Gold(I)-catalysed cascade reactions in the synthesis of 2,3-fused indole derivatives

Article abstract of DOI:10.1039/c5cc04606h

A gold(I)-catalysed hydroaminative/arylative cascade for the efficient synthesis of a variety of indole-fused skeletons has been developed. Factors controlling the catalyst loading required in these transformations involving 1,3-unsubstituted indole intermediates have been revealed, allowing isolation of an unprecedented 1,3-dimetallated 3H-indole gold complex characterized by X-ray diffraction.

Full text of DOI:10.1039/c5cc04606h

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Rodriguez-Gimeno, A. B. Cuenca, C. Ramirez de Arellano, M. Medio-Simon and G. Asensio, Chem.
Commun., 2015, DOI: 10.1039/C5CC04606H.
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Gold(I)-Catalysed Cascade Reactions in the Synt
D
h
O
e
I: 1
s
0.1039/C5CC04606H
i
s
of 2,3-Fused Indole Derivatives
Authors: Ana Gimeno, Alejandra Rodríguez, Ana B. Cuenca, Carmen Ramírez de
Arellano, Mercedes Medio-Simón and Gregorio Asensio
Departamento de Química Orgánica, Universidad de Valencia,
Avda. Vicente Andrés Estellés, s/n
Burjassot, Valencia 46100.
Gregorio.asensio@uv.es
Supporting Information
Table of Contents
General Remarks
S1
Synthesis of Starting Materials
S2-S6
Representative general procedure for the gold(I)-catalyzed synthesis
of annulated indoles derivatives 3a-3q.
S7-S11
S11-S13
S14
Preparation of Intermediates and Indole-Gold Complexes 4, 5 and 6.
Table 3. Solvent and acid additive effect on the [Au(JohnPhos)(MeCN)]SbF6
catalysed cascade formation of cycloheptaindole 3j from 1j
NMR spectra for new compounds
References
S15-S53
S54
General Remarks
General Methods
Chemicals were purchased from commercial suppliers and used as delivered. All reactions were
carried out in oven-dried resealable test tubes or Schlenk tubes under an atmosphere of Argon.
Solvents were refluxed and freshly distilled from desiccants. N,N-dimethylformamide and
deuterated solvents were purchased from Aldrich and used without further purification. NMR
spectra were, if not mentioned otherwise, recorded at room temperature on the spectrometers
Bruker DPX-300, Bruker AVANCE-400 or Bruker DRX-500. Chemical shifts are given in ppm
1
13
and coupling constants in Hz. In the H and C spectra chemical shifts are reported relative to
deuterated solvents (CDCl : 7.26 / 77.16 ppm; CD Cl : 5.32 / 54.00 ppm; Acetone-d : 2.05 /
3
2
2
6
31
2
9.84 ppm; DMF-d : 2.75 / 29.76 ppm; THF-d : 1.73 / 25.37 ppm). P chemical shifts are given
7
8
in  ppm relative to H PO (5% solution) as an external standard. The following abbreviations
3
4
1
were used for H-NMR to indicate the signal multiplicity: s (singlet), d (doublet), t (triplet), q
quartet), quint (quintet), sext (sextet), m (multiplet), bs (broad singlet). High Resolution Mass
(
Spectra were determined on a TRIPLETOFT5600 (ABSciex, USA) spectrometer. Analytical thin
S1

ChemComm
Page 2 of 54
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DOI: 10.1039/C5CC04606H
layer chromatography was carried out using commercial aluminium sheets pre-coated (0.2mm
layer thickness) with silica gel 60 F254 (E. Merck), and visualization was effected with shorts
wavelength UV light (254nm). Reactions were monitored by GC. Product purification by flash
chromatography was performed using E. Merck Silica gel (230-400 mesh). Melting points were
measured in a Cambridge Instrument Apparatus.
Materials
2-haloanilines derivatives, alkynes and alkenes were commercially available and were used
without further purification. All the commercial reagents and Gold/Silver catalysts were
purchased from Aldrich or Strem Chemical Co. The following non-commercially available
1
starting materials were prepared according to literature procedures: 2-iodo-4-methoxyaniline
Synthesis of Starting Materials
Preparation of enynes
The following non-commercially enynes were prepared according to described literature
2
procedures: dimethyl 2-allyl-2-(prop-2-ynyl)malonate, Dimethyl 2-(2-methylallyl)-2-(prop-2-
3
4
5
ynyl)malonate, N-allyl-4-methyl-N-(prop-2-ynyl)benzenesulfonamide, hept-1-en-6-yne, 3-
6
7
(
prop-2-ynyloxy)prop-1-ene, dimethyl 2-(but-3-enyl)-2-(prop-2-ynyl)malonate, N-(but-3-enyl)-4-
8
9
methyl-N-(prop-2-ynyl)benzenesulfonamide,
4-(prop-2-ynyloxy)but-1-ene,
dimethyl
2-
10
11
cinnamyl-2-(prop-2-ynyl)malonate, hex-1-en-5-yn-3-yl acetate .
Preparation of 2-aniline-enynes 1, 4 and 7. General procedure A
CuI (10 mol%), Pd(PPh ) Cl (5 mol %) were suspended in iPr NH (0.5 M) under Argon. The
3
2
2
2
corresponding 2-haloaniline (1.3 eq) and enyne (1 eq) were successively added and the
reaction mixture was stirred at room temperature until all the enyne was consumed. Next, the
mixture was diluted with dichloromethane and filtered over Celite®. The solvent was removed
under reduced pressure and the 2-aniline-enyne was isolated by silica gel column
chromatography.
Dimethyl 2-allyl-2-(3-(2-aminophenyl)prop-2-ynyl)malonate (1a).
Compound 1a was prepared according to the general procedure A
1
(
eluents:Hexane: ethyl acetate = 20:1). Yield: 90%. Yellow dense oil. H
3
HH
4
NMR (300 MHz, CDCl ): 7.20 (ddd, 1H, J
= 7.6 Hz, J
= 1.5 Hz,
HH
3
5
HH
3
HH
4
HH
5
J
5
6
= 0.3 Hz), 7.07 (ddd, 1H, J
= 8.2 Hz, J
=7.3 Hz, J
=1.6 Hz), 6.69 – 6.58 (m, 2H),
HH
3
3
3
.67 (ddt, 1H, J
= 17.5 Hz, J
= 10.0 Hz, J
= 7.4 Hz), 5.24 – 5.12 (m, 2H), 3.75 (s,
HH
HHtrans
HHcis
3
HH
4
HH
13
13
H), 3.07 (s, 2H), 2.87 (dt, J
= 7.4 Hz, J
= 1.0 Hz, 2H). C NMR (75 MHz, CDCl ): 
C
3
NMR (75 MHz, CDCl ) δ 170.4, 148.1, 131.9, 131.5, 129.2, 119.9, 117.4, 114.1, 107.5, 89.1,
3
+
8
0.4, 57.2, 52.7, 36.7, 24.0. HRMS (TOF) calc. for C H NO [M+H] 302.1387, found
17
20
4
302.1390.
S2

