The highly enantioselective addition of indoles and pyrroles to isatins-derived N-Boc ketimines catalyzed by chiral phosphoric acids

Article abstract of DOI:10.1039/c2cc33200k

The first asymmetric aza-Friedel-Crafts reaction of indoles and pyrroles with isatin-derived N-Boc ketimines catalyzed by chiral phosphoric acids is reported. In general, derivatives of substituted 3-amino-2-oxindoles were obtained with excellent enantios

Full text of DOI:10.1039/c2cc33200k

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Supporting Information
for
The Highly Enantioselective Addition of Indoles and Pyrroles to
Isatins-derived N-Boc Imines Catalysed by Chiral Phosphoric Acid
Jingchao Feng, Wenjin Yan, Dong Wang, Peng Li, and Rui Wang*
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Medicine, State Key
Laboratory of Applied Organic Chemistry, and Institute of Biochemistry and Molecular Biology,
Lanzhou University, Lanzhou, 730000, P. R. China.
Table of Contents:
General information
S1
Proposed transition-state models for our catalytic system
S2
General procedure for preparation of isatins-derived 3-N-Boc imines
S2
General procedure for the enantioselective F-C reaction Catalysed by Chiral
Phosphoric Acid
S2-29
X-Ray Structure of 4s
S30
References
S30
Copies of NMR spectra
S31-84
General information.
All commercially available reagents were used without further purification unless otherwise stated.
Reactions were monitored by thin layer chromatography (TLC), column chromatography purifications
1
were carried out using silica gel. Proton nuclear magnetic resonance ( HNMR) spectra were recorded
13
on 300 MHz spectrometer in CDCl
3
and carbon nuclear magnetic resonance ( CNMR) spectra were
using tetramethylsilane (TMS) as internal standard. Data
recorded on 75 MHz spectrometer in CDCl
3
are presented as follows: chemical shift, integration, multiplicity (s = singlet, d = doublet, dd = doublet
S 1

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of doublets, t = triplet, m = multiplet, br = broad) and coupling constant in Hertz (Hz). Methylene
chloride was freshly distilled from CaH before use; other solvents (THF, Et O, 1,4-dioxane, tBuOMe
and toluene) were freshly distilled from sodium. Racemates were obtained by reactions using catalytic
2
2
1
2
amounts of Binaphthylphosphoric acid. BINOL-derived phosphoric acid 1a-d, 1e were prepared
according to literature procedures.
Proposed transition-state models for our catalytic system
Figure 1. Transition-state model for addition of
N-Me indoles
Figure 2. Transition-state model for addition of
pyrrole
General procedure for preparation of isatins-derived 3-N-Boc ketimines.
3
This compound was prepared following the reported procedure.
A
solution of
N-Boc-triphenyliminophosphorane (12mmol) and N-Methylisatin (10 mol) in 1,4-dioxane (20 mL)
was refluxed for 6 h. The 1,4-dioxane was evaporated and the residue was purified by flash
chromatography to afford the ketimine as a yellow solid.
Boc
O
N
Boc
Ph
N
1,4-dioxane
reflux
O
O
P
Ph
N
N
Ph
General procedure for the enantioselective F-C reaction Catalysed by Chiral
Phosphoric Acids.
To a solution of isatins-derived ketimine 3a-j (0.15 mmol) and chiral phosphoric acid (0.0075 mmol, 5
mol%) in Et
2
O or other solvents (1.5 mL) were added 4 Å MS (4 beads, 0.12 – 0.14 g) and indole 2a-i
o
or pyrrole (0.3 mmol, 2.00 equiv) at 0 C. After the reaction was complete (monitored by TLC), the
solvent was removed and the residue was purified by flash column chromatography to afford the
product 4a-s or 6a-h.
S 2

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(
S)-tert-Butyl 1,1'-dimethyl-2-oxo-3,3'-biindolin-3-ylcarbamate (4a)
The ee value determination was carried out using chiral high-performance
liquid chromatography (HPLC) with Chiracel OD-H column (hexane :
2-propanol = 92 : 8, 1.0 mL/min, 94% ee). White solid, 96% yield; mp
N
H
N
o
20
1
Boc
=153-154 C ; [α]
8.18 (d, J = 7.8 Hz, 1H), 7.43 (d, J = 7.2 Hz, 1H), 7.37 (t, J = 7.8 Hz, 1H),
7.24-7.28 (m, 2H), 7.21 (t, J = 1.8 Hz, 1H), 7.11-7.19 (m, 1H), 6.87 (d, J =
.8 Hz, 1H), 6.52 (s, 1H), 5.72 (br.s, 1H), 3.63 (s, 3H), 3.18 (s, 3H), 1.28
br.s, 9H) ppm; C NMR (75 MHz, CDCl ) δ = 175.7, 153.9, 143.7, 137.9, 130.7, 129.0, 128.3, 125.1,
23.4, 122.5, 122.4, 121.9, 120.0, 111.5, 109.7, 108.1, 80.3, 62.0, 32.8, 28.1, 26.5 ppm; IR (KBr):
D
3 3
= +116 (c 1.0, CHCl ); H NMR (300 MHz, CDCl ): δ
O
=
N
7
1
3
(
3
1
3
-
1
446, 3007, 2927, 1718, 1613, 1470, 1368, 1160, 1016, 901, 743, 693 cm ; HRMS calcd for
+
C
23
H
26
N
3
O
3
(M+H) 392.1969, found 392.1978.
0
0
0
0
0
.4 0
.3 0
.2 0
.1 0
.0 0
0
.0 0
5 .0 0
1 0 .0 0
1 5 .0 0
2 0 .0 0
2 5 .0 0
3 0 .0 0
3 5 .0 0
min
Name Retention Time Area
% Area
Height
Int Type Peak Type Peak Codes
1
2
24.494
28.846
42606078 49.46
43530885 50.54
400316
294790
BV
VB
Unknown
Unknown
0.30
0.20
0.10
0.00
0.00
5.00
10.00
15.00
20.00
25.00
30.00
35.00
min
Name Retention Time Area
% Area
32348346 96.95
1017527 3.05
Height Int Type Peak Type Peak Codes
1
2
24.260
30.709
292922 bb
8712 bb
Unknown
Unknown
S 3

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(
S)-tert-Butyl 1-acetyl-1'-methyl-2-oxo-3,3'-biindolin-3-ylcarbamate (4b)
The ee value determination was carried out using chiral high-performance
liquid chromatography (HPLC) with Chiracel OD-H column (hexane :
N
H
2
-propanol = 80 : 20, 1.0 mL/min, 80% ee). White solid, 95% yield; mp =
N
Boc
o
20
1
O
144-146 C; [α]
.32 (d, J = 8.1 Hz, 1H), 8.19 (d, J = 7.8 Hz, 1H), 7.40-7.47 (m, 2H), 7.21-7.31
m, 4H), 6.36 (s, 1H), 5.89 (br.s, 0.52H) 5.63 (br.s, 0.46H), 3.64 (s, 3H), 2.59 (s,
D
3 3
= +257 (c 1.0, CHCl ); H NMR (300 MHz, CDCl ): δ =
8
N
O
(
1
3
3
3
H), 1.37 (br.s, 5H), 1.13 (br.s, 4H) ppm; C NMR (75 MHz, CDCl ) δ =
1
8
7
75.4, 171.2, 153.7, 140.0, 138.0, 129.4, 125.2, 124.8, 123.1, 122.8, 121.8, 120.4, 116.7, 110.8, 109.9,
0.8, 62.3, 32.9, 28.2, 26.6 ppm; IR (KBr): 3331, 2921, 1774, 1705, 1465, 1370, 1334, 1274, 1162,
-1
+
26 3 4
46 cm ; HRMS calcd for C23H N O (M+H) 420.1918, found 420.1921.
0
0
0
0
0
.40
.30
.20
.10
.00
0
.00
2.00
4.00
6.00
8.00
10.00
min
12.00
14 .00
16.00
18.00
20.00
Name Retention Time Area
% Area Height
Int Type Peak Type Peak Codes
1
2
12.611
17.349
11502726 51.30
10918695 48.70
392510
227344
bb
bb
Unknown
Unknown
1
1
0
0
0
0
0
.20
.00
.80
.60
.40
.20
.00
2
.00
4.00
6.00
8.00
10.00
min
12.00
14.00
16.00
18.00
Name Retention Time Area
% Area Height
31903781 89.88 1144127 bb
3593315 10.12 83764 bb
Int Type Peak Type Peak Codes
1
2
12.614
17.473
Unknown
Unknown
S 4

