Exploration of A KI-Catalyzed Oxidation System for …3 2. Preparations of tryptamine and tryptophol analogues Tryptamine and tryptophol analogues used in this research are known compounds

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Exploration of A KI-Catalyzed Oxidation System for Direct

Construction of Bispyrrolidino[2,3-b]indolines and Total Synthesis of

(+)-WIN 64821

Si-Kai Chen,†,§ Ju-Song Yang,†,§ Kun-Long Dai,† Fu-Min Zhang,*,† Xiao-Ming Zhang,*,† and Yong-

Qiang Tu.*,†,‡

†State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou

University, Lanzhou 730000, P.R. China

‡School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, P.R. China

E-mail: [email protected]; [email protected]; [email protected]; [email protected].

Contents

1. General information.......................................................................................... 2

2. Preparations of tryptamine and tryptophol analogues ........................... 3

3. Screening of KI-catalyzed oxidative dimerization conditions .......... 19

4. KI-catalyzed oxidative dimerization reactions ..................................... 25

5. Gram-scale of KI-catalyzed oxidative dimerization reactions .......... 45

6. Additional description of the proposed mechanism ............................... 46

7. Total synthesis of (+)-WIN 64821 .............................................................. 49

8. Crystals of 6b ................................................................................................. 56

9. References ......................................................................................................... 58

10.Copies of NMR ................................................................................................... 58

Electronic Supplementary Material (ESI) for ChemComm.This journal is © The Royal Society of Chemistry 2019

mailto:[email protected]




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1. General information

In addition to commercially available extra dry solvents, the solvents used in this work were

purified using standard operation and distilled prior to use. Dichloromethane (DCM or CH2Cl2),

trichloromethane (CHCl3) and 1,2-dichloroethane (DCE) were distilled from CaH2. Tetrahydrofuran

(THF), diethyl ether (Et2O), benzene and toluene were distilled from sodium. Acetonitrile (CH3CN)

was distilled from phosphorus pentoxide.

All commercial reagents were used without additional purification unless special stated. Air or

moisture sensitive operations were conducted under argon atmosphere using oven-dried glassware

(150℃).

All reactions were monitored by thin-layer chromatography (TLC) visualized by ultraviolet light

(254 nm) and the column chromatography purifications of organic compounds were performed via

silica gel (200~300 mesh) unless special stated.

1H NMR, 13C NMR and 19F NMR spectra were recorded on Bruker AM-600, Bruker AM-400,

Varian Mercury-600 or JEOL JNM-ECS-400. Chemical shift (δ) were quoted in ppm relative to

tetramethylsilane or residual protio solvent as internal standard, multiplicities are as indicated: s=

singley, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad. Infrared (IR) spectra were

recorded on a Nicolet FY-170SX spectrometer. High-resolution mass spectral analysis (HRMS) data

were determined on a Thermo Scientific Orbitrap Elite spectrometer. Optical rotations were detected

on RUDOLPH A21202-J APTV/GW. X-ray diffraction data were collected on Agilent SuperNova

Eos diffractometer. Melting points (m.p.) were collected on SGW X-4B Micromelting point

instrument. High performance liquid chromatography (HPLC) analyses were performed using Waters

e2695 Separations and 2998 PDA Detector instruments.

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2. Preparations of tryptamine and tryptophol analogues

Tryptamine and tryptophol analogues used in this research are known compounds except 5e, 5h,

5g, 5l. The syntheses and characterizations of these compounds are all described below:

2.1 Preparation of Na- substituted tryptamines

N-(2-(1H-indol-3-yl)ethyl)-4-methylbenzenesulfonamide, 5a:

Compound 5a was prepared according to literature’s procedure[1] as a pale yellow solid. m.p. 99-

102℃; 1H NMR (400 MHz, CDCl3): δ 8.24 (s, 1H), 7.58 (d, J = 8.0 Hz, 2H), 7.35 (d, J = 7.6 Hz, 1H),

7.26 (d, J = 8.0 Hz, 1H), 7.14-7.10 (m, 3H), 7.00 (t, J = 7.6 Hz, 1H), 6.82 (d, J = 2.4 Hz, 1H), 4.83 (t,

J = 6.0 Hz, 1H), 3.17 (q, J = 6.4 Hz, 2H), 2.83 (t, J = 6.8 Hz, 2H), 2.31 (s, 3H); 13C NMR (100 MHz,

CDCl3): δ 143.20, 136.35, 136.20, 129.48, 126.75, 126.71, 122.65, 121.81, 119.10, 118.22, 111.31,

111.12, 43.01, 25.24, 21.30; IR (KBr) 3406, 3282, 1597, 1316, 1155, 816, 744, 549 cm-1; HRMS (ESI)

calcd for [M+Na]+ C17H18N2NaO2S, m/z: 337.0987, found: 337.0973.

4-methyl-N-(2-(1-methyl-1H-indol-3-yl)ethyl)benzenesulfonamide, 5b:

To a stirred solution of 5a (2.35g, 7.5 mmol, 1.0 equiv) in DMF (35 mL) at 0℃ was added NaH (0.90

g, 22.5 mmol, 3.0 equiv, 60% dispersion in mineral oil) in portions. The system was reacted at room

temperature for 0.5 h, and then cooled to 0℃. A solution of MeI (0.50 mL, 8.25 mmol, 1.1 equiv) in

DMF (35 mL) was subsequently added to the reaction mixture dropwise at the same temperature and

the reaction mixture was stirred at room temperature for additional 2 h. The resulted reaction system

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was carefully quenched with saturated NH4Cl and extracted with EtOAc (100 mL x 3). The organic

layer was washed with water (6 times) and brine, then dried over Na2SO4, filtered, and concentrated

by vacuo. The residue was purified by flash column chromatography (petrol ether: EtOAc = 8:1 to 6:1)

to afford 5b (2.17 g, 85 % yield) as a white solid. m.p. 81-83℃; 1H NMR (400 MHz, CDCl3): δ 7.61

(d, J = 8.4 Hz, 2H), 7.36 (d, J = 7.6 Hz, 1H), 7.21-7.10 (m, 4H), 7.00 (t, J = 7.2 Hz, 1H), 6.73 (s, 1H),

4.94 (t, J = 4.0 Hz, 1H), 3.59 (s, 3H), 3.19 (q, J = 6.8 Hz, 2H), 2.84 (t, J = 6.8 Hz, 2H), 2.31 (s, 3H);

13C NMR (100 MHz, CDCl3): δ 142.95, 136.85, 136.64, 129.35, 127.18, 127.08, 126.75, 121.43,

118.64, 118.38, 109.86, 109.11, 43.15, 32.28, 25.15, 21.23; IR (KBr) 3288, 2928, 1598, 1326, 1159,

815, 740, 550 cm-1; HRMS (ESI) calcd for [M+Na]+ C18H20N2NaO2S, m/z: 351.1143, found: 351.1146.

N-(2-(1-ethyl-1H-indol-3-yl)ethyl)-4-methylbenzenesulfonamide, 5c:

Compound 5c (2.40 g, 93% yield) was synthesized from 5a (2.35 g, 7.5 mmol) and EtBr (0.62 mL,

8.25 mmol) as a light yellow oil following the synthetic procedure of 5b, purified by flash

chromatography (petrol ether: EtOAc = 10:1 to 6:1). 1H NMR (400 MHz, CDCl3): δ 7.63 (d, J = 8.4

Hz, 2H), 7.39 (d, J = 8.0 Hz, 1H), 7.27 (d, J = 8.4 Hz, 1H), 7.20-7.16 (m, 3H), 7.02 (t, J = 7.4 Hz, 1H),

6.85 (s, 1H), 4.83 (m, 1H), 4.05 (q, J = 7.2 Hz, 2H), 3.24-3.20 (m, 2H), 2.89 (t, J = 6.8 Hz, 2H), 2.36

(s, 3H), 1.38 (t, J = 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 143.10, 136.77, 136.04, 129.48,

127.41, 126.90, 125.37, 121.50, 118.79, 118.62, 110.03, 109.30, 43.18, 40.65, 25.37, 21.37, 15.29; IR

(KBr) 3285, 2931, 1598, 1327, 1159, 816, 742, 551 cm-1; HRMS (ESI) calcd for [M+Na]+

C19H22N2NaO2S, m/z: 365.1300, found: 365.1304.

N-(2-(1-allyl-1H-indol-3-yl)ethyl)-4-methylbenzenesulfonamide, 5d:

Compound 5d (2.25 g, 85% yield) was synthesized from 5a (2.35 g, 7.5 mmol) and allyl bromine (0.71

mL, 8.25 mmol) as a light yellow oil following the synthetic procedure of the 5b, purified by flash

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chromatography (petrol ether: EtOAc = 10:1 to 5:1). 1H NMR (400 MHz, CDCl3): δ 7.64 (d, J = 8.0

Hz, 2H), 7.40 (d, J = 8.0 Hz, 1H), 7.29-7.25 (m, 1H), 7.23-7.17 (m, 3H), 7.07-7.02 (m, 1H), 6.85 (s,

1H), 6.01-5.91 (m, 1H), 5.22-5.18 (m, 1H), 5.11-5.06 (m, 1H), 4.65 (td, J = 5.6 Hz, 1.6 Hz, 2H), 4.46

(t, J = 8.0 Hz, 1H), 3.26 (q, J = 6.4 Hz, 2H), 2.91 (t, J = 6.6 Hz, 2H), 2.40 (s, 3H); 13C NMR (100

MHz, CDCl3): δ 143.11, 136.78, 136.43, 133.30, 129.49, 127.48, 126.91, 126.10, 121.69, 119.01,

118.61, 117.25, 110.43, 109.63, 48.57, 43.14, 25.35, 21.38; IR (KBr) 3288, 2923, 1598, 1326, 1159,

815, 742, 551 cm-1; HRMS (ESI) calcd for [M+Na]+ C20H22N2NaO2S, m/z: 377.1300, found:

377.1309.

N-(2-(1-acetyl-1H-indol-3-yl)ethyl)-4-methylbenzenesulfonamide, 5e:

To a solution of 5a (1.57 g, 5.0 mmol, 1.0 equiv) in DCM (40 mL) was added Bu4NHSO4 (0.169 g,

0.25 mmol, 0.05 equiv). The solution was cooled to 0℃ and added NaOH (1.00 g, 12.5 mmol, 2.5

equiv). A solution of AcCl (1.06 mL, 7.5 mmol, 1.5 equiv) in DCM (20 mL) was then added to the

reaction system dropwise at 0℃. The resulted mixture was warm to room temperature and stirred for

additional 1.5 h, then, quenched with saturated NH4Cl (aqueous) and extracted with EtOAc (60 mL x

3). The combine organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated

by vacuo. The residue was purified by column chromatography (petrol ether: acetone =12:1) to afford

5e (1.57 g, 88 % yield) as a white solid. m.p. 130-135℃. 1H NMR (400 MHz, CDCl3)：δ 8.06 (s, 1H),

7.80-7.76 (m, 3H), 7.35 (d, J = 8.0 Hz, 1H), 7.31 (d, J = 8.0 Hz, 2H), 7.20 (td, J = 7.2 Hz, 1.2 Hz, 1H),

7.15 (td, J = 8.0 Hz, 1.2 Hz, 1H), 7.05 (d, J = 2.0 Hz, 1H), 4.06-4.01 (m, 2H), 3.22-3.17 (m, 2H), 2.42

(s, 3H), 2.28 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 170.27, 144.85, 136.73, 136.20, 129.84, 127.47,

127.26, 122.45, 122.14, 119.59, 118.93, 112.18, 111.15, 47.84, 25.98, 24.89, 21.58; IR (KBr) 3368,

1675, 1433, 1335, 1164, 746, 542 cm-1; HRMS (ESI) calcd for [M+Na]+ C19H20N2NaO3S, m/z:

379.1087, found: 379.1090.

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2.2 Preparation of Nb- substituted tryptamines

General procedure A:

To a stirred solution of tryptamine (1.0 equiv) in DCM (0.50 M) at 0℃ were added Et3N (1.2 equiv)

and R7Cl (1.05 equiv) successively. The reaction system was stirred at room temperature for 6 h and

then quenched with saturated NH4Cl. The resulted mixture was extracted with DCM and the organic

layer was dried over Na2SO4, filtered, and concentrated by vacuo. The residue was recrystallized (Et2O

and petrol ether as eluent) to provide the crude intermediate 1.

To a solution of the crude intermediate 1 (1.0 equiv) above in DMF (0.21 M) at 0℃ was added NaH

(3.5 equiv, 60% dispersion in mineral oil). The reaction system was stirred at room temperature for

0.5 h, and then cooled to 0℃. A solution of MeI (1.1 equiv, in DMF) was subsequently added to this

reaction mixture. The resulted solution was stirred at room temperature for 6 h, then quenched with

saturated NH4Cl (aqueous) and extracted with EtOAc. The organic layer was washed with water (6

times) and brine, then dried over Na2SO4, filtered, and concentrated by vacuo. The residue was purified

by column chromatography to afford 5f, 5g, 5i or 5m.

General procedure B:

To a solution of tryptamine (1.0 equiv) in DCM (0.63 M) was added Et3N (3.0 equiv) and then cooled

to -78℃. A solution of R72O (1.05 equiv) was then added to the reaction system dropwise. The

resulted mixture was warm to room temperature and stirred for additional 6 h, then, quenched with

water and extracted with DCM. The organic layers were washed with brine, dried over Na2SO4, filtered,

and concentrated by vacuo. The resulted residue (crude intermediate 2) was used to the next step

without further purification.



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reactiom mixture. The resulted solution was stirred at room temperature for 6 h, then quenched with

saturated NH4Cl (aqueous), and extracted with EtOAc. The organic layer was washed with water (6

times) and brine, then dried over Na2SO4, filtered, and concentrated by vacuo. The residue was purified

by column chromatography to afford 5j or 5l.

General procedure C:

To a stirred solution of tryptamine (1.0 equiv) in N,N-dimethylformamide (0.2 M) under 0℃ was

added NaH (60% dispersion in mineral oil, 3.0 equiv) portionwise. The reaction mixture was reacted

at room temperature for 2 h and cooled to 0℃ again. MeI (1.0 equiv, 0.2 M, in DMF) was then added

to the reaction system over 1 h, after which, the system was stirred at 0℃ for additional 3 h.

Whereafter, H2O (the volume is consistent with DMF), Na2CO3 (2.0 equiv) and R7Cl (1.0 equiv) were

added to the reaction system successively under 0℃. After stirring under the same temperature for 3

h, R7Cl (0.50 equiv) was added to the mixture and the system was reacted for additional 1 h. The

resulted mixture was extracted with EtOAc and washed with water (6 times). The organic layer was

dried with Na2SO4 (anhydrous), then filtered and concentrated. The residue was purified by column

chromatography to afford 5h or 5k.

N-(2-(1-methyl-1H-indol-3-yl)ethyl)benzenesulfonamide, 5f:

Compound 5f (0.80 g, 51% yield) was synthesized following the general procedure A as a light yellow

oil, purified by flash chromatography (petrol ether: EtOAc = 10:1 to 5:1). R7Cl = PhSO2Cl. 1H NMR

(400 MHz, CDCl3): δ 7.76 (d, J = 7.6 Hz, 2H), 7.53 (t, J = 7.6 Hz, 1H), 7.46-7.38 (m, 3H), 7.27 (t, J

= 8.4 Hz, 1H), 7.22 (t, J = 7.6 Hz, 1H), 7.05 (t, J = 7.6 Hz, 1H), 6.80 (s, 1H), 4.50 (t, J = 5.6 Hz, 1H),

3.72 (s, 3H), 3.28 (q, J = 6.4 Hz, 2H), 2.92 (t, J = 6.4 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 139.85,

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137.13, 132.47, 128.98, 127.30, 127.26, 126.94, 121.85, 119.03, 118.55, 109.84, 109.35, 43.19, 32.62,

25.40; IR (KBr) 3293, 2928, 1615, 1325, 1159, 815, 742, 585 cm-1; HRMS (ESI) calcd for [M+Na]+

C17H18N2NaO2S, m/z: 337.0987, found: 337.0984.

N-(2-(1-methyl-1H-indol-3-yl)ethyl)-4-nitrobenzenesulfonamide, 5g:

Compound 5g (1.10 g, 61% yield) was synthesized following the general procedure A as a yellow

solid, purified by flash chromatography (petrol ether: EtOAc = 7:1 to 5:1). R7Cl = p-NsCl. m.p. 106-

108℃; 1H NMR (400 MHz, CDCl3): δ 8.08 (d, J = 8.4 Hz, 2H), 7.75 (d, J = 8.8 Hz, 2H), 7.31 (d, J =

8.0 Hz, 1H), 7.26-7.16 (m, 2H), 7.00 (t, J = 7.2 Hz, 1H), 6.81 (s, 1H), 4.60 (t, J = 5.4 Hz, 1H), 3.71 (s,

3H), 3.34 (q, J = 6.0 Hz, 2H), 2.93 (d, J = 6.0 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 149.68, 145.35,

137.18, 127.85, 127.37, 127.01, 123.86, 122.08, 119.16, 118.36, 109.44, 43.24, 32.62, 25.38; IR (KBr)

3307, 2932, 1607, 1529, 1349, 1164, 855, 738, 611 cm-1; HRMS (ESI) calcd for [M+Na]+

C17H18N3NaO4S, m/z: 382.0837, found: 382.0840.

N-(2-(1-methyl-1H-indol-3-yl)ethyl)naphthalene-2-sulfonamide, 5h:

Compound 5h (2.90 g, 80% yield) was synthesized following the general procedure C as a light yellow

oil, purified by flash chromatography (petrol ether: EtOAc = 10:1 to 6:1). R7Cl = 2-naphthyl-SO2Cl.

1H NMR (400 MHz, CDCl3): δ 8.33 (s, 1H), 7.86-7.79 (m, 3H), 7.68 (dd, J = 8.8 Hz, 1.6 Hz, 1H),

7.62-7.53 (m, 2H), 7.32 (d, J = 7.6 Hz, 1H), 7.22-7.12 (m, 2H), 6.95 (d, J = 7.6 Hz, 1H), 6.73 (s, 1H),

4.76 (t, J = 6.0 Hz, 1H), 3.60 (s, 3H), 3.30 (q, J = 6.8 Hz, 2H), 2.89 (t, J = 6.8 Hz, 2H); 13C NMR (100

MHz, CDCl3): δ 137.03, 136.70, 134.65, 132.05, 129.26, 129.15, 128.59, 128.20, 127.80, 127.36,

127.25, 127.21, 122.20, 121.73, 118.90, 118.45, 109.86, 109.24, 43.30, 32.44, 25.36; IR (KBr) 3291,

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2932, 1325, 817, 741, 549 cm-1; HRMS (ESI) calcd for [M+Na]+ C21H20N2NaO2S, m/z: 387.1143,

found: 387.1142.

N-(2-(1-methyl-1H-indol-3-yl)ethyl)methanesulfonamide, 5i:

Compound 5i (0.65 g, 52% yield) was synthesized following the general procedure A as a pale yellow

solid, purified by flash chromatography (petrol ether: EtOAc = 5:1 to 3:1). R7Cl = MsCl. m.p. 101-

105℃; 1H NMR (400 MHz, CDCl3): δ 7.57 (d, J = 8.0 Hz, 1H), 7.32 (d, J = 8.0 Hz, 1H), 7.25 (td, J

= 7.6 Hz, 0.8 Hz, 1H), 7.12 (td, J = 7.4 Hz, 0.8 Hz, 1H), 6.94 (s, 1H), 4.30 (t, J = 6.4 Hz, 1H), 3.76 (s,

3H), 3.44 (q, J = 6.4 Hz, 2H), 3.04 (t, J = 6.4 Hz, 2H), 2.83 (s, 3H); 13C NMR (100 MHz, CDCl3): δ

137.21, 127.41, 127.30, 121.96, 119.14, 118.58, 109.97, 109.46, 43.37, 40.12, 32.68, 25.99; IR (KBr)

3236, 2922, 1615, 1325, 1156, 1071, 737, 521 cm-1; HRMS (ESI) calcd for [M+Na]+ C12H16N2NaO2S,

m/z: 275.0830, found: 275.0837.

1,1,1-trifluoro-N-(2-(1-methyl-1H-indol-3-yl)ethyl)methanesulfonamide, 5j:

Compound 5j (1.90 g, 56% yield) was synthesized following the general procedure B as a pale yellow

solid, purified by flash chromatography (petrol ether: EtOAc = 20:1 to 5:1). R72O = Tf2O. m.p. 52-

56℃; 1H NMR (400 MHz, CDCl3): δ 7.55 (d, J = 8.0 Hz, 1H), 7.33 (d, J = 8.0 Hz, 1H), 7.29-7.25 (m,

1H), 7.14 (td, J = 7.4 Hz, 1.2 Hz, 1H), 6.94 (s, 1H), 3.88 (bs, 1H), 3.78 (s, 3H), 3.60 (q, J = 6.4 Hz,

2H), 3.06 (t, J = 6.4 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 137.33, 127.45, 127.15, 122.20, 121.25,

119.40, 118.46, 118.06, 109.60, 109.03, 44.51, 32.74, 26.33; 19F NMR (376 MHz, CDCl3): δ -77.44;

IR (KBr) 3308, 2936, 1616, 1371 1193, 819, 743, 607 cm-1; HRMS (ESI) calcd for [M+Na]+

C12H13F3N2NaO2S, m/z: 329.0548, found: 329.0562.

