Indole synthesis by rhodium(III)-catalyzed hydrazine-directed C-H activation: Redox-neutral and traceless by N-N bond cleavage

Article abstract of DOI:10.1002/anie.201306098

Fishing for complements! There is an alternative to the useful Fischer indole synthesis. The new method utilizes the same retrosynthetic disconnection but is based on a Rh^III-catalyzed directed C-H activation step and a successive coupling with alkynes. Copyright

Full text of DOI:10.1002/anie.201306098

Supporting Information
ꢀ Wiley-VCH 2013
69451 Weinheim, Germany
À
Indole Synthesis by Rhodium(III)-Catalyzed Hydrazine-Directed C H
Activation: Redox-Neutral and Traceless by N N Bond Cleavage**
À
Dongbing Zhao, Zhuangzhi Shi, and Frank Glorius*
anie_201306098_sm_miscellaneous_information.pdf

Supporting Information
Table of content
1 General information
S2
2 Synthesis of 2-acetyl-1-arylhydrazines and diaryl substituted
alkynes S3
3 Rh(III)-catalyzed hydrazine-directed redox-neutral C-H annulation
to diverse indoles
S4
S16
S18
S19
4 Mechanistic Experiments
5 References
6 NMR spectra
S1

1 General information
Unless otherwise noted, all reactions were carried out under an atmosphere of argon in flame-
dried glassware. Reaction temperatures are reported as the temperature of the bath
surrounding the vessel unless otherwise stated. The solvents used were purified by distillation
over the drying agents indicated in parentheses and were transferred under argon.
Commercially available chemicals were obtained from Acros Organics, Aldrich Chemical
Co., Strem Chemicals, Alfa Aesar, ABCR and TCI Europe and used as received unless
otherwise stated.
Analytical thin layer chromatography was performed on Polygram SIL G/UV254 plates. Flash
chromatography was either performed on Merck silica gel (40-63 mesh) by standard
technique eluting with solvents as indicated.
GC-MS Spectra were recorded on an Agilent Technologies 7890A GC-system with an
Agilent 5975C VL MSD or an Agilent 5975 inert Mass Selective Detector (EI) and a HP-5MS
column (0.25 mm × 30 m, Film: 0.25 µm). The major signals are quoted in m/z with the
relative intensity in parentheses.
13
1H and C-NMR spectra were recorded on a Bruker AV 300 or AV 400, Varian 500 MHz
INOVA or Varian Unity plus 600 in solvents as indicate. Chemical shifts (δ) are given in ppm
relative to TMS. The residual solvent signals were used as references and the chemical shifts
converted to the TMS scale (CDCl3: δH = 7.26 ppm, δC = 77.16 ppm). ESI mass spectra were
recorded on a Bruker Daltonics MicroTof. No attempts were made to optimize yields for
substrate synthesis.
S2

2 Synthesis of 2-acetyl-1-arylhydrazines and diaryl substituted alkynes
2.1 General procedure for the synthesis of 2-acetyl-1-arylhydrazines [1]
Following a literature procedure,[1] to a suspension of aryl amine 1 (20 mmol) in water (65
mL) and conc. HCl (25 mL) cooled down to 0-5 °C, sodium nitrite (1.55 g, 22 mmol) in water
(15 mL) was added dropwise. It was kept under stirring at the same temperature for 45
minutes and, subsequently, a solution of SnCl2 (40 mmol) in conc. HCl (10 mL) was added.
Once the addition was performed, the temperature was allowed to slowly increase until
achieving room temperature, and the suspension was filtered. The remaining solid was
washed with saturated brine and diethyl ether and, subsequently, it was suspended in diethyl
ether with stirring during a few minutes. It was filtered and dried resulting in a crude brown
solid 2, which was used directly in the following synthesis step.
The arylhydrazine hydrochloride salt 2 (13 mmol) was dissolved in 1N NaOH (25 mL) and
THF (6 mL). With stirring, acetic anhydride (1.3 g, 13 mmol) was added dropwise, and after
stirring for 30 min the mixture was extracted with EtOAc (3x20 mL). The combined organic
solvent was evaporated to afford a solid residue. Recrystallization from a mixture of pentane
and dichloromethane (1:1) gave 2-acetyl-1-arylhydrazine 3.
2.2 General procedure for the synthesis of diaryl substituted alkynes [2]
Following
a
literature procedure,[2] Pd(PPh3)2Cl2 (105 mg, 0.15 mmol), 1,4-
bis(diphenylphosphino)butane (128 mg, 0.30 mmol), aryl halides (6.00 mmol), and propiolic
acid (212 mg, 3.0 mmol) were combined with DBU (913 mg, 6.0 mmol) in a small round-
bottomed flask. DMSO (15.0 mL) was added, and the flask was sealed with a septum. The
resulting mixture was placed in an oil bath at 80 °C for 3 h. The reaction was poured into 25
mL of saturated aqueous ammonium chloride and extracted with EtOAc (4x20 mL). The
combined EtOAc extracts were washed with brine (90 mL), dried over MgSO4, and filtered.
The solvent was removed under vacuum, and the resulting crude product was purified by flash
chromatography on silica gel. The product was eluted with 5% ethyl acetate in hexane.
S3

3 Rh(III)-catalyzed hydrazine-directed redox-neutral C-H annulation to
diverse indoles
3.1 Optimization of the Rh(III)-catalyzed hydrazine-directed redox-neutral
C−H annulation to indole
Table S1. Optimization of the Rh(III)-catalyzed hydrazine-directed redox-neutral C−H annulation to indole.[a]
Entry
1
R1
H
Additive
---
Solvent
DCE
Yield [%][b]
n.r
2
Ac
Piv
Ac
Ac
Ac
Ac
Ac
Ac
Ac
Ac
Ac
Ac
Ac
Ac
Ac
---
DCE
12
n.r
n.r
88
trace
41
n.r
56
58
n.r
73
62
89
77
28
3
---
DCE
4[c]
5
---
DCE
HOAc
TfOH
TFA
DCE
6
DCE
7
DCE
8
HOAc
HOAc
HOAc
HOAc
HOAc
HOAc
---
dioxane
methanol
CHCl3
toluene
DCE
9
10
11
12[d
13[e]
14[f]
15[g]
16[h]
DCE
DCE
HOAc
HOAc
DCE
DCE
[a] Reactions were carried out by using [RhCp*Cl2]2 (2.5 mol%), CsOAc (25 mol%), additive (0-1.2 equiv.), hydrazines (0.2
mmol), and diphenylacetylene (0.22 mmol) in solvent (1 mL) for 16 h at 70 °C under an argon atmosphere. [b] Isolated yield. [c]
N'-methyl-N'-phenylacetohydrazide was used as the substrate. [d] NaOAc (25 mol%) was used as the base; [e] CsOPiv (25
mol%) was used as the base; [f] RhCp*(OAc)2 (5 mol%) was used as the catalyst; [g] 12 h; [h] room temperature. n.r = no
reaction.
3.2 General procedure for the Rh(III)-catalyzed hydrazine-directed redox-
neutral C-H annulation
To a 50 mL screw-capped vial equipped with a 10 x 5 mm spinvane-shaped Teflon stirrer bar
were charged with 2-acetyl-1-arylhydrazine (0.2 mmol), alkyne 2 (0.22 mmol), [Cp*RhCl2]2
(2.5 mol%), CsOAc (25 mol%), acetic acid (1.2 equiv.), and 1,2-dichloroethane (1.5 mL)
under the Argon atmosphere. The resulting mixture was sealed with a Teflon-lined cap and
S4