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(
S)-tert-Butyl 1-benzyl-1'-methyl-2-oxo-3,3'-biindolin-3-ylcarbamate (4c)
The ee value determination was carried out using chiral high-performance liquid
chromatography (HPLC) with Chiracel OD-H column (hexane : 2-propanol =
N
o
20
H
97 : 3, 0.50 mL/min, 90% ee). White solid, 87% yield; mp = 122-124 C; [α]
D
N
Boc
1
=
+128 (c 1.0, CHCl
3
); H NMR (300 MHz, CDCl
3
): δ = 8.13 (d, J = 7.8 Hz,
O
1
H), 7.45 (d, J = 6.6 Hz, 1H), 7.16-7.30 (m, 9H), 7.07 (t, J = 7.5 Hz, 1H), 6.71
N
Bn
(d, J = 7.8 Hz, 1H), 6.58 (s, 1H), 5.77 (br.s, 1H), 4.98 (br.s, 2H), 3.64 (s, 3H),
1
3
3
1.34 (br.s, 9H) ppm; C NMR (75 MHz, CDCl ) δ = 175.9, 153.9, 142.8, 137.9,
1
8
7
36.0, , 128.8, 128.6, 128.2, 127.3, 125.2, 123.5, 122.49, 122.45, 121.8, 120.0, 111.7, 109.7, 109.2,
0.3, , 44.1, 32.9, 28.2, 25.4 ppm; IR (KBr): 3018, 2920, 1715, 1486, 1469, 1215, 1160, 1060, 1021,
-1
+
56 cm ; HRMS calcd for C29
H
29
N
3
3
NaO (M+Na) 490.2101, found 490.2118.
0.040
0.030
0.020
0.010
0.000
0.00
20.00
40.00
60.00
80.00
min
100. 00
120. 00
140.00
Name Retention Time Area
% Area Height
Int Type Peak Type Peak Codes
1
2
95.803
17545819 51.35
16621083 48.65
40438
26937
bb
bb
Unknown
Unknown
125.749
0.15
0.10
0.05
0.00
0.00
20.00
40.00
60.00
80.00
min
100.00
120.00
140.00
Name Retention Time
90.293
Area
% Area Height Int Type Peak Type Peak Codes
1
2
86591472 95.01
4544683 4.99
178012 Bb
7512 bb
Unknown
Unknown
130.537
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(
S)-tert-Butyl 5-methoxy-1,1'-dimethyl-2-oxo-3,3'-biindolin-3-ylcarbamate (4d)
The ee value determination was carried out using chiral high-performance
liquid chromatography (HPLC) with Chiracel OD-H column (hexane :
N
H
2
-propanol = 92 : 8, 1.0 mL/min, 92% ee). White solid, 94% yield; mp =
N
Boc
o
20
1
O
123-124 C; [α]
.09 (d, J = 7.5 Hz, 1H), 7.08-7.20 (m, 3H), 6.99 (d, J = 2.4 Hz, 1H), 6.80 (dd,
J = 8.4, 2.1 Hz, 1H), 6.79 (d, J = 8.4 Hz, 1H), 6.47 (s, 1H), 5.64 (br.s, 1H),
3 3
= +299 (c 1.0, CHCl ); H NMR (300 MHz, CDCl ): δ =
D
8
N
O
1
3
3
1
6
7
3
.74 (s, 3H), 3.55 (s, 3H), 3.08 (s, 3H), 1.22 (br.s, 9H) ppm; C NMR (75 MHz, CDCl ) δ = 175.4,
55.80, 153.75, 137.8, 137.2, 128.1, 125.0, 122.4, 121.8, 119.9, 112.8, 111.4, 111.0, 109.6, 108.3, 80.2,
2.1, 55.8, 32.7, 28.0, 26.5 ppm; IR (KBr): 3010, 2978, 1717, 1498, 1471, 1367, 1288, 1164, 1037,
-1
+
28 3 4
53 cm ; HRMS calcd for C24H N O (M+H) 422.2074, found 422.2070.
0
0
0
.04
.02
.00
0
.00
10.00
20.00
30.00
min
40.00
50.00
60.00
Name
Retention Time Area
% Area Height Int Type Peak Type Peak Codes
1
2
39.269
49.513
9267364 51.25
8813612 48.75
49002
33417
bb
bb
Unknown
Unknown
0.15
0.10
0.05
0.00
0.00
10.00
20.00
30.00
min
40.00
50.00
Name
Retention Time Area
% Area Height Int Type Peak Type Peak Codes
1
2
35.311
48.307
34401092 95.77
1519602 4.23
174526 bb
6818 bb
Unknown
Unknown
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(
S)-tert-Butyl 1,1',5-trimethyl-2-oxo-3,3'-biindolin-3-ylcarbamate (4e)
The ee value determination was carried out using chiral high-performance
liquid chromatography (HPLC) with Chiracel OD-H column (hexane :
N
H
2
1
8
1
-propanol = 92 : 8, 1.0 mL/min, 93% ee). White solid, 97% yield; mp =
N
Boc
o
20
1
O
08-110 C; [α]
D
3 3
= +104 (c 1.0, CHCl ); H NMR (300 MHz, CDCl ): δ =
.16 (d, J = 7.8 Hz, 1H), 7.14-7.28 (m, 5H), 6.75 (d, J = 7.8 Hz, 1H), 6.54 (s,
N
H), 5.65 (br.s, 1H), 3.64 (s, 3H), 3.16 (s, 3H), 2.38 (s, 3H), 1.26 (br.s, 9H)
1
3
ppm; C NMR (75 MHz, CDCl
3
) δ = 175.7, 153.9, 141.3, 137.9, 131.9, 129.1, 128.2, 125.1, 124.2,
1
1
22.4, 121.9, 120.0, 111.7, 109.6, 107.8, 80.2, 62.0, 32.8, 28.1, 26.5, 21.3 ppm; IR (KBr): 3314, 2920,
-
1
+
28 3 3
718, 1500, 1471, 1366, 1335, 1163, 746, 554 cm ; HRMS calcd for C24H N O (M+H) 406.2125,
found 406.2135.
0.40
0.30
0.20
0.10
0.00
0.00
5.00
10.00
15.00
20.00
min
25.00
30.00
35.00
Name
Retention Time Area
% Area Height Int Type Peak Type Peak Codes
1
2
22.568
27.627
43493313 50.04
43431731 49.96
386584 BV
289251 VB
Unknown
Unknown
0
.12
.10
.08
.06
.04
.02
.00
0
0
0
0
0
0
0.00
2.00
4.00
6.00
8.00
10.00
12.00
14.00
16.00
min
18.00
20.00
22.00
24.00
26.00
28.00
30.00
32.00
Name
Retention Time Area
% Area Height Int Type Peak Type Peak Codes
1
22.237
28.951
14566531 96.39
544814 3.61
128419 bb
4534 bb
Unknown
Unknown
2
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(
S)-tert-Butyl 1,1'-dimethyl-2-oxo-5-(trifluoromethoxy)-3,3'-biindolin-3-ylcarbamate (4f)
The ee value determination was carried out using chiral high-performance
liquid chromatography (HPLC) with Chiracel OD-H column (hexane :
N
H
N
2
-propanol = 60 : 40, 1.0 mL/min, 97% ee). White solid, 98% yield; mp =
Boc
o
20
1
O
96-97 C; [α]
D
3 3
= +243 (c 1.0, CHCl ); H NMR (300 MHz, CDCl ): δ
N
= 8.16 (d, J = 7.5 Hz, 1H), 7.34 (d, J = 1.5 Hz, 1H), 7.17-7.28 (m, 4H),
.84 (d, J = 2.7 Hz, 1H), 6.51 (s, 1H), 5.79 (br.s, 0.64H), 5.56 (br.s,
F3CO
6
1
3
0
.34H), 3.63 (s, 3H), 3.18 (s, 3H), 1.34 (br.s, 6H), 1.17 (br.s, 3H) ppm; C NMR (75 MHz, CDCl
3
) δ
=
175.6, 153.7, 144.57, 144.55, 142.5, 137.9, 128.1, 125.0, 122.7, 122.3,122.1, 121.7, 120.2, 118.9,
1
1
4
17.5, 110.6, 109.8, 108.6, 80.7, 62.0, 32.9, 28.1, 26.7 ppm; IR (KBr): 3313, 2976, 2921, 1716, 1496,
-
1
+
254, 1217, 1162, 1119, 1092 cm ; HRMS calcd for C24
98.1623.
24
H F
3
N
3
NaO
4
(M+Na) 498.1611, found
0
0
0
0
0
0
.050
.040
.030
.020
.010
.000
2
.00
4.00
6.00
8.00
10.00
12.00
14.00
16.00
min
Name Retention Time Area
% Area Height Int Type Peak Type Peak Codes
1
2
11.034
12.559
1691214
2431305
41.02
58.98
38162
50109
BV
VB
Unknown
Unknown
0
0
0
0
.60
.40
.20
.00
2
.00
4.00
6.00
8. 00
min
10.00
12.00
14.00
Name Retention Time Area
% Area Height Int Type Peak Type Peak Codes
1
2
11.008
11.977
501931
1.33
17226
bb
Unknown
Unknown
37135930 98.67
747498 bB
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(
S)-tert-Butyl 5-bromo-1,1'-dimethyl-2-oxo-3,3'-biindolin-3-ylcarbamate (4g)
The ee value determination was carried out using chiral high-performance
liquid chromatography (HPLC) with Chiracel IA-H column (hexane :
2-propanol = 60 : 40, 1.0 mL/min, 95% ee). White solid, 93% yield; mp =
N
H
N
Boc
o
20
1
123-124 C; [α]
D
= +274 (c 1.0, CHCl
3 3
); H NMR (300 MHz, CDCl ): δ
O
=
8.17 (d, J = 7.5 Hz, 1H), 7.54 (d, J = 1.8 Hz, 1H), 7.48 (d, J = 8.1 Hz, 1H),
N
Br
7.17-7.29 (m, 3H), 6.74 (d, J = 8.1 Hz, 1H), 6.53 (s, 1H), 5.76 (br.s, 1H),
1
3
3
3.64 (s, 3H), 3.16 (s, 3H), 1.34 (br.s, 9H) ppm; C NMR (75 MHz, CDCl )
δ = 175.2, 153.7, 142.8, 137.9, 131.8, 128.1, 126.5, 124.9, 122.6, 121.7, 120.2, 115.0, 110.7, 109.8,
0.6, 61.9, 32.9, 28.2, 26.6 ppm; IR (KBr): 3354, 2972, 1467, 1380, 1309, 1162, 1130, 1110, 953, 817
8
-
1
+
cm ; HRMS calcd for C23
H
24BrN
3
3
NaO (M+Na) 492.0893, found 492.0913.
0
0
0
0
0
0
.50
.40
.30
.20
.10
.00
2
.00
4.00
6. 00
8.00
min
10.00
12.00
14.00
16.00
Name Retention Time Area
% Area Height
Int Type Peak Type Peak Codes
1
2
6.052
6558084 51.01
6297579 48.99
529035
225534
bb
bb
Unknown
Unknown
14.624
1.00
0.50
0.00
2.00
4.00
6.00
8.00
10.00
12.00
14.00
16.00
min
Name Retention Time Area
% Area Height
84748
Int Type Peak Type Peak Codes
1
2
6.089
1091964 2.68
bb
Unknown
Unknown
14.873
39727255 97.32
1337814 bb
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(
S)-tert-Butyl 6-chloro-1,1'-dimethyl-2-oxo-3,3'-biindolin-3-ylcarbamate (4h)
The ee value determination was carried out using chiral
high-performance liquid chromatography (HPLC) with Chiracel IA-H
column (hexane : 2-propanol = 60 : 40, 1.0 mL/min, 89% ee). White
N
Boc NH
o
20
1
solid, 98% yield; mp = 94-96 C; [α]
NMR (300 MHz, CDCl ): δ = 8.16 (d, J = 7.5 Hz, 1H), 7.34 (d, J = 8.1
Hz, 1H), 7.16-7.24 (m, 2H), 7.16-7.22 (m, 1H), 7.10 (d, J = 7.2 Hz, 1H),
.86 (d, J = 1.5 Hz, 1H), 6.51 (s, 1H), 5.77 (br.s, 1H), 3.62 (s, 3H), 3.15
D
3
= +282 (c 1.0, CHCl ); H
O
3
N
Cl
6
1
3
(
s, 3H), 1.33 (br.s, 9H) ppm; C NMR (75 MHz, CDCl
3
) δ = 175.6, 153.8, 144.9, 137.9, 134.6, 128.2,
1
25.0, 124.3, 122.6, 122.2, 121.7, 120.1, 110.9, 109.8, 109.0, 80.5, 61.5, 32.9, 28.2, 26.7 ppm; IR
-
1
(
KBr): 3343, 2971, 1718, 1610, 1494, 1469, 1370, 1162, 952, 743 cm ; HRMS calcd for
+
C
23
H
25ClN
3
O
3
(M+H) 426.1579, found 426.1583.
0.80
0.60
0.40
0.20
0.00
2.00
4.00
6. 00
8.00
10.00
12.00
14.00
16.00
min
Name Retention Time
Area
% Area Height Int Type Peak Type Peak Codes
1
2
5.666
8107155
8204036
49.70 770491
50.30 310346
VV
VV
Unknown
Unknown
13.908
0
.80
.60
.40
.20
.00
0
0
0
0
2.00
4.00
6.00
8.00
10.00
12.00
14.00
16.00
min
Name Retention Time
Area
% Area Height Int Type Peak Type Peak Codes
1
2
5.668
1404023
23274501
5.69
127175
bb
Unknown
Unknown
13.988
94.31 884014
BV
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(
S)-tert-Butyl 7-fluoro-1,1'-dimethyl-2-oxo-3,3'-biindolin-3-ylcarbamate (4i)
The ee value determination was carried out using chiral high-performance
liquid chromatography (HPLC) with Chiracel OD-H column (hexane :
2-propanol = 80 : 20, 1.0 mL/min, 86% ee). White solid, 94% yield; mp =
N
Boc
NH
N
o
20
1
1
8
2
28-130 C; [α]
D
3 3
= +229 (c 1.0, CHCl ); H NMR (300 MHz, CDCl ): δ =
O
.18 (d, J = 7.8 Hz, 1H), 7.24-7.29 (m, 2H), 7.17-7.23 (m, 2H), 7.01-7.12 (m,
H), 6.49 (s, 1H), 5.78 (br.s, 1H), 3.64 (s, 3H), 3.40 (s, 3H), 1.34 (br.s, 9H)
F
13
ppm; C NMR (75 MHz, CDCl
3
) δ = 175.5, 153.8, 137.9, 130.4, 130.3,
1
28.3, 125.0, 122.9, 122.8, 122.6, 121.8, 120.1, 119.3, 119.2, 117.1, 116.8, 111.0, 109.8, 80.6, 62.0,
-
1
32.9, 29.0, 28.1 ppm; IR (KBr): 3019, 2400, 1716, 1486, 1369, 1238, 1216, 1161, 758, 669 cm ;
+
HRMS calcd for C23
H
24FN
3
NaO
3
(M+Na) 432.1694, found 432.1707.
0.15
0.10
0.05
0.00
0.00
2. 00
4.00
6.00
8.00
10.00
12.00
14.00
min
16.00
18.00
20.00
22.00
24.00
26.00
28.00
Name Retention Time
17.026
Area
% Area Height Int Type Peak Type Peak Codes
1
2
11201574 50.33
11056027 49.67
173483 bb
117248 bb
Unknown
Unknown
22.910
0.40
0.20
0.00
0. 00
2.00
4.00
6.00
8.00
10.00
12.00
14.00
min
16.00
18.00
20.00
22.00
24.00
26.00
Name Retention Time
16.597
Area
32491881 92.79
2523960 7.21
% Area Height Int Type Peak Type Peak Codes
1
2
484293 bb
31479 bb
Unknown
Unknown
23.434
S 11