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N-(2-(1-methyl-1H-indol-3-yl)ethyl)-1-phenylmethanesulfonamide, 5k:

Compound 5k (2.60 g, 79% yield) was synthesized following the general procedure C as a pale yellow

oil, purified by flash chromatography (petrol ether: EtOAc = 10:1 to 5:1). R7Cl = BnSO2Cl. 1H NMR

(400 MHz, CDCl3): δ 7.53 (d, J = 7.6 Hz, 2H), 7.32-7.24 (m, 3H), 7.23-7.17 (m, 4H), 7.13 (td, J = 7.4

Hz, 0.8 Hz, 1H), 6.82 (s, 1H), 4.15-4.11 (m, 3H), 3.71(s, 3H), 3.29 (q, J = 6.4 Hz, 2H), 2.94 (t, J = 6.4

Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 137.27, 130.46, 129.33, 128.67, 128.52, 127.36, 127.31,

121.95, 119.12, 118.63, 109.94, 109.43, 58.34, 43.65, 32.59, 26.05; IR (KBr) 3308, 2929, 1615, 1156,

1326, 1153, 742, 605 cm-1; HRMS (ESI) calcd for [M+Na]+ C18H20N2NaO2S, m/z: 351.1143, found:

351.1158.

2,2,2-trifluoro-N-(2-(1-methyl-1H-indol-3-yl)ethyl)acetamide, 5l:

Compound 5l (1.50 g, 75% yield) was synthesized following the general procedure B as a pale yellow

solid, purified by flash chromatography (petrol ether: EtOAc = 10:1 to 8:1). R72O = (CF3CO)2O. m.p.

90-92℃; 1H NMR (400 MHz, CDCl3): δ 7.57 (d, J = 8.0 Hz, 1H), 7.32 (d, J = 8.0 Hz, 1H), 7.28-7.23

(m, 1H), 7.15-7.11 (m, 1H), 6.88 (s, 1H), 6.43 (s, 1H), 3.75 (s, 3H), 3.65 (q, J = 6.4 Hz, 2H), 3.02 (t,

J = 6.4 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 157.64, 157.27, 156.90, 156.54, 137.20, 127.38,

126.92, 122.00, 120.10, 119.19, 118.51, 117.24, 114.38, 110.15, 109.46, 40.28, 32.63, 24.59; 19F NMR

(376 MHz, CDCl3): δ -75.97 ; IR (KBr) 3318, 2938, 1705, 1474, 1327, 1180, 1160, 741 cm-1; HRMS

(ESI) calcd for [M+Na]+ C17H18F3N2NaO2, m/z: 293.0878, found: 293.0882.

Methyl (2-(1-methyl-1H-indol-3-yl)ethyl)carbamate, 5m:

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Compound 5m (1.09 g, 67% yield) was synthesized following the general procedure A as pale yellow

solid, purified by flash chromatography (petrol ether: EtOAc = 10:1 to 5:1). R7Cl = MeCO2Cl. m.p.

91-93℃; 1H NMR (400 MHz, CDCl3): δ 7.58 (d, J = 7.6 Hz, 1H), 7.29 (d, J = 8.0 Hz, 1H), 7.23 (td,

J = 6.8 Hz, 0.8 Hz, 1H), 7.11 (td, J = 7.6 Hz, 0.8 Hz, 1H), 6.86 (s, 1H), 4.79 (s, 1H), 3.73 (s, 3H), 3.65

(s, 3H), 3.49 (q, J = 6.4 Hz, 2H), 2.94 (t, J = 6.8 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 156.98,

137.05, 127.62, 126.78, 121.67, 118.85, 118.77, 111.27, 109.22, 51.92, 41.35, 32.56, 25.62; IR (KBr)

3333, 2940, 1701, 1533, 1248, 1191, 739, 428 cm-1; HRMS (ESI) calcd for [M+Na]+ C13H16N2NaO2,

m/z: 255.1104, found: 255.1098.

2.2 Preparation of N- methyl tryptophol and 3-indolepropanol

To a stirred solution of tryptophol (2.50 g, 15.5 mmol, 1.0 equiv) in DMF (20 mL) at 0℃ was added

NaH (1.85 g, 46.5 mmol, 3.0 equiv, 60% dispersion in mineral oil) in portions. The system was reacted

at room temperature for 30 min, and then cooled to 0℃. A solution of MeI (0.97 mL, 17.1 mmol, 1.1

equiv) in DMF (10 mL) was subsequently added to the reaction mixture dropwise at the same

temperature and the reaction mixture was stirred at room temperature for additional 6 h. The resulted

reaction system was carefully quenched with saturated NH4Cl and extracted with EtOAc (100 mL x

3). The organic layer was washed with water (100 mL×8) and brine (100 mL), then dried over Na2SO4,

filtered, and concentrated by vacuo. The residue was purified by flash column chromatography (petrol

ether: EtOAc = 8:1 to 7:1) to afford 5n (1.80 g, 66% yield) as a yellow oil. 1H NMR (400 MHz,

CDCl3): δ 7.60 (d, J = 7.6 Hz, 1H), 7.30 (d, J = 8.4 Hz, 1H), 7.26-7.21 (m, 1H), 7.12 (td, J = 7.4 Hz,

1.2 Hz, 1H), 6.94 (s, 1H), 3.88 (t, J = 6.4 Hz, 2H), 3.75 (s, 3H) 3.02 (t, J = 6.4 Hz, 2H), 1.53 (s, 1H);

13C NMR (100 MHz, CDCl3): δ 137.18, 127.84, 127.27, 121.73, 118.91, 118.88, 110.66, 109.26, 62.74,

32.60, 28.64; IR (KBr) 3362, 2931, 1615, 1483, 1045, 740, 428 cm-1; HRMS (ESI) calcd for [M+Na]+

C11H13NNaO, m/z: 198.0895, found: 198.0902.

12

To a solution of 3-indolepropionic acid (1.89 g, 10 mmol, 1.0 equiv) in THF (50 mL) was added

BH3•Me2S (15 mL, 30 mmol, 3.0 equiv, 2 M in THF) at 0℃. The reaction mixture was stirred at 70℃

for 16 h and then carefully quenched with MeOH at 0℃. The resulted solution was extracted with

EtOAc (60 mL x 3), the combined organic layers were washed with brine and then dried over Na2SO4,

filtered, and concentrated by vacuo. The residue was used for next step directly without further

purification.

The residue product above was dissolved in DMF (50 mL) and cooled to 0℃. NaH (1.20 g, 30 mmol,

3.0 equiv, 60% dispersion in mineral oil) was added to the reaction system in one portion, and the

mixture was stirred at room temperature for 0.5 h, and then cooled to 0℃. A solution of MeI (1.42 g,

10 mmol, 1.0 equiv) in DMF (50 mL) was subsequently added to the mixture dropwise at 0℃. The

reaction system was stirred at the same temperature for 2 h, after which, quenched with saturated

NH4Cl (aqueous). The resulted mixture was extracted with EtOAc (100 mL x 3), the combined organic

layers were washed with water (100 mL x 6) and brine and dried over Na2SO4, filtered, and

concentrated by vacuo. The residue was purified by flash column chromatography (PE: EA=10:1 to

3:1) to afford 5o in 69% yield as a yellow oil. 1H NMR (400 MHz, CDCl3): δ 7.59 (d, J = 8.0 Hz, 1H),

7.28 (d, J = 8.0 Hz, 1H), 7.23-7.19 (m, 1H), 7.12-7.07 (m, 1H), 6.84 (s, 1H), 3.73-3.69 (m, 5H), 2.84

(t, J = 7.4 Hz, 2H), 2.00-1.92 (m, 2H), 1.44 (s, 1H); 13C NMR (100 MHz, CDCl3): δ 137.02, 127.79,

126.13, 121.47, 118.93, 118.56, 114.37, 109.11, 62.61, 33.13, 32.52, 21.23; IR (KBr) 3361, 2933,

1473, 1326, 1247, 1153, 1062, 740 cm-1; HRMS (ESI) calcd for [M+Na]+ C12H15NNaO, m/z:

212.1046, found: 212.1043.

2.3 Preparation of benzene ring-substituted tryptamines

Compound 7a-f,7h,7j, 7k were synthesized from corresponding indole over 5 steps according to the

literature procedures[2].

13

N-(2-(7- chloro-1-methyl-1H-indol-3-yl)ethyl)-4-methylbenzenesulfonamide, 7a:

Compound 7a (0.81 g, 38%) was obtained from 7-chloro-indole as a pale yellow solid. m.p. 99-102℃;

1H NMR (400 MHz, CDCl3): δ 7.61 (d, J = 8.4 Hz, 2H), 7.24 (dd, J = 8.0 Hz, 1.2 Hz, 1H), 7.18 (d, J

= 8.4 Hz, 2H), 7.09 (dd, J = 7.6 Hz, 0.8 Hz, 1H), 6.89 (t, J = 7.8 Hz, 1H), 6.73 (s, 1H), 4.74 (t, J = 6.0

Hz, 1H), 4.01 (s, 3H), 3.21 (q, J = 6.4 Hz, 2H), 2.84 (t, J = 6.6 Hz, 2H), 2.38 (s, 3H); 13C NMR (100

MHz, CDCl3): δ 143.20, 136.69, 132.24, 130.43, 129.96, 129.48, 126.88, 123.14, 119.66, 117.27,

116.97, 110.17, 43.02, 36.35, 25.13, 21.43; IR (KBr) 3274, 2948, 1489, 1315, 1154, 1084, 814, 735,

667 cm-1; HRMS (ESI) calcd for [M+Na]+ C18H19ClN2NaO2S, m/z: 385.0748, found: 385.0745.

N-(2-(1,7-dimethyl-1H-indol-3-yl)ethyl)-4-methylbenzenesulfonamide, 7b:

Compound 7b (0.89 g, 29%) was obtained from 7-methyl-indole as a pale yellow solid. m.p. 104-

109℃; 1H NMR (400 MHz, CDCl3): δ 7.63 (d, J = 8.4 Hz, 2H), 7.22-7.19 (m, 3H), 6.90-6.88 (m, 2H),

6.68 (s, 1H), 4.51 (t, J = 6.0 Hz, 1H), 3.96 (s, 3H), 3.22 (q, J = 6.8 Hz, 2H), 2.86 (t, J = 6.8 Hz, 2H),

2.72 (s, 3H), 2.39 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 143.16, 136.84, 135.80, 129.54, 128.91,

128.35, 126.98, 124.38, 121.36, 119.24, 116.58, 109.58 , 43.05, 36.51, 25.23, 21.45, 19.61; IR (KBr)

3289, 3046, 2927, 1599, 1321,1159, 1048, 740, 665 cm-1; HRMS (ESI) calcd for [M+Na]+

C19H22N2NaO2S, m/z: 365.1300, found: 365.1285.

N-(2-(6-fluoro-1-methyl-1H-indol-3-yl)ethyl)-4-methylbenzenesulfonamide, 7c:

Compound 7c (2.05 g, 47%) was obtained from 6-fluoro-indole as a white solid. m.p. 91-94℃; 1H

14

NMR (400 MHz, CDCl3): δ 7.62 (d, J = 8.4 Hz, 2H), 7.26 (dd, J = 5.2 Hz, 3.6 Hz, 1H), 7.18 (d, J =

8.0 Hz, 2H), 6.90 (dd, J = 7.6 Hz, 2.0 Hz, 1H), 6.80-6.74 (m, 2H), 4.75 (t, J = 6.0 Hz, 1H), 3.61 (s,

3H), 3.21 (q, J = 6.4 Hz, 2H), 2.85 (t, J = 6.4 Hz, 2H), 2.38 (s,3H); 13C NMR (100MHz, CDCl3): δ

161.06, 158.70, 143.20, 137.15, 137.03, 136.71, 129.48, 127.52, 127.49, 126.90, 123.84, 119.35,

119.25, 110.31, 107.64, 107.40, 95.74, 95.48, 43.09, 32.60, 25.23, 21.38; 19F NMR (376 MHz, CDCl3):

δ -120.79; IR (KBr) 3286, 3065, 2934, 1624, 1333, 1160, 1069, 737, 667 cm-1; HRMS (ESI) calcd

for [M+Na]+ C18H19FN2NaO2S, m/z: 369.1049, found: 369.1056.

N-(2-(6-chloro-1-methyl-1H-indol-3-yl)ethyl)-4-methylbenzenesulfonamide, 7d:

Compound 7d (1.12 g, 17%) was obtained from 6-chloro-indole as a pale yellow solid. m.p. 77-

79℃; 1H NMR (400 MHz, CDCl3): 1H NMR (400 MHz, CDCl3): δ 7.62 (d, J = 8.4 Hz, 2H), 7.25

(d, J = 2.0 Hz, 2H), 7.20 (d, J = 8.0 Hz, 2H), 6.99 (dd, J = 8.4 Hz, 2.0 Hz, 1H), 6.80 (s, 1H), 4.43 (t,

J = 6.0 Hz, 1H), 3.68 (s, 3H), 3.23 (q, J = 6.4 Hz, 2H), 2.88 (t, J = 6.8 Hz, 2H), 2.40 (s, 3H); 13C

NMR (100 MHz, CDCl3): δ 143.33, 137.55, 136.76, 129.55, 127.98, 127.93, 126.97, 125.89,

119.68, 119.47, 110.37, 109.38, 43.06, 32.71, 25.29, 21.48; IR (KBr) 3286, 3061, 2927, 1613, 1325,

1159, 1067, 737, 667 cm-1; HRMS (ESI) calcd for [M+Na]+ C18H19ClN2NaO2S, m/z: 385.0753,

found: 385.0744.

N-(2-(1,6-dimethyl-1H-indol-3-yl)ethyl)-4-methylbenzenesulfonamide, 7e:

Compound 7e (374 mg, 32%) was obtained from 6-methyl-indole as a brown oil. 1H NMR (400 MHz,

CDCl3): δ 7.62 (d, J = 8.4 Hz, 2H), 7.25 (s, 1H), 7.21 (d, J = 8.0 Hz, 2H), 7.07 (s, 1H), 6.88 (d, J =

8.0 Hz, 1H), 6.73 (s, 1H), 4.40(t, J = 6.0 Hz, 1H), 3.68 (s, 3H), 3.24(q, J = 6.8 Hz, 2H), 2.88(t, J = 6.4

Hz, 2H), 2.48 (s, 3H), 2.40 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 143.19, 137.61, 136.93, 131.74,

15

129.56, 127.04, 126.70, 125.19, 120.79, 118.29, 109.80, 109.33, 43.18, 32.54, 25.46, 21.82, 21.49; IR

(KBr) 3265, 3031, 2918, 1598, 1319,1158, 1065, 756, 667 cm-1; HRMS (ESI) calcd for [M+Na]+

C19H22N2NaO2S, m/z: 365.1300, found: 365.1286.

N-(2-(6-methoxy-1-methyl-1H-indol-3-yl)ethyl)-4-methylbenzenesulfonamide, 7f:

Compound 7f (3.04 g, 60%) was obtained from 6-methoxyl-indole as a grey solid. m.p. 108-110℃;

1H NMR (400 MHz, CDCl3): δ 7.62 (d, J = 8.4 Hz, 2H), 7.24-7.19 (m, 3H), 6.70 (d, J = 9.2 Hz, 3H),

4.48(t, J = 5.6 Hz, 1H), 3.86 (s, 3H), 3.65 (s, 3H), 3.22 (q, J = 6.4 Hz, 2H), 2.86 (t, J = 6.6 Hz, 2H),

2.39 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 156.52, 143.18, 137.87, 136.80, 129.53, 126.98, 126.09,

121.65, 119.23, 109.95, 108.95, 92.83 , 55.69, 43.11, 32.59, 25.36, 21.45; IR (KBr) 3288, 3056, 2937,

1624, 1329,1159, 1068, 736, 667 cm-1; HRMS (ESI) calcd for [M+Na]+ C19H22N2NaO3S, m/z:

381.1249, found: 381.1254.

N-(2-(4-fluoro-1-methyl-1H-indol-3-yl)ethyl)-4-methylbenzenesulfonamide, 7j:

Compound 7j (1.80 g, 52%) was obtained from 4-fluoro-indole as a white solid. m.p. 120-126℃; 1H

NMR (400 MHz, CDCl3): δ 7.62 (d, J = 8.4 Hz, 2H), 7.19 (d, J = 8.0 Hz, 2H), 7.12-7.06 (m, 1H), 7.02

(d, J = 8.0 Hz, 1H), 6.76 (s, 1H), 6.66 (dd, J = 10.8 Hz, 7.6 Hz, 1H), 4.46 (bs, 1H), 3.70 (s, 3H), 3.27

(q, J = 6.4 Hz, 2H), 2.96 (t, J = 6.4 Hz, 2H), 2.38 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 158.16,

155.71, 143.11, 140.08, 139.96, 136.81, 129.48, 127.75, 126.92, 122.25, 122.18, 115.90, 115.70,

108.80, 108.77, 105.48, 105.44, 104.22, 104.03, 43.62, 32.96, 26.48, 21.48; 19F NMR (376 MHz,

CDCl3): δ -123.68; IR (KBr) 3282, 2932, 1629, 1319, 1156, 1092, 734, 671 cm-1; HRMS (ESI) calcd

for [M+Na]+ C18H19FN2NaO2S, m/z: 369.1043, found: 369.1037.

16

N-(2-(4-chloro-1-methyl-1H-indol-3-yl)ethyl)-4-methylbenzenesulfonamide, 7k:

Compound 7k (0.78 g , 54%) was obtained from 4-chloro-indole as a pale yellow solid. m.p. 129-

132℃; 1H NMR (400 MHz, CDCl3): δ 7.63 (d, J = 8.4 Hz, 2H), 7.19 (d, J = 8.0 Hz, 2H), 7.14 (d, J =

8.4 Hz, 1H), 7.07 (t, J = 7.6 Hz, 1H), 6.99 (dd, J = 7.2 Hz, 0.4 Hz, 1H), 6.84 (s, 1H), 4.50 (t, J = 6.0

Hz, 1H), 3.70 (s, 3H), 3.30 (q, J = 6.4 Hz, 2H), 3.11 (t, J = 6.4 Hz, 2H), 2.38 (s, 3H); 13C NMR (100

MHz, CDCl3): δ 143.13, 138.66, 136.95, 129.49, 129.09, 126.97, 126.10, 124.07, 122.18, 119.99,

110.47, 108.10, 44.35, 32.87, 26.31, 21.46; IR (KBr) 3284, 3061, 2927, 1598, 1321,1158, 1073, 737,

669 cm-1; HRMS (ESI) calcd for [M+Na]+ C18H19ClN2NaO2S, m/z: 385.0753, found: 385.0742.

Compound 7g-i were synthesized from corresponding tryptamine over 2 steps .

To a stirred solution of substituted tryptamine (1.0 equiv) in DCM (0.50 M) at 0℃ were added Et3N

(1.2 equiv) and R7Cl (1.05 equiv) successively. The reaction system was stirred at room temperature

for 6h and then quenched with saturated NH4Cl. The resulted mixture was extracted with DCM and

the organic layer was dried over Na2SO4, filtered, and concentrated by vacuo. The residue was

recrystallized (Et2O and petrol ether as eluent) to provide the crude intermediate 3.




reactiom mixture. The resulted solution was stirred at room temperature for 6 h, then quenched with

saturated NH4Cl, and extracted with EtOAc. The organic layer was washed with water (6 times) and

brine, then dried over Na2SO4, filtered, and concentrated by vacuo. The residue was purified by

column chromatography to afford 7g-i.

17

N-(2-(5-chloro-1-methyl-1H-indol-3-yl)ethyl)-4-methylbenzenesulfonamide, 7g:

Compound 7g (2.48 g, 91%) was obtained from 5-chloro-tryptamine as a pale yellow solid. m.p. 105-

107℃; 1H NMR (400 MHz, CDCl3): δ 7.61 (d, J = 8.4 Hz, 2H), 7.26 (dd, J = 2.0 Hz, 0.8 Hz, 1H),

7.20 (d, J = 8.0 Hz, 2H), 7.17-7.10 (m, 2H), 6.83 (s, 1H), 4.66 (t, J = 6.0 Hz, 1H), 3.67 (s, 3H), 3.20

(q, J = 6.8 Hz, 2H), 2.82 (t, J = 6.8 Hz, 2H), 2.40 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 143.43,

136.52, 135.52, 129.66, 128.81, 128.26, 127.00, 124.80, 122.00, 118.03, 110.43, 109.62, 42.96, 32.85,

25.13, 21.57; IR (KBr) 3276, 3062, 2926, 1598, 1320, 1159, 1071, 737, 663 cm-1; HRMS (ESI) calcd

for [M+Na]+ C18H19ClN2NaO2S, m/z: 385.0753, found: 385.0748.

N-(2-(1,5-dimethyl-1H-indol-3-yl)ethyl)-4-methylbenzenesulfonamide, 7h:

Compound 7h (1.44 g, 44%) was obtained from 5-methyl-tryptamine as a pale yellow solid. m.p. 109-

113℃; 1H NMR (400 MHz, CDCl3) δ 7.63 (d, J = 6.8 Hz, 2H), 7.21 (d, J = 8.0 Hz, 2H), 7.16 (d, J =

8.4 Hz, 2H), 7.04 (d, J = 8.4 Hz, 1H), 6.76 (s, 1H), 4.53 (bs, 1H), 3.69 (s, 3H), 3.24 (q, J = 6.4 Hz,

2H), 2.87 (t, J = 6.6 Hz, 2H), 2.41 (s, 3H), 2.40 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 143.20,

136.85, 135.64, 129.58, 128.18, 127.51, 127.45, 127.07, 123.45, 118.27, 109.28, 109.09, 43.16, 32.68,

25.35, 21.52, 21.44; IR (KBr) 3261, 3032, 2929, 1599, 1318, 1148, 1064, 738, 668 cm-1; HRMS (ESI)

calcd for [M+Na]+ C19H22N2NaO2S, m/z: 365.1300, found: 365.1283.

