Alkylation of indoles by aziridinium ions: New rapid access to tetrahydro-β-carbolines (THBCs)

Article abstract of DOI:10.1016/j.tet.2014.05.009

The alkylation of indoles by aziridinium ions generated in situ from β-amino chlorides was explored. The outcome of this reaction strongly relied on the substitution pattern of the starting β-amino chloride and requires silver tetrafluoroborate activation to proceed in reasonable yield. Ephedrine- and pseudoephedrine-derived N-cyanomethyl-β-amino chlorides afforded the corresponding tryptamines in a regio- and stereoselective manner and subsequent silver(I)-promoted Pictet-Spengler reactions produced 4-phenyl substituted THBCs in good yields. Unexpected epimerization at C-3 was found in these reactions, producing trans-3,4-disubstituted THBCs stereoselectively.

Full text of DOI:10.1016/j.tet.2014.05.009

Accepted Manuscript
Alkylation of Indoles by Aziridinium ions: New Rapid Access to Tetrahydro-β-
Carbolines (THBCs)
Laurence Menguy , Cheikh Lo , Jérôme Marrot , François Couty
PII:
S0040-4020(14)00669-3
10.1016/j.tet.2014.05.009
TET 25558
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 28 March 2014
Revised Date: 2 May 2014
Accepted Date: 3 May 2014
Please cite this article as: Menguy L, Lo C, Marrot J, Couty F, Alkylation of Indoles by Aziridinium
ions: New Rapid Access to Tetrahydro-β-Carbolines (THBCs), Tetrahedron (2014), doi: 10.1016/
j.tet.2014.05.009.
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Alkylation of Indoles by Aziridinium ions:
New Rapid Access to Tetrahydro-β-
Carbolines (THBCs)
Leave this area blank for abstract info.
Laurence Menguy, Cheikh Lo, Jérôme Marrot and François Couty
a
Institute Lavoisier de Versailles, UMR 8180. Université de Versailles St-Quentin en Yvelines. 45, av. des Etats-
Unis, 78035 Versailles Cedex, France.

1
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Tetrahedron
journal homepage: www.elsevier.com
Alkylation of Indoles by Aziridinium ions: New Rapid Access to Tetrahydro-β-
Carbolines (THBCs)
[
a]
[a]
[a]
[a]
Laurence Menguy, Cheikh Lo, Jérôme Marrot and François Couty*
a
Institute Lavoisier de Versailles, UMR 8180. Université de Versailles St-Quentin en Yvelines. 45, av. des Etats-Unis, 78035 Versailles Cedex, France
Fax: +33 (0) 1 39 25 44 52. E-mail: couty@chimie.uvsq.fr
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
The alkylation of indoles by aziridinium ions generated in-situ from β-amino chlorides was
explored. The outcome of this reaction strongly relied on the substitution pattern of the starting
β-amino chloride and requires silver tetrafluoroborate activation to proceed in reasonable yield.
Ephedrine- and pseudoephedrine-derived N-cyanomethyl-β-amino chlorides afforded the
corresponding tryptamines in a regio- and stereoselective manner and subsequent silver(I)-
promoted Pictet-Spengler reactions produced 4-phenyl substituted THBCs in good yields.
Unexpected epimerization at C-3 was found in these reactions, producing trans-3,4-disubstituted
THBCs stereoselectively.
Available online
Keywords:
Aziridinium ions
Indoles
2
009 Elsevier Ltd. All rights reserved.
Tetrahydro-β-carbolines
Pictet-Spengler reaction
R3
R2
1
. Introduction
3
NO2
R2
NH
R3
R2
R3
4
Tetrahydro-β-carbolines 1 (THBCs) belong to a family of
PS
R3
R2
3
R4
R4
2
extensively studied alkaloids due to their strong biological
activity in the CNS and their privileged binding to serotonin
receptors. Classical access to this skeleton involves a Pictet-
Spengler (P-S) reaction of the required tryptamine 2, allowing
predictable stereocontrol of the produced C-1 stereocenter.
Therefore, synthetic routes to substituted tryptamines have been
particularly scrutinized, and the most direct ones rely on Friedel-
Crafts (F-C) reactions of the corresponding indoles with either
nitroalkenes 3 or aziridines 4 as electrophilic partners, both
reactions being promoted by Lewis acids and/or organocatalysts.
While the former route has been extensively studied, culminating
in enantioselective versions allowing introduction of substituents
NH
N
4
R3
5
PG
1
1
R1
N
N
H
H
R2
1
2
2
N
H
X
-
X = H, BF
3
Scheme 1. Synthetic routes to TBHCs 1
To the best of our knowledge, β-chloroamines 6 are as yet
unexplored electrophilic partners in such F-C reactions. These
compounds are prone to generate aziridinium ions through
intramolecular substitution that could further react with indoles.
We report herein the behaviour of such halides in F-C reactions
with indoles (Scheme 2).
3
at C-4 and/or C-3, this route still requires an extra reduction step
6
of the nitro group before performing the P-S reaction. On the
other hand, F-C reactions of indoles with aziridines 4 are
particularly sensitive to the nature of substituents on the aziridine
ring, and require specific Lewis acids activation, together with
R5
4
electron withdrawing groups on the aziridine heterocycle. A
much less explored route is the direct reaction of aziridinium ions
such as 5 with indoles, which might be due to the difficulties in
generating and controlling the reactivity of these electrophilic
species, though this way offers the advantage of directly
furnishing the target tryptamine devoid of a protecting group on
the nitrogen atom and ready for the ensuing P-S step (Scheme 1).
R3
N
R3
R4
R1
H
Cl
Tryptamines
N
R2
5
R1N R2
- HCl
R4
6
Scheme 2. β-Chloroamines as aziridinium precursors for F-C reactions.

2
Tetrahedron
ACCEPTED MANUSCRIPT
2
. Results and discussion
for two reasons. First, it is known that the lone pair of the
nitrogen atom in amino nitriles is deactivated by the anomeric
effect, thus preventing competitive complexation of the lone pair
of the nitrogen atom with Ag(I), which slows down formation of
the aziridinium ion. In addition, amino nitriles are direct
precursors of iminium ions by abstraction of cyanide anion,
N,N-Dibenzyl amino chloride 7 was first examined as the
electrophilic partner in such F-C reactions. 5-Methoxyindole 8,
with a nucleophilicity parameter N of 6.22, was selected as a
suitable nucleophilic indole. Refluxing these compounds (2
equiv. of chloride) in acetonitrile did not lead to any reaction,
however, addition of AgBF (2 equiv.) as a chloride scavenger
led, after 3h at reflux, to the expected tryptamine 9 in a low
isolated yield, that could not be improved by the use of other
refluxing solvents (Scheme 3). In order to gain a better
understanding of the reaction between chloride 7 and AgBF , it
was monitored by NMR in CD Cl . Thus, chloride 7 was added
7
8
which are intermediates in P-S reactions. Thus these compounds
4
appear at first sight to be ideal candidates in the Ag(I)-promoted
F-C reaction. The β-amino chloride 12 was tested first under
previously standardized conditions, yielding bis-indolylmethane
1
3 in 54% isolated yield. This product is formed through a
9
4
Mannich reaction which implies the competitive formation of an
2
2
iminium ion 14 from 12, upon activation with AgBF , which was
produced more efficiently than the aziridinium ion 15 required
for the F-C reaction. This was confirmed by monitoring the
reaction of 12 with AgBF by NMR, as depicted in Scheme 5:
4
to a solution of AgBF (1.2 equiv.) in CD Cl and samples were
4
2
2
1
examined by H NMR, showing that aziridinium ion was
produced almost quantitatively after 10 min, as shown by the
appearance of two singlets at 4.50 and 3.09 ppm, and proved to
be stable in solution for at least 40 min.
