Rhodium-catalyzed regioselective amidation of indoles with sulfonyl azides via C-H bond activation

Article abstract of DOI:10.1039/c2ob26767e

Direct C-2 amidation of indoles was reported using sulfonyl azides as the amino source to release N₂ as the single byproduct. This reaction exhibits high functional group tolerance and regioselectivity, providing a variety of 2-amino substituted indoles in high to excellent yield. The procedure is robust, reliable, and compatible with water and air.

Full text of DOI:10.1039/c2ob26767e

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry
This journal is © The Royal Society of Chemistry 2012
Rhodium-Catalyzed Regioselective Amidation of Indoles with
Sulfonyl Azides via C−H Bond Activation
Jingjing Shi, Bing Zhou,* Yaxi Yang and Yuanchao Li*
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road,
Zhangjiang Hi-Tech Park, Shanghai 201203, PR China. Fax: (+)86 21 50807288; Tel: (+)86
21 50807288; E-mail:zhoubing2012@hotmail.com; E-mail:ycli@mail.shcnc.ac.cn
Table of contents:
General Methods and Materials
1
1
Experimental Procedures and Characterizations
1H and 13C NMR Spectra of Compounds
19
1

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry
This journal is © The Royal Society of Chemistry 2012
General methods:
Mass spectra and high-resolution mass spectra were measured on a Finnigan MAT-95
1
13
mass spectrometer. H and C NMR spectra were determined on Bruker AM-300,
Bruker AM-400, Bruker AM-500 instruments using tetramethylsilane as internal
reference. Data are presented as follows: chemical shift, multiplicity (s = singlet, br s
= broad singlet, d = doublet, br d = broad doublet, t = triplet, m = multiplet), J =
coupling constant in hertz (Hz). Silica gel 60H (200-300 mesh) manufactured by
Qingdao Haiyang Chemical Group Co. (China) was used for general chromatography.
Materials:
AgSbF6 was purchased from Aldrich and used without further purification.
[Cp*RhCl2]2 S1, [Cp*Rh(MeCN)3][SbF6]2 S2， substrate 1-(Pyrimidin-2-yl)- 1H-indole
S3 and benzenesulfonyl azide S4 were synthesized according to published procedures.
Experimental Procedures and Characterizations:
General Procedure for Preparation of benzenesulfonyl azide: benzenesulfonyl
chloride (10.0 mmol) was dissolved in acetone (20 mL) and water (20 mL). The
solution was cooled on ice and NaN3 (10.0 mmol) was added. The reaction was stirred
for 2 h. The acetone was removed under vacuum and the remaining water layer was
extracted with EtOAc (150 mL), the EtOAc layer was washed with brine, dried on
Na2SO4, filtered and concentrated. The benzenesulfonyl azide was obtained for future
use without purification.
4-methylbenzenesulfonyl azide: This compound was obtained in 95% yield as a
1
colourless oil. H NMR (300 MHz, CDCl3): δ 7.84 (d, J = 7.8, 2H), 7.40 (d, J = 7.8,
2H), 2.48 (s, 3H). Spectral data matched those previously reported.S4
2

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry
This journal is © The Royal Society of Chemistry 2012
4-methoxybenzenesulfonyl azide: This compound was obtained in 98% yield as a
1
colourless oil. H NMR (300 MHz, CDCl3): δ 7.90 (d, J = 8.7, 2H), 7.05 (d, J = 8.7,
2H), 3.91 (s, 3H). Spectral data matched those previously reported.S4
4-nitrobenzenesulfonyl azide: This compound was obtained in 98% yield as a light
yellow solid. 1H NMR (300 MHz, CDCl3): δ 8.46 (d, J = 8.7, 1H), 8.17 (d, J = 8.7,
1H). Spectral data matched those previously reported.S4
General Procedure for Preparation of substrate 1-(Pyrimidin-2-yl)-1H-indole
S3
moiety : NaH (60% dispersion in mineral oil, 11.0 mmol) was added in portions at
0 °C to astirred solution of indole (10.0 mmol) in DMF (25 mL). After stirring for 30
min at 0 °C, 2-chloropyrimidine (12.0 mmol) was added and the mixture was stirred
at 130 °C for 24 h. Then, the reaction mixture was cooled to ambient temperature,
poured into H2O (300 mL) and extracted with EtOAc (250 mL). The organic phase
was dried over Na2SO4. After evaporation of the solvents under reduced pressure, the
crude product was purified by column chromatography on silica gel
(cyclohexane/EtOAc: 10/1) to give product.
1-(Pyrimidin-2-yl)-1H-indole (1f). This compound was obtained in 85% yield as a
1
white solid. M. p. = 86−88 °C. H NMR (300 MHz, CDCl3): δ 8.82 (d, J = 8.3 Hz,
1H), 8.70 (d, J = 4.8 Hz, 2H), 8.28 (d, J = 3.7 Hz, 1H), 7.63 (d, J = 7.7 Hz, 1H), 7.35
3

