Palladium-catalyzed sequential indole synthesis using sterically hindered amines

Article abstract of DOI:10.1016/j.tet.2009.07.073

A palladium catalyst derived from a bulky N-heterocyclic carbene ligand enabled a modular synthesis of indoles bearing sterically hindered N-alkyl or N-aryl substituents through a reaction sequence comprising an intermolecular N-arylation and an intramole

Full text of DOI:10.1016/j.tet.2009.07.073

Tetrahedron 65 (2009) 8930–8939
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Palladium-catalyzed sequential indole synthesis using sterically hindered amines
*
´
Lutz Ackermann , Rene Sandmann, Marvin Schinkel, Mikhail V. Kondrashov
Institut fuer Organische und Biomolekulare Chemie, Georg-August-Universitaet Goettingen, Tammannstr. 2, D-37077 Goettingen, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 12 May 2009
Received in revised form 9 July 2009
Accepted 27 July 2009
Available online 6 August 2009
A palladium catalyst derived from a bulky N-heterocyclic carbene ligand enabled a modular synthesis of
indoles bearing sterically hindered N-alkyl or N-aryl substituents through a reaction sequence com-
prising an intermolecular N-arylation and an intramolecular hydroamination.
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
and a final dehydration, albeit at a relatively high reaction tem-
perature of 240 ꢀC (Scheme 2).
Indoles are arguably the most abundant heterocyclic structural
motifs in drug discovery.1,2 Therefore, a continued strong demand
exists for the development of generally applicable syntheses of this
heteroarene.1–5 While the preparation of regioselectively substituted
indole derivatives remains challenging via classical methods,
significant progress has been accomplished more recently through
transition metal-catalysis.6–13 Despite these advances the synthesis
of indoles displaying sterically hindered N-substituents continued to
constitute a considerable challenge. Indeed, for example, simple
substitution reactions at nitrogen of free (NH)-indoles are hampered
by their relatively low nucleophilicities. A remarkable breakthrough
was, however, recently achieved by Willis through an application of
his elegantly developed N-annulation strategy14 to the conversion of
dihalogenated styrenes 1 with sterically demanding primary amines
2 (Scheme 1).15
R2
R2
O
R3
R1
+
R1
R3
H2N
µW, DMF
R3
N
F
240 °C, 1-2 h
R3
R3
R3
4
2
3
Scheme 2. Microwave-assisted synthesis of indoles 3.
In recent years, we exploited alkenyl or aryl vic-dihalides for
modular syntheses of heteroarenes, such as inter alias pyrroles17 or
benzo[b]furans.18 Furthermore, we established reaction conditions
for palladium-19,20 or copper-catalyzed19,21 syntheses of diversely
substituted indoles22 starting from ortho-alkynylhaloarenes 5.
Thus, reaction sequences involving intermolecular N-arylations23
and intramolecular hydroaminations24,25 set the stage for efficient
approaches to N-substituted indoles (Scheme 3).
5 mol% Pd(OAc)2
R2
12 mol% HP(t-Bu)3BF4
R1
+
R1
R2
H2N
X
NaOt-Bu, PhMe
R2
N
Br
130 °C, 4 h
R2
R2
R2
R2
cat. [TM]
R1
H2N R3
R1
R2
+
1
2
3
base, solvent
N
X
R3
Scheme 1. Palladium-catalyzed N-annulation route to indoles
demanding N-substituents.
3 with sterically
5
2
3
Scheme 3. Palladium-catalyzed N-arylation/hydroamination sequence for indole
syntheses.
Thereafter, Schirok devised a transition metal-free microwave-
assisted protocol for the preparation of N-sec- and N-tert-alkylated
indoles 3.16 Thus, ortho-(fluoroaryl)oxiranes 4 served as substrates
for a domino reaction relying on an intermolecular ring opening of
an oxirane, an intramolecular nucleophilic aromatic substitution
Given the important biological activities of indoles with steri-
cally hindered N-substituents,26 we became interested in employ-
ing our protocol for the more challenging conversion of bulky alkyl
amines.27 Herein, we wish to present a full account on a modular
palladium-catalyzed sequential synthesis of indoles displaying
sterically hindered substituents, which also proved broadly appli-
cable to the use of less nucleophilic anilines.
* Corresponding author. Tel.: þ49 (0)551 393202; fax: þ49 (0)551 396777.
E-mail address: lutz.ackermann@chemie.uni-goettingen.de (L. Ackermann).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.07.073

L. Ackermann et al. / Tetrahedron 65 (2009) 8930–8939
8931
2. Results and discussion
Table 2
Palladium-catalyzed sequential synthesis of indoles using amine 2aa
In initial studies, we probed in situ generated palladium com-
plexes derived from various phosphine or N-heterocyclic car-
bene28,29 ligands for the challenging preparation of indole 3aa
(Table 1). Unfortunately, diphosphines 6 and 7 provided only un-
satisfactory conversions of sterically demanding amine 2a (entries
2 and 3). On the contrary, electron-rich monophosphines 8, and 9a–
d30 led to improved isolated yields of desired product 3aa (Fig. 1,
and entries 4–8).
R2
5.0 mol% Pd(OAc)2
X
X
5.0 mol% 13
R1
+
(1-Ad)NH2
R1
R2
KOt-Bu, PhMe,
N
Cl
105-120 °C, 14 h
5
2a
3
Entry R1
R2
X
Isolated
yield (%)
Table 1
Optimization of the palladium catalysta
n-Bu
5.0 mol% Pd(OAc)2
n-Hex
5.0 mol% (pre)ligand
N
3ab 59b
3ac 80b
3ad 83
3ae 88
+
n-Bu
1
2
3
4
H
H
H
H
n-Hex
c-Pr
Ph
CH 5b
CH 5c
CH 5d
H2N
KOt-Bu, PhMe
105 °C, 12 h
N
Cl
N
5a
2a
3aa
Entry
(Pre)ligand
Isolated yield (%)
1
2
3
4
5
6
7
8
d
d
6
7
d
d
5b
38
30
51
59
45
Ph
dppf
BINAP
PCy3
N
8
R1¼i-Pr, R2¼H, R3¼H, R4¼H
R1¼Cy, R2¼NMe2, R3, R4¼H
R1¼Cy, R2, R3¼OMe, R4¼H
R1¼Cy, R2, R3, R4¼i-Pr
9a
9b
9c
9d
n-Pr
N
N
4-n-PrC6H4 CH 5e
4-MeOC6H4 CH 5f
4-CF3C6H4 CH 5g
Me
Cl
Me
Me
Me
9
10
11
d
N
N
Me
Me
OMe
CF3
Me Me
Cl
N
5
6
H
H
3af 79
Me
Me
10
9b
N
Me
Me
Me
Me
Me
Me
N
3ag 83
Cl
Cl
11
12
12
13
39
62
N
N
N
Me
Me
Me
Me
Me
Me
N
Me
Me
F
Me
N
7
8
9
H
4-FC6H4
CH 5h
3ah 94
3ai 55
3aj 94
Me
Me
13
74c
Me
MeO
a
n-Pr
Reaction conditions: 1a (0.5 mmol), 2a (0.6 mmol), Pd(OAc)2 (5.0 mol %),
(pre)ligand (5.0 mol %), KOt-Bu (1.5 mmol), PhMe (1.5 mL), 105 ꢀC, 12 h; yields of
isolated products.
N
4-MeO 4-n-PrC6H4 CH 5i
b
GC-conversion.
c
120 ꢀC.
Ph
N
Me
5-Me Ph
CH 5j
P(R1)2
R2
R3
N
Ph
R4
9
N
10
H
Ph
N
5k
3ak 46c
Figure 1. General structure of biaryl monophosphine ligands 9.
a
Reaction conditions: 5 (0.5–1.0 mmol), 2a (0.6–1.2 mmol), Pd(OAc)2 (5.0 mol %),
13 (5.0 mol %), KOt-Bu (1.5–3.0 mmol), PhMe (1.5–3.0 mL), 120 ꢀC, 14 h.
However, superior results were accomplished when using
N-heterocyclic carbene precursors. Interestingly, palladium com-
plexes derived from imidazolinium chlorides 10 and 12 (entries 9
b
105 ꢀC.
c
GC-conversion.

8932
L. Ackermann et al. / Tetrahedron 65 (2009) 8930–8939
Ph
and 11) displayed considerably lower catalytic activities than the
ones generated from the corresponding imidazolium salts 11 and
13, respectively (entries 10 and 12). Thus, optimal yields were
obtained with sterically hindered unsaturated imidazolium salt 13
as preligand (entry 12). The isolated yield of product 3aa was further
found improved at a slightly higher reaction temperature (entry 13).
With this optimized catalytic system in hand, we explored its
scope in the synthesis of indoles 3 using sterically hindered amine
1-AdNH2 (2a) as starting material (Table 2). Thus, alkyl-substituted
alkynes 5b and 5c yielded efficiently the desired products 3ab and
3ac, respectively (entries 1 and 2). Additionally, differently aryl-
substituted derivatives 5d–k enabled the regioselective synthesis
of the corresponding indoles (entries 3–9), notably, including
azaindole 3ak (entry 10). On the contrary, a TMS-substituted alkyne
did not deliver the corresponding 2-silylated indole.
Our protocol was not restricted to the use of amine 2a as ste-
rically hindered coupling partner, but allowed for an efficient in-
dole formation also with bulky t-BuNH2 (2b) (Table 3). Thereby,
products 3 bearing either aliphatic (entries 1 and 2) or aromatic
groups (entries 3–6) in position C-2 were obtained selectively.
Generally, slightly lower yields of indoles 3 were obtained in
transformations of alkynes 5 with primary alkyl-substituents,
which was due to an incomplete intramolecular hydroamination of
the quantitatively formed secondary amine.