4
Two doublets, J = 4.4 Hz,
at 7.93 and 8.20 ppm
Bn
N
CN
Bn
N
AgBF4
CD Cl
Cl
H
H
Cl
Bn
N
, BF4
Cl
Bn
N
MeO
7
MeO
Bn
2
2
Ph
>
50% after
12
14
1
5 min
Reflux, 3.5h
N
N
8
H
9
H
MeO
OMe
AgBF4
DCM, 8
Additive Solvent Yield (%)
N
, BF4
CN
None
AgBF
AgBF4
AgBF4
MeCN
MeCN
THF
0
26
7
Bn
54%
4
N
H
N
H
15
13
DCM
9
AgBF
4
Toluene
15
Scheme 5. AgBF
promotes formation of iminium 14 and not
aziridinium 15.
4
Scheme 3. F-C reaction of β-amino chloride 7 with indole 8 requires
In order to circumvent this problem, we next examined
silver tetrafluoroborate as additive.
ephedrine-derived and pseudoephedrine derived β-amino
chlorides 16-18, hoping that the benzylic chloride atom in these
substrates would be more reactive towards intramolecular
substitution. Gratifyingly, monitoring of the reaction of 16 in
Addition of 5-methoxy indole 8 to this solution (rt) showed
that formation of the tryptamine was not rapid since after 15min,
no appreciable reaction was observed and after 2h, 32% of
starting indole was still present. We thus modified our protocol
by adding 8 to a preformed solution of aziridinium (1.2 equiv.) in
DCM followed by stirring for 72h at rt and isolated 9 in 42%
yield. However, switching to N-benzyl-N-methyl amino chloride
10
CD CN unambiguously showed selective formation of the
3
aziridinium ion 19, instead of an iminium ion (Scheme 6):
Me
1
0 surprisingly gave no trace of the expected tryptamine under
Me
Me
Me
NC
Cl
Bn
Cl
Me
NC
Cl
these conditions. We thus monitored formation of aziridinium 11
by NMR and found that, in sharp contrast with 7, only trace
amounts of aziridinium 11 could be detected in the solution,
together with the starting chloride, after 30 min. Leaving the
mixture to stand overnight led to a complex mixture of products.
Other solvents (MeCN, DMSO, acetone) were tried with no
success (Scheme 4). Clearly, lower steric crowding around the
nitrogen atom compared to 7 is a critical parameter and
complexation of the amine with Ag (I), as suggested by
N
N
N
Ph
Ph
Ph
18
NC
1
6
17
two doublets, J = 6.5 Hz
at 1.81 and 1.85 ppm
Me
Me
Ph
,
AgBF , CD CN
4
3
N
BF4
>
66% after 15 min
two singlets at
2.71 and 3.30 ppm
CN
19: 1/1 ratio of
diastereoisomers
1
broadening of the signals in H NMR, probably competes with
chloride abstraction and hampers formation of the aziridinium
ion.
4
Scheme 6. AgBF promotes formation of aziridinium 19.
Reaction of these halides with different indoles was thus
studied under various conditions (solvent, Lewis acid), and these
experiments are shown in Table 1. The first three entries
conducted with N-Bn chloride 17 demonstrate that the best
conditions were with MeCN as solvent, with a slight excess of
preformed aziridinium ion. Under these conditions, tryptamine
20 was isolated in 51% yield and was produced regio- and
stereoselectively (entry 3). In contrast, tryptamine 21 was
produced in low yield and stereoselectivity. It should be
Multiplets at 3.05 and 3.25 ppm
AgBF4
CD Cl
Me
Cl
,
BF
4
N
N
Me
2
2
Bn
<
5% after 4.41 ppm
5 min
10
11
3.07 ppm
1
Scheme 4. Aziridinium 11 is not efficiently produced upon reaction
with AgBF
mentioned that other halide scavengers, such as AlCl , or
3
4
.
[
(MeCN) Cu]PF were tested without success. Next the reaction
4 6
Having learned through these experiments, we next turned to
of N-Me chloride 16 was examined under these conditions with a
the use of β-amino chlorides with a N-cyanomethyl substituent
series of indoles (entries 5-10). In all cases, tryptamines were

3
produced with high regio- and stereoselectivity
A
ex
C
ce
C
pt
E
f
P
or
T
in
E
do
D
le MAyi
N
eld
U
in
S
g
C
ep
R
im
I
e
P
ric tryptamines 28-30 at the benzylic position. It
T
8
(entry 5) albeit in modest yields. The main by-products found
should be noted that 3-methyl indole yielded the corresponding
2-substituted indoles (entries 10,14). The structure of tryptamine
23 was determined by X-ray crystallography showing that
were unreacted indoles and β-amino alcohols resulting from the
11
opening of the aziridinium ion by water. Nucleophilic indoles
7
such as 2-Me indole (N = 6.91, entry 8) reacted well, while
inversion had occurred at the benzylic position.
electron deficient 5-nitro indole reacted with poor yield (entry 9).
Pseudoephedrine-derived chloride 18 showed similar behaviour,
Table 1. Friedel-Crafts reactions of ephedrine-derived chlorides.
Entry
1
Halide
Indole
Conditions
Product
Yield (de) (%)
Bn
Ph
N
No additive,
CN
17
8
4 (>95)
MeO
Me
MeCN, Reflux, 40h
N
20
H
2
3
17
17
8
8
AgBF
4
(1.2 equiv.),
20
20
41 (22)
DCM, 2h30
AgBF
4
(1.2 equiv.),
51 (> 95)
MeCN, 2h30
Bn
Ph
N
CN
Me
4
5
17
16
indole
Id.
Id.
25 (20)
34 (50)
N
H
21
Me
Ph
N
CN
8
MeO
Me
N
22
H
Me
Ph
N
5
-Chloro
indole
CN
6
16
Id.
