Annulation of Indoles with 1,n-Dibromoalkanes by a Pd(II)-Catalyzed and Norbornene-Mediated Reaction Cascade

Article abstract of DOI:10.1055/s-0039-1690693

Employing 1,3-dibromopropane, 1,4-dibromobutane, and 1,5-dibromopentane as biselectrophiles, the annulation of indoles was probed in the presence of PdCl ₂ (MeCN) ₂ as a catalyst and norbornene as a transpositional ligand. Ring formation to a five-membered ring was observed at positions C2 and N, while annulation of a six-membered ring occurred at positions C2 and C3. The latter cascade process was successfully applied to the direct synthesis of 1,2,3,4-tetrahydrocarbazoles from indoles (11 examples, 31-68% yield). Seven-membered-ring annulation was feasible by an initial coupling at positon C2 followed by alkylation at C3.

Full text of DOI:10.1055/s-0039-1690693

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
©
Georg Thieme Verlag Stuttgart · New York
2019, 51, A–H
paper
A
en
Synthesis
M. Henkel, T. Bach
Paper
Annulation of Indoles with 1,n-Dibromoalkanes by a Pd(II)-Catalyzed
and Norbornene-Mediated Reaction Cascade
Michael Henkel
Thorsten Bach*
Br
Br
Br
n
0
0
0
0-0
0
0
2-1
3
4
2-
0
2
0
2
X
X
X
PdCl2(MeCN)2
norbornene
X
Department Chemie and Catalysis Research Center (CRC),
Technische Universität München, Lichtenbergstr. 4,
2
N
N
H
N
H
N
85747 Garching, Germany
H
thorsten.bach@ch.tum.de
n = 1
n = 2
n = 3
(11 examples, 31–68%)
Dedicated to Professor Mark Lautens on the occasion of his
th
60
birthday
Received: 30.08.2019
Accepted after revision: 16.09.2019
Published online: 02.10.2019
(0.5 M) are necessary for the reaction to be successful, pos-
sibly because the base needs to be dissolved in the organic
solvent.
DOI: 10.1055/s-0039-1690693; Art ID: ss-2019-c0495-op
Abstract Employing 1,3-dibromopropane, 1,4-dibromobutane, and
,5-dibromopentane as biselectrophiles, the annulation of indoles was
probed in the presence of PdCl (MeCN) as a catalyst and norbornene
as a transpositional ligand. Ring formation to a five-membered ring was
observed at positions C2 and N, while annulation of a six-membered
ring occurred at positions C2 and C3. The latter cascade process was
successfully applied to the direct synthesis of 1,2,3,4-tetrahydrocarba-
zoles from indoles (11 examples, 31–68% yield). Seven-membered-ring
annulation was feasible by an initial coupling at positon C2 followed by
alkylation at C3.
PdCl2(MeCN)2 (10 mol%)
norbornene (2 eq.)
1
(DMA, 0.5 M H2O)
RFG Br
(2 eq.)
2
2
2
+
RFG
N
70–90 °C, K2CO3 (2 eq.)
N
H
H
1a
56–82%
FG includes: OTHP, OTMS, COOMe, CH(OMe)2, NTsMe, CN
O N
2
O2N
standard conditions
see above)
(
+
Bu Br
Key words alkylation, C–H activation, domino reaction, indoles, Pd
catalysis
N
70 °C, K2HPO4 (3 eq.)
N
Bu
H
H
1b
2 (90%)
4
Scheme 1 Pd(II)-catalyzed, C2-selective alkylation of indoles 1a and
1
b with various alkyl bromides
The importance of indoles for many applications has
stimulated extensive research efforts towards their synthe-
1
sis and their functionalization. Positions C2 and C3 of the
For electron-deficient indoles such as 5-nitroindole (1b)
indole core can be addressed by electrophilic reagents and
there is a plethora of C–C bond-forming reactions known
that allow for the attachment of different substituents. De-
a milder base (K HPO ) was required to direct the alkylation
2 4
to position C2 and to avoid N-alkylation. The yield of butyl-
ated product 2 was high under these conditions. The C2-se-
lective indole alkylation method has been vividly embraced
by the synthetic community and several applications to the
2
spite the broad scope of reported methods, limitations re-
main and several desirable transformations lack a general
procedure. Along these lines, we recognized some time ago
that a C2 alkylation of N-unsubstituted indoles would be a
useful synthetic method for which no precedence existed. It
was found that Pd(II) serves, in combination with nor-
5
synthesis of substituted indoles have been reported.
Since the alkylation at position C2 leaves both the indole
nitrogen atom and the nucleophilic carbon atom C3 avail-
able for a second attack of an electrophile we wondered
how 1,n-dibromoalkanes would behave in the Pd(II)-cata-
lyzed alkylation reaction. Three dibromides (1,3-dibromo-
propane, 1,4-dibromobutane, and 1,5-dibromopentane)
were chosen to probe the reactivity of indoles towards a
twofold substitution. Ideally, a reaction cascade should oc-
cur which would lead to an annulation of a ring to the in-
3
bornene as a transpositional ligand, as an effective catalyst
to allow for C–H activation at position C2 of the indole core.
Indole (1a) itself and several substituted indoles undergo a
clean regioselective alkylation reaction with a large variety
4
of alkyl bromides (Scheme 1). The functional group (FG)
tolerance of the reaction is high and typical reaction condi-
6
tions include the use of K CO as a base in N,N-dimethyl-
dole core. Indeed, five-membered-ring formation occurred
2
3
acetamide (DMA) as the solvent. Minimal quantities of water
at C2 and the nitrogen atom (C2/N) and six-membered-ring
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Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–H

B
Synthesis
M. Henkel, T. Bach
Paper
formation at C2 and C3 (C2/C3) while seven-membered-
ring formation was retarded. Detailed results of our experi-
ments are described in this account.
there is also precedence for the formation of 2,3-dihydro-
1H-pyrrolo[1,2-a]indoles1 by an intramolecular C–C bond
formation at position C2.12 In our hands, the expected cy-
clization was mediated by the same base (K CO ) that was
previously used in the Pd(II)-catalyzed process. Starting
from 2-(3-bromopropyl)indole (4) the desired product was
obtained in 54% yield (Scheme 3). Given the precedence for
the cyclization to tricyclic product 3a, further optimization
was not attempted. In combination with the low yields ob-
tained for the direct conversion of indole into product 3a
(Scheme 1), the results suggest that palladium is not re-
quired for the cyclization, but rather has a detrimental in-
fluence.
1
In all reactions studied, we retained the same palladium
catalyst, norbornene (2 eq.), concentration (0.2 M), reaction
time (24 h), and solvent mixture identical (standard condi-
tions) and varied only the temperature, the base, and po-
tential additives. The reaction of indoles with 1,3-dibromo-
propane turned out to be sluggish and the reaction of in-
dole 1a at 70 °C with K CO as base delivered only 8% of
2
3
2
3
annulated product, the majority (7%) of which was the C2/N
annulation product 3a (Scheme 2). Monosubstitution at C2
was the predominant reaction pathway (31%) and some
substrate was recovered (17%). Optimization of the reaction
(for details, see the Supporting Information) revealed a ben-
90 °C, K2CO3 (2 eq.)
