol),
Cu(MeCN)4BF4 (3.1 mg, 0.01 mmol), and bis(tosyl)imide (3.3 mg, 0.01 mmol) in xylene (2.0 mL) was
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stirred at 130 ºC (oil bath) for 1 h under argon atmosphere. To the reaction mixture was added saturated
NaHCO3 aqueous solution (10 mL), and the product was extracted with AcOEt (15 mL×3). The
combined extracts were washed by brine (10 mL) and dried over Na2SO4. The organic phase was
concentrated under reduced pressure and the crude product was purified by silica gel column
chromatography (eluent: hexane/AcOEt = 5/1), to give the desired product 3a (97.2 mg, 93 % yield).
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Procedure for One-pot Synthesis of 3-Ammino Indole Derivatives (3) from Indoles (1) (Scheme 4).
A mixture of 1-(diacetoxyiodo)-2-butoxybenzene (94.6 mg, 0.24 mmol) and Ts2NH (104.1 mg, 0.32
mmol) in MeCN (2.0 mL) was stirred at room temperature for 30 min under argon atomosphere. Then,
N-pivalolylindole (1a) (40.3 mg, 0.20 mmol) was added, and the solution was stirred at 40 ºC (oil bath)
for 7 h under argon atmosphere. The reaction mixture was concentrated under reduced pressure and
crude product was dissolved xylene (2.0 mL). Cu(MeCN)4BF4 (3.1 mg, 0.01 mmol) was added to the
reaction mixture at room temperature, and further stirred at 130 ºC (oil bath) for 1 h under argon
atmosphere. To the reaction mixture was added saturated NaHCO3 aqueous solution (10 mL), and the
product was extracted with AcOEt (15 mL×3). The combined extracts were washed by brine (10 mL)
and dried over Na2SO4. The organic phase was concentrated under reduced pressure and the crude
product was purified by silica gel column chromatography (eluent: hexane/AcOEt = 5/1), to give the
desired product 3a (82.2 mg, 78% yield).
4-Methyl-N-(1-pivaloyl-1H-indol-3-yl)-N-tosylbenzenesulfonamide (3a): 97.2 mg, 93 %, White
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solid, mp 214.0–214.5 ºC, H NMR (500 MHz, CDCl3) δ 1.40 (s, 9H), 2.46 (s, 6H), 7.07 (d, J = 7.8 Hz,
1H), 7.14-7.19 (m, 1H), 7.30-7.37 (m, 1H), 7.32 (d, J = 8.2 Hz, 4H), 7.46 (s, 1H), 7.87 (d, J = 8.2 Hz,
4H), 8.46 (d, J = 8.3 Hz, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 21.7 (2C), 28.5 (3C), 41.3, 115.8,
117.3, 118.6, 124.1, 126.0, 126.8, 127.7, 128.6 (4C), 129.6 (4C), 135.7, 136.2 (2C), 145.2 (2C), 176.7.
IR (neat) 1702, 1374, 1357, 1316, 1165 cm–1. MS (ESI) calcd for C27H29N2O5S2 [M+H]+ 525.1512,
found 525.1501.
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Crystal data for 3a: Formula C27H28N2O5S2, colorless, crystal dimensions 0.30 × 0.20 × 0.20 mm3,
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Triclinic, space group P -1, a = 9.475(2) Å, b = 10.144(2) Å, c = 13.660(3) Å, α = 98.118(3) °, β =
91.348(3) °, γ = 100.871(3) °, V = 1274.7(5) Å3, Z = 2, ρcalc = 1.367 g cm-3, F(000) = 552, µ(MoKα) =
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0.250 mm-1, T = 173 K. 7413 reflections collected, 5602 independent reflections with I > 2σ(I) (2θmax
=
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27.572 °), and 330 parameters were used for the solution of the structure. The non-hydrogen atoms
were refined anisotropically. R1 = 0.0508 and wR2 = 0.1031. GOF = 1.015. Crystallographic data
(excluding structure factors) for the structure reported in this paper have been deposited with the
Cambridge Crystallographic Data Centre as supplementary publication no. CCDC-1860598. Copies of
the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ,
UK [Fax: int. code + 44(1223)336-033; E-mail: deposit@ccdc.cam.ac.uk].