Cl
32 (>95)
Me
N
23
H
Me
Ph
N
CN
N-Methyl
indole
Me
7
8
16
16
Id.
Id.
25 (>95)
40 (>95)
N
Me
Me
24
Ph
N
CN
2-Methyl
indole
Me
Me
N
H
25
Me
Ph
N
5
-Nitro
CN
9
16
16
18
Id.
Id.
Id.
O N
Me
5 (>95)
21 (>95)
40 (>95)
2
indole
N
H
26
Me Me Me
N
3
-Methyl
indole
1
1
0
1
CN
N
Ph
H
27
Me
Ph
N
5-Chloro
indole
CN
CN
Cl
Me
N
H
28
Me
Ph
N
1
2
18
5-Methyl
indole
Id.
44(>95)
Me
Me
N
29
H

4
Tetrahedron
ACCEPTED MANUSCRIPT
5
-Methoxy
indole
1
1
3
4
18
18
Id.
22
28(>95)
18 (>95)
3
-Methyl
indole
Me
Me
Id
Me
N
CN
N
Ph
H
30
It appears that this reaction is extremely sensitive to both the
performed to clarify this point (Scheme 8). This epimerization
leads to interesting questions on how simple amino nitriles can be
the precursors of azomethine ylides, and alerts the synthetic
community on possible epimerization at C-3 occurring during the
synthesis of THBCs through a Pictet-Spengler reaction.
nature of the β-amino chloride and of the indole. When the first
efficiently produces an intermediate aziridinium ion, and the
reacting indole is sufficiently nucleophilic, then tryptamines are
produced regio- and stereoselectively through an S 2 opening of
N
the aziridinium ion. Otherwise, an S 1 reaction competes,
leading to partial or extensive (entry 5) epimerization at the
benzylic position.
N
Me
Ph
Me
N
Ph
AgBF
4
Cl
N Me
2
3
Cl
Me
Next the Pictet-Spengler reaction of the prepared tryptamines
was studied. Simple heating in THF of tryptamines 23, 28, 22
and 29, bearing a N-cyanomethyl group, in the presence of 1.1
N
N
35
H
H
slow
equiv. of AgBF led to the corresponding THBCs 31, ent-31, 33
4
Me
N
Ph
and 34 in good yield (Scheme 7). However, we were surprised to
notice that epimerization had occurred when ephedrine-derived
chloro-indole 23 was reacted under these conditions. The major
isomer 31 produced gave suitable crystals for X-ray analysis and
allowed us to conclude that epimerization had occurred quite
surprisingly at C-3 and that the expected cis isomer 32 was
present in only 15% yield in the mixture. It should be noted that
the absolute configuration of the stereocenters was
unambiguously determined by X-ray crystallography, due to the
presence of the chloride atom on the aromatic ring and
32
Rapid Cl
Me
3
1
N
36
H
Scheme 8. Epimerization at C-3 may occur via an azomethine ylide.
3. Conclusion
In conclusion, we have demonstrated for the first time that β-
chloroamines are suitable precursors of aziridinium ions upon
chloride abstraction by Ag(BF ) and are able to react with indoles
1
2
convergence of the Flack parameter. Pseudoephedrine-derived
tryptamine 28 gave as the major product ent-31 but still minor
amounts (ca 5%) of the epimer at C-3 were detected in the crude
reaction mixture. The structure of the major epimer ent-31 was
4
through Friedel-Crafts reactions leading directly to tryptamines.
The nature of the substituents on the nitrogen atom is a crucial
factor since its lone pair needs to be deactivated either by bulky
substituents (Bn) or by a cyanomethyl group, to avoid interaction
between the silver salt and the nitrogen atom that can hamper
halide abstraction. With reactive benzylic chlorides, the reaction
gives tryptamines often with high regio- and stereoselectivity,
although yields are modest. Finally, the produced N-cyanomethyl
tryptamines can be efficiently transformed into TBHCs through a
11
again secured by X-ray crystallography, thereby confirming the
absolute and relative configurations in 31 and ent-31.
Me
N
Me
N
Ph
Ph
AgBF4, 1,1 equiv. Cl
THF, reflux 2h30
Me
Cl
Me
2
3
+
N
N
31
32
Me
N
6
0%
(X-Ray)
85 : 15
H
H
Pictet-Spengler reaction mediated by AgBF . During the course
of this reaction, unexpected epimerization was observed at C-3.
4
Me
N
Ph
Ph
Me
Me
Id
Cl
Cl
28
+
4. Experimental section
84%
N
N
H
ent-31
ent-32
H
General information: N-cyanomethyl-β-chloroamines 16-18
were prepared following our previously reported procedures
respectively from (1R,2S)-ephedrine, (1R,2S)-norephedrine,
(
X-Ray)
9
5 : 5
Me
N
Ph
1
0
Me
(1S,2S)-pseudoephedrine. Chlorides 7 and 10 were obtained
Id
Me
[15]
22
after respectively benzylation of ethanolamine and methylation
65%
16
N
H
33 (ed 90%)
of benzylaminoethanol. All chemicals were used as received.
Acetonitrile and dichloromethane was freshly distilled from
calcium hydride. Tetrahydrofuran was distilled from sodium
benzophenone ketyl. Purifications were performed by column
chromatography on silica gel 230-400 mesh or by preparative
Me
N
Ph
Id
MeO
Me
29
60%
N
34
1
13
TLCs. H and C NMR spectra were collected on a Bruker
Avance spectrometer respectively at 300 and 75 MHz. Data are
presented as follows: chemical shift (in ppm on the δ scale
relative to δTMS = 0), multiplicity (s = singlet, d = doublet, t =
triplet, m = multiplet, b = broad), coupling constant (J/Hz),
integration and attribution. High resolution mass spectra (HR-
MS) were obtained on a Waters Micromass Q-Tof Micro
instrument. Optical rotations were determined on a Perkin Elmer
H
Scheme 7. Pictet-Spengler reactions of N-cyanomethyl tryptamines.
This unexpected epimerization at C-3, which leads to the more
stable (trans) THBC 31 has seldom been reported in the
literature and may occur through an intermediate azomethine
[
13]
[
14]
ylide 35, though additional mechanistic studies need to be
3
41 polarimeter.