(DMA, 0.5 M H2O)
eficial influence of potassium bromide and tetrabutylam-
Br
N
N
7
54%
monium bromide (TBAB) on the reaction course, but the
H
4
3a
reaction remained incomplete and product 3a was isolated
together with 21% of substrate. The yield of product 3a
based on conversion was 46%, which is lower than the yield
Scheme 3 Preparation of 2,3-dihydro-1H-pyrrolo[1,2-a]indole (3a) by
intramolecular alkylation of bromide 4
(
60%) reported for the reaction in the presence of Cs CO as
2 3
8
disclosed in a recent patent procedure. Employing the
same additives, the reaction of 5-nitroindole to the respec-
Gratifyingly, the reactions of 1,4-dibromobutane and
indoles 1 delivered synthetically more useful results than
the reactions of 1,3-dibromopropane. It was found that par-
ticularly electron-deficient indoles underwent a smooth
cascade reaction that eventually led to 1,2,3,4-tetrahydro-
carbazoles in a single reaction step. Although reactions of
indoles with a related bond set have been previously re-
ported13 there is only limited precedence for the annula-
tion of an unsubstituted cyclohexane ring to indoles in a
single synthetic step. Table 1 summarizes the best results
for a given indole substrate 1 obtained from employing ei-
ther 2 equivalents of K CO or 3 equiv of K HPO as the base
tive nitro-substituted 2,3-dihydro-1H-pyrrolo[1,2-a]indole
9
(
3b) could be achieved in 39% yield.
standard conditions, 90 °C,
K2CO3 (2 eq.), KBr (1 eq.),
TBAB (20 mol%)
1
a
+
+
Br
Br
Br
Br
N
14
3
6%
3a
3b
O2N
standard conditions, 90 °C,
K2HPO4 (2 eq.), KBr (1 eq.),
TBAB (20 mol%)
1b
N
2
3
2
4
39%
under standard conditions at 80 °C.
Scheme 2 Annulation of indoles 1a and 1b with 1,3-dibromopropane
to 2,3-dihydro-1H-pyrrolo[1,2-a]indoles 3a and 3b
Remarkably, the reactions of indoles 1 did not generate
any 2-(4-bromobutyl)indole as side product indicating that
the cyclization to the 1,2,3,4-tetrahydrocarbazole is fast
once the C2–alkyl bond is formed. The weaker base K HPO
A possible explanation for the low conversion in the re-
2
4
action of 1a and 1b with 1,3-dibromopropane may be the
formation of allylic side products by 1,2-elimination of HBr
either in the starting material or in the initial coupling
turned out to be the preferred choice for most substrates,
potentially because it avoids any base-induced olefin for-
mation. In a test reaction, it was found that the presence of
allyl bromide completely suppresses the reactions of 1b to
5b under otherwise identical conditions. The annulation
reaction turned out to be compatible with nitro (Table 1,
entries 2, 8, 10), cyano (entries 3, 9), chloro (entries 4, 11),
bromo (entry 5), and alkoxycarbonyl substituents (entry 7).
As opposed to the reaction with 1,3-dibromopropane, the
presence of an additive did not have a beneficial effect on
the reaction. Rather, it led to the formation of minor quanti-
ties of the C2/N annulation product. With acidic indoles like
1b and stronger bases such as K CO the C2/N annulation
4a
product. In our previous work, we had noted that terminal
olefins are not compatible with the regioselective alkyla-
tion reaction presumably due to a competitive binding to
the active Pd(II) species. When applying 1,3-dibromopro-
pane as the reagent, the formation of olefins could not be
completely suppressed under any of the chosen conditions
and their presence may be responsible for the sluggish con-
version.
Since we observed in all experiments with 1,3-dibro-
mopropane as biselectrophile a monoalkylation at position
C2 we probed whether the ring formation was also possible
in the absence of palladium. Indeed, there is precedence for
an intramolecular alkylation at nitrogen and compound 3a
2
3
product could be detected, but the desired C2/C3 product
5b prevailed (see the Supporting Information). Blind exper-
iments performed with indole 1b in the absence of either
norbornene or palladium catalyst led to no reaction in the
10
has been previously prepared by this process. Likewise,
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Synthesis
M. Henkel, T. Bach
Paper
Table 1 Formation of 1,2,3,4-Tetrahydrocarbazoles from Indoles by a
Pd(II)-Catalyzed and Norbornene-Mediated Twofold Alkylation Cascade
temperature (100 °C) an intramolecular alkylation to prod-
uct 8 was observed. In the absence of palladium, the regio-
selectivity of the cyclization changed from a C3-alkylation
to an N-alkylation. The synthesis of 7,8,9,10-tetrahydro-6H-
azepino[1,2-a]indoles by intramolecular N-alkylation has
been previously reported.19
Br
4
5
X
standard conditions,
0 °C, base (n eq.)
X
8
+
6
N
N
H
H
1
Br
5
O2N
standard conditions,
Entry Xa
Indole
Base
Eq.b
Product Yield (%)c
2 4
80 °C, K HPO (3 eq.)
Br
48%
1
2
3
4
5
6
7
8
9
H
1a
1b
1c
1d
1e
1f
K
K
K
K
K
K
K
K
K
K
K
2
2
2
2
2
2
2
2
2
2
2
CO
3
2
3
3
2
2
3
2
3
3
3
2
5a
5b
5c
5d
5e
5f
31
68
60
58
47
38
56
55
50
58
53
O2N
N
H
7
5-NO
2
HPO
4
4
5-CN
5-Cl
5-Br
HPO
N
O2N
H
100 °C, K2HPO4 (2 eq.)
DMA, 0.5 M H2O)
6
(
CO
3
3
15%
CO
N
5-CF
3
HPO
4
8
5-CO
2
t-Bu
1g
1h
1i
CO
3
5g
5h
5i
Scheme 5 Regiodivergent cyclization of 2-(5-bromopentyl)-5-nitro-
indole (6) to products 7 and 8
4-NO
4-CN
6-NO
6-Cl
2
2
HPO
HPO
HPO
4
4
4
10
1j
5j
In combination with the results obtained for the other
1,n-dibromoalkanes it appears as if palladium coordination
to the indole nitrogen atom favors alkylation20 at carbon
atom C3 but retards N-alkylation. This hypothesis is sup-
ported by the exclusive formation of product 7 from 6 upon
palladium catalysis and by the fact that there was no forma-
tion of 2-(4-bromobutyl)indoles observed in the reaction of
indoles with 1,4-dibromobutane (Table 1). Rather, the C3
alkylation succeeded rapidly the initial C–C bond-forming
step at carbon atom C2. Mechanistically, the reaction is sug-
gested to follow the established pattern for a norbornene-
mediated C2 alkylation (Scheme 6).4b Palladation at the
11
1k
CO
3
5k
a
b
c
Position in starting indole 1.
Equivalents n of base employed in the individual reaction.
Yield of isolated product after column chromatography.
latter case and to a minimal conversion in the former case
with the respective N-substituted indole being the only
product.