5.0 mol% Pd(OAc)2
5.0 mol% 13
+
t-BuNH3Cl
Ph
KOt-Bu, PhMe,
N
Cl
120 °C, 14 h
Me
74%
Me
Me
5d
14
3an
Scheme 4. Indole synthesis with ammonium salt 14.
Likewise, sterically hindered amine 2c turned out to be a suit-
able substrate for N-annulations, thereby, providing indoles 3ar–au
(Table 4).
Table 4
Palladium-catalyzed sequential indole synthesis with amine 2ca
R
5.0 mol% Pd(OAc)2
13
5.0 mol%
+
t-PentNH2
R
KOt-Bu, PhMe,
N
Cl
120 °C, 14 h
Me
Me
Me
5
2c
3
Entry
1
R
Isolated yield (%)
43
Table 3
Scope of palladium-catalyzed indole synthesis with amine 2ba
n-Bu
R2
N
5.0 mol% Pd(OAc)2
n-Bu
5a
3ar
3as
3at
Me
Me
5.0 mol% 13
R1
R1
+
t-BuNH2
R2
KOt-Bu, PhMe,
Me
N
Cl
105-120 ° C,14 h
Me
Me
n-Pr
Me
N
Me
N
5
2b
3
2
3
4-n-PrC6H4
5e
5g
92
80
Me
Me
Entry R1
R2
Isolated
yield (%)
CF3
n-Bu
Me
4-CF3C6H4
Me
Me
N
1
H
n-Bu
5a
3al
63
Me
Me
Me
Me
N
2
3
H
H
c-Pr
5c
3am 87
4
3-MeC6H4
5l
3au
85
N
Me
Me
Me
Me
Me
Me
Ph
a
N
Ph
5d
3an
55
Conditions:
5 (0.5–1.0 mmol), 2c (0.6–1.2 mmol), Pd(OAc)2 (5.0 mol %), 13
(5.0 mol %), KOt-Bu (1.5–3.0 mmol), PhMe (3.0–6.0 mL), 120 ꢀC, 14 h.
Me
Me
Me
-Pr
Considering the remarkable efficacy of our catalytic system in
the synthesis of N-alkyl-substituted indoles, we became interested
in submitting sterically demanding aniline derivatives to the opti-
mized reaction conditions (Table 5). Thus, less nucleophilic amines
2d and 2e led to 2-alkyl- (entries 1 and 2) or 2-aryl-substituted
indoles 3 (entries 3–11) in high yields. Interestingly, excellent che-
moselectivies were observed when using substrate 5m bearing an
unprotected hydroxyl-group (entries 10, and 11), a valuable asset for
further applications of our protocol to sustainable syntheses of se-
rotonin analogues. Additionally, pyridine 5n provided direct access
to 4-azaindole 3bf through our N-annulation strategy (entry 12).
Various naturally occurring indole derivatives feature reverse-
prenyl substituents. For example, fungal natural products asterriqui-
nones26 exhibitvaluable biologicaldincluding antitumourdactivities,
and are decorated with an N-reverse-prenyl group. As a consequence,
we submitted amine 2fto our optimized reaction conditions, and were
delighted to observe the regioselective formation of indole 3bh
(Scheme 5).
n
4
5
6
H
4-n-PrC6H4 5e
3ao 84b
3ap 65b
3aq 90b
N
Me
Me
Me
MeO
n-Pr
4-MeO 4-n-PrC6H4 5i
N
Me
Me
Me
Ph
Me
N
5-Me
Ph
5j
Me
Me
Me
a
Conditions:
5
(0.5–1.0 mmol), 2b (0.6–3.0 mmol), Pd(OAc)2 (5.0 mol %), 13
(5.0 mol %), KOt-Bu (1.5–3.0 mmol), PhMe (1.5–3.0 mL), 105 ꢀC, 14 h.
b
120 ꢀC.
Given the relatively low boiling point of amine 2b, we were
delighted to note that ammonium salt 14 could be employed as
a more convenient N-nucleophile as well (Scheme 4).

L. Ackermann et al. / Tetrahedron 65 (2009) 8930–8939
8933
Table 5
Palladium-catalyzed preparation of indoles 3 with sterically hindered anilines 2a
R2
5.0 mol% Pd(OAc)2
X
X
5.0 mol% 13
R1
R1
R2
R3
+
H2NAr
KOt-Bu, PhMe,
N
Cl
105-120 °C, 14 h
R3
R4
5
2
3
Entry
R1
R2
X
Ar
Isolated yield (%)
N
Me
1
H
c-Pr
CH
CH
5c
5c
2,4,6-Me3C6H2
2d
2e
3av
85b
Me
Me
N
82b
91
94
95
i-Pr
2
3
4
5
H
H
H
H
c-Pr
2,6-(i-Pr)2C6H3
2,4,6-Me3C6H2
2,6-(i-Pr)2C6H3
2,4,6-Me3C6H2
3aw
i-Pr
Ph
Me
N
Ph
CH
CH
CH
5d
5d
5e
2d
2e
2d
3ax
3ay
3az
Me
Me
Ph
i-Pr
N
Ph
i-Pr
n-Pr
N
Me
4-n-PrC6H4
Me
Me
n-Pr
N
6
7
H
H
4-n-PrC6H4
CH
CH
5e
5l
2,6-(i-Pr)2C6H3
2e
2d
3ba
3bb
88
91
i-Pr
i-Pr
Me
N
3-MeC6H4
2,4,6-Me3C6H2
Me
Me
Me
Ph
Me
N
Me
8
9
5-Me
5-Me
Ph
Ph
CH
CH
5j
5j
2,4,6-Me3C6H2
2d
2e
3bc
3bd
56
Me
Me
Ph
i-Pr
N
Me
2,6-(i-Pr)2C6H3
91
i-Pr
(continued on next page)

8934
L. Ackermann et al. / Tetrahedron 65 (2009) 8930–8939
Table 5 (continued )
Entry
R1
R2
X
Ar
Isolated yield (%)
HO
Ph
Me
N
10
4-OH
Ph
CH
5m
5m
2,4,6-Me3C6H2
2d
2e
3be
3bf
75
Me
Me
Ph
HO
N
11
4-OH
6-CF3
Ph
CH
2,6-(i-Pr)2C6H3
71
i-Pr
i-Pr
F3C
N
Ph
i-Pr
N
12
Ph
N
5n
2,6-(i-Pr)2C6H3
2e
3bg
64b,c
i-Pr
a
Reaction conditions: 5 (0.5–1.0 mmol), 2 (0.6–1.2 mmol), Pd(OAc)2 (5.0 mol %), 13 (5.0 mol %), KOt-Bu (1.5–3.0 mmol), PhMe (1.5–6.0 mL), 120 ꢀC, 14 h.
b
c
105 ꢀC.
GC-conversion.
at 120 ꢀC. Then, H2O (25 mL) was added at ambient temperature.
The aqueous layer was extracted with Et2O (3ꢁ30 mL), the com-
bined organic layers were dried over Na2SO4 and concentrated in
vacuo. The remaining residue was purified by column chromatog-
raphy on silica gel (n-hexane/n-hexane/EtOAc 100:1) to yield 3aa
(113 mg, 74%) as a white solid. Mp: 143–145 ꢀC. 1H NMR (300 MHz,
n-Bu
5.0 mol% Pd(OAc)2
5.0 mol% 13
n-Bu
+
Me
Me
H2N
KOt-Bu, PhMe
105 °C, 14 h
53%
N
Cl
Me
Me
CDCl3):
d
7.77 (d, J¼8.1 Hz, 1H), 7.51–7.48 (m, 1H), 7.08–6.98 (m,
5a
2f
3bh
2H), 6.29 (s,1H), 3.01 (t, J¼7.2 Hz, 2H), 2.59 (d, J¼3.0 Hz, 6H), 2.27 (s,
3H), 1.81–1.68 (m, 8H), 1.49–1.39 (m, 2H), 0.98 (t, J¼7.2 Hz, 3H). 13C
Scheme 5. Synthesis of indole 3bh bearing an N-reverse-prenyl group.
NMR (125 MHz, CDCl3):
d 142.8, 136.4, 129.2, 119.8, 119.3, 118.4,
115.2, 103.0, 61.0, 42.3, 36.4, 33.2, 32.0, 30.3, 22.9, 14.2. IR (KBr):
3429, 2918, 2855, 2361, 2337,1653,1457, 777, 746, 731 cmꢂ1. MS (EI)
m/z (relative intensity): 307 (22) [Mþ], 265 (6), 135 (100), 107 (5).
HRMS (ESI) m/z calcd for C22H30N 308.2373, found 308.2374.
3. Conclusions
In summary, we disclosed a protocol for a modular synthesis of
(aza)indoles bearing sterically hindered aliphatic or aromatic
N-substituents. Namely, a palladium-catalyzed reaction sequence
consisting of an intermolecular N-arylation and an intramolecular
hydroamination allowed for a regioselective N-annulation, which
proved applicable to the preparation of an N-reverse-prenyl-
substituted indole.
