Switchable synthesis of 3-cyanoindoles and 3-amidylindoles via a palladium-catalyzed reaction of N,N-dimethyl-2-alkynylaniline with isocyanide

Article abstract of DOI:10.1002/adsc.201300382

A palladium-catalyzed reaction of N,N-dimethyl-2-alkynylanilines with isocyanides is reported, leading to the formation of 3-cyanoindoles and 3-amidylindoles. The isocyanide insertion is the key step during the process, and the presence of water is essential for the formation of 3-amidylindoles.

Full text of DOI:10.1002/adsc.201300382

UPDATES
DOI: 10.1002/adsc.201300382
Switchable Synthesis of 3-Cyanoindoles and 3-Amidylindoles via
a Palladium-Catalyzed Reaction of N,N-Dimethyl-2-alkynylani-
line with Isocyanide
Guanyinsheng Qiu,a Xiaochen Qiu,a Jianping Liu,b,* and Jie Wua,c,*
a
Department of Chemistry, Fudan University 220 Handan Road, Shanghai 200433, Peopleꢀs Republic of China
Fax : (+86)-21-6564-1740; e-mail: jie_wu@fudan.edu.cn
EENT Hospital, Fudan University, 83 Fenyang Road, Shanghai 200031, Peopleꢀs Republic of China
b
E-mail: jiulu123@sina.com
c
Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen
Graduate School, Shenzhen 518055, Peopleꢀs Republic of China
Received: May 3, 2013; Revised: June 6, 2013; Published online: August 13, 2013
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201300382.
Abstract: A palladium-catalyzed reaction of N,N-di-
methyl-2-alkynylanilines with isocyanides is report-
ed, leading to the formation of 3-cyanoindoles and
3-amidylindoles. The isocyanide insertion is the key
step during the process, and the presence of water
is essential for the formation of 3-amidylindoles.
methyl-2-alkynylanilines could be involved in a palla-
dium-catalyzed, three-component reaction of isocya-
nides with silver acetate [Scheme 1, Eq. (2)].[4f] In the
reaction process, silver acetate acted as a reagent as
well as the oxidant. Surprisingly, during the subse-
quent library construction, a distinct compound was
observed when the oxidant was switched to silver tri-
fluoroacetate. The new compound was identified to
be 3-cyano-2-phenyindole after structural determina-
tion [Scheme 1, Eq. (3)]. We reasoned that the tri-
fluoroacetate ion might be unfavorable for the reduc-
tive elimination compared with the acetate ion, due
to its weak coordination to the palladium center and
its weak nucleophilicity, thus predominantly leading
to the 3-cyanative product with the removal of tert-
butyl cation.[5] It is well-known that the 3-cyanoin-
Keywords: 3-amidylindoles; 3-cyanoindoles; N,N-di-
methyl-2-alkynylanilines; isocyanides; palladium
catalysts
Introduction
As a privileged structural motif, indole has been the
subject of continuous interest in organic synthesis due
to its ubiquity in many bioactive natural products,
pharmaceuticals, and agrochemicals.[1] To date, tre-
mendous efforts have been devoted by organic chem-
ists to the development of new synthetic methodolo-
gies for the synthesis of diverse indole architectures.[2]
Among these achievements, alkynes-based heteroan-
nulations using palladium as catalyst have emerged as
excellent representatives.[3] Recently, N,N-dimethyl-2-
alkynylanilines have been disclosed as a good reaction
partner for the formation of indoles by Larock, Zhu,
Bertrand, and Liang.[4] For example, Zhu and co-
workers found that N,N-dimethyl-2-alkynylanilines re-
acted with alkynes in the presence of palladium catal-
ysis affording to 3-alkynylindoles in moderate to ex-
cellent yields [Scheme 1, Eq. (1)].[4d] In the process,
a palladium-enabled intramolecular cyclization of the
tertiary amine to produce an s-indolylpalladium(II)
Scheme 1. Synthesis of 3-cyanoindole via a palladium-cata-
lyzed reaction of N,N-dimethyl-2-alkynylanilines with iso-
was the key step. Recently, we also found that N,N-di- cyanides.