Attempts to convert 1,5-dibromopentane with indoles
into the respective 5,6,7,8,9,10-hexahydrocyclohepta[b]in-
doles resulted mainly in C2-monosubstitution products
(Scheme 4). The reaction of 5-nitroindole (1b), for example,
provided at 80 °C the 2-(5-bromopentyl)indole 6 in 53%
yield together with the desired C2/C3 annulated indole as a
byproduct (10% yield).
H
5a
1a
N
14
Br
Br
II
Pd X2
O2N
Br
standard conditions,
0 °C, K2HPO4 (3 eq.)
8
1b
+
N
53%
N
9
II
Br
H
13
Pd LnBr
N
6
II
Pd LnX
Scheme 4 C2-selective alkylation of 5-nitroindole (3b) to 2-(5-bromo-
pentyl)indole 6
HX
Br
Br
The minor quantities of C2/C3 annulation product ob-
tained in the direct reaction of indole 1b indicated that it
was possible to achieve a cyclization in a subsequent step.
Indeed, application of the standard conditions to substrate
II
N
Pd Ln
N
Br
PdIV
II
Pd LnBr
N
L
Br
6
led to the expected product 715 in 48% yield (Scheme 5). In
L
12
10
contrast to 2-(3-bromopropyl)indoles, the cyclization to
1
1
16
Br
position C3 seems feasible for 2-(5-bromopentyl)indoles
17,18
and offers access to cyclohepta[b]indoles.
In the absence
Scheme 6 Mechanistic proposal for the cascade reaction of indoles to
,2,3,4-tetrahydrocarbazoles with the transformation 1a → 5a as a rep-
resentative example
1
of palladium and norbornene, base treatment of substrate 6
did not lead to a notable cyclization. However, at a higher
©
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D
Synthesis
M. Henkel, T. Bach
Paper
nitrogen atom generates intermediate 9 (L = ligand, X = Br,
General Alkylation Procedure (GP)
A round-bottom flask was charged with the corresponding indole
(1.0 eq.), norbornene (2.0 eq.), base [K CO (2.0 eq.) or K HPO (3.0
eq.); as indicated], PdCl (MeCN) (10 mol%), and the corresponding
bromide (2.0 eq.). A 0.5 M solution of water in DMA (ca. 5 mL per
mmol indole) was added. The mixture was then placed in a preheated
oil bath at 80 °C. Vigorous stirring was applied and the mixture was
kept under a balloon pressure of argon for 24 h. After cooling to r.t.,
Cl) which undergoes intermolecular aminopalladation at
21,22
norbornene
followed by C–H activation at position C2.
2
3
2
4
The intermediate palladacycle 10 could be isolated with
stabilizing ligands L at the palladium center and its struc-
ture was proven by single crystal X-ray crystallography.4b
Oxidative addition to 1,4-dibromobutane provides access to
Pd(IV) intermediate 11 which after reductive elimination
delivers the C2-alkylated intermediate 12. After liberation
of norbornene, palladium complex 13 is perfectly suited for
an intramolecular nucleophilic substitution of the second
bromide. This step is irreversible and closes the catalytic cy-
cle delivering indolenine 14 which tautomerizes to the final
product 5a.
2
2
the mixture was diluted with Et O (80 mL) and washed with water
2
(80 mL). The aqueous layer was extracted with Et O (2 × 80 mL). The
2
combined organic layers were washed with brine (80 mL) and dried
(
Na SO ). All volatiles were removed in vacuo and the crude material
2 4
was subjected to FCC (silica gel, pentane/Et O) to yield the respective
2
product.
2,3-Dihydro-1H-pyrrolo[1,2-a]indole (3a)
If the cyclization is slow the catalytic cycle can also be
closed by hydro-de-palladation which appears to be the
preferred reaction course for 1,5-dibromopentane as the
biselectrophile. For 1,3-dibromopropane, cyclization at C3
According to the GP, indole (117.1 mg, 1.00 mmol, 1.00 eq.), nor-
bornene (187.7 mg, 1.99 mmol, 1.99 eq.), K CO (276.5 mg,
2
3
2
.00 mmol, 2.00 eq.), PdCl (MeCN) (26.0 mg, 0.10 mmol, 0.10 eq.),
2 2
1,3-dibromopropane (210 L, 407.5 mg, 2.02 mmol, 2.02 eq.), KBr
(119.1 mg, 1.00 mmol, 1.00 eq.), and TBAB (64.1 mg, 200 mol,
23
seems not possible for stereoelectronic reasons and a slow
cyclization to 2,3-dihydro-1H-pyrrolo[1,2-a]indole occurs.
In summary, the reactions of indoles with 1,n-dibro-
moalkanes in the presence of PdCl (MeCN) and nor-
0.20 eq.) were converted as described above, but at 90 °C. After work-
up, the crude material was subjected to FCC (pentane/Et O 19:1) to af-
2
ford 3a (57.2 mg, 364 mol, 36%) as a white solid.
2
2
1
3
3
H NMR (500 MHz, CDCl , 300 K):  = 2.61 (virt p, J ≈ J = 7.2 Hz, 2 H,
3
1
2
bornene provide access to annulated indoles. Substitution
reactions at C2 and N prevail with 1,3-dibromopropane as
the biselectrophile but the overall transformation suffers
from a relatively low yield. The reaction with 1,4-dibro-
mobutane is a synthetically useful method for the prepara-
tion of 1,2,3,4-tetrahydrocarbazoles and offers options for
further optimization. Indeed, all reactions were performed
under standard conditions without a specific adaption to
the individual substrate. Finally, the attempted reaction
with 1,5-dibromopentane gave mainly monoalkylation at
C2, but the primary product could be cyclized to a cyclo-
hepta[b]indole.
3
3
H-2), 3.02 (t, J = 7.2 Hz, 2 H, H-1), 4.07 (t, J = 7.2 Hz, 2 H, H-3), 6.16
3
4
(s, 1 H, H-9), 7.05 (ddd, J = 7.1 Hz, 8.0 Hz, J = 1.1 Hz, 1 H, H-7)*, 7.11
3
4
3
(
ddd, J = 7.1 Hz, 8.0 Hz, J = 1.1 Hz, 1 H, H-6)*, 7.23 (virt dt, J = 8.0 Hz,
J ≈
4
4
3
4
J2 = 1.1 Hz, 1 H, H-5), 7.54 (dd,
J = 8.0 Hz,
J = 1.1 Hz, 1 H, H-8).
1
13
C NMR (126 MHz, CDCl , 300 K):  = 24.4, 28.0, 43.7, 92.4, 109.5,
3
119.2, 120.2, 120.4, 132.8, 133.4, 144.7.
The spectroscopic data match the literature values.10a,12a
7-Nitro-2,3-dihydro-1H-pyrrolo[1,2-a]indole (3b)
According to the GP, 5-nitroindole (162.5 mg, 1.00 mmol, 1.00 eq.),
norbornene (189.0 mg, 2.01 mmol, 2.02 eq.), K HPO (522.9 mg,
2
4
3.00 mmol, 3.03 eq.), PdCl
,3-dibromopropane (210 L, 407.5 mg, 2.02 mmol, 2.03 eq.), KBr
119.6 mg, 1.01 mmol, 1.01 eq.), and TBAB (64.4 mg, 200 mol,
(MeCN) (26.2 mg, 0.10 mmol, 0.10 eq.),
2
2
1
(
0
.20 eq.) were converted as described above. After workup, the crude
Thin-layer chromatography (TLC) was performed on silica-coated
glass plates (silica gel 60 F254) with detection by UV ( = 254 nm) and
9
material was subjected to FCC (pentane/Et O 9:1) to afford 3b (78.0
mg, 386 mol, 39%) as a yellow solid; mp 150 °C.