N-(2-(5-methoxy-1-methyl-1H-indol-3-yl)ethyl)-4-methylbenzenesulfonamide, 7i:

18

Compound 7i (1.60 g ,57%) was obtained from 5-methoxyl-tryptamine as a pale yellow solid. m.p.

114-116℃; 1H NMR (400 MHz, CDCl3): δ 7.60 (d, J = 8.4 Hz, 2H), 7.17 (d, J = 8.0 Hz, 2H), 7.14 (d,

J = 8.8 Hz, 1H), 6.85 (dd, J = 8.8 Hz, 2.4 Hz, 1H), 6.81 (d, J = 2.4 Hz, 1H), 6.76 (s, 1H), 4.66 (t, J =

5.6 Hz, 1H), 3.78 (s, 3H), 3.65 (s, 3H), 3.21 (q, J = 6.4 Hz, 2H), 2.86 (t, J = 6.4 Hz, 2H), 2.37 (s, 3H);

13C NMR (100 MHz, CDCl3): δ 153.81, 143.26, 136.76, 132.55, 129.58, 127.95, 127.62, 127.03,

112.04, 110.16, 109.41, 100.45, 55.88, 43.13, 32.79, 25.39, 21.49; IR (KBr) 3285, 3058, 2934, 1598,

1324, 1158, 1066, 736, 665 cm-1; HRMS (ESI) calcd for [M+Na]+ C19H22N2NaO3S, m/z: 381.1249,

found: 381.1254.

19

3. Screening of KI-catalyzed oxidative dimerization conditions

Table S1. Screening of solvents [a]

Entry Solvent Time[b] dr[c] Yield [d]

1 THF 24 h - NR[e]

2 DME (1,2-dimethoxyethane) 24 h - R.D.[f]

3 Et2O 24 h - NR

4 1,4-dioxane 24 h - NR

5 EtOAc 24 h - NR

6 CH3CN 24 h - NR

7 Acetone 24 h - NR

8 DMF (N,N-dimethylformamide) 24 h - NR

9 CH2Cl2 24 h - NR

10 CHCl3 24 h - NR

11 CCl4 24 h - R.D.

12 DCE (1,2-dichloroethane) 24 h - R.D.

13 MeOH 24 h - R.D.

14 EtOH 24 h - R.D.

15 i-PrOH 24 h - R.D.

16 TFE (Trifluoroethanol) 1.5 h 1.8:1 64%

17 1,1,1,3,3,3-hexafluoro-2-propanol 2 h 1.7:1 57%

18 H2O 24 h - ND

19 Benzene 24 h - R.D.

20 Toluene 24 h - R.D.

21 PhCl 24 h - R.D.

22 PhCF3 24 h - R.D.

[a] Unless otherwise noted, all reactions were carried with 5a (0.2 mmol), KI (20 mmol%) and NaBO3•4H2O (2.0 equiv) in 2 mL

solvent. [b] The time of which the reaction is completed (monitored by TLC) or the time of which the reaction is quenched (24 h). [c]

Determined by 1H NMR. [d] Determined by 1H NMR. [e] Not reacted. [f] Recovery of 5a and slightly decomposed.

On the basis of our initial efforts, additional solvents were screened to optimize the dimerization

reaction of 5a under the oxidative of NaBO3•4H2O. As shown in Table S1, various ether solvents

(entries 1-4), polar solvents (entries 5-8), halogenated alkane solvents (entries 9-12), protic solvents

(entries 13-18) and aromatic solvents (entries 19-22) were investigated. According to the results, only

polyfluoro substituted alcohol solvent could provide the desired products 6a and 6a′, while other

solvents screened generally behaved inactive in the catalytic oxidative dimerization of 5a.

20

Table S2. Optimization of oxidants [a]

Entry Oxidant Time[b] dr[c] Yield [d]

1 NaBO3•4H2O 1.5 h 1.8:1 64%

2 H2O2 4 h 1.8:1 44%

3 H2O2 (3 equiv) 4 h 1.9:1 40%

4 tBuO2H (75% aqueous) 10 h 1.8:1 47%

5 tBuO2H (5.5 M in decane) 10 h 1.8:1 53%

6 air 24 h - NR[e]

7 O2 (1atm) 24 h - NR

8 m-CPBA 10 min - ND[f]

9 tBuO2tBu 24 h - NR

10 tBuO2Ac 24 h 1.9:1 10%

11 Ammonium peroxodisulfate 18 h 1.8:1 43%

12 Sodium carbonate peroxide 24 h 1.9:1 23%

13 potassium peroxodisulfate 24 h 1.8:1 19%

14 Oxone 25 min - 42%

15 Benzoyl peroxide 10 min - trace

[a] Unless otherwise noted, all reactions were carried with 5a (0.2 mmol), KI (20 mmol%) and oxidant (2.0 equiv) in 2 mL TFE. [b]

The time of which the reaction is completed (monitored by TLC) or the time of which the reaction is quenched (24 h). [c] Determined

by 1H NMR. [d] Determined by 1H NMR. [e] Not reacted. [f] Not dected.

Next, numerous oxidants were also applied to this reaction (Table S2). As a result, most oxidants

(entries 1-5, 10-14) were able to drive the desired reactions, giving different reaction yields and similar

diastereoselectivities. Among these screenings, NaBO3•4H2O was proven to be the optimal (64%

yield). Interestingly, both O2 and tBuO2tBu exhibits very low activities, however, m-CPBA and

Benzoyl peroxide (BPO) were too active in the reaction.

21

Table S3. Screening of iodide catalysts [a]

Entry Catalyst Time[b] dr[c] Yield [d]

1 LiI 3.5 h 1.9:1 64%

2 NaI 2 h 1.9:1 65%

3 KI 1.5 h 1.8:1 64%

4 MgI2 5.5 h 1.9:1 65%

5 ZnI2 7 h 1.9:1 61%

6 CuI 24 h 1.9:1 45%

7 AgI 24 h - NR[e]

8 NH4+I- 1.5 h 1.9:1 63%

9 PhMe3+I- 2 h 1.8:1 65%

10 nBu4+I- 2 h 1.9:1 62%

11 Ph3(i-Pr)P+I- 2.5 h 1.9:1 63%

12 PhI 24 h - NR

[a] Unless otherwise noted, all reactions were carried with 5a (0.2 mmol), catalyst (20 mmol%) and NaBO3•4H2O (2.0 equiv) in 2

mL TFE. [b] The time of which the reaction is completed (monitored by TLC) or the time of which the reaction is quenched (24 h). [c]

Determined by 1H NMR. [d] Determined by 1H NMR. [e] Not reacted.

Subsequently, different iodide catalysts were also screened. Except for silver iodide and

iodobenzene, the other selected iodide catalysts could generally promote our target reaction with

similar results, although their reaction times were varied. Considering the reaction time and the cost

of material, potassium iodide was chosen as the optimal catalyst.

22

Table S4. Screening of additives [a]

Entry Additive Time[b] dr[c] Yield [d]

1 3 ÅMS (60 mg) 24 h 2.0:1 32%

2 4 ÅMS (60 mg) 24 h 1.9:1 56%

3 5 ÅMS (60 mg) 2.5 h 1.8:1 64%

4 HCO2H (60 mg) 1.5 h 1.9:1 43%

5 HOAc 1 h 1.8:1 52%

6 PhCO2H 1.5 h 1.9:1 55%

7 B(OH)3 2 h 1.9:1 58%

8 Phenol 1.5 h 1.8:1 58%

9 4-Methoxyphenol 1.5 h 1.8:1 63%

10 4-Nitrophenol 1.5 h 2.0:1 45%

11 NaH2PO4•2H2O 2.5 h 1.9:1 62%

12 Na2HPO4 1.5 h 1.7:1 62%

13 NH4Cl 1 h 1.9:1 60%

14 NH4OAc 1 h 1.9:1 48%

15 NH4PF6 1 h 1.9:1 60%

16 NaHCO3 1.5 h 2.0:1 61%

17 KOAc 2 h 2.0:1 38%

18 K2CO3 24 h - ND[e]

[a] Unless otherwise noted, all reactions were carried with 5a (0.2 mmol), KI (20 mmol%), additive (1.0 equiv) and NaBO3•4H2O

(2.0 equiv) in 2 mL TFE. [b] The time of which the reaction is completed (monitored by TLC) or the time of which the reaction is

quenched (24 h). [c] Determined by 1H NMR. [d] Determined by 1H NMR. [e] Not dected.

Next, we further optimized the target reaction with various additives such as molecular sieves,

acids, bases and salts (Table S4). Unfortunately, none of the above screenings gave better results.

23

Table S5. Screening of concentrations and the equivalent of reaction components. [a]

Entry x mol% y z Time[b] dr[c] Yield [d]

1 20 mol% 1.0 2 mL (c=0.1 M) 3 h 1.8:1 58%[e]

2 20 mol% 1.1 4 mL (c=0.05 M) 6.5 h 1.8:1 66%[e]

3 20 mol% 1.1 2 mL (c=0.1 M) 2 h 1.8:1 63%[e]

4 20 mol% 1.1 1 mL (c=0.2 M) 2 h 1.8:1 65%[e]

5 20 mol% 1.2 4 mL (c=0.05 M) 6 h 1.8:1 66%

6 20 mol% 1.2 2 mL (c=0.1 M) 2 h 1.8:1 68%

7 20 mol% 1.2 1 mL (c=0.2 M) 2 h 1.9:1 64%

8 20 mol% 1.3 4 mL (c=0.05 M) 4 h 1.8:1 66%

9 20 mol% 1.3 2 mL (c=0.1 M) 2 h 1.8:1 68%

10 20 mol% 1.3 1 mL (c=0.2 M) 2 h 1.8:1 64%

11 20 mol% 1.4 4 mL (c=0.05 M) 3 h 1.8:1 66%

12 20 mol% 1.4 2 mL (c=0.1 M) 2 h 1.8:1 67%

13 20 mol% 1.4 1 mL (c=0.2 M) 1 h 1.8:1 65%

14 20 mol% 1.5 4 mL (c=0.05 M) 2.5 h 1.8:1 67%

15 20 mol% 1.5 2 mL (c=0.1 M) 2 h 1.8:1 68%

16 20 mol% 1.5 4 mL (c=0.2 M) 2 h 1.8:1 65%

17 10 mol% 1.2 2 mL (c=0.1 M) 2 h 1.8:1 68%

[a] Unless otherwise noted, all reactions were carried with 5a (0.2 mmol), KI (x mmol%) and NaBO3•4H2O (y equiv) in z mL TFE.

[b] The time of which the reaction is completed (monitored by TLC). [c] Determined by 1H NMR. [d] Determined by 1H NMR. [e]

The repeatability of these reactions was not good.

Finally, we also carefully screened the concentrations of the reaction and the equivalent of

reaction components (Table S5). According to the results, when the concentration of the reaction was

chosen as 0.1 M, both 1.0 (entry 1) and 1.1 (entry 3) equivalent of oxidant (NaBO3•4H2O) were able

to provide the targeted products with acceptable results, but the repeatability of these reactions was

not good. However, when 1.2 equivalent of oxidant (entry 6) was used under this concentration, the

desired products could be well obtained with repeatable results (68% yield, 1.8:1 dr). In addition,

varying the concentrations (entries 5, 7) of the above reaction could not give a better result, however,

when the loading amount of catalyst (KI) was reduced to 10 mol%, the reaction could still provide 6a

and 6a′ with good results (entry 17). According to above screenings (Tables S1-5), we finally obtained

the optimal reaction conditions (Table S5, entry 17).

24

In addition, it is necessary to specifically state that our diastereo ratios is determined by 1HNMR

of the crude reaction products, and the yield (NMR) is calibrated with 1,3,5-trimethoxybenzene as an

internal standard (Fig. S1).

Figure S1. 1H NMR used to identify diastereo ratio and NMR yield of 6a/6a'.

25

4. KI-catalyzed oxidative dimerization reactions

4.1 General procedure:

To a dry 10 mL reaction tube were added corresponding tryptamine or tryptophol (0.2 mmol), KI

(3.3 mg, 10 mol%), TFE (2 mL) and NaBO3•4H2O (37.0 mg, 1.2 equiv) successively under argon

atmosphere. The reaction system was stirred (1500 rmp) at room temperature until TLC indicated that

5 or 7 disappeared (1-3 h). The mixture was then quenched with saturated Na2S2O3 (aqueous) and

extracted with EtOAc (60 mL). The organic layer was washed with brine (15 mL), dried over Na2SO4,

filtered, and concentrated by vacuo. The residue was purified by flash column chromatography to

afford the dimeric products.

4.2 Exemplificative explanation for the configurational assignments

In our study, most of the diastereomeric product pairs were not easy to be separated into single

isomer. In fact, similar situation was also occurred in recent related research.[3] For better

configurational assignments of each diastereoisomer (meso and racemic C2-symmetric dimer) of the

products, exemplificative explanations based on NMRs, HPLC, X-ray and other experimental data is

necessary.

At the beginning of this study, products provided by the KI-catalyzed dimerization of 5a were

purified by column chromatography and identified by NMRs respectively (Figure S2). It’s worth

noting that the racemic C2-symmetric dimer 6a has already been characterized by Xia and co-workers

previously (Figure S3).[4] Therefore, our major product showed in Fig. S2-A seems to be the C2-

symmetric dimer 6a and the minor (Fig. S2-B) was recognized as the meso dimer 6a' according to the

NMR characteristic and the high-resolution mass spectral analysis (HRMS) data. Investigating the

previous literature[4] in detail, we found that their configuration assignment of compound 6a was based

on the X-ray of a similar compound and the comparison of their NMR spectra. To further confirm this

conclusion, we performed a chiral HPLC analysis of compound Fig. S2-A (Figure S4). Since the

HPLC of this compound exhibits two peaks with equal integral areas, it is identified to be the C2-

symmetric 6a rather than the meso- 6a'.

26

Figure S2. 1HNMR of the products provided by the KI-catalyzed dimerization of 5a.

27

Figure S3. 1HNMR of 6a provided by Xia and co-workers.

Figure S4. Chiral HPLC analysis of compound from Fig. S2-A

Another example supports the configuration assignments of this manuscript is 6b/6b'. The relative

configuration of compound 6b is reported by Liang and co-workers via conversion to (±)-

folicanthine.[5] Here, we double-checked this conclusion via X-ray of 6b (Figure S5-A) and chiral

HPLC analysis (Figure S5-B) of the diastereomeric 6b/6b' mixture.

28

Figure S5. A) X-ray of 6b and B) the chiral HPLC of diastereomeric 6b/6b'

Moreover, compound 8k which is obtained in high diastereoselectivity (> 20:1 dr) was also subject

to chiral HPLC for confirming our configuration assignment. To our delight, this compound exhibits

two peaks with equal integral areas, revealing that 8k is the C2-symmetric dimer (Figure S6).

Figure S6. The chiral HPLC of 8k.

29

4.3 Characterization of the products:

1,1'-ditosyl-2,2',3,3',8,8a,8',8'a-octahydro-1H,1'H-3a,3'a-bipyrrolo[2,3-b]indole, 6a and 6a′:

Compound 6a and 6aʹ was obtained (38.9 mg, 62% yield, 1.8:1 dr) via the KI-catalyzed oxidative

dimerization of 5a following the general procedure. Compound 6a has already been characterized by

Xia and co-workers,[4] the configurational assignments of 6a and 6aʹ were confirmed by HPLC

spectrum and comparison of the NMRs.

Compound 6a: White solid; m.p. 226-227℃; 1H NMR (400 MHz, CDCl3): δ 7.28-7.25 (m, 4H), 7.16-

7.09 (m, 6H), 6.90 (d, J = 7.6 Hz, 2H), 6.69 (d, J = 7.6 Hz, 2H), 6.62-6.57 (m, 2H), 4.95 (s, 2H), 4.68

(s, 2H), 3.17-3.11 (m, 2H), 3.03-2.95 (m, 2H), 2.41 (s, 6H), 2.30-2.21 (m, 2H), 2.08-2.02 (m, 2H); 13C

NMR (100 MHz, CDCl3): δ 150.07, 142.97, 135.41, 129.83, 129.34, 127.37, 126.53, 124.49, 119.06,

110.37, 81.26, 61.33, 46.84, 32.31, 21.52; IR (KBr) 3393, 1607, 1467, 1334, 1158, 1031, 737, 662

cm-1; HRMS (ESI) calcd for [M+Na]+ C34H34N4NaO4S2, m/z: 649.1919, found: 649.1925. Relative

configuration of 6a is confirmed by HPLC (IA-3, Hexane/Isopropanol 70/30, flow rate = 1.0 mL/min,

240 nm): tr1 =17.56 min; tr2 = 24.63 min.

Compound 6a′: White solid; m.p. 252-255℃; 1H NMR (400 MHz, CDCl3): δ 7.62 (d, J = 8.4 Hz,

4H), 7.32 (d, J = 8.0 Hz, 4H), 7.06 (td, J = 7.8 Hz, 1.2 Hz, 2H), 6.58-6.51 (m, 4H), 6.44 (d, J = 6.4

Hz, 2H), 5.09 (s, 2H), 4.57 (bs, 2H), 3.33 (dd, J = 10.8 Hz, 8.0 Hz, 2H), 3.00 (td, J = 11.2 Hz, 6.0 Hz,

2H), 2.46 (s, 6H), 2.00 (dd, J = 12.4 Hz, 5.2 Hz, 2H), 1.58 (td, J = 11.6 Hz, 8.0 Hz, 2H); 13C NMR

(100 MHz, CDCl3): δ 149.78, 143.85, 136.35, 129.86, 129.20, 127.87, 126.83, 123.66, 119.00, 109.77,

80.01, 62.50, 47.13, 33.84, 21.58; IR (KBr) 3390, 2952, 1609, 1468, 1335, 1159, 1028, 734, 662 cm-

1; HRMS (ESI) calcd for [M+Na]+ C34H34N4NaO4S2, m/z: 649.1919, found: 649.1918.

8,8'-dimethyl-1,1'-ditosyl-2,2',3,3',8,8a,8',8'a-octahydro-1H,1'H-3a,3'a-bipyrrolo[2,3-b]indole, 6b and

6b′:

30

Compound 6b and 6b′ was obtained (60.9 mg, 93% yield, 2.9:1 dr) via the KI-catalyzed oxidative

dimerization of 5b following the general procedure as a white solid. Compound 6b has already been

characterized by Liang and co-workers,[5] the configurational assignments of 6b and 6bʹ were

confirmed by HPLC spectrum, X-ray and comparison of the NMRs. Actually, in view of the difficulty

in separating the diastereomeric products, most of the configurational assignments of racemic C2-

symmetric and meso dimeric product were established via comparison of the NMRs with 6a/6aʹ and

6b/6bʹ. These also proved to be consistent with previous reports[3] (6n and 6nʹ) and got verified by

representative examples mentioned in “section 4.2” of this supporting information.

m.p. 103-105℃; 1H NMR (400 MHz, CDCl3): δ 7.62 (d, J = 8.4 Hz, 1.43H), 7.38-7.34 (m, 4+1.51H),

7.23-7.19 (m, 6H), 7.07 (t, J = 7.8 Hz, 0.77H), 6.84 (d, J = 7.2 Hz, 2H), 6.63 (t, J = 7.4 Hz, 2H), 6.50-

6.44 (m, 2+0.67H), 6.30 (d, J = 7.6 Hz, 0.71H), 6.18 (d, J = 6.4 Hz, 0.60H), 5.04 (s, 2.0H), 4.99 (s,

0.68H), 3.51 (dd, J = 7.2 Hz, 4.8 Hz, 0.70H), 3.22 (dd, J = 6.8 Hz, 4.4 Hz, 2H), 2.97 (s, 6H), 2.88-

2.80 (m, 0.80H), 2.77-2.69 (m, 3.99H), 2.46 (s, 2.13H), 2.42 (s, 6H), 1.89-1.72 (m, 4+0.62H), 1.41-

1.32 (m, 0.77H); 13C NMR (100 MHz, CDCl3): δ 151.60, 151.49, 143.86, 142.94, 136.99, 136.05,

129.93, 129.48, 129.33, 128.27, 127.69, 127.13, 126.99, 124.54, 123.24, 117.69, 117.32, 106.92,

106.57, 87.21, 85.32, 62.06, 60.40, 47.67, 47.44, 34.23, 32.58, 31.57, 31.47, 21.53, 21.49; IR (KBr)

3053, 2949, 1604, 1491, 1343, 1157, 1010, 739, 659 cm-1; HRMS (ESI) calcd for [M+Na]+

C36H38N4NaO4S2, m/z: 677.2232, found: 677.2216. Relative configuration of 6b/6b' is confirmed by

HPLC (IA-3, Hexane/Isopropanol 70/30, flow rate = 1.0 mL/min, 240 nm): tr1 =10.59 min (6b'); tr2 =

11.43 min (6b); tr3 = 19.12 min (6b).