4.3. 1-(1-Adamantyl)-2-n-hexyl-1H-indole (3ab)
Following the general procedure, 2a (184 mg, 1.20 mmol), 5b
(220 mg, 1.00 mmol), 13 (21.2 mg, 0.05 mmol), Pd(OAc)2 (11.2 mg,
0.05 mmol), KOt-Bu (336 mg, 3.00 mmol) were stirred in PhMe
(3.0 mL) for 12 h at 105 ꢀC. Indole 3ab (200 mg, 59%) was obtained
as a white solid after purification by column chromatography on
silica gel (n-hexane). Mp: 129–131 ꢀC. 1H NMR (300 MHz, CDCl3):
4. Experimental section
4.1. General
d
7.77 (md, J¼7.8 Hz, 1H), 7.51–7.48 (m, 1H), 7.08–6.98 (m, 2H), 6.29
(s, 1H), 3.00 (t, J¼7.6 Hz, 2H), 2.59 (d, J¼3.0 Hz, 6H), 2.27 (s, 3H),
All reactions were carried out on a 0.5–1.0 mmol scale under N2
using pre-dried glassware. Chemicals were obtained from com-
mercial sources, and were used without further purification. PhMe
was distilled from sodium under nitrogen and stored over molec-
ular sieves (4 Å). Yields refer to isolated compounds, estimated to
be >95% pure as determined by 1H NMR and GC. Flash chroma-
tography: Merck silica gel 60 (230–400 mesh). NMR: Spectra were
recorded on a Varian Unity 300, Varian Mercury 300, or a Varian
1.88–1.69 (m, 8H), 1.46–1.32 (m, 6H), 0.92 (t, J¼7.2 Hz, 3H). 13C NMR
(75 MHz, CDCl3):
d 143.0, 136.4, 129.2, 119.9, 119.4, 118.5, 115.3,
102.9, 61.0, 42.2, 36.3, 32.2, 31.8, 30.9, 30.2, 29.4, 22.6, 14.1. IR (KBr):
3419, 2959, 2915, 2852, 2361, 1653, 1457, 772, 744, 729 cmꢂ1. MS
(EI) m/z (relative intensity): 335 (23) [Mþ], 265 (8),135 (100). HRMS
(ESI) m/z calcd for C24H34N 336.2686, found 336.2686.
Inova 500 in the solvent indicated; chemical shifts (d) are given in
parts per million, coupling constants (J) in hertz.
4.4. 1-(1-Adamantyl)-2-cyclopropyl-1H-indole (3ac)
Following the general procedure, 2a (91.0 mg, 1.20 mmol), 5c
(87.0 mg, 0.494 mmol), 13 (10.6 mg, 0.025 mmol), Pd(OAc)2
(5.6 mg, 0.025 mmol), KOt-Bu (168 mg, 1.50 mmol) were stirred in
PhMe (1.5 mL) for 14 h at 105 ꢀC. Indole 3ac (117 mg, 80%) was
obtained as a white solid after purification by column chromato-
graphy on silica gel (n-hexane). Mp: 211.4 ꢀC. 1H NMR (300 MHz,
4.2. Representative procedure for palladium-catalyzed indole
synthesis: 1-(1-adamantyl)-2-n-butyl-1H-indole (3aa)
To a suspension of 2a (91.0 mg, 0.60 mmol), Pd(OAc)2 (5.6 mg,
0.025 mmol), 13 (10.6 mg, 0.025 mmol) and KOt-Bu (168 mg,
1.50 mmol) in dry PhMe (1.5 mL) was added 5a (96.0 mg,
0.50 mmol) and the resulting reaction mixture was stirred for 14 h
CDCl3):
d 7.78–7.75 (m, 1H), 7.50–7.47 (m, 1H), 7.10–6.98 (m, 2H),
6.23 (s, 1H), 2.71 (d, J¼3.0 Hz, 6H), 2.28 (s, 3H), 2.21–2.12 (m, 1H),

L. Ackermann et al. / Tetrahedron 65 (2009) 8930–8939
8935
1.90–1.78 (m, 6H), 0.99–0.83 (m, 4H). 13C NMR (75 MHz, CDCl3):
143.7, 136.4, 128.7, 120.2, 119.8, 118.5, 115.0, 102.5, 60.7, 42.1, 36.3,
30.2, 13.5, 9.7. IR (KBr): 2913, 2361, 2338, 1653, 1635, 1558, 1540,
1457, 1314, 1271, 1228, 1100, 727 cmꢂ1. MS (EI) m/z (relative in-
tensity): 291 (44) [Mþ], 156 (2), 135 (100), 107 (7), 93 (11), 79 (14).
HRMS (ESI) m/z calcd for C21H26N 292.2060, found 292.2060.
(3.0 mL) for 14 h at 120 ꢀC. Indole 3ag (167 mg, 83%) was obtained
as a white solid after purification by column chromatography on
silica gel (n-pentane/Et2O 100:1). Mp: 205 ꢀC (decomp.). 1H NMR
d
(300 MHz, CDCl3):
d 7.84–7.82 (m, 1H), 7.60–7.50 (m, 5H), 7.20–7.07
(m, 2H), 6.28 (d, J¼0.6 Hz, 1H), 2.26 (d, J¼3.3 Hz, 6H), 2.11 (s, 3H),
1.73–1.63 (m, 6H). 13C NMR (75 MHz, CDCl3):
d 142.5, 139.7, 136.9,
130.2, 129.4 (2JC–F¼32 Hz), 129.0, 124.3 (3JC–F¼4 Hz), 124.2 (1JC–F
¼
4.5. 1-(1-Adamantyl)-2-phenyl-1H-indole (3ad)
272 Hz), 120.8, 120.8, 119.6, 115.8, 107.6, 61.0, 43.6, 36.1, 30.2. 19F
NMR (275 MHz, CDCl3):
d
ꢂ62.4 (s). IR (Nujol): 2921, 2361, 2338,
Following the general procedure, 2a (91.0 mg, 0.60 mmol), 5d
(102 mg, 0.481 mmol), 13 (10.6 mg, 0.025 mmol), Pd(OAc)2 (5.6 mg,
0.025 mmol), KOt-Bu (168 mg, 1.50 mmol) were stirred in PhMe
(3.0 mL) for 14 h at 120 ꢀC. Indole 3ad (131 mg, 83%) was obtained
as a white solid after purification by column chromatography on
silica gel (n-hexane/Et2O 100:1). Mp: 200–201 ꢀC. 1H NMR
1734, 1717, 1699, 1653, 1558, 1506, 1458, 1377, 1162, 722 cmꢂ1. MS
(EI) m/z (relative intensity): 396 (25) [Mþ], 368 (2), 311 (4), 261 (4),
233 (4), 204 (2), 188 (4), 135 (100), 119 (16). HRMS (ESI) m/z calcd
for C25H25NF3 396.1934, found 396.1932.
4.9. 1-(1-Adamantyl)-2-(4-fluorophenyl)-1H-indole (3ah)
(300 MHz, CDCl3): d 7.84–7.82 (m, 1H), 7.59–7.55 (m, 1H), 7.42–7.38
(m, 2H), 7.35–7.32 (m, 3H), 7.15–7.06 (m, 2H), 6.28 (s, 1H), 2.30 (d,
Following the general procedure, 2a (91.0 mg, 0.60 mmol), 5h
(122 mg, 0.530 mmol), 13 (10.6 mg, 0.025 mmol), Pd(OAc)2 (5.6 mg,
0.025 mmol), KOt-Bu (168 mg, 1.50 mmol) were stirred in PhMe
(3.0 mL) for 14 h at 120 ꢀC. Indole 3ah (173 mg, 94%) was obtained
as a white solid after purification by column chromatography on
silica gel (n-pentane/Et2O 100:1). Mp: 210 ꢀC (decomp.). 1H NMR
J¼3.0 Hz, 6H), 2.09 (s, 3H), 1.72–1.63 (m, 6H). 13C NMR (75 MHz,
CDCl3):
d 141.5, 138.7, 136.5, 130.2, 129.2, 127.3, 127.2, 120.6, 120.3,
119.3, 115.7, 106.7, 60.9, 43.5, 36.2, 30.2. IR (KBr): 3420, 2901, 2849,
2361, 2339, 1653, 1448, 1296, 774, 736 cmꢂ1. MS (EI) m/z (relative
intensity): 327 (32) [Mþ], 193 (9), 165 (10), 135 (100), 11 (19). HRMS
(ESI) m/z calcd for C24H26N 328.2060, found 328.2060.
(300 MHz, CDCl3): d 7.83–7.80 (m, 1H), 7.57–7.54 (m, 1H), 7.27–7.32
(m, 2H), 7.15–6.93 (m, 4H), 6.26 (d, J¼0.6 Hz, 1H), 2.26 (d, J¼3.0 Hz,
4.6. 1-(1-Adamantyl)-2-(4-n-propylphenyl)-1H-indole (3ae)
6H), 2.10 (s, 3H), 1.72–1.67 (m, 6H). 13C NMR (75 MHz, CDCl3):
d
162.2 (1JC–F¼247 Hz), 140.2, 136.5, 134.6, 131.7 (4JC–F¼4 Hz), 130.8,
Following the general procedure, 2a (91.0 mg, 0.60 mmol), 5e
(127 mg, 0.50 mmol), 13 (10.6 mg, 0.025 mmol), Pd(OAc)2 (5.6 mg,
0.025 mmol), KOt-Bu (168 mg, 1.50 mmol) were stirred in PhMe
(3.0 mL) for 14 h at 120 ꢀC. Indole 3ae (162 mg, 88%) was obtained
as a white solid after purification by column chromatography on
silica gel (n-pentane/Et2O 100:1). Mp: 144–145 ꢀC. 1H NMR
129.0, 120.5 (3JC–F¼7 Hz), 119.3, 115.7, 114.2 (2JC–F¼22 Hz), 106.9,
60.9, 43.5, 36.2, 30.2. 19F NMR (275 MHz, CDCl3):
d
ꢂ114.7 (tt, J¼9.1,
5.4 Hz). IR (KBr): 2906, 2361, 2338, 1699, 1653, 1635, 1540, 1496,
1456, 1296, 847, 791, 737 cmꢂ1. MS (EI) m/z (relative intensity): 345
(52) [Mþ], 311 (1), 211 (6),183 (6),135 (100),107 (4). HRMS (ESI) m/z
calcd for C24H25NF 346.1966, found 346.1965.