2
KMnO (0.5% in water) upon subsequent heating. Flash column chro-
4
IR (ATR): 3080 (w, C –H), 2953 (w, Calk–H), 1510 (s), 1312 (s), 1297
matography (FCC) was performed on silica gel 60 (Merck, 230–400
mesh) with the indicated eluent. Common solvents for chromatogra-
ar
–1
(s), 895 (m), 748 cm (s).
1
3
3
phy (pentane, Et O) were distilled prior to use. Solutions refer to satu-
H NMR (500 MHz, CDCl , 300 K):  = 2.67 (virt p, J ≈ J = 7.2 Hz, 2 H,
3 1 2
2
3
3
rated aqueous solutions unless otherwise stated. All melting points
were determined using a Büchi M 565 melting point apparatus, with
a range quoted to the nearest integer. IR spectra were recorded on a
JASCO IR-4100 instrument (ATR). HRMS measurements were per-
formed on a Thermo Scientific LTQ-FT Ultra (ESI) or a Thermo Scien-
H-2), 3.06 (t, J = 7.2 Hz, 2 H, H-1), 4.12 (t, J = 7.2 Hz, 2 H, H-3), 6.33
(s, 1 H, H-9), 7.20 (d, J = 9.0 Hz, 1 H, H-5), 8.01 (dd, J = 9.0 Hz, J = 2.2
Hz, 1 H, H-6), 8.47 (d, J = 2.2 Hz, 1 H, H-8).
13
3
3
4
4
C NMR (126 MHz, CDCl , 300 K):  = 24.5, 28.0, 44.1, 95.5, 109.1,
3
1
16.3, 117.6, 132.5, 135.6, 141.4, 148.2.
1
13
tific DFS-HRMS spectrometer (EI). H and C NMR spectra were re-
HRMS-ESI: m/z [M + H]+ calcd for C11H11N O : 203.0815; found:
2
2
2
corded in CDCl at 300 K on a Bruker AVHD-400, Bruker AV-500cr or a
3
03.0815.
Bruker AVHD-500 instrument. Chemical shifts are reported relative to
TMS ( = 0.00). Apparent multiplets that occur as a result of the acci-
dental equality of coupling constants to those of magnetically non-
equivalent protons are marked as virtual (virt). Assignments are
based on COSY, HMBC, and HSQC experiments. Signals that could not
be assigned unambiguously are marked with an asterisk (*).
2-(3-Bromopropyl)-1H-indole (4)
According to the GP, indole (117.2 mg, 1.00 mmol, 1.00 eq.), nor-
bornene (191.3 mg, 2.03 mmol, 2.03 eq.), K CO (276.7 mg,
2.00 mmol, 2.00 eq.), PdCl (MeCN) (26.0 mg, 0.10 mmol, 0.10 eq.),
2
3
2
2
and 1,3-dibromopropane (210 L, 407.5 mg, 2.02 mmol, 2.02 eq.)
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M. Henkel, T. Bach
Paper
13
were converted as described above, but at 70 °C. After workup, the
C NMR (126 MHz, CDCl , 300 K):  = 20.7, 23.0, 23.1, 23.3, 102.0,
3
crude material was subjected to FCC (pentane/Et O 9:1) to afford 4
111.1, 111.2, 121.3, 123.3, 124.3, 127.9, 136.7, 137.5.
2
(
1
74.9 mg, 315 mol, 31%) as a white solid.
The spectroscopic data match the literature values.26
3
3
H NMR (500 MHz, CDCl , 300 K):  = 2.26 (virt p, J ≈ J = 6.8 Hz, 2 H,
3
1
2
3
3
H-2′), 2.95 (t, J = 6.8 Hz, 2 H, H-1′), 3.47 (t, J = 6.8 Hz, 2 H, H-3′), 6.29
6-Chloro-1,2,3,4-tetrahydro-9H-carbazole (5d)
3
3
4
(s, 1 H, H-3), 7.09 (virt td, J ≈ J = 7.5 Hz, J = 1.1 Hz, 1 H, H-5), 7.15
1 2
According to the GP, 5-chloroindole (153.8 mg, 1.00 mmol, 1.00 eq.),
norbornene (189.5 mg, 2.01 mmol, 2.01 eq.), K CO (276.4 mg,
3
3
4
3
4
(
1
1
1
virt td, J ≈ J = 7.5 Hz, J = 1.3 Hz, 1 H, H-6), 7.32 (dd, J = 7.5 Hz, J =
1 2
2
3
3
4
.1 Hz, 1 H, H-7), 7.55 (dd, J = 7.5 Hz, J = 1.3 Hz, 1 H, H-4), 7.92 (br s,
H, N-H).
2
.00 mmol, 2.00 eq.), PdCl (MeCN) (26.9 mg, 0.10 mmol, 0.10 eq.),
2 2
and 1,4-dibromobutane (240 L, 439.2 mg, 2.03 mmol, 2.03 eq.) were
converted as described above. After workup, the crude material was
3
C NMR (126 MHz, CDCl , 300 K):  = 26.5, 32.1, 33.3, 100.2, 110.6,
3
119.9, 112.0, 121.4, 128.8, 136.0, 137.7.
subjected to FCC (pentane/Et O 7:1) to afford 5d (119.3 mg, 580 mol,
2
The spectroscopic data match the literature values.24
58%) as a white solid.
1
H NMR (500 MHz, CDCl , 300 K):  = 1.82–1.95 (m, 4 H, H-2, H-3),
3
3
3
3
1,2,3,4-Tetrahydro-9H-carbazole (5a)
2.66 (t, J = 6.0 Hz, 2 H, H-4), 2.72 (t, J = 6.1 Hz, 2 H, H-1), 7.05 (dd, J =
8
2
4
3
4
.5 Hz, J = 2.1 Hz, 1 H, H-7), 8.49 (d, J = 8.5 Hz, 1 H, H-8), 7.41 (d, J =
.1 Hz, 1 H, H-5), 7.69 (br s, 1 H, N-H).
According to the GP, indole (117.2 mg, 1.00 mmol, 1.00 eq.), nor-
bornene (189.9 mg, 2.02 mmol, 2.02 eq.), K CO (276.2 mg,
2
3
13
2
.00 mmol, 2.00 eq.), PdCl (MeCN) (26.3 mg, 0.10 mmol, 0.10 eq.),
C NMR (126 MHz, CDCl , 300 K):  = 20.8, 23.1, 23.1, 23.3, 110.1,
2
2
3
and 1,4-dibromobutane (240 L, 439.2 mg, 2.03 mmol, 2.03 eq.) were
111.2, 117.4, 121.0, 124.7, 129.0, 133.9, 135.7.
converted as described above. After workup, the crude material was
The spectroscopic data match the literature values.25
subjected to FCC (pentane/Et O 30:1) to afford 5a (53.8 mg, 314 mol,
2
3
1%) as a white solid.