5
4
.1. General procedure using AgBF for the synthesis of
( 300 MHz, CDCl ) : δ (ppm) : 7.86 ( bs, 1H, NH), 7.30-7.00
3
4
ACCEPTED MANUSCRIPT
tryptamine derivatives
(m, 14H, HAr), 6.64 (d, 1H, HAr), 4.17 (d, A part of AB syst., J
15Hz, 1H, H4-a), 3.97 (d, B part of AB syst., J = 15Hz , 1H, H-
b), 3.96 (d, A part of AB syst., J = 17Hz, 1H, H-5), 3.91 (d, J =
Hz 1H, H-2), 3.63 (d, B part of AB syst., J = 17Hz ,1H, H-5b),
.15-3.03 (m, 1H, H-1), 1.14 (d, J = 6Hz, 3H, H-3). C NMR (75
MHz, CDCl ) : δ (ppm): 142.9, 136.6, 113.8 (CqAr), 129.9,
29.0, 127.3, 127.1, 127.0, 126.5, 125.8, 117.9, 117.4 (CHAr),
0.5 (C-1), 54.4 (C-4), 52.3 (C-2), 41.7 (C-5), 15.9 (C-3). HRMS
ESI) m/z calcd for C H N [M+H] : 380.2127, found:
=
Silver tetrafluoroborate was quickly weighed (185 mg, 0,96
mmol, 1.24 eq.) and dissolved in 5 mL of MeCN under an argon
atmosphere and stirred for 10 min at room temperature.
β−Chlorinated amines (0,9 mmol, 1.16 eq.), dissolved in MeCN
4
9
3
13
3
(1 mL) was added dropwise leading to the formation of a
1
6
(
precipitate. After 30 min, the indole (0,77 mmol, 1 eq.) was
added and the mixture was monitored by TLC (EtOAc/PE). The
reaction was worked-up after 2.5 hours with 3 mL of a saturated
+
26
26
3
3
80.2127.
aqueous solution of NaHCO and 3 mL of 15% aqueous NH3
3
solution. The mixture was then filtered on Celite and rinsed with
4.5. (1S,2S) and (1S,2R)-{[2-(5-Methoxy-1H-indol-3-yl)-1-
methyl-2-phenyl-ethyl]-methyl-amino}-acetonitrile (22):
EtOAc. After usual workup (H O/EtOAc), the residue was
2
purified by column chromatography (silica gel; PE/EtOAc).
Orange oil (19 mg, 34%); R = 0.45 (EtOAc/PE: 30/70); NMR
f
1
4
.2. Dibenzyl-(5-methoxy-1H-indol-3-ylethyl)-amine (9):
of major epimer : H NMR ( 300 MHz, CDCl ) : δ (ppm) : 8.03 (
3
bs, 1H, NH), 7.35-7.12 (m, 7H, Ph, H-2, H-7), 6.96 (d, J = 2Hz,
1
Colorless oil (30 mg, 42%); R =0.43 (EtOAc/PE : 15/85); H
f
1
1
H, H-4), 6.82 (dd, J = 9Hz, J = 2Hz, 1H, H-6), 4.20 (d, J = 9Hz,
RMN (300 MHz, CDCl ) : δ (ppm) : 7.97 ( bs, 1H, NH), 7.47-
.23 (m, 11H, HAr), 6.95 (bs, 1H, HAr), 6.82-6.79 (m, 2H, HAr),
.76 (bs, 7H, H-3, H-4, ArOCH ), 3.02-2.98 (bm, 2H, H-1), 2.85-
.80 (bm, 2H, H-2); C NMR (75 MHz, CDCl ) : δ (ppm):
53.8, 139.9, 131.3, 128.9, 128.5, 128.3, 127.8, 126.9, 122.4,
12.3, 111.8, 100.4 (CqAr, CHAr), 58.26 (C-3, C-4), 55.90
ArOCH ), 53.68 (C-1), 23.08 (C-2); HRMS (ESI) m/z calcd for
3
H, H-2), 3.81 (s, 3H, ArOCH ), 3.59-3.48 (m, 1H, H-1), 3.42
3
7
3
2
1
1
(
bs, AB syst., 2H, H-5a, H-5b), 2.40 (s, 3H, H-4), 1.15 (d, J =
13
3
7
1
1
Hz, 3H, H-3); C NMR ( 75 MHz, CDCl ) : δ (ppm): 153.9,
13
3
3
43.4, 131.3, 129.9, 127.9, 127.7, 126.0, 122.6, 117.1, 117.0,
01.6 (CqAr, CHAr), 128.3, 128.2 (CHPh), 62.0 (C-1), 56.0
(
ArOCH ), 47.5 (C-2), 42.8 (C-5), 37.2 (C-4), 12.4 (C-3); NMR
3
(
1
3
of minor epimer : H NMR ( 300 MHz, CDCl ) : δ (ppm) : 8.21 (
+
3
C H N O [M+H] : 371.2123, found: 371.2127.
2
5
26
2
bs, 1H, NH), 7.35-7.12 (m, 7H, Ph, H-2, H-7), 6.74 (dd, J = 9Hz,
J = 2Hz, 1H, H-6), 6.30 (d, J = 2Hz, 1H, H-4), 4.39 (d, J = 5Hz,
4
1
.3. (1S,2S) and (1S,2R)-{benzyl-[2-(5-Methoxy-1H-indol-3-yl)-
-methyl-2-phenyl-ethyl]-amino}-acetonitrile (20):
1
H, H-2), 3.93 (d, A part of AB syst., J = 15Hz, 1H, H-5a,), 3.58
(
s, 3H, OCH ), 3.64 (d, B part of AB syst., J = 15Hz , 1H, H-5b),
3
Dark red amorphous solid (102 mg, 41%); Rf =0.62
EtOAc/PE : 30/70); NMR of major epimer: H NMR ( 300
MHz, CDCl ) : δ (ppm) : 8.11 ( bs, 1H, NH), 7.43-6.80 (m, 14H,
Ph, H-2, H-4, H-6, H-7), 4.32 (d, J = 9Hz, 1H, H-2), 4,00 (d, A
3.23-3.14 (m, 1H, H-1), 2.51 (s, 3H, H-4), 0.85 (d, J = 7Hz, 3H,
1
13
(
H-3); C NMR ( 75 MHz, CDCl ) : δ (ppm): 153.5, 131.5,
3
3
127.2, 126.6, 111.9, 111.8, 111.4, 111.0, 102.4 (CqAr, CHAr),
6
0.2 (C-1), 55.7 (ArOCH ), 43.7 (C-2), 48.2 (C-5), 42.1 (C-4),
3
part of AB syst., J = 14Hz, 1H, H-4a), 3.90 (s, 3H, ArOCH3),
11.7 (C-3). Major epimer was obtained pure starting from 200
3
1
.93-3.80 (m, 1H, H-1), 3.61 (d, B part of AB syst., J = 17Hz,
H, H-4b), 3.46 (d, A part of AB syst., J = 17Hz, 1H, H-5a), 3.30
mg of 18. White solid (84 mg, 28%); R = 0.41 (EtOAc/PE :
f
20
3
0/70); Mp 127°C; [α]D = -12.2 (c 0.3, CH Cl ); HRMS (ESI)
2 2
+
(d, B part of AB syst., J = 17Hz, 1H, H-5b), 1.33 (d, J = 6Hz, 3H,
m/z calcd for C H N O [M+H] : 334.1919, found: 334.1928.