stirred at 70 °C for 16 h in an oil bath. The reaction was cooled to room temperature, filtered
through a plug of celite and washed with dichloromethane (15 mL). The desired product was
obtained by column chromatography using an appropriate eluent.
3.3 Procedure for the gram scale preparation of 2,3-Diphenyl-1H-indole (3a)
To a 150 mL screw-capped vial equipped with a 10 x 5 mm spinvane-shaped Teflon stirrer
bar were charged with 2-acetyl-1-phenylhydrazine (1.5 g, 10 mmol), alkyne 2 (1.96 g, 11
mmol), [Cp*RhCl2]2 (155 mg, 0.25 mmol), CsOAc (480 mg, 2.5 mmol), acetic acid (720 μL,
12 mmol), and 1,2-dichloroethane (50 mL) under the Argon atmosphere. The resulting
mixture was sealed with a Teflon-lined cap and stirred at 70 °C for 16 h in an oil bath. The
reaction was cooled to room temperature, filtered through a plug of celite and washed with
dichloromethane (25 mL). The desired product was obtained by column chromatography
(pentane/ethyl acetate10:1). 2,3-Diphenyl-1H-indole (3a) was formed in 86% yield (2.32 g).
2,3-Diphenyl-1H-indole (3a)
Following the general procedure, the C-H activation/cyclization reaction
was carried out with 2-acetyl-1-phenylhydrazine (30 mg, 0.2 mmol),
[Cp*RhCl2]2 (3.1 mg, 0.005 mmol), diphenylacetylene (39.15 mg, 0.22
mmol), CsOAc (9.6 mg, 0.05 mmol), HOAc (14.4 μL, 0.24 mmol) and
1,2-dichloroethane (1 mL) at 70 ºC for 16 h. 2,3-Diphenyl-1H-indole (3a) was formed in 88%
yield. Rf (pentane/ethyl acetate 10:1): 0.25; 1H NMR (300 MHz, CDCl3): δ 8.24 (s, 1H), 7.70
(d, J = 7.9 Hz, 1H), 7.54 – 7.21 (m, 12H), 7.17 (t, J = 7.5 Hz, 1H); 13C NMR (75 MHz,
CDCl3): δ 136.01, 135.17, 134.21, 132.83, 132.80, 130.29, 128.88, 128.83, 128.66, 128.30,
127.84, 126.37, 122.85, 120.57, 119.84, 111.01. HRMS: m/z (ESI) calcd for [C20H16N]+:
270.1283, found: 270.1277.
6-Methyl-2,3-diphenyl-1H-indole (3b)
Following the general procedure, the C-H activation/cyclization
reaction was carried out with 2-acetyl-1-(3-methylphenyl)hydrazine
(32.8 mg, 0.2 mmol), [Cp*RhCl2]2 (3.1 mg, 0.005 mmol),
diphenylacetylene (39.15 mg, 0.22 mmol), CsOAc (9.6 mg, 0.05
mmol), HOAc (14.4 μL, 0.24 mmol) and 1,2-dichloroethane (1 mL) at 70 ºC for 16 h. 6-
Methyl-2,3-diphenyl-1H-indole (3b) was formed in 93% yield. Rf (pentane/ethyl acetate =
1
10:1): 0.30; H NMR (300 MHz, CDCl3): δ 8.09 (s, 1H), 7.60 (d, J = 8.2 Hz, 1H), 7.52 –
S5

7.27 (m, 10H), 7.22 (s, 1H), 7.02 (dd, J = 8.2, 0.9 Hz, 1H), 2.52 (s, 3H). 13C NMR (75 MHz,
CDCl3): δ 136.35, 135.26, 133.38, 132.88, 132.60, 130.09, 128.62, 128.46, 128.04, 127.46,
126.69, 126.12, 122.18, 119.36, 114.94, 110.80, 21.72. HRMS: m/z (ESI) calcd for
C21H17NNa (M + Na)+ 306.1259, found 306.1253.
5-Methyl-2,3-diphenyl-1H-indole (3c)
Following the general procedure, the C-H activation/cyclization
reaction was carried out with 2-acetyl-1-(4-methylphenyl)hydrazine
(32.8 mg, 0.2 mmol), [Cp*RhCl2]2 (3.1 mg, 0.005 mmol),
diphenylacetylene (39.15 mg, 0.22 mmol), CsOAc (9.6 mg, 0.05
mmol), HOAc (14.4 μL, 0.24 mmol) and 1,2-dichloroethane (1 mL) at 70 ºC for 16 h. 5-
Methyl-2,3-diphenyl-1H-indole (3c) was formed in 91% yield. Rf (pentane/ethyl acetate 10:1):
0.25; 1H NMR (300 MHz, CDCl3): δ 8.14 (s, 1H), 7.56 – 7.23 (m, 12H), 7.09 (d, J = 8.2 Hz,
1H), 2.46 (s, 3H); 13C NMR (75 MHz, CDCl3):δ 135.37, 134.33, 132.94, 130.32, 129.87,
129.13, 128.78, 128.64, 128.22, 127.70, 126.29, 124.43, 119.36, 114.77, 110.69, 21.70.
HRMS: m/z (ESI) calcd for [C21H17N +Na]+: 306.1259, found: 306.1253.
5,6-Dimethyl-2,3-diphenyl-1H-indole (3d)
Following the general procedure, the C-H activation/cyclization
reaction
was
carried
out
with
2-acetyl-1-(3,4-
dimethylphenyl)hydrazine (35.6 mg, 0.2 mmol), [Cp*RhCl2]2 (3.1
mg, 0.005 mmol), diphenylacetylene (39.15 mg, 0.22 mmol),
CsOAc (9.6 mg, 0.05 mmol), HOAc (14.4 μL, 0.24 mmol) and 1,2-dichloroethane (1 mL) at
70 ºC for 16 h. 5,6-Dimethyl-2,3-diphenyl-1H-indole (3d) was formed in 90% yield. Rf
(pentane/ethyl acetate = 10:1): 0.30; 1H NMR (300 MHz, CDCl3): δ 8.08 (s, 1H), 7.58 – 7.32
(m, 11H), 7.26 (s, 1H), 2.47 (s, 3H), 2.42 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 135.48,
134.91, 133.24, 133.00, 131.84, 130.15, 129.12, 128.58, 128.45, 127.98, 127.34, 127.23,
126.05, 119.64, 114.58, 111.25, 20.44, 20.10. HRMS: m/z (ESI) calcd for C21H17NONa (M +
Na)+ 322.1208, found 322.1202.
5-Methoxy-2,3-diphenyl-1H-indole (3e)
Following the general procedure, the C-H activation/cyclization
reaction
was
carried
out
with
2-acetyl-1-(4-
S6