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry
This journal is © The Royal Society of Chemistry 2012
(dd, J = 9.0, 6.5 Hz, 1H), 7.25 (t, J = 6.1 Hz, 1H), 7.04 (m, 1H), 6.71 (d, J = 3.7 Hz,
1H). 13C NMR (100 MHz, CDCl3): δ 158.1, 157.8, 135.4, 131.4, 125.9, 123.7, 122.2,
120.9, 116.3, 116.1, 107.0. Spectral data matched those previously reported.S3
3-methyl-1-(pyrimidin-2-yl)-1H-indole (1g). This compound was obtained in 79%
yield as a white solid. M. p. = 76−78 °C. 1H NMR (300 MHz, CDCl3): δ 8.78 (d, J =
8.2 Hz, 1H), 8.66 (d, J = 4.8 Hz, 2H), 8.04 (s, 1H), 7.57 (d, J = 7.7 Hz, 1H), 7.35 (t, J
= 7.7 Hz, 1H), 7.26 (t, J = 7.4 Hz, 1H), 6.98 (t, J = 4.8 Hz, 1H), 2.37 (d, J = 1.3 Hz,
3H). 13C NMR (100 MHz, CDCl3): δ 173.6, 158.1, 157.6, 135.7, 130.8, 123.9, 122.6,
121.9, 119.1, 118.6, 116.4, 115.8, 51.7, 34.0, 20.5. Spectral data matched those
previously reported.S3
methyl 3-(1-(pyrimidin-2-yl)-1H-indol-3-yl)propanoate (1h). This compound was
obtained in 81% yield as a white solid. M. p. = 72−74 °C. 1H NMR (300 MHz, CDCl3)
δ 8.79 (d, J = 8.3, 1H), 8.67 (d, J = 4.8, 2H), 8.08 (s, 1H), 7.59 (d, J = 7.8, 1H), 7.35 (t,
J = 7.7, 1H), 7.26 (t, J = 7.4, 1H), 7.01 (t, J = 4.8, 1H), 3.71 (s, 3H), 3.13 (t, J = 7.8,
13
2H), 2.80 (t, J = 7.8, 2H). C NMR (100 MHz, CDCl3) δ 173.58, 158.08, 157.59,
135.69, 130.85, 123.89, 122.61, 121.89, 119.12, 118.65, 116.37, 115.80, 51.72, 33.96,
20.54. HRMS (EI) calcd. for C16H15N3O2 [M]+ : 281.1164. Found: 281.1162.
4

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry
This journal is © The Royal Society of Chemistry 2012
5-methyl-1-(pyrimidin-2-yl)-1H-indole (1i). This compound was obtained in 76%
yield as a white solid. M. p. = 86−88 °C. 1H NMR (300 MHz, CDCl3): δ 8.69-8.65 (m,
3H), 8.22 (d, J = 3.6, 1H), 7.41 (s, 1H), 7.16 (d, J = 8.4, 1H), 7.02 (t, J = 4.8, 1H),
6.62 (d, J = 3.4, 1H), 2.47 (s, 3H).13C NMR (125 MHz, CDCl3): δ 167.4, 157.8, 157.1,
137.5, 130.6, 126.8, 124.5, 123.5, 122.8, 116.4, 115.5, 107.1, 51.8. HRMS (EI) calcd.
for C13H11N3 [M]+ : 209.0953. Found: 209.09458.
5-methoxy-1-(pyrimidin-2-yl)-1H-indole (1j). This compound was obtained in 83%
1
yield as a white solid. M. p. = 110−112 °C. H NMR (300 MHz, CDCl3): δ 8.75 –
8.63 (m, 3H), 8.25 (d, J = 3.6, 1H), 7.10 (d, J = 2.5, 1H), 7.04 – 6.92 (m, 2H), 6.63 (d,
J = 3.6, 1H), 3.88 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 158.1, 157.6, 1556, 132.15,
130.3, 126.4, 117.1, 115.9, 112.6, 106.8, 103.2, 55.7. Spectral data matched those
previously reported.S3
6-methyl-1-(pyrimidin-2-yl)-1H-indole (1k). This compound was obtained in 78%
yield as a white solid. M. p. = 120−122 °C. 1H NMR (300 MHz, CDCl3): δ 8.70 (d, J
= 4.8, 2H), 8.64 (s, 1H), 8.21 (d, J = 3.6, 1H), 7.51 (d, J = 7.8, 1H), 7.08 (d, J = 7.8,
13
1H), 7.03 (t, J = 4.8, 1H), 6.66 (d, J = 3.6, 1H), 2.55 (s, 3H). C NMR (125 MHz,
CDCl3): δ 167.4, 157.8, 157.1, 137.5, 130.6, 126.8, 124.5, 123.5, 122.8, 116.4, 115.5,
107.1, 51.6. HRMS (EI) calcd. for C13H11N3 [M]+ : 209.0953. Found: 209.09459.
6-methoxy-1-(pyrimidin-2-yl)-1H-indole (1l). This compound was obtained in 70%
yield as a white solid. M. p. = 78−80 °C. 1H NMR (300 MHz, CDCl3): δ 8.70 (d, J =
5