21
24
3
13
H-3); C NMR (75 MHz, CDCl ) : δ (ppm): 154.0, 143.8, 137.5,
1
1
3
4
.6. (1S,2S)-{[2-(5-Chloro-1H-indol-3-yl)-1-methyl-2-phenyl-
31.4, 127.5, 117.6, 117.5 (CqAr), 128.7, 128.4, 128.3, 128.2,
27.4, 126.0, 122.2, 112.0, 111.9, 101.3 (CHAr), 61.8 (C-1), 56.0
ethyl]-methyl-amino}-acetonitrile (23):
(ArOCH ), 53.3 (C-4), 48.3 (C-2), 38.3 (C-5), 13.0 (C-3). NMR
20
3
Orange oil (82 mg, 32%); R = 0.22 (EtOAc/PE : 30/70); [α]
D
1
f
of minor epimer: H NMR ( 300 MHz, CDCl ) : δ (ppm) : 7.43-
1
3
=
-69.8 (c 0.5, CH Cl ); H NMR ( 300 MHz, CDCl ) : δ (ppm) :
2
2
3
6
.80 (m, 15H, Ph, H-2, H-4, H-6, H-7), 4.20 (d, J = 15Hz, 1H,
H4-a), 4.04 (d, J = 14Hz , 2H, H-4b, H-5a), 3.98 (d, J = 10Hz,
H, H-2), 3.93 (s, 3H, OCH ), (d, J = 14Hz ,1H, H-5b), 3.12-3.03
8
.19 ( bs, 1H, NH), 7.55 (d, 1H, H-4), 7.36-7.11 (m, 8H, Ph, H-2,
H-6, H-7), 4.22 (d, J = 9Hz, 1H, H-2), 3.63-3.53 (m, 1H, H-1),
.46 (d, A part of AB syst., J = 18Hz, 1H, H-5a), 3.39 (d, B part
of AB syst., J = 18Hz, 1H, H-5b), 2.41 (s, 3H, H-4), 1.15 (d, J =
1
3
3
13
(m, 1H, H-1), 1.19 (d, J = 6Hz, 3H, H-3); C NMR (75 MHz,
CDCl ) : δ (ppm): 143.7, 137.2, 132.6, 130.0, 129.7, 129.1,
1
13
3
7
1
1
2
Hz, 3H, H-3); C NMR ( 75 MHz, CDCl ) : δ (ppm): 143.1,
3
28.9, 128.6, 127.8, 127.1, 127.0, 126.3, 126.0, 125.9, 114.8
34.3, 128.1, 125.2, 117.2, 117.1 (CqAr), 126.2, 123.1, 122.4,
18.5, 112.3 (CHAr), 128.3, 128.2 (CHPh), 62.0 (C-1), 47.4 (C-
(CqAr, CHAr), 60.2 (C-1), 54.6 (C-4), 56.0 (ArOCH ), 53.1 (C-
3
2
), 42.2 (C-5), 16.2 (C-3). HRMS (ESI) m/z calcd for C H N O
27 28 3
+
), 42.9 (C-5), 36.9 (C-4), 12.4 (C-3); HRMS (ESI) m/z calcd for
[
M+H] : 410.2232, found: 410.2234.
+
C H N Cl [M+H] : 338.1424, found: 338.1421.
20
21
3
4
.4. (1S,2S) and (1S,2R)-{benzyl-2-[1H-indol-3-yl)-1-methyl-2-
4
.7. (1S,2S)-{[2-(1-Methyl-indol-1H-3-yl)-1-methyl-2-phenyl-
phenyl-ethyl]-amino}-acetonitrile (21):
ethyl]-methyl-amino}-acetonitrile (24):
Dark red oil (102 mg, 25%); R =0.3 (EtOAc/PE : 20/80);
f
Orange needles (60 mg, 25%); R =0.35 (EtOAc/PE : 30/70);
1
f
NMR of major epimer: H NMR ( 300 MHz, CDCl ) : δ (ppm) :
20
1
3
Mp 132°C; [α]D = -33.9 (c 0.7, CH Cl ); H NMR (300 MHz,
2
2
8
1
2
(
3
.02 ( bs, 1H, NH), 7.58 (d, J = 8Hz, 1H, HAr), 7.30-7.00 (m,
2H, HAr), 6.80-6.77 (m, 2H, HAr), 4.26 (d, J = 11Hz, 1H, H-
), 3.92 (d, A part of AB syst., J = 14Hz, 1H, H-4a), 3.83-3.73
CDCl ) : δ (ppm) : 7.64 (d, 1H, ArH), 7.43-7.07 (m, 9H, Ar),
3
4
3
=
1
1
2
.33 (d, J = 9Hz, 1H, H-2), 3.77 (s, 3H, NCH of indole), 3.69-
3
.60 (m, 1H, H-1), 3.47 (s, 2H, H-5), 2.46 (s, 3H, H-4), 1.21 (d, J
m, 1H, H-1), 3.57 (d, B part of AB syst., J = 14Hz, 1H, H-4b),
13
7Hz , 3H, H-3); C NMR (75 MHz, CDCl ) : δ (ppm): 143.8,
3
.34 (d, A part of AB syst., J = 18Hz, 1H, H-5a), 3.18 (d, B part
36.8, 127.7, 126.5, 126.0, 121.7, 119.3, 118.0, 117.2, 115.9,
09.3 (CqAr, CHAr), 128.3, 128.3 (CHPh), 62.2 (C-1), 47.5 (C-
13
of AB syst., J = 18Hz, 1H, H-5b), 1.21 (d, J = 6Hz, 3H, H-3);
C
NMR (75 MHz, CDCl ) : δ (ppm): 143.7, 137.2, 136.0 (CqAr),
3
), 42.8 (C-5), 37.2 (C-4), 32.8 (NCH of indole), 12.4 (C-3);
3
1
1
(
29.5, 128.7, 128.6, 128.4, 128.3, 128.2, 127.4, 126.0, 122.1,
+
HRMS (ESI) m/z calcd for C H N [M+H] : 318.1970, found:
21
24
3
21.2, 119.5, 119.0, 111.2, (CHAr), 61.9 (C-1), 53.2 (C-4), 48.2
3
18.1973.