methoxyphenyl)hydrazine (36 mg, 0.2 mmol), [Cp*RhCl2]2 (3.1 mg, 0.005 mmol),
diphenylacetylene (39.15 mg, 0.22 mmol), CsOAc (9.6 mg, 0.05 mmol), HOAc (14.4 μL,
0.24 mmol) and 1,2-dichloroethane (1 mL) at 70 ºC for 16 h. 5-Methoxy-2,3-diphenyl-1H-
1
indole (3e) was formed in 92% yield. Rf (pentane/ethyl acetate = 10:1): 0.30; H NMR (400
MHz, CDCl3): δ 8.15 (s, 1H), 7.48 – 7.37 (m, 6H), 7.36 – 7.28 (m, 5H), 7.13 (d, J = 2.4 Hz,
13
1H), 6.92 (dd, J = 8.7, 2.4 Hz, 1H), 3.83 (s, 3H). C NMR (101 MHz, CDCl3): δ 154.76,
135.18, 134.92, 132.70, 131.02, 130.06, 129.14, 128.63, 128.58, 128.04, 127.59, 126.16,
114.91, 112.99, 111.67, 101.18, 55.91. HRMS: m/z (ESI) calcd for C21H17NONa (M + Na)+
322.1208, found 322.1202.
2,3,5-Triphenyl-1H-indole (3f)
Following the general procedure, the C-H activation/cyclization
reaction was carried out with 2-acetyl-1-(4-phenylphenyl)hydrazine
(45.2 mg, 0.2 mmol), [Cp*RhCl2]2 (3.1 mg, 0.005 mmol),
diphenylacetylene (39.15 mg, 0.22 mmol), CsOAc (9.6 mg, 0.05
mmol), HOAc (14.4 μL, 0.24 mmol) and 1,2-dichloroethane (1 mL) at 70 ºC for 16 h. 2,3,5-
1
Triphenyl-1H-indole (3f) was formed in 86% yield. Rf (pentane/ethyl acetate 8:1): 0.25; H
NMR (300 MHz, CDCl3): δ 8.16 (s, 1H), 7.79 (s, 1H), 7.55 (dt, J = 8.3, 1.8 Hz, 2H), 7.48 –
7.17 (m, 15H); 13C NMR (75 MHz, CDCl3): δ 142.65, 135.58, 135.10, 134.93, 134.28,
132.76, 130.37, 129.46, 128.85, 128.75, 128.28, 127.91, 127.56, 126.53, 126.49, 122.74,
118.34, 115.61, 111.26. HRMS: m/z (ESI) calcd for [C26H19N +Na]+: 368.1415, found
368.1405.
7-Fluoro-2,3-diphenyl-1H-indole (3g)
Following the general procedure, the C-H activation/cyclization reaction
was carried out with 2-acetyl-1-(2-fluorophenyl)hydrazine (33.6 mg, 0.2
mmol), [Cp*RhCl2]2 (3.1 mg, 0.005 mmol), diphenylacetylene (39.15 mg,
0.22 mmol), CsOAc (9.6 mg, 0.05 mmol), HOAc (14.4 μL, 0.24 mmol)
and 1,2-dichloroethane (1 mL) at 70 ºC for 16 h. 7-Fluoro-2,3-diphenyl-
1H-indole (3g) was formed in 83% yield. Rf (pentane/ethyl acetate 10:1): 0.30; 1H NMR (300
MHz, CDCl3):8.40 (s, 1H), 7.57 – 7.27 (m, 11H), 7.08 (td, J = 7.9, 4.9 Hz, 1H), 6.98 (ddd, J
= 10.9, 7.9, 0.9 Hz, 1H); 13C NMR (75 MHz, CDCl3): 151.14, 147.91, 135.01, 134.72,
132.49, 132.43, 132.29, 130.21, 128.90, 128.73, 128.34, 128.18, 126.64, 124.41, 124.23,
S7