6
-Bromo-1,2,3,4-tetrahydro-9H-carbazole (5e)
1
H NMR (500 MHz, CDCl , 300 K):  = 1.86–1.99 (m, 4 H, H-2, H-3),
3
According to the GP, 5-bromoindole (198.7 mg, 1.00 mmol, 1.00 eq.),
norbornene (190.3 mg, 2.01 mmol, 2.01 eq.), K CO (276.4 mg,
2
.70–2.78 (m, 4 H, H-1, H-4), 7.08–7.17 (m, 2 H, H-6, H-7), 7.28 (dd,
2
3
3
4
3
4
J = 7.3 Hz, J = 1.6 Hz, 1 H, H-8), 7.50 (dd, J = 7.0 Hz, J = 1.6 Hz, 1 H,
H-5), 7.61 (br s, 1 H, N-H).
2.00 mmol, 1.99 eq.), PdCl (MeCN) (26.9 mg, 0.10 mmol, 0.10 eq.),
2 2
and 1,4-dibromobutane (240 L, 439.2 mg, 2.03 mmol, 2.03 eq.) were
converted as described above. After workup, the crude material was
13
C NMR (126 MHz, CDCl , 300 K):  = 21.0, 23.3, 23.3, 23.4, 110.2,
3
110.5, 117.8, 119.2, 121.1, 127.9, 134.2, 135.7.
subjected to FCC (pentane/Et O 7:1) to afford 5e (118.0 mg, 472 mol,
2
The spectroscopic data match the literature values.25
47%) as a white solid.
1
H NMR (500 MHz, CDCl , 300 K):  = 1.83–1.94 (m, 4 H, H-2, H-3),
3
3
3
3
6-Nitro-1,2,3,4-tetrahydro-9H-carbazole (5b)
2.65 (t, J = 5.9 Hz, 2 H, H-4), 2.72 (t, J = 6.0 Hz, 2 H, H-1), 7.13 (d, J =
3
4
8
.5 Hz, 1 H, H-8), 7.18 (dd, J = 8.5 Hz, J = 1.8 Hz, 1 H, H-7), 7.57 (d,
According to the GP, 5-nitroindole (164.1 mg, 1.00 mmol, 1.00 eq.),
norbornene (189.6 mg, 2.01 mmol, 2.01 eq.), K HPO (523.3 mg,
4
J = 1.8 Hz, 1 H, H-5), 7.69 (br s, 1 H, N-H).
2
4
13
3
.00 mmol, 3.00 eq.), PdCl (MeCN) (26.4 mg, 0.10 mmol, 0.10 eq.),
C NMR (126 MHz, CDCl , 300 K):  = 20.9, 23.2, 23.3, 23.3, 110.1,
2
2
3
and 1,4-dibromobutane (240 L, 439.2 mg, 2.03 mmol, 2.03 eq.) were
111.8, 112.4, 120.5, 123.7, 129.8, 134.4, 135.7.
converted as described above. After workup, the crude material was
The spectroscopic data match the literature values.27
subjected to FCC (pentane/Et O 4:1) to afford 5b (148.3 mg, 686 mol,
2
6
8%) as a yellow solid.
6
-(Trifluoromethyl)-1,2,3,4-tetrahydro-9H-carbazole (5f)
According to the GP, 5-(trifluoromethyl)indole (114.6 mg, 600 mol,
.00 eq.), norbornene (113.9 mg, 1.21 mmol, 2.01 eq.), K HPO4
1
H NMR (500 MHz, CDCl , 300 K):  = 1.87–1.98 (m, 4 H, H-2, H-3),
3
3
2
.71–2.78 (m, 4 H, H-1, H-4), 7.28 (d, J = 8.9 Hz, 1 H, H-8), 8.03 (dd,
1
2
3
4
4
J = 8.9 Hz, J = 2.2 Hz, 1 H, H-7), 8.08 (br s, 1 H, N-H), 8.42 (d, J = 2.2
Hz, 1 H, H-5).
(313.7 mg, 1.80 mmol, 3.00 eq.), PdCl (MeCN) (16.3 mg, 61.6 mol,
2 2
0.10 eq.), and 1,4-dibromobutane (145 L, 265.4 mg, 1.23 mmol, 2.05
13
C NMR (126 MHz, CDCl , 300 K):  = 20.8, 23.0, 23.1, 23.3, 110.2,
eq.) were converted as described above. After workup, the crude ma-
3
112.9, 115.1, 117.0, 127.5, 137.8, 138.9, 141.4.
terial was subjected to FCC (pentane/Et O 7:1) to afford 5f (54.9 mg,
2
The spectroscopic data match the literature values.25
229 mol, 38%) as a white solid.
1
H NMR (500 MHz, CDCl , 300 K):  = 1.86–1.97 (m, 4 H, H-2, H-3),
3
3
1,2,3,4-Tetrahydro-9H-carbazole-6-carbonitrile (5c)
2.70–2.77 (m, 4 H, H-1, H-4), 7.31 (d, J = 8.5 Hz, 1 H, H-8), 7.36 (dd,
3
4
4
J = 8.5 Hz, J = 1.8 Hz, 1 H, H-7), 7.75 (d, J = 1.8 Hz, 1 H, H-5), 7.84 (br
s, 1 H, N-H).
According to the GP, indole-5-carbonitrile (145.1 mg, 1.00 mmol, 1.00
eq.), norbornene (189.0 mg, 2.01 mmol, 2.01 eq.), K HPO (522.6 mg,
2
4
1
3
3
.00 mmol, 3.00 eq.), PdCl (MeCN) (26.6 mg, 0.10 mmol, 0.10 eq.),
C NMR (126 MHz, CDCl , 300 K):  = 20.8, 23.2, 23.2, 23.3, 110.5,
3
2
2
3
3
and 1,4-dibromobutane (240 L, 439.2 mg, 2.03 mmol, 2.03 eq.) were
converted as described above. After workup, the crude material was
111.3, 115.5 (q, J = 4.3 Hz, C-5), 117.9 (q, J = 3.6 Hz, C-7), 121.6 (q,
C
F
C
F
2
JCF = 31 Hz, C-6), 125.8 (q, 1JCF = 271 Hz, CF ), 127.4, 136.1, 137.2.
3
subjected to FCC (pentane/Et O 4:1) to afford 5c (116.8 mg, 595 mol,
The spectroscopic data match the literature values.27
2
60%) as a white solid.
1
H NMR (500 MHz, CDCl , 300 K):  = 1.85–1.97 (m, 4 H, H-2, H-3),
3
tert-Butyl 1,2,3,4-Tetrahydro-9H-carbazole-6-carboxylate (5g)
According to the GP, tert-butyl indole-5-carboxylate28 (222.2 mg,
3
3
3
2
.69 (t, J = 6.0 Hz, 2 H, H-4), 2.75 (t, J = 6.0 Hz, 2 H, H-1), 7.30 (d, J =
3
4
8
.4 Hz, 1 H, H-8), 7.35 (dd, J = 8.4 Hz, J = 1.5 Hz, 1 H, H-7), 7.78 (d,
1.01 mmol, 1.00 eq.), norbornene (190.7 mg, 2.03 mmol, 2.01 eq.),
4
J = 1.5 Hz, 1 H, H-5), 8.02 (br s, 1 H, N-H).