1
C-2), 38.2 (C-5), 13.0 (C-3). NMR of minor epimer: H NMR

6
Tetrahedron
4
.8. (1S,2S)-{[2-(2-Methyl-1H-indol-3-yl)-1-methyl-2-phenyl-
syst., J = 17Hz, 1H, H-5a), 3.29 (d, B part of AB syst., J = 17Hz,
ACCEPTED MANUSCRIPT
ethyl]-methyl-amino}-acetonitrile (25):
1H, H-5b), 2.40 (s, 3H, H-4), 2.15 (s, 3H, ArCH ), 1.10 (d, J =
3
13
7
1
1
2
Hz ,3H, H-3); C NMR ( 75 MHz, CDCl ) : δ (ppm): 141.8,
35.5, 134.7, 129.1, 116.9, 108.5 (CqAr), 126.7, 121.1, 118.9,
18.1, 110.7 (CHAr), 128.7, 128.0 (CHPh), 61.3 (C-1), 48.1 (C-
3
Brown amorphous solid (98 mg, 40%); R =0.42 (EtOAc/PE :
f
20
1
3
0/70); Mp 80°C; [α]D = +29.5 (c 0.1, CH Cl ); H NMR (300
2 2
MHz, CDCl ) : δ (ppm) : 7.75 (bd, 2H, NH, Ar), 7.47 (d, 2H,
Ar), 7.32-7.12 (m, 6H, Ar), 4.18 (d, J = 10Hz, 1H, H-2), 4.18-
3
), 42.6 (C-5), 37.7 (C-4), 13.1 (C-3), 9.0 (ArCH ); HRMS (ESI)
3
+
m/z calcd for C H N [M+H] : 318.1970, found: 318.1967.
21
24
3
4
5
3
.05 (m, 1H, H-1), 3.53 (d, A part of AB syst., J = 17Hz, 1H, H-
a), 3.44 (d, B part of AB syst., J = 17Hz, 1H, H-5b), 2.46, (s,
H, ArCH ), 2.43 (s, 3H, H-4), 1.06 (d, J = 7Hz, 3H, H-3);
4.13. General procedure using AgBF
tetrahydro-β-carboline
for the synthesis of
4
13
C
3
NMR (75 MHz, CDCl ) : δ (ppm): 143.6, 135.4, 131.5, 127.2,
3
To a solution of tryptamine derivative (0.54 mmol) in dry
THF (5 mL) was added silver tetrafluoroborate (127 mg, 0.59
mmol, 1.1 eq.) under argon atmosphere. The suspension was
1
1
4
25.8, 120.9, 119.4, 119.2, 117.7, 113.1, 110.6 (CqAr, CHAr),
28.2, 128.1 (CHPh), 59.7 (C-1), 47.1 (C-2), 42.4 (C-5), 36.1 (C-
), 12.4, 11.8 (C-3, ArCH ); HRMS (ESI) m/z calcd for C H N
3
3
21 24
+
heated to reflux for 3h and monitored by TLC (CH
Cl /EtOH,
2 2
[
M+H] : 318.1970, found: 318.1972.
9
/1). The reaction was quenched with 1 mL of a saturated
4
.9. (1S,2R)-{[2-(3-Methyl-1H-indol-2-yl)-1-Methyl-2-phenyl-
aqueous solution of NaHCO , filtered through Celite and rinsed
3
ethyl]-methyl-amino}-acetonitrile (27):
with EtOAc. After usual workup (H O/EtOAc), the residue was
2
purified by column chromatography (silica gel; CH Cl /EtOH,
1
2
2
Orange oil (51mg, 21%); R =0.50 (EtOAc/PE : 30/70); H
f
1
3/1 to 9/1). Samples were then crystallized from small volume
NMR (300 MHz, CDCl ) : δ (ppm) : 8.39 ( bs, 1H, NH), 7.54-
.09 (m, 9H, Ar), 4.31 (d, J = 9Hz, 1H, H-2), 3.65-3.56 (m, 1H,
3
of EtOAc.
7
H-1), 3.41 (bs, 2H, H-5), 2.43 (s, 3H, H-4), 2.29 (s, 3H, ArCH ),
4.14. (3R,4S)-6-Chloro-2,3-methyl-4-phenyl-1,2,3,4-tetrahydro-
β-carboline (31):
3
13
1
.15 (d, J = 6Hz , 3H, H-3); C NMR ( 75 MHz, CDCl ) : δ
3
(
1
ppm): 140.4, 135.6, 135.0, 129.0, 117.0, 108.0 (CqAr) 126.8,
21.5, 119.2, 118.4, 110.6, (CHAr), 128.7, 128.3 (CHPh), 60.7
Starting from 180 mg of 23. White needles (101 mg, 60%);
20
R = 0.33 (CH Cl /EtOH : 90/10); Mp 236°C; [α]
= -69.4 (c
f
2
2
D
(C-1), 47.1 (C-2), 42.9 (C-5), 37.6 (C-4), 11.8 (C-3), 9.0
1
+
0.2, acetone); H NMR ( 300 MHz, (CD
bs, 1H, NH), 7.29-7.18 (m, 6H, HAr), 6.92 (dd, J = 9Hz, J = 2Hz,
H, HAr), 6.53 (d, J = 2Hz, 1H, HAr), 3.90 (d, A part of AB
3 2
) SO) : δ (ppm) : 11.08 (
(ArCH ); HRMS (ESI) m/z calcd for C H N [M+H] :
3
21 24
3
3
18.1970, found: 318.1969.
1
4
.10. (1S,2R)-{[2-(5-Chloro-1H-indol-3-yl)-1-methyl-2-phenyl-
syst., J = 15Hz, 1H, H-1a), 3.81 (d, J = 6Hz, 1H, H-4), 3.72 (d, B
part of AB syst., J = 15Hz, 1H, H-1b), 2.83-2.74 (m, 1H, H-3),
ethyl]-methyl-amino}-acetonitrile (28):
13
2
.35 (s, 3H, NCH ), 1.00 (d, J = 6Hz, 3H, H-5); C NMR (75
3
Starting from 175 mg of 18. Yellow solid (61 mg, 40%); R =
f
MHz, (CD ) SO) : δ (ppm): 144.2, 134.9, 134.5, 127.5, 122.6,
20
D
3 2
0
.49 (EtOAc/PE : 30/70); Mp 164°C; [α]
= +2.5 (c 0.1,
1
08.8 (CqAr), 126.2, 119.8, 116.9, 112.3 (CHAr), 128.5, 128.0
1
CH Cl ); H NMR (200 MHz, CDCl ) : δ (ppm) : 8.14 ( bs, 1H,
NH), 7,53 (d, J = 2Hz, 1H, H-4), 7.36-7.09 (m, 9H, Ph, H-2, H-6,
H-7), 4.20 (d, J = 10Hz, 1H, H-2), 3.68-3.43 (m, 1H, H-1), 3.47
2
2
3
(
CHPh), 61.9 (C-4), 50.0 (C-1), 45.2 (C-3), 39.8 (NCH ), 14.2
3
+
(C-5); HRMS (ESI) m/z calcd for C H N Cl [M+H] : 311.1315,
19
20
2
found: 311.1317.