120.75, 120.66, 115.80, 115.76, 115.61, 115.57, 107.69, 107.48. 19F NMR (282.3 MHz,
CDCl3): δ 135.6. HRMS: m/z (ESI) calcd for [C20H14FN]: 287.1110, found 287.1105.
5-Fluoro-2,3-diphenyl-1H-indole (3h)
Following the general procedure, the C-H activation/cyclization
reaction was carried out with 2-acetyl-1-(4-fluorophenyl)hydrazine
(33.6 mg, 0.2 mmol), [Cp*RhCl2]2 (3.1 mg, 0.005 mmol),
diphenylacetylene (39.15 mg, 0.22 mmol), CsOAc (9.6 mg, 0.05
mmol), HOAc (14.4 μL, 0.24 mmol) and 1,2-dichloroethane (1 mL) at 70 ºC for 16 h. 5-
Fluoro-2,3-diphenyl-1H-indole (3h) was formed in 64% yield. Rf (pentane/ethyl acetate =
10:1): 0.30; 1H NMR (400 MHz, CDCl3): δ 8.22 (s, 1H), 7.54 – 7.28 (m, 12H), 7.00 (td, J =
9.0, 2.5 Hz, 1H). 13C NMR (101 MHz, CDCl3): δ 158.46 (d, J1F = 236.34 Hz), 135.84,
134.57, 132.34, 129.91, 129.20 (d, J3F = 9.09 Hz), 128.68 (d, J3F = 11.11 Hz), 128.11, 127.94,
126.41, 115.20, 115.53 (d, J4F = 4.04 Hz), 110.00 (d, J2F = 27.27 Hz), 104.57 (d, J2F = 24.24
Hz). 19F NMR (282.3 MHz, CDCl3): δ 123.55. HRMS: m/z (ESI) calcd for C20H14NFNa (M
+ Na)+ 310.1108, found 310.1102.
5-Chloro-2,3-diphenyl-1H-indole (3i)
Following the general procedure, the C-H activation/cyclization
reaction was carried out with 2-acetyl-1-(4-chlorophenyl)hydrazine
(36.8 mg, 0.2 mmol), [Cp*RhCl2]2 (3.1 mg, 0.005 mmol),
diphenylacetylene (39.15 mg, 0.22 mmol), CsOAc (9.6 mg, 0.05
mmol), HOAc (14.4 μL, 0.24 mmol) and 1,2-dichloroethane (1 mL) at 70 ºC for 16 h. 5-
Chloro-2,3-diphenyl-1H-indole (3i) was formed in 78% yield. Rf (pentane/ethyl acetate =
1
10:1): 0.30; H NMR (300 MHz, CDCl3): δ 8.25 (s, 1H), 7.65 (d, J = 2.0 Hz, 1H), 7.49 –
7.28 (m, 11H), 7.20 (dd, J = 8.6, 2.0 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 135.40, 134.37,
134.20, 132.17, 130.02, 129.92, 128.73, 128.65, 128.10, 128.00, 126.54, 126.16, 122.91,
119.10, 114.78, 111.88. HRMS: m/z (ESI) calcd for C20H14NClNa (M + Na)+ 326.0712,
found 326.0708.
5-Bromo-2,3-diphenyl-1H-indole (3j)
Following the general procedure, the C-H activation/cyclization
reaction was carried out with 2-acetyl-1-(4-bromophenyl)hydrazine
S8

(45.8 mg, 0.2 mmol), [Cp*RhCl2]2 (3.1 mg, 0.005 mmol), diphenylacetylene (39.15 mg, 0.22
mmol), CsOAc (9.6 mg, 0.05 mmol), HOAc (14.4 μL, 0.24 mmol) and 1,2-dichloroethane (1
mL) at 70 ºC for 16 h. 5-Bromo-2,3-diphenyl-1H-indole (3g) was formed in 92% yield. Rf
1
(pentane/ethyl acetate 10:1): 0.30; H NMR(300 MHz, CDCl3): δ 8.25 (s, 1H), 7.80 (d, J =
1.7 Hz, 1H), 7.46 – 7.37 (m, 6H), 7.37 – 7.27 (m, 6H); 13C NMR (75 MHz, CDCl3): δ 135.33,
134.56, 134.43, 132.21, 130.64, 130.16, 128.89, 128.81, 128.24, 128.17, 126.70, 125.59,
122.29, 114.76, 113.82, 112.47, 77.58, 77.16, 76.74. HRMS: m/z (ESI) calcd for
[C20H14BrN+Na]+: 370.0207, found 370.0197.
5,6-Dichloro-2,3-diphenyl-1H-indole (3k)
Following the general procedure, the C-H activation/cyclization
reaction
was
carried
out
with
2-acetyl-1-(3,4-
dichlorophenyl)hydrazine (43.6 mg, 0.2 mmol), [Cp*RhCl2]2 (3.1 mg,
0.005 mmol), diphenylacetylene (39.15 mg, 0.22 mmol), CsOAc (9.6
mg, 0.05 mmol), HOAc (14.4 μL, 0.24 mmol) and 1,2-dichloroethane (1 mL) at 70 ºC for 16
h. 5,6-Dichloro-2,3-diphenyl-1H-indole (3k) was formed in 60% yield. Rf (pentane/ethyl
acetate = 10:1): 0.30; 1H NMR (300 MHz, CDCl3): δ 8.24 (s, 1H), 7.71 (s, 1H), 7.51 (s, 1H),
7.47 – 7.28 (m, 11H). 13C NMR (75 MHz, CDCl3): δ 135.87, 134.58, 133.92, 131.80,
129.95, 128.82, 128.75, 128.68, 128.26, 128.07, 126.78, 126.28, 124.56, 120.66, 114.69,
112.31. HRMS: m/z (ESI) calcd for C20H13NCl2Na (M + Na)+ 360.0323, found 360.0317.
6-Iodo-5-methyl-2,3-diphenyl-1H-indole (3l)
Following the general procedure, the C-H activation/cyclization
reaction
was
carried
out
with
2-acetyl-1-(4-iodo-3-
methylphenyl)hydrazine (58 mg, 0.2 mmol), [Cp*RhCl2]2 (3.1 mg,
0.005 mmol), diphenylacetylene (39.15 mg, 0.22 mmol), CsOAc
(9.6 mg, 0.05 mmol), HOAc (14.4 μL, 0.24 mmol) and 1,2-dichloroethane (1 mL) at 70 ºC for
16 h. 6-Iodo-5-methyl-2,3-diphenyl-1H-indole (3l) was formed in 81% yield. Rf
1
(pentane/ethyl acetate 8:1): 0.30; H NMR (300 MHz, CDCl3): δ 8.09 (s, 1H), 7.91 (s, 1H),
7.53 (s, 1H), 7.49 – 7.27 (m, 10H), 2.51 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 135.72,
134.81, 132.45, 132.26, 130.25, 129.55, 128.87, 128.75, 128.23, 128.04, 126.59, 121.01,
119.71, 114.80, 93.84, 28.30. HRMS: m/z (ESI) calcd for [C21H16IN+Na]+: 432.0225, found
432.0215.
S9

