The reactions of nitrones with indoles

Article abstract of DOI:10.1016/S0040-4020(99)01051-0

The reaction of nitrones with various indole derivatives has been studied. When the reaction was promoted by C1SiMe₃, the isolated products were 3,3'-diindolylalkanes. With HC1 as the activating reagent, 3- indolylhydroxylamines were isolated. The diastereoselectivity of this condensation with a nitrone derived from cysteine was investigated. A method for the introduction of an alkylhydroxylamino group onto position 2 of indole, the synthesis of three natural 3,3'-diindolylalkanes and of non- symmetric diindolylalkanes are also reported. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(99)01051-0

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 791–804
The Reactions of Nitrones with Indoles
´ `
´ `
¨
Helene Chalaye-Mauger, Jean-Noel Denis, Marie-Therese Averbuch-Pouchot and
*
´
Yannick Vallee
´
L.E.D.S.S., Laboratoire mixte CNRS, Universite Joseph Fourier, B.P. 53, 38041 Grenoble, France
Received 10 September 1999; accepted 6 December 1999
Abstract—The reaction of nitrones with various indole derivatives has been studied. When the reaction was promoted by ClSiMe3, the
isolated products were 3,30-diindolylalkanes. With HCl as the activating reagent, 3-indolylhydroxylamines were isolated. The diastereo-
selectivity of this condensation with a nitrone derived from cysteine was investigated. A method for the introduction of an alkylhydroxyl-
amino group onto position 2 of indole, the synthesis of three natural 3,30-diindolylalkanes and of non-symmetric diindolylalkanes are also
reported. ᭧ 2000 Elsevier Science Ltd. All rights reserved.
The chemistry of nitrones is a rapidly growing area. Even
though the greatest part of the work is devoted to the study of
their 1,3-dipolar cycloaddition reactions,1 they are also
involved in numerous reactions with nucleophiles. Not
only organometallics,2,3 but also electron-rich aromatic
compounds can be made to react with nitrones. In a pre-
liminary communication,4 we have reported that indole
derivatives react with nitrones (Scheme 1). The obtained
products are of two types: (i) the hydroxylamines 3 resulting
from the condensation of one molecule of nitrone with one
indole nucleus, and (ii) bis-indole derivatives of type 4
formed by the reaction of an intermediate 3-alkylidene-
3H-indolium cation with the starting indole.
first diastereoselective examples of these condensations are
presented. A method for introducing an alkylhydroxylamino
group on position 2 of indole is also described.
Activation of Nitrones
No reaction occurred when a nitrone and indole were mixed
in toluene, methanol or dichloromethane. This means that, if
any reaction is wanted, the nitrone has to be activated. The
goal of such activation should be to render the nitrone more
electrophilic, i.e. to make the carbon atom of the nitrone
function more positive. This can be obtained by introducing
a proton or a silyl group5 on its oxygen atom. Four test
experiments were run with the benzyl nitrone of propanal
1a (Scheme 2). This nitrone was dissolved in CDCl3 and
In this paper, we detail our findings about these reactions. In
particular, the role of the activation agent is studied and the
Scheme 1.
Keywords: indoles; nitrones; hydroxylamines; natural products.
* Corresponding author. Tel.: ϩ33-4-76-63-57-96; fax: ϩ33-4-76-51-43-82; e-mail: yannick.vallee@ujf-grenoble.fr
0040–4020/00/$ - see front matter ᭧ 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(99)01051-0

792
H. Chalaye-Mauger et al. / Tetrahedron 56 (2000) 791–804
Scheme 2.
Table 1. NMR data (d ppm) for nitrone 1a, and nitrone 1a mixed with various activating agents
Activating agent
None
TfOSiMe3
ClSiMe3
ClSiEt3
33% HCl/H2O
1H NMR
H-1
H-2
6.61
2.50
1.08
4.88
8.76
2.84
1.40
5.42
7.07
2.47
1.04
4.95
6.81
2.51
1.08
4.93
7.91
2.63
1.14
5.27
H-3
CH2Ph
13C NMR
C-1
140.6
170.9
144.4
mixed in NMR tubes with 1 equiv. of different sources of
silicon (TfOSiMe3, ClSiMe3 and ClSiEt3) and with 33%
aqueous HCl. The obtained 1H and 13C NMR data are listed
in Table 1. In each case, the resonance of the ‘aldehydic’
proton is shifted towards low fields as compared to the free
nitrone. This demonstrates the formation of new species.
Clearly, the more iminium-like product is the triflate salt
(H-1: 8.76 ppm). In the case of a chloride counterion, one
must be in presence of a more tightly bonded pair and the
observed species might be described as a mixture of the two
limit forms I and II (Scheme 2). The triflate anion being
much less nucleophilic than ClϪ, the bonded sp3 form II is
probably much less important when XϪˆTfOϪ. Examina-
tion of 13C NMR data confirms this proposal: in the case of
the triflate, the CyN carbon is observed in the iminium
carbon region; with the chloride anion, the observed shift
is intermediate between the shifts of an iminium (ca.
170 ppm) and of an a-chloramine (80–90 ppm).6 Thus,
TfOSiMe3 is expected to be a stronger activation agent
than ClSiMe3. It should be noticed that ClSiEt3 seems to
be the worst tested reagent. This is probably due to the
electron-donating properties of its three ethyl groups.
Finally, a proton should be an acceptable reagent. Care
must be taken, however, due to the fact that the acidic
water solution rapidly hydrolyses the nitrone to give the
corresponding aldehyde, propanal.
Condensations using Trimethylsilyl Triflate
A first experiment was run using the benzylnitrone of
propanal 1a and indole 2a in the presence of TfOSiMe3
(1:1 ratio) in anhydrous CH2Cl2 at room temperature.
After 2 h, a complex mixture resulted in which we were
able to identify 1,1-bis(30-indolyl)propane 4aa as the
major product and some remaining starting nitrone. As the
formation of the diindolylalkane requires 2 mol of indole
per mole of nitrone, the reaction was repeated using a
nitrone to indole ratio of 1–2. The reaction was run at 0ЊC
to minimize the formation of side products. It was rapid and
relatively clean giving 4aa in high yield. However, 4aa was
accompanied by some indole dimer 5a7 (ca. 5%, Scheme 3).
The formation of 5a can be explained by protonation of
indole by the formed triflic acid. The obtained cation is
then attacked by another indole molecule to give the
dimer 5a. Even though 5a was a very minor by-product,
we were unable to separate it from 4aa by liquid chromato-
graphy, and were unable to obtain pure 4aa in this way.
Thus, the formation of triflic acid during the condensation of
a nitrone onto indole is a severe drawback to the use of
TfOSiMe3 as the activation reagent. HCl being less acidic
than TfOH, we thought that such drawback could be absent
for ClSiMe3.
Scheme 3.

H. Chalaye-Mauger et al. / Tetrahedron 56 (2000) 791–804
Table 2. Yields of the reaction of nitrones with indoles in the presence of ClSiMe3
793
Entry
Nitrone
R
Indole
X, Y
H, H
Reaction time (h)
Bis-indole
Yield (%)
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
1g
1a
1a
1c
1e
1e
Et
2a
2
17
14
15.5
8.5
48
72
8.5
72
4aa
4ba
4ca
4da
4ea
4fa
4ga
4ab
4ac
4cc
4ec
4ed
85
83
97
91
56
88
75
86
88
60
46
31
Me
Pri
CH2OBn
CH2NHBoc
Ph
p-NO2–C6H4
Et
2b
2c
MeO, H
Br, H
9
Et
10
11
12
Pri
64
48
54
CH2NHBoc
CH2NHBoc
2d
H, Br
Condensations using Trimethylsilyl Chloride
Aromatic nitrones also give the bis-indole derivatives. It
should be noticed that the other possible products of
these reactions, compounds 3 (Scheme 1), were never
detected.
A series of condensations was run with various indole
derivatives 2a–d (2 equiv.) and nitrones 1a–g (1 equiv.)
using 1 equiv. ClSiMe3 as the activator (Table 2). They
were monitored by TLC and found to be relatively slow at
room temperature. Yields however were generally good
except in the case of the a-amino nitrone 1e. This nitrone
was found to be poorly stable under the reaction conditions,
probably because of the possible cleavage of the N-Boc
protective group by the formed HCl. Not only indole 2a
but also an electron-rich indole such as 2b, and the electron-
poor derivatives 2c,d can take part in this reaction, without
noticeable change in the yield (compare entries 1, 8 and 9).
It is probable that the first formed intermediate is the
O-silylated derivative of 3 (Scheme 4). Formation of the
3-alkylidene-3H-indolium ion, which must be formed en
route to compound 4, thus requires the protonation of
3-SiMe3. This protonation is possible because of the
liberation of HCl during the first condensation step. We
reasoned that trapping of HCl by a base could eliminate
the protonation of 3-SiMe3, and would allow the isolation
of mono-adduct 3.
Scheme 4.