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Dimethyl 2-allyl-2-(3-(2-amino-3-bromo-5-methylphenyl)prop-2-
ynyl)malonate (1b). Compound 1b was prepared according to the
general procedure A (eluents:Hexane: ethyl acetate = 50:1). Yield:
1
7
0%. White solid, m.p.: 79-81 ºC. H NMR (300 MHz, CDCl ) 7.18
3
4
HH
4
HH
3
3
(
d, 1H, J
= 1.3 Hz), 6.98 (d, 1H, J
1.3 Hz), 5.65 (ddt, 1H, J
= 17.4 Hz, J = 10.0
HHcis
HHtrans
3
HH
3
Hz, J
=7.4 Hz), 5.24-5.12 (m, 2H), 4.54 (bs, 2H), 3.76 (s, 6H), 3.05 (s, 2H), 2.86 (dt, 2H, J HH
4
13
=
1
7.5 Hz, J
= 0.9 Hz), 2.17 (s, 3H). C NMR (75 MHz, CDCl ) 170.5, 143.5, 133.1, 131.5,
HH
3
31.5, 127.4, 120.1, 108.5, 108.3, 89.7, 80.1, 57.2, 52.9, 36.8, 24.0, 19.9. HRMS (TOF) calc. for
+
C H BrNO [M+H] 394.0648, found 394.0633.
18
20
4
Dimethyl
2-allyl-2-(3-(2-amino-5-chlorophenyl)prop-2-
ynyl)malonate (1c). Compound 1c was prepared according to the
general procedure A (eluents: Hexane: ethyl acetate = 20:1). Yield:
1
4
9
5%. Yellow dense oil. H NMR (300 MHz, CDCl ) 7.15 (d, 1H, J
= 2.5 Hz), 7.01 (dd, 1H,
HH
3
3
HH
4
HH
3
HH
3
3
J
= 8.6 Hz, J
=2.5 Hz), 6.57 (d, 1H, J
= 8.6 Hz), 5.64 (ddt, 1H, J
= 17.4 Hz, J
HHtrans HHcis
3
=
2
1
3
10.0 Hz, J
= 7.4 Hz), 5.25 – 5.10 (m, 2H), 4.14 (bs, 2H), 3.75 (s, 6H), 3.04 (s, 2H), 2.84 (d,
HH
3
HH
13
H, J
= 7.4 Hz). C NMR (75 MHz, CDCl )  170.4, 146.8, 131.4, 131.1, 129.3, 121.6, 120.1,
3
+
15.2, 108.8, 90.3, 79.3, 57.1, 52.8, 36.8, 23.9. HRMS (TOF) calc. for C H ClNO [M+H]
17
19
4
36.0997, found 336.0993.
Dimethyl
2-allyl-2-(3-(2-amino-5-isopropylphenyl)prop-2-
ynyl)malonate (1d). Compound 1d was prepared according to the
general procedure A (eluents:Hexane: ethyl acetate = 20:1). Yield:
1
4
3
9
=
1
3%. Pale yellow oil. H NMR (300 MHz, CDCl )  7.07 (d, 1H, J
= 2.1 Hz), 6.96 (dd, 1H, J
3
HH
HH
4
HH
3
HH
3
3
8.4 Hz, J
= 2.1 Hz), 6.61 (d, 1H, J
= 8.1 Hz), 5.67 (ddt, 1H, J
= 17.7 Hz, J
=
HHtrans
HHcis
3
HH
0,2 Hz, J
= 7.5 Hz), 5.24-5.13 (m, 2H), 4.10 (bs, 2H), 3.76 (s, 6H), 3.07 (s, 2H), 2.88 (dt, 2H,
3
HH
4
HH
3
HH
3
13
J
= 7.2 Hz, J
= 1.2 Hz), 2.75 (sept, 1H, J
= 6.9 Hz), 1.18 (d, 6H, J = 6.9 Hz).
HH
C
NMR (75 MHz, CDCl ) 170.5, 146.1, 138.1, 131.6, 129.5, 127.6, 120.0, 114.3, 107.5, 88.7,
3
+
8
0.8, 57.3, 52.8, 36.8, 33.0, 24.0, 24.0. HRMS (TOF) calc. for C H NO [M+H] 344.1856,
20
26
4
found 344.1855.
Dimethyl
2-allyl-2-(3-(2-amino-5-methoxyphenyl)prop-2-
ynyl)malonate (1e). Compound 1e was prepared according to the
general procedure A (eluents:Hexane: ethyl acetate = 10:1). Yield:
1
4
9
2%. Orange dense oil. H NMR (300 MHz, CDCl ) 6.77 (d, 1H, J
= 2.8 Hz), 6.72 (dd, 1H,
HH
3
3
4
3
3
J
J
= 8.7 Hz, J
= 2.9 Hz), 6.61 (d, 1H, J
= 8.7 Hz), 5.66 (ddt, 1H, J
= 17.4 Hz,
HHtrans
HH
HH
HH
3
3
= 10.0 Hz, J
= 7.2 Hz, J
= 7.5 Hz), 5.18 (m, 2H), 3.76 (s, 6H), 3.71 (s, 3H), 3.06 (s, 2H), 2.87(dt,
HH
HHcis
3
HH
4
13
2H, J
= 0.9 Hz). C NMR (75 MHz, CDCl )  170.5, 151.7, 142.3, 131.6, 120.0,
HH
3
S3