(d, A part of AB syst., J = 18Hz, 1H, H-5a), 3.38 (d, B part of
AB syst., J = 18Hz, 1H, H-5b), 2.40 (s, 3H, H-4), 1.15 (d, J =
4.15. (3S,4R)-6-Chloro-2,3-methyl-4-phenyl-1,2,3,4-tetrahydro-
β-carboline (ent-31):
13
6
1
1
2
Hz, 3H, H-3); C NMR (75 MHz, CDCl ) : δ (ppm): 143.0,
3
34.3, 128.3, 125.2, 117.2, 117.1 (CqAr), 126.2, 123.0, 122.4,
18.4, 112.1 (CHAr), 128.2, 128.0 (CHPh), 61.9 (C-1), 47.3 (C-
Starting from 60 mg of 28. White needles (46 mg, 84%); R =
f
20
D
0
.33 (CH Cl /EtOH : 90/10); Mp 233°C; [α] = +71.3 (c 0.2,
2
2
), 42.8 (C-5), 37.0 (C-4), 12.3 (C-3); HRMS (ESI) m/z calcd for
1
+
acetone); H NMR ( 300 MHz, (CD
3
)
2
SO) : δ (ppm) : 11.10 ( bs,
C H N Cl [M+H] : 338.1424, found: 338.1427.
20
21
3
1
H, NH), 7.29-7.18 (m, 6H, HAr), 6.92 (dd, J = 8Hz, J = 2Hz,
4
.11. (1S,2R)-{[2-(5-Methyl-1H-indol-3-yl)-1-methyl-2-phenyl-
1H, HAr), 6.53 (d, J = 2Hz, 1H, HAr), 3.92 (d, A part of AB
syst., J = 16Hz, 1H, H-1a), 3.82 (d, J = 7Hz, 1H, H-4), 3.73 (d, B
ethyl]-methyl-amino}-acetonitrile (29):
part of AB syst., J = 16Hz, 1H, H-1b), 2.86-2.77 (m, 1H, H-3),
Starting from 200 mg of 18. Orange solid (128 mg, 44%); R =
13
f
2
.37 (s, 3H, NCH ), 1.01 (d, J = 6Hz, 3H, H-5); C NMR ( 75
20
3
0
.40 (EtOAc/PE : 30/70); Mp 139°C; [α]
= -32.3 (c 0.2,
D
MHz, (CD ) SO) : δ (ppm): 144.3, 134.9, 134.8, 127.7, 122.8,
1
3 2
CH Cl ); H NMR (300 MHz, CDCl ) : δ (ppm) : 7.96 ( bs, 1H,
2
2
3
1
09.0 (CqAr), 126.4, 120.1, 117.1, 112.6 (CHAr), 128.7, 128.3
NH), 7.39-6.97 (m, 9H, Ph, H-2, H-4, H-6, H-7), 4.23 (d, J =
2Hz, 1H, H-2), 3.63-3.54 (m, 1H, H-1), 3.51 (d, A part of AB
syst., J = 18Hz, 1H, H-5a), 3.41 (d, B part of AB syst., J = 18Hz,
(
CHPh), 62.1 (C-4), 50.3 (C-1), 45.4 (C-3), 40.0 (NCH ), 14.4
3
1
+
(C-5); HRMS (ESI) m/z calcd for C H N Cl [M+H] : 311.1315,
19
20
2
found: 311.1311.
1
6
1
1
H, H-5b), 2.44 (s, 3H, ArCH ), 2.42 (s, 3H, H-4), 1.04 (d, J =
3
13
Hz, 3H, H-3); C NMR ( 75 MHz, CDCl ) : δ (ppm): 143.3,
4.16. (3S,4R)-6-Methyl-2,3-methyl-4-phenyl-1,2,3,4-tetrahydro-
β-carboline (33):
3
34.3, 127.5, 117.4, 116.6 (CqAr), 126.2, 123.4, 121.7, 118.6,
10.7 (CHAr), 128.6, 128.4 (CHPh), 61.5 (C-1), 47.8 (C-2), 42.1
Starting from 100 mg of 22. Pale yellow solid (59 mg, 65%);
(
C-5), 37.3 (C-4), 21.5 (ArCH ), 12.0 (C-3); HRMS (ESI) m/z
20
3
+
R
0
f
= 0.33 (CH
2
Cl
2
/EtOH : 90/10); Mp 262°C; [α]
D
= +44.4 (c
calcd for C H N [M+H] : 318.1970, found : 318.1971.
1
21
24
3
.1, acetone); H NMR ( 300 MHz, (CD ) SO) : δ (ppm) : 10.68 (
3 2
4
.12. (1S,2S)-{[2-(3-Methyl-1H-indol-2-yl)-1-Methyl-2-phenyl-
bs, 1H, NH), 7.27-7.12 (m, 6H, HAr), 6.74 (bd, J = 8Hz , 1H,
HAr), 6.43 (bs, 1H, HAr), 3.86 (A part of AB syst., J = 15Hz,
ethyl]-methyl-amino}-acetonitrile (30):
1
=
2
H, H-5a), 3.79 (d, J = 6Hz, 1H, H-2), 3.64 (B part of AB syst., J
15Hz, 1H, H-5b), 2.83-2.75 (m, 1H, H-1), 2.34 (s, 3H, ArCH ),
.13 (s, 3H, H-4), 1.01 (d, J = 7Hz, 3H, H-3); C NMR (75
Starting from 500 mg of 18. White solid (124 mg, 18%); R =
f
20
3
0
.81 (EtOAc/PE : 30/70); Mp 51°C; [α]
= -58.6 (c 0.6,
13
D
1
CH Cl ); H NMR (300 MHz, CDCl ) : δ (ppm) : 8.87 ( bs, 1H,
2
2
3
MHz, (CD ) SO) : δ (ppm): 144.9, 134.4, 126.2, 125.9, 108.0
3
2
NH), 7.50 (d, 1H, HAr), 7.39-7.08 (m, 8H, HAr), 4.21 (d, J =
Hz, 1H, H-2), 3.67-3.58 (m, 1H, H-1), 3.41(d, A part of AB
(CqAr), 140.2, 117.6, 110.5 (CHAr), 128.5, 127.8 (CHPh), 62.0
9

7
Nagayama, S. I.; Desadee, W.; Yajima, N.; Kumamoto, T.;
Watanabe, T.; Ishikawa, T.; Kawahata, M.; Yamaguchi, K. Helv.
Chim. Acta, 2007, 90, 128-142.
(
C-3), 49.8 (C-1), 45.5 (C-4), 36.6 (NCH ), 2
A
1.2
C
(
C
Ar
E
CHPT),
ED
.7 MANUSCRIPT
13
3
3
+
(C-5); HRMS (ESI) m/z calcd for C H N [M+H] : 291.1861,
20
23
2
found: 291.1870.
5
.