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Guanyinsheng Qiu et al.
UPDATES
doles are important synthetic targets[6] due to their
promising bioactivities and potential for further struc-
tural elaboration.[7] Significant contributions have
been achieved for the synthesis of 3-cyanoindoles.[6]
For instance, Jiao and co-workers disclosed the direct
cyanation of indoles using N,N-dimethylformamide
(DMF) as both reagent and solvent.[6e] Chang de-
scribed a copper-mediated selective cyanation of in-
doles with ammonium iodide and DMF.[6g] Based on
the above results we obtained, we envisioned that
a palladium-catalyzed tandem process starting from
N,N-dimethyl-2-alkynylanilines and isocyanides would
provide a facile access to 3-cyanoindoles.
Table 1. Initial studies for the palladium-catalyzed reaction
of N,N-dimethyl-2-alkynylaniline 1a with tert-butyl isocya-
nide 2a.[a]
Temp. [8C] Yield [%][b]
Recently, the transition metal-catalyzed imidoyla-
tive reactions of isocyanides have attracted much at-
tention.[8–10] Among the reports, a palladium-catalyzed
cyanation of N-heterocycles using isocyanide as the
cyano source was highlighted by Zhu and Xu.[5] The
transformation proceeded with high efficiency and
good regioselectivity in the presence of a stoichiomet-
ric amount of copper trifluroacetate as the oxidant.
However, no isocyanides other than tertiary amine-
derived isocyanides (such as tert-butyl isocyanide)
could be compatible in these cyanative reactions.
Since this method is convenient and safe compared
with conventional approaches, it seemed that the gen-
eration of 3-cyanoindoles by using isocyanide as the
cyano source was feasible. Prompted by the achieve-
ment of the N,N-dimethyl-2-alkynylaniline chemistry
as mentioned above and the attractiveness of isocya-
nide insertion, we therefore started to explore the
possibility of this transformation.
Entry Oxidant
Solvent
3a
4a
1
2
3
4
5
6
7
8
air
O2
Cu
MeCN
MeCN
(TFA)2 MeCN
70
70
70
70
70
11
18
complex
52
90
82
complex
81
–
–
–
–
–
–
–
–
–
G
AgTFA
AgTFA
AgTFA
AgTFA
AgTFA
AgTFA
AgTFA
AgTFA
AgTFA
MeCN
DCE
dioxane 70
DMSO
toluene
THF
THF
DCE
DCE
70
70
70
70
50
70
9
44
72
–
10[c]
11[d]
12[e]
–
62
73
–
[a]
Reaction conditions: N,N-dimethyl-2-alkynylaniline 1a
(1.0 equiv.), isocyanide 2a (2.5 equiv.), palladium triflur-
oacetate (5 mol%), oxidant (2.0 equiv.), N2, 708C over-
night.
Isolated yield based on N,N-dimethyl-2-alkynylaniline 1a.
5 equivalents of H2O were added.
[b]
[c]
[d]
[e]
After 48 h.
In the presence of 5 mol% of PdACTHNUTRGENUG(N OAc)2.
Results and Discussion
Initially, a model reaction of N,N-dimethyl-2-aniline due to the presence of a trace amount of H2O in THF
1a with tert-butyl isocyanide 2a was selected. Some re- (Table 1, entry 9). To verify this hypothesis, 5.0 equiv-
sults of the investigation are presented in Table 1. At alents of water were added in the reaction mixture.
the outset, the reaction was performed under air in As expected, the product 4a was furnished in 72%
the presence of PdACTHNUTRGNE(UNG TFA)2 (5 mol%) at 708C in aceto- yield (Table 1, entry 10). Reducing the temperature to
nitrile. Gratifyingly, the expected product 3a was de- 508C provided the compound 3a in 62% yield, how-
tected and isolated in 11% yield (Table 1, entry1). En- ever, the reaction time was prolonged to 48 h
couraged by this result, the parameters including oxi- (Table 1, entry 11). An inferior result was obtained
dant, solvent, and temperature were then evaluated. when palladium trifluroacetate was replaced by palla-
It seemed that silver trifluroacetate was the best dium acetate (Table 1, entry 12).