2,3-Diphenyl-5-(trifluoromethoxy)-1H-indole (3m)
Following the general procedure, the C-H activation/cyclization
reaction was carried out with 2-acetyl-1-(3-trifluoromethoxy
phenyl)hydrazine (46.8 mg, 0.2 mmol), [Cp*RhCl2]2 (3.1 mg,
0.005 mmol), diphenylacetylene (39.15 mg, 0.22 mmol), CsOAc
(9.6 mg, 0.05 mmol), HOAc (14.4 μL, 0.24 mmol) and 1,2-dichloroethane (1 mL) at 70 ºC for
16 h. 2,3-Diphenyl-5-(trifluoromethoxy)-1H-indole (3m) was formed in 92% yield. Rf
1
(pentane/ethyl acetate 8:1): 0.25; H NMR (300 MHz, CDCl3): δ 8.30 (s, 1H), 7.65 (d, J = 8.7 Hz,
1H), 7.50 – 7.27 (m, 11H), 7.06 (ddq, J = 8.7, 1.9, 0.9 Hz, 1H); 13C NMR (75 MHz, CDCl3): δ
145.59, 145.56, 135.58, 135.52, 134.57, 132.34, 130.21, 128.93, 128.80, 128.23, 128.17,
127.70, 126.73, 122.64, 120.59, 119.25, 115.22, 114.60, 104.04; 19F NMR (282.3 MHz,
CDCl3): δ 57.89. HRMS: m/z (ESI) calcd for [C21H14F3NO +Na]+: 376.0925, found
376.0920.
Methyl 2,3-diphenyl-1H-indole-5-carboxylate (3n)
Following
the
general
procedure,
the
C-H
activation/cyclization reaction was carried out with 2-acetyl-1-
(methyl-4-phenyl carboxylate)hydrazine (41.6 mg, 0.2 mmol),
[Cp*RhCl2]2 (3.1 mg, 0.005 mmol), diphenylacetylene (39.15
mg, 0.22 mmol), CsOAc (9.6 mg, 0.05 mmol), HOAc (14.4 μL,
0.24 mmol) and 1,2-dichloroethane (1 mL) at 70 ºC for 16 h. 5-Methyl 2,3-diphenyl-1H-
1
indole-5-carboxylate (3n) was formed in 82% yield. Rf (pentane/ethyl acetate 5:1): 0.30; H
NMR (300 MHz, CDCl3): δ 8.50 (s, 1H), 8.46 – 8.37 (m, 1H), 7.96 (dd, J = 8.6, 1.6 Hz, 1H),
13
7.51 – 7.27 (m, 11H), 3.91 (s, 3H); C NMR (75 MHz, CDCl3): δ 168.23, 138.55, 135.39,
134.36, 132.21, 130.30, 128.94, 128.85, 128.61, 128.26, 128.22, 126.79, 124.27, 122.84,
122.66, 116.29, 110.72, 52.03. HRMS: m/z (ESI) calcd for [C22H17NO2 +Na]+: 350.1157,
found 350.1159.
2,3-Diphenyl-1H-indole-5-carbonitrile (3o)
Following the general procedure, the C-H activation/cyclization
reaction was carried out with 2-acetyl-1-(4-cyanophenyl
S10

carboxylate)hydrazine (35 mg, 0.2 mmol), [Cp*RhCl2]2 (3.1 mg, 0.005 mmol),
diphenylacetylene (39.15 mg, 0.22 mmol), CsOAc (9.6 mg, 0.05 mmol), HOAc (14.4 μL,
0.24 mmol) and 1,2-dichloroethane (1 mL) at 70 ºC for 16 h. 2,3-Diphenyl-1H-indole-5-
1
carbonitrile (3o) was formed in 41% yield. Rf (pentane/ethyl acetate = 3:1): 0.30; H NMR
(400 MHz, CDCl3): δ 8.60 (s, 1H), 8.00 (s, 1H), 7.53 – 7.30 (m, 12H). 13C NMR (101 MHz,
CDCl3): δ 137.58, 136.21, 133.67, 131.65, 130.10, 129.05, 128.99, 128.85, 128.62, 128.31,
127.16, 125.66, 125.57, 120.81, 115.65, 111.89, 103.67. HRMS: m/z (ESI) calcd for
C21H14N2Na (M + Na)+ 317.1055, found 326.0707.
2,3-Di-p-tolyl-1H-indole (4a)
Following the general procedure, the C-H activation/cyclization
reaction was carried out with 2-acetyl-1-phenylhydrazine (30 mg,
0.2 mmol), [Cp*RhCl2]2 (3.1 mg, 0.005 mmol), 1,2-di-p-
tolylethyne (45.32 mg, 0.22 mmol), CsOAc (9.6 mg, 0.05 mmol),
HOAc (14.4 μL, 0.24 mmol) and 1,2-dichloroethane (1 mL) at 70
ºC for 16 h. 2,3-Di-p-tolyl-1H-indole (4a) was formed in 93%
yield. Rf (pentane/ethyl acetate 10:1): 0.25; 1H NMR (300 MHz, CDCl3): δ 8.16 (s, 1H), 7.67
(d, J = 7.9 Hz, 1H), 7.45 – 7.28 (m, 5H), 7.27 – 7.07 (m, 6H), 2.39 (s, 3H), 2.35 (s, 3H); 13C
NMR (75 MHz, CDCl3): δ 137.60, 135.91, 135.80, 134.14, 132.25, 130.09, 130.02, 129.50,
129.38, 129.01, 128.11, 122.56, 120.37, 119.75, 114.62, 110.92, 21.40. HRMS: m/z (ESI)
calcd for [C22H19N]: 297.1517, found 297.1512.
2,3-Bis(4-methoxyphenyl)-1H-indole (4b)
Following
the
general
procedure,
the
C-H
activation/cyclization reaction was carried out with 2-acetyl-
1-phenylhydrazine (30 mg, 0.2 mmol), [Cp*RhCl2]2 (3.1 mg,
0.005 mmol), 1,2-bis(4-methoxyphenyl)ethyne (52.36 mg,
0.22 mmol), CsOAc (9.6 mg, 0.05 mmol), HOAc (14.4 μL,
0.24 mmol) and 1,2-dichloroethane (1 mL) at 70 ºC for 16 h.
2,3-Bis(4-methoxyphenyl)-1H-indole (4b) was formed in 91% yield. Rf (pentane/ethyl acetate
7:1): 0.25; 1H NMR (300 MHz, CDCl3): δ 8.24 (s, 1H), 7.67 (d, J = 7.8 Hz, 1H), 7.47 – 7.31
(m, 5H), 7.18 (dt, J = 14.9, 7.3 Hz, 2H), 6.96 (d, J = 8.7 Hz, 2H), 6.87 (d, J = 8.8 Hz, 2H),
13
3.87 (s, 3H), 3.82 (s, 3H); C NMR (75 MHz, CDCl3): δ 159.17, 158.11, 135.82, 133.86,
131.26, 129.44, 129.08, 127.69, 125.42, 122.37, 120.29, 119.51, 114.22, 114.12, 113.80,
S11