794
H. Chalaye-Mauger et al. / Tetrahedron 56 (2000) 791–804
Scheme 5.
The best results were obtained with pyridine as the base in
anhydrous toluene at room temperature. Under these con-
ditions (Scheme 5), the condensation of nitrone 1a with
indole gave the hydroxylamine 3aa as the major isolated
product. However, the yield was only moderate. Further-
more, when the same conditions were applied to 5-bromo-
indole, the isolated yield was only 14%. Clearly, better
conditions were to be looked for if the goal was to obtain
reasonable yields of indolic hydroxylamines 3.
anhydrous methanol. The best results were obtained using
2 equiv. of AcCl (and thus 2 equiv. of HCl) for 1 equiv. of
indole and 1 equiv. of nitrone (Table 3). Alternatively,
trifluoroacetic acid in methanol or pyridinium p-toluenesul-
fonate (PPTS) in toluene could also be used. The yields
however are lower and with PPTS the presence of some
4aa was noticed.
Yields using HCl in methanol were generally good. Excep-
tions were condensations using the nitrones derived from
isobutyraldehyde and benzaldehyde (entries 3 and 6), in
which the formation of the 3H-indolium cation is favored
by the good electron-donating properties of the substituents
and, for the phenyl group, by the possible delocalization of
the positive charge. In these cases it was not possible to stop
the reaction at the hydroxylamine stage and the bis-indoles
were the only products. Interestingly, when an electron-with-
drawing group was introduced on the phenyl group (NO2,
entry 7), isolation of the hydroxylamine was again possible.
Condensations using HCl
When equimolar amounts of indole and nitrone 1a were
mixed at room temperature in CH2Cl2 in the presence of
1 equiv. of aqueous HCl, a mixture of the starting nitrone
and the bis-indole derivative 4aa (ratio 44:56) was obtained.
The formation of a small amount of the indole dimer 5a was
also noticed. When the same reaction was conducted at 0ЊC,
the major product was the hydroxylamine 3aa still accom-
panied by some bis-indole and starting compounds. As the
formation of 4aa may be due in some part to the transient
formation of propanal in the reaction mixture by hydrolysis
of the nitrone (vide supra), we decided to use anhydrous
HCl. It was generated by addition of acetyl chloride into
Diastereoselective Condensations
The condensation of a nitrone with an indole to give a
hydroxylamine creates a new stereogenic center. Such chiral
Table 3. Yields of the reaction of nitrones with indoles in the presence of HCl
Entry
Nitrone
R
Indole
X, Y
H, H
Temperature (ЊC)
Reaction time (h)
Hydroxylamine
Yield (%)
1
2
3
4
5
6
1a
1b
1c
1d
1e
1f
Et
2a
0
0
0
0
0
0
2
2
2
1
1
1
3aa
3ba
3ca
3da
3ea
3fa
94
87
0
88
95
0
Me
Pri
CH2OBn
CH2NHBoc
Ph
7
8
9
10
11
12
13
14
15
1g
1a
1b
1d
1e
1a
1b
1e
1e
p-NO2C6H4
Et
Me
CH2OBn
CH2NHBoc
Et
Me
CH2NHBoc
CH2NHBoc
0
0.5
1
1
1
1
3
3
4
4
3ga
3ab
3bb
3db
3eb
3ac
3bc
3ec
3ed
44
83
88
93
95
70
82
83
78
2b
MeO, H
Ϫ10
Ϫ10
Ϫ10
Ϫ10
r.t.
r.t.
0
2c
Br, H
H, Br
2d
0

H. Chalaye-Mauger et al. / Tetrahedron 56 (2000) 791–804
795
Scheme 6.
centers are present for instance in some newly described
azaelliptitoxine analogues.8 With the goal of performing
the synthesis of such compounds we needed to determine
if these condensations could be diastereoselective.
dimer 5a and we were unable to isolate it in pure form. From
what can be observed in the H NMR spectrum of impure
3ia, it seems that one diastereomer, to which we attribute the
(R,R)-configuration by analogy with the previous example,
largely dominates. However, it was not pure enough to
ensure that only one isomer was present.
1
Two a-chiral nitrones 1h,i were prepared respectively from
l-cysteine and l-serine (Scheme 6). The best result was
obtained from the sulfurated nitrone 1h. Treatment of 1h
and indole by dry HCl (2 equiv.) in methanol for 4 h at 0ЊC
leads to the expected hydroxylamine 3ha in 68% yield
(traces of the corresponding bis-indole and of indole
dimer 5a were also detected by TLC). As expected, 3ha
was obtained as a mixture of stereoisomers. These stereo-
isomers were separated by liquid chromatography and the
diastereoisomeric ratio was found to be 92:8. The
(R,R)-configuration of the major isomer was determined
by X-ray crystallography of a single crystal obtained by
recrystallization from ethanol (Fig. 1). This configuration
can be rationalized using a cyclic Cram model (Scheme 6)
in which the activating proton is chelated between the nitrone
oxygen atom and the sulfur atom of the thiazolidine ring.
Condensations on Position 2 of Indole
Position 3 of indole is the most reactive position for
Friedel–Crafts type reactions such as the condensation of
nitrones described supra. However, it could be interesting to
introduce an alkylhydroxylamino group on other positions
of indole. For instance, some eudistomins,9 which are
powerful antiviral molecules, possess a C–N–O sub-unit
attached on an indole nucleus at position 2. In order to create
such a framework, we have tested an ortho-lithiation
process.
Among the various possible ortho-lithiation procedures, we
chose a method developed by Katritzky et al.10 The major
advantage of this method is that the orienting group is both
easily introduced and removed in situ just before and after
the condensation step (Scheme 7). Thus, indole 2a was
The result with the serine derived nitrone was less clear. The
crude product contained the hydroxylamine 3ia as the major
component. However, it was contaminated by some indole
Figure 1.

796
H. Chalaye-Mauger et al. / Tetrahedron 56 (2000) 791–804
Scheme 7.
deprotonated by n-BuLi and the formed anion was treated
by solid CO2. Subsequent treatment of the obtained
carboxylate by t-BuLi gave a dianion which reacted with
nitrones 1a,b. Even though the yields were only moderate,
the possibility of obtaining condensations on position 2 was
demonstrated. The hydroxylamines 6a,b were isolated in 58
and 36% yields.
synthesis of three simple natural diindolylalkanes4 with the
goal of showing that the detour through nitrones, rather than
the direct condensation of aldehydes, is of reasonable
synthetic interest.
1,1-Bis(30-indolyl)ethane 4ba (Table 2) is a metabolite of the
bacteria Vibrio parahaemolyticus isolated from the toxic mucus
of the Australian box-fish Ostracion cubicus.14 This molecule
has been named vibrindole A and biological tests demonstrated
its activity against Bacillus subtilis, Staphylococcus aureus
and Staphylococcus albus. It has already been synthesized
from acetaldehyde and indole in acetic acid and the reported
yield was 58%12 (to be compared with 83% in our case).
Synthesis of Naturally Occurring 3,30-Diindolylalkanes
The usual way to obtain 3,30-diindolylalkanes consists of
treating an indole derivative with an aldehyde in an acidic
medium.11–13 However, yields are often only moderate. In
particular, because of the relatively strong acid conditions
needed, the indole dimer 5a (or one of its homologues) can
be expected to be a usual by-product.7,11 Furthermore, acid-
sensitive aldehydes cannot be used. We report thereafter the
Streptindole 7 (Scheme 8) is the adduct of two molecules of
indole with one molecule of acetoxyacetaldehyde.15,16 It has
been isolated from intestinal bacteria Streptococcus faecium
IB37 and causes DNA lesions in Bacillus subtilis cells. It
Scheme 8.

H. Chalaye-Mauger et al. / Tetrahedron 56 (2000) 791–804
Table 4. Yields of bis-indoles from hydroxylamines 3 and indoles 2
797
Entry
Hydroxylamine
R, X, Y
Et, H, H
Indole
X0, Y0, Z
Reaction time (h)
Bis-indole
Yield (%)
1
2
3
4
5
6
7
8
3aa
3aa
3aa
3aa
3ba
3bc
3ba
3bb
3da
3da
3ea
2c
2d
2b
2e
2c
2a
2b
2a
2c
2b
2d
Br, H, H
H, Br, H
MeO, H, H
H, H, Me
Br, H, H
H, H, H
MeO, H, H
H, H, H
Br, H, H
MeO, H, H
H, Br, H
24
18
14
14
24
18
14
18
24
14
20
9aac
9aad
9aab
9aae
9bac
9bac
9bab
9bab
9dac
9dab
9ead
76
84
83
74
51
53
63
57
83
76
48
Me, H, H
Me, Br, H
Me, H, H
Me, MeO, H
CH2OBn, H, H
9
10
11
CH2NHBoc, H, H
was first synthesized in 2% yield by reaction of acetoxy-
acetaldehyde with indole.16 Using glyoxylic acid as starting
material, Hogan and Sainsbury17 obtained 7 in four steps
and with a 42% overall yield from indole. Our synthesis
(Scheme 8) started with indole and nitrone 1d. The overall
yield of this three step strategy was 72% from indole. As
nitrone 1d was obtained in 95% yield from benzyloxy-
acetaldehyde, the overall yield from this aldehyde was 68%.
shows that the substituents can be introduced in the final
products 9 (9bac for entries 5 and 6 and 9bab for entries 7
and 8) either from the hydroxylamine 3 or from the added
indole 2 without major change in the yields.
Experimental
Tetrahydrofuran (THF) was distilled from sodium-benzo-
phenone. Dichloromethane was distilled from calcium
hydride and methanol from magnesium. Acetyl chloride,
trimethylsilyl chloride and trifluoroacetic acid were distilled
before use. All other commercially available reactants and
solvents were used without purification. Thin-layer chroma-
tography was performed on Merck 60F254 (0.2 mm) sheets.
Merck Kieselgel SI 60 silica gel (0.063–0.200 mm) was
employed for column chromatography. Brucker AC 200,
AM 300, WM 250 and Avance 300 spectrometers were
used to record the 1H and 13C NMR spectra. Chemical shifts
(d) are reported in ppm and coupling constants (J) in Hertz.
Mass spectra were obtained on a Nermag R10 mass spectro-
meter. Optical rotations were measured on a Perkin–Elmer
341 polarimeter. Melting points were obtained with a
Bu¨chi–Tottoli apparatus and are not corrected. Micro-
analysis were performed by the ‘Service Central d’Analyse
du CNRS’ at Vernaison (France).
2,2-Bis(60-bromo-30-indolyl)ethylamine 8 was isolated in
1991 from the tunicate Didemnum candidum.18 It is also
present in Orina sp. sponges.19 We have synthesized this
compound for the first time4 in two steps from 6-bromo-
indole 2d and nitrone 1e (Scheme 8). The overall yield,
however, was only 24%, due to the low yield of the first
step (31%).
Synthesis of Non-Symmetric 3,30-Diindolylalkanes
In Scheme 4 we have presented a mechanism which
explains the formation of bis-indole derivatives from
indoles and nitrones in the presence of ClSiMe3. We
proposed that an alkylidene-3H-indolium cation was formed
and reacted with another indole molecule. If this is true,
treatment of an isolated hydroxylamine 3 by ClSiMe3
should give the same alkylidene-3H-indolium cation,
which would be able to react with any added nucleophile.
We decided to test this possibility,4 using as the new nucleo-
phile an indole derivative different from the one which was
used to synthesize the hydroxylamine. The expected
products are then non-symmetric diindolylalkanes. Our
results are summarized in Table 4.
Synthesis of nitrones
Nitrones were prepared according to the procedure
described by Dondoni and coworkers.20 Most of them
were previously known.3a,5,20–23
(Z)-N-[2-(Benzyloxy)ethylidene]benzylamine N-oxide (1d).
Yield: 95%. Mp: 95.5–96.5ЊC. 1H NMR (CDCl3,
200 MHz): 2.92 (dd, Jˆ1.4, 4.4 Hz, 2H, OCH2); 4.52 (s,
2H, OCH2Ph); 4.85 (s, 2H, NCH2Ph); 6.78 (t, Jˆ4.4 Hz,
To the best of our knowledge, this is the first reported
general synthesis of non-symmetric diindolylalkanes.4
Yields are moderate to good. Examination of entries 5–8