choice among the selected oxidants, leading to the de-
With the above conditions in hand, we then exam-
sired product 3a in 52% yield (Table 1, entry 4). By ined the scope and generality of this palladium-cata-
altering the solvent to 1,2-dichloroethane, the yield of lyzed reaction of 2-alkynylaniline 1 with isocyanide 2.
the product 3a was improved dramatically (90%, The reactions occurred in DCE firstly, and the results
Table 1, entry 5). The reaction gave a lower yield are illustrated in Table 2. A series of substituted 3-cy-
when the solvent was switched to 1,4-dioxane, tolu- anoindoles was constructed as expected. Different 2-
ene, or dimethyl sulfoxide (Table 1, entries 6–8). In- alkynylanilines 1 with an aryl or alkyl group at the R1
terestingly, the reaction afforded the 3-amidylindole position were all good substrates with the formation
4a in 44% yield when tetrahydrofuran was employed of the corresponding products 3b–3f (Table 2). Fur-
as the solvent. Under these conditions, the product 3a thermore, variations of the R2 substituents attached
was not observed. We assumed that this is probably on the aromatic ring of 2-alkynylanilines 1 were also
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Switchable Synthesis of 3-Cyanoindoles and 3-Amidylindoles via a Palladium-Catalyzed Reaction
Table 2. Synthesis of subtituted 3-cyanoindoles via a palladi-
um-catalyzed reaction of N,N-dimethyl-2-alkynylanilines
with isocyanides.[a]
Table 3. Synthesis of subtituted 3-amidylindoles via a palladi-
um-catalyzed reaction of N,N-dimethyl-2-alkynylanilines,
isocyanides, and H2O.[a]
[a]
Isolated yield based on N,N-dimethyl-2-alkynylaniline 1.
60% yields, respectively. 2-(Hex-1-ynyl)-N,N-dimethyl-
aniline was a good partner as well in the transforma-
tion, resulting in the 3-amidylindole 4g in 46% yield.
In the light of these results, a plausible mechanism
was proposed which is shown in Scheme 2. The possi-
ble intermediate A, which was generated through
[a]
Isolated yield based on N,N-dimethyl-2-alkynylaniline 1.
PdACTHUNTRGENNG(U TFA)2-catalyzed cyclization of 2-alkynylaniline,
explored. It is noteworthy that the ester group could would undergo isocyanide insertion, producing the in-
be compatible as well under the standard conditions. termediate B. The intermediate B might go through
À
Additionally, not only tert-butyl isocyanide 2a but also two pathways: a) cleavage of C N bond and removal
cyclohexyl isocyanide 2b could be tolerated in the re- of tertiary carbon cation would occur to generate the
action, leading to 3-cyanated indole 3a in good yields, 3-cyanoindoles 3, with the formation of Pd(0); b) the
which to some extent overcame the drawback that intermediate B would react with water if water was
tert-butyl isocyanide was the only appropriate type of presented in the reaction, producing the intermediate
isocyanide in the procedures developed by Zhu and C. The subsequent reductive elimination and isomeri-
Xu.[5]
zation would provide the 3-amidated indole 4. Mean-
To expand the scope of this tandem reaction, we time, Pd(0) would be re-oxidized to Pd(II) to trigger
subsequently explored the 3-amidylindole formation the catalytic cycle again.
under the conditions highlighted in Table 1, entry 10.
The results are presented in Table 3. For most of the
cases, the corresponding 3-amidylindoles were afford- Conclusions
ed in reasonable yields. For instance, 2-[2-(4-chloro-
phenyl)ethynyl]-N,N-dimethylaniline 1b reacted with In conclusion, we have described a switchable synthe-
tert-butyl isocyanide and H2O, providing the product sis of 3-cyanoindoles and 3-amidylindoles via a palladi-
4b in 57% yield, while the reactions of 4-methoxy- um-catalyzed reaction of N,N-dimethyl-2-alkynylani-
substituted and 2-methoxy-subtituted 2-alkynylani- lines and isocyanide. The isocyanide insertion is the
lines gave rise to the products 4c and 4d in 68% and key step during the process. The presence of water is
Adv. Synth. Catal. 2013, 355, 2441 – 2446
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Guanyinsheng Qiu et al.