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry
This journal is © The Royal Society of Chemistry 2012
4.8, 2H), 8.45 (d, J = 2.4, 1H), 8.17 (d, J = 3.6, 1H), 7.49 (d, J = 8.4, 1H), 7.03 (t, J =
4.8, 1H), 6.90 (dd, J = 8.4, 2.4, 1H), 6.63 (dd, J = 4.2, 0.6, 1H), 3.93 (s, 3H). 13C
NMR (100 MHz, CDCl3): δ 158.1, 157.8, 157.4, 136.3, 125.4, 124.8, 121.1, 116.0,
111.1, 106.8, 101.1, 55.8. HRMS (EI) calcd. for C13H11N3O [M]+ : 225.0902. Found:
225.0899.
1-(pyrimidin-2-yl)-6-(trifluoromethyl)-1H-indole (1m). This compound was
1
obtained in 78% yield as a white solid. M. p. = 98−100 °C. H NMR (300 MHz,
CDCl3): δ 9.16 (s, 1H), 8.74 (d, J = 4.8, 2H), 8.42 (d, J = 3.6, 1H), 7.70 (d, J = 8.4,
1H), 7.48 (d, J = 8.8, 1H), 7.11 (t, J = 4.8, 1H), 6.75 (d, J = 3.6, 1H). 13C NMR (100
MHz, CDCl3): δ 158.3, 157.5, 134.4, 133.8, 129.3, 128.3, 126.6, 125.6 (q, J = 31.7),
125.2 (q, J = 272.2), 123.9, 121.2, 121.0, 11878 (q, J = 3.6), 116.8, 114.0 (q, J = 4.5),
106.6. HRMS (EI) calcd. for C13H8 F3N3 [M]+ : 263.0670. Found: 263.0666.
6-nitro-1-(pyrimidin-2-yl)-1H-indole (1n). This compound was obtained in 80%
yield as a light yellow solid. M. p. = 179−181 °C. 1H NMR (300 MHz, CDCl3): δ 9.77
(d, J = 2.1, 1H), 8.79 (d, J = 4.8, 2H), 8.55 (d, J = 3.6, 1H), 8.14 (dd, J = 8.7, 2.1, 1H),
7.68 (d, J = 8.7, 1H), 7.18 (t, J = 4.8, 1H), 6.79 (d, J = 3.6, 1H). 13C NMR (100 MHz,
CDCl3): δ 158.4, 157.1, 144.5, 136.1, 134.0, 131.0, 120.6, 117.5, 117.3, 113.1, 106.7.
HRMS (EI) calcd. for C12H8N4O2 [M]+ : 240.0647. Found: 240.0653.
5-nitro-1-(pyrimidin-2-yl)-1H-indole (1o). This compound was obtained in 80%
yield as a light yellow solid. M. p. = 244−246 °C. 1H NMR (300 MHz, CDCl3): δ 8.92
6

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry
This journal is © The Royal Society of Chemistry 2012
(d, J = 9.3, 1H), 8.77 (d, J = 4.8, 2H), 8.55 (s, 1H), 8.44 (d, J = 3.9, 1H), 8.22 (d, J =
9.3, 1H), 7.18 (t, J = 4.8, 1H), 6.84 (d, J = 3.6, 1H). 13C NMR (100 MHz, CDCl3): δ
158.4, 157.2, 143.3, 138.39, 131.0, 128.9, 118.9, 117.4, 117.2, 116.4, 107.7. HRMS
(EI) calcd. for C12H8N3O2 [M]+ : 240.0647. Found: 240.0650.
methyl 1-(pyrimidin-2-yl)-1H-indole-5-carboxylate (1p). This compound was
1
obtained in 80% yield as a white solid. M. p. = 120−122 °C. H NMR (300 MHz,
CDCl3): δ 8.84 (d, J = 8.7, 1H), 8.73 (d, J = 4.8, 2H), 8.42 – 8.27 (m, 2H), 8.03 (dd, J
13
= 8.7, 1.5, 1H), 7.10 (t, J = 4.8, 1H), 6.77 (dd, J = 3.6, 0.6, 1H), 3.95 (s, 3H). C
NMR (125 MHz, CDCl3) δ 167.4, 157.8, 157.1, 137.5, 130.6, 126.8, 124.5, 123.5,
122.8, 116.4, 115.5, 107.1, 51.6. HRMS (EI) calcd. for C14H11N3O2 [M]+ : 253.0851.
Found: 253.0847.
5-chloro-1-(pyrimidin-2-yl)-1H-indole (1q). This compound was obtained in 89%
yield as a white solid. M. p. = 110−112 °C. 1H NMR (300 MHz, CDCl3): δ 8.76 (dd, J
= 9.1, 4.8, 1H), 8.71 – 8.64 (m, 2H), 8.31 (d, J = 3.6, 1H), 7.27 (dd, J = 8.8, 2.8, 1H),
7.10-7.03 (m, 2H), 6.65 (d, J = 3.6, 1H). 13C NMR (100 MHz, CDCl3): δ 158.2, 133.8,
132.5, 127.7, 127.1, 123.7, 120.3, 117.3, 116.4, 106.2. HRMS (EI) calcd. for
C12H8ClN3 [M]+ : 229.0407. Found: 229.0403.
5-bromo-1-(pyrimidin-2-yl)-1H-indole (1r). This compound was obtained in 83%
1
yield as a white solid. M. p. = 120−122 °C. H NMR (300 MHz, CDCl3): δ 8.73 –
8.63 (m, 3H), 8.28 (d, J = 3.4, 1H), 7.75 (s, 1H), 7.42 (d, J = 9.0, 1H), 7.08 (t, J = 4.8,
7