(a) Pfeil, E.; Harder, U. Angew. Chem. Int. Ed. Engl. 1967, 6, 178.
b) Styngach, E. P.; Kuchkova, K.; Efremova, T. M.; Semenov, A.
(
4
.17. (3S,4R)-6-Methoxy-2,3-methyl-4-phenyl-1,2,3,4-
A. Chem. Heterocycl. Compd. 1973, 1378-1382.
tetrahydro-β-carboline (34):
6
.
(a) Couty, F.; Evano, G.; Menguy, L.; Steinmetz, V.; Toumi, M.
Tetrahedron Lett. 2006, 47, 4817-4821. (b) Couty, F.; Evano, G.;
Prim, D. Tetrahedron Lett. 2005, 46, 2253-2257. (c) Couty, F.;
Durrat, F.; Prim, D. Tetrahedron Lett. 2004, 45, 3725-3728. See
also inter alia: (d) Wakselman, M.; Mauna, A. M.; Xie, J.;
Mazaleyrat, J. P.; Bouley, R.; Lelièvre, Y.; Bousseau, A.;
Nachmansohn, C.; Hénin, Y. Bioorg. Med. Chem. Lett. 1994, 4,
533-2537. (e) Gmeiner, P.; Junge, D.; Kaertner, A. J. Org. Chem.
994, 59, 6766-6776. (f) Weber, K.; Kuklinski, S.; Gmeiner, P.
Org. Lett. 2000, 647-649. (g) D’hooghe, M.; De Kimpe, N.
Synlett, 2006, 2089-2093. (h) D’hooghe, M.; Waterinckx, A.;
Vanlangendonck, T.; De Kimpe, N. Tetrahedron, 2006, 62, 2295-
Starting from 40 mg of 29. White needles (22 mg, 60%); R =
f
20
0
.29 (CH Cl /EtOH : 90/10); Mp 236°C; [α] = +78.0 (c 0.2,
2 2 D
1
acetone); H NMR ( 300 MHz, (CD ) SO) : δ (ppm) : 10.66 ( bs,
3
2
1
1
1
H, NH), 7.33-7.13 (m, 6H, HAr), 6.57 (dd, J = 9Hz , J = 3Hz,
H, HAr), 6.05 (bd, 1H, HAr), 3.89 (d, A part of AB syst., J =
5Hz, 1H, H-5a), 3.79 (d, J = 6Hz, 1H, H-2), 3.71 (d, B part of
2
1
AB syst., J = 15Hz, 1H, H-5b), 3.45 (s, 3H, OCH ), 2.85-2.77
3
13
(m, 1H, H-1), 2.37 (s, 3H, H-4), 1.02 (d, J = 6Hz, 3H, H-3);
C
NMR ( 75 MHz, (CD ) SO) : δ (ppm): 152.5, 144.5, 133.5,
1
1
3
2
2
303. (i) Chang, H-S.; Song, H. A.; Dadwal, M.; Sun, X.; Sin. I.;
31.3, 126.9, 108.7 (CqAr), 126.0, 111.3, 109.1, 100.8 (CHAr),
Chen, Y. J. Org. Chem. 2009, 74, 219-221. (j) D’hooghe, M.;
Catak, S.; Stanković, S.; Waroquier, M.; Kim, Y.; Ha, H-J.; Van
Speybroeck, V.; De Kimpe, N. Eur. J. Org. Chem. 2010, 4920-
4931.
28.7, 128.0 (CHPh), 62.1 (C-3), 55.0 (OCH ), 50.4 (C-1), 45.6
3
(
C-4), 39.9 (NCH ), 14.3 (C-5); HRMS (ESI) m/z calcd for
3
+
C H N O [M+H] : 307.1810, found: 307.1814.
20
23
2
7
8
.
.
Lakhdar, S.; Westermaier, M.; Terrier, F.; Goumont, R.;
Boubaker, T.; Ofial, A. R.; Mayr, H. J. Org. Chem. 2006, 71,
Acknowledgments
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088-9095.
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University of Versailles St-Quentin-en-Yvelines and CNRS
are acknowledged for financial support.
References and notes
(c) Lebold, T. P.; Wood, J. L.; Deitch, J.; Lodewyk, M. W.;
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9
1
1
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3, 297-302.
1
1. X-ray structures of 23, 31 and ent-31 have been deposited on the
(d) Larghi, E. L.; Amongero, M.; Bracca, A. B. J. Kaufman, T. S.
Cambridge database and have been assigned CCDC numbers
Arkivoc, 2005, (xii), 98-153. (e) Youn, S. W. Org. Prep. Proced.
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9
84738, 984739 and 984740 respectively. See supplementary
materials for details.
3
.
For examples using Lewis acids, see: (a) Harrington, P. E.; Kerr,
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Reddy, B. V. S.; Sabitha, G. Synthesis, 2002, 2165-2169. (c)
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Rovinetti, M.; Tommasi, S.; Umani-ronchi, A. Chirality, 2005, 17,
1
1
2. Flack, H. D. Acta Cryst. 1983, A39, 876-881.
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Laronze, M.; Seghir, H.; Augé, F.; Laronze, J-Y. Tetrahedron,
2
000, 56, 5479-5492.
1
1
1
4. Grigg, R.; Sridharan, V.; Thorton-Pett, M.; Wang, J.; Xu, J.;
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006.
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2
008, 1193-1198.
Supplementary Material
4
.
(a) Sato, K.; Kozikowski, A. P. Tetrahedron Lett. 1989, 30, 4073-
4
7
076. (b) Bennani, Y. L.; Zhu, G. D.; Freeman, J. C. Synlett, 1998,
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1
13
Copies of H NMR and C NMR spectra for all new compounds. All
compounds appear following the numbering in the experimental section.
Synlett, 2001, 945-947. (d) Nischikawa, T.; Kajii, S.; Wada, K.;
Ishikawa, M.; Isobe, M. Synthesis, 2002, 1658-1662. (e)
Nischikawa, T.; Koide, Y.; Kanakubo, A.; Yoshimura, H.; Isobe,
M. Org. Biomol. Chem. 2006, 4, 1268-1277. (f) Manaka, T.;
Crystallographic data for compounds 23, 31 and ent-31.
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Supporting information
Alkylation of Indoles by Aziridinium ions: New Rapid
Access to Tetrahydro-β-Carbolines (THBCs)
[a]
[a]
[a]
[a]
Laurence Menguy, Cheikh Lo, Jérôme Marrot and François Couty*
[
a]
Institut Lavoisier, Université de Versailles St Quentin-en-Yvelines, UMR 8180, 45 avenue
des Etats-Unis, 78035, Versailles, France
Corresponding author. e-mail: couty@chimie.uvsq.fr
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Copies of H NMR and C NMR spectra for all new compounds.
All compounds appear following numbering of experimental section.
Crystallographic data for compounds 23, 31 and ent-31.
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