K CO (276.1 mg, 2.00 mmol, 1.98 eq.), PdCl (MeCN) (27.1 mg, 0.10
2
3
2
2
mmol, 0.10 eq.), and 1,4-dibromobutane (240 L, 439.2 mg, 2.03
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–H

F
Synthesis
M. Henkel, T. Bach
Paper
mmol, 2.03 eq.) were converted as described above. After workup, the
converted as described above. After workup, the crude material was
crude material was subjected to FCC (pentane/Et O 4:1) to afford 5g
subjected to FCC (pentane/Et O 3:1) to afford 5j (126.4 mg, 585 mol,
2
2
(153.4 mg, 565 mol, 56%) as a white solid; mp 154 °C.
58%) as a yellow solid; mp 171 °C.
IR (ATR): 3370 (s, NH), 2927 (m, Calk–H), 2841 (w, Calk–H), 1682 (vs),
IR (ATR): 3359 (m, NH), 2929 (w, Calk–H), 2844 (w, Calk–H), 1556 (m),
1501 (m), 1316 (s), 1292 (vs), 1065 (s), 886 (m), 754 (s), 731 cm (s).
–1
–1
1477 (m), 1312 (m), 1243 (m), 1171 (s), 1085 (vs), 765 (s), 738 cm
(
1
m).
1
H NMR (500 MHz, CDCl , 300 K):  = 1.85–1.98 (m, 4 H, H-2, H-3),
3
3
3
3
H NMR (500 MHz, CDCl , 300 K):  = 1.62 (s, 9 H, 3 CH ), 1.84–1.95
2.73 (t, J = 6.0 Hz, 2 H, H-4), 2.80 (t, J = 6.1 Hz, 2 H, H-1), 8.71 (d, J =
8.7 Hz, 1 H, H-5), 7.99 (dd, J = 8.7 Hz, J = 2.0 Hz, 1 H, H-6), 8.15 (br s,
1 H, N-H), 8.24 (d, J = 2.0 Hz, 1 H, H-8).
13
3
3
3
3
4
(m, 4 H, H-2, H-3), 2.71–2.75 (m, 4 H, H-1, H-4), 7.24 (d, J = 8.5 Hz, 1
3
4
4
H, H-8), 7.78 (dd, J = 8.5 Hz, J = 1.8 Hz, 1 H, H-7), 7.82 (br s, 1 H, N-H),
8
4
.16 (d, J = 1.8 Hz, 1 H, H-5).
C NMR (126 MHz, CDCl , 300 K):  = 20.8, 22.8, 23.0, 23.7, 107.3,
3
1
3
C NMR (126 MHz, CDCl , 300 K):  = 20.9, 23.2, 23.2, 23.3, 28.5, 80.3,
111.9, 115.3, 117.4, 132.8, 134.1, 141.3, 142.4.
3
1
09.8, 111.7, 120.5, 122.7, 123.1, 127.6, 135.4, 138.2, 167.4.
+
HRMS-EI (70 eV): m/z [M] calcd for C12H12N O : 216.0893; found:
2
2
HRMS-ESI: m/z [M + H]+ calcd for C17H22NO : 272.1645; found:
216.0888; calcd for C11 C1H12N O : 217.0927; found: 217.0926.
13
2
2 2
272.1645.
7-Chloro-1,2,3,4-tetrahydro-9H-carbazole (5k)
5
-Nitro-1,2,3,4-tetrahydro-9H-carbazole (5h)
According to the, 6-chloroindole (154.1 mg, 1.00 mmol, 1.00 eq.), nor-
bornene (192.0 mg, 2.04 mmol, 2.04 eq.), K CO (277.4 mg,
According to the GP, 4-nitroindole (165.0 mg, 1.00 mmol, 1.00 eq.),
norbornene (190.5 mg, 2.02 mmol, 2.02 eq.), K HPO (524.3 mg,
2
3
2.01 mmol, 2.00 eq.), PdCl (MeCN) (27.3 mg, 0.10 mmol, 0.10 eq.),
2
4
2
2
3
.01 mmol, 3.00 eq.), PdCl (MeCN) (26.5 mg, 0.10 mmol, 0.10 eq.),
and 1,4-dibromobutane (240 L, 439.2 mg, 2.03 mmol, 2.03 eq.) were
2
2
and 1,4-dibromobutane (240 L, 439.2 mg, 2.03 mmol, 2.03 eq.) were
converted as described above. After workup, the crude material was
converted as described above. After workup, the crude material was
subjected to FCC (pentane/Et O 7:1) to afford 5k (109.8 mg, 534 mol,
2
subjected to FCC (pentane/Et O 3:1) to afford 5h (118.9 mg, 550 mol,
53%) as a white solid; mp 180 °C.
2
5
5%) as a yellow solid; mp 156 °C.
IR (ATR): 3389 (s, NH), 2941 (m, Calk–H), 2853 (w, Calk–H), 1619 (w),
1424 (m), 1302 (m), 1234 (m), 1060 (m), 800 cm (vs).
–1
IR (ATR): 3341 (m, NH), 2931 (m, Calk–H), 2861 (m, Calk–H), 1505 (m),
–1
1310 (s), 1271 (s), 1252 (s), 982 (s), 729 cm (vs).
1
H NMR (500 MHz, CDCl , 300 K):  = 1.83–1.94 (m, 4 H, H-2, H-3),
3
1
3
3
3
H NMR (500 MHz, CDCl , 300 K):  = 1.81–1.94 (m, 4 H, H-2, H-3),
2.67 (t, J = 6.0 Hz, 2 H, H-4), 2.71 (t, J = 6.0 Hz, 2 H, H-1), 7.03 (dd, J =
8.4 Hz, J = 1.8 Hz, 1 H, H-6), 7.25 (d, J = 1.8 Hz, 1 H, H-8), 7.34 (d, J =
3
3
3
4
4
3
2
.80 (t, J = 6.2 Hz, 2 H, H-4), 2.91 (t, J = 6.1 Hz, 2 H, H-1), 7.11 (virt t,
3
3
3
4
J ≈ J = 8.0 Hz, 1 H, H-7), 7.51 (dd, J = 8.0 Hz, J = 1.0 Hz, 1 H, H-8),
8.4 Hz, 1 H, H-5), 7.66 (br s, 1 H, N-H).
1
2
3
4
7.82 (dd, J = 8.0 Hz, J = 1.0 Hz, 1 H, H-6), 8.14 (br s, 1 H, N-H).
13
C NMR (126 MHz, CDCl , 300 K):  = 20.9, 23.2, 23.3, 23.4, 110.4,
3
13
C NMR (126 MHz, CDCl , 300 K):  = 22.3, 23.7, 23.8, 24.1, 109.8,
111.2, 118.6, 119.8, 126.6, 126.8, 135.0, 136.1.
3
1
16.2, 117.3, 119.7, 120.8, 138.1, 139.4, 142.0.
HRMS-ESI: m/z [M + H]+ calcd for C12H13N35Cl: 206.0731; found:
206.0731.
