Copper-Catalyzed Indole-Selective CâN Coupling Reaction of Indolyl

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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 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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The Journal of Organic Chemistry

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 [email protected] RECEIVED DATE (to be automatically inserted after your manuscript is accepted if required according to the journal that you are submitting your paper to)

ACS Paragon Plus Environment

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Abstract:

High induction of chemoselectivity O I N(SO2R’)2

R

Cu(MeCN)4BF4 (5 mol%) (R’SO2)2NH (5 mol%) Xylene, 130 ºC 1h

N Piv

High indole selectivity

N(SO2R’)2 R N Piv up to 97% yield

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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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 2iodo-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.

Figure 1. Design of unsymmetric diaryliodonium salt.


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A) Unsymmetric iodonium salt containing 2,4,6-substituted benzene for chemoselective arylation a) Transition-metal-catalyzed coupling reaction

b) Transition-metal-free arylation R

I OTf Ar

I OTf Ar

R R

OMe I OTf R Ar

(R = Me, i-Pr)

I OTf Ar OMe (R = H, OMe)

B) A design of 2-alkoxy iodoarene for chemoselective amination (This work)

Novel Dummy Ligand for Coupling Reaction

O

• One substituted iodoarene I N(SO2R’)2

R

N

• Easy preparation and tailoring of various indolyl(aryl)iodonium imides • Increase chemoselectivity of coupling reaction by steric hindrance of alkyl group

EWG

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 3amination 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 indoleselective 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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R

R

+ (RSO2)2NH (1.2 equiv.)

N Piv

OAc (1.2 equiv.) I OAc

I N(SO2R)2

R

MeCN, 40 ºC

N Piv

1

2

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.

Table 1. Screening of dummy ligand on indolyl(aryl)iodonium imides (2).

I NTs2

R

Piv

NTs2

+

Xylene, 130 ºC 1h

N 2

NTs2

CuI (20 mol%) Ts2NH (20 mol%)

R

N Piv 3a

4

Substrate (2) and Yield (3a/4) (%) t-Bu

I NTs2 N Piv (2aa) 3a/4aa, 21%/74%

N Piv (2ab) 3a/4ab, 30%/69% Cl

O2N

Piv (2ad) 3a/4ad, 11%/67%

I NTs2

I NTs2

I NTs2

N Piv (2ae) 3a/4ae, 30%/64%

N Piv (2af) 3a/4af, 72%/25%

N Piv (2ag) 3a/4ag, 62%/17%

O

N (2ah) 3a/4ah, 76%/7%

OPh

O I NTs2 N

Piv

OEt

Cl

N

I NTs2

I NTs2

N Piv (2ac) 3a/4ac, 25%/70% OMe

I NTs2

O

MeO

I NTs2

I NTs2 N

Piv

(2ai) 3a/4ai, 83%/9%

Piv (2aj) 3a/4aj, 77%/15%

I NTs2 N Piv (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 ACS Paragon Plus Environment

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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%

1

H-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).

Table 2. Screening of Cu catalyst for C–N coupling reaction. O I NTs2 N 2ai

Piv

NTs2

“Cu” (x mol%) Ts2NH (y mol%) Xylene, 130 ºC 1h

Entry Cu catalyst

N Piv 3a

y

Solvent

(x mol%)

Temp. Yield (ºC)

(%)

1

CuI (20)

20 Xylene

130

83

2

CuI (20)

20 MeCN

reflux

trace


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3

CuI (20)

20 ClCH2CH2Cl reflux

70

4

CuI (20)

20 THF

reflux

65

5

CuI (20)

20 DMF

130

42

6

CuI (20)

20 DMSO

130

18

7

CuI (20)

20 Toluene

reflux

82

8

CuCl (20)

20 Xylene

130

85

9

CuBr (20)

20 Xylene

130

78

10

Cu(OAc)2 (20)

20 Xylene

130

95

11

Cu(OBz)2 (20)

20 Xylene

130

89

12

CuCl2 (20)

20 Xylene

130

52

13

Cu(OTf)2 (20)

20 Xylene

130

58

14

Cu(MeCN)2BF4 20 Xylene (20)

130

92

15

CuOAc (20)

20 Xylene

130

88

16

-

20 Xylene

130

5

17

Cu(MeCN)2BF4 0 (20)

Xylene

130

81

18

Cu(OAc)2 (5)

5

Xylene

130

86

19

Cu(MeCN)2BF4 5 (5)

Xylene

130

93 (82)a

20b

Cu(MeCN)2BF4 5 (5)

Xylene

130

92

a

Number in parentheses indicates degree of recovery of 2-butoxy-iodobenzene. b 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 3amino indole derivatives (3b–3e) in high yields (75–97%). The indole selectivity of 2qs was reduced for ACS Paragon Plus Environment

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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%).