8,8'-diethyl-1,1'-ditosyl-2,2',3,3',8,8a,8',8'a-octahydro-1H,1'H-3a,3'a-bipyrrolo[2,3-b]indole, 6c and

6c′:

31

Compound 6c and 6c′ was obtained (61.9 mg, 91% yield, 1.4:1 dr) via the KI-catalyzed oxidative

dimerization of 5c following the general procedure as a pale yellow solid. m.p. 191-193℃; 1H NMR

(400 MHz, CDCl3): δ 7.68 (d, J = 8.0 Hz, 2.87H), 7.46 (d, J = 8.0 Hz, 4H), 7.35 (d, J = 8.0 Hz, 2.90H),

7.24 (d, J = 8.0 Hz, 4H), 7.15 (m, 2H), 7.06-7.01 (m, 1.23H), 6.87-6.84 (m, 2H), 6.58 (t, J = 7.4 Hz,

2H), 6.46 (d, J = 7.6 Hz, 2H), 6.41 (t, J = 7.2 Hz, 1.25H), 6.33-6.21 (m, 2.21H), 5.29 (s, 3H), 3.62-

3.38 (m, 4+2.95H), 3.28-3.22 (m, 2+1.29H), 2.86 (td, J = 11.8 Hz, 4.8 Hz, 1.39H), 2.75 (td, J = 12.4

Hz, 4.8 Hz, 2H), 2.45 (s, 3.97H), 2.42 (s, 6H), 1.89-1.73 (m, 2+3.37H), 1.46 (bs, 1.39H), 1.25 (t, J =

7.0 Hz, 6H), 0.92 (bs, 2+1.35H); 13C NMR (100 MHz, CDCl3): δ 150.46, 150.28, 143.73, 143.08,

137.30, 136.35, 129.92, 129.88, 129.26, 129.13, 128.14, 127.52, 127.26, 127.10, 124.80, 123.67,

116.95, 116.62, 106.32, 105.67, 85.64, 83.36, 62.05, 60.90, 47.31, 47.18, 38.84, 38.29, 35.12, 33.30,

21.51, 12.70, 11.89; IR (KBr) 3051, 2972, 1603, 1491, 1344, 1157, 1031, 741, 660 cm-1; HRMS (ESI)

calcd for [M+Na]+ C38H42N4NaO4S2, m/z: 705.2545, found: 705.2527.

8,8'-diallyl-1,1'-ditosyl-2,2',3,3',8,8a,8',8'a-octahydro-1H,1'H-3a,3'a-bipyrrolo[2,3-b]indole, 6d and

6d′:

Compound 6d and 6d′ was obtained (65.6 mg, 93% yield, 1.5:1 dr) via the KI-catalyzed oxidative

dimerization of 5d following the general procedure as a pale white solid. m.p. 113-115℃; 1H NMR

(400 MHz, CDCl3): δ 7.61 (d, J = 8.0 Hz, 2.98H), 7.43 (d, J = 7.6 Hz, 4H), 7.35 (d, J = 6.4 Hz, 2.97H),

7.22 (d, J = 8.0 Hz, 4H), 7.13 (t, J = 7.6 Hz, 2H), 7.04 (t, J = 7.6 Hz, 1.52H), 6.85 (d, J = 7.2 Hz, 2H),

6.61 (t, J = 7.4 Hz, 2H), 6.52 (d, J = 8.0 Hz, 2H), 6.46 (m, 1.45H), 6.33 (d, J = 7.6 Hz, 1.57H), 5.94-

32

5.84 (m, 2H), 5.29-5.06 (m, 11.98H), 4.31 (dd, J = 12.0 Hz, 4.8 Hz, 2H), 4.13 (bs, 1.26H), 3.89 (dd, J

=11.2 Hz, 5.6 Hz, 2H), 3.75 (d, J = 13.6 Hz, 1.36H), 3.49-3.46 (m, 1.36H), 3.26 (dd, J = 6.8 Hz, 4.8

Hz, 2H), 2.87 (td, J = 12.0 Hz, 4.4 Hz, 1.40H), 2.76 (td, J = 11.6 Hz, 4.8 Hz, 2H), 2.45 (s, 3.84H),

2.42 (s, 6H), 1.88-1.73 (m, 4+1.21H), 1.32 (bs, 1.36H); 13C NMR (100 MHz, CDCl3): δ 150.85,

150.68, 143.96, 143.19, 136.98, 136.00, 134.59, 133.96, 130.01, 129.94, 129.18, 129.12, 128.14,

127.70, 127.20, 127.05, 124.68, 123.35, 117.70, 117.32, 116.37, 107.95, 107.04, 86.72, 84.28, 62.13,

60.82, 48.10, 47.41, 47.31, 35.03, 33.14, 21.54; IR (KBr) 3056, 2975, 1603, 1489, 1344, 1157, 1051,

741, 660 cm-1; HRMS (ESI) calcd for [M+Na]+ C34H34N4NaO4S2, m/z: 729.2545, found: 729.2530.

8,8'-dimethyl-1,1'-bis(phenylsulfonyl)-2,2',3,3',8,8a,8',8'a-octahydro-1H,1'H-3a,3'a-bipyrrolo[2,3-

b]indole, 6f and 6f′:

Compound 6f and 6f′ was obtained (58.9 mg, 93% yield, 2.7:1 dr) via the KI-catalyzed oxidative

dimerization of 5f following the general procedure as pale yellow solid. m.p. 123-125℃; 1H NMR

(400 MHz, CDCl3): δ 7.77 (d, J = 7.6 Hz, 1.55H), 7.74 (t, J = 7.2 Hz, 0.85H), 7.58-7.50 (m, 2+1.78H),

7.45-7.39 (m, 8H), 7.23 (t, J = 7.6 Hz, 2H), 7.07 (d, J = 7.6 Hz, 0.79H), 6.84 (d, J = 7.2 Hz, 2H), 6.64

(t, J = 7.4 Hz, 2H), 6.51-6.45 (m, 2.74H), 6.31 (d, J = 8.0 Hz, 0.73H), 6.21 (d, J = 6.0 Hz, 0.63H),

5.06 (s, 2+0.66H), 3.54 (dd, J = 7.2 Hz, 4.4 Hz, 0.74H), 3.23 (dd, J = 6.8 Hz, 4.8 Hz, 2H), 2.99 (s,

6H), 2.90-2.71 (m, 2+2.94H), 1.92-1.76 (m, 4+0.69H), 1.47-1.42 (m, 0.82H); 13C NMR (100 MHz,

CDCl3): δ 151.54, 151.51, 140.08, 139.11, 132.85, 132.21, 129.57, 129.39, 129.28, 128.31, 127.57,

127.13, 127.05, 124.51, 123.32, 117.96, 117.45, 106.99, 106.67, 87.30, 85.42, 62.22, 60.41, 47.65,

47.38, 34.35, 32.58, 31.80, 31.57; IR (KBr) 3057, 2947, 1605, 1492, 1344, 1157, 1051, 741, 690 cm-


8,8'-dimethyl-1,1'-bis((4-nitrophenyl)sulfonyl)-2,2',3,3',8,8a,8',8'a-octahydro-1H,1'H-3a,3'a-

bipyrrolo[2,3-b]indole, 6g and 6g′:

33

Compound 6g and 6g′ was obtained (63.9 mg, 89% yield, 2.6:1 dr) via the KI-catalyzed oxidative

dimerization of 5g following the general procedure as a yellow solid. m.p. 127-131℃; 1H NMR (400

MHz, CDCl3): δ 8.35 (d, J = 8.8 Hz, 1.54H), 8.16 (d, J = 8.8 Hz, 4H), 7.99 (d, J = 8.8 Hz, 1.51H),

7.43 (d, J = 8.8 Hz, 4H), 7.35 (t, J = 7.6 Hz, 2H), 7.11 (t, J = 7.8 Hz, 0.83H), 6.75 (d, J = 7.2 Hz, 2H),

6.74-6.55 (m, 4+0.78H), 6.36-6.31 (m, 1.47H), 5.22 (s, 0.75H), 4.89 (s, 2H), 3.67 (dd, J = 7.2 Hz, 4.0

Hz, 0.81H), 3.27-3.22 (m, 2H), 3.04 (s, 6H), 2.91-2.77 (m, 2+0.98H), 2.62 (s, 2.19H), 2.13 (dd, J =

7.2 Hz, 4.8 Hz, 0.84H), 2.01-1.84 (m, 4+0.75H); 13C NMR (100 MHz, CDCl3): δ 151.57, 151.44,

150.06, 149.50, 145.90, 144.63, 130.19, 129.81, 128.17, 128.02, 127.02, 124.70, 124.52, 124.40,

123.61, 118.43, 118.34, 107.60, 107.29, 87.33, 86.03, 62.49, 59.99, 47.70, 47.67, 35.01, 32.79, 32.32,

31.76; IR (KBr) 3103, 3057, 2949, 1604, 1492, 1350, 1161, 1091, 740, 686 cm-1; HRMS (ESI) calcd

for [M+Na]+ C34H32N6NaO8S2, m/z: 739.1621, found: 739.1593.

8,8'-dimethyl-1,1'-bis(naphthalen-2-ylsulfonyl)-2,2',3,3',8,8a,8',8'a-octahydro-1H,1'H-3a,3'a-

bipyrrolo[2,3-b]indole, 6h and 6h′:

Compound 6h and 6h′ was obtained (65.2 mg, 90% yield, 2.7:1 dr) via the KI-catalyzed oxidative

dimerization of 5h following the general procedure as a white solid. m.p. 83-86℃; 1H NMR (400

MHz, CDCl3): δ 8.28 (s, 2+0.60H), 7.98 (d, J = 8.4 Hz, 0.77H), 7.93 (d, J = 8.0 Hz, 2+0.74H), 7.89

(d, J = 8.0 Hz, 2H), 7.83 (d, J = 8.4 Hz, 2H), 7.74 (d, J = 8.0 Hz, 0.74H), 7.68-7.56 (m, 4+2.66H),

7.26 (dd, J = 7.2 Hz, 1.6 Hz, 2H), 7.11 (dd, J = 7.6 Hz, 0.8 Hz, 2H), 7.05 (dd, J = 7.8 Hz, 1.2 Hz,

34

0.73H), 6.77 (d, J = 7.2 Hz, 2H), 6.48-6.41 (m, 4+0.79H), 6.30 (d, J = 8.0 Hz, 0.74H), 6.14 (d, J = 6.4

Hz, 0.69H), 5.21 (s, 0.71H), 5.12 (s, 2H), 3.46 (dd, J = 7.2 Hz, 4.4 Hz, 0.74H), 3.30 (dd, J = 4.8 Hz,

6.8Hz, 2H), 2.96 (s, 6H), 2.84-2.73 (m, 2+3.37H), 1.87-1.79 (m, 2H), 1.77-1.72 (m, 2H), 1.63-1.59

(m, 1.29H), 1.36-1.22 (m, 1.97H); 13C NMR (150 MHz, CDCl3): δ 151.47, 151.41, 136.63, 135.89,

134.70, 134.59, 132.02, 131.90, 129.93, 129.86, 129.55, 129.37, 129.35, 128.94, 128.87, 128.72,

128.50, 128.25, 128.01, 127.73, 127.70, 127.46, 127.36, 124.32, 123.29, 121.97, 117.66, 117.38,

106.74, 106.64, 87.22, 85.50, 62.14, 60.56, 47.58, 47.47, 34.32, 32.76, 31.80, 31.49; IR (KBr) 3057,

2948, 1605, 1340, 1156, 1077, 749, 657 cm-1; HRMS (ESI) calcd for [M+Na]+ C42H38N4NaO4S2, m/z:

749.2232, found: 749.2201.

8,8'-dimethyl-1,1'-bis(methylsulfonyl)-2,2',3,3',8,8a,8',8'a-octahydro-1H,1'H-3a,3'a-bipyrrolo[2,3-

b]indole, 6i and 6i′:

Compound 6i and 6i′ was obtained (38.5 mg, 77% yield, 2.0:1 dr) via the KI-catalyzed oxidative

dimerization of 5i following the general procedure as a white solid. m.p. 243-248℃; 1H NMR (400

MHz, d6-DMSO): δ 7.39 (d, J = 7.2 Hz, 2H), 7.22 (t, J = 7.6 Hz, 2H), 7.12 (d, J = 7.6 Hz, 0.99H),

6.71(t, J = 7.4 Hz, 2H), 6.63-6.57 (m, 2+0.95H), 6.53 (d, J = 8.0 Hz, 1.02H), 5.08 (s, 1.00H), 4.40 (s,

2H), 4.04 (s, 1.22H), 3.62-3.53 (m, 2+0.66H), 3.34 (s, 6H), 2.91 (s, 2.74H), 2.80 (s, 6H), 2.75- 2.53(m,

2+5.44H), 2.34-2.23 (m, 4+0.21H), 2.14 (s, 6H); 13C NMR (150 MHz, d6-DMSO): δ 157.15, 156.60,

134.97, 134.57, 134.45, 132.73, 130.78, 128.98, 123.10, 122.65, 112.76, 111.66, 91.21, 90.72, 67.40,

65.82, 53.17, 52.26, 43.39, 40.80, 39.39, 38.17, 37.64, 36.12; IR (KBr) 1602, 1493, 1328, 1150, 1085,

764, 601, 518 cm-1; HRMS (ESI) calcd for [M+Na]+ C24H30N4NaO4S2, m/z: 525.1606, found:

525.1589.

8,8'-dimethyl-1,1'-bis((trifluoromethyl)sulfonyl)-2,2',3,3',8,8a,8',8'a-octahydro-1H,1'H-3a,3'a-

bipyrrolo[2,3-b]indole, 6j and 6j′:

35

Compound 6j and 6j′ was obtained (52.3 mg, 80% yield, 2.7:1 dr) via the KI-catalyzed oxidative

dimerization of 5j following the general procedure as a white solid. m.p. 166-170℃; 1H NMR (400

MHz, CDCl3): δ 7.25 (t, J = 7.6 Hz, 2H), 7.19-7.14 (m, 2+0.76H), 6.81 (t, J = 7.4 Hz, 2H), 6.61 (t, J

= 7.2 Hz, 0.75H), 6.51 (d, J = 7.6 Hz, 2H), 6.39-6.32 (m, 1.28H), 5.27 (s, 0.66H), 4.84 (s, 2H), 3.89-

3.83 (m, 0.75H), 3.70 (dd, J = 7.2 Hz, 4.0 Hz, 2H), 3.16-3.08 (m, 0.83H), 3.03-2.97 (m, 2H), 2.93 (s,

6H), 2.67-2.59 (m, 2+2.18H), 2.39-2.35 (m, 1.43H), 2.31 (dd, J = 7.6 Hz, 4.4 Hz, 2H); 13C NMR (100

MHz, CDCl3): δ 150.98, 150.46, 130.47, 130.09, 127.30, 126.20, 124.80, 124.29, 123.56, 121.76,

121.58, 118.77, 118.54, 118.40, 118.37, 115.15, 107.10, 87.64, 86.91, 62.53, 61.14, 48.90, 48.45,

35.04, 33.12, 32.12, 31.75; 19F NMR (376 MHz, CDCl3): δ -73.52, -75.64; IR (KBr) 3057, 2956, 1605,

1343, 1147, 1078, 750, 626, 598 cm-1; HRMS (ESI) calcd for [M+Na]+ C24H24F6N4NaO4S2, m/z:

633.1041, found: 633.1015.

1,1'-bis(benzylsulfonyl)-8,8'-dimethyl-2,2',3,3',8,8a,8',8'a-octahydro-1H,1'H-3a,3'a-bipyrrolo[2,3-

b]indole, 6k and 6k′:

Compound 6k and 6k′ was obtained (58.5 mg, 89% yield, 1.5:1 dr) via the KI-catalyzed oxidative

dimerization of 5k following the general procedure as a white solid. m.p. 211-213℃; 1H NMR (600

MHz, CDCl3): δ 7.31-7.21 (m, 15.77H), 7.19 (d, J = 12.6 Hz, 2H), 7.16-7.13 (m, 5.55H), 6.68 (t, J =

7.5 Hz, 2H), 6.59-6.55 (m, 2+1.27H), 6.41 (d, J = 7.8 Hz, 1.36H), 5.17 (s, 0.85H), 4.85 (s, 2H), 4.19

(q, J = 13.2 Hz, 2.74H), 3.77 (q, J = 13.2 Hz, 2H), 3.53 (dd, J = 7.8 Hz, 4.2 Hz, 2H), 3.40 (t, J = 8.4

36

Hz, 1.34H), 3.01 (d, J = 13.2 Hz, 2H), 2.89 (s, 6H), 2.83-2.78 (m, 2H), 2.61-2.51 (m, 2+4.92H), 2.23-

2.16 (m, 2+1.50H), 2.10-2.07 (m, 1.35H); 13C NMR (150 MHz, CDCl3): δ 152.11, 151.84, 130.88,

130.72, 130.21, 129.55, 129.21, 128.86, 128.54, 128.52, 128.47, 128.41, 128.37, 127.13, 124.90,

123.82, 118.13, 117.59, 107.68, 106.80, 86.12, 85.91, 62.71, 61.03, 59.40, 56.40, 48.10, 47.50, 34.93,

33.64, 33.42, 31.28; IR (KBr) 3059, 2950, 1604, 1338,1150, 1075, 738, 624 cm-1; HRMS (ESI) calcd

for [M+Na]+ C36H38N4NaO4S2, m/z: 677.2232, found: 677.2207.

1,1'-(-8,8'-dimethyl-2,2',3,3',8,8a,8',8'a-octahydro-1H,1'H-[3a,3'a-bipyrrolo[2,3-b]indole]-1,1'-

diyl)bis(2,2,2-trifluoroethan-1-one), 6l and 6l′:

Compound 6l and 6l′ was obtained (40.5 mg, 75% yield, 2.9:1 dr) via the KI-catalyzed oxidative

dimerization of 5l following the general procedure as a colorless oil. 1H NMR (400 MHz, CDCl3): δ

7.19-7.13 (m, 2+0.85H), 7.10 (d, J = 7.2 Hz, 2H), 6.69 (t, J = 7.4 Hz, 2H), 6.60 (t, J = 7.4 Hz, 0.72H),

6.43-6.38 (m, 2+1.31H), 5.50 (s, 0.61H), 5.31 (s, 2H), 3.99-3.94 (m, 0.70H), 3.90-3.85 (m, 2 H), 3.26-

3.16 (m, 0.72H), 3.11 (td, J = 11.6 Hz, 5.2 Hz, 2H), 3.00 (s, 6H), 2.72(s, 1.84H), 2.50 (td, J = 12.4 Hz,

7.2 Hz, 2H), 2.38-2.25 (m, 2+1.59H); 13C NMR (150 MHz, CDCl3): δ 156.31, 156.27, 156.07, 156.03,

155.82, 155.78, 155.58, 155.54, 130.05, 129.87, 128.03, 127.21, 123.73, 123.58, 119.05, 118.99,

118.10, 117.91, 117.14, 117.08, 115.23, 115.17, 113.32, 113.26, 107.20, 106.62, 84.18, 83.59, 60.11,

59.21, 45.80, 34.60, 33.62, 33.33, 32.89; 19F NMR (376 MHz, CDCl3): δ -71.66, -71.67; IR (KBr)

3056, 2953, 1606, 1349,1143, 1060, 744, 639 cm-1; HRMS (ESI) calcd for [M+Na]+ C26H24F6N4NaO2,

m/z: 561.1701, found: 561.1691.

8,8'-dimethyl-2,2',3,3',8,8a,8',8'a-octahydro-3a,3'a-bifuro[2,3-b]indole, 6o and 6o′:

37

Compound 6n and 6n′ was obtained (32.8 mg, 94% yield, 3.4:1 dr) via the KI-catalyzed oxidative

dimerization of 5n following the general procedure as a colorless oil. Compound 6n and 6n′ has

already been characterized by Ren and co-workers,[3] the configurational assignments of 6n and 6nʹ

were confirmed by comparison of the NMRs.

1H NMR (400 MHz, CDCl3): δ 7.13-7.05 (m, 4+0.50H), 6.60 (t, J = 7.2 Hz, 2H), 6.53-6.51 (m, 0.70H),

6.33 (d, J = 7.6 Hz, 2H), 6.29 (d, J = 7.6 Hz, 0.57H), 5.22 (s, 2H), 5.11 (s, 0.58H), 4.02 (t, J = 8.0 Hz,

0.58H), 3.92 (t, J = 8.0 Hz, 2H), 3.46-3.40 (m, 0.58H), 3.37-3.30 (m, 2H), 2.92 (s, 6H), 2.72 (s, 1.75H),

2.48-2.39 (m, 2+0.57H), 2.23 (dd, J = 7.2 Hz, 4.8 Hz, 0.59H), 2.06 (dd, J = 12.0 Hz, 4.8 Hz, 2H); 13C

NMR (100 MHz, CDCl3): δ 151.88, 151.84, 130.46, 130.28, 128.69, 124.08, 123.86, 116.98, 116.94,

105.02, 104.95, 101.28, 100.72, 66.84, 66.76, 61.35, 60.93, 37.75, 36.76, 30.97, 30.62; IR (KBr) 3051,

2942, 1605, 1303, 1156, 1040, 744, 659 cm-1; HRMS (ESI) calcd for [M+Na]+ C22H24N2NaO2, m/z:

371.1735, found: 371.1738.