798
H. Chalaye-Mauger et al. / Tetrahedron 56 (2000) 791–804
1H, HCyN); 7.21–7.44 (m, 10H, CHarom). 13C NMR
(CDCl3, 75.5 MHz): 66.0 (CH2); 68.8 (CH2); 73.6 (CH2);
127.8 (CH); 128.3 (CH); 128.9 (CH); 129.0 (CH); 129.4
(CH); 132.0 (C); 137.0 (CyN). SM (CI, NH3ϩisobutane):
m/z 256 (MHϩ). Anal. calcd for C16H17NO2: C: 75.27%, H:
6.71%, N: 5.49%; found: C: 75.23%, H: 6.69%, N: 5.46%.
Jˆ7.1 Hz, 1H, CH); 6.63 (d, Jˆ2.4 Hz, 2H, CHarom);
6.94–7.22 (m, 11H, CHarom); 7.47 (d, Jˆ7.9 Hz, 2H,
CHarom); 7.59 (broad s, 2H, NH). 13C NMR (CDCl3,
62.5 MHz): 34.4 (CH); 72.8 (CH2); 73.3 (CH2); 111.1
(CH); 116.6 (C); 118.9 (CH); 119.3 (CH); 121.6 (CH);
122.5 (CH); 126.8 (C); 127.5 (CH); 127.7 (CH); 128.2
(CH); 136.2 (C); 138.2 (C). MS (CI, NH3ϩisobutane):
m/z 366 (Mϩ). Anal. calcd for C25H22N2O: C: 81.94%,
H: 6.05%, N: 7.64%; found C: 81.75%, H: 6.24%, N:
7.43%.
(Z)-N-[2-(tert-Butoxycarbonylamino)ethylidene]benzyl-
1
amine N-oxide (1e). Yield: 88%. Mp: 91–92ЊC. H NMR
(CDCl3, 300 MHz): 1.42 (s, 9H, C(CH3)3); 4.02 (t,
Jˆ5.0 Hz, 2H, CH2); 4.86 (s, 2H, CH2Ph); 5.49 (broad s,
1H, NHBoc); 6.86 (broad s, 1H, HCyN); 7.34–7.52 (m, 5H,
CHarom). 13C NMR (CDCl3, 75.5 MHz): 28.2 (C(CH3)3);
37.0 (CH2); 69.1 (CH2); 79.7 (C(CH3)3); 128.9 (CH);
129.0 (CH); 129.2 (CH); 132.4 (C); 135.8 (CyN); 156.0
(CO2). SM (CI, NH3ϩisobutane): m/z 265 (MHϩ). Anal.
calcd for C14H20N2O3: C: 63.64%, H: 7.57%, N: 10.60%;
found: C: 63.63%, H: 7.47%, N: 10.49%.
N-(tert-Butoxycarbonyl)-2,2-di(30-indolyl)ethylamine
1
(4ea). Yield: 56%. Mp: 203–203.5ЊC. H NMR (CDCl3,
200 MHz): 1.42 (s, 9H, C(CH3)3); 3.92 (t, Jˆ6.6 Hz, 2H,
CH2); 4.57–4.74 (m, 1H, NH); 4.71 (nearly t, Jˆ7.2, 7.5 Hz,
1H, CH); 6.98 (d, Jˆ2.0 Hz, 2H, CHarom); 7.01–7.21 (m, 4H,
CHarom); 7.35 (d, Jˆ8.2 Hz, 2H, CHarom); 7.61 (d, Jˆ7.9 Hz,
2H, CHarom); 8.02 (broad s, 2H, NH). 13C NMR (DMSO,
100.6 MHz): 28.3 (C(CH3)3); 33.8 (CH); 45.0 (CH2); 77.5
(C(CH3)3); 111.3 (CH); 116.4 (C); 118.0 (CH); 118.9 (CH);
120.7 (CH); 122.3 (CH); 126.9 (C); 136.4 (C); 155.7 (CO2).
MS (CI, NH3ϩisobutane): m/z 375 (MHϩ). Anal. calcd for
C23H25N3O2: C: 73.57%, H: 6.71%, N: 11.19%; found: C:
73.29%, H: 6.66%, N: 11.22%.
(Z)-N-(4-Nitrobenzylidene)benzylamine N-oxide (1g).
1
Yield 73%. Mp: 117–118ЊC. H NMR (CDCl3, 300 MHz):
5.11 (s, 2H, CH2Ph); 7.42–7.51 (m, 6H, C6H5, HCyN); 8.23
(d, Jˆ9.0 Hz, 2H, CHarom); 8.35 (d, Jˆ9.5 Hz, 2H, CHarom).
13C NMR (CDCl3, 75.5 MHz): 72.1 (CH2); 123.7 (CH);
128.8 (CH); 129.1 (CH); 129.4 (CH); 132.1 (CyN); 132.5
(C); 135.9 (C); 147.8 (C). MS (CDI, NH3ϩisobutane): m/z
257 (MHϩ). Anal. calcd for C14H12N2O3: C: 65.62%, H:
4.69%, N: 10.94%; found: C: 65.87%, H: 4.64%, N:
10.96%.
1,1-Di(50-methoxy-30-indolyl)propane (4ab). Yield: 86%.
1
Amorphous solid. H NMR (CDCl3, 200 MHz): 1.01 (t,
Jˆ7.2 Hz, 3H, CH3); 2.15–2.30 (m, 2H, CH2); 3.76 (s,
6H, 2×OCH3); 4.26 (t, Jˆ7.5 Hz, 1H, CH); 6.80 (dd,
Jˆ2.0, 8.6 Hz, 2H, CHarom); 6.96 (d, Jˆ2.0 Hz, 2H, CHarom);
7.03 (d, Jˆ2.0 Hz, 2H, CHarom); 7.20 (d, Jˆ8.6 Hz, 2H,
CHarom); 7.77 (broad s, 2H, NH). 13C NMR (CDCl3,
100.6 MHz): 13.0 (CH3); 28.4 (CH2); 35.9 (OCH3); 55.9
(CH); 101.9 (CH); 111.5 (CH); 111.6 (CH); 119.8 (C);
122.3 (CH); 127.6 (C); 131.8 (C); 153.5 (C). MS (CI,
NH3ϩisobutane): m/z 335 (MHϩ). Anal. calcd for
Synthesis of diindolylalkanes
A mixture of the nitrone (1 mmol) and Me3SiCl (1 mmol) in
10 mL of anhydrous CH2Cl2 was stirred for 5 min at r.t. The
indole derivative (2 mmol) was then added and the reaction
was monitored by TLC (silica gel, diethyl ether/pentane;
1:1). After completion of the reaction, the mixture was
treated by an aqueous solution of NaHCO3. The organic
layer was washed twice with water, once with brine
and dried over anhydrous MgSO4. After filtration, the
solvent was evaporated under vacuum and the obtained
residue was purified by column chromatography over
silica gel.
1
C2 H22N2O2: C: 75.42%, H: 6.63%, N: 8.38%; C: 75.51%,
H: 6.77%, N: 8.07%.
1,1-Di(50-bromo-30-indolyl)propane (4ac). Yield: 88%.
Mp: 60–64ЊC. 1H NMR (CDCl3, 200 MHz): 0.95 (t,
Jˆ7.4 Hz, 3H, CH3); 2.17 (quint., Jˆ7.4 Hz, 2H, CH2);
4.19 (t, Jˆ7.4 Hz, 1H, CH); 6.95 (d, Jˆ2.2 Hz, 2H, CHarom);
7.01–7.29 (m, 4H, CHarom); 7.64 (d, Jˆ1.6 Hz, 2H, CHarom);
7.86 (broad s, 2H, NH). 13C NMR (CDCl3, 75.5 MHz): 12.8
(CH3); 28.1 (CH2); 35.7 (CH); 112.2 (C); 112.6 (CH); 119.1
(C); 121.9 (CH); 122.7 (CH); 124.5 (CH); 128.5 (C); 135.1
(C). MS (CI, NH3ϩisobutane): m/z 448, 450 and 452
(MHϩϩNH3). Anal. calcd for C19H16Br2N2: C: 52.81%,
H: 3.73%, N: 6.48%; found: C: 52.62%, H: 3.78%, N:
6.21%.
Compounds 4aa,24 4ba,12,24 4fa12 and 4ga12 were previously
known.
1,1-Di(30-indolyl)-2-methylpropane (4ca). Yield: 97%.
1
Amorphous solid. H NMR (CDCl3, 300 MHz): 0.99 (d,
1
Jˆ6.5 Hz, 6H, 2×CH3); 2.55–2.70 (m, H, CH); 4.23 (d,
Jˆ8.0 Hz, 1H, CH); 6.97 (d, Jˆ2.0 Hz, 2H, CHarom);
7.00–7.13 (m, 4H, CHarom); 7.22 (d, Jˆ8.0 Hz, 2H, CHarom);
7.62 (d, Jˆ8.0 Hz, 2H, CHarom); 7.71 (broad s, 2H, NH). 13
C
1,1-Di(50-bromo-30-indolyl)-2-methylpropane (4cc). Yield:
1
60%. Mp: 150–152ЊC. H NMR (CDCl3, 200 MHz): 0.99
NMR (CDCl3, 75.5 MHz): 21.8 (2×CH3); 32.8 (CH); 41.0
(CH); 111.0 (CH); 118.9 (CH); 119.6 (CH); 121.5 (CH);
121.6 (CH); 127.6 (C); 136.2 (C). MS (CI, NH3ϩiso-
butane): m/z 288 (Mϩ). Anal. calcd for C20H20N2: C:
83.31%, H: 6.99%, N: 9.71%; found: C: 83.40%, H:
6.99%, N: 9.47%.
1
(d, Jˆ6.8 Hz, 6H, 2×CH3); 2.50–2.70 (m, H, CH(CH3)2);
1
4.07 (d, Jˆ8.4 Hz, H, CH); 7.12–7.41 (m, 6H, CHarom);
7.19 (s, 2H, CHarom); 7.97 (broad s, 2H, NH). 13C NMR
(CDCl3, 75.5 MHz): 21.8 (2×CH3); 32.5 (CH); 41.4 (CH);
112.5 (CH); 119.0 (C); 122.2 (CH); 124.9 (CH); 129.2 (C);
135.0 (C). MS (CI, NH3ϩisobutane): m/z 462, 464 and 466
(MHϩϩNH3), 445, 447 and 449 (MHϩ). Anal. calcd for
C20H18Br2N2: C: 53.84%, H: 4.07%, N: 6.28%; found C:
54.24%, H: 4.09%, N: 6.26%.
1-Benzyloxy-2,2-di(30-indolyl)ethane (4da). Yield: 91%.
Mp: 59–60ЊC. 1H NMR (CDCl3, 250 MHz): 4.04 (d,
Jˆ7.1 Hz, 2H, CH2); 4.51 (s, 2H, CH2Ph); 4.82 (t,