N-(Phenylsulfonyl)-N-(1-pivaloyl-1H-indol-3-yl)benzenesulfonamide (3b): 79.0 mg, 80 %, White
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solid, mp 182.0–183.0 ºC, H NMR (500 MHz, CDCl3) δ 1.39 (s, 9H), 7.01 (d, J = 8.0 Hz, 1H), 7.12-
7.18 (m, 1H), 7.31-7.37 (m, 1H), 7.48 (s, 1H), 7.50-7.56 (m, 4H), 7.67 (t, J = 7.5 Hz, 2H), 7.97-8.02 (m,
4H), 8.47 (d, J = 8.5 Hz, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 28.5 (3C), 41.3, 115.5, 117.3, 118.5,
124.2, 126.1, 126.6, 127.7, 128.5 (4C), 129.0 (4C), 134.1 (2C), 135.6, 139.0 (2C), 176.7. IR (neat)
1704, 1381, 1344, 1315, 1159 cm–1. MS (ESI) calcd for C25H25N2O5S2 [M+H]+ 497.1199, found
497.1205.
4-Methyl-N-(methylsulfonyl)-N-(1-pivaloyl-1H-indol-3-yl)benzenesulfonamide (3c): 73.2 mg,
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82%, White solid, mp 221.5–22.0 ºC, H NMR (500 MHz, CDCl3) δ 1.44 (s, 9H), 2.43 (s, 3H), 3.56 (s,
3H), 7.23-7.30 (m, 3H), 7.30-7.34 (m, 1H), 7.34-7.40 (m, 1H), 7.62 (s, 1H), 7.79 (d, J = 8.3 Hz, 2H),
8.48 (d, J = 8.3 Hz, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 21.7, 28.5 (3C), 41.4, 44.0, 115.2, 117.4,
118.2, 124.4, 126.2, 126.7, 127.2, 128.8 (2C), 129.6 (2C), 135.1, 135.7, 145.6, 176.7. IR (neat) 1704,
1366, 1349, 1317, 1157 cm–1. MS (ESI) calcd for C21H25N2O5S2 [M+H]+ 449.1199, found 449.1198.
N-(1-Pivaloyl-1H-indol-3-yl)-N-(propylsulfonyl)propane-1-sulfonamide (3d): 65.7 mg, 77 %,
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White solid, mp 190.0–191.0 ºC, H NMR (500 MHz, CDCl3, 60ºC) δ 1.07 (t, J = 7.3 Hz, 6H), 1.52 (s,
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9H), 1.88-2.01 (m, 4H), 3.37-3.55 (m, 2H), 3.55-3.75 (m, 2H), 7.31-7.41 (m, 2H), 7.62 (d, J = 7.5 Hz,
1H), 7.88 (s, 1H), 8.50 (d, J = 8.0 Hz, 1H). 13C{1H} NMR (125 MHz, CDCl3, 60 ºC) δ 12.8 (2C), 17.1
(2C), 28.7 (3C), 41.5, 57.7 (2C), 115.5, 117.6, 118.5, 124.5, 126.2, 126.9, 127.2, 135.9, 176.7. IR (neat)
1703, 1370, 1347, 1316, 1151 cm–1. MS (ESI) calcd for C19H29N2O5S2 [M+H]+ 429.1512, found
429.1512.