Electronic Supplementary Material (ESI) for Chemical Communications
This journal is © The Royal Society of Chemistry 2012
(
S)-tert-Butyl 5'-methoxy-1,1'-dimethyl-2-oxo-3,3'-biindolin-3-ylcarbamate (4j)
The ee value determination was carried out using chiral high-performance
liquid chromatography (HPLC) with Chiracel IA-H column (hexane :
N
H
2
-propanol = 60 : 40, 1.0 mL/min, 90% ee). White solid, 98% yield; mp =
Boc N
O
O
o
20
1
1
18-120 C; [α]
7.59 (s, 1H), 7.39 (dd, J = 18.0, 7.5 Hz, 2H)), 7.11-7.15 (m, 2H), 6.85-6.91
m, 2H), 6.51 (s, 1H), 5.69 (br.s, 0.44H), 5.51 (br.s, 0.53H), 3.89 (s, 3H),
D
3 3
= +274 (c 1.0, CHCl ); H NMR (300 MHz, CDCl ): δ =
N
(
1
3
3
1
6
3
.59 (s, 3H), 3.18 (s, 3H), 1.30 (br.s, 4H), 1.16 (br.s, 5H) ppm; C NMR (75 MHz, CDCl ) δ = 175.8,
54.2, 153.9, 143.8, 133.1, 129.0, 128.7, 125.5, 123.5, 122.4, 113.0, 110.7, 110.4, 108.1, 103.2, 80.3,
1.9, 55.9, 33.0, 28.1, 26.5 ppm; IR (KBr): 3017, 2979, 1715, 1494, 1472, 1367, 1217, 1165, 754, 667
-
1
+
28 3 4
cm ; HRMS calcd for C24H N O (M+H) 422.2074, found 422.2091.
1.50
1.00
0.50
0.00
0. 00
2.00
4.00
6.00
8.00
10.00
12.00
min
14.00
16.00
18.00
20.00
22.00
24.00
Name Retention Time
Area
% Area Height Int Type Peak Type Peak Codes
1
2
5.890
19357448
19446709
49.88 1680162
BB
BB
Unknown
Unknown
20.197
50.12
498620
0.20
0.10
0.00
0.00
2.00
4.00
6. 00
8.00
10.00
12.00
14.00
min
16.00
18.00
20.00
22.00
24.00
26.00
Name Retention Time
Area
% Area Height Int Type Peak Type Peak Codes
1
2
5.930
470233
4.98
38865
bb
20.382
8967377
95.02 229692
BV
S 12