H. Chalaye-Mauger et al. / Tetrahedron 56 (2000) 791–804
799
N-(tert-Butoxycarbonyl)-2,2-di(50-bromo-30-indolyl)-
ethylamine (4ec). Yield: 46%. Mp: 203–203.5ЊC. 1H NMR
(CDCl3, 200 MHz): 1.43 (s, 9H, C(CH3)3); 3.86 (nearly t,
Jˆ6.4 Hz, 2H, CH2N); 4.57 (nearly t, Jˆ6.4 Hz, 2H, CHN,
NH); 7.05 (broad s, 2H, CHarom); 7.24 (broad s, 4H, CHarom);
7.64 (broad s, 2H, CHarom); 8.12 (broad s, 2H, NH). 13C
NMR (CDCl3, 75.5 MHz): 28.4 (C(CH3)3); 34.6 (CH);
44.9 (CH2); 79.5 (C(CH3)3); 112.7 (CH); 116.4 (C); 122.0
(CH); 123.2 (CH); 125.1 (CH); 128.5 (C); 135.3 (C); 156.0
(CO2). MS (CI, NH3ϩisobutane): m/z 531, 533 and 535
(Mϩ).
(CH); 122.5 (CH); 126.7 (C); 127.0 (CH); 128.1 (CH);
129.4 (CH); 136.2 (C); 138.6 (C). MS (CI, NH3ϩiso-
butane): m/z 267 (MHϩ). Anal. calcd for C17H18N2O: C:
76.66%, H: 6.81%, N: 10.52%; found C: 76.28%, H:
6.72%, N: 10.24%.
N-Benzyl-2-benzyloxy-N-hydroxy-1-(30-indolyl)ethyl-
amine (3da). Yield: 88%. Mp: 49–51ЊC. 1H NMR (CDCl3,
200 MHz): 3.76 (ABq, JABˆ13.7 Hz, dAϪdBˆ26.1, 2H,
1
1
NCH2Ph); 3.81 (dd, Jˆ5.1, 9.9 Hz, H, H of CH2); 4.13
(dd, Jˆ7.2, 9.9 Hz, 1H, 1H of CH2); 4.42 (dd, Jˆ5.1, 7.2 Hz,
1H, CHN); 4.52 (s, 2H, OCH2Ph); 5.68 (s, 1H, NOH); 7.10–
7.32 (m, 14H, CHarom); 7.65 (d, Jˆ7.2 Hz, 1H, CHarom); 8.21
(broad s, 1H, NH). 13C (CDCl3, 50.3 MHz): 61.7 (CH2); 63.0
(CHN); 72.1 (CH2); 73.1 (CH2); 108.9 (C); 111.2 (CH);
111.9 (C); 119.7 (CH); 119.8 (CH); 122.1 (CH); 123.8
(CH); 127.0 (CH); 127.6 (CH); 127.7 (CH); 128.1 (CH);
128.3 (CH); 129.3 (CH); 136.0 (C); 138.2 (C); 138.4 (C).
MS (CI, NH3ϩisobutane): m/z 373 (MHϩ). Anal. calcd for
C24H24N2O2: C: 77.42%, H: 6.45%, N: 7.53%; found: C:
77.11%, H: 6.45%, N: 7.26%.
N-(tert-Butoxycarbonyl)-2,2-di(60-bromo-30-indolyl)-
1
ethylamine (4ed). Yield: 31%. Mp: 240–242ЊC. H NMR
(DMSO, 200 MHz): 1.32 (s, 9H, C(CH3)3); 3.58 (t,
1
Jˆ6.2 Hz, 2H, CH2); 4.60 (t, Jˆ6.2 Hz, H, CH); 6.82 (t,
Jˆ6.2 Hz, 1H, NH); 6.97–7.48 (m, 8H, CHarom); 10.96
(broad s, 2H, NH). 13C NMR (DMSO, 100.6 MHz): 28.2
(C(CH3)3); 33.5 (CH); 44.9 (CH2); 77.5 (C(CH3)3); 113.6
(C); 113.9 (CH); 116.4 (C); 120.5 (CH); 120.9 (CH); 123.5
(CH); 125.9 (C); 137.3 (C); 155.7 (CO2). MS (CI, NH3ϩiso-
butane): m/z 531, 533 and 535 (Mϩ). Anal. calcd for
C23H23Br2N3O2: C: 51.80%, H: 4.35%, N: 7.88%; found:
C: 52.05%, H: 4.64%, N: 7.67%.
N-Benzyl-2-tert-butoxycarbonylamino-N-hydroxy-1-(30-
indolyl)ethylamine (3ea). Yield: 95%. Mp: 145–146ЊC. 1H
NMR (CDCl3, 200 MHz): 1.51 (s, 9H, C(CH3)3); 3.50–3.70
(m, 2H, CH2N); 3.75 (ABq, JABˆ14.4 Hz, dAϪdBˆ38.9,
2H, CH2Ph); 4.14 (nearly t, Jˆ5.5, 5.8 Hz, 1H, CHN);
Synthesis of 3-indolylhydroxylamines
1
1
4.88 (t, Jˆ6.5 Hz, H, NHBoc); 6.56 (broad s, H, NOH);
7.08–7.39 (m, 9H, CHarom); 7.66 (d, Jˆ7.5 Hz, 1H, CHarom);
8.36 (broad s, 1H, NH). 13C NMR (CDCl3, 75.5 MHz): 28.5
(C(CH3)3); 43.7 (CH2); 60.6 (CH2); 63.8 (CHN); 79.7
(C(CH3)3); 111.2 (CH); 112.3 (C); 119.6 (CH); 119.7
(CH); 122.2 (CH); 123.4 (CH); 126.7 (CH); 127.2 (C);
128.0 (CH); 128.6 (CH); 136.0 (C); 139.0 (C); 157.7
(CO2). MS (CI, NH3ϩisobutane): m/z 382 (MHϩ). Anal.
calcd for C22H27N3O3: C: 69.27%, H: 7.13%, N: 11.01%;
found: C: 69.23%, H: 7.36%, N: 10.77%.
A cold solution (0ЊC) of dry HCl in methanol was prepared
by addition of acetyl chloride (2 mmol) to methanol. The
nitrone and the indole (1 mmol each) were added to this
solution. The reaction was monitored by TLC (silica gel,
diethyl ether/pentane; 1:1) until completion. A saturated
aqueous solution of NaHCO3 was then added. The mixture
was extracted three times with CH2Cl2, and the collected
organic phases washed with brine and dried over anhydrous
MgSO4. After filtration and evaporation of the solvent under
vacuum, the crude product was purified either by several
washings with pentane, by crystallization from a CH2Cl2/
pentane mixture or by column chromatography on silica gel.
N-Benzyl-N-hydroxy-1-(30-indolyl)-1-(p-nitrophenyl)-
1
methylamine (3ga). Yield: 44%. Mp: 87–89ЊC. H NMR
N-Benzyl-N-hydroxy-1-(30-indolyl)propylamine (3aa).
Yield: 94%. Mp: 142–143ЊC. 1H NMR (CDCl3,
200 MHz): 0.86 (t, Jˆ7.4 Hz, 3H, CH3); 1.84–2.06 (m,
1H, 1H of CH2); 2.14–2.34 (m, 1H, 1H of CH2); 3.71
(ABq, JABˆ13.5 Hz, dAϪdBˆ36.3, 2H, CH2Ph); 3.97 (dd,
(CDCl3, 300 MHz): 3.55–3.70 (m, 2H, CH2); 3.72 (ABq,
JABˆ14.0 Hz, dAϪdBˆ57.8, 2H, CH2Ph); 4.07 (t,
1
1
Jˆ5.7 Hz, H, CHN); 4.78–4.91 (nearly t, H, NHBoc);
6.52 (broad s, 1H, NOH); 7.18–7.35 (m, 7H, CHarom);
7.51–7.55 (m, 2H, CHarom); 8.22 (broad s, H, NH). 13C
1
1
1
NMR (CDCl3, 50.3 MHz): 61.8 (CH2); 68.7 (CHN); 111.4
(CH); 114.5 (C); 119.6 (CH); 119.8 (CH); 120.2 (CH);
122.7 (CH); 123.5 (CH); 123.6 (CH); 126.1 (C); 127.3
(C); 128.3 (CH); 128.6 (CH); 129.2 (CH); 136.3 (C);
146.8 (C); 150.1 (C). MS (CI, NH3ϩisobutane): m/z 374
(MHϩ). Anal. calcd for C22H19N3O3: C: 70.78%, H:
5.09%, N: 11.26%; found: C: 71.03%, H: 5.29%, N:
10.99%.
Jˆ5.1, 9.1 Hz, H, CHN); 4.78 (broad s, H, NOH); 7.01–
7.80 (m, 10H, CHarom); 8.12 (broad s, H, NH). 13C NMR
1
(CDCl3, 50.3 MHz): 11.4 (CH3); 26.3 (CH2); 61.8 (CH2);
66.2 (CHN); 111.1 (CH); 114.6 (C); 119.5 (CH); 120.2
(CH); 122.1 (CH); 123.2 (CH); 126.9 (CH); 127.4 (C);
128.1 (CH); 129.2 (CH); 136.3 (C); 138.8 (C). MS (CI,
NH3ϩisobutane): m/z 281 (MHϩ). Anal. calcd for
C18H20N2O: C: 77.11%, H: 7.19%, N: 9.99%; found C:
76.66%, H: 7.17%, N: 9.88%.
N-Benzyl-N-hydroxy-1-(50-methoxy-30-indolyl)propyl-
1
N-Benzyl-N-hydroxy-1-(30-indolyl)ethylamine
(3ba).
amine (3ab). Yield: 83%. Mp: 136–137ЊC. H NMR (d6
1
acetone, 200 MHz): 0.83 (t, Jˆ7.3 Hz, 3H, CH3); 1.84–
Yield: 87%. Mp: 97–99ЊC. H NMR (CDCl3, 200 MHz):
1.61 (d, Jˆ6.9 Hz, 3H, CH3); 3.74 (ABq, JABˆ13.4 Hz,
1
1
1
1
2.04 (m, H, H of CH2); 2.04–2.35 (m, H, H of CH2);
2.81 (s, 1H, NOH); 3.66 (ABq, JABˆ14.0 Hz, dAϪdBˆ53.4,
2H, CH2Ph); 3.79 (s, 3H, OCH3); 3.80–3.91 (m, 1H, CHN);
6.72–6.82 (m, 2H, CHarom); 7.10–7.32 (m, 7H, CHarom);
1
dAϪdBˆ26.7, 2H, CH2Ph); 4.27 (q, Jˆ6.9 Hz, H, CHN);
1
5.05 (broad s, H, NOH); 7.13–7.40 (m, 9H, CHarom); 7.80
(d, Jˆ7.5 Hz, 1H, CHarom); 8.09 (broad s, 1H, NH). 13C NMR
(CDCl3, 50.3 MHz): 18.5 (CH3); 59.1 (CHN); 61.1 (CH2);
111.1 (CH); 117.0 (C); 119.5 (CH); 120.2 (CH); 122.0
1
9.97 (broad s, H, NH). 13C NMR (d6 acetone, 50.3 MHz):
11.7 (CH3); 26.9 (CH2); 55.8 (OCH3); 62.2 (CH2); 67.8