(300 MHz, CDCl3): d 7.86–7.83 (m, 1H), 7.60–7.57 (m, 1H), 7.33–7.31
(m, 2H), 7.19–7.07 (m, 4H), 6.29 (d, J¼0.6 Hz, 1H), 2.66 (t, J¼7.2 Hz,
4.10. 1-(1-Adamantyl)-5-methoxy-2-(4-n-propylphenyl)-
1H-indole (3ai)
2H), 2.31 (d, J¼2.7 Hz, 6H), 2.11 (s, 3H), 1.75–1.65 (m, 8H), 0.99 (t,
J¼7.2 Hz, 3H). 13C NMR (125 MHz, CDCl3):
d 141.7, 141.6, 136.4, 135.8,
129.9, 129.1, 127.2, 120.5, 120.0, 119.1, 115.6, 106.4, 60.8, 43.3, 37.9,
36.3, 30.3, 24.5, 13.9. IR (film): 2960, 2912, 2854, 2361, 2253, 1499,
1450, 1335, 1296, 1103, 909, 738, 650 cmꢂ1. MS (ESI) m/z (relative
intensity): 370 (100) [MþHþ], 301 (2), 269 (6), 211 (4). HRMS (ESI)
m/z calcd for C27H32N 370.2535, found 370.2529.
Following the general procedure, 2a (91.0 mg, 0.60 mmol), 5i
(145 mg, 0.512 mmol), 13 (10.6 mg, 0.025 mmol), Pd(OAc)2 (5.6 mg,
0.025 mmol), KOt-Bu (168 mg, 1.50 mmol) were stirred in PhMe
(3.0 mL) for 14 h at 120 ꢀC. Indole 3ai (113 mg, 55%) was obtained as
a light yellow solid after purification by column chromatography on
silica gel (n-pentane/Et2O 100:1/50:1). Mp: 125–126 ꢀC. 1H NMR
4.7. 1-(1-Adamantyl)-2-(4-methoxyphenyl)-1H-indole (3af)
(300 MHz, CDCl3):
d
7.71 (d, J¼9.0 Hz, 1H), 7.31–7.28 (m, 2H), 7.14–
7.12 (m, 2H), 7.02 (d, J¼2.7 Hz, 1H), 6.80 (dd, J¼9.0, 2.7 Hz, 1H), 6.20
(s,1H), 3.85 (s, 3H), 2.64 (t, J¼7.5 Hz, 2H), 2.26 (d, J¼2.7 Hz, 6H), 2.08
(s, 3H), 1.72–1.63 (m, 8H), 0.97 (t, J¼7.5 Hz, 3H). 13C NMR (125 MHz,
Following the general procedure, 2a (91.0 mg, 0.60 mmol), 5f
(125 mg, 0.517 mmol), 13 (10.6 mg, 0.025 mmol), Pd(OAc)2 (5.6 mg,
0.025 mmol), KOt-Bu (168 mg, 1.50 mmol) were stirred in PhMe
(3.0 mL) for 14 h at 120 ꢀC. Indole 3af (147 mg, 79%) was obtained
as an off-white solid after purification by column chromatography
on silica gel (n-pentane/Et2O 50:1/20:1/5:1). Mp: 193–194 ꢀC.
CDCl3):
d 153.4, 142.1, 141.7, 135.7, 131.5, 129.9, 129.5, 127.1, 116.2,
110.2, 106.0, 101.8, 60.6, 55.7, 43.4, 37.8, 36.3, 30.3, 24.5, 13.9. IR
(film): 2912, 2253, 1616, 1466, 1435, 1358, 1342, 1302, 1215, 1162,
1121,1035, 909, 840, 737 cmꢂ1. MS (ESI) m/z (relative intensity): 822
(55) [2MþNaþ], 422 (33) [MþNaþ], 400 (100) [MþHþ], 284 (15).
HRMS (ESI) m/z calcd for C28H34NO 400.2640, found 400.2635.
1H NMR (300 MHz, CDCl3):
d 7.83–7.80 (m, 1H), 7.60–7.54 (m, 1H),
7.30 (ddd, J¼9.0, 5.1, 2.7 Hz, 2H), 7.14–7.05 (m, 2H), 6.86 (ddd, J¼8.7,
5.1, 3.0 Hz, 2H), 6.25 (d, J¼0.9 Hz, 1H), 3.85 (s, 3H), 2.28 (d, J¼3.0 Hz,
6H), 2.10 (s, 3H), 1.72–1.63 (m, 6H). 13C NMR (75 MHz, CDCl3):
4.11. 1-(1-Adamantyl)-6-methyl-2-phenyl-1H-indole (3aj)
d
158.9, 141.2, 136.3, 131.2, 130.9, 129.1, 120.4, 120.1, 119.1, 115.7,
112.6, 106.4, 60.8, 55.2, 43.3, 36.2, 30.2. IR (film): 2907, 2853, 2253,
1612, 1499, 1450, 1283, 1245, 1174, 1104, 1028, 908, 734 cmꢂ1. MS
(ESI) m/z (relative intensity): 358 (100) [MþHþ], 242 (13), 211 (5).
HRMS (ESI) m/z calcd for C25H28NO 358.2171, found 358.2165.
Following the general procedure, 2a (91.0 mg, 0.60 mmol), 5j
(113 mg, 0.513 mmol), 13 (10.6 mg, 0.025 mmol), Pd(OAc)2 (5.6 mg,
0.025 mmol), KOt-Bu (168 mg, 1.50 mmol) were stirred in PhMe
(3.0 mL) for 14 h at 120 ꢀC. Indole 3aj (164 mg, 94%) was obtained
as a pale brown solid after purification by column chromatography
on silica gel (n-pentane/Et2O 100:1). Mp: 176–177 ꢀC. 1H NMR
4.8. 1-(1-Adamantyl)-2-(4-trifluoromethylphenyl)-
1H-indole (3ag)
(300 MHz, CDCl3):
J¼7.8 Hz,1H), 6.26 (s,1H), 2.55 (s, 3H), 2.31 (s, 6H), 2.13 (s, 3H),1.71–
1.41 (m, 6H). 13C NMR (125 MHz, CDCl3):
140.8, 138.8, 137.0, 130.0,
129.6, 127.1, 127.1, 126.9, 120.8, 120.1, 115.7, 106.5, 60.7, 43.4, 36.3,
30.3, 22.5. IR (film): 3054, 3025, 2912, 2854, 2252, 1483, 1445, 1300,
d 7.65 (s, 1H), 7.50–7.33 (m, 6H), 6.96 (d,
Following the general procedure, 2a (91.0 mg, 0.60 mmol), 5g
(166 mg, 0.509 mmol), 13 (10.6 mg, 0.025 mmol), Pd(OAc)2 (5.6 mg,
0.025 mmol), KOt-Bu (168 mg, 1.50 mmol) were stirred in PhMe
d

8936
L. Ackermann et al. / Tetrahedron 65 (2009) 8930–8939
1262, 1103, 1028, 909, 805, 734 cmꢂ1. MS (EI) m/z (relative in-
tensity): 341 (67) [Mþ], 235 (3), 206 (18), 179 (5), 135 (100), 107 (4),
93 (11). HRMS (ESI) m/z calcd for C25H28N 342.2216, found
342.2217.
119.2, 114.9, 105.9, 58.8, 37.8, 32.0, 24.5, 13.8. IR (film): 2962, 2933,
2873, 2246, 1499, 1450, 1336, 1293, 1202, 1024, 909, 789, 735,
650 cmꢂ1. MS (EI) m/z (relative intensity): 291 (28) [Mþ], 235 (100),
217 (1), 206 (60), 178 (4), 165 (1). HRMS (ESI) m/z calcd for C21H26
N
292.2060, found 292.2061.
4.12. 1-tert-Butyl-2-n-butyl-1H-indole (3al)
4.16. 1-tert-Butyl-5-methoxy-2-(4-n-propylphenyl)-
1H-indole (3ap)
Following the general procedure, 2b (262 mg, 3.00 mmol), 5a
(192 mg, 1.00 mmol), 13 (21.2 mg, 0.05 mmol), Pd(OAc)2 (11.2 mg,
0.05 mmol), KOt-Bu (336 mg, 3.00 mmol) were stirred in PhMe
(3.0 mL) for 12 h at 105 ꢀC. Purification by column chromatography
on silica gel (n-hexane) yielded indole 3al (144 mg, 63%) as an or-
Following the general procedure, 2b (44.0 mg, 0.60 mmol), 5i
(143 mg, 0.503 mmol), 13 (10.6 mg, 0.025 mmol), Pd(OAc)2 (5.6 mg,
0.025 mmol), KOt-Bu (168 mg, 1.50 mmol) were stirred in PhMe
(3.0 mL) for 14 h at 120 ꢀC. Indole 3ap (104 mg, 65%) was obtained
as a yellow solid after purification by column chromatography on
silica gel (n-pentane/Et2O 100:1/50:1). Mp: 75–76 ꢀC. 1H NMR
ange oil. 1H NMR (300 MHz, C6D6):
d 7.67–7.64 (m, 1H), 7.57–7.54
(m, 1H), 7.19–7.12 (m, 2H), 6.33 (d, J¼0.9 Hz, 1H), 2.73 (t, J¼9.0 Hz,
2H), 1.64–1.54 (m, 2H), 1.45 (s, 9H), 1.33–1.20 (m, 2H), 0.85 (t,
J¼7.5 Hz, 3H). 13C NMR (75 MHz, C6D6):
d
142.5, 138.0, 130.2, 120.5,
(300 MHz, CDCl3):
d
7.62–7.59 (m, 1H), 7.30 (ddd, J¼8.1, 3.6, 1.8 Hz,
120.4, 119.2, 114.8, 103.8, 58.5, 33.1, 31.6, 31.4, 23.0, 14.1. IR (film):
2957, 2930, 2871, 1653, 1455, 1400, 1369, 1287, 776, 732 cmꢂ1. MS
(EI) m/z (relative intensity): 229 (5) [Mþ], 173 (5), 131 (18). HRMS
(ESI) m/z calcd for C16H24N 230.1903, found 230.1905.