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N-(Benzylsulfonyl)-1-phenyl-N-(1-pivaloyl-1H-indol-3-yl)methanesulfonamide (3e): 78.3 mg,
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75 %, White solid, mp 187.0–188.0 ºC, H NMR (500 MHz, CDCl3, 60 ºC) δ 1.33 (s, 9H), 4.57 (d, J =
13.5 Hz, 2H), 5.10 (d, J = 13.5 Hz, 2H), 7.02 (s, 1H), 7.25-7.30 (m, 1H), 7.31-7.39 (m, 7H), 7.44-7.49
(m, 5H), 8.41 (d, J = 8.5 Hz, 1H). 13C{1H} NMR (125 MHz, CDCl3, 60 ºC) δ 28.7 (3C), 41.4, 61.7 (2C),
115.4, 117.6, 118.1, 124.4, 126.0, 126.8, 127.3 (2C), 127.5, 128.9 (4C), 129.5 (2C), 131.4 (4C), 135.7,
176.8. IR (neat) 1699, 1372, 1351, 1317, 1156 cm–1. MS (ESI) calcd for C27H29N2O5S2 [M+H]+
525.1512, found 525.1517.
4-Methyl-N-(5-methyl-1-pivaloyl-1H-indol-3-yl)-N-tosylbenzenesulfonamide (3f): 99.8 mg, 93 %,
1
White solid, mp 217.0–217.5 ºC, H NMR (500 MHz, CDCl3) δ 1.39 (s, 9H), 2.28 (s, 3H), 2.47 (s, 6H),
6.71-6.73 (m, 1H), 7.12-7.16 (m, 1H), 7.32 (d, J = 8.2 Hz, 4H), 7.42 (s, 1H), 8.87 (d, J = 8.2 Hz, 4H),
8.31 (d, J = 8.6 Hz, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 21.2, 21.7 (2C), 28.5 (3C), 41.2, 115.6,
116.9, 118.4, 126.9, 127.4, 127.6, 128.7 (4C), 129.5 (4C), 133.8, 133.9, 136.3 (2C), 145.2 (2C), 176.6.
IR (neat) 1701, 1379, 1353, 1308, 1156 cm–1. MS (ESI) calcd for C28H31N2O5S2 [M+H]+ 539.1669,
found 539.1672.
N-(5-Fluoro-1-pivaloyl-1H-indol-3-yl)-4-methyl-N-tosylbenzenesulfonamide (3g):
100.9 mg,
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93 %, White solid, mp 214.5–215.2 ºC, H NMR (500 MHz, CDCl3) δ 1.40 (s, 9H), 2.47 (s, 6H), 6.66
(dd, J = 8.5, 2.5 Hz, 1H), 7.05 (td, J = 9.0, 2.5 Hz, 1H), 7.33 (d, J = 8.5 Hz, 4H), 7.51 (s, 1H), 7.86 (d, J
= 8.5 Hz, 4H), 8.43 (dd, J = 9.0, 4.5 Hz, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 21.7 (2C), 28.5 (3C),
41.3, 104.3 (d, JC–F = 25.0 Hz), 113.9 (d, JC–F = 25.0 Hz), 115.5 (d, JC–F = 3.5 Hz), 118.6 (d, JC–F = 9.5
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Hz), 128.1 (d, JC–F = 9.5 Hz), 128.5 (4C), 129.0, 129.7 (4C), 131.9, 136.1 (2C), 145.5 (2C), 159.9 (d, JC–
F = 240.8 Hz), 176.5. 19F NMR (471 MHz, CDCl3) δ –117.9. IR (neat) 1708, 1376, 1359, 1311, 1237,
1169 cm–1. MS (ESI) calcd for C27H28FN2O5S2 [M+H]+ 543.1418, found 543.1422.
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N-(5-Chloro-1-pivaloyl-1H-indol-3-yl)-4-methyl-N-tosylbenzenesulfonamide (3h):
101.2 mg,
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91 %, White solid, mp 205.5–206.0 ºC, H NMR (500 MHz, CDCl3) δ 1.41 (s, 9H), 2.48 (s, 6H), 6.81
(d, J = 2.0 Hz, 1H), 7.27 (d, J = 8.9, 2.0 Hz, 1H), 7.33 (d, J = 8.5 Hz, 4H), 7.52 (s, 1H), 7.85 (d, J = 8.5
Hz, 4H), 8.38 (d, J = 8.9 Hz, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 21.7 (2C), 28.4 (3C), 41.3, 115.2,
118.2, 118.4, 126.2, 128.0, 128.6 (4C), 128.7, 129.7 (4C), 130.0, 133.9, 136.0 (2C), 145.6 (2C), 176.6.