800
H. Chalaye-Mauger et al. / Tetrahedron 56 (2000) 791–804
(CHN); 102.8 (CH); 112.4 (CH); 112.7 (CH); 115.3 (C);
125.1 (C); 125.3 (CH); 127.1 (CH); 128.5 (CH); 129.8
(CH); 132.9 (C); 141.1 (C); 154.5 (C). MS (CI, NH3ϩiso-
butane): m/z 311 (MHϩ). Anal. calcd for C19H22N2O2: C:
73.52%, H: 7.14%, N: 9.03%; found: C: 73.60%, H: 7.19%,
N: 9.09%.
2.81 (s, 1H, NOH); 3.64 (ABq, JABˆ13.5 Hz, dAϪdBˆ54.7,
2H, CH2Ph); 3.90 (dd, Jˆ5.2, 8.9 Hz, 1H, CHN); 6.89 (s, 1H,
CHarom); 7.13–7.45 (m, 8H, CHarom); 7.98 (broad s, 1H, NH).
13C NMR (d6 acetone, 75.5 MHz): 11.0 (CH3); 26.3 (CH2);
61.5 (CH2); 66.7 (CHN); 111.7 (C); 113.3 (CH); 114.7 (C);
123.1 (CH); 124.0 (CH); 125.7 (CH); 126.5 (CH); 127.9
(CH); 129.2 (CH); 129.4 (C); 135.8 (C); 140.1 (C). MS
(CI, NH3ϩisobutane): m/z 359 and 361 (MHϩ).
N-Benzyl-N-hydroxy-1-(50-methoxy-30-indolyl)ethyl-
1
amine (3bb). Yield: 88%. Mp: 134–135ЊC. H NMR (d6
acetone, 300 MHz): 1.59 (d, Jˆ6.7 Hz, 3H, CH3); 2.89 (s,
1H, NOH); 3.70 (ABq, JABˆ14.0 Hz, dAϪdBˆ45.8, 2H,
CH2Ph); 3.80 (s, 3H, OCH3); 4.22 (q, Jˆ6.7 Hz, 1H,
N-Benzyl-1-(50-bromo-30-indolyl)-N-hydroxyethylamine
1
(3bc). Yield: 82%. Mp: 106–107ЊC. H NMR (d6 acetone,
250 MHz): 1.60 (d, Jˆ6.3 Hz, 3H, CH3); 2.94 (s, 1H, NOH);
3.68 (ABq, JABˆ13.5 Hz, dAϪdBˆ41.5, 2H, CH2Ph); 4.24
(q, Jˆ6.3 Hz, 1H, CHN); 6.99 (broad s, 1H, CHarom); 7.13–
1
1
CHN); 6.72–6.78 (m, H, CHarom); 6.82 (s, H, CHarom);
7.09–7.37 (m, 7H, CHarom); 9.94 (broad s, H, NH). 13C
1
1
NMR (d6 acetone, 75.5 MHz): 19.0 (CH3); 55.8 (OCH3);
60.9 (CHN); 61.4 (CH2); 102.8 (CH); 112.5 (CH); 112.7
(CH); 119.1 (C); 124.3 (CH); 127.1 (CH); 128.0 (C);
128.5 (CH); 129.8 (CH); 132.9 (C); 141.1 (C); 154.5 (C).
MS (CI, NH3ϩisobutane): m/z 297 (MHϩ). Anal. calcd for
C18H20N2O2: C: 72.97%, H: 7.76%, N: 9.46%; found: C:
73.23%, H: 7.71%, N: 9.49%.
7.37 (m, 7H, CHarom); 8.04 (s, H, CHarom); 10.32 (broad s,
1H, NH). 13C NMR (d6 acetone, 62.5 MHz): 18.5 (CH3);
60.3 (CHN); 61.0 (CH2); 112.1 (C); 113.7 (CH); 117.7
(C); 123.5 (CH); 124.4 (CH); 125.1 (CH); 127.0 (CH);
128.3 (CH); 129.3 (C); 129.6 (CH); 136.2 (C); 140.5 (C).
MS (CI, NH3ϩisobutane): m/z 345 and 347 (MHϩ). Anal.
calcd for C17H17BrN2O: C: 59.14%, H: 4.96%, N: 8.11%;
found: C: 58.96%, H: 5.00%, N: 7.81%.
N-Benzyl-2-benzyloxy-N-hydroxy-1-(50-methoxy-30-
1
indolyl)ethylamine (3db). Yield: 93%. Mp: 44–46ЊC. H
N-Benzyl-1-(50-bromo-30-indolyl)-2-tert-butoxycarbonyl-
amino-N-hydroxyethylamine (3ec). Yield: 83%. Mp:
170–171ЊC. 1H NMR (CDCl3, 200 MHz): 1.53 (s, 9H,
C(CH3)3); 3.47–3.73 (m, 2H, CH2); 3.71 (ABq,
JABˆ14.1 Hz, dAϪdBˆ43.0, 2H, CH2Ph); 4.03 (t,
Jˆ5.5 Hz, 1H, CHN); 4.89 (nearly t, Jˆ6.9 Hz, 1H,
NHBoc); 6.73 (broad s, 1H, NOH); 7.15–7.50 (m, 8H,
NMR (CDCl3, 300 MHz): 3.74 (s, 3H, OCH3); 3.77 (ABq,
JABˆ13.5 Hz, dAϪdBˆ55.9, 2H, NCH2Ph); 3.79 (dd,
1
1
Jˆ5.0, 10.0 Hz, H, H of CH2); 4.12 (dd, Jˆ7.0, 10.0 Hz,
1
1
1H, H of CH2); 4.34 (dd, Jˆ5.0, 7.0 Hz, H, CHN); 4.48
(ABq, JABˆ12.0 Hz, dA-dBˆ9.8, 2H, OCH2Ph); 6.03 (broad
s, 1H, NOH); 6.81 (dd, Jˆ2.5, 9.0 Hz, 1H, CHarom); 7.01 (d,
Jˆ2.5 Hz, 1H, CHarom); 7.05 (d, Jˆ2.5 Hz, 1H, CHarom); 7.09
1
1
CHarom); 7.83 (s, H, CHarom); 8.42 (broad s, H, NH). 13C
NMR (CDCl3, 75.5 MHz): 28.4 (C(CH3)3); 44.0 (CH2); 60.6
(CH2); 63.9 (CHN); 80.0 (C(CH3)3); 112.2 (C); 112.7 (CH);
113.0 (C); 122.5 (CH); 124.6 (CH); 125.1 (CH); 126.8
(CH); 128.0 (CH); 128.6 (CH); 128.8 (C); 134.7 (C);
138.7 (C); 157.7 (CO2). MS (CI, NH3ϩisobutane): m/z
460 and 462 (MHϩ). Anal. calcd for C22H26BrN3O3: C:
57.39%, H: 5.65%, N: 9.13%; found: C: 57.07%, H:
5.65%, N: 9.22%.
1
(d, Jˆ9.0 Hz, H, CHarom); 7.16–7.28 (m, 10H, CHarom);
8.25 (broad s, H, NH). 13C NMR (CDCl3, 75.5 MHz):
1
55.7 (OCH3); 61.5 (CH2); 62.5 (CHN); 71.9 (CH2); 73.0
(CH2); 101.5 (CH); 111.3 (C); 111.9 (CH); 112.3 (CH);
124.7 (CH); 126.9 (CH); 127.5 (CH); 127.6 (CH); 128.0
(CH); 128.2 (CH); 129.4 (CH); 131.1 (C); 138.2 (C);
153.9 (C). MS (CI, NH3ϩisobutane): m/z 403 (MHϩ).
Anal. calcd for C25H26N2O3: C: 74.63%, H: 6.47%, N:
6.96%; found: C: 74.41%, H: 6.54%, N: 6.93%.
N-Benzyl-1-(60-bromo-30-indolyl)-2-tert-butoxycarbonyl-
amino-N-hydroxyethylamine (3ed). Yield: 78%. Mp:
159–160ЊC. 1H NMR (CDCl3, 300 MHz): 1.50 (s, 9H,
C(CH3)3); 3.55–3.70 (m, 2H, CH2); 3.72 (ABq,
JABˆ14.0 Hz, dAϪdBˆ57.8, 2H, CH2Ph); 4.07 (t,
N-Benzyl-2-tert-butoxycarbonylamino-N-hydroxy-1-(50-
methoxy-30-indolyl)ethylamine (3eb). Yield: 95%. Mp:
141–143ЊC. 1H NMR (CDCl3, 200 MHz): 1.51 (s, 9H,
C(CH3)3); 3.46–3.78 (m, 2H, CH2); 3.78 (ABq,
JABˆ14.1 Hz, dAϪdBˆ47.7, 2H, CH2Ph); 3.83 (s, 3H,
1
1
Jˆ5.7 Hz, H, CHN); 4.78–4.91 (nearly t, H, NHBoc);
1
OCH3); 4.09 (t, Jˆ5.5 Hz, H, CHN); 4.92 (t, Jˆ5.5 Hz,
6.52 (broad s, 1H, NOH); 7.18–7.35 (m, 7H, CHarom);
1
1
1H, NHBoc); 6.58 (broad s, H, NOH); 6.87 (dd, Jˆ2.4,
7.51–7.55 (m, 2H, CHarom); 8.22 (broad s, H, NH). 13C
8.9 Hz, 1H, CHarom); 7.10 (d, Jˆ2.4 Hz, 1H, CHarom);
NMR (CDCl3, 75.5 MHz): 28.4 (C(CH3)3); 43.9 (CH2);
60.5 (CH2); 63.2 (CHN); 79.9 (C(CH3)3); 112.2 (C); 114.2
(CH); 115.8 (C); 120.9 (CH); 122.9 (CH); 124.1 (CH);
126.0 (C); 126.8 (CH); 128.1 (CH); 128.5 (CH); 136.7
(C); 138.8 (C); 157.7 (CO2). MS (CI, NH3ϩisobutane):
m/z 460 and 462 (MHϩ). Anal. calcd for C22H26BrN3O3:
C: 57.39%, H: 5.69%, N: 9.13%; found: C: 57.09%, H:
5.87%, N: 9.05%.
1
7.20–7.33 (m, 7H, CHarom); 8.18 (broad s, H, NH). 13C
NMR (CDCl3, 75.5 MHz): 28.4 (C(CH3)3); 43.8 (CH2);
55.9 (OCH3); 60.6 (CH2); 63.7 (CHN); 79.7 (C(CH3)3);
101.5 (CH); 111.9 (CH); 112.5 (CH); 124.2 (CH); 126.7
(CH); 127.5 (C); 128.0 (CH); 128.6 (CH); 131.2 (C);
139.0 (C); 154.1 (C); 157.7 (CO2). MS (CI, NH3ϩiso-
butane): m/z 412 (MHϩ). Anal. calcd for C23H29N3O4: C:
67.15%, H: 7.06%, N: 10.22%; found: C: 67.15%, H:
7.36%, N: 10.09%.
Diastereoselective condensations
N-Benzyl-1-(50-bromo-30-indolyl)-N-hydroxypropyl-
amine (3ac). Yield: 70%. Mp: 159–160ЊC. H NMR (d6
The reaction conditions were similar to those reported for
the synthesis of other hydroxylamines 3 (4 h, 0ЊC). Starting
with nitrone 1h (0.224 g, 0.696 mmol), indole (0.081 g,
0.696 mmol), acetyl chloride (0.109 g, 1.39 mmol) and
1
acetone, 300 MHz): 0.84 (t, Jˆ7.4 Hz, 3H, CH3); 1.85–
1
1
1
1
1.95 (m, H, H of CH2); 2.21–2.38 (m, H, H of CH2);