UPDATES
Scheme 2. A plausible mechanism for the palladium-catalyzed reaction of N,N-dimethyl-2-alkynylanilines 1 with isocyanides
2.
136.6, 145.9, 157.4; HR-MS (ESI): m/z=263.1187, calcd. for
C17H15N2O+ (M+H+): 263.1179.
essential for the formation of 3-amidylindoles. The
different outcome could provide a new insight for the
chemistry of isocyanide insertion. Currently, explora-
tion of isocyanide insertion in other transformations
is ongoing in our laboratory, and the results will be re-
ported in due course.
2-(4-Chlorophenyl)-1-methyl-1H-indole-3-carbonitrile
(3d): 1H NMR (400 MHz, CDCl3): d=3.76 (s, 3H), 7.32–
7.46 (m, 3H), 7.51–7.57 (m, 4H), 7.77 (d, J=7.6 Hz, 1H);
13C NMR (100 MHz, CDCl3): d=31.7, 110.6, 116.4, 119.6,
122.6, 124.2, 127.1, 127.4, 129.4, 131.1, 136.3, 136.9, 146.7;
+
HR-MS (ESI): m/z=267.0668, calcd. for C16H12ClN2 (M+
H+): 267.0684.
2-Cyclopropyl-1-methyl-1H-indole-3-carbonitrile
(3e):
1H NMR (400 MHz, CDCl3): d=1.11–1.15 (m, 2H), 1.17–
1.22 (m, 2H), 1.93–1.98 (m, 1H), 3.84 (s, 3H), 7.23–7.33 (m,
3H), 7.66 (d, J=8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d=6.34, 7.42, 30.2, 109.7, 114.6, 116.5, 119.1, 121.9, 123.3,
127.3, 136.0, 149.2; HR-MS (ESI): m/z=197.1070, calcd. for
Experimental Section
General Procedure for the Synthesis of Subtituted 3-
Cyanoindoles 3 via a Palladium-Catalyzed Reaction
of N,N-Dimethyl-2-alkynylaniline and Isocyanide
+
C13H13N2 (M+H+): 197.1073.
2-Butyl-1-methyl-1H-indole-3-carbonitrile (3f): 1H NMR
(400 MHz, CDCl3): d=0.98 (t, J=7.2 Hz, 3H), 1.43–1.49
(m, 2H), 1.66–1.74 (m, 2H), 2.93–2.97 (m, 2H), 3.73 (s, 3H),
7.24–7.35 (m, 3H), 7.67 (d, J=7.2 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d=13.7, 22.3, 25.9, 30.2, 31.2, 109.8,
116.7, 119.1, 121.9, 122.9, 127.1, 136.4, 149.9; HR-MS (ESI):
Pd
a
ACHTUNGTRENNUNG
1
(2.0 mL). Then isocyanide (2.5 equiv.) was added. The reac-
tion mixture was stirred at 708C. After completion of the re-
action as indicated by TLC, the solvent was evaporated and
the residue was purified on silica gel to provide the desired
product 3.
+
m/z=213.1380, calcd. for C14H17N2 (M+H+): 213.1386.