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry
This journal is © The Royal Society of Chemistry 2012
1H), 6.63 (d, J = 3.5, 1H). 13C NMR (100 MHz, CDCl3): δ 158.1, 157.5, 134.1, 133.1,
127.0, 126.4, 123.3, 117.8, 116.4, 115.4, 106.1. HRMS (EI) calcd. for C12H8BrN3
[M]+ : 272.9902. Found: 272.9904.
5-fluoro-1-(pyrimidin-2-yl)-1H-indole (1s). This compound was obtained in 76%
yield as a white solid. M. p. = 112−114 °C. 1H NMR (300 MHz, CDCl3): δ 8.76 (dd, J
= 9.1, 4.8, 1H), 8.71 – 8.64 (m, 2H), 8.31 (d, J = 3.6, 1H), 7.27 (dd, J = 8.8, 2.8, 1H),
7.10-7.03 (m, 2H), 6.65 (d, J = 3.6, 1H). 13C NMR (100 MHz, CDCl3): δ 158.89 (d, J
= 265.9 Hz), 158.13, 157.8, 131.86, 127.35, 117.24 (d, J = 9.0), 116.29, 111.36 (d, J =
24.8), 106.62 (d, J = 4.1), 106.03 (d, J = 23.5). HRMS (EI) calcd. for C12H8FN3 [M]+ :
213.0702. Found: 213.0699.
6-bromo-1-(pyrimidin-2-yl)-1H-indole (1t). This compound was obtained in 80%
1
yield as a white solid. M. p. = 130−132 °C. H NMR (300 MHz, CDCl3): δ 9.04 (s,
1H), 8.72 (d, J = 4.8, 2H), 8.25 (d, J = 3.9, 1H), 7.47 (d, J = 8.4, 1H), 7.35 (d, J = 8.4,
1H), 7.09 (t, J = 4.2, 1H), 6.66 (d, J = 3.0, 1H). 13C NMR (125 MHz, CDCl3): δ 167.4,
157.8, 157.1, 137.5, 130.6, 126.8, 124.5, 123.5, 122.8, 116.4, 115.5, 107.1, 51.6.
HRMS (EI) calcd. for C12H8BrN3 [M]+ : 272.9902. Found: 272.9907.
4-chloro-1-(pyrimidin-2-yl)-1H-indole (1u). This compound was obtained in 76%
1
yield as a white solid. M. p. = 118−120 °C. H NMR (300 MHz, CDCl3): δ 8.75 –
8.64 (m, 3H), 8.31 (d, J = 3.7, 1H), 7.28 – 7.21 (m, 2H), 7.05 (td, J = 4.8, 1.2, 1H),
8

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry
This journal is © The Royal Society of Chemistry 2012
6.82 (d, J = 3.6, 1H). 13C NMR (100 MHz, CDCl3): δ 158.2, 157.6, 136.1, 130.0,
126.4, 125.9, 124.2, 121.9, 116.6, 114.9, 105.0. HRMS (EI) calcd. for C12H8ClN3
[M]+ : 229.0407. Found: 229.0404.
General Procedure for Preparation of substrate N-(1-(pyrimidin-2-yl)-
1H-indol-2-yl)benzenesulfonamide
moiety:
The
mixture
of
[Cp*Rh(MeCN)3][SbF6]2 (8 mg, 0.01 mmol)，substrate A (0.2 mmol), B (0.26 mmol,
1.3 equiv) and H2O (36 mg, 2 mmol)were dissolved in DCE (1 mL) and refluxed for 5
h. The resulting mixture was cooled to room temperature, silica gel column directly to
give product.
Following general procedure, the indicated compound was purified by flash column
chromatography on silica gel using cyclohexane:EtOAc (2:1) in a 86% as a white
solid (M. p. = 152−154 °C ). IR (film): 3048, 2917, 1583, 1427, 1344, 1172, 1091, 802,
1
684, 543 cm-1. H NMR (300 MHz, CDCl3): δ 11.07 (s, 1H), 8.68 (d, J = 4.8, 2H),
8.48 (dd, J = 6.3, 3.3, 1H), 7.61 (d, J = 8.1, 2H), 7.48 (dd, J = 6.0, 3.0, 1H), 7.23 –
13
7.16 (m, 2H), 7.11 – 7.06 (m, 3H), 6.64 (s, 1H), 2.28 (s, 3H). C NMR (100 MHz,
CDCl3): δ 153.1, 152.7, 138.9, 131.1, 128.6, 128.5, 124.5, 123.6, 122.1, 118.1, 118.0,
115.0, 111.4, 110.8, 92.6, 16.5. HRMS (EI) calcd. for C19H16N4O2S [M]+ : 364.0994.
Found: 364.0989.
9

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry
This journal is © The Royal Society of Chemistry 2012
Following general procedure, the indicated compound was purified by flash column
chromatography on silica gel using cyclohexane:EtOAc (2:1) in a 86% as a white
solid (M. p. = 195−197 °C ). IR (film): 3049, 2915, 1563, 1428, 1346, 1169, 1090, 814,
746, 681, 550 cm-1. 1H NMR (300 MHz, CDCl3) δ 9.25 (s, 1H), 8.49 (d, J = 4.8, 2H),
8.27 – 8.23 (m, 1H), 7.64 – 7.52 (m, 1H), 7.34 – 7.16 (m, 4H), 6.94 (t, J = 4.8, 1H),
13
6.85 (d, J = 8.7, 2H), 2.47 (s, 3H), 2.22 (s, 3H). C NMR (125 MHz, CDCl3): δ
157.51, 157.16, 143.54, 135.87, 134.01, 129.15, 128.92, 127.16, 126.87, 124.61,
122.53, 119.30, 115.98, 115.59, 114.66, 21.49, 9.26. HRMS (EI) calcd. for
C20H18N4O2S [M]+ : 378.1150. Found: 378.1155.
Following general procedure, the indicated compound was purified by flash column
chromatography on silica gel using cyclohexane:EtOAc (2:1) in a 81% as a white
solid (M. p. = 132−134 °C). IR (film): 3049, 2923, 1732, 1558, 1443, 1339, 1156,
1092, 826, 741, 667, 542 cm-1. 1H NMR (300 MHz, CDCl3) δ 9.21 (s, 1H), 8.49 (d, J
= 4.8, 2H), 8.28 – 8.13 (m, 1H), 7.69 – 7.52 (m, 1H), 7.34 – 7.22 (m, 2H), 7.19 (d, J =
8.1, 2H), 6.96 (t, J = 4.8, 1H), 6.84 (d, J = 8.1, 2H), 3.71 (s, 3H), 3.33 (d, J = 8.1, 2H),
13
2.89 (d, J = 8.1, 2H), 2.22 (s, 3H). C NMR (101 MHz, CDCl3): δ 173.8, 157.5,
157.0, 143.6, 135.7, 134.1, 129.1, 127.6, 127.3, 126.8, 124.6, 122.6, 119.3, 117.8,
116.2, 114.7, 51.6, 33.5, 21.4, 19.6. HRMS (EI) calcd. for C23H22N4O4S [M]+ :
450.1362. Found: 450.1366.
10