IR (neat) 1708, 1379, 1351, 1307, 1163, 1085 cm–1. MS (ESI) calcd for C27H28ClN2O5S2 [M+H]+
559.1123, found 559.1119.
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N-(5-Bromo-1-pivaloyl-1H-indol-3-yl)-4-methyl-N-tosylbenzenesulfonamide (3i): 109.3 mg, 91 %,
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White solid, mp 215.0–216.0 ºC, H NMR (500 MHz, CDCl3) δ 1.41 (s, 9H), 2.48 (s, 6H), 6.09 (d, J =
1.8 Hz, 1H), 7.31-7.35 (m, 4H), 7.40 (dd, J = 9.0, 1.8 Hz, 1H), 7.51 (s, 1H), 7.82-7.86 (m, 4H), 8.32 (d,
J = 9.0 Hz, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 21.7 (2C), 28.4 (3C), 41.3, 115.0, 117.7, 118.7,
121.3, 128.4, 128.50, 128.55 (4C), 128.8, 129.7 (4C), 134.3, 136.0 (2C), 145.6 (2C), 176.6. IR (neat)
1703, 1382, 1348, 1306, 1164, 659 cm–1. MS (ESI) calcd for C27H28BrN2O5S2 [M+H]+ 603.0618, found
603.0620.
N-(5-Methoxy-1-pivaloyl-1H-indol-3-yl)-4-methyl-N-tosylbenzenesulfonamide (3j): 102.1 mg,
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92 %, White solid, mp 220.0–221.0 ºC, H NMR (500 MHz, CDCl3) δ 1.39 (s, 9H), 2.46 (s, 6H), 3.62
(s, 3H), 6.37 (d, J = 2.6 Hz, 1H), 6.92 (dd, J = 9.1, 2.6 Hz, 1H), 7.32 (d, J = 8.2 Hz, 4H), 7.43 (s, 1H),
7.88 (d, J = 8.2 Hz, 4H), 8.34 (d, J = 9.1 Hz, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 21.7 (2C), 28.6
(3C), 41.2, 55.2, 100.1, 115.4, 115.6, 118.3, 127.8, 128.0, 128.6 (4C), 129.6 (4C), 130.2, 136.4 (2C),
145.2 (2C), 156.7, 176.4. IR (neat) 1701, 1380, 1358, 1312, 1162, 1086 cm–1. MS (ESI) calcd for
C28H31N2O6S2 [M+H]+ 555.1618, found 555.1621.
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3-((4-Methyl-N-tosylphenyl)sulfonamido)-1-pivaloyl-1H-indol-5-yl pivalate (3k): 116.2 mg, 93 %,
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White solid, mp 225.0 ºC (dec.), H NMR (500 MHz, CDCl3) δ 1.35 (s, 9H), 1.40 (s, 9H), 2.45 (s, 6H),
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6.64 (d, J = 2.5 Hz, 1H), 7.02 (dd, J = 9.0, 2.5 Hz, 1H), 7.33 (d, J = 8.3 Hz, 4H), 7.48 (s, 1H), 7.88 (d, J
= 8.3 Hz, 4H), 8.46 (d, J = 9.0 Hz, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 21.7 (2C), 27.1 (3C), 28.5
(3C), 38.9, 41.3, 113.3, 115.7, 118.1, 120.0, 127.6, 128.58 (4C), 128.63, 129.7 (4C), 133.2, 136.2 (2C),
145.3 (2C), 147.7, 176.5, 176.8. IR (neat) 1750, 1708, 1377, 1358, 1311, 1167, 1119 cm–1. MS (ESI)
calcd for C32H37N2O7S2 [M+H]+ 625.2037, found 625.2037.