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1
16.8, 116.1, 115.7, 108.4, 89.3, 80.5, 57.2, 55.8, 52.8, 36.8, 24.0. HRMS (TOF) calc. for
+
C H NO [M+H] 332.1492, found 332.1503.
18
21
5
N-allyl-N-(3-(2-aminophenyl)prop-2-ynyl)-4-methylbenzenesulfonamide
(
1f). Compound 1f was prepared according to the general procedure A
1
(
eluents:Hexane: ethyl acetate = 5:1). Yield: 83%. Yellow dense oil. H NMR
3
HH
3
HH
3
(
300 MHz, )  7.77 (d, 2H, J
= 8.4 Hz), 7.27 (d, 2H, J
= 8.0 Hz), 7.08 (ddd, 1H, J
= 8.2
HH
3
HH
4
HH
3
HH
4
HH
Hz, J
= 7.3 Hz, J
=1.6 Hz), 6.90 (dd, 1H, J
= 7.7 Hz, J
=1.5 Hz), 6.66 – 6.56 (m, 2H),
3
3
3
HH
3
5.79 (ddt, 1H, J
= 16.4 Hz, J
=10.0 Hz, J
= 6.4 Hz), 5.32 (dq, 1H, J
= 17.1 Hz,
HH
HHtrans
HHcis
2
HH
4
HH
3
HH
2
HH
4
J
2
1
= J
= 1.5 Hz), 5.26 (dq, 1H, J
= 10.0 Hz, J
= J
= 1.2 Hz), 4.34 (s, 2H), 3.90 (d,
HH
3
13
H, J
= 6.4 Hz), 2.35 (s, 3H). C NMR (75 MHz, )  147.9, 143.6, 135.9, 132.2, 132.1, 129.8,
HH
29.6, 127.7, 119.8, 117.5, 114.2, 106.8, 87.0, 82.4, 49.3, 36.9, 21.4. HRMS (TOF) calc. for
+
C19H21N O S [M+H] 341.1318, found 341.1315.
2
2
2-(hept-6-en-1-ynyl)aniline (1g). Compound 1g was prepared according to
the general procedure A (eluents:Hexane: ethyl acetate = 200:1). Yield: 96%.
1
3
HH
4
Pale yellow oil. H NMR (300 MHz, CDCl )  7.13 (dd, 1H, J
= 8.1 Hz, J
HH
3
3
4
HH
3
=
1.5 Hz), 6.99 (td, 1H, J
= 7.7 Hz, J
= 1.5 Hz), 6.59 (d, 1H, J = 7.8 Hz), 6.57 (td, 1H,
HH
HH
3
HH
4
HH
3
3
3
J
5
2
1
1
= 6.3 Hz, J
= 1.2 Hz) 5.75 (ddt, 1H, J
= 16.9 Hz, J
= 10.2 Hz, J
= 6.7 Hz),
HH
HHtrans
HHcis
3
.04 - 4.89 (m, 2H), 4.06 (bs, 2H), 2.40 (t, 2H, J
= 7.1 Hz), 2.18 - 2.10 (m, 2H), 1.64 (quint,
HH
3
HH
13
H, J
= 7.2 Hz). C NMR (75 MHz, CDCl )  147.7, 137.9, 132.1, 129.0, 117.9, 115.4, 114.2,
3
+
09.0, 95.4, 77.4, 33.0, 28.2, 19.1. HRMS (TOF) calc. for C H NO [M+H] 186.1277, found
13
16
86.1277.
2-(3-(allyloxy)prop-1-ynyl)aniline (1h). Compound 1h was prepared
according to the general procedure A (eluents:Hexane: ethyl acetate = 20:1).
1
3
Yield: 70%. Yellow oil. H NMR (300 MHz, CDCl )  7.29 (dd, 1H, J
= 8.1
HH
3
4
HH
3
HH
3
HH
4
Hz, J
= 1.5 Hz), 7.12 (ddd, 1H, J
= 9.3 Hz, J
= 6.9 Hz, J = 1.6 Hz), 6.72 – 6.64 (m,
HH
3
3
3
HH
3
2H), 5.96 (ddt, 1H, J
= 17.3 Hz, J
=10.4 Hz, J
=5.8 Hz), 5.35 (dq, 1H, J
= 17.3
HH
HHtrans
HHcis
2
HH
4
HH
3
HH
2
HH
4
Hz, J
= J
= 1.6 Hz), 5.25 (ddt, 1H, J
=10.4 Hz, J
= 1.7 Hz, J
=1.2 Hz), 4.44 (s,
HH
3
HH
4
HH
13
2H), 4.22 (bs, 2H), 4.15(dt, 2H, J
= 6 Hz, J
= 1.5 Hz). C NMR (75 MHz, CDCl )  148.0,
3
134.0, 132.4, 129.8, 117.8, 117.7, 114.2, 107.2, 90.3, 82.9, 70.6, 58.0. HRMS (TOF) calc. for
+
C H NO [M+H] 188.1070, found 188.1068.
12
14
Dimethyl
2-(3-(2-aminophenyl)prop-2-ynyl)-2-(2-
methylallyl)malonate (1i). Compound 1i was prepared according to
the general procedure A (eluents:Hexane: ethyl acetate = 20:1). Yield:
1
3
HH
7
8%. Orange dense oil. H NMR (400 MHz, CDCl )  7.20 (dd, 1H, J
3
4
HH
3
HH
3
HH
4
HH
3
=
7.6 Hz, J
=1.5 Hz), 7.08 (ddd, 1H, J
= 8.2, J
=7.4, J
=1.6 Hz), 6.65 (dd, 1H, J
HH
=
4
HH
3
HH
4
8.1 Hz, J
=0.6 Hz), 6.63 (td, 1H, J
= 7.5, J
=1.1 Hz), 4.95-4.92 (m, 1H), 4.88 (m, 1H),
HH
13
4
.25 (bs, 2H), 3.76 (s, 6H), 3.11 (s, 2H), 2.91 (s, 2H), 1.69 (s, 3H). C NMR (101 MHz, CDCl ) 
3
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1
71.0, 148.3, 139.8, 132.1, 129.4, 117.6, 116.5, 114.2, 107.8, 89.6, 80.8, 56.9, 52.9, 39.9, 24.2,
+
23.3. HRMS (TOF) calc. for C H NO [M+H] 316.1543, found 316.1549.
18
22
4
Dimethyl 2-(3-(2-aminophenyl)prop-2-ynyl)-2-(but-3-enyl)malonate
(
1j). Compound 1j was prepared according to the general procedure A
1
(
eluents:Hexane: ethyl acetate = 10:1). Yield: 87%. Yellow dense oil. H
3
HH
4
NMR (300 MHz, CDCl )  7.20 (ddd, 1H, J
= 7.5 Hz, J
= 1.5 Hz,
HH
3
4
HH
3
HH
3
HH
4
J
= 0.3 Hz), 7.08 (ddd, 1H, J
= 8.2 Hz, J
= 7.3 Hz, J = 1.6 Hz), 6.68-6.59 (m, 2H),
HH
3
3
3
HH
3
5.79 (ddt, 1H, J
= 16.6 Hz, J
= 10.2 Hz, J
= 6.4 Hz), 5.06 (dq, 1H, J
= 17.1 Hz,
HH
HHtrans
HHcis
2
HH
4
HH
3
HH
2
HH
4
J
6
1
= J
= 1.6 Hz), 4.98 (dq, 1H, J
= 10.2 Hz, J
= J
= 1.2 Hz), 4.23 (bs, 2H), 3.76 (s,
HH
1
3
H), 3.11 (s, 2H), 2.28-2.18 (m, 2H), 2.08-1.97 (m, 2H). C NMR (75 MHz, CDCl )  170.9,
3
48.1, 137.1, 132.0, 129.3, 117.5, 115.3, 114.1, 107.6, 89.1, 80.3, 57.0, 52.8, 31.5, 28.3, 24.3.
+
HRMS (TOF) calc. for C H NO [M+H] 316.1543, found 316.1536.
18
22
4
Dimethyl 2-(3-(2-amino-3-bromo-5-methylphenyl)prop-2-ynyl)-2-
but-3-enyl)malonate (1k). Compound 1k was prepared according to
(
the general procedure A (eluents: Hexane: ethyl acetate = 30:1).
1
Yield: 70%. Colorless oil. H NMR (400 MHz, CDCl )  7.17 (d, 1H,
3
4
3
4
3
3
J
J
= 1.4 Hz), 6.97 (d, 1H, J
= 1.3 Hz), 5.78 (ddt, 1H, J
= 16.7 Hz, J = 10.2 Hz,
HHcis
HH
HH
HH
HHtrans
3
2
HH
4
HH
3
HH
= 6.5 Hz), 5.05 (dq, 1H, J
= 17.1 Hz, J
= J
= 1.6 Hz), 4.98 (ddd, 1H, J
= 10.2
HH
2
HH
4
Hz, J
= 2.9 Hz, J
= 1.2 Hz), 4.53 (s, 2H), 3.76 (s, 6H), 3.10 (s, 2H), 2.25-2.18 (m, 2H),
HH
13
2
.16 (s, 3H), 2.06-1.97 (m, 2H). C NMR (101 MHz, CDCl ) δ 171.0, 143.6, 137.2, 133.3, 131.6,
3
127.5, 115.6, 108.6, 108.5, 89.8, 80.2, 57.1, 53.0, 31.7, 28.5, 24.4, 20.0. HRMS (TOF) calc. for
+
C H BrNO [M+H] 408.0805, found 408.0802.
19
23
4
Dimethyl 2-(3-(2-amino-5-chlorophenyl)prop-2-ynyl)-2-(but-3-
enyl)malonate (1l). Compound 1l was prepared according to the
general procedure A (eluents: Hexane: ethyl acetate = 20:1). Yield:
1
9
0%. Yellow dense oil. H NMR (300 MHz, CDCl )  7.13 (d, 1H,
3
4
HH
3
HH
4
HH
3
HH
J
= 2.5 Hz), 6.99 (dd, 1H J
= 8.6 Hz, J
= 2.5 Hz), 6.55 (d, 1H, J
= 8.6 Hz), 5.77 (ddt,
3
3
3
HH
3
HH
2
1H, J
= 16.6 Hz, J
= 10.2 Hz, J
= 6.4 Hz,), 5.04 (dq, 1H, J
= 17.1 Hz, J
=
HH
HHtrans
HHcis
4
HH
3
HH
2
HH
4
J
= 1.6 Hz), 4.97 (ddd, 1H, J
= 10.2 Hz, J
= 2.9 Hz, J
= 1.3 Hz), 4.26 (bs, 2H), 3.74
HH
13
(
s, 6H), 3.08 (s, 2H), 2.25-2.15 (m, 2H), 2.06-1.95 (m, 2H). C NMR (75 MHz, CDCl )  170.9,
3
147.0, 137.1, 131.2, 129.4, 121.7, 115.5, 115.3, 108.9, 90.4, 79.3, 57.0, 52.9, 31.6, 28.4, 24.3.
+
HRMS (TOF) calc. for C H ClNO [M+H] 350.1154, found 350.1159.
18
21
4
Dimethyl 2-(3-(2-amino-5-methoxyphenyl)prop-2-ynyl)-2-(but-
3-enyl)malonate (1m). Compound 1m was prepared according to
the general procedure A (eluents: Hexane: ethyl acetate = 10:1).
1
Yield: 90%. orange oil. H NMR (300 MHz, CDCl )  6.76 (d, 1H,
3
4
HH
3
HH
4
HH
3
J
= 2.8 Hz), 6.71 (dd, 1H, J
= 8.7 Hz, J
= 2.9 Hz), 6.60 (d, 1H, J
= 8.7 Hz), 5.79 (ddt,
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3
3
3
3
2
4
View Article Online
1
=
6
H, J
= 16.6 Hz, J
= 10.2 Hz, J
= 6.4 Hz), 5.05 (dq, 1H, J
= 17.1 Hz, J
= J
HH
HHtrans
HHcis
HH
HH
HH
DOI: 10.1039/C5CC04606H
3
2
4
1.6 Hz,), 4.98 (ddd, 1H, J
= 10.2 Hz, J
= 2.9 Hz, J
= 1.3 Hz), 3.94 (bs, 2H), 3.75 (s,
HH
HH
HH
13
H), 3.71 (s, 3H), 3.10 (s, 2H), 2.27 - 2.17 (m, 2H), 2.08 - 1.96 (m, 2H). C NMR (75 MHz,
CDCl )  171.0, 151.8, 142.5, 137.3, 117.0, 116.2, 115.8, 115.5, 108.5, 89.3, 80.5, 57.2, 56.0,
3
+
5
2.9, 31.6, 28.5, 24.4. HRMS (TOF) calc. for C H NO [M+H] 346.1649, found 346.1664.
19
24
5
Dimethyl 2-(3-(2-amino-4-(trifluoromethyl)phenyl)prop-2-ynyl)-
-(but-3-enyl)malonate (1n). Compound 1n was prepared
2
according to the general procedure A (eluents: Hexane: ethyl
1
acetate = 20:1). Yield: 80%. Yellow oil. H NMR (300 MHz, CDCl )
3
3
HH
3
HH
3