+
HRMS-EI (70 eV): m/z [M] calcd for C12H12N O : 216.0893; found:
2
2
13
216.0890; calcd for C11 C1H12N O : 217.0927; found: 217.0925.
2 2
2-(5-Bromopentyl)-5-nitro-1H-indole (6)
1
,2,3,4,-Tetrahydro-9H-carbazole-5-carbonitrile (5i)
According to the GP, 5-nitroindole (165.7 mg, 1.01 mmol, 1.00 eq.),
norbornene (189.1 mg, 2.01 mmol, 1.99 eq.), K HPO (523.9 mg,
According to the GP, indole-4-carbonitrile (144.7 mg, 1.00 mmol,
.00 eq.), norbornene (189.1 mg, 2.01 mmol, 2.00 eq.), K HPO
2
4
1
3.01 mmol, 2.97 eq.), PdCl (MeCN) (26.4 mg, 0.10 mmol, 0.10 eq.),
2
4
2 2
(
522.7 mg, 3.00 mmol, 2.99 eq.), PdCl (MeCN) (26.8 mg, 0.10 mmol,
and 1,5-dibromopentane (280 L, 466.5 mg, 2.03 mmol, 2.01 eq.)
2
2
0.10 eq.), and 1,4-dibromobutane (240 L, 439.2 mg, 2.03 mmol,
were converted as described above. After workup, the crude material
2.03 eq.) were converted as described above. After workup, the crude
was subjected to FCC (pentane/Et O 2:1) to afford 6 (167.8 mg, 539
2
material was subjected to FCC (pentane/Et O 3:1) to afford 5i (97.5
mol, 53%) as a yellow solid; mp 67 °C.
2
mg, 497 mol, 50%) as a white solid; mp 137 °C.
IR (ATR): 3324 (m, NH), 2934 (w, Calk–H), 2856 (w, Calk–H), 1473 (s),
1068 (s), 892 (m), 750 cm (s).
–1
IR (ATR): 3285 (m, NH), 3061 (w, C –H), 2915 (w, C –H), 2850 (w,
ar
alk
–1
Calk–H), 2220 (m), 1328 (m), 1285 (m), 1141 (m), 778 (s), 733 cm (s).
1
H NMR (500 MHz, CDCl , 300 K):  = 1.53–1.59 (m, 2 H, H-3′), 1.74–
3
1
3
H NMR (500 MHz, CDCl , 300 K):  = 1.86–1.95 (m, 4 H, H-2, H-3),
1.86 (m, 2 H, H-2′), 1.88–1.97 (m, 2 H, H-4′), 2.82 (t, J = 7.6 Hz, 2 H, H-
1′), 3.42 (t, J = 6.7 Hz, 2 H, H-5′), 6.41 (s, 1 H, H-3), 7.32 (d, J = 9.0 Hz,
1 H, H-7), 8.04 (dd, J = 9.0 Hz, J = 2.3 Hz, 1 H, H-6), 8.37 (br s, 1 H, N-
H), 8.48 (d, J = 2.3 Hz, 1 H, H-4).
3
3
3
3
3
2
.77 (t, J = 5.7 Hz, 2 H, H-4), 3.03 (t, J = 5.6 Hz, 2 H, H-1), 7.10 (virt t,
3
3
3
3
3
4
J ≈ J = 7.8 Hz, 1 H, H-7), 7.38 (d, J = 7.8 Hz, 1 H, H-8), 7.46 (d, J =
1
2
4
7.8 Hz, 1 H, H-6), 7.97 (br s, 1 H, N-H).
13
13
C NMR (126 MHz, CDCl , 300 K):  = 21.1, 22.7, 23.1, 23.5, 100.9,
C NMR (126 MHz, CDCl , 300 K):  = 27.9, 28.1, 28.2, 32.5, 33.7,
3
3
110.4, 115.0, 119.9, 120.6, 125.4, 128.1, 135.7, 137.8.
102.0, 110.3, 117.0, 117.1, 128.3, 139.2, 142.0, 143.0.
HRMS-ESI: m/z [M
+
H]+ calcd for C13H13N : 197.1073; found:
HRMS-EI (70 eV): m/z [M]+ calcd for C13H N O279Br: 310.0311;
2
15
79
2
13
197.1073.
found: 310.0304; calcd for C12 C1H15 N O Br: 311.0345; found:
2
2
311.0341.
7-Nitro-1,2,3,4-tetrahydro-9H-carbazole (5j)
2
-Nitro-5,6,7,8,9,10-hexahydrocyclohepta[b]indole (7)
According to the GP, 6-nitroindole (164.9 mg, 1.00 mmol, 1.00 eq.),
norbornene (188.1 mg, 2.00 mmol, 1.99 eq.), K HPO (526.2 mg,
According to the GP, 2-(5-bromopentyl)-5-nitro-1H-indole (6;
31.1 mg, 99.9 mol, 1.00 eq.), norbornene (18.9 mg, 200 mol,
2.01 eq.), K HPO (51.9 mg, 298 mol, 2.98 eq.), and PdCl (MeCN)2
2
4
3
.02 mmol, 3.02 eq.), PdCl (MeCN) (26.5 mg, 0.10 mmol, 0.10 eq.),
2 2
and 1,4-dibromobutane (240 L, 439.2 mg, 2.03 mmol, 2.03 eq.) were
2
4
2
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–H

G
Synthesis
M. Henkel, T. Bach
Paper
(
3.00 mg, 11.3 mol, 0.11 eq.) were converted as described above. Af-
Chem. Soc. Rev. 2012, 41, 3929. (f) Inman, M.; Moody, C. J. Chem.
Sci. 2013, 4, 29. (g) Gribble, G. W. Indole Ring Synthesis: From
Natural Products to Drug Discovery; Wiley: Chichester, 2016.
(h) Mancuso, R.; Dalpozzo, R. Catalysts 2018, 8, 458.
ter workup, the crude material was subjected to FCC (pentane/Et O
2
15
3
°
:1) to afford 7 (11.0 mg, 47.8 mol, 48%) as a yellow solid; mp 163
C.
IR (ATR): 3328 (m, NH), 3101 (w, C –H), 2921 (m, Calk–H), 2847 (w,
(
2) Selected reviews: (a) Cacchi, S.; Fabrizi, G. Chem. Rev. 2005, 105,
ar
–1
2873. (b) Seregin, I. V.; Gevorgyan, V. Chem. Soc. Rev. 2007, 36,
Calk–H), 1475 (m), 1316 (s), 1276 cm (m).
1
1173. (c) Bandini, M.; Eichholzer, A. Angew. Chem. Int. Ed. 2009,
H NMR (500 MHz, CDCl , 300 K):  = 1.75–1.84 (m, 4 H, H-7, H-8)*,
3
48, 9608. (d) Bartoli, G.; Bencivenni, G.; Dalpozzo, R. Chem. Soc.
3
1
8
1
.88–1.95 (m, 2 H, H-9)*, 2.82–2.89 (m, 4 H, H-6, H-10), 7.26 (d, J =
.9 Hz, 1 H, H-4), 8.01 (dd, J = 8.9 Hz, J = 2.2 Hz, 1 H, H-3), 8.10 (br s,
H, N-H), 8.44 (d, J = 2.2 Hz, 1 H, H-1).