110.87, 55.36, 55.34. HRMS: m/z (ESI) calcd for [C22H19NO2+Na]+: 352.1313, found:
352.1296.
2,3-Bis(3-methoxyphenyl)-1H-indole (4c)
Following the general procedure, the C-H activation/cyclization
reaction was carried out with 2-acetyl-1-phenylhydrazine (30 mg,
0.2 mmol), [Cp*RhCl2]2 (3.1 mg, 0.005 mmol), 1,2-bis(3-
methoxyphenyl)ethyne (52.36 mg, 0.22 mmol), CsOAc (9.6 mg,
0.05 mmol), HOAc (14.4 μL, 0.24 mmol) and 1,2-
dichloroethane (1 mL) at 70 ºC for 16 h. 2,3-Bis(3-
methoxyphenyl)-1H-indole (4b) was formed in 70% yield. Rf
1
(pentane/ethyl acetate 7:1): 0.25; H NMR (400 MHz, CDCl3): δ 8.24 (s, 1H), 7.67 (d, J =
8.0 Hz, 1H), 7.38 (d, J = 8.1 Hz, 1H), 7.30 – 7.17 (m, 3H), 7.12 (ddd, J = 8.0, 7.1, 1.0 Hz, 1H),
7.03 – 6.97 (m, 3H), 6.96 – 6.91 (m, 1H), 6.85 – 6.76 (m, 2H), 3.72 (s, 3H), 3.63 (s, 3H); 13C
NMR (101 MHz, CDCl3): δ 159.77, 159.68, 136.54, 135.88, 134.07, 133.97, 129.83, 129.60,
128.80, 122.90, 120.58, 120.49, 119.86, 115.54, 115.20, 113.85, 113.55, 112.29, 111.03,
55.32, 55.25. HRMS: m/z (ESI) calcd for [C22H19NO2+Na]+: 352.1313, found: 352.1308.
2,3-Bis(4-chlorophenyl)-1H-indole (4d)
Following the general procedure, the C-H activation/cyclization
reaction was carried out with 2-acetyl-1-phenylhydrazine (30
mg, 0.2 mmol), [Cp*RhCl2]2 (3.1 mg, 0.005 mmol), 1,2-bis(4-
chlorophenyl)ethyne (54.34 mg, 0.22 mmol), CsOAc (9.6 mg,
0.05 mmol), HOAc (14.4 μL, 0.24 mmol) and 1,2-
dichloroethane (1 mL) at 100 ºC for 16 h. 2,3-Bis(4-
chlorophenyl)-1H-indole (4d) was formed in 58% yield. Rf (pentane/ethyl acetate 9:1): 0.25;
1H NMR (300 MHz, CDCl3): δ 8.18 (s, 1H), 7.58 (d, J = 7.9 Hz, 1H), 7.39 (d, J = 8.1 Hz,
1H), 7.36 – 7.17 (m, 9H), 7.18 – 7.06 (m, 1H); 13C NMR (75 MHz, CDCl3): δ 136.05,
134.00, 133.35, 133.20, 132.80, 132.38, 131.43, 130.95, 129.51, 129.23, 129.04, 128.51,
123.31, 120.94, 119.60, 114.38, 111.18. HRMS: m/z (ESI) calcd for [C20H13Cl2N+Na]+:
360.0323, found: 360.0317.
2,3-Bis(3-chlorophenyl)-1H-indole (4e)
S12

Following the general procedure, the C-H activation/cyclization
reaction was carried out with 2-acetyl-1-phenylhydrazine (30 mg,
0.2 mmol), [Cp*RhCl2]2 (3.1 mg, 0.005 mmol), 1,2-bis(3-
chlorophenyl)ethyne (54.34 mg, 0.22 mmol), CsOAc (9.6 mg, 0.05
mmol), HOAc (14.4 μL, 0.24 mmol) and 1,2-dichloroethane (1 mL)
at 70 ºC for 16 h. 2,3-Bis(3-chlorophenyl)-1H-indole (4e) was
1
formed in 72% yield. Rf (pentane/ethyl acetate 8:1): 0.25; H NMR (300 MHz, CDCl3): δ
13
8.19 (s, 1H), 7.62 (d, J = 8.0 Hz, 1H), 7.46 – 7.34 (m, 3H), 7.31 – 7.10 (m, 8H); C NMR
(75 MHz, CDCl3): δ 136.64, 136.04, 134.83, 134.51, 134.16, 133.00, 130.17, 130.03, 129.98,
128.45, 128.40, 128.12, 127.92, 126.79, 126.70, 123.48, 121.04, 119.70, 114.59, 111.23.
HRMS: m/z (ESI) calcd for [C20H13Cl2N+Na]+: 360.0323, found: 360.0322.
2,3-Bis(4-fluorophenyl)-1H-indole (4f)
Following the general procedure, the C-H activation/cyclization
reaction was carried out with 2-acetyl-1-phenylhydrazine (30 mg,
0.2 mmol), [Cp*RhCl2]2 (3.1 mg, 0.005 mmol), 1,2-bis(4-
fluorophenyl)ethyne (47.08 mg, 0.22 mmol), CsOAc (9.6 mg,
0.05 mmol), HOAc (14.4 μL, 0.24 mmol) and 1,2-dichloroethane
(1 mL) at 70 ºC for 16 h. 2,3-Bis(4-fluorophenyl)-1H-indole (4f)
was formed in 91% yield. Rf (pentane/ethyl acetate 10:1): 0.25; 1H NMR (400 MHz, CDCl3):
δ 8.19 (s, 1H), 7.64 (d, J = 7.9 Hz, 1H), 7.44 (d, J = 8.1 Hz, 1H), 7.42 – 7.33 (m, 4H), 7.31 –
7.24 (m, 1H), 7.18 (t, J = 7.5 Hz, 1H), 7.15 – 6.98 (m, 4H); 13C NMR (101 MHz, CDCl3): δ
163.71, 162.96, 161.24, 160.53, 135.89, 133.33, 131.72, 131.64, 130.86, 130.83, 130.07,
129.99, 128.76, 128.72, 128.71, 123.03, 120.77, 119.56, 116.11, 115.90, 115.83, 115.62,
114.13, 111.08, 77.48, 77.16, 76.84. 19F NMR (282.3 MHz, CDCl3): δ 118.3, 116.2. HRMS:
m/z (ESI) calcd for [C14H20N]+: 202.1596, found: 202.1576.
2,3-Diethyl-1H-indole (4g)
Following the general procedure, the C-H activation/cyclization reaction
was carried out with 2-acetyl-1-phenylhydrazine (30 mg, 0.2 mmol),
[Cp*RhCl2]2 (3.1 mg, 0.005 mmol), hex-3-yne (18 mg, 0.22 mmol),
CsOAc (9.6 mg, 0.05 mmol), HOAc (14.4 μL, 0.24 mmol) and 1,2-
dichloroethane (1 mL) at 100 ºC for 16 h. 2,3-Diethyl-1H-indole (4g) was formed in 68%
yield. Rf (pentane/ethyl acetate 12:1): 0.25; 1H NMR (400 MHz, CDCl3): δ 7.70 (s, 1H), 7.59
S13