Ethyl 3-cyano-1-methyl-2-phenyl-1H-indole-5-carboxylate
(3g): 1H NMR (400 MHz, CDCl3): d=1.44 (t, J=7.2 Hz,
3H), 3.79 (s, 3H), 4.40–4.45 (m, 2H), 7.45 (d, J=8.8 Hz,
1H), 7.56–7.59 (m, 5H), 8.08 (d, J=8.8 Hz, 2H), 8.51 (s,
1H); 13C NMR (100 MHz, CDCl3): d=14.2, 32.0, 61.1, 110.3,
115.9, 121.9, 124.8, 125.3, 127.0, 128.2, 129.1, 129.8, 130.4,
139.2, 149.7, 166.8; HR-MS (ESI): m/z=305.1268, calcd. for
1-Methyl-2-phenyl-1H-indole-3-carbonitrile
(3a):[5a]
1H NMR (400 MHz, CDCl3): d=3.75 (s, 3H), 7.30–7.43 (m,
3H), 7.53–7.56 (m, 5H), 7.77 (d, J=7.6 Hz, 1H).
2-(4-Methoxyphenyl)-1-methyl-1H-indole-3-carbonitrile
1
(3b): H NMR (400 MHz, CDCl3): d=3.75 (s, 3H), 3.89 (s,
3H), 7.08 (d, J=8.4 Hz, 2H), 7.31–7.40 (m, 3H), 7.51 (d, J=
8.8 Hz, 2H), 7.76 (d, J=7.6 Hz, 1H); 13C NMR (100 MHz,
CDCl3): d=31.7, 55.5, 110.5, 114.5, 116.9, 119.4, 120.9, 122.3,
123.7, 127.6, 131.2, 136.8, 148.2, 160.8; HR-MS (ESI): m/z=
263.1169, calcd. for C17H15N2O+ (M+H+): 263.1179.
+
C19H17N2O2 (M+H+): 305.1285.
1,5-Dimethyl-2-phenyl-1H-indole-3-carbonitrile
(3h):
1H NMR (400 MHz, CDCl3): d=2.62 (s, 3H), 3.74 (s, 3H),
7.20 (d, J=8.0 Hz, 1H), 7.32 (d, J=8.4 Hz, 1H), 7.51–7.57
(m, 6H); 13C NMR (100 MHz, CDCl3): d=21.5, 31.8, 110.2,
116.9, 119.2, 125.5, 127.8, 129.0, 129.8, 132.1, 136.3, 147.8;
2-(2-Methoxyphenyl)-1-methyl-1H-indole-3-carbonitrile
1
(3c): H NMR (400 MHz, CDCl3): d=3.63 (s, 3H), 3.84 (s,
+
HR-MS (ESI): m/z=247.1228, calcd. for C17H15N2 (M+
3H), 7.07 (d, J=8.0 Hz, 1H), 7.12–7.16 (m, 1H), 7.30–7.47
(m, 4H), 7.51–7.55 (m, 1H), 7.79 (d, J=7.6 Hz, 1H);
13C NMR (100 MHz, CDCl3): d=31.5, 55.8, 110.4, 110.9,
116.7, 117.7, 119.5, 121.1, 122.0, 123.5, 127.6, 131.9, 132.3,
H+): 247.1230.
5-Isopropyl-1-methyl-2-phenyl-1H-indole-3-carbonitrile
(3i): 1H NMR (400 MHz, CDCl3): d=1.35 (d, J=6.8 Hz,
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Switchable Synthesis of 3-Cyanoindoles and 3-Amidylindoles via a Palladium-Catalyzed Reaction
6H), 3.04–3.12 (m, 1H), 3.75 (s, 3H), 7.28 (d, J=7.2 Hz,
1H), 7.36 (d, J=8.4 Hz, 1H), 7.53–7.57 (m, 5H), 7.64 (s,
1H); 13C NMR (100 MHz, CDCl3): d=24.5, 31.7, 34.2, 110.4,
116.5, 116.9, 123.3, 127.8, 128.9, 129.0, 129.8, 135.6, 143.6,
140.3, 164.9; HR-MS (ESI): m/z=321.1907, calcd. for
C21H25N2O+ (M+H+): 321.1961.