7.26 (d, 1H, J
= 7.9 Hz), 6.86 (s, 1H), 6.83 (d, J
= 8.8Hz, 1H), 5.78 (ddt, 1H, J
=
HHtrans
3
3
3
HH
2
HH
4
15.0 Hz, J
= 9.0 Hz, J
= 6.0 Hz), 5.05 (dq, 1H, J
=17.1Hz, J
= J
= 1.6 Hz), 4.98
HH
HHcis
HH
3
HH
2
HH
4
HH
(
ddd, 1H, J
= 10.2 Hz, J
= 2.9 Hz, J
= 1.2 Hz, 4.48 (bs, 2H), 3.75 (s, 6H), 3.11 (s, 2H),
1
3
2
1
1
6
.27 - 2.18 (m, 2H), 2.08 - 1.96 (m, 2H). C NMR (75 MHz, CDCl )  171.0, 148.5, 137.1,
3
2
CF
1
CF
3
32.5, 131.1 (q, J
= 32.0 Hz), 124.1 (q, J
= 272.3 Hz), 115.6, 113.8 (q, J
= 3.8 Hz),
CF
3
CF
19
10.5 (q, J
= 3.9 Hz), 91.5, 79.4, 57.1, 52.9, 31.7, 28.4, 24.4. F NMR (471 MHz, CDCl )  -
3
+
3.15. HRMS (TOF) calc. for C H NO F [M+H] 384.1417, found 384.1401.
19
21
4 3
N-(3-(2-aminophenyl)prop-2-ynyl)-N-(but-3-enyl)-4-
methylbenzenesulfonamide (1o). Compound 1o was prepared
according to the general procedure A (eluents: Hexane: ethyl acetate =
1
1
0:1). Yield: 85%. Yellow dense oil. H NMR (400 MHz, CDCl )  7.76
3
3
HH
3
HH
3
HH
3
(
d, 2H, J
= 8.3 Hz), 7.6 (d, 2H, J
= 8.3 Hz), 7.08 (ddd, 1H, J
= 8.2 Hz, J
=7.4 Hz,
HH
4
HH
3
HH
4
HH
3
HH
J
=1.6 Hz), 6.91 (dd, 1H, J
= 7.7 Hz, J
=1.3 Hz), 6.62 (d, 1H, J
= 8.2 Hz), 6.60 (td,
3
HH
4
HH
3
3
3
1H, J
= 7.5 Hz, J
=1.1 Hz), 5.79 (ddt, 1H, J
= 17.0 Hz, J
= 10.2 Hz, J
= 6.8
HH
HHtrans
HHcis
3
HH
2
HH
4
HH
3
HH
2
Hz), 5.13 (dq, J
= 17.1 Hz, J
= J
= 1.6 Hz), 5.07 (ddd, J
= 10.2 Hz, J
= 2.9 Hz,
HH
4
HH
3
J
3
1
= 1.2 Hz, 4.39 (s, 2H), 3.93 (bs, 2H), 3.34 (t, 2H, J
= 7.2 Hz), 2.43 -2.36 (m, 2H), 2.35 (s,
HH
1
3
H). C NMR (100 MHz, CDCl )  148.0, 143.7, 136.1, 134.7, 132.4, 130.0, 129.7, 127.8,
3
17.8, 117.4, 114.4, 106.9, 87.2, 82.6, 46.0, 37.5, 32.5, 21.6. HRMS (TOF) calc. for
+
C H N O S [M+H] 355.1475, found 355.1489.
20
23
2
2
6-(2-aminophenyl)hex-1-en-5-yn-3-yl acetate (1p). Compound 1p was
prepared according to the general procedure A (eluents: Hexane: ethyl
1
acetate = 30:1). Yield: 54%. Yellow oil. H NMR (300 MHz, CDCl )  7.23
3
3
HH
4
3
HH
3
HH
4
(
dd, 1H, J
= 7.5 Hz, J
= 1.5 Hz), 7.09 (ddd, 1H, J
= 8.2 Hz, J
= 7.4 Hz, J
= 1.6
HH
HH
3
3
3
Hz), 6.68 – 6.62 (m, 2H), 5.95 (ddd, 1H, J HHtrans = 17.2 Hz, J
= 10.5 Hz, J
= 6.2 Hz),
HH
HHcis
3
HH
4
HH
3
HH
4
HH
5.49 (qt, 1H, J
= 6.2 Hz, J
=1.2 Hz), 5.39 (dt, 1H, J
= 17.2 Hz, J
= 1.3 Hz), 5.29 (dt,
3
HH
4
HH
3
HH
13
1H, J
= 10.5 Hz, J
= 1.2 Hz), 4.20 (bs, 2H), 2.82 (d, 2H, J
= 6.2 Hz), 2.11 (s, 3H).
C
NMR (75 MHz, CDCl )  170.3, 148.1, 135.2, 132.1, 129.4, 118.0, 117.8, 114.3, 108.1, 90.1,
3
+
7
9.5, 72.6, 25.8, 21.3. HRMS (TOF) calc. for C H NO [M+H] 230.1176, found 230.1173.
14
16
2
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DOI: 10.1039/C5CC04606H
Representative general procedure for the gold(I)-catalyzed synthesis of
annulated indoles derivatives 3a-3p.
An oven dried resealable test tube with a Teflon stirring bar was charged with the 1,X-enynes 1
(
0.3 mmol) in dried DMF (0.125M). Subsequently, [Au(JohnPhos)(NCMe)]SbF (5 mol%) were
6
added. The tube was sealed with a Teflon screw-cap and placed in an oil bath at 60 ºC (80 ºC).
As indicated extra 5 mol% [Au(JohnPhos)(NCMe)]SbF was added after 8 h of reaction. The
6
reaction was heated at this temperature until consumption of the starting material. Next, the
mixture was cooled to room temperature, diluted with dichloromethane (2-3 mL), and filtered
over Aluminium oxide activated. The solvent was removed under reduced pressure and the
annulated indoles were isolated by silica gel column chromatography.
Dimethyl 4-methyl-3,4-dihydro-1H-carbazole-2,2(9H)-dicarboxylate
(
3a). (eluents: Hexane: ethyl acetate = 10:1). Yield: 91%. Yellow dense
1
3
oil. H NMR (300 MHz, CDCl )  7.79 (bs, 1H), 7.50 (dm, 1H, J
= 7.5
HH
3
Hz), 7.22 - 7.16 (m, 1H), 7.08 - 6.94 (m, 2H), 3.71 (s, 3H), 3.58 (s, 3H),
2
4
2
3
.35 (dt, 1H, J
= 16.2 Hz, J
= 1.5 Hz), 3.11 - 3.05 (m, 2H), 2.64 (ddd, 1H, J
= 13.3 Hz,
= 6.7 Hz,
HH
HH
HH
3
4
2
HH
3
HH
3
HH
J
= 5.4 Hz, J
= 1.7 Hz), 1.80 (dd, 1H, J
= 13.4, J
= 10.1 Hz), 1.37 (d, J
HH
HH
13
3
H). C NMR (75 MHz, CDCl )  172.3, 171.0, 136.5, 130.7, 127.0, 121.3, 119.6, 119.3, 113.5,
3
+
1
10.9, 54.7, 53.1, 52.9, 38.7, 29.5, 26.1, 21.3. HRMS (EI) calc. for C H NO [M] 301.1314,
17
19
4
found 301.1302.
Dimethyl 8-bromo-4,6-dimethyl-3,4-dihydro-1H-carbazole-2,2(9H)-
dicarboxylate (3b). (eluents: Hexane: ethyl acetate = 10:1). Yield:
1
7
5%. Pale yellow solid, m.p.: 195-197 ºC. H NMR (300 MHz, CDCl ) 
3
7.97 (bs, 1H), 7.28 (s, 1H), 7.10 (s, 1H), 3.80 (s, 3H), 3.67 (s, 3H), 3.47
2
HH
4
2
HH
4
(
dt, 1H, J
= 16.5 Hz, J
= 1.6 Hz,), 3.18 (dd, 1H, J
= 14.2 Hz, J
= 3.9 Hz), 3.18 – 3.05
HH
HH
2
3
HH
4
(m, 1H), 2.71 (ddd, 1H, J
= 13.4 Hz, J
= 5.6 Hz, J
= 1.9 Hz), 2.41 (s, 3H), 1.86 (dd, 1H,
HH
HH
2
HH
3
HH
3
HH
13
J
= 13.5 Hz, J
= 10.2 Hz), 1.42 (d, 3H, J
= 6.7 Hz). C NMR (75 MHz, CDCl )  172.1,
3
170.9, 133.3, 131.6, 130.1, 128.2, 124.9, 118.6, 114.2, 104.0, 54.6, 53.2, 53.0, 38.5, 29.5, 26.2,
+
2
1.4, 21.2. HRMS (TOF) calc. for C H NO Br [M+H] 394.0648, found 394.0641.
18
21
4
Dimethyl
6-chloro-4-methyl-3,4-dihydro-1H-carbazole-2,2(9H)-
dicarboxylate (3c). (eluents: Hexane: ethyl acetate = 10:1). Yield:
1
8
1%. Pale yellow solid, m.p.: 192-194 ºC. H NMR (300 MHz, CDCl )
3
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4
3
4
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DOI: 10.1039/C5CC04606H