– 7.53 (m, 1H), 7.32 – 7.27 (m, 1H), 7.18 – 7.06 (m, 2H), 2.76 (dq, J = 10.4, 7.6 Hz, 4H),
1.28 (dt, J = 15.3, 7.6 Hz, 6H); 13C NMR (101 MHz, CDCl3): δ 136.15, 135.35, 128.59,
120.95, 119.07, 118.35, 113.26, 110.40, 77.48, 77.16, 76.84, 19.46, 17.44, 15.92, 14.60.
HRMS: m/z (ESI) calcd for [C12H16N]+: 174.1283, found: 4174.1251.
2,3-Dipropyl-1H-indole (4h)
Following the general procedure, the C-H activation/cyclization
reaction was carried out with 2-acetyl-1-phenylhydrazine (30 mg, 0.2
mmol), [Cp*RhCl2]2 (3.1 mg, 0.005 mmol), oct-4-yne (24.2 mg, 0.22
mmol), CsOAc (9.6 mg, 0.05 mmol), HOAc (14.4 μL, 0.24 mmol) and
1,2-dichloroethane (1 mL) at 100 ºC for 16 h. 2,3-Dipropyl-1H-indole
1
(4h) was formed in 86% yield. Rf (pentane/ethyl acetate 12:1): 0.25; H NMR (300 MHz,
CDCl3): δ 7.63 (s, 1H), 7.48 – 7.40 (m, 1H), 7.22 – 7.16 (m, 1H), 7.08 – 6.91 (m, 2H), 2.71 –
2.51 (m, 4H), 1.59 (hept, J = 7.4 Hz, 4H), 0.90 (q, J = 7.4 Hz, 6H); 13C NMR (101 MHz,
CDCl3): δ 135.38, 135.33, 128.92, 120.85, 118.95, 118.46, 112.28, 110.31, 33.39, 32.20,
25.97, 24.04, 22.93, 22.66, 14.21, 14.06. HRMS m/z (ESI) calcd for [C14H19N]: 201.1517,
found: 201.1513.
2,3-Dibutyl-1H-indole (4i)
Following the general procedure, the C-H activation/cyclization
reaction was carried out with 2-acetyl-1-phenylhydrazine (30 mg, 0.2
mmol), [Cp*RhCl2]2 (3.1 mg, 0.005 mmol), dec-5-yne (30.4 mg,
0.22 mmol), CsOAc (9.6 mg, 0.05 mmol), HOAc (14.4 μL, 0.24
mmol) and 1,2-dichloroethane (1 mL) at 100 ºC for 16 h. 2,3-
1
Dibutyl-1H-indole (4i) was formed in 80% yield. Rf (pentane/ethyl acetate 12:1): 0.25; H
NMR (400 MHz, CDCl3): δ 7.70 (s, 1H), 7.60 – 7.54 (m, 1H), 7.32 – 7.27 (m, 1H), 7.13 (pd,
J = 7.1, 1.4 Hz, 2H), 2.81 – 2.65 (m, 4H), 1.65 (ddd, J = 12.5, 9.2, 6.3 Hz, 4H), 1.44 (dq, J =
13
14.4, 7.4 Hz, 4H), 0.99 (td, J = 7.3, 3.4 Hz, 6H); C NMR (101 MHz, CDCl3): δ 135.38,
135.33, 128.92, 120.85, 118.95, 118.46, 112.28, 110.31, 33.39, 32.20, 25.97, 24.04, 22.93,
22.66, 14.21, 14.06. HRMS m/z (ESI) calcd for [C16H24N]+: 230.1909, found: 230.1856.
3-Methyl-2-phenyl-1H-indole (4j)[3]
S14

Following the general procedure, the C-H activation/cyclization
reaction was carried out with 2-acetyl-1-phenylhydrazine (30 mg, 0.2
mmol), [Cp*RhCl2]2 (3.1 mg, 0.005 mmol), prop-1-yn-1-ylbenzene
(25.5 mg, 0.22 mmol), CsOAc (9.6 mg, 0.05 mmol), HOAc (14.4 μL,
0.24 mmol) and 1,2-dichloroethane (1 mL) at 100 ºC for 16 h. 3-Methyl-2-phenyl-1H-indole
1
(4j) was formed in 49% yield. Rf (pentane/ethyl acetate 12:1): 0.25; H NMR (400 MHz,
CDCl3): δ 8.03 (s, 1H), 7.64 – 7.57 (m, 3H), 7.49 (t, J = 7.7 Hz, 2H), 7.40 – 7.33 (m, 2H),
7.22 (td, J = 8.1, 7.6, 1.3 Hz, 1H), 7.15 (td, J = 7.5, 7.1, 1.1 Hz, 1H), 2.48 (s, 3H); 13C NMR
(101 MHz, CDCl3): δ 135.94, 134.14, 133.47, 130.14, 128.95, 127.86, 127.45, 122.45,
119.65, 119.11, 110.78, 108.84, 9.80. HRMS m/z (ESI) calcd for [C15H14N]+: 208.1126,
found: 208.1076.
3-Ethyl-2-phenyl-1H-indole (4k)
Following the general procedure, the C-H activation/cyclization
reaction was carried out with 2-acetyl-1-phenylhydrazine (30 mg, 0.2
mmol), [Cp*RhCl2]2 (3.1 mg, 0.005 mmol), but-1-yn-1-ylbenzene
(28.6 mg, 0.22 mmol), CsOAc (9.6 mg, 0.05 mmol), HOAc (14.4 μL,
0.24 mmol) and 1,2-dichloroethane (1 mL) at 100 ºC for 16 h. 3-
Ethyl-2-phenyl-1H-indole (4k) was formed in 58% yield. Rf (pentane/ethyl acetate 12:1): 0.25;
1H NMR (300 MHz, CDCl3): δ 7.99 (s, 1H), 7.68 (d, J = 7.7 Hz, 1H), 7.57 (dt, J = 8.0, 1.7
Hz, 2H), 7.49 (td, J = 6.8, 6.3, 1.7 Hz, 2H), 7.38 (tt, J = 6.8, 1.4 Hz, 2H), 7.19 (dtd, J = 19.3,
13
7.1, 1.2 Hz, 2H), 2.94 (q, J = 7.5 Hz, 2H), 1.37 (t, J = 7.5 Hz, 3H); C NMR (75 MHz,
CDCl3): δ 136.08, 133.82, 133.50, 129.14, 128.96, 127.99, 127.61, 122.34, 119.59, 119.33,
115.56, 110.93, 17.93, 15.77. HRMS m/z (ESI) calcd for [C16H16N]+: 222.1283, found:
222.1255.
2-Phenyl-3-propyl-1H-indole (4l)
Following the general procedure, the C-H activation/cyclization
reaction was carried out with 2-acetyl-1-phenylhydrazine (30 mg, 0.2
mmol), [Cp*RhCl2]2 (3.1 mg, 0.005 mmol), pent-1-yn-1-ylbenzene
(31.7 mg, 0.22 mmol), CsOAc (9.6 mg, 0.05 mmol), HOAc (14.4 μL,
0.24 mmol) and 1,2-dichloroethane (1 mL) at 100 ºC for 16 h. 2-
Phenyl-3-propyl-1H-indole (4l) was formed in 77% yield. Rf (pentane/ethyl acetate 12:1):
0.25; 1H NMR (400 MHz, CDCl3): δ 7.99 (s, 1H), 7.67 (d, J = 7.8 Hz, 1H), 7.60 – 7.55 (m,
S15