Electronic Supplementary Material (ESI) for Chemical Communications
This journal is © The Royal Society of Chemistry 2012
(
S)-tert-Butyl 1,1',5'-trimethyl-2-oxo-3,3'-biindolin-3-ylcarbamate (4k)
The ee value determination was carried out using chiral high-performance
liquid chromatography (HPLC) with Chiracel OD-H column (hexane :
2-propanol = 90 : 10, 1.0 mL/min, 92% ee). White solid, 96% yield; mp =
N
Boc NH
o
20
1
1
39-140 C; [α]
= 8.01 (br.s, 1H), 7.33-7.43 (m, 2H), 7.04-7.15 (m, 3H), 6.85 (d, J = 7.8 Hz,
H), 6.43 (s, 1H), 5.54 (br.s, 1H), 3.57 (s, 3H), 3.17 (s, 3H), 2.50 (s, 3H),
.16 (br.s, 9H) ppm; C NMR (75 MHz, CDCl ) δ = 175.8, 153.9, 143.7, 136.4, 129.3, 128.9, 128.3
25.3, 124.2, 123.4, 122.4, 121.5, 110.8, 109.4, 108.0, 80.3, 62.0, 32.8, 28.1, 26.5, 21.7 ppm; IR
D
3 3
= +279 (c 1.0, CHCl ); H NMR (300 MHz, CDCl ): δ
O
N
1
1
3
1
1
3
-
1
(
(
KBr): 3018, 2921, 1715, 1614, 1492, 1472, 1371, 1216, 754, 667 cm ; HRMS calcd for C24
H
28
N
3
O
3
+
M+H) 406.2125, found 406.2144.
0.010
0.005
0.000
2.00
4.00
6.00
8.00
10.00
min
12.00
14.00
16.00
18.00
20.00
Name Retention Time
14.015
Area
% Area Height Int Type Peak Type Peak Codes
1
2
779996
648982
54.58
45.42
13422 bb
8439 bb
Unknown
Unknown
17.122
0.20
0.15
0.10
0.05
0.00
2.00
4.00
6.00
8.00
10.00
min
12.00
14.00
16.00
18.00
Name Retention Time Area
% Area Height Int Type Peak Type Peak Codes
1
2
13.787
17.151
11065094
489911
95.76
4.24
196775 bb
7575 bb
Unknown I08
Unknown
S 13

Electronic Supplementary Material (ESI) for Chemical Communications
This journal is © The Royal Society of Chemistry 2012
(
S)-tert-Butyl 5'-bromo-1,1'-dimethyl-2-oxo-3,3'-biindolin-3-ylcarbamate (4l)
The ee value determination was carried out using chiral high-performance
liquid chromatography (HPLC) with Chiracel OJ-H column (hexane :
N
O
Boc
2
-propanol = 97 : 3, 0.8 mL/min, 90% ee). White solid, 96% yield; mp =
NH
N
o
20
1
117-119 C; [α]
D
3 3
= +268 (c 1.0, CHCl ); H NMR (300 MHz, CDCl ):
δ = 8.31 (s, 1H), 7.41 (dd, J = 15.0, 7.5 Hz, 2H), 7.27 (d, J = 9.6 Hz, 1H),
Br
7.14 (t, J = 7.5 Hz, 1H) 7.08 (d, J = 9.0 Hz, 1H), 6.87 (d, J = 7.8 Hz,
1
H), 6.52 (s, 1H), 5.57 (br.s, 1H), 3.59 (s, 3H), 3.17 (s, 3H), 1.25 (br.s, 9H)
1
3
ppm; C NMR (75 MHz, CDCl
3
) δ = 175.5, 153.8, 143.7, 136.6, 129.4, 129.1, 126.7, 125.5, 124.3,
1
1
23.4, 122.5, 113.6, 111.2, 111.1, 108.2, 80.5, 61.7, 33.0, 28.1, 26.5 ppm; IR (KBr): 2920, 2848, 1720,
-
1
+
471, 1422, 1369, 1288, 1250, 1164, 752 cm ; HRMS calcd for C23
H
24BrN
3
3
NaO (M+Na) 492.0893,
found 492.0915.
0.04
0.02
0.00
0.00
10.00
20.00
30.00
40.00
50.00
min
60.00
70.00
80.00
90.00
100.00
Name Retention Time
Area
% Area Height Int Type Peak Type Peak Codes
1
2
53.901
81.169
27160079
24389411
52.69
47.31
54998
25326
bb
bb
Unknown
Unknown
0.15
0.10
0.05
0.00
0.00
10.00
20.00
30.00
40.00
50.00
min
60.00
70.00
80.00
90.00
Name Retention Time
Area
% Area Height Int Type Peak Type Peak Codes
1
2
52.556
86.527
92490248
5129374
94.75 174466
5.25 6407
bb
bb
Unknown
Unknown
S 14

Electronic Supplementary Material (ESI) for Chemical Communications
This journal is © The Royal Society of Chemistry 2012
(
S)-tert-Butyl 1,1',6'-trimethyl-2-oxo-3,3'-biindolin-3-ylcarbamate (4m)
The ee value determination was carried out using chiral high-performance
liquid chromatography (HPLC) with Chiracel OD-H column (hexane :
2-propanol = 90 : 10, 1.0 mL/min, 94% ee). White solid, 98% yield; mp =
N
H
N
o
20
1
Boc
149-150 C; [α]
D
3 3
= +275 (c 1.0, CHCl ); H NMR (300 MHz, CDCl ): δ
O
=
8.06 (d, J = 7.8 Hz, 1H), 7.41 (d, J = 7.2 Hz, 1H), 7.32 (t, J = 7.8 Hz, 1H),
N
7
.11 (t, J = 7.5 Hz, 1H), 7.04 (s, 1H), 7.02 (d, J = 8.4 Hz, 1H), 6.85 (d, J =
7
.8 Hz, 1H), 6.45 (s, 1H), 5.65 (br.s, 1H), 3.58 (s, 3H), 3.18 (s, 3H), 2.47 (s,
1
3
3
H), 1.26 (br.s, 9H) ppm; C NMR (75 MHz, CDCl
3
) δ = 175.8, 153.9, 143.7, 138.3, 132.4, 128.9,
1
27.7, 123.4, 122.9, 122.4, 121.8, 121.5, 111.4, 109.6, 108.0, 80.2, 61.9, 32.7, 28.1, 26.5, 21.8 ppm;
-
1
IR (KBr): 3015, 2921, 1716, 1614, 1473, 1371, 1351, 1216, 753, 666 cm ; HRMS calcd for
+
C
24
H
28
N
3
O
3
(M+H) 406.2125, found 406.2144.
0
.25
0
0
0
0
0
.20
.15
.10
.05
.00
0
.00
2. 00
4.00
6.00
8.00
10.00
12.00
14.00
min
16.00
18.00
20.00
22.00
24.00
26.00
Name Retention Time
17.727
Area
% Area Height Int Type Peak Type Peak Codes
1
2
21286228 57.40
15797245 42.60
242293 BV
123955 VV
Unknown
Unknown
22.810
0
0
0
0
0
0
0
.60
.50
.40
.30
.20
.10
.00
0
.00
2. 00
4.00
6.00
8.00
10.00
12.00
14.00
min
16.00
18.00
20.00
22.00
24.00
26.00
Name Retention Time
16.921
Area
51129984 96.96
1605365 3.04
% Area Height Int Type Peak Type Peak Codes
1
2
569216 bb
14454 bb
Unknown
Unknown
23.486
S 15