7.97 (s, 1H), 7.55 (d, 1H, J
= 2.0 Hz), 7.21 (dd, 1H, J
= 8.6 Hz, J = 0.5 Hz), 7.09 (dd,
HH
HH
HH
3
HH
4
HH
2
HH
4
1
1
1
3
1
H, J
= 8.6 Hz, J
= 2.0 Hz), 3.82 (s, 3H), 3.71 (s, 3H), 3.45 (dt, 1H, J
= 14.8 Hz, J
=
=
HH
2
HH
4
2
.7 Hz), 3.18 (dd, 1H, J
= 16.2 Hz, J
= 2.0 Hz), 3.19-3.08 (m, 1H), 2.74 (ddd, 1H, J
HH
HH
3
HH
3
2
3
3.5 Hz, J
= 5.5 Hz, J
= 1.8 Hz), 1.91 (dd, 1H, J
= 13.5 Hz, J
= 10.2 Hz), 1.45 (d,
HH
HH
HH
3
HH
13
H, J
= 6.7 Hz C NMR (75 MHz, CDCl )  172.1, 170.9, 134.8, 132.3, 128.0, 125.0, 121.5,
3
19.1, 113.4, 111.8, 54.6, 53.1, 53.0, 38.5, 29.5, 26.0, 21.1. HRMS (TOF) calc. for C H NO Cl
17
19
4
+
[
M+H] 336.0997, found 336.0963.
Dimethyl
6-isopropyl-4-methyl-3,4-dihydro-1H-carbazole-
2,2(9H)-dicarboxylate (3d). (eluents: Hexane: ethyl acetate = 5:1).
1
Yield: 78%. Pale yellow solid, m.p.: 64-66 ºC. H NMR (300 MHz,
4
HH
3
CDCl )  7.79 (bs, 1H), 7.41 (d, 1H, J
= 0.9 Hz), 7.21 (d, 1H, J
HH
3
3
4
=
8.3 Hz), 7.03 (dd, 1H, J
= 8.4 Hz, J
= 1.6 Hz), 3.79 (s, 3H), 3.67 (s, 3H), 3.42 (dt, 1H,
HH
HH
2
4
3
J
J
= 14.7 Hz, J
= 1.7 Hz), 3.24-3.11 (m, 2H), 3.00 (hept, 1H, J
= 7.0 Hz), 2.72 (ddd, 1H,
HH
HH
HH
2
HH
3
HH
4
HH
2
HH
3
= 13.4 Hz, J
= 5.4 Hz, J
= 1.7 Hz), 1.88 (dd, 1H, J
= 13.4 Hz, J
= 10.1 Hz), 1.47
HH
3
HH
3
HH
13
(
d, 3H, J
= 6.7 Hz), 1.31 (d, 6H, J
= 6.9 Hz). C NMR (75 MHz, CDCl )  172.4, 171.0,
3
140.0, 135.0, 130.8, 127.0, 120.3, 116.7, 113.3, 110.7, 54.7, 53.1, 52 9, 38.7, 34.4, 29.5, 26.1,
+
2
4.9, 24.8, 21.3.HRMS (TOF) calc. for C H NO [M+H] 344.1856 found 344.1844.
20
26
4
Dimethyl
6-methoxy-4-methyl-3,4-dihydro-1H-carbazole-
2,2(9H)-dicarboxylate (3e). (eluents: Hexane: ethyl acetate = 5:1).
1
Yield: 90%. Pale yellow solid, m.p.: 105-107 ºC. H NMR (300 MHz,
3
HH
4
HH
4
CDCl )  7.77 (bs, 1H), 7.16 (dd, 1H, J
= 8.7 Hz, J
= 0.5 Hz), 7.03 (d, 1H, J
= 2.4 Hz),
HH
3
3
HH
4
6.77 (dd, 1H, J
= 8.7 Hz, J
= 2.4 Hz), 3.84 (s, 3H), 3.78 (s, 4H), 3.66 (s, 3H), 3.40 (dt, 1H,
HH
2
4
2
3
J
J
= 14.7 Hz, J
=1.7 Hz), 3.19-3.09 (m, 2H), 2.70 (ddd, 1H, J
= 13.3 Hz, J = 5.4 Hz,
HH
HH
HH
HH
HH
4
2
HH
3
HH
3
HH
13
= 1.6 Hz,), 1.87 (dd, 1H, J
= 13.4 Hz, J
= 10.0 Hz), 1.43 (d, 3H, J
= 6.7 Hz).
C
NMR (75 MHz, CDCl )  172.3, 171.0, 153.8, 131.7, 127.4, 113.3, 111.4, 110.7, 102.5, 56.2,
3
+
5
4.7, 53.1, 52.9, 38.6, 29.6, 26.1, 21.1. HRMS (TOF) calc. for C H NO [M+H] 332.1492
18
22
5
found 332.1498.
4-methyl-2-tosyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole (3f). (eluents:
Hexane: ethyl acetate = 5:1). Yield: 90%. Pale yellow solid, m.p.: 80-83 ºC.
1
H NMR (300 MHz, CDCl )  7.87 (bs, 1H), 7.77 - 7.70 (m, 2H), 7.52 (d, 1H,
3
3
HH
2
J
= 7.7 Hz), 7.30 (m, 3H), 7.18 - 7.04 (m, 2H), 4.40 (d, 1H, J
= 14.4
HH
2
HH
3
Hz), 4.18 (d, 1H, J
= 14.4 Hz), 3.38 - 3.14 (m, 3H), 2.42 (s, 3H), 1.38 (d, 3H, J
= 6.6 Hz).
HH
13
C NMR (75 MHz, CDCl )  143.9, 136.5, 133.8, 129.9, 128.2, 127.8, 126.3, 122.0, 119.8,
3
+
1
18.8, 113.6, 111.2, 51.3, 43.8, 28.1, 21.7, 18.9. HRMS (TOF) calc. for C H N O S [M+H]
19
21
2
2
341.1318 found 341.1308.
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DOI: 10.1039/C5CC04606H
4
=
1
-methyl-2,3,4,9-tetrahydro-1H-carbazole (3g). (eluents: Hexane: ethyl acetate
1
20:1). Yield: 91%. Colorless dense oil. H NMR (500 MHz, CDCl )  7.65 (bs,
3
3
HH
3
3
H), 7.57 (d, 1H, J
= 7.6 Hz), 7.28 (d, 1H, J
= 7.7 Hz,), 7.08 (ddt, 2H, J
HH HH
3
HH
4
=
8.0 Hz, J
= 7.2 Hz, J
=4.1 Hz), 3.14-3.10 (m, 1H), 2.73-2.67 (m, 2H), 2.03-1.94 (m, 2H),
HH
3
13
1
.87-1.77 (m, 1H), 1.62-1.58 (m, 1H), 1.38 (d, 3H, J HH = 6.9 Hz). C NMR (126 MHz, CDCl3)
134.0, 133.9, 127.6, 120.9, 119.1, 118.8, 115.2, 110.6, 32.3, 27.3, 23.6, 21.4, 20.6. HRMS
+
(
TOF) calc. for C H N [M+H] 186.1277 found 186.1274.
13
15
4-methyl-1,3,4,9-tetrahydropyrano[3,4-b]indole (3h). (eluents: Hexane: ethyl
1
acetate = 20:1). Yield: 48%. Yellow dense oil. H NMR (300 MHz, CDCl )  7.71
3
(
bs, 1H), 7.62 - 7.56 (m, 1H), 7.36 - 7.30 (m, 1H), 7.21 - 7.07 (m, 3H), 4.80 (t,
3
HH
2
HH
3
HH
2H, J
= 1.4 Hz), 4.02 (dd, 1H, J
= 11.1 Hz, J
= 4.5 Hz), 3.67 (dd, 1H,
2
HH
3
3
HH
13
J
= 11.1 Hz, J
= 5.3 Hz), 3.24- 3.08 (m, 1H), 1.38 (d, 3H, J
HH
= 6.9 Hz). C NMR (75
MHz, CDCl )  136.2, 131.3, 126.8, 121.7, 119.7, 118.9, 113.1, 111.1, 72.6, 63.9, 28.4, 18.0.
3
+
HRMS (TOF) calc. for C H NO [M+H] 188.1070 found 188.1063.
12
14
Dimethyl
4,4-dimethyl-3,4-dihydro-1H-carbazole-2,2(9H)-
dicarboxylate (3i). (eluents: Hexane: ethyl acetate = 20:1). Yield: 80%.
1
White solid, m.p.: 133-135 ºC. H NMR (500 MHz, CDCl )  7.96 (s, 1H),
3
3
HH
3
HH
3
7.65 (d, 1H, J
= 7.7 Hz), 7.29 (d, 1H, J
= 7.6 Hz), 7.14 (t, 1H, J
= 7.1 Hz), 7.09 (t, 1H,
HH
3
HH
13
J