Rev. 2010, 39, 4449. (e) Lebrasseur, N.; Larrosa, I. Adv. Hetero-
cycl. Chem. 2012, 105, 309. (f) Dalpozzo, R. Chem. Soc. Rev. 2015,
3
4
4
44, 742. (g) Leitch, J. A.; Bhonoah, Y.; Frost, C. G. ACS Catal. 2017,
1
3
C NMR (126 MHz, CDCl , 300 K):  = 24.7, 27.3, 28.5, 29.7, 31.6,
7, 5618. (h) Vorobyeva, D. V.; Osipov, S. N. Synthesis 2018, 50,
227. (i) Kalepu, J.; Gandeepan, P.; Ackermann, L.; Pilarski, L. T.
Chem. Sci. 2018, 9, 4203. (j) Sandtorv, A. H. Adv. Synth. Catal.
2018, 357, 2403. (k) Le Bras, J.; Muzart, J. Synthesis 2019, 51,
3
1
10.1, 115.2, 116.4, 116.6, 128.9, 137.5, 140.9, 141.5.
+
HRMS-EI (70 eV): m/z [M] calcd for C13H14N O : 230.1050; found:
2
2
2
13
30.1047; calcd for C12 C1H14N O : 231.1083; found: 231.1081.
2 2
2871.
(
3) Reviews: (a) Ye, J.; Lautens, M. Nat. Chem. 2015, 7, 863. (b) Della
Ca’, N.; Fontana, M.; Motti, E.; Catellani, M. Acc. Chem. Res. 2016,
2
-Nitro-7,8,9,10-tetrahydro-6H-azepino[1,2-a]indole (8)
2-(5-Bromopentyl)-5-nitro-1H-indole (6; 30.9 mg, 99.3 mol, 1.00
49, 1389. (c) Wang, J.; Dong, G. Chem. Rev. 2019, 119, 7478.
eq.) and K HPO (34.9 mg, 200 mol, 2.02 eq.) were dissolved in 0.5 M
2
4
(4) (a) Jiao, L.; Bach, T. J. Am. Chem. Soc. 2011, 133, 12990. (b) Jiao,
L.; Herdtweck, E.; Bach, T. J. Am. Chem. Soc. 2012, 134, 14563.
water in DMA solution (5 mL). The mixture was heated at 100 °C for
4 h. After usual workup (see GP), the crude material was subjected
2
(
(
c) Potukuchi, H. K.; Bach, T. J. Org. Chem. 2013, 78, 12263.
d) Jiao, L.; Bach, T. Synthesis 2014, 46, 35.
to FCC (pentane/Et O 9:1) to afford 8 (3.5 mg, 15.2 mol, 15%) as a yel-
low solid; mp 115 °C.
2
(5) Recent review: Wegmann, M.; Henkel, M.; Bach, T. Org. Biomol.
IR (ATR): 3089 (w, C –H), 2932 (m, C –H), 2854 (w, Calk–H), 1510 (s),
Chem. 2018, 16, 5376.
ar
alk
–1
1332 (s), 1285 (m), 1070 (m), 753 cm (m).
(6) Recent reviews: (a) Haak, E. Synlett 2019, 30, 245. (b) Ciulla, M.
G.; Zimmermann, S.; Kumar, K. Org. Biomol. Chem. 2019, 17,
413.
(7) (a) Jeffery, T. J. Chem. Soc., Chem. Commun. 1984, 1287.
(b) Jeffery, T. Tetrahedron Lett. 1985, 26, 2667.
8) Synthesis of [a]-indole derivatives by the cyclization method:
Jiang, C.; Gao, Y.; Li, J. CN 108003160, 2018.
9) Ishikura, M.; Terashima, M. Tetrahedron Lett. 1992, 33, 6849.
1
H NMR (500 MHz, CDCl , 300 K):  = 1.74–1.85 (m, 4 H, H-7, H-8),
3
3
3
1
4
.86–1.93 (m, 2 H, H-9), 2.93 (t, J = 5.5 Hz, 2 H, H-10), 4.20 (t, J =
3
.5 Hz, 2 H, H-6), 6.41 (s, 1 H, H-11), 7.25 (d, J = 9.2 Hz, 1 H, H-4), 8.05
3
4
4
(dd, J = 9.2 Hz, J = 2.3 Hz, 1 H, H-3), 8.47 (d, J = 2.3 Hz, 1 H, H-1).
(
13
C NMR (126 MHz, CDCl , 300 K):  = 27.9, 28.8, 29.4, 31.0, 45.5,
3
101.8, 108.5, 116.5, 117.2, 127.2, 139.9, 141.2, 146.9.
(
+
HRMS-EI (70 eV): m/z [M] calcd for C13H14N O : 230.1050; found:
2
2
(10) (a) Wender, P. A.; Cooper, C. B. Tetrahedron 1986, 42, 2985.
(b) Chen, H. G.; Hoechstetter, C.; Knochel, P. Tetrahedron Lett.
13
2
30.1048; calcd for C12 C1H N O : 231.1083; found: 231.1083.
14 2 2
1989, 30, 4795.
(11) Review: Monakhova, N.; Ryabova, S.; Makarov, V. J. Heterocycl.
Chem. 2016, 53, 685.
Funding Information
(
12) (a) Ziegler, F. E.; Jeroncic, L. O. J. Org. Chem. 1991, 56, 3479.
(b) Artis, D. R.; Cho, I.-S.; Jaime-Figueroa, S.; Muchowski, J. M.
J. Org. Chem. 1994, 59, 2456. (c) Caddick, S.; Aboutayab, K.;
Jenkins, K.; West, R. I. J. Chem. Soc., Perkin Trans. 1 1996, 675.
This project was supported by the Deutsche Forschungsgemeinschaft
BA 1372/19-1) and by the Technische Universität München (TUM)
(
Graduate School.
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(d) Venning, A. R. O.; Bohan, P. T.; Alexanian, E. J. J. Am. Chem.
Soc. 2015, 137, 3731. (e) Kaldas, S. J.; Cannillo, A.; McCallum, T.;
Barriault, L. Org. Lett. 2015, 17, 2864.
Supporting Information
(
13) (a) Noland, W. E.; Xia, G.-M.; Gee, K. R.; Konkel, M. J.;
Supporting information for this article is available online at
Whalstrom, M. J.; Condoluci, J. J.; Rieger, D. L. Tetrahedron 1996,
https://doi.org/10.1055/s-0039-1690693.
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52, 4555. (b) Youn, S. W.; Pastine, S. J.; Sames, D. Org. Lett. 2004,
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Primary Data
Huang, P.; Wen, S. Org. Biomol. Chem. 2014, 12, 9777. (e) El-
Sayed, M. T.; Mahmoud, K. A.; Heinemann, F. W.; Hilgeroth, A.
J. Heterocycl. Chem. 2017, 54, 714. (f) Hansen, C. L.; Ohm, R. G.;
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for this article are available online at https://doi.org/10.1055/s-0039-
1
690693 and can be cited using the following DOI: 10.4125/pd0108th. Pri
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5990. (g) Chen, S.; Li, Y.; Ni, P.; Yang, B.; Huang, H.; Deng, G.-J.
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H
Synthesis
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©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–H