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Methyl 3-((4-methyl-N-tosylphenyl)sulfonamido)-1-pivaloyl-1H-indole-5-carboxylate (3l): 97.4
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mg, 84 %, White solid, mp 221.0–221.5 ºC, H NMR (500 MHz, CDCl3) δ 1.41 (s, 9H), 2.46 (s, 6H),
3.89 (s, 3H), 7.33 (d, J = 8.3 Hz, 4H), 7.54 (s, 1H), 7.63 (d, J = 1.5 Hz, 1H), 7.86 (d, J = 8.3 Hz, 4H),
8.02 (d, J = 8.9, 1.5 Hz, 1H), 8.50 (d, J = 8.9 Hz, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 21.7 (2C),
28.4 (3C), 41.4, 52.0, 116.2, 117.1, 120.7, 126.1, 126.6, 127.2, 128.6 (4C), 128.8, 129.7 (4C), 136.0
(2C), 138.1, 145.5 (2C), 166.7, 176.7. IR (neat) 1717, 1379, 1360, 1313, 1165 cm–1. MS (ESI) calcd
for C29H31N2O7S2 [M+H]+ 583.1567, found 583.1571.
N-(5-Cyano-1-pivaloyl-1H-indol-3-yl)-4-methyl-N-tosylbenzenesulfonamide (3m): 106.7 mg,
1
97 %, White solid, mp 214.0–215.0 ºC, H NMR (500 MHz, CDCl3) δ 1.42 (s, 9H), 2.49 (s, 6H), 7.17
(d, J = 1.5 Hz, 1H), 7.34 (d, J = 8.0 Hz, 4H), 7.55 (dd, J = 9.0, 1.5 Hz, 1H), 7.64 (s, 1H), 7.83 (d, J = 8.0
Hz, 4H), 8.55 (d, J = 8.5 Hz, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 21.7 (2C), 28.2 (3C), 41.5, 107.6,
115.5, 118.2, 118.8, 123.4, 126.9, 128.5 (4C), 128.7, 129.5, 129.8 (4C), 135.7 (2C), 137.2, 145.8 (2C),
176.6. IR (neat) 2221, 1715, 1363, 1348, 1308, 1169, 1086 cm–1. MS (ESI) calcd for C28H28N3O5S2
[M+H]+ 550.1465, found 550.1470.
N-(5-(1,3-Dioxoisoindolin-2-yl)-1-pivaloyl-1H-indol-3-yl)-4-methyl-N-tosylbenzenesulfonamide
1
(3n): 99.8 mg, 75 %, White solid, mp 227.5–228.0 ºC, H NMR (500 MHz, CDCl3) δ 1.39 (s, 9H),
2.44 (s, 6H), 7.23 (d, J = 2.0 Hz, 1H), 7.38 (d, J = 8.3 Hz, 4H), 7.42 (dd, J = 9.0, 2.0 Hz, 1H), 7.47 (s,
1H), 7.80 (dd, J = 5.5, 3.0 Hz, 2H), 7.92 (d, J = 8.3 Hz, 4H), 7.96 (dd, J = 5.5, 3.0 Hz, 2H), 8.61 (d, J =
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9.0 Hz, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 21.7 (2C), 28.4 (3C), 41.3, 115.6, 117.5, 118.0, 123.6
(2C), 124.7, 127.3, 127.9, 128.6 (4C), 128.9, 129.8 (4C), 131.8 (2C), 134.3 (2C), 134.9, 136.0 (2C),
145.3 (2C), 167.1 (2C), 176.6. IR (neat) 1727, 1705, 1375, 1355, 1308, 1167, 1080 cm–1. MS (ESI)
calcd for C35H32N3O7S2 [M+H]+ 670.1676, found 670.1678.