2H), 7.15 (ddd, J¼8.0, 3.5,1.8 Hz, 2H), 7.03 (d, J¼2.4 Hz,1H), 6.82 (dd,
J¼9.0, 2.7 Hz, 1H), 6.22 (d, J¼0.6 Hz, 1H), 3.85 (s, 3H), 2.64 (t,
J¼7.5 Hz, 2H), 1.78–1.62 (m, 2H), 1.57 (s, 9H), 0.97 (t, J¼7.2 Hz, 3H).
13C NMR (75 MHz, CDCl3):
d 153.5, 142.5, 141.9, 135.2, 132.3, 129.9,
129.4, 127.3, 115.5, 110.5, 105.5, 101.7, 58.7, 55.8, 37.8, 32.1, 24.5, 13.9.
IR (film): 2960, 2933, 2873, 2361, 2253, 1466, 1344, 1297, 1214, 1130,
1043, 907, 735, 650 cmꢂ1. MS (ESI) m/z (relative intensity): 344
(100) [MþNaþ], 322 (51) [MþHþ], 266 (91), 167 (10). HRMS (ESI) m/z
calcd for C22H28NO 322.2171, found 322.2165.
4.13. 1-tert-Butyl-2-cyclopropyl-1H-indole (3am)
Following the general procedure, 2b (44.0 mg, 0.60 mmol), 5c
(84.0 mg, 0.48 mmol), 13 (10.6 mg, 0.025 mmol), Pd(OAc)2 (5.6 mg,
0.025 mmol), KOt-Bu (168 mg, 1.50 mmol) were stirred in PhMe
(1.5 mL) for 14 h at 105 ꢀC. Indole 3am (89 mg, 87%) was obtained
as a colourless oil after purification by column chromatography on
4.17. 1-tert-Butyl-6-methyl-2-phenyl-1H-indole (3aq)
silica gel (n-pentane). 1H NMR (300 MHz, CDCl3):
d
7.69–7.66 (m,
Following the general procedure, 2b (44.0 mg, 0.60 mmol), 5j
(117 mg, 0.518 mmol), 13 (10.6 mg, 0.025 mmol), Pd(OAc)2 (5.6 mg,
0.025 mmol), KOt-Bu (168 mg, 1.50 mmol) were stirred in PhMe
(3.0 mL) for 14 h at 120 ꢀC. Indole 3aq (123 mg, 90%) was obtained
as a pale yellow solid after purification by column chromatography
on silica gel (n-pentane/Et2O 100:1). Mp: 136 ꢀC. 1H NMR
1H), 7.51–7.48 (m, 1H), 7.11–7.00 (m, 2H), 6.24 (s, 1H), 2.16–2.04 (m,
1H), 1.94 (s, 9H), 1.01–0.84 (m, 4H). 13C NMR (75 MHz, CDCl3):
d
143.9, 137.1, 128.5, 120.1, 120.0, 118.6, 114.3, 102.3, 58.7, 31.3, 13.0,
9.5. IR (film): 3053, 2986, 2361, 1456, 1420, 1371, 1304, 1265, 1204,
896, 739, 705 cmꢂ1. MS (ESI) m/z (relative intensity): 236 (9)
[MþNaþ], 214 (36) [MþHþ], 158 (100). HRMS (ESI) m/z calcd for
C15H20N 214.1596, found 214.1590.
(300 MHz, CDCl3):
d
7.54–7.34 (m, 7H), 6.98–6.95 (m, 1H), 6.27 (s,
141.2,
1H), 2.54 (s, 3H), 1.61 (s, 9H). 13C NMR (75 MHz, CDCl3):
d
138.3, 137.7, 130.1, 130.1, 127.3, 126.8, 126.8, 121.0, 120.1, 115.1, 106.0,
58.7, 32.0, 22.3. IR (film): 3421, 3003, 2968, 2918, 2356, 1653, 1540,
1443, 1332, 1206, 1104, 1028, 814, 705, 607 cmꢂ1. MS (EI) m/z (rel-
ative intensity): 263 (22) [Mþ], 235 (4), 220 (4), 207 (100), 178 (5),
152 (2). HRMS (ESI) m/z calcd for C19H21NNa 286.1566, found
286.1567. The spectral data are in accordance with those reported
in the literature.31
4.14. 1-tert-Butyl-2-phenyl-1H-indole (3an)
Following the general procedure, 2b (262 mg, 3.00 mmol), 5d
(212 mg, 1.00 mmol), 13 (21.2 mg, 0.05 mmol), Pd(OAc)2 (11.2 mg,
0.05 mmol), KOt-Bu (336 mg, 3.00 mmol) were stirred in PhMe
(3.0 mL) for 12 h at 105 ꢀC. Purification by column chromatography
on silica gel (n-hexane) yielded indole 3an (136 mg, 55%) as a white
solid. Mp: 105–107 ꢀC. 1H NMR (300 MHz, C6D6):
d
7.66–7.59 (m,
2H), 7.34–7.31 (m, 2H), 7.24–7.16 (m, 2H), 7.09–7.07 (m, 3H), 6.41 (s,
1H), 1.34 (s, 9H). 13C NMR (75 MHz, C6D6):
141.7, 138.8, 138.0,
130.4, 130.0, 127.9, 127.6, 121.2, 121.2, 119.9, 115.3, 107.1, 58.6, 31.9. IR
4.18. 2-n-Butyl-1-tert-pentyl-1H-indole (3ar)
d
Following the general procedure, 2c (104 mg, 1.19 mmol), 5a
(193 mg, 1.00 mmol), 13 (21.2 mg, 0.05 mmol), Pd(OAc)2 (11.2 mg,
0.05 mmol), KOt-Bu (337 mg, 3.00 mmol) were stirred in PhMe
(3.0 mL) for 14 h at 120 ꢀC. Purification by column chromatography
on silica gel (n-hexane/EtOAc 400:1) yielded indole 3ar (104 mg,
(KBr): 3441, 2362, 2339, 1653, 1635, 1450, 1292, 782, 736, 673 cmꢂ1
.
MS (EI) m/z (relative intensity): 249 (14) [Mþ], 193 (100), 165 (9).
HRMS (EI) m/z calcd for C18H19N 249.1517, found 249.1513. The
spectral data are in accordance with those reported in the
literature.31
43%) as a yellow oil. 1H NMR (300 MHz, CDCl3):
d 7.74–7.62 (m, 1H),
7.56–7.46 (m, 1H), 7.12–6.97 (m, 2H), 6.32 (s, 1H), 2.96 (t, J¼7.7 Hz,
2H), 2.19 (q, J¼7.3 Hz, 2H), 1.86 (s, 6H), 1.83–1.70 (m, 2H), 1.57–1.39
(m, 2H), 1.00 (t, J¼7.3 Hz, 3H), 0.69 (t, J¼7.3 Hz, 3H). 13C NMR
4.15. 1-tert-Butyl-2-(4-n-propylphenyl)-1H-indole (3ao)
(125 MHz, CDCl3):
d 143.7, 137.3, 129.1, 119.6, 119.6, 118.5, 114.2,
Following the general procedure, 2b (44.0 mg, 0.60 mmol), 5e
(128 mg, 0.504 mmol), 13 (10.6 mg, 0.025 mmol), Pd(OAc)2 (5.6 mg,
0.025 mmol), KOt-Bu (168 mg, 1.50 mmol) were stirred in PhMe
(3.0 mL) for 14 h at 120 ꢀC. Indole 3ao (122 mg, 84%) was obtained
as a pale yellow solid after purification by column chromatography
on silica gel (n-pentane/Et2O 100:1). Mp: 36.5 ꢀC. 1H NMR
102.5, 62.1, 34.6, 32.6, 31.4, 30.0, 22.9, 14.1, 8.8. IR (film): 3104, 3065,
2959, 2872, 1577, 1539, 1455, 1379, 1285, 1230, 1190, 1086, 1055,
1028, 922, 807, 776, 747, 732, 699 cmꢂ1. MS (EI) m/z (relative in-
tensity): 243 (48) [Mþ], 173 (31), 131 (100), 58 (17), 43 (62). HRMS
(ESI) m/z calcd for C17H26N 244.2060, found 244.2060.
(300 MHz, CDCl3):
d
7.79–7.76 (m, 1H), 7.64–7.61 (m, 1H), 7.38–7.35
4.19. 1-tert-Pentyl-2-(4-n-propylphenyl)-1H-indole (3as)
(m, 2H), 7.23–7.13 (m, 4H), 6.36 (d, J¼0.9 Hz, 1H), 2.69 (t, J¼7.5 Hz,
2H), 1.86–1.60 (m, 11H), 1.03 (t, J¼7.2 Hz, 3H). 13C NMR (75 MHz,
Following the general procedure, 2c (101 mg, 1.16 mmol), 5e
(257 mg, 1.01 mmol), 13 (21.2 mg, 0.05 mmol), Pd(OAc)2 (11.2 mg,
CDCl3):
d 142.0, 141.9, 137.1, 135.3, 130.0, 129.0, 127.4, 120.4, 120.4,

L. Ackermann et al. / Tetrahedron 65 (2009) 8930–8939
8937
0.05 mmol), KOt-Bu (365 mg, 2.98 mmol) were stirred in PhMe
(6.0 mL) for 14 h at 120 ꢀC. Purification by column chromatography
on silica gel (n-hexane/EtOAc 500:1) yielded indole 3as (282 mg,
772 cmꢂ1. MS (EI) m/z (relative intensity): 275 (100) [Mþ], 260 (8),
246 (33), 218 (10), 204 (2), 158 (5), 133 (7). HRMS (ESI) m/z calcd for
C20H22N 276.1747, found 276.1747.