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry
This journal is © The Royal Society of Chemistry 2012
Following general procedure, the indicated compound was purified by flash column
chromatography on silica gel using cyclohexane:EtOAc (2:1) in a 86% as a white
solid (M. p. = 138−140 °C ). 1H NMR (300 MHz, CDCl3): δ 11.12 (br s, 1H), 8.64 (d,
J = 4.8, 2H), 8.35 (d, J = 8.4, 1H), 7.60 (d, J = 8.1, 2H), 7.26 (d, J = 2.1, 1H), 7.12 –
6.93 (m, 4H), 6.57 (s, 1H), 2.41 (s, 3H), 2.27 (s, 3H). 13C NMR (100 MHz, CDCl3): δ
158.1, 157.6, 143.8, 136.2, 133.6, 132.6, 131.8, 129.5, 128.8, 127.1, 124.3, 120.0,
116.2, 115.6, 97.5, 21.4, 21.3. HRMS (EI) calcd. for C20H18N4O2S [M]+ : 378.1150.
Found: 378.1154.
Following general procedure, the indicated compound was purified by flash column
chromatography on silica gel using cyclohexane:EtOAc (2:1) in a 77% as a white
solid (M. p. = 146−148 °C). IR (film): 2937, 2832, 1585, 1452, 1342, 1157, 1093, 956,
789, 653, 540 cm-1. 1H NMR (300 MHz, CDCl3): δ 11.23 (s, 1H), 8.63 (ddd, J = 4.9,
1.4, 0.7, 2H), 8.39 (d, J = 9.0, 1H), 7.62 (d, J = 8.4, 2H), 7.10 – 7.03 (m, 3H), 6.95 (d,
J = 2.7, 1H), 6.79 (dd, J = 9.0, 2.7, 1H), 6.56 (s, 1H), 3.84 (s, 3H), 2.27 (s, 3H). 13C
NMR (125 MHz, CDCl3): δ 158.1, 158.0, 157.7, 156.1, 144.0, 136.1, 134.2, 129.6,
128.2, 127.2, 117.0, 116.2, 111.4, 102.7, 97.2, 55.7, 21.6. HRMS (EI) calcd. for
C20H18N4O3S [M]+ : 394.1100. Found: 394.1104.
11

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry
This journal is © The Royal Society of Chemistry 2012
Following general procedure, the indicated compound was purified by flash column
chromatography on silica gel using cyclohexane:EtOAc (2:1) in a 90% as a white
solid (M. p. = 188−190 °C). IR (film): 2921, 2852, 1585, 1463, 1427, 1338, 1159,
1087, 912, 817, 659, 553 cm-1. 1H NMR (300 MHz, CDCl3): δ 10.87 (s, 1H), 8.65 (d,
J = 4.8, 2H), 8.27 (s, 1H), 7.56 (d, J = 8.1, 2H), 7.37 (d, J = 7.8, 1H), 7.08 – 7.02 (m,
13
4H), 6.62 (s, 1H), 2.45 (s, 3H), 2.26 (s, 3H). C NMR (100 MHz, CDCl3): δ 157.8,
157.6, 143.7, 136.0, 133.9, 132.9, 132.6, 129.4, 127.0, 126.0, 124.4, 119.6, 116.2,
115.7, 98.4, 22.0, 21.4. HRMS (EI) calcd. for C20H18N4O2S [M]+ : 378.1150. Found:
378.1155.
Following general procedure, the indicated compound was purified by flash column
chromatography on silica gel using cyclohexane: EtOAc (2:1) in a 83% as a white
solid (M. p. = 143−145 °C). IR (film): 2990, 2940, 1585, 1427, 1342, 1160, 1087, 903,
1
796, 661, 557 cm-1. H NMR (300 MHz, CDCl3) δ 10.69 (br s, 1H), 8.64 (d, J = 4.8,
2H), 8.09 (d, J = 2.4, 1H), 7.52 (d, J = 8.4, 2H), 7.37 (d, J = 8.4, 1H), 7.13 – 6.99 (m,
13
3H), 6.85 (dd, J = 8.4, 2.4, 1H), 6.60 (d, J = 0.6, 1H), 3.84 (s, 3H), 2.26 (s, 3H). C
NMR (100 MHz, CDCl3) δ 158.0, 157.7, 157.0, 143.8, 136.2, 134.7, 132.1, 129.5,
127.1, 122.4, 120.6, 116.4, 111.2, 101.3, 99.2, 55.9, 21.6. HRMS (EI) calcd. for
C20H18N4O3S [M]+ : 394.1100. Found: 394.1094.
12