Electronic Supplementary Material (ESI) for Chemical Communications
This journal is © The Royal Society of Chemistry 2012
(
S)-tert-Butyl 1,1',7'-trimethyl-2-oxo-3,3'-biindolin-3-ylcarbamate (4n)
The ee value determination was carried out using chiral high-performance liquid
chromatography (HPLC) with Chiracel OD-H column (hexane : 2-propanol =
N
o
H
90 : 10, 1.0 mL/min, 96% ee). White solid, 98% yield; mp = 126-128 C;
N
Boc
20
1
O
[α]
Hz, 1H), 7.41 (d, J = 7.2 Hz, 1H), 7.35 (t, J = 7.5 Hz, 1H), 7.11 (t, J = 7.5 Hz,
H), 7.04 (t, J = 7.8 Hz, 1H), 6.92 (d, J = 7.2 Hz, 1H), 6.85 (d, J = 7.8 Hz, 1H),
D
3 3
= +276 (c 1.0, CHCl ); H NMR (300 MHz, CDCl ): δ = 8.05 (d, J = 7.8
N
1
1
3
6
.38 (br.s, 1H), 5.65 (br.s, 1H), 3.87 (s, 3H), 3.17 (s, 3H), 2.69 (s, 3H), 1.26 (br.s, 9H) ppm; C NMR
75 MHz, CDCl ) δ = 175.7, 153.9, 143.7, 136.7, 129.9, 128.9, 126.2, 125.1, 123.4, 122.4, 121.6,
20.2, 120.0, 111.1, 108.1, 80.3, 61.9, 37.0, 28.1, 26.5, 19.8 ppm; IR (KBr): 2976, 2931, 1720, 1614,
(
3
1
1
4
-
1
+
493, 1471, 1368, 1347, 1164, 753 cm ; HRMS calcd for C24
06.2139.
28 3 3
H N O (M+H) 406.2125, found
0
0
0
0
0
0
.10
.08
.06
.04
.02
.00
0
.00
2.00
4.00
6.00
8.00
10.00
12 .0 0
14.00
16.00
min
18.00
20.00
22.00
24 .0 0
26.00
28.00
30.00
32.00
Name Retention Time
19.912
Area
% Area Height Int Type Peak Type Peak Codes
1
2
8815195 57.55
6501299 42.45
106909 Bb
45976 Bb
Unknown
Unknown
24.753
0
0
0
0
0
.40
.30
.20
.10
.00
0.00
2.00
4.00
6.00
8.00
10.00
12.00
14.00
min
16 .0 0
18.00
20.00
22.00
24.00
26.00
28.00
Name Retention Time Area
% Area Height Int Type Peak Type Peak Codes
1
2
18.836
25.106
35956220
823015
97.76
2.24
397654 Bb
7192 Bb
Unknown
Unknown
S 16

Electronic Supplementary Material (ESI) for Chemical Communications
This journal is © The Royal Society of Chemistry 2012
(
S)-tert-Butyl 1,1',2'-trimethyl-2-oxo-3,3'-biindolin-3-ylcarbamate (4o)
The ee value determination was carried out using chiral high-performance
liquid chromatography (HPLC) with Chiracel IA-H column (hexane :
N
2
-propanol = 70 : 30, 1.0 mL/min, 87% ee). White solid, 98% yield; mp =
H
o
20
1
Boc N
210-211 C; [α]
7.35-7.42 (m, 2H), 7.18 (d, J = 8.1 Hz, 1H), 7.06-7.11 (m, 2H), 6.86-6.92
(m, 3H), 5.70 (br.s, 1H), 3.56 (s, 3H), 3.18 (s, 3H), 2.37 (s, 3H), 1.25 (br.s,
D
3 3
= +126 (c 1.0, CHCl ); H NMR (300 MHz, CDCl ): δ
O
=
N
1
3
9H) ppm; C NMR (75 MHz, CDCl
3
) δ = 176.5, 154.0, 144.0, 136.6, 131.7,
1
29.1, 125.4, 124.3, 122.5, 121.0, 120.1, 119.6, 108.9, 108.1, 107.0, 80.4, 62.6, 29.5, 28.1, 26.5, 12.2
-
1
ppm; IR (KBr): 3005, 2920, 1719, 1612, 1491, 1470, 1368, 1242, 1165, 748 cm ; HRMS calcd for
+
C
24
H
28
N
3
O
3
(M+H) 406.2125, found 406.2140.
0.15
0.10
0.05
0.00
1.00
2.00
3.00
4.00
5.00
min
6.00
7.00
8. 00
9. 00
Name Retention Time Area
% Area Height Int Type Peak Type Peak Codes
1
2
6.702
8.749
2088680
2121730
49.61
50.39
152583 bb
124026 bb
Unknown
Unknown
0
0
0
0
0
0
0
.60
.50
.40
.30
.20
.10
.00
1
.00
2. 00
3.00
4.00
5.00
6.00
7.00
8.00
min
9.00
10.00
11.00
12.00
13.00
14.00
15 .0 0
Name Retention Time Area
% Area Height Int Type Peak Type Peak Codes
1
2
6.698
8.728
719207
6.73
56109
bb
Unknown
Unknown
9961817
93.27
573829 bb
S 17

Electronic Supplementary Material (ESI) for Chemical Communications
This journal is © The Royal Society of Chemistry 2012
(
S)-tert-Butyl 1-methyl-2-oxo-3,3'-biindolin-3-ylcarbamate (4p)
The ee value determination was carried out using chiral high-performance
liquid chromatography (HPLC) with Chiracel IA-H column (hexane :
H
N
2
-propanol = 60 : 40, 1.0 mL/min, 64% ee). White solid, 97% yield; mp =
H
N
o
20
1
Boc
142-143 C; [α]
3 3
= +184 (c 1.0, CHCl ); H NMR (300 MHz, CDCl ): δ =
D
O
8
7
6
.78 (s, 1H), 8.10 (d, J = 8.4 Hz, 1H), 7.36 (d, J = 7.2 Hz, 1H), 7.31 (s, 1H),
N
.24 (dd, J = 7.2, 1.5 Hz, 1H), 7.08-77.16 (m, 3H), 6.79 (d, J = 6.6 Hz, 1H),
1
3
.50 (d, J = 2.1 Hz, 1H), 5.81 (br.s, 1H), 3.09 (s, 3H), 1.29 (br.s, 9H) ppm; C
NMR (75 MHz, CDCl
3
) δ = 175.9, 154.0, 143.6, 137.2, 129.0, 124.5, 124.2, 123.4, 122.61, 122.55,
1
1
4
21.4, 120.1, 112.5, 111.9, 108.2, 80.5, 62.0, 28.1, 26.5 ppm; IR (KBr): 3328, 3019, 1714, 1615, 1472,
-
1
+
370, 1216, 1165, 758, 669 cm ; HRMS calcd for C22
00.1647.
23 3 3
H N NaO (M+Na) 400.1637, found
1
1
0
0
0
0
0
.2 0
.0 0
.8 0
.6 0
.4 0
.2 0
.0 0
1
.0 0
2. 0 0
3 .0 0
4 .0 0
m in
5 .0 0
6 .0 0
7 .0 0
8 .0 0
Name Retention Time
Area
% Area Height
Int Type Peak Type Peak Codes
1
2
5.261
6.531
13957363 49.94
13992568 50.06
1222237 bb
989766 bb
Unknown
Unknown
1
.00
.00
0
1.00
2.00
3.00
4.00
5.00
6.00
7.00
8.00
9.00
min
Name Retention Time
Area
% Area Height
Int Type Peak Type Peak Codes
1
2
5.244
6.480
5289329 18.09
23953365 81.91
479636
bb
Unknown I08
Unknown
1798727 bb
S 18

Electronic Supplementary Material (ESI) for Chemical Communications
This journal is © The Royal Society of Chemistry 2012
(
S)-tert- Butyl 1'-benzyl-1-methyl-2-oxo-3,3'-biindolin-3-ylcarbamate (4q)
The ee value determination was carried out using chiral high-performance liquid
chromatography (HPLC) with Chiracel IA-H column (hexane : 2-propanol = 80 :
Bn
N
o
20
H
N
2
0, 1.0 mL/min, 98% ee). White solid, 96% yield; mp = 102-104 C; [α]
D
=
Boc
1
O
+244 (c 1.0, CHCl
3
); H NMR (300 MHz, CDCl
3
): δ = 8.21 (d, J = 6.0 Hz, 1H),
7.42 (d, J = 7.5 Hz, 1H), 7.35 (t, J = 7.5 Hz, 1H), 7.23-7.24 (m, 8H), 7.08-7.19
N
(
m, 8H), 7.00 (d, J = 5.7 Hz, 1H), 6.98 (s, 1H), 6.86 (d, J = 7.8 Hz, 1H), 6.64 (s,
1
3
1
1
1
1
4
3
H), 5.72 (br.s, 1H), 5.14 (s, 2H), 3.19 (s, 3H), 1.27 (br.s, 9H) ppm; C NMR (75 MHz, CDCl ) δ =
75.7, 153.8, 143.8, 137.5, 136.9, 129.0, 128.8, 127.9, 127.7, 126.5, 125.4, 123.4, 122.7, 122.5, 122.1,
20.3, 112.3, 110.3, 108.2, 80.3, 61.9, 50.2, 28.1, 26.6 ppm; IR (KBr): 3005, 2922, 1719, 1613, 1492,
-
1
+
469, 1369, 1164, 746, 695 cm ; HRMS calcd for C29
90.2112.
H
29
N
3
3
NaO (M+Na) 490.2107, found
0.030
0.020
0.010
0.000
2.00
4.00
6.00
8.00
10.00
12.00
14.00
16.00
18.00
min
name Retention Time Area
% Area
Height Int Type Peak Type Peak Codes
1
2
11.372
14.529
1331611 50.71
1294480 49.29
29464
19684
bb
bb
Unknown
Unknown
0.10
0.05
0.00
2.00
4.00
6. 00
8.00
min
10.00
12.00
14.00
16.00
Name Retention Time Area
% Area Height Int Type Peak Type Peak Codes
1
2
10.786
14.325
5798655 98.96
61186 1.04
136394 BB
1386 bb
Unknown
Unknown
S 19