2H), 7.49 (td, J = 7.0, 1.7 Hz, 2H), 7.38 (dddd, J = 8.7, 4.0, 2.9, 1.3 Hz, 2H), 7.22 (ddd, J =
8.1, 7.1, 1.3 Hz, 1H), 7.16 (ddd, J = 8.0, 7.1, 1.1 Hz, 1H), 2.94 – 2.85 (m, 2H), 1.78 (dq, J =
15.0, 7.4 Hz, 2H), 1.02 (t, J = 7.4 Hz, 3H); 13C NMR (101 MHz, CDCl3): δ 136.01, 134.24,
133.62, 129.48, 128.93, 128.08, 127.59, 122.28, 119.56, 119.49, 114.11, 110.86, 26.85, 24.39,
14.58. HRMS: m/z (ESI) calcd for [C17H17N]: 235.1361, found: 235.1356.
4 Mechanistic Experiments
4.1 Isotope-labeled experiments
To a 10 mL Schlenk tube was added [Cp*RhCl2]2 (3.1 mg, 2.5 mol %), CsOAc (9.6 mg, 25.0
mol %), 15N-1a (30.2 mg, 0.20 mmol), 2a (40.0 mg, 0.22 mmol) and the tube was purged with
Ar for three times, followed by addition of AcOH (14.4 μL, 1.2 equiv), DCE (1.0 mL). The
formed mixture was stirred at 70 ºC under Ar for 16 h as monitored by TLC. The solution was
then cooled to rt, and the solvent was removed under vaccum directly. The crude product was
purified by column chromatography on silica gel (eluent: pentane/ethyl acetate = 10:1) to
afford 47.0 mg (87%) of 15N-3a. The ratio of 3a and 15N-3a was determined by 15N NMR and
HRMS. 1H NMR (300 MHz, CDCl3): δ 8.08 (d, 1H), 7.60 (d, J = 7.9 Hz, 1H), 7.40 – 7.11
(m, 12H), 7.11 – 7.01 (m, 1H). 13C NMR (75 MHz, CDCl3): δ 135.97, 135.77, 135.07,
134.14, 133.95, 132.71, 130.15, 128.65, 128.49, 128.16, 127.66, 126.21, 122.70, 122.67,
120.41, 119.69, 115.04, 110.87. 15N NMR: δ -253.70. HRMS: m/z (ESI) calcd for
C20H1515NNa (M + Na)+ 293.1073, found 293.1067.
Product
m/z
Res
-
S/N
-
I
-
FWHM
-
3a+Na
292.1097
293.1067
15N-3a+Na
7522
96.1
5341
0.0390
S16

4.2 Deuteration experiments
[Cp*RhCl2]2 (3.1 mg, 2.5 mol %), CsOAc (9.6 mg, 25.0 mol %), AcOH (14.4 μL, 1.2 equiv),
1a (30.0 mg, 0.20 mmol) or D5-1a (31.0 mg, 0.20 mmol), 2a (40.0 mg, 0.22 mmol) and DCE
(1.0 mL) were added in two separated Schlenk tubes. They were stirred at 70 ºC under Ar for
30 minutes, then immediately quenched with EtOAc at the same time. Then two reaction
mixtures were combined and the volatiles were removed under reduced pressure. The crude
product was purified by column chromatography on silica gel (eluent: pentane/ethyl acetate =
10:1) to afford 24.0 mg of 3a and D4-3a. The ratio of 3a and D4-3a was determined by
HRMS to be 2.9 : 1.
Product
3a+Na
m/z
Res
7897
7607
S/N
I
FWHM
0.0370
0.0389
292.1103
296.1331
433.8
149.5
23914
8410
D4-3a+Na
S17

[Cp*RhCl2]2 (3.1 mg, 2.5 mol %), CsOAc (9.6 mg, 25.0 mol %), AcOH (14.4 μL, 1.2 equiv),
D1-1a (30.2 mg, 0.20 mmol), 2a (40.0 mg, 0.22 mmol) and DCE (1.0 mL) were added in a
Schlenk tube. It was stirred at 70 ºC under Ar for 30 minutes, then immediately quenched
with EtOAc. Then the crude product was purified by column chromatography on silica gel
(eluent: pentane/ethyl acetate = 10:1) to afford 16.0 mg of 3a and D1-3a. The ratio of 3a and
D4-3a was determined by HRMS to be 2.3 : 1.
Product
3a+Na
m/z
Res
7868
7599
S/N
I
FWHM
0.0371
0.0386
292.1097
293.1159
701.2
303.1
28195
12248
D1-3a+Na
5 References
[1] a) L.-L. Jiang, Y. Tan, X.-L. Zhu, Z.-F. Wang, Y. Zuo, Q. Chen, Z. Xi, G.-F. Yang, J.
Agric. Food Chem. 2010, 58, 2643; b) D. W. Brooks, A. Basha, L. Forest, B. P. Gunn, I.
Lake, P. A. Bhatia, US 4970210.
[2] K. Park, G. Bae, J. Moon, J. Choe, K. H. Song, S. Lee, J. Org. Chem. 2010, 75, 6244.
[3] a) K. Sun, S. Liu, P. M. Bec, T. G. Driver, Angew. Chem. Int. Ed. 2011, 50, 1702; b) S.
Gore, S. Baskaran, B. König, Org. Lett. 2012, 14, 4568; c) Q. Nguyen, T. Nguyen, T. G.
Driver, J. Am. Chem. Soc. 2013, 135, 620.
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6 NMR spectra
S19

S20

S21

S22

S23

S24

S25

S26

S27

S28

S29