2
= 7.4 Hz), 3.77 (s, 6H), 3.23 (s, 2H), 2.45 (s, 2H), 1.44 (s, 6H). C NMR (126 MHz, CDCl3)
172.0, 136.6, 129.6, 126.0, 121.1, 119.9, 119.1, 116.7, 111.1, 53.3, 52.8, 44.4, 31.7, 30.1,
+
9.2. HRMS (TOF) calc. for C H NO [M+H] 316.1543 found 316.1544.
18
22
4
Dimethyl 10-methyl-6,8,9,10-tetrahydrocyclohepta[b]indole-7,7(5H)-
dicarboxylate (3j).(eluents: Hexane: ethyl acetate = 10:1). Yield: 90%.
1
Pale yellow solid, m.p.: 134-136 ºC. H NMR (300 MHz, CDCl )  7.94
3
(
bs, 1H), 7.52-7.46 (m, 1H), 7.27- 7.23 (m, 1H), 7.14- 7.02 (m, 2H), 3.76
2
3
(
s, 3H), 3.61 (s, 3H), 3.47- 3.32 (m, 2H), 3.35- 3.23 (m, 1H), 2.51 (ddd, 1H, J HH = 14.6 Hz, J
HH
3
HH
2
HH
3
HH
3
=10.7 Hz, J
= 2.2 Hz), 2.26 (ddd, 1H, J
= 14.6 Hz, J
= 7.8 Hz, J
= 1.0 Hz), 2.10-1.80
HH
3
HH
13
(m, 2H), 1.31 (d, 3H, J
= 7.1 Hz). C NMR (75 MHz, CDCl )  172.6, 171.3, 135.1, 130.3,
3
128.5, 121.2, 119.1, 118.1, 117.4, 110.7, 57.0, 53.0, 52.7, 32.7, 30.6, 30.2, 29.8, 20.3. HRMS
+
(
TOF) calc. for C H NO [M+H] 316.1543 found 316.1549.
18
22
4
Dimethyl
4-bromo-2,10-dimethyl-6,8,9,10-
(3k).
eluents: Hexane: ethyl acetate = 20:1). Yield: 80%. White solid, m.p.:
tetrahydrocyclohepta[b]indole-7,7(5H)-dicarboxylate
(
1
1
75-177 ºC. H NMR (500 MHz, CDCl )  7.84 (bs, 1H), 7.20 (s, 1H),
3
2
2
7.11 (s, 1H), 3.77 (s, 3H), 3.62 (s, 3H), 3.41 (d, 1H, J
= 15.2 Hz), 3.37 (d, 1H, J
= 15.3
HH
HH
2
3
HH
3
Hz), 3.28-3.17 (m, 1H), 2.49 (ddd, 1H, J HH = 14.4 Hz, J
= 11.1 Hz, J
= 1.8 Hz), 2.41 (s,
HH
2
HH
3
HH
2
3H), 2.27 (dd, 1H, J
= 14.4 Hz, J
= 7.4 Hz), 2.02-1.93 (m, 1H), 1.86 (ddd, 1H, J
= 14.7
HH
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3
HH
3
HH
3
HH
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DOI: 10.1039/C5CC04606H
Hz, J
= 8.3 Hz, J
= 1.8 Hz), 1.29 (d, J
= 7.1 Hz, 3H). C NMR (75 MHz, CDCl ) 
3
1
3
4
72.4, 171.1, 132.1, 131.4, 130.1, 129.7, 124.9, 118.3, 117.1, 103.9, 56.8, 53.1, 52.7, 32.8,
+
0.5, 30.1, 29.9, 21.4, 20.2. HRMS (TOF) calc. for C H BrNO [M+H] 408.0805 found
19
23
4
08.0813.
Dimethyl
2-chloro-10-methyl-6,8,9,10-
tetrahydrocyclohepta[b]indole-7,7(5H)-dicarboxylate
(3l).
(
eluents: Hexane: ethyl acetate = 10:1). Yield: 77%. White solid,
1
m.p.: 58-60 ºC. H NMR (300 MHz, CDCl ) 8.03 (bs, 1H), 7.45 (d,
3
4
3
5
3
4
1
2
3
=
H, J
= 2.0 Hz), 7.15 (dd, 1H, J HH = 8.5 Hz, J
=0.4 Hz), 7.04 (dd, 1H, J
= 8.6, J
=
HH
HH
HH
HH
2
2
.0 Hz), 3.77 (s, 3H), 3.62 (s, 3H), 3.41 (d, 1H, J
= 15.2 Hz), 3.34 (d, 1H, J
= 15.4 Hz),
HH
HH
2
3
3
HH
2
HH
.29-3.15 (m, 1H), 2.51 (ddd, 1H, J
=14.6 Hz, J
=10.6, J
= 2.3 Hz), 2.26 (ddd, 1H, J
HH
HH
3
HH
3
HH
3
13
14.6 Hz, J
= 7.7 Hz, J
= 1.4 Hz), 2.04- 1.81 (m, 2H), 1.30 (d, 3H, J = 7.1 Hz).
HH
C
NMR (75 MHz, CDCl )  172.5, 171.3, 133.5, 132.0, 129.6, 124.9, 121.4, 117.6, 117.3, 111.7,
3
+
56.9, 53.1, 52.7, 32.8, 30.5, 30.1, 29.7, 20.2. HRMS (TOF) calc. for C H ClNO [M+H]
18 21 4
350.1154 found 350.1136.
Dimethyl
tetrahydrocyclohepta[b]indole-7,7(5H)-dicarboxylate
eluents: Hexane: ethyl acetate = 5:1). Yield: 82%. Pale yellow
2-methoxy-10-methyl-6,8,9,10-
(3m).
(
1
solid, m.p.: 175-177 ºC. H NMR (300 MHz, CDCl ) 7.80 (bs, 1H),
3
3
HH
4
HH
4
HH
3
7.16 (dd, 1H, J
= 8.7 Hz, J
= 0.3 Hz), 6.95 (d, 1H, J
= 2.4 Hz), 6.78 (dd, 1H, J
= 8.7
HH
4
HH
2
Hz, J
= 2.4 Hz), 3.85 (s, 3H), 3.77 (s, 3H), 3.62 (s, 3H), 3.42 (d, 1H, J HH = 15.1 Hz), 3.32
2
HH
4
2
HH
3
(
dd, 1H, J
= 15.2 Hz, J
= 0.7 Hz), 3.26- 3.19 (m, 1H), 2.50 (ddd, 1H, J
= 14.6, J
=
HH
HH
3
2
3
1
3
1
0.8 Hz, J
= 2.0 Hz), 2.26 (dd, 1H, J
= 14.6 Hz, J
= 6.9 Hz), 2.05-1.81 (m, 2H), 1.31 (d,
HH
HH
HH
3
HH
13
H, J
= 7.1 Hz). C NMR (75 MHz, CDCl )  172.6, 171.3, 154.0, 131.3, 130.3, 128.9, 117.3,
3
11.4, 111.0, 100.5, 56.9, 56.1, 53.0, 52.7, 32.8, 30.5, 30.2, 29.8, 20.2. HRMS (TOF) calc. for
+
C H NO [M+H] 346.1649 found 346.1657.
19
24
5
Dimethyl
tetrahydrocyclohepta[b]indole-7,7(5H)-dicarboxylate
eluents: Hexane: ethyl acetate = 5:1). Yield: 76%. Pale yellow
10-methyl-3-(trifluoromethyl)-6,8,9,10-
(3n).
(
1
solid, m.p.: 152-154 ºC. H NMR (300 MHz, CDCl )  8.34 (bs,
3
3
HH
4
HH
3
HH
4
1H), 7.55 (d, 1H, J
= 8.3 Hz), 7.48 (t, 1H, J
= 0.9 Hz), 7.28 (dd, 1H, J
= 8.4 Hz, J
=
HH
2
1.1 Hz), 3.79 (s, 3H), 3.65 (s, 3H), 3.43 (s, 2H), 3.38-3.26 (m, 1H), 2.55 (ddd, 1H, J
= 14.6
HH
3
HH
3
HH
2
HH
3
HH
3
Hz, J
= 10.5 Hz, J
= 2.4 Hz), 2.30 (ddd, 1H, J
= 14.7 Hz, J
= 7.5 Hz, J
= 2.1 Hz),
HH
3
HH
13
2.06-1.84 (m, 2H), 1.32 (d, 3H, J
= 7.1 Hz). C NMR (75 MHz, CDCl )  172.4, 171.4, 133.9,
3
1
2
CF
3
133.5, 130.7, 125.5 (q, J
= 269.3 Hz), 123.1 (q, J
= 31.5 Hz), 118.3, 115.9 (q, J
= 3.0
CF
CF
3
CF
19
Hz), 108.2 (q, J
= 4.5 Hz), 56.9, 53.2, 52.8, 32.9, 30.5, 30.2, 29.7, 20.2. F NMR (471 MHz,
+
CDCl )  -60.47. HRMS (TOF) calc. for C H F NO [M+H] 384.1417 found 384.1425.
3
19 21
3
4
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DOI: 10.1039/C5CC04606H
5-methyl-2-tosyl-1,2,3,4,5,10-hexahydroazepino[3,4-b]indole
(3o).
(
eluents: Hexane: ethyl acetate = 10:1). Yield: 80%. Yellow solid, m.p.: 95-
1
3
9
7 ºC. H NMR (400 MHz, CDCl )  8.12 (bs, 1H), 7.62 (d, 1H, J
= 8.3
HH
3
3
HH
3
Hz), 7.46 (d, 1H, J
= 7.6 Hz), 7.22 (d, 1H, J
= 7.8 Hz), 7.17 (d, 1H,
HH
3
HH
3
HH
4
HH
3
HH
4
J
= 8.0 Hz), 7.12 (td, 1H, J
= 6.8 Hz, J
=1.2 Hz), 7.07 (td, 1H, J
= 7.4 Hz, J = 1.2
HH
2
HH
2
HH
2
HH
3
HH
Hz), 4.71 (d, 1H, J
= 15.8 Hz), 4.46 (d, 1H, J
= 15.8 Hz), 3.70 (dt, 1H, J
= 14.0 Hz, J
2
3
HH
3
HH
=
4.0 Hz), 3.54 (ddd, 1H, J
= 13.5 Hz, J
= 11.1 Hz, J
= 2.5 Hz), 3.39-3.26 (m, 1H), 2.35
HH
3
13
(
s, 3H), 2.15-2.04 (m, 1H), 1.95-1.84 (m, 1H), 1.25 (d, 1H, J HH = 7.2 Hz). C NMR (101 MHz,
CDCl )  143.5, 136.1, 135.0, 130.5, 129.8, 128.1, 127.22, 121.8, 119.5, 118.4, 118.3, 111.1,
3
+
4
6.3, 45.7, 33.6, 28.6, 21.6, 19.9. HRMS (TOF) calc. for C H N O S [M+H] 355.1475 found
20
22
2
2
355.1464.
4
8
1
,9-dihydro-1H-carbazole (3p). (eluents: Hexane: ethyl acetate = 50:1). Yield:
1
1%. White solid, m.p.: 142-144 ºC. H NMR (400 MHz, Acetone)  9.83 (bs,
3
HH
3
HH
4
H), 7.41 (d, 1H, J
= 7.7 Hz,), 7.32 (dt, 1H, J
= 7.9 Hz, J
= 0.8 Hz), 7.05
HH
3
HH
4
HH
3
4
(
td, 1H, J
= 7.5 Hz, J
= 1.2 Hz), 6.98 (td, 1H, J
= 7.4 Hz, J
= 1.1 Hz), 6.05-6.00 (m,
HH
HH
1
3
1
1
1
H), 5.95-5.89 (m, 1H), 3.47-3.34 (m, 4H). C NMR (101 MHz, Acetone)  137.3, 132.2, 128.2,
+
23.8, 121.5, 119.4, 118.3, 111.4, 106.9, 24.9, 23.9. HRMS (TOF) calc. for C H N [M+H]
12
12
70.0964 found 170.0962.
Preparation of Intermediates and Indole-Gold Compexes
Procedure for the gold(I)-catalyzed synthesis of indole 3b.
An oven dried resealable test tube with a Teflon stirring bar was charged with the 2-aniline-
enyne 2b (0.5 mmol) in dried EtOH (0.125M). Subsequently, NaAuCl ·2H O (5 mol %) were
4
2
added. The tube was sealed with a Teflon screw-cap and placed in an oil bath at 60 ºC. The
reaction was heated at this temperature until consumption of the starting material. Next, the
mixture was cooled to room temperature, diluted with dichloromethane (2-3 mL), and filtered
over Aluminium oxide activated. The solvent was removed under reduced pressure and indole
3b was isolated by silica gel column chromatography (eluents: Hexane: ethyl acetate = 20:1).
Dimethyl 2-((1H-indol-2-yl)methyl)-2-(but-3-enyl)malonate. Yield:
1
8
7%. Pale yellow solid, m.p.: 72-74 ºC. H NMR (300 MHz, CDCl ) 
3
3
HH
3
8.62 (bs, 1H), 7.53 (d, 1H, J
= 7.8 Hz), 7.32 (dd, 1H, J
= 8.0 Hz,
HH
4
HH
4
J
= 0.8 Hz), 7.17-7.04 (m, 2H), 6.25 (d, 1H, J
= 1.4 Hz), 5.87-5.65
HH
13
(
m, 1H), 5.10-4.92 (m, 2H), 3.70 (s, 6H), 3.37 (s, 2H), 2.07-2.06 (m, 4H). C NMR (75 MHz,
CDCl )  172.3, 137.2, 136.3, 133.7, 128.3, 121.5, 120.1, 119.6, 115.5, 110.8, 102.8, 58.8, 52.8,
3
+
3
3.5, 32.9, 28.8. HRMS (TOF) calc. for C H NO [M+H] 316.1543 found 316.1535.
18
22
4
Synthesis of indole-gold complex 4.
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An oven dried resealable test tube with a Teflon stirring bar was charged under argon with
[
Au(JohnPhos)(NCMe)]SbF (0.1 mmol) and compound 3a (0.1 mmol) in dried CH Cl (1 mL).
6 2 2
The tube was sealed with a Teflon screw-cap and the reaction was stirred at room temperature
for 1 h. Then the solvent was removed under vacuum, and the solid residue was washed with
diethyl ether to give complex 4 as a white solid (98%).
1
Complex 4. m.p.: 78-80 ºC. H NMR (400 MHz, CD Cl )  8.02-
2
2
7.95 (m, 1H), 7.69-7.62 (m, 3H), 7.54-7.45 (m, 2H), 7.36 (d, 1H,
3
3
J
J
= 7.5 Hz), 7.33-7.28 (m, 1H), 7.21 (dd, 2H, J
= 8.2 Hz,
HH
HH
4
HH
3
HH
= 1.2 Hz), 7.02 (t, 2H, J = 7.8 Hz), 6.72 (t, 1H, J
= 7.5
Hz), 5.74 (bs, 1H), 5.03 (m, 2H), 3.91 (s, 2H), 3.72 (s, 6H), 3.37
3
PH
13
(
s, 2H), 2.12-1.95 (m, 4H), 1.53 (d, 18H, J
= 16.1 Hz).
C
1
PC
2
NMR (126 MHz, CD Cl )  186.5, 170.7, 151.1, 149.4 (d, J
= 12.3 Hz), 144.2 (d, J
= 6.1
PC
2
2
3
PC
2
PC
4
Hz), 136.9, 134.3 (d, J
= 3.5 Hz), 133.9 (d, J
= 7.6 Hz), 132.2 (d, J
= 2.0 Hz), 129.9,
PC
3
1
29.2, 128.7, 128.4 (d, J
= 7.5 Hz), 127.5, 125.4, 124.8, 124.4, 120.4, 119.4, 116.3, 57.9,
PC
1
2
PC
31
5
3.8, 45.1, 41.7, 38.8 (d, J PC = 26.6 Hz), 35.5, 31.3 (d, J
= 5.9 Hz), 29.42. P NMR (162
+
MHz, CD Cl )  58.7.HRMS (TOF) calc. for C H AuNO P [M] 810.2981 found 810.2972.
2
2
38 48
4
Synthesis of indole-gold complexes 5 and 6.
An oven dried resealable test tube with a Teflon stirring bar was charged under argon with
Au(IPr)]SbF (0.1 mmol) (generated from a stoichiometric mixture of [AuCl(IPr)] and AgSbF )
[
6
6
and compound 3a (0.1 mmol) in dried CH Cl (1 mL). The tube was sealed with a Teflon screw-
2
2
cap and the reaction was stirred at room temperature for 1 h. Then the solvent was removed
under vacuum, and the solid residue was washed with diethyl ether to give complex 5 as a
violet solid in quantitative yield.
1
Complex 5. m.p.: 88-90 ºC. H NMR (400 MHz, CD Cl )  7.67 (t,
2
2
3
HH
3
HH
4
2H, J
= 7.8 Hz), 7.51 (s, 2H), 7.47 (dd, 1H, J
= 7.4 Hz, J
HH
3
HH
3
=
1.0 Hz), 7.44 (d, 4H, J
= 7.8 Hz), 7.33 (td, 1H, J
= 7.6 Hz,
HH
4
HH
3
HH
3
J
= 1.0 Hz), 7.17 (td, 1H, J
= 7.9 Hz, J
= 1.1 Hz), 6.32 (d,
HH
3
1H, J
= 7.9 Hz,), 5.85-5.72 (m, 1H), 5.16-5.05 (m, 2H), 3.75 (s,
HH
2H), 3.60 (s, 6H), 3.00 (s, 2H), 2.66-2.52 (m, 4H), 1.87-1.78 (m,
3
HH
3
13
2H), 1.77-1.70 (m, 2H), 1.30 (d, J
= 6.9 Hz, 12H), 1.29 (d, J
= 6.9 Hz, 12H). C NMR (101
HH
MHz, CD Cl )  188.3, 171.2, 170.4, 151.3, 146.7, 137.0, 134.3, 134.1, 131.9, 128.5, 128.4,
2
2
125.4, 125.1, 125.1, 118.3, 116.3, 57.8, 53.6, 45.0, 41.1, 35.7, 29.5, 29.1, 24.9, 24.4. HRMS
+
(
TOF) calc. for C H AuN O [M] 900.4009 found 900.3990.
45
57
3
4
Complex 6
S12