92%) as a yellow oil. 1H NMR (300 MHz, CDCl3):
d
7.72 (d, J¼8.3 Hz,
1H), 7.61–7.54 (m, 1H), 7.36–7.28 (m, 2H), 7.21–7.05 (m, 4H), 6.29 (s,
1H), 2.64 (t, J¼7.5 Hz, 2H), 2.12 (q, J¼7.3 Hz, 2H), 1.69 (sext.,
J¼7.3 Hz, 2H), 1.48 (s, 6H), 0.97 (t, J¼7.3 Hz, 3H), 0.61 (t, J¼7.3 Hz,
4.23. 2-Cyclopropyl-1-(2,6-di-iso-propylphenyl)-
1H-indole (3aw)
3H). 13C NMR (125 MHz, CDCl3):
d
142.8, 141.9, 137.1, 135.4, 130.0,
Following the general procedure, 2e (106 mg, 0.60 mmol), 5c
(84.0 mg, 0.477 mmol), 13 (10.6 mg, 0.025 mmol), Pd(OAc)2
(5.6 mg, 0.025 mmol), KOt-Bu (168 mg, 1.50 mmol) were stirred in
PhMe (1.5 mL) for 14 h at 105 ꢀC. Indole 3aw (125 mg, 82%) was
obtained as a colourless solid after purification by column chro-
matography on silica gel (n-pentane). Mp: 124.6 ꢀC. 1H NMR
128.9, 127.3, 120.4, 120.3, 119.2, 114.7, 105.9, 62.1, 37.9, 34.6, 30.6,
24.5, 13.9, 8.6. IR (film): 3044, 3017, 2963, 2930, 2872, 1499, 1450,
1393, 1377, 1336, 1299, 1280, 1189, 1025, 844, 826, 756, 752, 734,
682 cmꢂ1. MS (EI) m/z (relative intensity): 305 (18) [Mþ], 235 (100),
206 (67), 178 (4), 43 (11). HRMS (ESI) m/z calcd for C22H28
N
306.2216, found 306.2217.
(300 MHz, CDCl3): d 7.57–7.46 (m, 2H), 7.34–7.31 (m, 2H), 7.10–6.98
(m, 2H), 6.77–6.75 (m, 1H), 6.12 (s, 1H), 2.30 (sept., J¼6.0 Hz, 2H),
4.20. 1-tert-Pentyl-2-(4-trifluoromethylphenyl)-
1H-indole (3at)
1.45–1.36 (m, 1H), 1.14 (d, J¼6.0 Hz, 6H), 0.97 (d, J¼6.0 Hz, 6H),
0.87–0.75 (m, 4H). 13C NMR (75 MHz, CDCl3):
d 148.6, 145.1, 138.5,
132.6, 129.4, 127.7, 123.9, 120.6, 119.7, 119.4, 110.1, 94.3, 28.1, 24.7,
23.7, 9.3, 7.8. IR (KBr): 2962, 2926, 2865, 2360, 2340, 1473, 1457,
1400, 1381, 1358, 1298, 1215, 805, 775, 737 cmꢂ1. MS (ESI) m/z
(relative intensity): 340 (5) [MþNaþ], 318 (100) [MþHþ], 223 (1),
163 (4). HRMS (ESI) m/z calcd for C23H28N 318.2222, found
318.2216.
Following the general procedure, 2c (52.0 mg, 0.60 mmol), 5g
(143 mg, 0.51 mmol), 13 (10.6 mg, 0.025 mmol), Pd(OAc)2 (5.6 mg,
0.025 mmol), KOt-Bu (168 mg, 1.50 mmol) were stirred in PhMe
(3.0 mL) for 14 h at 120 ꢀC. Purification by column chromatography
on silica gel (n-pentane/MTBE 200:1/150:1) yielded indole 3at
(146 mg, 80%) as a light yellow solid. Mp: 103–104 ꢀC. 1H NMR
(300 MHz, CDCl3):
d
7.74–7.71 (m, 1H), 7.62–7.51 (m, 5H), 7.21–7.09
4.24. 1-(2,4,6-Trimethylphenyl)-2-phenyl-1H-indole (3ax)
(m, 2H), 6.30 (d, J¼0.6 Hz, 1H), 2.12 (q, J¼7.5 Hz, 2H), 1.48 (s, 6H),
0.59 (t, J¼7.5 Hz, 3H). 13C NMR (75 MHz, CDCl3):
d
142.0,141.0,137.6,
Following the general procedure, 2d (81.0 mg, 0.60 mmol), 5d
(106 mg, 0.50 mmol), 13 (10.6 mg, 0.025 mmol), Pd(OAc)2 (5.6 mg,
0.025 mmol), KOt-Bu (168 mg, 1.50 mmol) were stirred in PhMe
(3.0 mL) for 14 h at 105 ꢀC. Indole 3ax (143 mg, 91%) was obtained
as a colourless oil after purification by column chromatography on
130.3, 129.6 (2JC–F¼33 Hz), 128.9, 124.3 (3JC–F¼4 Hz), 124.2 (1JC–F
¼
272 Hz),121.2, 120.6, 119.7,114.9, 107.0, 62.3, 34.5, 30.8, 8.5. 19F NMR
(275 MHz, CDCl3):
d
ꢂ62.4 (s). IR (KBr): 2973, 2938, 1931, 1804,
1614, 1448, 1378, 1299, 1098, 1062, 1021, 847, 784, 752, 736 cmꢂ1
.
MS (EI) m/z (relative intensity): 331 (14) [Mþ], 302 (1), 261 (100),
242 (4), 233 (4). HRMS (ESI) m/z calcd for C20H21NF3 332.1621,
found 332.1621.
silica gel (n-hexane). 1H NMR (300 MHz, CDCl3):
1H), 7.32–7.11 (m, 7H), 6.96 (s, 2H), 6.88–6.83 (m, 2H), 2.36 (s, 3H),
1.84 (s, 6H). 13C NMR (75 MHz, CDCl3):
140.5, 138.0, 137.9, 136.9,
d 7.72–7.69 (m,
d
133.8, 132.8, 129.2, 128.2, 128.2, 127.5, 127.2, 122.1, 120.3, 120.2,
110.5, 102.0, 21.1, 17.7. IR (film): 3053, 2985, 2305, 1653, 1558, 1489,
1457, 1375, 1322, 1265, 1210, 1029, 896, 857 cmꢂ1. MS (EI) m/z
(relative intensity): 311 (100) [Mþ], 296 (4), 218 (4), 140 (2). HRMS
(ESI) m/z calcd for C23H22N 312.1747, found 312.1747.
4.21. 1-tert-Pentyl-2-(3-methylphenyl)-1H-indole (3au)
Following the general procedure, 2c (103 mg, 1.18 mmol), 5l
(228 mg, 1.01 mmol), 13 (21.2 mg, 0.05 mmol), Pd(OAc)2 (11.2 mg,
0.05 mmol), KOt-Bu (336 mg, 3.00 mmol) were stirred in PhMe
(5.0 mL) for 14 h at 120 ꢀC. Purification by column chromatography
on silica gel (n-hexane/EtOAc 500:1) yielded indole 3au (236 mg,
4.25. 2-Phenyl-1-(2,6-di-iso-propylphenyl)-1H-indole (3ay)
85%) as a yellow oil. 1H NMR (300 MHz, CDCl3):
d
7.77–7.68 (m, 1H),
Following the general procedure, 2e (106 mg, 0.60 mmol), 5d
(106 mg, 0.500 mmol), 13 (10.6 mg, 0.025 mmol), Pd(OAc)2 (5.6 mg,
0.025 mmol), KOt-Bu (168 mg, 1.50 mmol) were stirred in PhMe
(3.0 mL) for 14 h at 120 ꢀC. Indole 3ay (167 mg, 94%) was obtained
as a colourless solid after purification by column chromatography
on silica gel (n-hexane). Mp: 83–84 ꢀC. 1H NMR (300 MHz, CDCl3):
7.62–7.54 (m, 1H), 7.30–7.05 (m, 6H), 6.28 (s, 1H), 2.38 (s, 3H), 2.12
(q, J¼7.6 Hz, 2H), 1.50 (s, 6H), 0.61 (t, J¼7.3 Hz, 3H). 13C NMR
(75 MHz, CDCl3):
d 142.9, 138.2, 137.2, 136.8, 130.9, 129.0, 128.2,
127.4, 127.1, 120.5, 120.4, 119.3, 114.8, 105.9, 62.1, 34.5, 30.6, 21.4, 8.5.
IR (film): 3014, 2970, 2935, 2877, 1606, 1450, 1393, 1373, 1338,1300,
1281, 1226, 1189, 1091, 1026, 784, 752, 735, 709 cmꢂ1. MS (EI) m/z
(relative intensity): 277 (14) [Mþ], 207 (100), 86 (5), 84 (8), 43 (4).
HRMS (ESI) m/z calcd for C20H23NNa 300.1723, found 300.1723.
d
7.71–7.68 (m, 1H), 7.49–7.44 (m, 1H), 7.29–7.24 (m, 4H), 7.22–7.07
(m, 5H), 6.93 (d, J¼0.9 Hz, 1H), 6.85–6.82 (m, 1H), 2.34 (sept.,
J¼6.0 Hz, 2H), 0.96 (d, J¼6.0 Hz, 6H), 0.84 (d, J¼6.0 Hz, 6H). 13C NMR
(75 MHz, CDCl3):
d 147.7, 140.8, 139.6, 133.6, 132.4, 129.4, 128.0,
4.22. 2-Cyclopropyl-1-(2,4,6-trimethylphenyl)-
1H-indole (3av)
127.7, 127.6, 127.1, 124.2, 121.9, 120.2, 120.2, 111.1, 101.8, 28.2, 25.1,
23.2. IR (KBr): 3048, 2961, 2925, 2866, 1487, 1458, 1442, 1352, 1331,
1176, 1055, 801, 747, 668 cmꢂ1. MS (EI) m/z (relative intensity): 353
(98) [Mþ], 338 (12), 310 (8), 280 (5), 220 (11), 204 (6), 165 (100), 105
(23). HRMS (ESI) m/z calcd for C26H28N 354.2216, found 354.2217.