Electronic Supplementary Material (ESI) for Chemical Communications
This journal is © The Royal Society of Chemistry 2012
(
S)-tert-Butyl 5,5'-dibromo-1,1'-dimethyl-2-oxo-3,3'-biindolin-3-ylcarbamate (4s)
The ee value determination was carried out using chiral
high-performance liquid chromatography (HPLC) with Chiracel IA-H
column (hexane : 2-propanol = 70 : 30, 1.0 mL/min, 96% ee). White
N
H
N
Boc
Br
o
20
1
O
solid, 96% yield; mp = 243-244 C; [α]
NMR (300 MHz, CDCl ): δ = 8.34 (s, 1H), 7.44-7.57 (m, 2H),
.26-7.33 (m, 1H), 7.12 (d, J = 8.7 Hz, 1H), 6.76 (d, J = 8.4 Hz, 1H),
D
3
= +237 (c 1.0, CHCl ); H
3
N
Br
7
1
3
6
.52 (s, 1H), 5.62 (br.s, 1H), 3.63 (s, 3H), 3.16 (s, 3H), 1.37 (br.s, 9H) ppm; C NMR (75 MHz,
CDCl ) δ = 174.9, 153.7, 142.8, 136.6, 133.1, 132.0, 129.3, 128.6, 126.5, 125.7, 124.3, 115.0, 113.8,
11.2, 110.4, 109.7, 80.9, 61.6, 33.1, 28.1, 26.6 ppm; IR (KBr): 3425, 2258, 1709, 1659, 1051, 1027,
3
1
-
1
+
1
2 3 3
005, 825, 763, 624 cm ; HRMS calcd for C23H23Br N NaO (M+Na) 569.9998, found 570.0007.
0.40
0.20
0.00
0.00
5.00
10.00
15.00
min
20.00
25.00
Name Retention Time
Area
% Area Height Int Type Peak Type Peak Codes
1
2
6.309
6276531
6184168
50.37 467641
49.63 145790
VB
BV
Unknown
Unknown
22.442
0.20
0.10
0.00
0.00
2.00
4. 00
6.00
8. 00
10.00
12.00
min
14.00
16.00
18.00
20.00
22.00
24.00
Name Retention Time Area
% Area Height Int Type Peak Type Peak Codes
1
2
6.284
211196
2.06
12596
bb
bb
Unknown
Unknown
22.973
10055122 97.94 228711
S 20

Electronic Supplementary Material (ESI) for Chemical Communications
This journal is © The Royal Society of Chemistry 2012
(
R)-tert- Butyl 1-methyl-2-oxo-3-(1H-pyrrol-2-yl)indolin-3-ylcarbamate (6a)
The ee value determination was carried out using chiral high-performance
liquid chromatography (HPLC) with Chiracel AD-H column (hexane :
Boc
NH
N
NH
2
9
1
-propanol = 60 : 40, 1.0 mL/min, 99% ee). White solid, 97% yield; mp =
o
20
1
3-94 C; [α]
0.11 (br.s, 1H), 7.40 (d, J = 6.9 Hz, 1H), 7.28 (t, J = 7.5 Hz, 1H), 7.08 (t, J
7.5 Hz, 1H), 6.80 (s, 1H), 6.77 (s, 1H), 6.14 (br.s, 1H), 5.91 (d, J = 1.8 Hz,
D
3 3
= +143 (c 1.0, CHCl ); H NMR (300 MHz, CDCl ): δ =
O
=
1
3
1
H), 5.74 (s, 1H), 3.15 (s, 3H), 1.14 (br.s, 9H) ppm; C NMR (75 MHz, CDCl
3
) δ = 174.8, 152.1,
1
42.4, 128.1, 124.0, 122.5, 121.8, 120.3, 108.6, 107.6, 107.0, 106.5, 79.6, 59.3, 26.9, 25.6 ppm; IR
-
1
(
KBr): 3318, 3007, 2975, 2932, 1709, 1616, 1495, 1472, 1371, 1255, 1161, 988, 895, 753, 541 cm ;
+
HRMS calcd for C18
H
22
N
3
O
3
(M+H) 328.1656, found 328.1657.
0
0
0
0
0
.08
.06
.04
.02
.00
2
.00
4.00
6.00
8.00
min
10.00
12.00
14.00
Name Retention Time Area
% Area Height Int Type Peak Type Peak Codes
1
2
9.521
2650216 49.11
2745923 50.89
90835 bb
72257 bb
Unknown
Unknown
12.547
0
0
0
0
0
.08
.06
.04
.02
.00
2
.00
4. 00
6.00
8.00
min
10.00
12.00
14.00
16.00
Name Retention Time Area
% Area Height Int Type Peak Type Peak Codes
1
2
9.198
17467
0.39
543
bb
Unknown
Unknown
12.098
4406629 99.61
91726 BV
S 21

Electronic Supplementary Material (ESI) for Chemical Communications
This journal is © The Royal Society of Chemistry 2012
(
R)-tert- Butyl 5-methoxy-1-methyl-2-oxo-3-(1H-pyrrol-2-yl)indolin-3-ylcarbamate (6b)
The ee value determination was carried out using chiral
high-performance liquid chromatography (HPLC) with Chiracel AD-H
column (hexane : 2-propanol = 60 : 40, 1.0 mL/min, 99% ee). White solid,
Boc
NH
N
NH
O
O
o
20
1
9
6% yield; mp = 91-93 C; [α]
MHz, CDCl ): δ = 10.24 (br.s, 1H), 7.10 (d, J = 2.1 Hz, 1H), 6.84-6.89
m, 2H), 6.76 (t, J = 8.1 Hz, 1H), 6.22 (br.s, 1H), 5.99 (d, J = 3.0 Hz, 1H),
D
3
= +167 (c 1.0, CHCl ); H NMR (300
3
(
1
3
5
.85 (s, 1H), 3.84 (s, 3H), 3.21 (br.s, 3H), 1.21 (br.s, 6H), 1.09 (br.s, 3H) ppm; C NMR (75 MHz,
) δ = 175.5, 156.1, 153.1, 136.9, 130.6, 125.0, 121.4, 112.9, 111.3, 109.6, 108.9, 107. 5, 80.7,
0.5, 55.9, 27.9, 26.7 ppm; IR (KBr): 3315, 2922, 1705, 1498, 1473, 1368, 1289, 1162, 1935, 754
CDCl
3
6
-
1
+
24 3 4
cm ; HRMS calcd for C19H N O (M+H) 358.1761 found 358.1761.
0.04
0.02
0.00
0. 00
2.00
4.00
6.00
8.00
10.00
min
12.00
14.00
16.00
18.00
20.00
Name Retention Time Area
% Area Height Int Type Peak Type Peak Codes
1
2
8.948
1886636 46.74
2149629 53.26
56363
31670
bb
bb
Unknown
16.597
Unknown I08
0.20
0.10
0.00
0. 00
2.00
4.00
6.00
8.00
10.00
12.00
min
14.00
16.00
18.00
20.00
22.00
Name Retention Time Area
% Area Height Int Type Peak Type Peak Codes
1
2
8.986
108670
0.64
2882
bb
Unknown
Unknown
16.662
16832993 99.36
219258 BB
S 22