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry
This journal is © The Royal Society of Chemistry 2012
Following general procedure, the indicated compound was purified by flash column
chromatography on silica gel using cyclohexane:EtOAc (2:1) in a 75% as a white
solid (M. p. = 256−258 °C). IR (film): 2967, 2927, 1583, 1500, 1326, 1159, 1087, 896,
802, 660, 563 cm-1. 1H NMR (300 MHz, CDCl3): δ 11.37 (s, 1H), 8.86 (s, 1H), 8.76 (d,
J = 4.8, 2H), 7.67 (d, J = 7.2, 2H), 7.54 (d, J = 8.1, 1H), 7.44 (d, J = 8.4, 1H), 7.20 (t,
13
J = 4.8, 1H), 7.13 (d, J = 7.8, 2H), 6.64 (s, 1H), 2.31 (s, 3H). C NM (125 MHz,
CDCl3): δ 158.0, 157.9, 144.6, 143.3, 139.3, 135.8, 134.4, 131.8, 129.8, 127.2, 119.0,
119.0, 117.5, 113.1, 94.4, 21.5. HRMS (EI) calcd. for C20H15F3N4O2S [M]+ : 432.0868.
Found: 432.0866.
Following general procedure, the indicated compound was purified by flash column
chromatography on silica gel using cyclohexane:EtOAc (2:1) in a 79% as a light
yellow solid (M. p. = 299−301 °C). IR (film): 3138, 2924, 1577, 1511, 1461, 1423,
1
1330, 1155, 1087, 789, 659, 543 cm-1. H NMR (300 MHz, CDCl3): δ 11.72 (s, 1H),
9.54 (d, J = 2.1, 1H), 8.83 (d, J = 4.8, 2H), 8.12 (dd, J = 8.7, 2.1, 1H), 7.75 (d, J = 8.4,
2H), 7.48 (d, J = 8.7, 1H), 7.29 – 7.26 (m, 1H), 7.19 (d, J = 8.1, 2H), 6.63 (s, 1H),
2.34 (s, 3H). 13C NMR (126 MHz, CDCl3): δ 158.0, 157.9, 144.2, 136.3, 135.9, 132.5,
131.4, 129.6, 127.1, 119.9, 119.8, 117.0, 113.6, 113.6, 95.7, 21.5. HRMS (EI) calcd.
for C19H15N5O4S [M]+ : 409.0845. Found: 409.0844.
13

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry
This journal is © The Royal Society of Chemistry 2012
Following general procedure, the indicated compound was purified by flash column
chromatography on silica gel using cyclohexane:EtOAc (2:1) in a 84% as a light
yellow solid (M. p. = 206−208 °C). IR (film): 3142, 2968, 2924, 1598, 1512, 1423,
1
1355, 1184, 1088, 904, 838, 667, 551 cm-1. H NMR (300 MHz, CDCl3): δ 11.24 (s,
1H), 8.78 (d, J = 4.8, 2H), 8.60 (d, J = 9.3, 1H), 8.32 (d, J = 2.4, 1H), 8.03 (dd, J = 9.3,
2.4, 1H), 7.68 (d, J = 8.4, 2H), 7.26 (t, J = 4.8, 1H), 7.15 (d, J = 8.4, 2H), 6.66 (s, 1H),
2.32 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 158.0, 157.7, 144.4, 143.9, 136.7, 136.5,
135.9, 129.7, 128.7, 127.2, 117.9, 117.6, 116.1, 115.6, 96.1, 21.5. HRMS (EI) calcd.
for C19H15N5O4S [M]+ : 409.0845. Found: 409.0850.
Following general procedure, the indicated compound was purified by flash column
chromatography on silica gel using cyclohexane:EtOAc (2:1) in a 87% as a white
solid (M. p. = 186−188 °C). IR (film): 2986, 2923, 1719, 1604, 1585, 1423, 1344,
1165, 1089, 946, 815, 661, 546 cm-1. 1H NMR (300 MHz, CDCl3): δ 11.08 (br s, 1H),
8.71 (d, J = 4.8, 2H), 8.50 (d, J = 8.7, 1H), 8.17 (s, 1H), 7.87 (d, J = 9.0, 1H), 7.62 (d,
J = 7.8, 2H), 7.16 (t, J = 4.8, 1H), 7.08 (d, J = 7.8, 2H), 6.65 (s, 1H), 3.92 (s, 3H),
2.28 (s, 3H). 13C NMR (125 MHz, CDCl3): δ 167.5, 157.8, 144.1, 136.1, 135.8, 134.8,
129.6, 128.3, 127.1, 124.9, 124.2, 121.9, 117.0, 115.5, 97.2, 52.0, 21.5. HRMS (EI)
calcd. for C21H18N4O4S [M]+ : 422.1049. Found: 422.1045.
14

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry
This journal is © The Royal Society of Chemistry 2012
Following general procedure, the indicated compound was purified by flash column
chromatography on silica gel using cyclohexane:EtOAc (2:1) in a 83% as a white
solid (M. p. = 184−186 °C). IR (film): 2970, 2927, 1578, 1461, 1419, 1341, 1148,
1094, 917, 803, 680, 555 cm-1. 1H NMR (300 MHz, CDCl3): δ 11.24 (s, 1H), 8.68 (d,
J = 4.8, 2H), 8.42 (d, J = 8.7, 1H), 7.64 (d, J = 8.4, 2H), 7.41 (d, J = 2.1, 1H), 7.18 –
7.02 (m, 4H), 6.53 (s, 1H), 2.29 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 157.9, 157.7,
144.1, 136.0, 135.0, 131.8, 130.0, 129.6, 128.6, 127.1, 122.8, 119.3, 117.1, 116.7,
95.9, 21.5. HRMS (EI) calcd. for C19H15ClN4O2S [M]+ : 398.0604. Found: 398.0608.
Following general procedure, the indicated compound was purified by flash column
chromatography on silica gel using cyclohexane:EtOAc (2:1) in a 83% as a white
solid (M. p. = 193−195 °C). IR (film): 2923, 2871, 1583, 1448, 1425, 1336, 1162,
1091, 956, 788, 678, 563 cm-1. 1H NMR (300 MHz, CDCl3): δ 11.23 (s, 1H), 8.70 (d,
J = 4.7, 2H), 8.39 (d, J = 8.8, 1H), 7.63 (d, J = 8.1, 2H), 7.58 (s, 1H), 7.28 – 7.25 (m,
13
2H), 7.16 – 7.09 (m, 3H), 6.53 (s, 1H), 2.30 (s, 3H). C NMR (100 MHz, CDCl3): δ
157.8, 157.7, 144.1, 135.8, 134.8, 132.1, 130.4, 129.5, 127.1, 125.4, 122.3, 117.4,
116.7, 116.3, 95.6, 21.4. HRMS (EI) calcd. for C19H15BrN4O2S [M]+ : 442.0099.
Found: 442.0096.
15