Following the general procedure, 2d (81.0 mg, 0.60 mmol), 5c
(87.0 mg, 0.494 mmol), 13 (10.6 mg, 0.025 mmol), Pd(OAc)2
(5.6 mg, 0.025 mmol), KOt-Bu (168 mg, 1.50 mmol) were stirred in
PhMe (1.5 mL) for 14 h at 105 ꢀC. Indole 3av (117 mg, 85%) was
obtained as a colourless oil after purification by column chroma-
tography on silica gel (n-hexane). 1H NMR (300 MHz, CDCl3):
4.26. 2-(4-n-Propylphenyl)-1-(2,4,6-trimethylphenyl)-1H-
indole (3az)
d
7.57–7.54 (m, 1H), 7.10–7.00 (m, 4H), 6.77–6.74 (m, 1H), 6.16 (s,
1H), 2.39 (s, 3H), 1.88 (s, 6H), 1.45–1.38 (m, 1H), 0.84–0.72 (m, 4H).
13C NMR (75 MHz, CDCl3):
143.8, 138.1, 137.6, 137.0, 133.1, 128.9,
Following the general procedure, 2d (161 mg, 1.19 mmol), 5e
(256 mg, 1.00 mmol), 13 (21.2 mg, 0.05 mmol), Pd(OAc)2 (11.2 mg,
0.05 mmol), KOt-Bu (336 mg, 3.00 mmol) were stirred in PhMe
(6.0 mL) for 14 h at 120 ꢀC. Purification by column chromatography
on silica gel (n-hexane/EtOAc 500:1) yielded indole 3az (335 mg,
d
128.0, 120.7, 119.6, 119.6, 109.4, 95.3, 21.1, 17.4, 7.9, 7.5. IR (film):
3009, 2919, 1653, 1611, 1557, 1489, 1457, 1302, 1219, 1012, 883, 854,

8938
L. Ackermann et al. / Tetrahedron 65 (2009) 8930–8939
95%) as a white solid. Mp: 125 ꢀC. 1H NMR (300 MHz, CDCl3):
7.72–7.63 (m, 1H), 7.22–6.99 (m, 6H), 6.94 (s, 2H), 6.86–6.76 (m,
4.30. 6-Methyl-2-phenyl-1-(2,6-di-iso-propylphenyl)-
1H-indole (3bd)
d
2H), 2.52 (t, J¼8.3 Hz, 2H), 2.35 (s, 3H), 1.82 (s, 6H), 1.61 (sext.,
J¼7.5 Hz, 2H), 0.92 (t, J¼7.3 Hz, 3H). 13C NMR (75 MHz, CDCl3):
Following the general procedure, 2e (109 mg, 0.61 mmol), 5j
(114 mg, 0.51 mmol), 13 (21.2 mg, 0.025 mmol), Pd(OAc)2 (6.0 mg,
0.027 mmol), KOt-Bu (170 mg, 1.52 mmol) were stirred in PhMe
(1.5 mL) for 14 h at 120 ꢀC. Purification by column chromatography
on silica gel (n-pentane/Et2O 200:1) yielded indole 3bd (168 mg,
d
141.8, 140.7, 138.0, 137.1, 134.1, 130.2, 129.2, 128.4, 128.3, 127.3,
121.9, 120.2, 120.1, 110.4, 101.6, 37.7, 24.2, 21.1, 17.7, 13.8. IR (KBr):
3020, 2956, 2918, 2865, 2361, 1488, 1470, 1452, 1415, 1372, 1354,
1316, 1301, 857, 840, 827, 780, 750, 734, 611 cmꢂ1. MS (EI) m/z
(relative intensity): 353 (100) [Mþ], 324 (29), 57 (7), 43 (18). HRMS
(ESI) m/z calcd for C26H28N 354.2216, found 354.2215.
91%) as a yellow solid. Mp: 105 ꢀC. 1H NMR (300 MHz, CDCl3):
d 7.59
(d, J¼8.3 Hz, 1H), 7.48 (t, J¼7.5 Hz, 1H), 7.32–7.11 (m, 7H), 7.03–6.88
(m, 2H), 6.64 (s, 1H), 2.45–2.30 (m, 5H), 0.98 (d, J[6.8 Hz, 6H), 0.85
4.27. 2-(4-n-Propylphenyl)-1-(2,6-di-iso-propylphenyl)-
1H-indole (3ba)
(d, J[6.8 Hz, 6H). 13C NMR (125 MHz, CDCl3):
d 147.8, 140.2, 140.1,
133.7, 132.6, 131.8, 129.3, 128.0, 127.6, 126.9, 125.5, 124.2, 122.0,
119.8, 110.9, 101.7, 28.2, 25.1, 23.2, 21.9. IR (KBr): 2961, 2924, 2845,
1617, 1599, 1468, 1381, 1346, 1315, 1255, 1176, 1057, 812, 790, 759,
742, 693, 608, 589 cmꢂ1. MS (EI) m/z (relative intensity): 367 (100)
Following the general procedure, 2e (208 mg, 1.17 mmol), 5e
(253 mg, 0.99 mmol), 13 (21.2 mg, 0.05 mmol), Pd(OAc)2 (11.2 mg,
0.05 mmol), KOt-Bu (337 mg, 3.00 mmol) were stirred in PhMe
(6.0 mL) for 14 h at 120 ꢀC. Purification by column chromatography
on silica gel (n-hexane/EtOAc 500:1) yielded indole 3ba (348 mg,
88%) as a white solid. Mp: 104 ꢀC. 1H NMR (300 MHz, CDCl3):
[Mþ], 352 (7), 325 (14), 232 (5). HRMS (ESI) m/z calcd for C27H30
N
368.2373, found 368.2375.
4.31. 5-Hydroxy-2-phenyl-1-(2,4,6-trimethylphenyl)-
d
7.73–7.64 (m, 1H), 7.46 (t, J¼7.7 Hz, 1H), 7.32–6.76 (m, 10H), 2.49
(t, J¼7.2 Hz, 2H), 2.33 (sept., J¼7.2 Hz, 2H), 1.57 (sext., J¼7.7 Hz, 2H),
1.01–0.75 (m, 15H). 13C NMR (75 MHz, CDCl3):
147.9, 141.8, 141.1,
1H-indole (3be)
d
Following the general procedure, 2d (130 mg, 0.96 mmol), 5m
(177 mg, 0.77 mmol), 13 (16.3 mg, 0.039 mmol), Pd(OAc)2 (8.5 mg,
0.04 mmol), KOt-Bu (261 mg, 2.32 mmol) were stirred in PhMe
(1.0 mL) for 14 h at 120 ꢀC. Purification by column chromatography
on silica gel (n-hexane/EtOAc 15:1) yielded indole 3be (190 mg,
139.6, 129.8, 129.4, 128.2, 127.8, 127.7, 124.2, 121.7, 120.2, 120.1, 111.0,
101.3, 37.5, 28.1, 25.0, 24.3, 23.1, 13.7. IR (KBr): 3049, 2961, 2926,
2867, 1497, 1468, 1416, 1383, 1360, 1314, 1255, 1191, 829, 800, 784,
756, 746, 734, 608, 427 cmꢂ1. MS (EI) m/z (relative intensity): 395
(100) [Mþ], 267 (26), 252 (10), 236 (14), 191 (22), 165 (14), 111 (9),
97 (15), 91 (15), 69 (20), 57 (34), 43 (26). HRMS (ESI) m/z calcd for
C29H34N 396.2686, found 396.2684.
75%) as a brown solid. Mp: 72 ꢀC. 1H NMR (300 MHz, CDCl3):
d 7.28–
7.17 (m, 5H), 7.10–7.08 (m, 1H), 6.93 (s, 2H), 6.73 (s, 1H), 6.71–6.65
(m, 2H), 4.73 (br s, 1H), 2.33 (s, 3H), 1.82 (s, 6H). 13C NMR (75 MHz,
CDCl3):
d 149.8, 141.3, 138.0, 136.9, 133.9, 133.4, 132.7, 129.1, 128.7,
4.28. 2-(3-Methylphenyl)-1-(2,4,6-trimethylphenyl)-
1H-indole (3bb)
128.2, 127.3, 127.2, 111.7, 111.1, 104.7, 101.3, 21.2, 17.7. IR (KBr): 3059,
3027, 2951, 2917, 2855, 2733, 2361, 2338, 1650, 1619, 1580, 1539,
1465, 1372, 1279, 1211, 1139, 1027, 1028, 951, 867, 848, 793, 759, 735,
694, 601 cmꢂ1. MS (EI) m/z (relative intensity): 327 (100), 312 (16),
250 (9), 228 (8), 148 (5). HRMS (ESI) m/z calcd for C23H22NO
328.1696, found 328.1695.