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N-(6-Chloro-1-pivaloyl-1H-indol-3-yl)-4-methyl-N-tosylbenzenesulfonamide (3o):
106.5 mg,
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95 %, White solid, mp 212.5–213.0 ºC, H NMR (500 MHz, CDCl3) δ 1.40 (s, 9H), 2.47 (s, 6H), 6.94
(d, J = 8.6 Hz, 1H), 7.14 (dd, J = 8.6, 1.7 Hz, 1H), 7.30-7.35 (m, 4H), 7.46 (s, 1H), 7.82-7.87 (m, 4H),
8.54 (d, J = 1.7 Hz, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 21.7 (2C), 28.4 (3C), 41.3, 115.7, 117.6,
119.4, 124.8, 125.4, 128.1, 128.5 (4C), 129.7 (4C), 132.1, 135.8, 136.1 (2C), 145.4 (2C), 176.6. IR
(neat) 1706, 1381, 1360, 1337, 1160, 1083 cm–1. MS (ESI) calcd for C27H28ClN2O5S2 [M+H]+ 559.1123,
found 559.1123.
4-Methyl-N-(7-methyl-1-pivaloyl-1H-indol-3-yl)-N-tosylbenzenesulfonamide (3p): 100.9 mg,
1
94 %, White solid, mp 190.0–191.0 ºC, H NMR (500 MHz, CDCl3) δ 1.41 (s, 9H), 2.30 (s, 3H), 2.45
(s, 6H), 6.94 (dd, J = 7.5, 1.5 Hz, 1H), 7.06-7.12 (m, 2H), 7.20 (s, 1H), 7.29-7.33 (m, 4H), 7.84-7.89 (m,
4H). 13C{1H} NMR (125 MHz, CDCl3) δ 21.2, 21.7 (2C), 28.9 (3C), 42.1, 114.8, 116.6, 123.8, 125.4,
127.5, 128.00, 128.03, 128.6 (4C), 129.5 (4C), 134.9, 136.3 (2C), 145.1 (2C), 178.2. IR (neat) 1715,
1377, 1361, 1303, 1171 cm–1. MS (APCI) calcd for C28H31N2O5S2 [M+H]+ 539.1669, found 539.1670.
N-(4-Bromo-1-pivaloyl-1H-indol-3-yl)-4-methyl-N-tosylbenzenesulfonamide (3q): 48.4 mg, 40 %,
1
White solid, mp 224.5–225.0 ºC, H NMR (500 MHz, CDCl3) δ 1.42 (s, 9H), 2.46 (s, 6H), 7.19 (t, J =
8.0 Hz, 1H), 7.32 (d, J = 8.0 Hz, 4H), 7.37 (d, J = 8.0 Hz, 1H), 7.56 (s, 1H), 7.88 (d, J = 8.0 Hz, 4H),
8.52 (d, J = 8.0 Hz, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 21.7 (2C), 28.4 (3C), 41.6, 112.6, 115.0,
116.3, 124.9, 126.7, 129.1 (4C), 129.4, 129.5 (4C), 129.6, 135.9 (2C), 136.8, 145.2 (2C), 176.5. IR
(neat) 1711, 1382, 1356, 1308, 1157, 657 cm–1. MS (APCI) calcd for C27H28BrN2O5S2 [M+H]+
603.0618, found 603.0616.