7,7'-dichloro-8,8'-dimethyl-1,1'-ditosyl-2,2',3,3',8,8a,8',8'a-octahydro-1H,1'H-3a,3'a-bipyrrolo[2,3-

b]indole, 8a and 8a′:

Compound 8a and 8a′ was obtained (48.5 mg, 68% yield, 2.1:1 dr) via the KI-catalyzed oxidative

dimerization of 7a following the general procedure as a white solid. m.p. 86-89℃; 1H NMR (400

MHz, CDCl3) δ 7.74 (d, J = 8.0 Hz, 0.86H), 7.62 (d, J = 8.4 Hz, 2H), 7.30-7.26 (m, 2+0.90H), 7.06

(dd, J = 8.0 Hz, 1.2 Hz, 1H), 7.03 (dd, J = 8.0 Hz, 1.2 Hz, 0.44H), 6.75 (dd, J = 7.6 Hz, 1.2 Hz, 1H),

38

6.59-6.52 (m, 1+0.44H), 6.18 (bs, 0.38H), 5.05 (s, 0.40H), 4.99 (s, 1H), 3.65-3.59 (m, 0.48H), 3.45-

3.39 (m, 1H), 3.32 (s, 3H), 2.90 (s, 1.09H), 2.77-2.69 (m, 1+0.46H), 2.42 (s, 3H), 2.41 (s, 1.33H),

2.12-1.93 (m, 2H), 1.82 (dd, J = 12.4 Hz, 4.8 Hz, 0.93H); 13C NMR (100 MHz, CDCl3): δ 147.87,

146.62, 143.50, 143.39, 136.83, 136.45, 132.89, 131.65, 131.34, 131.25, 129.86, 129.60, 127.29,

127.18, 123.01, 122.06, 120.29, 119.22, 116.57, 115.17, 88.52, 88.08, 62.52, 60.91, 46.86, 46.64,

37.09, 36.23, 34.53, 33.53, 21.49; IR (KBr) 3065, 2949, 1598, 1344, 1159, 1093, 733, 663 cm-1;

HRMS (ESI) calcd for [M+Na]+ C36H36Cl2N4NaO4S2, m/z: 745.1447, found: 745.1425.

7,7',8,8'-tetramethyl-1,1'-ditosyl-2,2',3,3',8,8a,8',8'a-octahydro-1H,1'H-3a,3'a-bipyrrolo[2,3-b]indole,

8b and 8b′:

Compound 8b and 8b′ was obtained (64.1 mg, 94% yield, 3.2:1 dr) via the KI-catalyzed oxidative

dimerization of 7b following the general procedure as a white solid. m.p. 105-108℃; 1H NMR (400

MHz, CDCl3): δ 7.73 (d, J = 8.4 Hz, 1.34H), 7.48 (d, J = 8.0 Hz, 4H), 7.26-7.21 (m, 4+1.60H), 6.90

(d, J = 7.2 Hz, 2H), 6.80 (d, J = 7.6 Hz, 0.64H), 6.76 (d, J = 7.2 Hz, 2H), 6.61 (t, J = 7.6 Hz, 2H), 6.52

(bs, 0.48H), 4.98 (bs, 0.62H), 4.86 (s, 2H), 3.64 (dd, J = 9.6 Hz, 7.6 Hz, 0.62H), 3.32 (dd, J = 10.8 Hz,

7.6 Hz, 2H), 3.20 (s, 6H), 2.79-2.71 (m, 2+1.14H), 2.41 (s, 6H), 2.39 (s, 2.04H), 2.31 (s, 6H), 2.27-

2.13 (m, 1.14H), 2.09-1.99 (m, 2+2.47H), 1.83 (dd, J = 12.0 Hz, 4.8 Hz, 2H); 13C NMR (150 MHz,

CDCl3): δ 149.73, 143.02, 142.86, 137.66, 136.90, 132.62, 131.91, 129.63, 129.29, 129.12, 127.21,

127.15, 122.59, 121.45, 120.02, 119.93, 118.94, 89.25, 89.07, 62.76, 60.54, 46.71, 46.52, 38.62, 37.24,

34.78, 33.34, 21.45, 21.40, 19.20, 18.57; IR (KBr) 3054, 2958, 1596, 1340, 1158, 1072, 737, 671 cm-


6,6'-difluoro-8,8'-dimethyl-1,1'-ditosyl-2,2',3,3',8,8a,8',8'a-octahydro-1H,1'H-3a,3'a-bipyrrolo[2,3-

b]indole, 8c and 8c′:

39

Compound 8c and 8c′ was obtained (57.1 mg, 83% yield, 2.8:1 dr) via the KI-catalyzed oxidative

dimerization of 7c following the general procedure as a colorless oil. 1H NMR (400 MHz, CDCl3): δ

7.61 (d, J = 8.0 Hz, 1.46H), 7.41-7.36 (m, 4+1.46H), 7.22 (d, J = 8.0 Hz, 4H), 6.66 (dd, J = 7.6 Hz,

5.2 Hz, 2H), 6.23-6.13 (m, 4+1.35H),6.02 (d, J = 10 Hz, 0.73H), 4.98 (s, 0.73H), 4.96 (s, 2H), 3.54

(dd, J = 12.0 Hz, 7.2 Hz, 0.73H), 3.35-3.30 (m, 2H), 2.96 (s, 6H), 2.91-2.74 (m, 2+2.97H), 2.47 (s,

2.07H), 2.44 (s, 6H), 1.80-1.66 (m, 4+0.92H), 1.37-1.30 (m, 0.81H); 13C NMR (150 MHz, CDCl3): δ

165.42, 165.40, 163.81, 163.78, 153.26, 153.18, 153.07, 152.99, 144.12, 143.31, 136.82, 135.99,

130.01, 129.93, 127.11, 126.96, 124.99, 124.92, 123.88, 123.81, 123.55, 122.90, 103.84, 103.69,

103.47, 103.31, 94.97, 94.80, 94.48, 94.30, 87.10, 85.51, 61.60, 60.09, 47.66, 47.63, 34.33, 32.59,

31.43, 31.33, 21.53, 21.46; 19F NMR (376 MHz, CDCl3): δ -111.89, -112.37; IR (KBr) 3061, 2950,

1614, 1345, 1158, 1093, 738, 692 cm-1; HRMS (ESI) calcd for [M+Na]+ C36H36F2N4NaO4S2, m/z:

713.2044, found: 713.2016.


b]indole, 8d and 8d′:

Compound 8d and 8d′ was obtained (50.3 mg, 70% yield, 2.8:1 dr) via the KI-catalyzed oxidative

dimerization of 7d following the general procedure as a colorless oil. 1H NMR (400 MHz, CDCl3): δ

7.43 (d, J = 8.4 Hz, 0.62H), 7.39-7.34 (m, 2+0.62H), 7.24 (d, J = 8.0 Hz, 2H), 6.62 (d, J = 8.4 Hz, 1H),

6.50-6.45 (m, 2+0.39H), 6.30 (d, J = 1.6 Hz, 0.32H), 6.16 (bs, 0.29H), 5.00 (s, 0.27H), 4.93(s, 1H),

40

3.54 (dd, J = 12.0 Hz, 7.2 Hz, 0.33H), 3.45-3.30 (m, 1H), 2.97(s, 3H), 2.88-2.74 (m, 1+1.26H), 2.47

(s, 0.90H), 2.45 (s, 3H), 1.75-1.68 (m, 2+0.39H), 1.40-1.31(m, 0.42H); 13C NMR (100 MHz, CDCl3):

δ 152.66, 152.44, 144.15, 143.33, 136.76, 135.83, 135.51, 135.35, 130.02, 129.94, 126.98, 126.87,

126.65, 126.02, 125.04, 123.89, 117.66, 117.20, 107.26, 106.75, 86.89, 85.27, 61.60, 59.96, 47.62,

34.30, 32.42, 31.43, 31.30, 21.56, 21.51. IR (KBr) 3056, 2924, 1600, 1345, 1159, 1092, 739, 660 cm-

1; HRMS (ESI) calcd for [M+Na]+ C36H36Cl2N4NaO4S2, m/z: 745.1447, found: 745.1421.


8e and 8e′:

Compound 8e and 8e′ was obtained (61.6 mg, 90% yield, 3.9:1 dr) via the KI-catalyzed oxidative

dimerization of 7e following the general procedure as a white solid. m.p. 188-195℃; 1H NMR (400

MHz, CDCl3): δ 7.61 (d, J = 8.0 Hz, 1.02H), 7.36-7.31 (m, 4+1.02H), 7.18 (d, J = 8.0 Hz, 4H), 6.70(d,

J = 7.6 Hz, 2H), 6.43 (d, J = 7.6 Hz, 2H), 6.32 (s, 2H), 6.29 (d, J = 7.6 Hz, 0.51H), 6.14-6.09 (m,

0.91H), 4.99 (s, 2H), 4.98 (s, 0.51H), 3.48 (dd, J = 12.0 Hz, 7.2 Hz, 0.51H), 3.19 (dd, J = 11.6 Hz, 7.2

Hz, 2H), 2.96 (s, 6H), 2.88-2.80 (m, 0.57H), 2.78-2.70 (m, 2+1.54H) , 2.45 (s, 1.55H), 2.42 (s, 6H),

2.37 (s, 6H), 2.24 (s, 1.53H), 1.85-1.77 (m, 2H), 1.74-1.67 (m, 2+0.56H), 1.38-1.29 (m, 1.09H); 13C

NMR (100 MHz, CDCl3): δ 151.82, 151.71, 143.74, 142.84, 139.27, 139.21, 137.11, 136.16, 129.86,

129.76, 127.16, 127.00, 125.63, 125.04, 124.29, 123.00, 118.49, 118.08, 107.86, 107.45, 87.56, 85.69,

61.86, 60.13, 47.60, 47.42, 34.32, 32.49, 31.60, 31.47, 21.81, 21.64, 21.50; IR (KBr) 3046, 2948,

1612, 1343, 1159, 1093, 740, 692 cm-1; HRMS (ESI) calcd for [M+Na]+ C38H42N4NaO4S2, m/z:

705.2545, found: 705.2516.

6,6'-dimethoxy-8,8'-dimethyl-1,1'-ditosyl-2,2',3,3',8,8a,8',8'a-octahydro-1H,1'H-3a,3'a-bipyrrolo[2,3-

b]indole, 8f and 8f′:

41

Compound 8f and 8f′ was obtained (79% yield, 2.8:1 dr) via the KI-catalyzed oxidative dimerization

of 7f following the general procedure as a white solid. m.p. 163-165℃; 1H NMR[7] (400 MHz, CDCl3):

δ 7.61 (d, J = 8.0 Hz, 0.30H), 7.37 (d, J = 8.0 Hz, 2H), 7.21 (d, J = 8.0 Hz, 2H), 6.71 (d, J = 10.4 Hz,

0.14H), 6.67 (d, J = 8.0 Hz, 0.93H), 6.13 (dd, J = 8.4 Hz, 2.4 Hz, 1H), 6.06 (d, J = 2.0 Hz, 1H), 6.01

(dd, J = 8.0 Hz, 1.6 Hz, 0.11H), 5.88 (d, J = 2.0 Hz, 0.11H), 5.00 (s, 1H), 4.96 (s, 0.11H), 3.85 (s, 3H),

3.74(s, 0.34H), 3.50 (dd, J = 12 Hz, 7.2 Hz, 0.12H), 3.23 (dd, J = 11.6 Hz, 6.8 Hz, 1H), 2.97 (s, 3H),

2.91-2.84 (m, 0.23H), 2.81-2.74 (m, 1.25H), 2.46 (s, 0.36H), 2.43 (s, 3H), 1.82-1.67 (m, 2H), 1.35-

1.29 (m, 0.27H); 13C NMR[7] (100 MHz, CD3CN): δ 162.91, 154.12, 145.81, 144.92, 138.20, 137.56,

131.63, 131.31, 128.27, 128.22, 126.24, 125.36, 121.44, 104.24, 103.63, 94.72, 94.35, 88.94, 87.31,

61.69, 56.36, 49.20, 49.02, 35.23, 33.63, 32.55, 21.99; IR (KBr) 2948, 1618, 1597, 1331, 1158, 1091,



b]indole, 8g and 8g′:

Compound 8g and 8g′ was obtained (79% yield, 2.9:1 dr) via the KI-catalyzed oxidative dimerization

of 7g following the general procedure as a colorless oil. 1H NMR[8] (400 MHz, CDCl3): δ 7.61 (d, J =

8.0 Hz, 2.58H), 7.39 (d, J = 8.0 Hz, 2.58H), 7.22-7.20 (m, 10H), 7.07 (dd, J = 8.4 Hz, 2.0 Hz, 1.29H),

6.71 (d, J = 2.0 Hz, 2H), 6.48 (d, J = 8.4 Hz, 2H), 6.26 (d, J = 8.4 Hz, 1.28H), 6.15 (bs, 1.28H), 5.00

(s, 2H), 4.95(s, 1.30H), 3.54 (dd, J = 12.0 Hz, 7.2 Hz, 1.29H), 3.23 (dd, J = 12.0 Hz, 6.8 Hz, 2H), 3.01

(s, 6H), 2.91-2.77 (m, 2+5.46H), 2.48 (s, 4.00H), 2.45 (s, 6H), 1.78-1.67 (m, 4+1.39H), 1.35-1.28 (m,

42

1.86H); 13C NMR[8] (100 MHz, CDCl3): δ 150.36, 150.06, 144.19, 143.52, 136.79, 135.48, 130.10,

130.06, 129.65, 129.60, 129.42, 129.18, 127.03, 126.92, 124.91, 123.43, 122.63, 122.07, 108.03,

107.33, 87.21, 85.34, 61.98, 59.90, 47.74, 47.44, 34.03, 32.30, 31.64, 31.55, 21.58; IR (KBr) 3059,

2925, 1599, 1340, 1159, 1092, 742, 661 cm-1; HRMS (ESI) calcd for [M+Na]+ C34H34Cl2N4NaO4S2,

m/z: 745.1453, found: 745.1421.


8h and 8h′:

Compound 8h and 8h′ was obtained (63.3 mg, 93% yield, 1.5:1 dr) via the KI-catalyzed oxidative

dimerization of 7h following the general procedure as a white solid. m.p. 219-223℃; 1H NMR (400

MHz, CDCl3): δ 7.61 (d, J = 8.0 Hz, 2.77H), 7.35 (d, J = 8.0 Hz, 2.87H), 7.32 (d, J = 8.0 Hz, 4H),

7.16 (d, J = 8.0 Hz, 4H), 7.02 (d, J = 8.0 Hz, 2H), 6.87 (d, J = 8.0 Hz, 1.35H), 6.61 (s, 2H), 6.41 (d, J

= 7.6 Hz, 2H), 6.20 (d, J = 7.6 Hz, 1.36H), 5.96 (s, 1.24H), 5.07 (s, 2H), 4.95 (s, 1.37H), 3.50 (dd, J =

12.0 Hz, 7.6 Hz, 1.37H), 3.19 (dd, J = 11.2 Hz, 6.8 Hz, 2H), 2.96 (s, 6H), 2.86 (td, J = 12.4 Hz, 4.8

Hz, 1.46H), 2.74 (td, J = 11.6 Hz, 4.8 Hz, 2H), 2.68 (s, 3.63H), 2.45 (s, 4.11H), 2.41 (s, 6H), 2.20 (s,

6H), 2.07 (s, 4.11H), 1.85-1.70 (m, 4+1.38H), 1.38-1.30 (m, 1.68H); 13C NMR (100 MHz, CDCl3): δ

149.65, 149.57, 143.73, 142.69, 137.11, 136.14, 129.85, 129.82, 129.50, 128.51, 127.90, 127.12,

127.00, 126.50, 126.44, 125.70, 124.13, 106.86, 106.35, 87.52, 85.71, 62.21, 60.14, 47.67, 47.48,

34.01, 32.37, 31.95, 31.69, 21.50, 21.46, 21.00, 20.63; IR (KBr) 3024, 2922, 1598, 1340, 1158, 1092,


5,5'-dimethoxy-8,8'-dimethyl-1,1'-ditosyl-2,2',3,3',8,8a,8',8'a-octahydro-1H,1'H-3a,3'a-bipyrrolo[2,3-

b]indole, 8i and 8i′:

43

Compound 8i and 8i′ was obtained (52.5 mg, 73% yield, 2.3:1 dr) via the KI-catalyzed oxidative

dimerization of 7i following the general procedure as a white solid. m.p. 199-203℃; 1H NMR (400

MHz, CDCl3): δ 7.62 (d, J = 8.4 Hz, 4H), 7.36 (d, J = 8.0 Hz, 4H), 7.27 (d, J = 8.0 Hz, 2.20H), 7.17

(d, J = 8.0 Hz, 1.89H), 6.81 (dd, J = 8.4 Hz, 2.4 Hz, 0.92H), 6.66 (dd, J = 8.4 Hz, 2.4 Hz, 2H), 6.44

(d, J = 8.4 Hz, 0.98H), 6.41 (d, J = 2.4 Hz, 0.93H), 6.25 (d, J = 8.4 Hz, 2H), 5.87 (s, 2H), 5.05 (s,

0.92H), 4.99 (s, 2H), 3.70 (s, 2.78H), 3.55 (s, 6H), 3.52-3.48 (m, 2H), 3.19 (dd, J = 11.6 Hz, 6.8 Hz,

0.95H), 2.95 (s, 2.77H), 2.84 (td, J = 12.4 Hz, 4.8 Hz, 2H), 2.77-2.69 (m, 6+0.94H), 2.46 (s, 6H), 2.42

(s, 2.78H), 1.84-1.69 (m, 2+2.02H), 1.39-1.25 (m, 2+1.14H); 13C NMR (150 MHz, CDCl3): δ 152.42,

152.39, 146.11, 143.85, 142.93, 137.00, 135.86, 129.90, 129.83, 129.64, 128.99, 127.11, 127.04,

114.55, 114.09, 111.99, 110.48, 107.50, 107.23, 87.98, 86.00, 62.13, 60.19, 56.02, 55.51, 47.62, 47.39,

34.24, 32.47, 32.39, 31.99, 21.54, 21.43; IR (KBr) 3057, 2949, 1597, 1344, 1158, 1092, 738, 659 cm-


4,4'-difluoro-8,8'-dimethyl-1,1'-ditosyl-2,2',3,3',8,8a,8',8'a-octahydro-1H,1'H-3a,3'a-bipyrrolo[2,3-

b]indole, 8j and 8j′:

Compound 8j and 8j′ was obtained (53.9 mg, 72% yield, 11.7:1 dr) via the KI-catalyzed oxidative

dimerization of 7j following the general procedure as a white solid. m.p. 215-218℃; 1H NMR (400

MHz, CDCl3): δ 7.28 (d, J = 8.4 Hz, 2H), 7.18-7.13 (m, 3H), 6.29-6.24 (m, 2H), 5.14 (s, 1H), 3.32

(dd, J = 12.0 Hz, 7.2 Hz, 2H), 3.30 (s, 3H), 2.88 (td, J = 11.6 Hz, 4.0 Hz, 1H), 2.42 (s, 3H), 2.26 (dd,

44

J = 12.4 Hz, 4.4 Hz, 1H), 1.59-1.50 (m, 1H); 13C NMR (100 MHz, CDCl3): δ 160.68, 158.25, 153.89,

153.80, 143.04, 135.81, 131.50, 131.40, 129.88, 126.94, 112.22, 112.06, 105.68, 105.45, 102.87,

102.85, 87.41, 87.39, 61.48, 48.30, 31.63, 31.22, 31.19, 21.53; IR (KBr) 3064, 2925, 1595, 1346, 1160,

1093, 743, 658 cm-1; 19F NMR (376 MHz, CDCl3): δ -116.10; HRMS (ESI) calcd for [M+Na]+

C36H36F2N4NaO4S2, m/z: 713.2038, found: 713.2020.


b]indole, 8k and 8k′:

Compound 8k and 8k′ was obtained (33.6 mg, 46% yield, >20:1 dr) via the KI-catalyzed oxidative

dimerization of 7k following the general procedure as a white solid. m.p. 198-202℃; 1H NMR (400

MHz, CDCl3): δ 7.19-7.15 (m, 3H), 7.11 (d, J = 8.0 Hz, 2H), 6.58 (d, J = 8.0 Hz, 1H), 6.45 (d, J = 8.0

Hz, 1H), 5.15 (s, 1H), 3.24 (dd, J = 11.6 Hz, 6.8 Hz, 1H), 3.02 (s, 3H), 2.87-2.74 (m, 2H), 2.41 (s, 3H),

1.62-1.53 (m, 1H); 13C NMR (100 MHz, CDCl3): δ 153.94, 142.97, 135.25, 131.71, 130.94, 129.87,

126.90, 122.90, 120.19, 105.79, 87.71, 63.19, 48.79, 31.71, 30.80, 21.50; IR (KBr) 3057, 2924, 1598,

1341, 1159, 1092, 743, 659 cm-1; HRMS (ESI) calcd for [M+Na]+ C36H36Cl2N4NaO4S2, m/z:

745.1453, found: 745.1420. Relative configuration of 8k is confirmed by HPLC (IA-3,

Hexane/Isopropanol 70/30, flow rate = 1.0 mL/min, 240 nm): tr1 =9.07 min; tr2 = 12.06 min.

45

5. Gram-scale of KI-catalyzed oxidative dimerization reactions

To a dry 100 mL reaction round-bottom flask were added tryptamine 7f (1.00 g, 2.79 mmol, 1.0 equiv),

KI (46.3 mg, 0.279 mmol, 0.1 equiv), TFE (28 mL) and NaBO3•4H2O (515 mg, 3.35 mmol, 1.2 equiv)

successively under argon atmosphere. The reaction system was stirred at room temperature until TLC

indicated that 7f disappeared (3h). The mixture was then quenched with saturated Na2S2O3 (aqueous)

and extracted with EtOAc (60 mL). The organic layer was washed with brine (15 mL), dried over

Na2SO4, filtered, and concentrated by vacuo. The residue was purified by flash column

chromatography (Toluene:EtOAc=200:1 to 60:1) to afford the dimeric products 8f and 8f′ (69% yield,

2.8:1 dr). The dr of 8f/8f' were determined by 1H NMR (Fig. S7).

Figure S7. The dr of 8f/8f' were determined by 1H NMR.