Following the general procedure, 2d (163 mg, 1.21 mmol), 5l
(217 mg, 0.96 mmol), 13 (21.2 mg, 0.05 mmol), Pd(OAc)2 (11.2 mg,
0.05 mmol), KOt-Bu (338 mg, 3.01 mmol) were stirred in PhMe
(6.0 mL) for 14 h at 120 ꢀC. Purification by column chromatography
on silica gel (n-hexane/EtOAc 333:1) yielded indole 3bb (285 mg,
4.32. 5-Hydroxy-2-phenyl-1-(2,6-di-iso-propylphenyl)-
1H-indole (3bf)
91%) as a white solid. Mp: 90 ꢀC. 1H NMR (300 MHz, CDCl3):
d
7.72–
7.62 (m, 1H), 7.20–6.77 (m, 10H), 2.34 (s, 3H), 2.26 (s, 3H), 1.82 (s,
6H). 13C NMR (75 MHz, CDCl3):
140.7, 138.0, 137.9, 137.8, 137.0,
d
Following the general procedure, 2e (211 mg, 1.20 mmol), 5m
(229 mg, 1.00 mmol), 13 (21.2 mg, 0.05 mmol), Pd(OAc)2 (11.2 mg,
0.05 mmol), KOt-Bu (339 mg, 3.02 mmol) were stirred in PhMe
(2.0 mL) for 14 h at 120 ꢀC. Purification by column chromatography
on silica gel (n-hexane/EtOAc 15:1) yielded indole 3bf (262 mg, 71%)
134.0, 132.7, 129.1, 129.1, 128.5, 128.2, 128.1, 124.4, 122.0, 120.3,
120.2, 110.5, 101.9, 21.5, 21.1, 17.7. IR (KBr): 2917, 2371, 1604, 1485,
1456,1373,1353,1315,1299,1214,1010, 850, 799, 781, 750, 767, 694,
669, 615, 449 cmꢂ1. MS (EI) m/z (relative intensity): 325 (100) [Mþ],
310 (13), 234 (7), 131 (14), 84 (8), 57 (8). HRMS (ESI) m/z calcd for
C24H24N 326.1903, found 326.1904.
as a white solid. Mp: 155 ꢀC. 1H NMR (300 MHz, CDCl3):
d 7.49–7.41
(m, 1H), 7.31–7.12 (m, 7H), 7.12–7.06 (m, 1H), 6.83 (s, 1H), 6.69 (s,
2H), 4.67 (br s, 1H), 2.34 (sept., J¼6.9 Hz, 2H), 0.96 (d, J¼6.8 Hz, 6H),
4.29. 6-Methyl-2-phenyl-1-(2,4,6-trimethylphenyl)-
1H-indole (3bc)
0.88 (d, J¼6.9 Hz, 6H).13C NMR (75 MHz, CDCl3):
d 149.8,147.8,141.7,
135.3, 133.6, 132.3, 129.3, 128.2, 128.0, 127.6, 127.1, 124.2, 111.7, 111.7,
104.5, 101.1, 28.2, 25.1, 23.1. IR (KBr): 3060, 2962, 2926, 2866, 2361,
2338, 1617, 1600, 1523, 1470, 1437, 1373, 1313, 1205, 1174, 1143, 1118,
842, 805, 761, 737, 695 cmꢂ1. MS (EI) m/z (relative intensity): 369
(100), 354 (11), 326 (10), 248 (5), 194 (6), 171 (5). HRMS (ESI) m/z
calcd for C26H28NO 370.2165, found 370.2165.
Following the general procedure, 2e (81 mg, 0.60 mmol), 5j
(115 mg, 0.51 mmol), 13 (10.6 mg, 0.025 mmol), Pd(OAc)2 (5.5 mg,
0.025 mmol), KOt-Bu (170 mg, 1.52 mmol) were stirred in PhMe
(1.5 mL) for 14 h at 120 ꢀC. Purification by column chromatography
on silica gel (n-pentane/Et2O 200:1) yielded indole 3bc (91 mg,
56%) as a yellow solid. Mp: 48 ꢀC. 1H NMR (300 MHz, CDCl3):
d
7.56
4.33. 2-n-Butyl-1-(2-methylbut-3-en-2-yl)-1H-indole (3bh)
(d, J¼7.0 Hz, 1H), 7.29–7.14 (m, 5H), 7.01–6.89 (m, 3H), 6.80 (s, 1H),
6.60 (s, 1H), 2.38 (s, 3H), 2.34 (s, 3H), 1.82 (s, 6H). 13C NMR
Following the general procedure, 2f (51.1 mg, 0.60 mmol), 5a
(91.0 mg, 0.474 mmol), 13 (10.6 mg, 0.025 mmol), Pd(OAc)2 (5.6 mg,
0.025 mmol), KOt-Bu (168 mg, 1.50 mmol) were stirred in PhMe
(1.5 mL) for 14 h at 105 ꢀC. Indole 3bh (60 mg, 53%) was obtained as
a yellow oil after purification by column chromatography on silica
(125 MHz, CDCl3):
d 139.9, 138.3, 137.9, 136.9, 134.0, 132.9, 131.9,
129.1, 128.1, 127.3, 127.0, 126.0, 122.0, 120.0, 110.2, 101.9, 21.9, 21.2,
17.8. IR (KBr): 3020, 2946, 2916, 1616, 1602, 1486, 1456, 1437, 1372,
1346, 1322, 1302, 1028, 854, 810, 759, 744, 694, 611, 604 cmꢂ1. MS
(EI) m/z (relative intensity): 325 (100) [Mþ], 310 (6), 294 (4),148 (5).
HRMS (ESI) m/z calcd for C24H24N 326.1903, found 326.1911.
gel (n-pentane/Et2O 100:1). 1H NMR (300 MHz, CDCl3):
(m, 1H), 7.50–7.46 (m, 1H), 7.04–6.99 (m, 2H), 6.38–6.28 (m, 2H),
d 7.67–7.61

L. Ackermann et al. / Tetrahedron 65 (2009) 8930–8939
8939
Madsen, R.; Jørgensen, M. Angew. Chem., Int. Ed. 2008, 47, 888–890; (k) Ohno,
H.; Ohta, Y.; Oishi, S.; Fujii, N. Angew. Chem., Int. Ed. 2007, 46, 2295–2298; (l)
Cacchi, S.; Fabrizi, G.; Goggiamani, A. Adv. Synth. Catal. 2006, 348, 1301–1305;
(m) Shimada, T.; Nakamura, I.; Yamamoto, Y. J. Am. Chem. Soc. 2004, 126, 10546–
10547; (n) Siebeneicher, H.; Bytschkov, I.; Doye, S. Angew. Chem., Int. Ed. 2003,
42, 3042–3044; (o) Campo, M. A.; Huang, Y.; Yao, T.; Tian, Q.; Larock, R. C. J. Am.
Chem. Soc. 2003, 125, 11506–11507 and references cited therein.
14. Willis, M. C.; Brace, G. N.; Holmes, I. P. Angew. Chem., Int. Ed. 2005, 44, 403–406.
15. Fletcher, A. J.; Bax, M. N.; Willis, M. C. Chem. Commun. 2007, 4764–4766.
16. Schirok, H. Synthesis 2008, 1404–1414.
5.16–5.10 (m, 2H), 2.90 (t, J¼7.2 Hz, 2H), 1.87–1.68 (m, 8H), 1.49–
1.39 (m, 2H), 0.97 (t, J¼7.5 Hz, 3H). 13C NMR (75 MHz, CDCl3):
d
147.4, 143.2, 137.3, 128.9, 119.8,119.5, 118.8, 114.5, 111.4, 102.4, 62.0,
32.2, 30.8, 29.5, 22.8, 14.0. IR (KBr): 3048, 2959, 2932, 2872, 1456,
1379,1291,1265,1184, 918, 778, 738, 704 cmꢂ1. MS (EI) m/z (relative
intensity): 241 (60) [Mþ], 190 (9), 173 (29), 131 (100), 115 (2). HRMS
(ESI) m/z calcd for C17H24N 242.1903, found 242.1906.
17. Ackermann, L.; Sandmann, R.; Kaspar, L. T. Org. Lett. 2009, 11, 2031–2034.
18. Ackermann, L.; Kaspar, L. T. J. Org. Chem. 2007, 72, 6149–6153.
19. Ackermann, L. Org. Lett. 2005, 7, 439–442.
Acknowledgements
20. Kaspar, L. T.; Ackermann, L. Tetrahedron 2005, 61, 11311–11316.
21. Ackermann, L.; Barfu¨ßer, S.; Potukuchi, H. K. Adv. Synth. Catal. 2009, 351, 1064–
1072.
22. For selected indole syntheses from our laboratories, see: (a) Ackermann, L.;
Kaspar, L. T.; Gschrei, C. J. Chem. Commun. 2004, 2824–2825; (b) Ackermann, L.;
Born, R. Tetrahedron Lett. 2004, 45, 9541–9544; (c) Ackermann, L.; Althammer,
A. Synlett 2006, 3125–3129; (d) Ackermann, L.; Sandmann, R.; Villar, A.; Kaspar,
L. T. Tetrahedron 2008, 64, 769–777; (e) Ackermann, L.; Barfu¨ßer, S. Synlett
2009, 808–812.
Support by the DFG is gratefully acknowledged.
References and notes
1. Horton, D. A.; Bourne, G. T.; Smythe, M. L. Chem. Rev. 2003, 103, 893–930.
2. Humphrey, G. R.; Kuethe, J. T. Chem. Rev. 2006, 106, 2875–2911.
3. Eicher, T.; Hauptmann, S. The Chemistry of Heterocycles, 2nd ed.; Wiley-VCH:
Weinheim, Germany, 2003.
23. For palladium-catalyzed aminations of aryl halides from our laboratories, see:
(a) Ackermann, L.; Born, R. Angew. Chem., Int. Ed. 2005, 44, 2444–2447; (b)
Ackermann, L.; Spatz, J. H.; Gschrei, C. J.; Born, R.; Althammer, A. Angew. Chem.,
Int. Ed. 2006, 45, 7627–7630.
4. Gilchrist, T. L. Heterocyclic Chemistry, 3rd ed.; Addison Wesley Longman: Har-
low, 1997.
5. Joule, J. A.; Mills, K. Heterocyclic Chemistry, 4th ed.; Blackwell Science: Oxford,
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