N-tert-Butyl-2-butyl-1-methyl-1H-indole-3-carboxamide
(4g): 1H NMR (400 MHz, CDCl3): d=0.96 (t, J=7.2 Hz,
3H), 1.43–1.49 (m, 2H), 1.52 (s, 9H), 1.60–1.68 (m, 2H),
3.14–3.18 (m, 2H), 3.70 (s, 3H), 5.82 (s, 1H), 7.18–7.23 (m,
2H), 7.32 (d, J=8.8 Hz, 1H), 7.69 (d, J=8.4 Hz, 1H);
13C NMR (100 MHz, CDCl3): d=13.9, 22.6, 24.8, 29.3, 29.5,
31.9, 51.2, 109.5, 118.4, 120.8, 121.4, 125.2, 136.4, 145.4,
165.6; HR-MS (ESI): m/z=287.2101, calcd. for C18H27N2O+
(M+H+): 287.2118.
N-tert-Butyl-2-cyclopropyl-1-methyl-1H-indole-3-carboxa-
mide (4h): 1H NMR (400 MHz, CDCl3): d=0.82–0.86 (m,
2H), 1.18–1.23 (m, 2H), 1.52 (s, 9H), 1.88–1.93 (m, 1H),
3.80 (s, 3H), 5.95 (s, 1H), 7.15–7.25 (m, 3H), 8.05 (d, J=
7.6 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=6.64, 8.17,
29.1, 30.1, 51.1, 108.8, 111.1, 120.6, 120.8, 122.2, 126.2, 136.0,
141.1, 165.0; HR-MS (ESI): m/z=271.1808, calcd. for
C17H23N2O+ (M+H+): 271.1805.
+
148.0; HR-MS (ESI): m/z=275.1544, calcd. for C19H19N2
(M+H+): 275.1543.
1,5-Dimethyl-2-p-tolyl-1H-indole-3-carbonitrile
(3j):
1H NMR (400 MHz, CDCl3): d=2.46 (s, 3H), 2.51 (s, 3H),
3.73 (s, 3H), 7.18 (d, J=8.4 Hz, 1H), 7.30 (d, J=8.4 Hz,
1H), 7.36 (d, J=8.0 Hz, 2H), 7.46 (d, J=8.0 Hz, 2H), 7.56
(s, 1H); 13C NMR (100 MHz, CDCl3): d=21.4, 31.7, 110.1,
116.9, 119.1, 125.3, 125.9, 127.9, 129.7, 132.0, 135.2, 139.9,
+
148.2; HR-MS (ESI): m/z= calcd. for C18H17N2 (M+H+):
261.1386.
General Procedure for the Synthesis of Subtituted 3-
Amidylindole 4 via a Palladium-Catalyzed Reaction
of N,N-Dimethyl-2-alkynylaniline, Isocyanide, and
H2O
PdACHTUNGTRENNUNG(TFA)2 (5 mol%) and AgTFA (2.0 equiv.) were added to
a solution of 2-alkynylaniline 1 (0.2 mmol) in THF (2.0 mL).
Then H2O (5.0 equiv.) and isocyanide (2.5 equiv.) was
added. The reaction was stirred at 608C. After completion
of the reaction as indicated by TLC (8–12 h), the solvent
was evaporated and the residue was purified on silica gel to
provide the desired product 4.
Acknowledgements
Financial support from the National Natural Science Founda-
tion of China (Nos. 21032007, 21172038) is gratefully ac-
knowledged.
N-tert-Butyl-1-methyl-2-phenyl-1H-indole-3-carboxamide
(4a):[8g] 1H NMR (400 MHz, CDCl3): d=1.14 (s, 9H), 3.54
(s, 3H), 5.00 (s, 1H), 7.25–7.35 (m, 3H), 7.46–7.48 (m, 2H),
7.57–7.58 (m, 3H), 8.39 (d, J=7.6 Hz, 1H).
References
N-tert-Butyl-2-(4-chlorophenyl)-1-methyl-1H-indole-3-
1
carboxamide (4b): H NMR (400 MHz, CDCl3): d=1.22 (s,
[1] a) Indoles (Ed.: R. J. Sundberg), Academic Press,
London, 1996; b) J. A. Joule, Indole and its Derivatives,
in: Science of Synthesis (Houben-Weyl Methods of Mo-
lecular Transformations), Vol. 10, (Ed.: E. J. Thomas),
Thieme, Stuttgart, 2000, chap. 10.13.