46

6. Additional description of the proposed mechanism

Scheme S1. Control experiments for the mechanistic study.

Scheme S2. The plausible mechanism of electrophilic (hypo)iodites “I+” pathway in our reaction

In our manuscript, we have already elucidated the mechanism (Scheme S2) of the catalytic

oxidative coupling/cyclizations reaction according to the control experiments (Scheme S1). Herein,

we will make an interpretation of the proposed stereo-control model (Scheme S2) based on our

experimental results and previous reports.

47

Scheme S3. The proposed stereo-control model

According to the proposed model (Scheme S3), the observed major product 6 or 8 could be

obtained from stereo-control model M-1, while the minor product 6′ or 8′ was generated via M-2.

Therefore, we suspect that the key to the diastereoselectivity of our reaction lies in the difference in

steric hindrance between the above two models. As shown in Scheme S3, the main steric hindrance of

M-1 and M-2 lie in Region 1(the steric hindrance between pyrrolidine “c” of the carbocation

intermediate and the aromatic ring region of another tryptamine) and Region 2 (the steric hindrance

between aromatic ring region of the carbocation intermediate and the aromatic ring region of another

tryptamine) respectively. Since the later behaved to be more hindered than the former, the reaction

gives the dimeric 6 or 8 rather than 6′ or 8′ as the major product.

Scheme S4. The observed diastereoselectivity in our reaction

Based on the stereo-control model, the substituents at C4 of tryptamine substrates might have

great influence on the stereoselectivity of the reaction. To further illustrate this model, the reaction of

5b, 7j and 7k were selected for discussion. As shown in Scheme S4, the less hindered C4-H substituted

tryptamine 5b gave a moderate diastereoselectivity (Scheme S4, a, 6b:6b′=2.9:1), while the hindered

C4-F substituted tryptamine 7j provided good diastereoselectivity (Scheme S4, b, 8j:8j′=11.7:1). In

48

additional, the more hindered C4-Cl substituted tryptamine 7k could react to give excellent

diastereoselectivity (Scheme S4, c, 8k:8k′>20:1). These experimental results could strongly support

our speculated stereo-control model.

49

7. Total synthesis of (+)-WIN 64821

Scheme S5. Asymmetric total synthesis of (+)-WIN 64821.

Methyl 1-allyl-Na-((4-nitrophenyl)sulfonyl)-L-tryptophanate, 10:

To a stirred solution of L-tryptophane 9 (4.08 g, 20 mmol, 1.0 equiv) in N,N-dimethylformamide (80

mL) under 0℃ was added NaH (60% dispersion in mineral oil, 2.40 g, 3.0 equiv) portionwise (0.80

g×3). The reaction mixture was reacted at room temperature for 2 h and cooled to 0℃ again. Allyl

bromide (1.73 mL, 1.0 equiv, dissolved in 40 mL DMF) was then added to the reaction system over 3

h, after which, the system was stirred at 0℃ for additional 3 h. Whereafter, H2O (150 mL), Na2CO3

(4.24 g, 2.0 equiv) and p-NsCl (4.43 g, 1.0 equiv) were added to the reaction system successively

under 0℃. After stirring under the same temperature for 3 h, p-NsCl (2.22 g, 0.5 equiv) was added

to the mixture and the system was reacted for additional 1 hour. Then the reaction mixture was diluted

50

with EtOAc (200 mL) and H2O (100 mL). The resulted mixture was extracted and the organic layer

was extracted again with 200 mL NaOH (aqueous, 0.5 M). All the aqueous layers were combined and

carefully acidified with HCl (concentrated, 12 M) to PH 1. Then, the resulted mixture was extracted

with EtOAc (400 mL×3). The combined organic layer were wash with 0.1 M HCl (aqueous, 300 mL

× 6), dried over Na2SO4 (anhydrous), then filtered and concentrated. The resulted solid was

recrystallized (CH2Cl2 and petrol ether as solvents) to give the crude intermediate 9-1(7.58 g).

To a solution of the crude intermediate 9-1 (4.00 g, 10 mmol, 1.0 equiv) obtained above in MeOH

(60 mL) was added TMSCl (2.66 mL, 2.1 equiv) dropwise over 2 min. The reaction system was

refluxed at 70℃ for 1 hour and then cooled to room temperature.[6] Subsequently, the result mixture

was concentrated and recrystallized (CH2Cl2 and petrol ether as solvents) to give compound 10 (4.07

g, 86% yield over 2 steps) as a green solid. [α]D25 -38 (c 0.50, CHCl3); m.p. 109-111℃; 1H NMR (400

MHz, CDCl3): δ 7.93 (d, J = 6.8 Hz, 2H), 7.65 (d, J = 7.6 Hz, 2H), 7.35 (d, J = 7.6 Hz, 1H), 7.14-7.10

(m, 2H), 7.01 (t, J = 6.4 Hz, 2H), 6.89 (s, 1H), 5.96-5.88 (m, 1H), 5.61 (s, 1H), 5.19 (d, J = 10.0 Hz,

1H), 5.06 (d, J = 16.8 Hz, 1H), 4.60 (d, J = 3.2 Hz, 2H), 4.27 (s, 1H), 3.67 (s, 3H), 3.28 (d, J = 11.2

Hz, 1H), 3.12-3.06 (m, 1H); 13C NMR (100 MHz, CDCl3): δ 171.76, 149.41, 144.91, 136.22, 133.01,

127.66, 127.26, 126.99, 123.48, 122.00, 119.45, 118.38, 117.66, 109.68, 107.82, 56.34, 52.79, 48.62,

28.95; IR (KBr) 3352, 3244, 1723, 1521, 1351, 1165, 1090, 738, 682 cm-1; HRMS (ESI) calcd for

[M+Na]+ C21H21N3NaO6S, m/z: 466.1049, found: 466.1040;

Dimethyl(2S,2'S,3aR,3'aR,8aS,8'aS)-8,8'-diallyl-1,1'-bis((4-nitrophenyl)sulfonyl)-

2,2',3,3',8,8a,8',8'a-octahydro-1H,1'H-[3a,3'a-bipyrrolo[2,3-b]indole]-2,2'-dicarboxylate, 11

dimethyl(2S,2'S,3aR,3'aS,8aR,8'aS)-8,8'-diallyl-1,1'-bis((4-nitrophenyl)sulfonyl)-2,2',3,3',8,8a,8',8'a-

octahydro-1H,1'H-[3a,3'a-bipyrrolo[2,3-b]indole]-2,2'-dicarboxylate, 11′:

51

To a 10 mL dry reaction tube were added compound 10 (1.33 g, 3 mmol, 1.0 equiv), KI (49.8 mg, 0.1

equiv), TFE (30 mL) and NaBO3•4H2O under argon atmosphere at room temperature. The mixture

was stirred (1500 rpm) for 16 h and then quenched with saturated Na2S2O3 (aqueous). Then TFE was

removed under vacuum, and the resulted mixture was extracted with EtOAc (200 mL), the organic

layer washed with brine (50 mL) and dried over anhydrous Na2SO4, concentrated under vacuum. The

crude residue was purified by column chromatography (petrol ether: EtOAc =10: 1 to 1: 1 as eluent)

to give the dimeric product 11 (578.4 mg) and 11′ (471.9 mg) with acceptable over-all results (79%

yield, 1.2:1 dr).

Compound 11: Yellow solid; [α]D26 54.5 (c 0.22, CHCl3/MeOH= 2:1); m.p. 123-126℃; 1H NMR (600

MHz, CDCl3): δ 8.16 (d, J = 8.4 Hz, 2H), 7.53 (d, J = 7.8 Hz, 2H), 7.25 (t, J = 7.8 Hz, 1H), 6.74 (d, J

= 7.2 Hz, 1H), 6.66 (d, J = 7.8 Hz, 1H), 6.54 (t, J = 7.2 Hz, 1H), 6.06-6.00 (m, 1H), 5.40 (d, J = 17.4

Hz, 1H), 5.33 (d, J = 10.8 Hz, 1H), 5.24 (s, 1H), 4.36 (dd, J = 16.8 Hz, 4.8 Hz, 1H), 4.10 (d, J = 8.4

Hz, 1H), 4.04 (dd, J = 17.4 Hz, 4.8 Hz, 1H), 3.10 (s, 3H), 2.53 (d, J = 12.6 Hz, 1H), 2.30 (dd, J = 10.5

Hz, 1H); 13C NMR (100 MHz, CDCl3): δ 169.81, 151.08, 149.78, 143.93, 134.09, 130.51, 128.17,

126.12, 125.37, 124.64, 118.03, 117.00, 108.85, 87.53, 61.04, 59.54, 52.43, 48.32, 36.41; IR (KBr)

3436, 1746, 1531, 1351, 1166, 739, 618 cm-1; HRMS (ESI) calcd for [M+Na]+ C42H40N6NaO12S2,

m/z: 927.2043, found: 907.2033.

Compound 11′: Yellow solid. [α]D25 48 (c 0.50, CHCl3); m.p. 110-114℃; 1H NMR (400 MHz, CDCl3):

δ 8.36 (d, J = 8.8 Hz, 2H), 8.22-8.16 (m, 3H), 7.11 (t, J = 8.0 Hz, 1H), 7.00 (t, J = 8.0 Hz, 1H), 6.82

(bs, 1H), 6.40 (d, J = 8.0 Hz, 1H), 6.34 (bs, 1H), 6.26 (d, J = 8.0 Hz, 1H), 5.87 (bs, 2H), 5.43 (s, 1H),

5.28-5.20 (m, 2H), 4.91-4.85 (m, 2H), 4.62 (d, J = 8.0 Hz, 1H), 4.15-4.01 (m, 2H), 3.86 (s, 3H), 3.30

(bs, 1H), 3.02 (s, 3H), 2.74 (d, J = 12.0 Hz, 1H), 2.61 (q, J = 7.2 Hz, 1H), 2.32 (t, J = 9.8 Hz, 2H); 13C

NMR (100 MHz, CDCl3): δ 171.01, 169.67, 150.53, 150.31, 150.28, 149.69, 146.85, 145.20, 134.12,

133.64, 129.99, 129.91, 128.87, 127.98, 126.08, 124.82, 124.45, 123.79, 123.46, 119.94, 117.86,

117.79, 117.16, 110.40, 107.59, 87.09, 86.08, 61.90, 61.37, 60.94, 60.27, 53.07, 52.34, 52.27, 47.94,

39.75, 38.38; IR (KBr) 3432, 1735, 1531, 1351, 1169, 741, 608 cm-1; HRMS (ESI) calcd for [M+Na]+

52

C42H40N6NaO12S2, m/z: 907.2043, found: 907.2055;

Dimethyl(2S,2'S,3aR,3'aR,8aS,8'aS)-8,8'-diallyl-2,2',3,3',8,8a,8',8'a-octahydro-1H,1'H-[3a,3'a-

bipyrrolo[2,3-b]indole]-2,2'-dicarboxylate, 12:

To a stirred solution of compound 11 (600 mg, 0.68 mmol, 1.0 equiv) in CH3CN (30 mL) under argon

atmosphere at 0℃ was added K2CO3. Methoxybenzenethiol (279 μL, 4.0 equiv, in 10 mL CH3CN)

was then added to the reaction mixture dropwise over 3 min. Subsequently, the resulted system was

stirred at room temperature until the complete conversion of 12 on TLC (about 2 days). The reaction

mixture was filtered through a pad of celite (washed by EtOAc and MeOH) and then concentrated

under vacuum. The crude residue was purified by column chromatography (petrol ether: EtOAc =2:1

to 1:2, then EtOAc, then CH2Cl2: MeOH= 100:1 to 50:1) to give compound 12 (205.7 mg, 59% yield)

as a light yellow oil. [α]D25 225 (c 1.00, CHCl3); 1H NMR (400 MHz, CDCl3): δ 7.15 (d, J = 7.2 Hz,

2H), 7.06 (t, J = 7.6 Hz, 2H), 6.60 (t, J = 7.6 Hz, 2H), 6.35 (d, J = 7.2 Hz, 2H), 6.02-5.92 (m, 2H),

5.33 (dd, J = 17.2 Hz, 1.6 Hz, 2H), 5.20 (dd, J = 10.0 Hz, 1.2 Hz, 2H), 4.68 (s, 2H), 3.94-3.82 (m, 4H),

3.78 (dd, J = 8.0 Hz, 2.0 Hz, 2H), 3.21 (s, 6H), 2.82-2.76 (m, 2H), 2.56 (dd, J = 12.4 Hz, 1.6 Hz, 2H),

2.41 (bs, 2H); 13C NMR (100 MHz, CDCl3): δ 174.14, 151.57, 134.70, 129.87, 129.02, 125.55, 116.86,

116.61, 106.30, 85.11, 60.31, 59.93, 51.66, 47.89, 38.86; IR (KBr) 3362, 2949, 1735, 1602, 1489,

1255, 748, 666 cm-1; HRMS (ESI) calcd for [M+Na]+ C30H35N4O4, m/z: 515.2658, found: 515.2637;

53

Dimethyl(2S,2'S,3aR,3'aR,8aS,8'aS)-2,2',3,3',8,8a,8',8'a-octahydro-1H,1'H-[3a,3'a-bipyrrolo[2,3-

b]indole]-2,2'-dicarboxylate, 13:

To a stirred solution of compound 12 (311.2 mg, 0.6 mmol, 1.0 equiv) in EtOH (12 mL) under argon

atmosphere were added DMBA (188.8 mg, 2.0 equiv) and Pd(PPh3)4 (69.9 mg, 0.1 equiv). The reaction

mixture was degassed with argon and then stirred at 40℃ for about 2 h. The reaction mixture was

filtered through a pad of silica gel (washed by CH2Cl2 :MeOH = 10:1) and then concentrated under

vacuum. The crude residue was purified by column chromatography (CH2Cl2: MeOH= 100:1 to 20:1)

to give compound 13 (222.7 mg, 85% yield) as a light yellow oil. Compound 13 has already been

characterized by Xia and co-workers,[4] and our experimental characterization data is consistent with

the literature.

[α]D26 117 (c 0.14, MeOH); 1H NMR (400 MHz, CDCl3): δ7.19 (d, J = 7.6 Hz, 2H), 7.07 (td, J = 8.0

Hz, 0.8 Hz, 2H), 6.72 (td, J = 7.2 Hz, 0.4 Hz, 2H), 6.59 (d, J = 7.6 Hz, 2H), 4.66 (s, 2H), 3.79 (dd, J

= 8.4 Hz, 2.4 Hz, 2H), 3.24 (s, 6H), 2.81 (dd, J = 12.8 Hz, 8.4 Hz, 2H), 2.58 (dd, J = 12.8 Hz, 2.4 Hz,

2H); 13C NMR (100 MHz, CDCl3): δ 173.89, 151.02, 129.46, 129.04, 125.87, 118.46, 109.83, 80.81,

61.84, 60.02, 51.77, 38.71; IR (KBr) 3428, 1638, 1483, 1244, 742, 601 cm-1; HRMS (ESI) calcd for

[M+Na]+ C24H26N4NaO4, m/z: 457.1852, found: 457.1859;

54

Dimethyl(2S,2'S,3aR,3'aR,8aR,8'aR)-1,1'-bis(((benzyloxy)carbonyl)-L-phenylalanyl)-

2,2',3,3',8,8a,8',8'a-octahydro-1H,1'H-[3a,3'a-bipyrrolo[2,3-b]indole]-2,2'-dicarboxylate, 14:

To a stirred solution of compound 13 (43.6 mg, 0.1 mmol) in N,N-Dimethylformamide (1.5 mL) under

argon atmosphere was added Cbz-L-phenylalanine (89.8 mg, 3.0 equiv). The system was cooled to 0℃

and Et3N (48.6μL, 3.5 equiv), HATU (114.0 mg, 3.0 equiv) were added successively. The reaction

mixture was then stirred at room temperature for 14 h. 3 mL LiCl (aqueous, 5%) was subsequent added

to the system, the resulted solution was extracted with EtOAc (30 mL×3). The combined organic layers

were washed with 40 mL LiCl (aqueous, 5%) and then dried over anhydrous Na2SO4, concentrated

under vacuum. The crude residue was purified by column chromatography (petrol ether: EtOAc =10:

1 to 2: 1 as eluent) to give 14 (89.9 mg, 90% yield) as a white solid. Compound 13 has already been

characterized by Xia and co-workers,[4] and our experimental characterization data is consistent with

the literature.

m.p. 115-118℃; [α]D25 221 (c 0.38, CHCl3); 1H NMR (600 MHz, CDCl3): δ 7.45-7.38 (m, 6H), 7.32-

7.28 (m, 12H), 7.19 (d, J = 7.2 Hz, 4H), 7.05 (t, J = 7.5 Hz, 2H), 6.77 (d, J = 7.2 Hz, 2H), 6.62 (t, J =

7.2 Hz, 2H), 6.55 (d, J = 7.8 Hz, 2H), 5.89 (d, J = 9.6 Hz, 2H), 5.09-5.04 (m, 4H), 4.87 (s, 2H), 4.40-

4.36 (m, 2H), 3.55 (d, J = 9.6 Hz, 2H), 3.14 (dd, J = 12.6 Hz, 4.2 Hz, 2H), 2.94 (s, 6H), 2.88 (t, J =

11.4 Hz, 2H), 2.06 (d, J = 13.2 Hz, 2H), 1.90-1.86 (m, 2H); 13C NMR (150 MHz, CDCl3): δ 171.66,

169.95, 154.94, 150.85, 136.30, 135.51, 129.63, 129.14, 128.98, 128.35, 127.93, 127.58, 126.71,

125.46, 117.95, 109.53, 79.93, 66.68, 59.50, 58.44, 53.69, 52.21, 41.14, 34.73; IR (KBr) 3409, 3325,

2925, 1719, 1638, 1449, 1055, 757 cm-1; HRMS (ESI) calcd for [M+Na]+ C58H56N6NaO10, m/z:

1019.3956, found: 1019.3996;

55

To a solution of compound 14 (89.9 mg, 0.09 mmol, 1.0 equiv) in MeOH (6 mL) was added Pd(OH)2/C

(30 mg). The reaction system was degassed with H2 and then stirred at H2 atmosphere (1 atm) for

about 1.5 h. Subsequently, the reaction mixture was subject to a pad of silica gel (washed with

CH2Cl2:MeOH = 5:1) and then concentrated under vacuum. The resulted crude residue was used to

the next step without further purification.

To the crude product above were added CH2Cl2 (3 mL) and morpholine (0.3 mL). The resulted solution

was stirred at room temperature for 2 h, and then quenched with HCl (1 M, 10 mL), extracted with

EtOAc (30 mL×3). The combine organic layers were washed with brine, dried over anhydrous Na2SO4,

concentrated under vacuum. The crude residue was purified by column chromatography (CH2Cl2:

Acetone =20: 1 to 3: 1 as eluent) to give (+)-WIN 64821 (42.1 mg, 75% yield over 2 steps) as a white

solid. (+)-WIN 64821 has already been characterized by Xia and co-workers,[4] and our experimental

characterization data is consistent with the literature.

m.p. 175-178℃; [α]D26 228 (c 0.72, MeOH); 1H NMR (400 MHz, CD3CN): δ 7.36 (d, J = 7.6 Hz,

2H), 7.15-7.11 (m, 12H), 6.75 (t, J = 7.6 Hz, 2H), 6.69 (d, J = 7.6 Hz, 2H), 6.04 (s, 2H), 5.90 (s, 2H),

4.91 (s, 2H), 4.17 (t, J = 5.4 Hz, 2H), 4.08 (t, J = 8.6 Hz, 2H), 3.15-3.07 (m, 2H), 3.04-2.97 (m, 4H),

2.53(dd, J = 14.4 Hz, 8.0 Hz, 2H); 13C NMR (100 MHz, CD3CN): δ 169.78, 168.88, 149.98, 137.34,

131.39, 130.29, 130.09, 129.32, 127.60, 126.04, 120.18, 110.40, 80.53, 60.94, 57.73, 56.95, 36.76,

36.07; IR (KBr) 3405, 1655, 1459, 1313, 1257, 1096, 702, 603 cm-1; HRMS (ESI) calcd for [M+Na]+

C40H36N6NaO4, m/z: 687.2696, found: 687.2675.

56

8. Crystals of 6b

CCDC: 1940250

Datablock: yangJs_0320

Bond precision: C-C = 0.0055 A Wavelength=0.71000

Cell: a=16.4849(8) b=10.3567(3) c=19.7384(8)

alpha=90 beta=98.596(5) gamma=90

Temperature: 293 K

Calculated Reported

Volume 3332.1(2) 3332.0(2)

Space group P 21/c P 1 21/c 1

Hall group -P 2ybc -P 2ybc

Moiety formula C36 H38 N4 O4 S2 C36 H38 N4 O4 S2

57

Sum formula C36 H38 N4 O4 S2 C38 H38 N2 O4 S2

Mr 654.82 650.82

Dx,g cm-3 1.305 1.297

Z 4 4

Mu (mm-1) 0.205 0.203

F000 1384.0 1376.0

F000' 1385.52

h,k,lmax 20,12,24 20,12,24

Nref 6563 6550

Tmin,Tmax 0.964,0.976 0.658,1.000

Tmin' 0.964

Correction method= # Reported T Limits: Tmin=0.658 Tmax=1.000 AbsCorr = MULTI-

SCAN

Data completeness= 0.998 Theta(max)= 25.992

R(reflections)= 0.0579( 3838) wR2(reflections)= 0.1617( 6550)

S = 0.940 Npar= 419

58

9. References

[1] H. Zhang, R. B. Hu, N. Liu, S. X. Li, S. D. Yang, Org. Lett. 2016, 18, 28.