Scheme 2. Cu-catalyzed C–N coupling of indolyl(2-butoxyphenyl)iodonium imides (2i).

O I N(SO2R’)2

2i

R

Xylene, 130 ºC 1h

N

R

N(SO2R’)2

Cu(MeCN)4BF4 (5 mol%) (R’SO2)2NH (5 mol%)

N Piv 3

Piv

Product (3) and Yield (%) NTsMs

N(SO2Ph)2

N Piv 3c, 82%

N Piv 3b, 80% NTs2

NTs2

NTs2

N Piv 3k, 93%

3l, 84%

3n, 75% NTs2

3r,b

a

N Piv 77%

NTs2

NTs2 N Piv

Cl Cl

NTs2

N Piv

Cl

3o, 95% NTs2 N Piv 3s, 93%

N Piv 3p, 94% NTs2 N Bz 3t, 84%

NTs2

NC

N Piv

O

O

N Piv 3i, 91% NTs2

MeO2C

NTs2

Br

N Piv 3h, 91%

N Piv

3j, 92%

N

N Piv 3e,a 75% NTs2

Cl

N Piv 3g, 93% PivO

N(SO2Bn)2

N Piv 3d, 77%

NTs2

F

N Piv 3f, 93% MeO

N(SO2n-Pr)2

N Piv 3m, 97% Br

NTs2 N Piv

3q, 40% NTs2 N Ts 3u, 81%

For 2 h. b At 100 ºC.

The proposed reaction mechanism of the copper-catalyzed C–N coupling reaction of indolyl(2butoxyphenyl)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 ACS Paragon Plus Environment

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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

Scheme 3. Plausible reaction mechanism.

O CuIN(SO

2R’)2

(R’SO2)2NH

I N(SO2R’)2 N

R CuI

2i L CuIII

N(SO2R’)2 R N Piv 3

N(SO2R’)2

Piv

O I

R

N Piv A

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 I(OAc)2 N Piv

R

+

Ts2NH (1.6 equiv.)

(1.2 equiv.)

Cu(MeCN)4BF4 (5 mol%)

MeCN, 40 ºC 7h

Xylene, 130 ºC 1h

NTs2

R 3

1 Product (3) and Yield (%) NTs2

N Piv 3a, 78% (81%)a NTs2 N Piv 3o,b 68%

Cl

a

NTs2

MeO

N Piv 3j, 79%

NTs2

Cl

NTs2 N Piv 3p, 69%

NTs2 N Piv 3r,c 69%

NTs2

MeO2C

N Piv 3h, 75%

N Piv

N Piv 3l,b 55% NTs2

Cl

N Piv 3s, 54%

Cl

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-3sulfonamido-indole (5) in 70% yield (Scheme 5). The structure of 5 was determined by X-ray crystalstructure analysis.13

Scheme 5. Derivatization of 3-aminoindole derivatives (3a). O

O S N

NHTs

NTs2 TBAF (3.0 equiv.) N Piv 3a

In

conclusion,

O

Ts

THF, rt 24 h

N H

N

S O

5 (70%)

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 dummy ligands and its use in transition-metal-catalyzed transformation are under way in our laboratory.

Experimental Section General Procedure 1

H 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.

13

C 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 ACS Paragon Plus Environment

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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).

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 solid, mp 214.0–214.5 ºC, 1H 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).

13

C{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, 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) = 0.250 mm-1, T = 173 K. 7413 reflections collected, 5602 independent reflections with I > 2σ(I) (2θmax = 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: [email protected]]. N-(Phenylsulfonyl)-N-(1-pivaloyl-1H-indol-3-yl)benzenesulfonamide (3b): 79.0 mg, 80 %, White solid, mp 182.0–183.0 ºC, 1H NMR (500 MHz, CDCl3) δ 1.39 (s, 9H), 7.01 (d, J = 8.0 Hz, 1H), 7.127.18 (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).

13

C{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,

82%, White solid, mp 221.5–22.0 ºC, 1H 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).