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4-Methyl-N-(2-methyl-1-pivaloyl-1H-indol-3-yl)-N-tosylbenzenesulfonamide (3r): 83.4 mg, 77 %,
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White solid, mp 158.0–159.0 ºC, H NMR (500 MHz, CDCl3) δ 1.34 (s, 9H), 1.79 (s, 3H), 2.45 (s, 6H),
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6.99-7.06 (m, 2H), 7.12-7.18 (m, 1H), 7.21 (d, J = 8.0 Hz, 1H), 7.30 (d, J = 8.5 Hz, 4H), 7.85 (d, J = 8.5
Hz, 4H). 13C{1H} NMR (125 MHz, CDCl3) δ 10.8, 21.6 (2C), 28.0 (3C), 44.4, 110.5, 111.7, 118.7,
121.7, 122.8, 125.8, 128.6 (4C), 129.5 (4C), 133.8, 136.7 (2C), 137.9, 145.0 (2C), 185.8. IR (neat)
1710, 1384, 1360, 1313, 1165, 1084 cm–1. MS (APCI) calcd for C28H31N2O5S2 [M+H]+ 539.1669, found
539.1671.
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N-(5,6-Dichloro-1-pivaloyl-1H-indol-3-yl)-4-methyl-N-tosylbenzenesulfonamide (3s): 109.9 mg,
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93 %, White solid, mp 223.5–224.2 ºC, H NMR (500 MHz, CDCl3) δ 1.41 (s, 9H), 2.48 (s, 6H), 6.87
(s, 1H), 7.32-7.36 (m, 4H), 7.52 (s, 1H), 7.82-7.86 (m, 4H), 8.65 (s, 1H). 13C{1H} NMR (125 MHz,
CDCl3) δ 21.7 (2C), 28.3 (3C), 41.3, 115.0, 119.1, 119.5, 126.4, 128.5 (5C), 129.0, 129.8 (4C), 130.1,
134.0, 135.9 (2C), 145.7 (2C), 176.4. IR (neat) 1710, 1382, 1361, 1330, 1158, 1084 cm–1. MS (ESI)
calcd for C27H27Cl2N2O5S2 [M+H]+ 593.0733, found 593.0732.
N-(1-Benzoyl-1H-indol-3-yl)-4-methyl-N-tosylbenzenesulfonamide (3t): 91.1 mg, 84 %, White
1
solid, mp 214.0–215.0 ºC, H NMR (500 MHz, CDCl3) δ 2.47 (s, 6H), 7.10 (d, J = 8.0 Hz, 1H), 7.12 (s,
1H), 7.19-7.24 (m, 1H), 7.32 (d, J = 8.5 Hz, 4H), 7.36-7.41 (m, 1H), 7.45-7.51 (m, 2H), 7.59-7.65 (m,
3H), 7.87 (d, J = 8.5 Hz, 4H), 8.37 (d, J = 8.0 Hz, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 21.7 (2C),
116.2, 116.3, 119.0, 1124.5, 125.8, 128.0, 128.59 (4C), 128.64 (2C), 129.3, 129.4 (2C), 129.6 (4C),
132.5, 133.4, 135.0, 136.2 (2C), 145.2 (2C), 168.1. IR (neat) 1694, 1376, 1359, 1325, 1166 cm–1. MS
(ESI) calcd for C29H25N2O5S2 [M+H]+ 545.1199, found 545.1205.
4-Methyl-N-tosyl-N-(1-tosyl-1H-indol-3-yl)benzenesulfonamide (3u): 96.7 mg, 81 %, White solid,
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mp 182.0–183.0 ºC, H NMR (500 MHz, CDCl3) δ 2.35 (s, 3H), 2.44 (s, 6H), 7.04 (d, J = 8.0 Hz, 1H),
7.08-7.13 (m, 1H), 7.23-7.30 (m, 7H), 7.43 (s, 1H), 7.70-7.77 (m, 6H), 7.92 (d, J = 8.5 Hz, 1H).
13C{1H} NMR (125 MHz, CDCl3) δ 21.5, 21.7 (2C), 113.5, 116.8, 119.4, 123.9, 125.4, 126.9 (2C),
128.2, 128.3, 128.5 (4C), 129.5 (4C), 130.0 (2C), 133.7, 134.5, 136.0 (2C), 145.3 (2C), 145.5. IR (neat)
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1595, 1372, 1355, 1283, 1168, 1086 cm–1. MS (ESI) calcd for C29H27N2O6S3 [M+H]+ 595.1026, found
595.1027.