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Attempts to crystallize complex 5 from a dichloromethane-pentane solution at low temperature
allowed to isolate the diaurated species 6 derived from [Au(IPr)]SbF6)
X-ray Data
a)
b)
Figure 1. Thermal ellipsoid plot (50% probability level) for 6: (a) IPr ellipsoids and hydrogen
atoms omitted, (b) labelling scheme with IPr ligands [C(22) and C(52)] omitted. Selected bond
lengths (Ǻ) and angles (º): Au(1)-N(11) 2.044(7), Au(1)-C(52) 1.978(8), Au(2)-C(13) 2.122(8),
Au(2)-C(22) 2.016(7), N(11)-C(12) 1.325(9), N(11)-C(17A) 1.382(10), C(12)-C(13) 1.429(12),
C(13)-C(13A) 1.483(10), C(13A)-C(17A) 1.382(11), C(13A)-C(14) 1.410(11), C(14)-C(15)
1.392(11), C(15)-C(16) 1.387(13), C(16)-C(17) 1.377(12) , C(17)-C(17A) 1.413(10), C(52)-
Au(1)- N(11) 178.0(3), C(22)-Au(2)-C(13) 173.8(3), C(12)-N(11)-C(17A) 107.1(7), C(12)-N(11)-
Au(1) 129.8(6), C(17A)-N(11)-Au(1) 123.0(5), N(11)-C(12)-C(13) 113.5(7), C(12)-C(13)-C(13A)
101.4(7) , C(12)-C(13)-Au(2) 105.6(5), C(13A)-C(13)-Au(2) 105.5(5), C(17A)-C(13A)-C(14)
120.1(7), C(17A)-C(13A)-C(13) 107.1(7), C(14)-C(13A)-C(13) 132.8(8), C(15)-C(14)-C(13A)
118.7(8), C(16)-C(15)-C(14) 120.4(8), C(17)-C(16)-C(15) 121.8(8), C(16)- C(17)-C(17A)
117.9(8), C(13A)-C(17A)-N(11) 110.4(6), C(13A)-C(17A)-C(17) 121.0(8), N(11)-C(17A)-C(17)
128.6(8).
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Table
3.
Solvent
and acid
additive
effect
on
the
[
Au(JohnPhos)(MeCN)]SbF6 catalysed cascade formation of
cycloheptaindole 3j from 1j
a
Entry Solvent
Additive
t (h)
2j(%)
3j(%)
1
2
3
4
5
6
7
8
9
1
1
1
1
1
DCM
none
none
none
none
none
none
none
none
none
AcOH
BzOH
30
30
30
30
30
30
30
30
30
45
45
45
45
45
>95
>95
>95
92
37
36
50
>95
-
38
14
5
55
55
-
-
-
1,2-DCE
Toluene
THF
DMA
DMF
EtOH
HFIP
DMF/HFIP
DMF
DMF
DMF
DMF
DMF
8
63
64
50
-
>95
72
86
95
45
45
b
0
1
2
3
4
p-NO
TfOH
p-TsOH
2
C
6 4 2
H CO H
a)
b)
7
.5 mol% of the corresponding acid were added. 50% v/v mixture
S14