[2] R. S. Klausen, C. R. Kennedy, A. M. Hyde, E. N. Jacobsen, J. Am. Chem. Soc. 2017, 139, 12299.

[3] H. Ren, J. -R. Song, Z. -Y. Li, W. -D. Pan, Org. Lett. 2019, 21, 6774-6778.

[4] K. Liang, X. Deng, X. Tong, D. Li, M. Ding, A. Zhou, C. Xia, Org. Lett. 2015, 17, 206-209.

[5] Y. -X. Li, H. -X. Wang, S. Ali, X. -F. Xia, Y. -M. Liang, Chem. Commun. 2012, 48, 2343-2345.

[6] J. Li, Y. Sha, Molecules 2008, 13, 1111-1119.

[7] Note: NMR spectra of 8f/8f' here were obtained from the gram-scale dimerization (section 6 of SI)

of 7f (selective collection of the products after column chromatography).

[8] Note: NMR spectra (8g/8g') here were obtained from selective collection of the products after

column chromatography (trying to separate the 8g and 8g', but failed), The repeatability of the

reaction was confirmed by at least three parallel experiments.

10. Copies of NMR

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

f1 (ppm)

3.00

2.00

2.00

1.00

1.001.003.001.001.002.00

1.00

0.000

2.309

2.8102.8272.8443.1503.1673.1833.199

4.8144.8294.844

6.8216.8276.9817.0007.0197.1007.1207.1327.2477.2677.3417.3607.5717.591

8.236

59

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

240

f1 (ppm)

21.30

25.24

43.01

76.6877.0077.32

111.12111.31118.22119.10121.81122.65126.71126.75129.48136.20136.35

143.20

60

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

3.00

2.00

2.00

3.00

1.00

1.00

1.024.211.022.00

0.000

2.314

2.8252.8422.8593.1613.1783.1943.2113.586

4.9284.9434.958

6.7286.9857.0027.0217.1097.1307.1577.1747.1887.2097.3527.3727.5987.619

61

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

240

f1 (ppm)

21.23

25.15

32.28

43.15

76.6877.0077.32

109.11109.86

118.38118.64121.43126.75127.08127.18129.35136.64136.85

142.95

62

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

2.99

3.01

1.98

1.99

2.01

0.96

0.971.003.041.011.032.00

-0.000

1.3641.3821.401

2.357

2.8722.8882.9053.2093.2243.239

4.0204.0384.0564.074

4.8144.8324.845

6.8507.0037.0207.0407.1607.1807.1927.2627.2837.3787.3987.6237.644

63

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

240

f1 (ppm)

15.29

21.37

25.37

40.6543.18

76.6877.0077.32

109.30110.03

118.62118.79121.50125.37126.90127.41129.48136.04136.77

143.10

64

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

3.02

2.01

2.01

1.00

2.01

1.001.00

0.99

0.991.003.001.321.011.92

0.000

2.3952.8982.9142.9313.2383.2543.2703.2864.4494.4664.4694.6404.6444.6494.6544.6584.6625.0605.0645.0675.0715.1025.1065.1105.1145.1805.1835.1875.1915.2055.2095.2125.2165.9095.9235.9365.9495.9525.9625.9665.9785.9916.0056.8487.0247.0267.0447.0617.0647.1707.1737.1877.1907.1947.2057.2087.2117.2257.2517.2667.2877.3877.4077.6277.647

65

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

240

f1 (ppm)

21.38

25.35

43.14

48.57

76.6877.0077.32

109.63110.43117.25118.61119.01121.69126.10126.91127.48129.49133.30136.43136.78143.11

66

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

3.003.00

2.00

2.00

0.991.011.042.001.04

3.01

1.00

0.000

2.2782.422

3.1743.1873.1943.2013.214

4.0114.0244.0314.0374.051

7.0477.0527.1267.1297.1467.1637.1667.1797.1827.1997.2017.2167.2197.2507.2987.3187.3427.3627.7617.7727.7777.7938.056

67

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

f1 (ppm)

21.5824.8925.98

47.84

76.6877.0077.32

111.15112.18118.93119.59122.14122.45127.26127.47129.84136.20136.73

144.85

170.27

68

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

2.01

2.01

3.00

1.01

1.001.001.011.323.051.142.00

0.000

2.9022.9192.9353.2513.2673.2833.299

3.719

4.4814.4964.510

6.8047.0327.0497.0697.1957.2157.2337.2497.2697.2907.3857.4057.4157.4347.4547.5137.5317.5507.7477.766

69

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

240

f1 (ppm)

25.40

32.62

43.19

76.6877.0077.32

109.35109.84

118.55119.03121.85126.94127.26127.30128.98132.47137.13139.85

70

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

2.07

2.03

3.01

1.00

0.991.022.021.01

2.00

2.00

0.000

2.9112.9272.9423.3183.3343.3493.3643.713

4.5864.5994.613

6.8136.9827.0017.0187.1637.1837.2017.2117.2317.2537.2967.3167.7377.759

8.0688.089

71

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

240

f1 (ppm)

25.38

32.62

43.24

76.6877.0077.32

109.44

118.36119.16122.08123.86127.01127.37127.85

137.18

145.35

149.68

72

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

1.97

1.99

2.97

1.00

1.001.002.081.00

2.031.003.00

1.00

-0.000

2.8692.8862.903

3.2723.2883.3043.3213.601

4.7494.7644.7796.7256.9286.9466.9657.1277.1477.1647.1867.2067.2167.3147.3337.5377.5547.5757.5807.5837.6027.6187.6657.6697.6877.6917.7957.8167.8367.854

8.330

73

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

240

f1 (ppm)

25.36

32.44

43.30

76.6877.0077.32

109.24109.86118.45118.90121.73122.20127.21127.25127.36127.80128.20128.59129.15129.26132.05134.65136.70137.03

74

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

f1 (ppm)

3.01

2.00

2.01

3.01

1.00

1.001.001.321.00

1.00

-0.000

2.8253.0223.0383.055

3.4123.4283.4443.4603.760

4.2874.3034.319

6.9377.1057.1077.1247.1427.1447.2287.2307.2487.2527.2667.2687.3067.3267.5637.583

75

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

240

f1 (ppm)

25.99

32.68

40.1243.37

76.6877.0077.32

109.46109.97

118.58119.14121.96127.30127.41

137.21

76

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

f1 (ppm)

2.08

2.113.170.91

0.971.011.240.991.00

0.000

3.0423.0593.075

3.5863.6023.6183.7763.882

6.9377.1247.1277.1427.1447.1617.1647.2517.2687.2717.2867.2887.3247.3447.5407.560

77

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

240

f1 (ppm)

26.33

32.74

44.51

76.6977.0177.33

109.03109.60118.06118.46119.40121.25122.20127.15127.45

137.33

78

-210

-200

-190

-180

-170

-160

-150

-140

-130

-120

-110

-100

-90

-80

-70

-60

-50

-40

-30

-20

-10

010

f1 (ppm)

-77.442

79

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

2.01

2.01

3.00

3.01

1.00

1.024.303.001.00

0.000

2.9252.9412.9573.2633.2793.2943.3103.706

4.1144.1294.147

6.8247.1077.1097.1267.1447.1467.1757.1877.1947.2027.2177.2237.2287.2307.2427.2497.2517.2587.2657.2797.2927.3127.5217.540

80

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

240

f1 (ppm)

26.05

32.59

43.65

58.34

76.6877.0077.32

109.43109.94

118.63119.12121.95127.31127.36128.52128.67129.33130.46137.27

81

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

f1 (ppm)

2.01

2.033.04

1.00

1.001.011.131.00

1.00

0.000

3.0063.0233.040

3.6303.6463.6623.6783.752

6.4316.8847.1137.1167.1337.1517.1537.2357.2567.2587.2737.2757.3097.3297.5587.578

82

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

f1 (ppm)

24.59

32.63

40.28

76.6877.0077.32

109.46110.15114.38117.24118.51119.19120.10122.00126.92127.38

137.20

156.54156.90157.27157.64

83

-210

-200

-190

-180

-170

-160

-150

-140

-130

-120

-110

-100

-90

-80

-70

-60

-50

-40

-30

-20

-10

010

f1 (ppm)

-75.974

84

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

f1 (ppm)

2.00

2.003.033.07

0.85

1.001.001.121.00

1.00

0.000

2.9252.9422.959

3.4643.4803.4973.5133.6473.729

4.791

6.8647.0887.0907.1087.1257.1277.2077.2087.2277.2297.2447.2467.2797.2997.5737.592

85

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

240

f1 (ppm)

25.62

32.56

41.35

51.92

76.6877.0077.32

109.22111.27

118.77118.85121.67126.78127.62

137.05

156.98

86

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

1.00

2.09

3.082.07

1.001.001.221.00

1.00

-0.000

1.528

3.0023.0173.033

3.7533.8683.8833.899

6.9357.0957.0987.1127.1157.1327.1357.2167.2187.2367.2397.2447.2547.2567.2947.3157.5957.614

87

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

240

f1 (ppm)

28.64

32.60

62.74

76.6877.0077.32

109.26110.66

118.88118.91121.73127.27127.84

137.18

88

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

f1 (ppm)

0.97

2.01

2.00

4.99

0.94

0.981.080.94

0.94

0.000

1.439

1.9291.9451.9631.9821.998

2.8182.8372.855

3.6903.7063.722

6.8387.0747.0767.0947.1117.1137.1937.1957.2137.2157.2307.2687.2887.5847.604

89

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

f1 (ppm)

21.23

32.5233.13

62.61

76.6877.0077.32

109.11114.37118.56118.93121.47126.13127.79

137.02

90

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

2.092.096.02

2.062.06

1.92

1.94

2.002.002.015.994.60

-0.000

2.0242.0362.0552.0672.0782.2182.2382.2442.2482.2652.2692.2752.2952.4092.9572.9722.9832.9983.0093.0243.1113.1153.1323.1363.1413.1583.161

4.680

4.946

6.5746.5766.5936.5946.6136.6766.6956.8876.9067.0957.1167.1367.1387.1557.1587.2537.2607.273

91

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

240

f1 (ppm)

21.52

32.31

46.84

61.33

76.6877.0077.3281.26

110.37

119.06124.49126.53127.37129.34129.83135.41

142.97

150.07

92

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

1.98

2.00

5.81

1.99

2.00

1.66

1.96

1.753.96

1.96

3.93

3.89

-0.000

1.5431.5641.5731.5931.6021.6221.9771.9902.0082.0212.4572.9672.9812.9953.0093.0223.0373.3073.3273.3343.354

4.565

5.090

6.4286.4446.5166.5356.5526.5717.0437.0467.0627.0647.0817.0847.2597.3167.3367.6077.628

93

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

240

f1 (ppm)

21.58

33.84

47.13

62.50

76.6877.0077.3280.01

109.77

119.00123.66126.83127.87129.20129.86

136.35

143.85

149.78

94

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

0.77

4.62

5.872.13

3.990.805.972.00

0.70

0.681.87

0.600.712.671.932.010.775.965.51

1.43

1.3221.3411.3521.3711.3831.4011.7211.7331.7461.7581.7761.7881.8051.8221.8341.8521.8641.8822.4202.4602.6982.7102.7272.7372.7562.7692.8072.8192.8382.8502.8682.8802.9723.1973.2153.2263.2433.4853.5033.5153.5334.9895.0396.1756.1916.2956.3146.4416.4606.4726.4926.6116.6296.6486.8356.8537.0497.0687.0887.1987.2187.2307.2567.3427.3627.3757.6077.628

95

-20

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

f1 (ppm)

21.4921.53

31.4731.5732.5834.23

47.4447.67

60.4062.06

76.6877.0077.32

85.3287.21

106.57106.92117.32117.69123.24124.54126.99127.13127.69128.27129.33129.48129.93136.05136.99

142.94143.86

151.49151.60

96

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

3.35

6.00

1.39

5.37

5.813.97

2.001.39

3.293.251.412.23

3.19

2.211.252.112.06

2.001.232.074.282.904.212.87

-0.0000.9151.2351.2521.2701.4521.4641.7351.7471.7651.7771.8051.8221.8351.8521.8651.8822.4242.4452.7132.7252.7432.7552.7722.7842.8192.8312.8492.8622.8802.8923.2293.2463.2583.2753.3803.3983.4163.4343.4523.4773.4953.5063.5243.5433.5613.5793.5973.6155.2906.2156.2366.2666.2856.3106.3306.3926.4106.4286.4516.4706.5596.5776.5966.8436.8606.8617.0187.0207.0387.0587.1317.1337.1517.1697.1717.2307.2507.2567.3427.3627.4457.4657.6667.686

97

-20

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

f1 (ppm)

11.8912.70

21.51

33.3035.1238.2938.84

47.1847.31

60.9062.05

76.6877.0077.3283.3685.64

105.67106.32116.62116.95123.67124.80127.10127.26127.52128.14129.13129.26129.88129.92136.35137.30

143.08143.73

150.28150.46

98

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

f1 (ppm)

1.36

5.21

5.963.84

2.031.40

2.021.361.362.061.262.05

11.98

2.17

1.571.452.172.092.001.522.314.102.974.082.98

-0.0001.3171.6251.7361.7481.7661.7771.8021.8191.8311.8491.8611.8792.4172.4542.7202.7322.7502.7622.7792.7912.8352.8472.8652.8772.8962.9073.2343.2523.2643.2813.4693.4873.7263.7653.8653.8793.9073.9214.1254.2834.2954.3254.3375.0655.1885.2145.2585.2945.8445.8575.8705.8835.8985.9135.9265.9396.3226.3416.4566.5146.5346.5966.6156.6336.8386.8567.0197.0387.0577.1147.1337.1527.2117.2317.2557.3407.3567.4177.4367.612

99

-20

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

f1 (ppm)

21.54

33.1435.03

47.3147.4148.10

60.8262.13

76.6877.0077.3284.2886.72107.04107.95116.37117.32117.70123.35124.68127.05127.20127.70128.14129.12129.18129.94130.01133.96134.59136.00136.98143.19143.96150.68150.85

100

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

0.82

4.69

2.432.370.876.182.00

0.74

2.66

0.630.732.742.042.000.792.288.013.780.851.55

0.0001.2531.4201.4371.4481.4671.7671.7831.7961.8131.8261.8521.8641.8811.8931.9112.7172.7332.7502.7632.7792.7922.8042.8192.8322.8502.8622.8802.8922.9853.2063.2233.2353.2523.5183.5363.5473.565

5.0626.2006.2156.2976.3176.4576.4766.4896.5096.6256.6436.6626.8346.8527.0557.0747.0937.2067.2257.2447.2567.3907.4107.4297.4507.5027.5197.5377.5567.5757.6207.6387.6567.7577.776

101

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

240

f1 (ppm)

31.5731.8032.5834.35

47.3847.65

60.4162.22

76.6877.0077.32

85.4287.30

106.67106.99117.45117.96123.32124.51127.05127.13127.57128.31129.28129.39129.57132.21132.85139.11140.08

151.51151.54

102

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

4.75

0.84

2.192.986.002.08

0.81

1.93

0.75

1.471.183.522.01

0.832.043.88

1.513.871.54

1.8491.8651.8781.9021.9191.9421.9541.9721.9842.0032.1102.1222.1402.1522.6192.7792.7962.8082.8222.8362.8502.8632.8752.8932.9063.0423.2223.2283.2353.2413.2543.2683.6473.6653.6753.693

4.893

5.219

6.3096.3296.3566.5506.5696.5806.5986.6176.6376.7366.7547.0957.1147.1347.2627.3337.3527.3717.4177.4397.9757.9978.1458.1678.3408.362

103

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

240

f1 (ppm)

31.7632.3232.7935.01

47.6747.70

59.9962.49

76.6877.0077.32

86.0387.33

107.29107.60118.34118.43123.61124.40124.52124.70127.02128.02128.17129.81130.19144.63145.90149.50150.06151.44151.57

104

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

1.89

1.252.002.01

5.37

6.01

2.00

0.74

2.000.71

0.690.744.79

1.99

0.732.052.02

6.660.742.002.002.740.772.60

-0.0001.2461.2581.2991.3111.3291.5901.6011.6191.6321.7241.7361.7541.7661.7911.8091.8211.8381.8501.8682.7312.7482.7592.7722.7892.7962.8012.8082.9623.2773.2943.3063.3233.4563.4675.1185.2106.2916.3116.4156.4276.4416.4476.4586.4766.7646.7827.0317.0337.0507.0527.0697.0727.0877.0897.1087.1257.1277.2427.2477.2517.2697.2737.5767.5947.6107.6147.6187.6227.6397.6427.6507.6557.6597.6727.6767.7327.7527.8237.8447.8787.8987.9157.9357.9717.9928.275

105

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

f1 (ppm)

31.4931.8032.7634.32

47.4747.58

60.5662.14

76.7977.0077.21

85.5087.22

106.64106.74117.38117.66121.97123.29124.32127.36127.46127.70127.73128.01128.25128.50128.72128.87128.94129.35129.37129.55129.86129.93131.90132.02134.59134.70135.89136.63151.41151.47

106

0.51.0

1.52.0

2.53.0

3.54.0

4.55.0

5.56.0

6.57.0

7.58.0

8.59.0

9.510.0

f1 (ppm)

6.22

4.21

7.446.132.74

5.53

2.66

1.22

2.00

1.00

1.022.952.11

0.992.042.14

2.1392.2332.2472.2972.3062.3262.3352.4962.5002.5032.5312.5492.5612.5792.5922.6232.6322.6512.6622.6812.6932.7062.7342.7492.7972.9063.3393.5373.5533.5663.5823.6003.618

4.041

4.404

5.076

6.5156.5356.5726.6096.6296.6936.7116.7307.1037.1247.1447.1977.2167.2357.3817.399

107

-100

1020

3040

5060

7080

90100

110120

130140

150160

170180

190200

210f1 (ppm

)

36.1237.6438.1739.3940.8043.3944.3344.4744.6144.7444.8845.0245.1645.2852.2653.17

65.8267.40

90.7291.21

111.66112.76

122.65123.10128.98130.78132.73134.45134.57134.97

156.60157.15

108

-1.0-0.5

0.00.5

1.01.5

2.02.5

3.03.5

4.04.5

5.05.5

6.06.5

7.07.5

8.08.5

9.0f1 (ppm

)2.021.434.18

6.272.230.83

2.000.75

1.91

0.66

1.282.010.752.00

2.762.17

0.000

2.2892.3002.3192.3302.3512.3672.3802.3902.5912.6092.6222.6402.6512.6702.9302.9722.9933.0213.0833.1003.1253.1523.6813.6993.7093.7273.8383.8473.8563.8683.882

4.837

5.272

6.3206.3856.4046.5026.5216.5896.6076.6256.7916.8106.8287.1437.1697.1887.2327.2517.270

109

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

240

f1 (ppm)

31.7532.1233.1235.04

48.4548.90

61.1462.53

76.6877.0077.32

86.9187.64

107.10

115.15118.37118.40118.54118.77121.58121.76123.56124.29124.80126.20127.30130.09130.47150.46150.98

110

-210

-200

-190

-180

-170

-160

-150

-140

-130

-120

-110

-100

-90

-80

-70

-60

-50

-40

-30

-20

-10

010

f1 (ppm)

-75.639-73.517

111

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

f1 (ppm)

1.353.50

6.92

2.096.002.00

1.342.001.94

2.74

1.90

0.85

1.363.272.02

5.552.1915.77

0.0002.0712.0792.0912.0992.1652.1842.1982.2052.2182.2262.5182.5252.5352.5432.5562.5702.5772.5902.6102.7872.7942.8072.8142.8272.8853.0023.0243.3853.4003.4143.5163.5283.5353.5483.7563.7784.1614.1844.2064.228

4.850

5.174

6.3996.4126.5406.5536.5886.6646.6766.6897.1307.1427.1577.1837.1957.2107.2237.2307.2417.2557.2727.2857.296

112

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

f1 (ppm)

31.2833.4233.6434.93

47.5048.10

56.4059.4061.0362.71

76.7977.0077.21

85.9186.12

106.80107.68

117.59118.13123.82124.90127.13128.37128.41128.47128.52128.54128.86129.21129.55130.21130.72130.88151.84152.11

113

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

3.592.081.84

6.332.110.72

2.000.70

1.93

0.61

3.310.722.06

2.062.85

0.0002.2502.2642.2812.2942.3142.3312.3452.3622.3762.4642.4832.4952.5132.5262.5442.7162.9983.0693.0823.0983.1123.1283.1413.1673.1803.1953.2093.2243.2393.2533.8533.8573.8763.8803.8993.9033.9443.9653.9713.989

5.311

5.503

6.3856.4066.4266.5836.6026.6206.6726.6916.7097.0947.1127.1387.1467.1487.1577.1657.1747.1847.1877.259

114

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

f1 (ppm)

32.8933.3333.6234.60

45.80

59.2160.11

76.7977.0077.2183.5984.18

106.62107.20113.26113.32115.17115.23117.08117.14117.91118.10118.99119.05123.58123.73127.21128.03129.87130.05155.54155.58155.78155.82156.03156.07156.27156.31

115

-210

-200

-190

-180

-170

-160

-150

-140

-130

-120

-110

-100

-90

-80

-70

-60

-50

-40

-30

-20

-10

010

f1 (ppm)

-71.666-71.660

116

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

2.000.592.57

1.75

6.01

2.000.58

2.000.58

0.582.00

0.571.920.702.33

4.50

2.0412.0532.0712.0832.2102.2212.2392.2512.3972.4092.4162.4262.4382.4452.4562.4742.7212.9243.3063.3183.3283.3353.3403.3473.3563.3683.4003.4123.4223.4303.4343.4423.4523.4643.9003.9203.9404.0034.0234.043