9H), 3.53 (s, 3H), 5.10 (s, 1H), 7.25–7.35 (m, 3H), 7.42 (d,
J=8.4 Hz, 2H), 7.55 (d, J=8.4 Hz, 2H), 8.26 (d, J=7.6 Hz,
1H); 13C NMR (100 MHz, CDCl3): d=28.8, 30.7, 50.9, 109.5,
110.9, 121.6, 122.9, 126.6, 129.3, 129.7, 132.1, 135.9, 136.8,
139.2, 164.4; HR-MS (ESI): m/z=341.1401, calcd. for
C20H22ClN2O+ (M+H+): 341.1415.
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line-based palladium-catalyzed syntheses of indoles,
see: a) D. Yue, R. C. Larock, Org. Lett. 2004, 6, 1037;
b) X. Feng, R. Kinjo, B. Donnadieu, G. Bertrand,
Angew. Chem. 2010, 122, 954; Angew. Chem. Int. Ed.
2010, 49, 942; c) B. Yao, Q. Wang, J. Zhu, Angew.
Chem. 2012, 124, 5260; Angew. Chem. Int. Ed. 2012, 51,
5170; d) B. Yao, Q. Wang, J. Zhu, Angew. Chem. 2012,
124, 12477; Angew. Chem. Int. Ed. 2012, 51, 12311;
e) X.-F. Xia, N. Wang, L.-L. Zhang, X.-R. Song, X.-Y.
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N-tert-Butyl-2-(4-methoxyphenyl)-1-methyl-1H-indole-3-
1
carboxamide (4c): H NMR (400 MHz, CDCl3): d=1.18 (s,
9H), 3.51 (s, 3H), 3.90 (s, 3H), 5.17 (s, 1H), 7.09 (d, J=
8.8 Hz, 2H), 7.24–7.33 (m, 3H), 7.38 (d, J=8.8 Hz, 2H),
8.39 (d, J=6.4 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=
28.3, 30.6, 50.6, 55.5, 109.3, 110.2, 114.6, 121.4, 122.0, 122.6,
123.0, 127.0, 132.1, 136.6, 140.3, 160.7, 164.9; HR-MS (ESI):
+
m/z=337.1873, calcd. for C21H25N2O2 (M+H+): 337.1911.
N-tert-Butyl-2-(2-methoxyphenyl)-1-methyl-1H-indole-3-
1
carboxamide (4d): H NMR (400 MHz, CDCl3): d=1.15 (s,
9H), 3.48 (s, 3H), 3.80 (s, 3H), 5.28 (s, 1H), 7.08–7.18 (m,
2H), 7.22–7.53 (m, 4H), 7.55–7.57 (m, 1H), 8.38 (d, J=
8.4 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=28.8, 30.4,
50.4, 55.6, 109.2, 110.6, 111.4, 119.9, 121.1, 121.2, 122.0,
122.4, 127.1, 131.7, 132.8, 136.7, 137.3, 157.9, 164.9; HR-MS
+
(ESI): m/z=337.1899, calcd. for C21H25N2O2 (M+H+):
337.1911.
N-tert-Butyl-1,5-dimethyl-2-phenyl-1H-indole-3-carboxa-
mide (4e): 1H NMR (400 MHz, CDCl3): d=1.13 (s, 9H),
2.49 (s, 3H), 3.50 (s, 3H), 5.03 (s, 1H), 7.11–7.26 (m, 2H),
7.46–7.47 (m, 2H), 7.55–7.57 (m, 3H), 8.22 (s, 1H);
13C NMR (100 MHz, CDCl3): d=21.5, 28.7, 30.7, 50.6, 108.9,
121.7, 124.3, 127.3, 129.2, 129.7, 130.8, 131.0, 131.5, 135.1,
Adv. Synth. Catal. 2013, 355, 2441 – 2446
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2445

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2446
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Adv. Synth. Catal. 2013, 355, 2441 – 2446