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NMR Spectra of New Compounds
Dimethyl 2-allyl-2-(3-(2-aminophenyl)prop-2-ynyl)malonate
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Dimethyl 2-allyl-2-(3-(2-amino-3-bromo-5-methylphenyl)prop-2-ynyl)malonate
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Dimethyl 2-allyl-2-(3-(2-amino-5-chlorophenyl)prop-2-ynyl)malonate
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Dimethyl 2-allyl-2-(3-(2-amino-5-isopropylphenyl)prop-2-ynyl)malonate
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Dimethyl 2-allyl-2-(3-(2-amino-5-methoxyphenyl)prop-2-ynyl)malonate
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N-allyl-N-(3-(2-aminophenyl)prop-2-ynyl)-4-methylbenzenesulfonamide
S20

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2-(hept-6-en-1-ynyl)aniline
S21

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2-(3-(allyloxy)prop-1-ynyl)aniline
S22

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Dimethyl 2-(3-(2-aminophenyl)prop-2-ynyl)-2-(2-methylallyl)malonate
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Dimethyl 2-(3-(2-aminophenyl)prop-2-ynyl)-2-(but-3-enyl)malonate
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Dimethyl 2-(3-(2-amino-3-bromo-5-methylphenyl)prop-2-ynyl)-2-(but-3-enyl)malonate
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Dimethyl 2-(3-(2-amino-5-chlorophenyl)prop-2-ynyl)-2-(but-3-enyl)malonate
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Dimethyl 2-(3-(2-amino-5-methoxyphenyl)prop-2-ynyl)-2-(but-3-enyl)malonate
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Dimethyl 2-(3-(2-amino-4-(trifluoromethyl)phenyl)prop-2-ynyl)-2-(but-3-enyl)malonate
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S29