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry
This journal is © The Royal Society of Chemistry 2012
Following general procedure, the indicated compound was purified by flash column
chromatography on silica gel using cyclohexane:EtOAc (2:1) in a 81% as a white
solid (M. p. = 166−168 °C). IR (film): 2969, 2923, 1572, 1500, 1458, 1338, 1081, 886,
793, 669, 560 cm-1.1H NMR (300 MHz, CDCl3): δ 11.29 (s, 1H), 8.67 (dd, J = 4.8, 0.7,
2H), 8.45 (dd, J = 9.3, 4.8, 1H), 7.64 (d, J = 8.1, 2H), 7.18 – 7.04 (m, 4H), 6.88 (td, J
= 9.3, 2.7, 1H), 6.55 (s, 1H), 2.29 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 159.5 (d, J
= 239.1), 157.9, 157.7, 144.1, 136.1, 135.2, 129.8, 129.6 (d, J = 5.9), 129.6, 127.1,
117.1 (d, J = 8.9), 116.6, 110.22 (d, J = 24.4), 105.3 (d, J = 24.1), 96.3 (d, J = 3.8),
21.5. HRMS (EI) calcd. for C19H15FN4O2S [M]+ : 382.0900. Found: 382.0894.
Following general procedure, the indicated compound was purified by flash column
chromatography on silica gel using cyclohexane:EtOAc (2:1) in a 74% as a white
solid (M. p. = 215−217 °C). IR (film): 3126, 2956, 1594, 1500, 1427, 1340, 1164,
1087, ,890, 820, 667, 563 cm-1. 1H NMR (300 MHz, CDCl3): δ 11.07 (s, 1H), 8.69 (d,
J = 4.8, 3H), 7.60 (d, J = 8.4, 2H), 7.36 – 7.27 (m, 2H), 7.15 – 7.04 (m, 3H), 6.58 (s,
13
1H), 2.29 (s, 3H). C NMR (100 MHz, CDCl3): δ 157.9, 144.2, 136.0, 134.2, 134.2,
129.7, 127.6, 127.2, 126.3, 121.1, 119.0, 116.9, 116.3, 97.2, 21.6. HRMS (EI) calcd.
for C19H15 BrN4O2S [M]+ : 442.0099. Found: 442.0093.
16

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry
This journal is © The Royal Society of Chemistry 2012
Following general procedure, the indicated compound was purified by flash column
chromatography on silica gel using cyclohexane:EtOAc (2:1) in a 79% as a white
solid (M. p. = 210−212 °C). IR (film): 3140, 2937, 1585, 1452, 1342, 1160,
1088, ,886, 811, 665, 542 cm-1. 1H NMR (300 MHz, CDCl3): δ 11.16 (s, 1H), 8.70 (d,
J = 4.8, 2H), 8.40 (d, J = 7.8, 1H), 7.66 (d, J = 7.8, 2H), 7.23 – 7.03 (m, 5H), 6.73 (s,
13
1H), 2.30 (s, 3H). C NMR (100 MHz, CDCl3): δ 157.9, 157.8, 144.1, 136.1, 134.4,
134.1, 129.6, 127.5, 127.2, 125.0, 123.4, 122.9, 116.8, 114.4, 95.0, 21.5. HRMS (EI)
calcd. for C19H15ClN4O2S [M]+ : 398.0604. Found: 398.0610.
Following general procedure, the indicated compound was purified by flash column
chromatography on silica gel using cyclohexane:EtOAc (2:1) in a 74% as a yellow
solid (M. p. = 168−170 °C). IR (film): 3143, 2963, 2924, 1617, 1452, 1429, 1329,
1150, 1088, 775, 659, 539 cm-1. 1H NMR (300 MHz, CDCl3): δ 11.32 (s, 1H), 8.69 (d,
J = 4.8, 2H), 8.47 (s, 1H), 8.12 (d , J = 7.2, 2H), 7.90 (d, J = 8.4, 2H), 7.50 (s, 1H),
7.25 – 7.13 (m, 3H), 6.71 (s, 1H). 13C NMR (125 MHz, CDCl3): δ 157.9, 157.8, 150.2,
144.8, 133.6, 132.2, 128.3, 128.1, 124.1, 123.6, 123.4, 120.2, 116.6, 116.0, 98.5.
HRMS (EI) calcd. for C18H13N5O4S [M]+ : 395.0688. Found: 395.0691.
17