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Derivatization of 3-Aminoindole Derivatives (3a) (Scheme 5).
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To a solution of 3a (262.3 mg, 0.50 mmol) in THF (2.5 mL) was added TBAF (2.0 mL, 2.0 mmol),
and the reaction mixture was stirred at room temperature for 24 h. Water (5.0 mL) was added to the
mixture at 0 ºC, and the product was extracted with AcOEt (10 mL × 3). The organic phase was washed
with brine (10 mL), and dried over Na2SO4. The solvent was removed under reduced pressure. The
crude mixture was purified by column chromatography (eluent: hexane/AcOEt=3/1) to give the desired
product 5 (154.0 mg, 70% yield).
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4-Methyl-N-(2-tosyl-1H-indol-3-yl)benzenesulfonamide (5): 153.3 mg, 70 %, White solid, mp
1
188.0–189.0 ºC, H NMR (500 MHz, CDCl3) δ 2.36 (s, 3H), 2.37 (s, 3H), 7.10-7.22 (m, 5H), 7.22-7.29
(m, 1H), 7.33 (t, J = 7.5 Hz, 1H), 7.49 (d, J = 8.0 Hz, 2H), 7.61 (d, J = 8.0 Hz, 2H), 7.76 (s, 1H), 8.05 (d,
J = 8.0 Hz, 1H), 8.64 (s, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 21.6 (2C), 112.0, 119.7, 121.8,
122.25, 122.29, 123.3, 126.9 (2C), 127.1, 127.7 (2C), 129.5 (2C), 130.0 (2C), 135.6, 135.7, 137.6, 144.0,
144.8. IR (neat) 3308, 3281, 1346, 1303, 1163, 1150, 1077 cm–1. MS (ESI) calcd for C22H21N2O4S2
[M+H]+ 441.0937, found 441.0939.
Crystal data for 5: Formula C22H20N2O4S2, colorless, crystal dimensions 0.20 × 0.10 × 0.10 mm3,
Monoclinic, space group C 1 2/c 1, a = 32.963(3) Å, b = 8.7052(9) Å, c = 15.5575(15) Å, α = 90 °, β =
114.780(3) °, γ = 90 °, V = 4053.2(7) Å3, Z = 8, ρcalc = 1.444 g cm-3, F(000) = 1840, µ(MoKα) = 2.663
mm-1, T = 173 K. 13824 reflections collected, 3709 independent reflections with I > 2σ(I) (2θmax
=
68.302 °), and 277 parameters were used for the solution of the structure. The non-hydrogen atoms
were refined anisotropically. R1 = 0.0343 and wR2 = 0.0940. GOF = 1.067. Crystallographic data
(excluding structure factors) for the structure reported in this paper have been deposited with the
Cambridge Crystallographic Data Centre as supplementary publication no. CCDC-1860599. Copies of
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the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ,
UK [Fax: int. code + 44(1223)336-033; E-mail: deposit@ccdc.cam.ac.uk].
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Supporting Infomation:
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The Supporting Information is available free of charge on the ACS Publications website.
1H and 13C NMR spectra of compounds in the copper-catalyzed indole-selective C–N coupling
reaction, and crystallographic data of 3a and 5.
Acknowledgments:
Financial support in the form of a Grant-in-Aid for Scientific Research (No.G15K17819) from the
Ministry of Education, Culture, Sports, Science and Technology in Japan is gratefully acknowledged.
References:
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A.; Olofsson, B. α-Functionalization of Carbonyl Compounds Using Hypervalent Iodine
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(h) Martin, F.-M. Copper-Catalyzed Arylation with Diaryliodonium Salts. Synthesis 2017, 49,
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(8) Ortiz, Jr., G. X.; Heric, B. N.; Wang, Q. Direct and Selective 3-Amidation of Indoles Using
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(13) For a detail of X-ray crystal-structure analysis of 5, see the Supporting Information.
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