H. Chalaye-Mauger et al. / Tetrahedron 56 (2000) 791–804
801
1
1
methanol (7 mL), the two diastereoisomers (R,R)-3ha and
(S,R)-3ha were isolated after column chromatography
(silica gel, ethyl acetate/pentane; 1:9) in 62.5% (0.191 g,
0.435 mmol) and 5.5% (0.017 g, 0.0387 mmol) yields,
respectively.
(d, Jˆ8.9 Hz, H, H of OCH2); 3.70 (ABq, JABˆ14.1 Hz,
dAϪdBˆ19.4, 2H, CH2Ph); 3.70–3.74 (m, 1H, 1H of
1
OCH2); 4.07 (d, Jˆ10.3 Hz, H, CHNOH); 4.39–4.53 (m,
1H, CHNBoc); 7.03–7.67 (m, 11H, CHarom and NOH); 8.43
(broad s, H, NH). 13C NMR (CDCl3, 50.3 MHz): 24.7
1
(CH3); 27.7 (CH3); 28.5 (C(CH3)3); 56.3 (CH); 60.3
(CH2); 62.8 (CH); 65.9 (CH2); 80.9 (C(CH3)3); 94.0
(C(CH3)2); 110.2 (C); 111.1 (CH); 119.6 (CH); 121.8
(CH); 124.7 (CH); 126.7 (CH); 127.8 (CH); 128.6 (CH);
135.4 (C); 136.7 (C); 138.8 (C); 154.7 (CO2). MS (CI,
NH3ϩisobutane): m/z 452 (MHϩ).
(R,R)-3ha: Yield: 62.5%. Mp: 73–76ЊC. [a]2D0ˆϪ31.4
(cˆ1.08; chloroform). 1H NMR (d8 toluene, 300 MHz,
343 K): 1.30 (broad s, 9H, C(CH3)3); 2.86 (dd, Jˆ7.0,
1
1
1
9.0 Hz, H, H of SCH2); 3.14 (pseudo d, Jˆ9.0 Hz, H,
1H of SCH2); 3.72 (ABq, JABˆ13.5 Hz, dAϪdBˆ77.4, 2H,
CH2Ph); 4.10 (ABq, JABˆ9.0 Hz, dA-dBˆ273.9, 2H,
1
NCH2S); 4.17 (d, Jˆ6.0 Hz, H, CHNOH); 5.27 (broad s,
Condensations on position 2 of indole
1H, CHNBoc); 6.37 (broad s, 1H, NOH); 6.98–7.30 (m, 7H,
CHarom); 7.14 (d, Jˆ7.0 Hz, 1H, CHarom); 7.23 (d, Jˆ7.5 Hz,
1H, CHarom); 7.39 (broad s, 1H, NH); 7.72 (d, Jˆ7.0 Hz, 1H,
CHarom). 13C NMR (d8 toluene, 75.5 MHz, 343 K): 28.4
(C(CH3)3); 33.6 (CH2); 49.4 (CH2); 62.0 (CH); 62.3
(CH2); 67.0 (CH); 80.6 (C(CH3)3); 111.0 (C); 111.5 (CH);
120.1 (CH); 120.5 (CH); 122.4 (CH); 125.0 (CH); 127.0
(CH); 128.3 (CH); 128.8 (C); 129.6 (CH); 136.8 (C);
139.6 (C); 154.9 (CO2). MS (CI, NH3ϩisobutane): m/z
440 (MHϩ). Anal. calcd for C24H29N3O3S: C: 65.60%, H:
6.61%, N: 9.57%, S: 7.29%; found: C: 65.43%, H: 6.59%,
N: 9.39%, S: 7.21%.
These reactions were performed under an argon atmosphere.
Typical experimental procedure: to a solution of indole
(0.351 g, 3 mmol) in dry THF (6 mL), cooled at Ϫ78ЊC
was added a solution of n-butyllithium in hexane (1.6 M,
2.06 mL, 3.3 mmol). The reaction mixture was stirred for
30 min before addition of excess dry ice. After another
5 min at Ϫ78ЊC and 30 min at r.t., the solvent and the excess
of CO2 were evaporated. The resulting white solid was
dissolved in THF (6 mL). The obtained solution was cooled
to Ϫ78ЊC and t-butyllithium (1.7 M in hexane, 1.94 mL,
3.3 mmol) was added. The reaction mixture was then stirred
for 1.5 h at Ϫ78ЊC and transferred via syringe onto a
suspension of nitrone 1a (0.49 g, 3 mmol) in THF (6 mL)
previously cooled to Ϫ78ЊC. After 2 h stirring, the reaction
was quenched by water (0.22 mL) and the reaction mixture
was warmed to r.t. A saturated aqueous solution of NH4Cl
was then added. The aqueous phase was extracted three
times with CH2Cl2. The collected organic layers were washed
with brine, dried over anhydrous MgSO4, filtered and the
solvent was evaporated under reduced pressure. The crude
product was purified by column chromatography (silica gel,
ethyl acetate/pentane: 5/95) to yield hydroxylamine 6a as a
white solid (0.483 g, 1.73 mmol).
Crystal structure: Single crystals were obtained by slow
evaporation of a solution of (R,R)-3ha in ethanol. A crystal
of 0:50×0:40×0:32 mm3 was used for the crystallographic
study. The unit-cell dimensions, aˆ13:283ꢀ3† and
ꢀ
cˆ48:318ꢀ15† A were refined by a least squares method
from a set of 25 reflexions measured in a range of 10–12Њ.
The space group is P3221 and Zˆ12: Intensity data
were collected with an Enraf-Nonius four-circle CAD4
diffractometer operating with molybdenum radiation mono-
chromatized with
a
graphite plate.25 Measurements
performed at room temperature with an v-type scan in the
range 2–23Њ(u) led to a set of 3991 reflexions which,
processed using the TeXsan software,26 provided a set of
3940 independent ones ꢀRint:ˆ0:02† used for the structure
determination, itself performed using a direct method,
SIR92.27 All non-hydrogen atoms were refined aniso-
tropically, hydrogen ones, isotropically. The final R value
is 0.062 ꢀRwˆ0:058†: During the structural investigation a
molecule of ethanol was found in the atomic arrangement.
Additional data are: Dxˆ1.22, mˆ1.63 cmϪ1, GOFˆ2.06.
All calculations were performed using the TeXsan soft-
ware26 and the drawing with the ORTEP system.28
N-Benzyl-N-hydroxy-1-(20-indolyl)propylamine
(6a).
Yield: 58%. Mp: 119–121ЊC. 1H NMR (CDCl3,
200 MHz): 0.90 (t, Jˆ7.5 Hz, 3H, CH3); 1.78–2.14 (m,
2H, CH2); 3.66 (ABq, JABˆ13.0 Hz, dAϪdBˆ18.9, 2H,
1
CH2Ph); 3.78 (dd, Jˆ6.2, 8.6 Hz, H, CHN); 5.85 (broad
1
1
s, H, NOH); 6.38 (d, Jˆ1.4 Hz, H, CHarom); 7.08 (dd,
1
1
Jˆ1.4, 7.2 Hz, H, CHarom); 7.14 (dd, Jˆ1.7, 2.4 Hz, H,
1
CHarom); 7.20 (dd, Jˆ1.4, 7.2 Hz, H, CHarom); 7.25–7.45
(m, 5H, CHarom); 7.60 (d, Jˆ7.5 Hz, 1H, CHarom); 8.73
(broad s, H, NH). 13C NMR (CDCl3, 50.3 MHz): 11.3
1
(CH3); 25.6 (CH2); 60.9 (CH2); 66.0 (CHN); 102.8 (CH);
110.9 (CH); 119.5 (CH); 120.2 (CH); 121.6 (CH); 127.4
(CH); 127.6 (C); 128.3 (CH); 129.7 (CH); 136.3 (C);
136.9 (C); 137.5 (C). MS (CI, NH3ϩisobutane): m/z 281
(MHϩ). Anal. calcd for C18H20N2O: C: 77.11%, H: 7.19%,
N: 9.99%; found: C: 76.89%, H: 7.20%, N: 9.83%.
(S,R)-3ha: Yield: 5.5%. Mp: 87–89ЊC. [a]2D0ˆϪ2.4
1
(cˆ1.06; chloroform). H NMR (CDCl3, 300 MHz): 1.59
1
1
(broad s, 9H, C(CH3)3); 2.50 (d, Jˆ11.3 Hz, H, H of
1
1
SCH2); 2.92 (dd, Jˆ6.2, 11.3 Hz, H, H of SCH2); 3.70
(ABq, JABˆ14.1 Hz, dAϪdBˆ14.6, 2H, CH2Ph); 4.27 (d,
Jˆ11.7 Hz, 1H, CHNOH); 4.45 (ABq, JABˆ8.6 Hz,
1
N-Benzyl-N-hydroxy-1-(20-indolyl)ethylamine (6b). Yield:
dAϪdBˆ76.3, 2H, NCH2S); 4.87–4.95 (m, H, CHNBoc);
1
7.08–7.60 (m, 11H, CHarom and NOH); 8.36 (broad s, H,
1
36%. H (CDCl3, 200 MHz): 1.44 (d, Jˆ6.9 Hz, 3H, CH3);
NH).
3.55 (ABq, JABˆ13.0 Hz, dAϪdBˆ23.0, 2H, CH2Ph); 3.97
1
1
(q, Jˆ6.9 Hz, H, CHN); 6.28 (broad s, H, CHarom); 6.47
1
1
We were unable to isolate compound 3ia in pure form.
Spectroscopic data obtained from impure 3i are the follow-
(broad s, H, NOH); 7.00 (dd, Jˆ1.4, 7.2 Hz, H, CHarom);
7.05–7.26 (m, 6H, CHarom); 7.30 (d, Jˆ8.2 Hz, 1H, CHarom);
1
7.52 (d, Jˆ7.2 Hz, 1H, CHarom); 8.67 (broad s, 1H, NH). 13
C
ing: H NMR (CDCl3, 300 MHz): 1.52 (broad s, 3H, CH3);
1.56 (broad s, 3H, CH3); 1.61 (broad s, 9H, C(CH3)3); 3.49
NMR (CDCl3, 75.5 MHz): 17.1 (CH3); 59.5 (CHN); 60.0