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry
This journal is © The Royal Society of Chemistry 2012
Following general procedure, the indicated compound was purified by flash column
chromatography on silica gel using cyclohexane:EtOAc (2:1) in a 82% as a yellow
solid (M. p. = 122−124 °C). IR (film): 2938, 2832, 1585, 1486, 1342, 1160, 1084, 884,
659, 561 cm-1. 1H NMR (300 MHz, CDCl3): δ 11.04 (br s, 1H), 8.66 (d, J = 4.8, 2H),
8.48 (dd, J = 6.0, 3.3, 1H), 7.65 (d, J = 8.7, 2H), 7.48 (dd, J = 6.3, 3.0, 1H), 7.24 –
7.14 (m, 2H), 7.08 (t, J = 4.8, 1H), 6.73 (d, J = 9.0, 2H), 6.64 (s, 1H), 3.73 (s, 3H).
13C NMR (126 MHz, CDCl3): δ 163.1, 158.0, 157.7, 133.6, 133.6, 130.5, 129.2, 128.6,
123.0, 123.0, 119.9, 116.4, 115.8, 114.1, 97.6, 55.5. HRMS (EI) calcd. for
C19H16N4O3S [M]+ : 380.0943. Found: 380.0942.
Deprotection of 3f and 3g
Under Ar, 3f (36mg) was dissolved in dry DMSO 1 mL, 20% EtONa in EtOH (50 μL)
was added, the mixture was stirred at 100 ℃ for 10 min, then cooled, extracted with
EtOAc, washed with water. The organic phase was dried over Na2SO4. After
evaporation of the solvents under reduced pressure, the crude product was purified by
column chromatography on silica gel (DCM/MeOH : 100/1) to give product 4f (15mg
yeild 50%) two dynamic isomers (4:3) as a white solid (M. p. = 210 − 212 °C). IR
(film): 3091, 2923, 1591, 1300, 1145, 1087, 854, 773, 669, 545 cm-1. 1H NMR (4f-a,
18

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry
This journal is © The Royal Society of Chemistry 2012
300 MHz, DMSO): δ 10.86 (s, 1H), 10.58 (s, 1H), 7.64 (d, J = 8.3 Hz, 2H), 7.39 –
7.17 (m, 4H), 6.99 – 6.92 (m, 1H), 6.91 – 6.84 (m, 1H), 5.70 (d, J = 1.5 Hz, 1H), 2.32
(s, 3H). 1H NMR (4f-b, 300 MHz, DMSO): δ 11.57 (s, 1H), 7.76 (d, J = 8.4 Hz, 1H),
7.39 – 7.17 (m, 4H), 7.03 (t, J = 7.0 Hz, 2H), 5.70 (d, J = 1.5 Hz, 1H), 4.08 (s, 2H),
13
2.35 (s, 3H). C NMR (4f-a and 4f-b, 100 MHz, DMSO): δ 143.78, 142.88, 140.09,
137.13, 134.16, 132.59, 130.13, 129.93, 128.27, 127.49, 127.22, 126.65, 125.03,
123.28, 120.97, 119.68, 119.61, 111.65, 111.28, 92.38, 55.43, 37.39, 21.48. HRMS
(EI) calcd. for C15H14N2O2S [M]+ : 286.0776. Found: 287.0768.
Following procedure of 4f, to give product 4g (yeild 73%) as a light yellow viscous
liquid. IR (film): 3062, 2925, 1618, 1471, 1278, 1203, 1083, 924, 868, 777, 678, 551
1
cm-1. H NMR (300 MHz, DMSO): δ 11.07 (s, 1H), 7.81 (d, J = 8.4 Hz, 2H), 7.40 –
13
7.21 (m, 5H), 7.10 – 7.02 (m, 1H), 6.15 (s, 1H), 2.36 (s, 3H), 1.36 (s, 3H). C NMR
(125 MHz, DMSO): δ 171.45, 142.78, 140.79, 139.06, 133.50, 129.46, 129.23,
126.20, 123.52, 123.18, 112.29, 77.77, 25.66, 21.00. HRMS (EI) calcd. for
C15H13FN2O2S [M]+ : 300.0932. Found: 300.0927.
Reference:
S1: K. Fujita, Y. Takahashi, M. Owaki, K. Yamamoto, R. Yamaguchi, Org. Lett.
2004, 6, 2785.
S2: Yang Li, Bi-Jie Li, Wen-Hua Wang, Wei-Ping Huang, Xi-Sha Zhang, Kang Chen,
and Zhang-Jie Shi, Angew. Chem. Int. Ed. 2011, 50, 2115.
S3: Lutz Ackermann, Alexander V. Lygin, Org. Lett. 2011, 13, 3332.
S4: Joshua V. Ruppel, Jess E. Jones, Chelsea A. Huff, Rajesh M. Kamble, Ying Chen,
and X. Peter Zhang, Org. Lett. 2008, 10, 1995.
19

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry
This journal is © The Royal Society of Chemistry 2012
1H and 13C NMR Spectra of Compounds
Compound 3f
20

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry
This journal is © The Royal Society of Chemistry 2012
Compound 3g
21

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry
This journal is © The Royal Society of Chemistry 2012
Compound 3h
22

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry
This journal is © The Royal Society of Chemistry 2012
Compound 3i
23

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry
This journal is © The Royal Society of Chemistry 2012
Compound 3j
24

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry
This journal is © The Royal Society of Chemistry 2012
Compound 3k
25

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry
This journal is © The Royal Society of Chemistry 2012
Compound 3l
26

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry
This journal is © The Royal Society of Chemistry 2012
Compound 3m
27

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry
This journal is © The Royal Society of Chemistry 2012
Compound 3n
28

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry
This journal is © The Royal Society of Chemistry 2012
Compound 3o
29

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry
This journal is © The Royal Society of Chemistry 2012
Compound 3p
30