13

C{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 %, White solid, mp 190.0–191.0 ºC, 1H NMR (500 MHz, CDCl3, 60ºC) δ 1.07 (t, J = 7.3 Hz, 6H), 1.52 (s, ACS Paragon Plus Environment

13


Page 14 of 24

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).

13

C{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. N-(Benzylsulfonyl)-1-phenyl-N-(1-pivaloyl-1H-indol-3-yl)methanesulfonamide (3e):

78.3 mg,

75 %, White solid, mp 187.0–188.0 ºC, 1H 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).

13

C{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 %, White solid, mp 217.0–217.5 ºC, 1H 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).

13

C{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,

93 %, White solid, mp 214.5–215.2 ºC, 1H 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).

13

C{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 ACS Paragon Plus Environment

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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.

19

F 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. N-(5-Chloro-1-pivaloyl-1H-indol-3-yl)-4-methyl-N-tosylbenzenesulfonamide (3h):

101.2 mg,

91 %, White solid, mp 205.5–206.0 ºC, 1H 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).

13


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. N-(5-Bromo-1-pivaloyl-1H-indol-3-yl)-4-methyl-N-tosylbenzenesulfonamide (3i): 109.3 mg, 91 %, White solid, mp 215.0–216.0 ºC, 1H 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).

13

C{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,

92 %, White solid, mp 220.0–221.0 ºC, 1H 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).

13

C{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.


15


Page 16 of 24

3-((4-Methyl-N-tosylphenyl)sulfonamido)-1-pivaloyl-1H-indol-5-yl pivalate (3k): 116.2 mg, 93 %, White solid, mp 225.0 ºC (dec.), 1H NMR (500 MHz, CDCl3) δ 1.35 (s, 9H), 1.40 (s, 9H), 2.45 (s, 6H), 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).

13

C{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. Methyl 3-((4-methyl-N-tosylphenyl)sulfonamido)-1-pivaloyl-1H-indole-5-carboxylate (3l): 97.4 mg, 84 %, White solid, mp 221.0–221.5 ºC, 1H 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).

13

C{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,

97 %, White solid, mp 214.0–215.0 ºC, 1H 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).

13


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 (3n): 99.8 mg, 75 %, White solid, mp 227.5–228.0 ºC, 1H 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 = ACS Paragon Plus Environment

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9.0 Hz, 1H).

13

C{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. N-(6-Chloro-1-pivaloyl-1H-indol-3-yl)-4-methyl-N-tosylbenzenesulfonamide (3o):

106.5 mg,

95 %, White solid, mp 212.5–213.0 ºC, 1H 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).

13

C{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,

94 %, White solid, mp 190.0–191.0 ºC, 1H 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).

13

C{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 %, White solid, mp 224.5–225.0 ºC, 1H 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).

13

C{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.


17


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4-Methyl-N-(2-methyl-1-pivaloyl-1H-indol-3-yl)-N-tosylbenzenesulfonamide (3r): 83.4 mg, 77 %, White solid, mp 158.0–159.0 ºC, 1H NMR (500 MHz, CDCl3) δ 1.34 (s, 9H), 1.79 (s, 3H), 2.45 (s, 6H), 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).

13

C{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. N-(5,6-Dichloro-1-pivaloyl-1H-indol-3-yl)-4-methyl-N-tosylbenzenesulfonamide (3s): 109.9 mg, 93 %, White solid, mp 223.5–224.2 ºC, 1H 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).

13

C{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 solid, mp 214.0–215.0 ºC, 1H 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).

13

C{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, mp 182.0–183.0 ºC, 1H 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). 13

C{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) ACS Paragon Plus Environment

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1595, 1372, 1355, 1283, 1168, 1086 cm–1. MS (ESI) calcd for C29H27N2O6S3 [M+H]+ 595.1026, found 595.1027. Derivatization of 3-Aminoindole Derivatives (3a) (Scheme 5). 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). 4-Methyl-N-(2-tosyl-1H-indol-3-yl)benzenesulfonamide (5): 153.3 mg, 70 %, White solid, mp 188.0–189.0 ºC, 1H 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).

13

C{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: [email protected]].

Supporting Infomation: The Supporting Information is available free of charge on the ACS Publications website. 1

H and

13

C 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.

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Copper-Catalyzed Indole-Selective CâN Coupling Reaction of Indolyl

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