802
H. Chalaye-Mauger et al. / Tetrahedron 56 (2000) 791–804
(CH2); 101.3 (CH); 110.9 (CH); 119.6 (CH); 120.3 (CH);
121.7 (CH); 127.5 (CH); 127.8 (C); 128.3 (CH); 129.7
(CH); 136.3 (C); 137.5 (C); 138.8 (C). MS (CI, NH3ϩiso-
butane): m/z 267 (MHϩ). Anal. calcd for C17H18N2O: C:
76.66%, H: 6.81%, N: 10.52%; found: C: 76.37%, H:
6.80%, N: 10.26%.
by CH2Cl2. The collected organic layers were washed with
water and brine, dried over anhydrous MgSO4 and filtered.
The solvent was evaporated under vacuum and the obtained
crude product was purified by column chromatography
(ethyl acetate/hexane or ether/pentane).
1-(50-Bromo-30-indolyl)-1-(300-indolyl)propane (9aac).
Yield: 76%. Amorphous solid. 1H NMR (CDCl3,
250 MHz): 0.96 (t, Jˆ7.1 Hz, 3H, CH3); 2.09–2.27 (m,
2H, CH2); 4.26 (t, Jˆ7.1 Hz, 1H, CH); 6.87 (s, 1H, CHarom);
Synthesis of naturally occurring diindolylalkanes
Streptindole (7). To
a solution of 4da (0.127 g,
1
6.90 (s, H, CHarom); 6.90–7.21 (m, 4H, CHarom); 7.28 (d,
0.347 mmol) in dry methanol (5 mL) were added acetic
acid (0.2 mL) and Pearlman reagent (Pd(OH)2/C, 0.052 g).
The reaction mixture was stirred under a H2 atmosphere for
18 h and then filtered through celite. The solvents were
removed under vacuum. The obtained crude product was
dissolved in ethyl acetate and treated with NaHCO3 until
basic pH. After extraction (EtOAc, three times), washing of
the organic phase with brine, drying over anhydrous
MgSO4, filtration and evaporation of the solvent, the crude
product was purified by column chromatography (silica gel,
diethyl ether) to yield the expected alcohol17 in 95% yield
(0.091 g, 0.33 mmol). This alcohol (0.050 g, 0.18 mmol)
was stirred in acetic anhydride (2 mL) in the presence of
sodium acetate (0.060 g, 0.73 mmol) for 17 h. Ethyl acetate
(1.4 mL) and ethanol (0.2 mL) were then added and the
resulting mixture was stirred for 24 h. The mixture was
washed three times (first water, then aqueous solution of
NaHCO3, then brine). The organic layer was dried over
anhydrous MgSO4, filtered and the solvent evaporated to
give the crude acetate which was purified by preparative
TLC (silica gel, diethyl ether/pentane; 1:1). Streptindole 7
was isolated in 83% yield (0.048 g, 0.151 mmol). Its IR and
1H NMR spectra were in agreement with those previously
reported.17 Anal. calcd for C20H18N2O2: C: 75.47%, H:
5.66%, N: 8.80%; found: C: 75.32%, H: 5.65%, N: 8.73%.
Jˆ7.9 Hz, 1H, CHarom); 7.53 (d, Jˆ7.9 Hz, 1H, CHarom); 7.69
1
1
1
(s, H, CHarom); 7.75 (broad s, H, NH); 7.78 (broad s, H,
NH). 13C NMR (CDCl3, 62.5 MHz): 13.0 (CH3); 28.4
(CH2); 35.8 (CH); 111.1 (CH); 112.2 (C); 112.5 (CH);
118.9 (CH); 119.5 (CH); 119.8 (C); 121.4 (CH); 121.7
(CH); 122.0 (CH); 122.7 (CH); 124.4 (CH); 126.9 (C);
128.8 (C); 135.1 (C); 136.5 (C). MS (CI, NH3ϩisobutane):
m/z 353 and 355 (MHϩ), 352 and 354 (Mϩ). Anal. calcd for
C19H17BrN2: C: 64.60%, H: 4.85%, N: 7.93%; found: C:
64.87%, H: 5.03%, N: 7.65%.
1-(60-Bromo-30-indolyl)-1-(300-indolyl)propane (9aad).
Yield: 84%. Amorphous solid. 1H NMR (CDCl3,
200 MHz): 0.99 (t, Jˆ7.2 Hz, 3H, CH31); 2.21 (quint.,
Jˆ7.2 Hz, 2H, CH2); 4.32 (t, Jˆ7.2 Hz, H, CH); 6.97–
1
7.56 (m, 9H, CHarom); 7.85 (broad s, H, NH); 7.88 (broad
s, 1H, NH). 13C NMR (CDCl3, 50.3 MHz): 12.9 (CH3); 28.5
(CH2); 35.7 (CH); 111.1 (CH); 113.9 (CH); 115.2 (C); 119.0
(CH); 119.5 (CH); 120.8 (CH); 121.4 (CH); 121.8 (CH);
122.0 (CH); 122.2 (CH); 126.0 (C); 127.0 (C); 136.5 (C);
137.2 (C). MS (CI, NH3ϩisobutane): m/z 353 and 355
(MHϩ).
1-(30-Indolyl)-1-(500-methoxy-300-indolyl)propane (9aab).
Yield: 83%. 1H NMR (CDCl3, 250 MHz): 1.00 (t,
Jˆ7.1 Hz, 3H, CH3); 2.22 (q, Jˆ7.1 Hz, 2H, CH2); 3.76
(s, 3H, OCH3); 4.31 (t, Jˆ7.1 Hz, 1H, CH); 6.80 (dd,
2,2-Bis(60-bromo-30-indolyl)ethylamine
(8).
This
compound was obtained by treatment of its N-Boc-protected
precursor 4ed (0.054 g, 0.1 mmol) with trifluoroacetic acid
(0.1 M solution in CH2Cl2, 1 mL) at r.t. The reaction was
monitored by TLC (silica gel, ethyl acetate/hexane; 3:7) and
was finished after 2 h. The reaction mixture was then diluted
with ethyl acetate and treated with a saturated aqueous solu-
tion of NaHCO3 until the pH became basic. The aqueous
layer was extracted three times with ethyl acetate. The
collected organic layers were dried over anhydrous
MgSO4 and filtered. The solvents were evaporated under
vacuum and the crude product was purified by column
1
Jˆ2.4, 8.7 Hz, H, CHarom); 6.93 (broad s, 2H, CHarom);
6.99–7.23 (m, 4H, CHarom); 7.29 (d, Jˆ7.9 Hz, 1H, CHarom);
7.59 (d, Jˆ7.9 Hz, 1H, CHarom); 7.73 (broad s, 1H, NH); 7.83
1
(broad s, H, NH). 13C NMR (CDCl3, 62.5 MHz): 13.1
(CH3); 28.5 (CH2); 35.8 (CH); 55.9 (OCH3); 101.9 (CH);
111.0 (CH); 111.5 (CH); 111.6 (CH); 118.9 (CH); 119.6
(CH); 119.9 (C); 120.1 (C); 121.4 (CH); 121.6 (CH);
122.3 (CH); 127.2 (C); 127.6 (C); 131.7 (C); 136.6 (C);
153.5 (C). MS (CI, NH3ϩisobutane): m/z 305 (MHϩ).
Anal. calcd for C20H20N2O: C: 78.92%, H: 6.62%, N:
9.20%; found: C: 79.13%, H: 6.61%, N: 9.07%.
chromatography to yield pure amine
8
(0.034 g,
1
0.078 mmol, 78% yield) as an amorphous solid. Its H and
13C NMR spectra were in agreement with those reported for
the natural compound.18 Anal. calcd for C18H15Br2N3: C:
49.91%, H: 3.49%; found: C: 49.89%, H: 3.55%.
1-(30-Indolyl)-1-(200-methyl-300-indolyl)propane (9aae).
Yield: 74%. Mp: 156–158ЊC. 1H NMR (CDCl3,
250 MHz): 0.93 (t, Jˆ7.1 Hz, 3H, CH3); 2.12–2.48 (m,
2H, CH2); 2.38 (s, 3H, CH3); 4.29 (dd, Jˆ5.5, 10.3 Hz,
1H, CH); 6.94–7.13 (m, 5H, CHarom); 7.21–7.30 (m, 2H,
CHarom); 7.42 (d, Jˆ7.9 Hz, 1H, CHarom); 7.57 (d, Jˆ
Synthesis of non-symmetric diindolylalkanes
1
1
7.1 Hz, H, CHarom); 7.65 (broad s, H, NH); 7.84 (broad
A solution of the hydroxylamine 3 (1 mmol) and freshly
distilled ClSiMe3 (1 mmol) in anhydrous CH2Cl2 (10 mL)
was stirred at r.t. for 5 min. The indole derivative 2 was then
added and the reaction was monitored by TLC (silica gel,
diethyl ether/pentane: 1/1) until completion. The reaction
mixture was then treated with a saturated aqueous solution
of NaHCO3 and the aqueous layer was extracted three times
s, H, NH). 13C NMR (CDCl3, 62.5 MHz): 12.2 (CH3);
1
13.0 (CH3); 27.5 (CH2); 35.4 (CH); 110.0 (CH); 110.9
(CH); 113.8 (C); 118.6 (CH); 118.9 (CH); 119.4 (CH);
120.4 (CH); 120.7 (C); 121.0 (CH); 121.6 (CH); 127.3
(C); 128.1 (C); 131.0 (C); 135.3 (C); 136.4 (C). MS (DCI,
NH3ϩisobutane): m/z 288 (Mϩ). Anal. calcd for C20H20N2:

H. Chalaye-Mauger et al. / Tetrahedron 56 (2000) 791–804
803
C: 83.33%, H: 6.94%, N: 9.72%; found: C: 83.60%, H:
6.89%, N: 9.59%.
131.5 (C); 136.3 (C); 138.3 (C); 153.5 (C). MS (CI,
NH3ϩisobutane): m/z 396 (Mϩ). Anal. calcd for
C26H24N2O2: C: 78.79%, H: 6.06%, N: 7.07%; found: C:
78.67%, H: 6.05%, N: 6.99%.
1-(50-Bromo-30-indolyl)-1-(300-indolyl)ethane (9bac). Yields:
51% from 3ba; 53% from 3bc. Amorphous solid. 1H NMR
(CDCl3, 250 MHz): 1.73 (d, Jˆ7.1 Hz, 3H, CH3); 4.54 (q,
Jˆ7.1 Hz, 1H, CH); 6.86 (s, 1H, CHarom); 6.89 (s, 1H,
CHarom); 6.91–7.19 (m, 4H, CHarom); 7.26 (d, Jˆ7.9 Hz,
1-(60-Bromo-30-indolyl)-N-tert-butoxycarbonyl-1-(300-
indolyl)ethylamine (9ead). Yield: 48%. Amorphous solid.
1H NMR (CDCl3, 200 MHz): 1.42 (s, 9H, C(CH3)3); 3.86 (t,
Jˆ6.5 Hz, 2H, CH2); 4.56–4.73 (m, 2H, CH and NH); 6.92
(broad s, 2H, CHarom); 6.95–7.57 (m, 7H, CHarom); 8.11
(broad s, 2H, NH). 13C NMR (CDCl3, 50.3 MHz): 28.4
(C(CH3)3); 34.5 (CH); 44.8 (CH2); 79.3 (C(CH3)3); 111.2
(CH); 114.1 (CH); 115.5 (C); 116.6 (CH); 117.2 (C); 119.4
(CH); 120.8 (CH); 122.0 (CH); 122.1 (CH); 122.6 (CH);
125.8 (C); 126.7 (C); 136.5 (C); 137.3 (C); 156.1 (CO2).
1
1H, CHarom); 7.50 (d, Jˆ7.9 Hz, H, CHarom); 7.64 (s, H,
1
CHarom); 7.69 (broad s, 1H, NH); 7.72 (broad s, 1H, NH). 13
C
NMR (CDCl3, 62.5 MHz): 21.4 (CH3); 28.1 (CH); 109.9
(CH); 111.8 (C); 113.2 (CH); 118.9 (CH); 119.3 (CH);
119.7 (C); 121.0 (CH); 121.4 (CH); 121.7 (CH); 122.8
(CH); 124.1 (CH); 126.9 (C); 128.8 (C); 135.1 (C); 136.5
(C). MS (CI, NH3ϩisobutane): m/z 340 (MHϩ). Anal. calcd
for C18H15BrN2: C: 63.72%, H: 4.42%, N: 8.26%; found: C:
64.00%, H: 4.39%, N: 8.01%.
Acknowledgements
1-(30-Indolyl)-1-(500-methoxy-300-indolyl)ethane (9bab).
Yields: 63% from 3ba; 57% from 3bb. Mp: 54–56ЊC. H
1
This work has been generously supported by the
‘Association pour la Recherche sur le Cancer’ (ARC).
NMR (CDCl3, 250 MHz): 1.77 (d, Jˆ7.1 Hz, 3H, CH3);
1
3.74 (s, 3H, OCH3); 4.59 (q, Jˆ7.1 Hz, H, CH); 6.80–
6.83 (m, 3H, CHarom); 7.00–7.20 (m, 4H, CHarom); 7.27 (d,
Jˆ7.9 Hz, 1H, CHarom); 7.56 (d, Jˆ7.9 Hz, 1H, CHarom); 7.67
(broad s, 1H, NH); 7.77 (broad s, 1H, NH). 13C NMR
(CDCl3, 62.5 MHz): 21.5 (CH3); 28.1 (CH); 55.9 (OCH3);
101.7 (CH); 111.0 (CH); 111.7 (CH); 111.9 (CH); 118.9
(CH); 119.7 (CH); 121.1 (CH); 121.3 (C); 121.5 (C);
121.7 (CH); 122.0 (CH); 126.8 (C); 127.2 (C); 131.7 (C);
136.6 (C); 153.5 (C). MS (CI, NH3ϩisobutane): m/z 291
(MHϩ).
References
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2-Benzyloxy-1-(50-bromo-30-indolyl)-1-(300-indolyl)-
1
ethane (9dac). Yield: 83%. H NMR (CDCl3, 250 MHz):
4.05 (d, Jˆ7.1 Hz, 2H, CH2); 4.53 (s, 2H, CH2Ph); 4.77 (t,
´
3. (a) Denis, J.-N.; Tchertchian, S.; Tomassini, A.; Vallee, Y.
Jˆ7.1 Hz, 1H, CH); 6.80 (broad s, 1H, CHarom); 6.84 (broad
Tetrahedron Lett. 1997, 38, 5503–5506. (b) Dagoneau, C.;
1
s, H, CHarom); 7.01–7.14 (m, 4H, CHarom); 7.19–7.23 (m,
´
Denis, J.-N.; Vallee, Y. Synlett 1999, 602–604.
5H, CHarom); 7.32 (d, Jˆ7.9 Hz, 1H, CHarom); 7.56 (d,
´
4. Denis, J.-N.; Mauger, H.; Vallee, Y. Tetrahedron Lett. 1997, 38,
1
1
Jˆ7.9 Hz, H, CHarom); 7.72 (s, H, CHarom); 7.80 (broad
8515–8518.
s, H, NH); 7.84 (broad s, H, NH). 13C NMR (CDCl3,
62.5 MHz): 34.6 (CH); 72.8 (CH2); 73.1 (CH2); 109.6
(CH); 112.2 (C); 112.5 (CH); 119.0 (CH); 119.4 (CH);
119.7 (C); 121.2 (CH); 121.5 (CH); 122.1 (CH); 122.9
(CH); 124.3 (CH); 127.0 (C); 127.5 (CH); 127.7 (CH);
128.2 (CH); 128.7 (C); 131.5 (C); 136.4 (C); 138.2 (C).
MS (CI, NH3ϩisobutane): m/z 443 and 445 (Mϩ). Anal.
calcd for C25H21BrN2O: C: 67.42%, H: 4.72%, N: 6.29%;
found: C: 67.23%, H: 4.71%, N: 6.23%.
1
1
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2-Benzyloxy-1-(30-indolyl)-1-(500-methoxy-300-indolyl)-
1
ethane (9dab). Yield: 76%. Amorphous solid. H NMR
(CDCl3, 250 MHz): 3.69 (s, 3H, OCH3); 4.09 (d, Jˆ
7.1 Hz, 2H, CH2); 4.56 (s, 2H, CH2Ph); 4.82 (t, Jˆ6.3 Hz,
1H, CH); 6.79 (dd, Jˆ2.4, 6.7 Hz, 1H, CHarom); 6.81 (broad
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1
Jˆ2.4 Hz, H, CHarom); 7.02 (d, Jˆ7.9 Hz, H, CHarom);
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1
1
7.52 (d, Jˆ7.9 Hz, H, CHarom); 7.77 (broad s, H, NH);
1
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