5.1105.218

6.2836.3026.3196.3386.5126.5276.5866.6046.6227.0567.0747.0947.1117.1297.248

117

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

240

f1 (ppm)

30.6230.9736.7637.75

60.9361.3566.7666.84

76.6877.0077.32

100.72101.28104.95105.02

116.94116.98123.86124.08128.69130.28130.46

151.84151.88

118

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

3.07

2.06

2.09

3.03

1.01

1.001.011.002.001.11

2.00

0.000

2.379

2.8262.8432.8593.1863.2023.2183.234

4.014

4.7234.7384.753

6.7266.8686.8876.9077.0837.0857.1027.1047.1697.1907.2297.2327.2447.2497.2527.6027.623

119

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

f1 (ppm)

21.43

25.13

36.35

43.02

76.6877.0077.32

110.17

116.97117.27119.66123.14126.88129.48129.96130.43132.24136.69143.20

120

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

3.00

3.002.00

2.00

3.00

1.00

1.00

2.00

3.00

2.00

0.000

2.387

2.7232.8392.8552.8723.1933.2093.2253.242

3.958

4.4974.5124.527

6.6806.8806.8866.8967.1917.1997.2067.2157.2207.6247.645

121

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

240

f1 (ppm)

19.6121.4525.23

36.51

43.05

76.6877.0077.32

109.58116.58119.24121.36124.38126.98128.35128.91129.54

135.80136.84

143.16

122

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

3.01

2.01

2.04

3.00

1.00

2.011.00

2.011.04

2.00

-0.000

2.375

2.8342.8502.8673.1853.2023.2183.2343.611

4.7324.7474.762

6.7446.7496.7666.7906.7956.8826.8886.9076.9127.1687.1887.2407.2537.2627.2757.6067.627

123

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

240

f1 (ppm)

21.38

25.23

32.60

43.09

76.6877.0077.32

95.4895.74

107.40107.64110.31119.25119.35123.84126.90127.49127.52129.48136.71137.03137.15143.20

158.70161.06

124

-210

-200

-190

-180

-170

-160

-150

-140

-130

-120

-110

-100

-90

-80

-70

-60

-50

-40

-30

-20

-10

010

f1 (ppm)

-120.790

125

-2.0

-1.5

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

3.00

2.02

2.10

3.00

1.00

1.011.001.991.99

2.00

-0.000

2.404

2.8592.8752.8923.2023.2183.2343.2503.679

4.4124.4274.442

6.8036.9756.9806.9967.0017.1937.2137.2517.2567.2727.5987.619

126

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

240

f1 (ppm)

21.48

25.29

32.71

43.06

76.6877.0077.32

109.38110.37

119.47119.68125.89126.97127.93127.98129.55136.76137.55

143.33

127

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

f1 (ppm)

3.003.00

2.00

2.04

3.00

1.00

1.001.001.002.000.99

2.00

0.000

2.3972.479

2.8632.8792.8953.2123.2283.2433.260

3.680

4.3834.3984.413

6.7256.8656.8676.8857.0657.2027.2227.2517.6147.635

128

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

240

f1 (ppm)

21.4921.8225.46

32.54

43.18

76.7077.0277.34

109.33109.80

118.29120.79125.19126.70127.04129.56131.74136.93137.61143.19

129

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

f1 (ppm)

2.99

2.01

2.01

2.99

2.99

1.00

3.02

3.00

2.00

0.000

2.392

2.8402.8572.8733.1983.2143.2303.246

3.653

3.864

4.4654.4794.493

6.6916.714

7.1987.2187.2217.2427.2427.6107.631

130

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

240

f1 (ppm)

21.45

25.36

32.59

43.11

55.69

76.6877.0077.32

92.83

108.95109.95

119.23121.65126.09126.98129.53

136.80137.87143.18

156.52

131

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

3.11

2.07

2.08

3.07

1.00

0.97

2.091.991.02

2.00

0.000

2.393

2.8052.8222.8383.1753.1923.2073.224

3.670

4.6474.6624.677

6.8327.1037.1077.1257.1297.1397.1407.1607.1627.1887.2087.2557.2567.2597.2617.5957.616

132

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

240

f1 (ppm)

21.5725.13

32.85

42.96

76.7877.1077.42

109.62110.43118.03122.00124.80127.00128.26128.81129.66135.52136.52

143.43

133

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

6.06

2.02

2.01

3.00

1.01

0.97

1.011.952.02

2.01

0.000

2.3992.410

2.8582.8742.8913.2193.2353.2513.267

3.685

4.525

6.7607.0257.0467.1507.1717.2037.2237.6237.640

134

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

240

f1 (ppm)

21.4421.5225.35

32.68

43.16

76.7377.0577.37

109.09109.28

118.27123.45127.07127.45127.51128.18129.58135.64136.85

143.20

135

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

3.14

2.02

2.04

3.012.97

1.00

1.000.991.091.032.02

2.00

-0.000

2.371

2.8432.8602.8763.1833.1993.2153.231

3.6503.781

4.6524.6624.676

6.7566.8106.8166.8396.8456.8616.8677.1247.1467.1637.1837.5937.614

136

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

240

f1 (ppm)

21.49

25.39

32.79

43.13

55.88

76.8177.1277.44

100.45

109.41110.16112.04

127.03127.62127.95129.58132.55136.76

143.26

153.81

137

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

3.04

2.03

2.05

3.07

1.01

1.001.00

1.011.032.00

2.00

0.000

2.383

2.9392.9552.9713.2443.2603.2763.2923.702

4.462

6.6416.6606.6686.6876.7647.0127.0327.0627.0757.0827.0947.1027.1147.1767.1967.2567.6077.628

138

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

f1 (ppm)

21.48

26.48

32.96

43.62

76.6877.0077.32

104.03104.22105.44105.48108.77108.80115.70115.90122.18122.25126.92127.75129.48

136.81139.96140.08143.11

155.71158.16

139

-210

-200

-190

-180

-170

-160

-150

-140

-130

-120

-110

-100

-90

-80

-70

-60

-50

-40

-30

-20

-10

010

f1 (ppm)

-123.684

140

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

3.00

2.09

2.05

3.00

1.00

1.001.001.081.012.01

2.00

-0.000

2.377

3.0903.1073.1233.2793.2953.3113.3273.696

4.4814.4964.511

6.8396.9786.9806.9976.9987.0527.0727.0917.1347.1547.1767.1967.2537.6227.643

141

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

240

f1 (ppm)

21.46

26.31

32.87

44.35

76.6877.0077.32

108.10110.47

119.99122.18124.07126.10126.97129.09129.49

136.95138.66143.13

142

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

0.93

1.98

4.33

1.46

1.09

2.951.000.48

1.000.40

0.38

1.44

0.97

0.440.942.90

1.900.86

0.0001.8031.8141.8331.8451.9301.9491.9601.9781.9902.0072.0192.0362.0472.0652.0772.0952.1202.4052.4202.6962.7032.7082.7162.7242.7302.7362.7442.7532.7572.7652.9043.3173.3963.4133.4233.4413.5973.6143.6233.6393.653

4.9915.051

6.1816.5186.5376.5496.5686.5876.7436.7466.7626.7657.0187.0217.0387.0417.0497.0527.0697.0727.2647.2697.2797.2897.3007.6127.6337.7317.751

143

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

f1 (ppm)

21.49

33.5334.5336.2337.09

46.6446.86

60.9162.52

76.6877.0077.32

88.0888.52

115.17116.57119.22120.29122.06123.01127.18127.29129.60129.86131.25131.34131.65132.89136.45136.83143.39143.50146.62147.87

144

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

2.004.471.145.582.045.64

3.14

5.882.00

0.62

1.880.62

0.481.951.860.642.00

5.604.001.34

0.0001.8131.8251.8431.8551.9902.0092.0192.0382.0492.0692.0862.1392.1522.1662.1852.2132.2302.2462.2672.3112.3872.4062.7192.7302.7462.7582.7742.7863.1953.2933.3113.3193.3383.6153.6333.6383.657

4.8624.979

6.5886.6076.6266.7496.7676.8946.9127.2107.2317.2407.2607.4677.4877.7187.739

145

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

f1 (ppm)

18.5719.2021.4021.45

33.3434.7837.2438.62

46.5246.71

60.5462.76

76.7977.0077.21

89.0789.25

118.94119.93120.01121.45122.59127.15127.21129.12129.29129.63131.91132.62136.90137.66142.86143.02149.73

146

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

0.81

4.92

6.082.07

4.976.00

2.00

0.73

2.000.73

0.735.35

2.00

4.015.461.46

0.0001.3021.3141.3321.3441.3631.6621.6741.6931.7031.7271.7431.7691.7821.7982.4362.4672.7492.7612.7762.7902.8022.8192.8282.8412.8592.8712.8902.9022.9613.3013.3153.3283.3343.3413.3473.5113.5293.5413.559

4.9584.977

6.0076.0326.1366.1726.1966.2166.2216.6496.6636.6696.6827.2137.2337.2647.3697.3827.4037.6037.623

147

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

f1 (ppm)

21.4621.53

31.3331.4332.5934.33

47.6347.66

60.0961.60

76.7977.0077.2185.5187.1094.3094.4894.8094.97103.31103.47103.69103.84122.90123.55123.81123.88124.92124.99126.96129.93130.01135.99136.82143.31144.12

152.99153.07153.18153.26163.78163.81165.40165.42

148

-210

-200

-190

-180

-170

-160

-150

-140

-130

-120

-110

-100

-90

-80

-70

-60

-50

-40

-30

-20

-10

010

f1 (ppm)

-112.37-111.89

149

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

0.42

2.39

2.930.90

2.26

3.03

1.00

0.33

1.020.27

0.290.322.391.05

2.092.620.62

0.000

1.3191.3491.3671.3981.6771.6891.7161.7261.7371.7522.4532.4702.7412.7662.7832.7922.8132.8262.8452.8572.8762.9743.3003.3093.3143.3243.3343.3443.5113.5303.5423.560

4.9294.999

6.1626.2946.2986.4516.4556.4756.4936.4976.6136.6347.2297.2497.2617.3447.3647.3857.6047.625

150

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

f1 (ppm)

21.5121.56

31.3031.4332.4234.30

47.62

59.9661.60

76.6877.0077.32

85.2786.89

106.75107.26117.20117.66123.89125.04126.02126.65126.87126.98129.94130.02135.35135.51135.83136.76143.33144.15

152.44152.66

151

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

1.09

2.562.00

1.535.996.001.55

3.540.576.002.00

0.51

0.512.00

0.910.511.931.98

1.97

4.00

5.02

1.02

0.0001.2851.3031.3161.3341.3461.3641.3801.6781.6981.7101.7281.7401.7721.7901.8021.8201.8321.8502.2422.3712.4232.4532.7062.7182.7342.7472.7652.7772.8072.8192.8382.8502.8682.8802.9573.1693.1863.1973.2153.4543.4723.4843.5024.9754.990

6.0996.1166.1386.2786.2976.3206.4226.4416.6876.7067.1727.1927.2567.3197.3397.3587.5957.615

152

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

240

f1 (ppm)

21.5021.6421.81

31.4731.6032.4934.32

47.4247.60

60.1361.86

76.6877.0077.32

85.6987.56

107.45107.86118.08118.49123.00124.29125.04125.63127.00127.16129.76129.86136.16137.11139.21139.27142.84143.74151.71151.82

153

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

f1 (ppm)

0.27

2.03

2.700.36

1.250.232.70

1.00

0.120.342.93

0.110.90

0.110.110.911.00

0.930.14

1.952.000.30

0.0001.2911.3021.3211.3311.3501.6681.6801.6981.7101.7341.7511.7631.7811.7931.8112.4252.4602.7402.7522.7692.7812.7972.8102.8462.8632.8782.8962.9082.9683.2023.2193.2313.2483.4723.4903.5023.5203.7373.8514.9635.0065.8815.8865.9996.0046.0206.0246.0606.0656.1126.1176.1326.1386.6616.6816.6946.7207.1967.2167.2627.3617.3817.6007.620

154

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

f1 (ppm)

1.091.301.511.711.922.132.33

21.99

32.5533.6335.23

49.0249.20

56.36

61.69

87.3188.9494.3594.72

103.63104.24

118.69121.44125.36126.24128.22128.27131.31131.63137.56138.20

144.92145.81

154.12

162.91

155

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

f1 (ppm)

1.86

5.39

6.014.00

7.466.002.00

1.29

1.302.00

1.281.282.002.00

1.299.882.582.58

-0.0001.2801.2921.3111.3221.3411.5751.6751.6871.7061.7191.7371.7501.7641.7802.4452.4772.7532.7772.7902.8062.8192.8322.8442.8632.8752.8942.9063.0123.2053.2193.2323.2493.5133.5323.5443.562

4.9544.999

6.1456.2506.2716.4656.4866.7116.7167.0577.0627.0787.0837.2017.2067.2197.2617.3777.3977.5997.619

156

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

240

f1 (ppm)

21.58

31.5531.6432.3034.03

47.4447.74

59.9061.98

76.6877.0077.32

85.3487.21

107.33108.03122.07122.63123.43124.91126.92127.03129.18129.42129.60129.65130.06130.10135.48136.79143.52144.19150.06150.36

157

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

1.68

5.38

4.116.006.004.113.632.291.466.032.00

1.37

1.372.01

1.241.361.971.97

1.351.994.034.022.872.77

-0.0001.3171.3291.3471.3591.7021.7141.7311.7431.7681.7861.7981.8161.8282.0672.2022.4112.4542.6792.7012.7142.7312.7432.7602.7722.8332.8512.8632.8822.9643.1713.1893.2003.217

3.4713.4893.5003.519

4.9535.070

5.9566.1956.2146.3996.4186.6106.8646.8837.0117.0317.1527.1737.2577.3077.3277.3437.3637.6017.621

158

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

240

f1 (ppm)

20.6321.0021.4621.5031.6931.9532.3734.01

47.4847.67

60.1462.21

76.6877.0077.32

85.7187.52

106.35106.86124.13125.70126.44126.50127.00127.12127.90128.51129.50129.82129.85136.14137.11142.69143.73

149.57149.65

159

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

3.14

4.02

2.786.04

6.942.182.770.95

8.17

2.78

2.000.92

1.84

2.050.930.982.020.92

1.892.204.05

4.03

0.0001.2571.3031.3231.3341.3521.3641.3821.6291.6991.7111.7291.7411.7551.7731.7851.8032.4162.4632.6982.7202.7332.7492.8062.8182.8362.8482.8672.8792.9523.1623.1793.1913.208

3.4883.5063.5173.5483.699

4.9905.047

5.8726.2376.2586.4086.4146.4346.4556.6466.6526.6676.6736.7936.7996.8146.8207.1607.1807.2637.2837.3547.3747.6087.629

160

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

f1 (ppm)

21.4321.54

31.9932.3932.4734.24

47.3947.62

55.5156.0260.1962.13

76.7977.0077.21

86.0087.98

107.23107.50110.48111.99114.09114.55127.04127.11128.99129.64129.83129.90135.86137.00

142.93143.85146.11

152.39152.42

161

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

1.01

1.00

3.00

1.003.00

1.00

1.00

2.00

3.002.10

1.5021.5211.5331.5511.5631.582

2.2342.2452.2652.2762.4242.8442.8552.8742.8852.9042.9142.9973.2953.3133.3253.343

5.139

6.2436.2636.2686.290

7.1267.1427.1627.1817.2637.2697.290

162

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

f1 (ppm)

21.53

31.1931.2231.63

48.30

61.48

76.6877.0077.32

87.3987.41

102.85102.87105.45105.68112.06112.22

126.94129.88131.40131.50135.81

143.04

153.80153.89158.25160.68

163

-210

-200

-190

-180

-170

-160

-150

-140

-130

-120

-110

-100

-90

-80

-70

-60

-50

-40

-30

-20

-10

010

f1 (ppm)

-116.10

164

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

1.05

3.05

2.063.021.01

1.00

1.001.00

2.002.99

0.000

1.5341.5511.5651.5821.5951.614

2.4142.7432.7532.7732.7832.8032.8132.8252.8352.8572.8663.0233.2193.2373.2493.266

5.148

6.4366.4566.5726.5927.0997.1197.1577.1737.1787.1927.262

165

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

240

f1 (ppm)

21.50

30.8031.71

48.79

63.19

76.6877.0077.32

87.71

105.79

120.19122.90126.90129.87130.94131.71135.25

142.97

153.94

166

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

1.06

1.07

3.00

1.03

1.98

1.021.01

0.98

1.01

1.001.072.021.03

1.97

2.01

0.000

3.0593.0803.0943.1153.2703.298

3.674

4.267

4.5994.607

5.0375.0795.1805.2055.6115.8885.9015.9155.9295.9435.9556.8906.9967.0127.0287.1007.1217.1357.2577.3427.3617.6407.6597.9187.935

167

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

240

f1 (ppm)

28.95

48.6252.7956.34

76.6877.0077.32

107.82109.68

117.66118.38119.45122.00123.48126.99127.26127.66133.01136.22

144.91

149.41

171.76

168

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

0.95

0.98

3.07

1.051.00

0.98

1.090.981.03

0.98

1.001.011.07

1.08

1.81

2.05

0.000

2.2872.3072.3222.5162.537

3.100

4.0264.0334.0544.0624.0924.1064.3434.3514.3714.3795.2415.3165.3345.3885.4176.0056.0136.0226.0316.0416.0516.0596.5226.5346.5466.6516.6646.7366.7487.2397.2527.2657.5227.535

8.1578.171

169

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

f1 (ppm)

36.41

48.32

52.43

59.5461.04

76.6877.0077.32

87.53

108.85

117.00118.03124.64125.37126.12128.17130.51134.09

143.93

149.78151.08

169.81

170

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

1.88

1.001.00

2.94

0.98

3.60

1.95

1.05

2.39

2.10

1.01

1.88

1.040.841.01

1.051.061.05

1.79

3.79

1.93

0.000

1.622

2.2952.3222.3442.5822.6012.6152.6332.7282.7593.023

3.8604.0154.0444.1104.1304.149

4.6074.6274.8574.911

5.2085.2235.2805.431

5.872

6.2546.2746.3406.3906.4106.8186.9806.9997.0187.0277.0857.1057.1257.2667.8767.8988.1578.1798.2008.2228.3648.386

171

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

f1 (ppm)

38.3839.75

47.9452.2752.3453.0760.2760.9461.3761.90

76.6877.0077.32

86.0887.09

107.59110.40117.16117.79117.86119.94123.46123.79124.45124.82126.08127.98128.87129.91129.99133.64134.12145.20146.85149.69150.28150.31150.53

169.67171.01

172

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

2.032.042.00

5.88

1.954.00

1.93

2.042.04

1.98

1.97

2.01

1.962.06

0.000

2.4112.5402.5452.5722.5762.7592.7792.7912.8113.2083.7693.7743.7893.7943.8263.8403.8663.8813.8833.8983.9233.9384.6825.1825.1865.2085.2115.3105.3145.3535.3575.9215.9365.9475.9615.9785.9926.0046.0186.3436.3626.5816.5996.6177.0417.0607.0797.1377.1557.266

173

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

240

f1 (ppm)

38.86

47.89

51.66

59.9360.31

76.6877.0077.32

85.11

106.30

116.61116.86

125.55129.02129.87134.70

151.57

174.14

174

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

2.00

2.06

6.01

2.21

2.00

1.991.98

1.981.96

0.000

2.5572.5632.5892.5952.7802.8012.8122.8333.237

3.7813.7863.8013.807

4.663

6.5796.5986.6986.6996.7166.7186.7356.7367.0467.0497.0667.0677.0857.0877.1767.1957.275

175

-20

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

f1 (ppm)

38.71

51.77

60.0261.84

76.6877.0077.3280.81

109.83

118.46

125.87129.04129.46

151.02

173.89

176

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

f1 (ppm)

1.96

2.17

2.216.12

1.94

1.93

1.86

1.94

4.65

2.00

2.202.052.01

2.204.0012.496.88

1.8641.8781.8861.9002.0462.068

2.8652.8842.9032.9393.1233.1303.1443.151

3.5413.555

4.3644.3804.403

4.8745.0425.0635.0685.0895.2705.3115.324

5.8805.894

6.5466.5596.6086.6206.6326.7616.7737.0367.0487.0617.1827.1947.2857.2927.2987.3087.3247.3317.3857.3967.4097.4207.4327.443

177

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

f1 (ppm)

34.73

41.14

52.2153.6958.4459.50

66.68

76.7977.0077.2179.93

109.53

117.95125.46126.71127.58127.93128.35128.98129.14129.63135.51136.30

150.85

154.94

169.95171.66

178

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

8.5

9.0

9.5

10.0

f1 (ppm)

2.00

4.14

2.34

2.261.91

1.79

1.951.97

2.052.00

13.19

2.37

1.9481.9541.9601.9661.9722.2122.5052.5242.5402.5602.9692.9843.0053.0223.0403.0703.0973.1093.1343.1464.0594.0804.1024.1574.1704.184

4.907

5.9006.035

6.6846.7036.7346.7536.7727.1127.1317.1497.3547.373

179

-20

-10

010

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

f1 (ppm)

0.650.851.061.271.471.681.89

36.0736.76

56.9557.7360.94

80.53

110.40

118.26120.18126.04127.60129.32130.09130.29131.39137.34

149.98

168.88169.78

180

Documents

Exploration of A KI-Catalyzed Oxidation System for …3 2. Preparations of tryptamine and tryptophol analogues Tryptamine and tryptophol analogues used in this research are known compounds