Electronic Supplementary Material (ESI) for Chemical Communications
This journal is © The Royal Society of Chemistry 2012
(
R)-tert-Butyl 1,5-dimethyl-2-oxo-3-(1H-pyrrol-2-yl)indolin-3-ylcarbamate (6c)
The ee value determination was carried out using chiral high-performance
liquid chromatography (HPLC) with Chiracel OD-H column (hexane :
Boc
NH
N
NH
2
-propanol = 60 : 40, 1.0 mL/min, 99% ee). White solid, 97% yield; mp =
O
o
20
1
111-113 C; [α]
D
= +168 (c 1.0, CHCl
3 3
); H NMR (300 MHz, CDCl ): δ =
10.26 (br.s, 0.62H), 10.04 (br.s, 0.36H), 7.27 (d, J = 6.3 Hz, 1H), 7.15 (d, J =
7.8 Hz, 1H), 6.84 (dd, J = 4.2, 1.8 Hz, 1H), 6.75 (d, J = 7.5 Hz, 1H), 6.22 (br.s, 0.66H), 5.98 (d, J =
3
.0 Hz, 1H), 5.90 (br.s, 0.33H), 5.82 (s, 1H), 3.21 (s, 3H), 2.40 (s, 3H), 1.22 (br.s, 6H), 1.08 (br.s, 3H)
1
3
ppm; C NMR (75 MHz, CDCl
3
) δ = 175.7, 153.1, 141.1, 132.3, 129.4, 125.3, 124.3, 121.3, 109.6,
1
8
08.4, 107.4, 80.7, 60.4, 28.0, 26.7, 21.3 ppm; IR (KBr): 3314, 2921, 1707, 1501, 1366, 1161, 1094,
-
1
+
24 3 3
11, 754, 698 cm ; HRMS calcd for C19H N O (M+H) 342.1812 found 342.1810.
0.60
0.40
0.20
0.00
1.00
2.00
3.00
4.00
5.00
6.00
7.00
min
Name Retention Time Area
% Area Height Int Type Peak Type Peak Codes
1
2
4.289
4.990
7281242 48.02
600877 VV
562256 VV
Unknown
Unknown
7881982 51.98
1.50
1.00
0.50
0.00
1. 00
2.00
3.00
4.00
5.00
min
Name Retention Time Area
% Area Height
Int Type Peak Type Peak Codes
1
2
4.054
4.712
57322
0.24
4245
VB
Unknown
Unknown
24015884 99.76
1808176 Bb
S 23

Electronic Supplementary Material (ESI) for Chemical Communications
This journal is © The Royal Society of Chemistry 2012
(
R)-tert-Butyl 1-methyl-2-oxo-3-(1H-pyrrol-2-yl)-5-(trifluoromethoxy)indolin-3-ylcarbamate (6d)
The ee value determination was carried out using chiral
high-performance liquid chromatography (HPLC) with Chiracel OD-H
column (hexane : 2-propanol = 60 : 40, 1.0 mL/min, 98% ee). White
Boc
NH
N
NH
O
F3C
O
o
20
1
solid, 98% yield; mp = 119-120 C; [α]
NMR (300 MHz, CDCl ): δ = 10.12 (br.s, 1H), 7.37 (s, 1H), 7.25 (d, J =
.2 Hz, 1H), 6.86 (dd, J = 7.5, 3.0 Hz, 2H), 6.18 (br.s, 0.63H), 6.05 (br.s, 0.31H), 6.11 (dd, J = 6.0, 1.8
D
3
= +186 (c 1.0, CHCl ); H
3
7
1
3
Hz, 1H), 5.81 (s, 1H), 3.25 (s, 3H), 1.23 (br.s, 6H), 1.07 (br.s, 3H) ppm; C NMR (75 MHz, CDCl
176.0, 153.9, 153.0, 144.9, 142.1, 130.9, 125.7, 123.8, 122.3, 122.0, 118.9, 117.6, 115.5, 109.8,
09.3, 108.9, 107.6, 81.3, 61.0, 60.4, 27.8, 26.8 ppm; IR (KBr): 3325, 2976, 1713, 1498, 1369, 1257,
3
) δ
=
1
1
-
1
+
20 3 3 4
218, 1162, 1120, 736 cm ; HRMS calcd for C19H F N NaO (M+Na) 434.1298, found 434.1298.
0
0
0
0
.30
.20
.10
.00
1
.00
2.00
3.00
4.00
5.00
6.00
7.00
8.00
min
Name Retention Time Area
% Area Height
1.07 17077
16801303 98.93 1051520 BB
Int Type Peak Type Peak Codes
1
2
4.794
5.818
181507
bb
Unknown
Unknown
1
.00
.80
.60
.40
.20
.00
0
0
0
0
0
0.50
1.00
1.50
2.00
2.50
3.00
3.50
min
4.00
4. 50
5.00
5.50
6.00
6.50
7.00
Name Retention Time Area
% Area Height
1.05 16930
16720730 98.95 1050996 Bb
Int Type Peak Type Peak Codes
1
2
4.794
5.818
178022
bb
Unknown
Unknown
S 24

Electronic Supplementary Material (ESI) for Chemical Communications
This journal is © The Royal Society of Chemistry 2012
(
R)-tert-Butyl 5-bromo-1-methyl-2-oxo-3-(1H-pyrrol-2-yl)indolin-3-ylcarbamate (6e)
The ee value determination was carried out using chiral high-performance
liquid chromatography (HPLC) with Chiracel OD-H column (hexane :
Boc
NH
N
NH
Br
2
2
-propanol = 80 : 20, 1.0 mL/min, 99% ee). White solid, 95% yield; mp =
o
20
1
O
03-205 C; [α]
D
3 3
= +151 (c 1.0, CHCl ); H NMR (300 MHz, CDCl ):
δ = 10.15 (br.s, 1H), 7.56 (s, 1H), 7.49 (d, J = 8.1 Hz, 1H), 6.84 (d, J =
1
.2 Hz, 1H), 6.74 (d, J = 8.4 Hz, 1H), 6.15 (br.s, 1H), 6.00 (d, J = 1.8 Hz,
1
3
1
H), 5.83 (s, 1H), 3.20 (s, 3H), 1.23 (br.s, 9H) ppm; C NMR (75 MHz, CDCl
3
) δ = 175.3, 153.2,
1
42.5, 135.0, 132.0, 126.6, 124.1, 121.7, 115.5, 110.2, 109.9, 107.7, 81.1, 60.2, 28.3, 28.0, 26.8 ppm;
-1
IR (KBr): 3328, 2919, 1711, 1610, 1489, 1420, 1366, 1162, 1097, 754 cm ; HRMS calcd for
+
C
18
H
20BrN
3
NaO
3
(M+Na) 428.0580, found 428.0587.
0
.12
.10
.08
.06
.04
.02
.00
0
0
0
0
0
0
0.50
1.00
1.50
2.00
2.50
3.00
3.50
4.00
4.50
5.00
5.50
6.00
6.50
7. 00
7.50
8.00
8.50
9.00
min
Name Retention Time Area
% Area
Height Int Type Peak Type Peak Codes
1
2
5.470
7.267
1991068 47.49
2201238 52.51
126387 bb
82411 bb
Unknown
Unknown
0
0
0
0
0
.80
.60
.40
.20
.00
1
.00
2.00
3.00
4.00
5.00
6.00
7.00
8.00
9.00
min
Name Retention Time Area
% Area
0.46
Height Int Type Peak Type Peak Codes
1
2
5.478
7.182
100743
5800
VB
Unknown
Unknown
21780650 99.54
845747 BB
S 25

Electronic Supplementary Material (ESI) for Chemical Communications
This journal is © The Royal Society of Chemistry 2012
(
R)-tert-Butyl 6-chloro-1-methyl-2-oxo-3-(1H-pyrrol-2-yl)indolin-3-ylcarbamate (6f)
The ee value determination was carried out using chiral high-performance
liquid chromatography (HPLC) with Chiracel AD-H column (hexane :
Boc
NH
N
NH
2
1
-propanol = 60 : 40, 1.0 mL/min, 99% ee). White solid, 98% yield; mp =
O
o
20
1
42-143 C; [α]
10.19 (br.s, 1H), 7.38 (d, J = 7.8 Hz, 1H), 7.14 (d, J = 7.5 Hz, 1H),
.84-6.88 (m, 2H), 6.26 (br.s, 1H), 5.99 (d, J = 3.0 Hz, 1H) 5.79 (s, 1H),
D
3 3
= +187 (c 1.0, CHCl ); H NMR (300 MHz, CDCl ): δ
Cl
=
6
1
3
3
1
3
.21 (br.s, 3H), 1.20 (br.s, 7H), 1.10 (br.s, 2H) ppm; C NMR (75 MHz, CDCl
3
) δ = 175.9, 153.0,
44.7, 134.9, 127.7, 124.3, 122.7, 121.7, 109.8, 109.5, 107.6, 81.0, 60.0, 27.9, 26.8 ppm; IR (KBr):
-
1
328, 2974, 1712, 1612, 1496, 1370, 1244, 1161, 1074, 734 cm ; HRMS calcd for C18
H20ClN
3
NaO
3
+
(
M+Na) 384.1085, found 384.1090.
0.15
0.10
0.05
0.00
2.00
4.00
6.00
8.00
10.00
12.00
14.00
min
Name Retention Time Area
% Area Height Int Type Peak Type Peak Codes
1
2
8.459
4977619 49.72
5033007 50.28
172406 bb
112944 bb
Unknown
Unknown
11.518
0
0
0
0
.15
.10
.05
.00
2
.00
4.00
6.00
8.00
10.00
12.00
14.00
min
Name Retention Time Area
% Area Height Int Type Peak Type Peak Codes
1
2
8.491
55877
0.68
2443
bb
Unknown I08
Unknown
11.530
8124417 99.32
170951 BB
S 26

Electronic Supplementary Material (ESI) for Chemical Communications
This journal is © The Royal Society of Chemistry 2012
(
R)-tert-Butyl 7-fluoro-1-methyl-2-oxo-3-(1H-pyrrol-2-yl)indolin-3-ylcarbamate (6g)
The ee value determination was carried out using chiral high-performance
liquid chromatography (HPLC) with Chiracel AD-H column (hexane :
NH 2-propanol = 60 : 40, 1.0 mL/min, 99% ee). White solid, 95% yield; mp =
Boc
NH
N
o
20
1
9
1
7
0
2-94 C; [α]
D
3 3
= +150 (c 1.0, CHCl ); H NMR (300 MHz, CDCl ): δ =
O
0.24 (br.s, 0.68H), 10.13 (br.s, 0.30H), 7.26 (s, 1H), 7.10 (d, J = 4.5 Hz, 1H),
.07 (s, 1H), 6.86 (dd, J = 7.2, 1.8 Hz, 1H), 6.29 (br.s, 0.67H), 6.04 (br.s,
.31H), 5.99 (dd, J = 5.7, 1.8 Hz, 1H), 5.77-5.80 (m, 1H), 3.45 (s, 3H), 1.21
F
1
3
(
3
br.s, 6H), 1.12 (br.s, 3H) ppm; C NMR (75 MHz, CDCl ) δ = 175.6, 153.8, 153.1, 149.6, 146.4,
1
32.2, 130.1, 124.3, 123.4, 123.3, 121.7, 119.4, 117.4, 117.1, 109.9, 107.6, 81.0, 60.4, 29.3, 27.9 ppm;
-
1
IR (KBr): 3327, 2976, 1713, 1632, 1484, 1369, 1236, 1161, 753, 733 cm ; HRMS calcd for
+
C
18
H
21FN
3
O
3
(M+H) 346.1561, found 346.1559.
0
.050
.040
.030
.020
.010
.000
0
0
0
0
0
2
.00
4.00
6. 00
8.00
10.00
12.00
14.00
min
Name Retention Time Area
% Area Height Int Type Peak Type
Peak Codes
1
2
7.045
1360136 45.48
1630381 54.52
53572
39294
bb
bb
Unknown
Unknown
11.174
0.15
0.10
0.05
0.00
2. 00
4.00
6.00
8.00
min
10 .0 0
12.00
14.00
16.00
Name Retention Time Area
% Area Height Int Type Peak Type
Peak Codes
1
2
7.247
53183
0.73
2201
bb
Unknown
Unknown
11.502
7251616 99.27
159899 Bb
S 27

Electronic Supplementary Material (ESI) for Chemical Communications
This journal is © The Royal Society of Chemistry 2012
(
R)-tert-Butyl 1'-methyl-2'-oxo-2,3'-biindolin-3'-ylcarbamate (6h)
The ee value determination was carried out using chiral high-performance
liquid chromatography (HPLC) with Chiracel AD-H column (hexane :
2-propanol = 80 : 20, 1.0 mL/min, 92% ee). White solid, 96% yield; mp =
Boc
NH
N
o
20
1
NH
126-128 C; [α]
D
3 3
= +144 (c 1.0, CHCl ); H NMR (300 MHz, CDCl ): δ =
O
10.34 (br.s, 0.68H), 9.54 (br.s, 0.24H), 7.45 (d, J = 7.2 Hz, 1H), 7.34-7.39 (m,
1H), 7.16 (t, J = 7.5 Hz, 1H), 6.90 (d, J = 7.5 Hz, 1H), 6.45 (br.s, 1H), 5.77 (s,
2
H), 5.58 (s, 1H), 3.16-3.29 (m, 5H), 3.01-3.06 (m, 2H), 1.15 (br.s, 9H) ppm;
1
3
C NMR (75 MHz, CDCl
3
) δ = 176.1, 152.8, 143.4, 129.4, 129.0, 128.3, 125.2, 123.4, 123.2, 122.7,
1
1
4
13.1, 108.7, 108.2, 80.7, 60.4, 27.7, 26.6, 24.6, 23.9 ppm; IR (KBr): 3381, 3309, 3025, 2971, 2928,
-
1
+
708, 1616, 1493, 1369, 1246, 1157, 1122, 752 cm ; HRMS calcd for C22
02.1794, found 402.1804.
25 3 3
H N NaO (M+Na)
0
0
0
0
.15
.10
.05
.00
0
.00
2.00
4.00
6.00
8.00
10.00
12.00
min
14.00
16.00
18.00
20.00
22 .00
24.00
Name Retention Time Area
% Area Height Int Type Peak Type Peak Codes
1
2
8.096
5254251 43.72
6765022 56.28
149796 bb
Unknown I08
Unknown
20.111
76682
bb
0
0
0
0
0
0
0
.12
.10
.08
.06
.04
.02
.00
0. 00
2.00
4.00
6.00
8.00
10.00
12.00
min
14.00
16.00
18.00
20.00
22.00
24.00
Name Retention Time Area
% Area Height Int Type Peak Type Peak Codes
1
2
8.239
469955
4.04
13489
bb
Unknown
Unknown
20.451
11151960 95.96
123719 bb
S 28

Electronic Supplementary Material (ESI) for Chemical Communications
This journal is © The Royal Society of Chemistry 2012
(
R)-tert- Butyl 1-methyl-2-oxo-3-(1H-pyrrol-2-yl)indolin-3-ylcarbamate (6i)
The ee value determination was carried out using chiral high-performance liquid
chromatography (HPLC) with Chiracel OD-H column (hexane : 2-propanol =
Boc
NH
N
N
o
20
8
0 : 20, 0.8 mL/min, 70% ee). White solid, 49% yield; mp = 90-91 C; [α]
D
=
O
1
+
160 (c 1.0, CHCl
3
); H NMR (300 MHz, CDCl
3
): δ = 7.34 (d, J = 7.2 Hz, 1H),
7.12 (t, J = 7.5 Hz, 1H), 6.81 (d, J = 8.1 Hz, 1H), 6.64 (t, J = 2.1 Hz, 1H), 5.84 (t,
6
i
J = 3.0 Hz, 1H), 5.84 (br.s, 1H), 5.47 (t, J = 1.8 Hz, 1H), 4.09 (s, 3H), 3.14 (s,
1
3
3
1
1
3
H), 1.20 (br.s, 9H) ppm; C NMR (75 MHz, CDCl
3
) δ = 174.6, 153.8, 143.6, 130.5, 129.2, 127.0,
26.6, 124.0, 122.6, 111.7, 107.9, 106.4, 80.7, 62.1, 36.9, 28.0, 26.5 ppm; IR (KBr): 3336, 2976, 2929,
-
1
+
22 3 3
723, 1613, 1493, 1472, 1370, 1164, 754 cm ; HRMS calcd for C18H N O (M+H) 342.1812, found
42.1809.
1.50
1.00
0.50
0.00
1.00
2.00
3.00
4. 00
min
5.00
6.00
7. 00
8.00
Name Retention Time
52.556
Area
% Area Height Int Type Peak Type Peak Codes
1
92490248 94.75 174466
bb
bb
Unknown
Unknown
2
86.527
5129374
5.25
6407
0.40
0.30
0.20
0.10
0.00
1.00
2.00
3.00
4.00
5.00
6.00
7.00
8.00
9.00
min
Name Retention Time
5.695
Area
% Area Height Int Type Peak Type Peak Codes
1
934925
14.89
75216 BV
Unknown
Unknown
2
6.439 5345020
85.11 418858 VB
S 29

Electronic Supplementary Material (ESI) for Chemical Communications
This journal is © The Royal Society of Chemistry 2012
X-Ray Structure of 4s
(
S)-tert-Butyl 5,5'-dibromo-1,1'-dimethyl-2-oxo-3,3'-biindolin-3-ylcarbamate (CCDC: 879849)
N
H
N
Br
Boc
O
Br
N
Reference
1
(a) X-H. Chen, Q. Wei, S.-W. Luo, H. Xiao, L.-Z. Gong, J. Am. Chem. Soc. 2009, 131, 13819. (b)
T. W. Wu, L. Shen, J. M. Chong, Org. Lett. 2004, 6, 2701. (c) M. Hatano, T. Ikeno,; T.
Matsumura, S. Torii, K. Ishihara, Adv. Synth. Catal. 2008, 350, 1776
2
3
M. Klussmann, L. Ratjen, S. Hoffmann, V. Wakchaure, R. Goddard, B. List, Synlett. 2010, 14,
2189.
W. Yan, D. Wang, J. Feng, P. Li, D. Zhao, R. Wang, Org. Lett. 2012, DOI: 10.1021/ol3007953.
S 30