Leaving group and regioselectivity switches in the aminoalkylation reaction of indoles and related heterocycles with α-amido sulfones

Article abstract of DOI:10.1002/ejoc.201300369

The regioselective aminoalkylation of indoles and related heterocycles with α-amido sulfones under basic conditions has been studied. The reaction that employed the MeMgBr/MgBr₂ system provided high yields of 3-(1-carbamoylalkyl)indoles. On the other hand, the reaction that used Cs ₂CO₃ afforded 1-(1-carbamoylalkyl)indoles exclusively in high yields. The first reaction constitutes a switch of the leaving group of the α-amido sulfone in comparison to previously reported reactions between indoles and α-amido sulfones, which provided 3-(1-arylsulfonylalkyl) indoles. The second reaction constitutes a switch in the regioselectivity. The extensions of these C- and N-aminoalkylations starting from pyrroles and 7-azaindole have also been studied. Structurally diverse aminoalkylated indoles, pyrroles, and 7-azaindoles were obtained with excellent yield in most of the cases. The regioselective aminoalkylation of indoles and heterocycles with α-amido sulfones under basic conditions is described. The reaction with MeMgBr/MgBr₂ gives 3-(1-carbamoylalkyl)indoles, whereas employing Cs₂CO₃ yields 1-(1-carbamoylalkyl)indoles. The first case presents a switch of the leaving group of the α-amido sulfone, whereas the second demonstrates a switch in the regioselectivity. Copyright

Full text of DOI:10.1002/ejoc.201300369

FULL PAPER
DOI: 10.1002/ejoc.201300369
Leaving Group and Regioselectivity Switches in the Aminoalkylation Reaction
of Indoles and Related Heterocycles with α-Amido Sulfones
Gonzalo Blay,[a] Rosa M. Girón,[a] Marc Montesinos-Magraner,[a] and José R. Pedro*[a]
Keywords: Synthetic methods / Nitrogen heterocycles / Regioselectivity / Sulfur / Alkylation
The regioselective aminoalkylation of indoles and related
heterocycles with α-amido sulfones under basic conditions
has been studied. The reaction that employed the MeMgBr/
MgBr2 system provided high yields of 3-(1-carbamoylalkyl)-
indoles. On the other hand, the reaction that used Cs2CO3
afforded 1-(1-carbamoylalkyl)indoles exclusively in high
yields. The first reaction constitutes a switch of the leaving
group of the α-amido sulfone in comparison to previously re-
ported reactions between indoles and α-amido sulfones,
which provided 3-(1-arylsulfonylalkyl)indoles. The second
reaction constitutes a switch in the regioselectivity. The ex-
tensions of these C- and N-aminoalkylations starting from
pyrroles and 7-azaindole have also been studied. Structurally
diverse aminoalkylated indoles, pyrroles, and 7-azaindoles
were obtained with excellent yield in most of the cases.
Introduction
The indole framework represents a key structural motif
in a large number of biologically active natural products
and pharmaceutical compounds.[1] Therefore, intense efforts
have been devoted to the modification of the indole struc-
ture, particularly to the introduction of functionalized alkyl
frameworks at the C-3 position of the indole system, includ-
ing the development of enantioselective variants.[2] The ma-
jority of available methods to attain this goal use a Friedel–
Crafts (F-C) reaction, which exploits the electron-rich na-
ture of the indole nucleus and uses epoxides,[3] α,β-unsatu-
rated carbonyl compounds,[4] and nitroalkenes[5] as electro-
philic reagents. However, the use of imines and their deriva-
tives to form 3-indolylalkylamines is challenging because of
the poor electrophilicity of the azomethine carbon atom
and the trend towards the formation of double addition
products through the elimination of the amine moiety (see
Scheme 1).[6]
Scheme 1. Proposed mechanism for the addition of indoles to α-
amido sulfones under acidic conditions (previous work).
Some general methods to synthesize 3-indolylalkyl-
amines involve the enhancement of the electrophilic charac-
ter of the carbon–nitrogen double bond by binding elec-
tron-withdrawing groups to the nitrogen atom to lead to
N-protected 3-indolylalkylamines. Thus, N-sulfinyl and N-
sulfonyl imines have been widely used as electrophiles in F-
C reactions with indoles to afford N-sulfinyl and N-sulfonyl
3-indolylalkylamines, respectively.[7] Additionally, N-acyl-
imines and N-acyliminium cations have also been used as
electrophiles.[8] These species are very reactive, but also
highly unstable and generally need to be generated in situ
from appropriate precursors, such as α-amido sulfones. α-
Amido sulfones can be conveniently prepared from alde-
hydes, sodium arenesulfinates, and carbamates, and most of
them are stable solids that can be stored for a prolonged
time.[9] α-Amido sulfones 2 react either with acid reagents
to give N-acyliminium ions or with base to afford the corre-
sponding N-acylimines. The acidic approach has been used
by several authors who have described the F-C reaction of
aromatic compounds with α-amido sulfones to give the cor-
responding adducts.[10] However, when these reaction con-
ditions were applied to indole (1a) as the nucleophilic com-
[a] Departament de Química Orgànica, Facultat de Química
Universitat de València,
C/Dr. Moliner 50, 46100 Burjassot, València, Spain
Fax: +34-963544328
E-mail: jose.r.pedro@uv.es
Homepage: www.uv.es
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201300369.
Eur. J. Org. Chem. 2013, 3885–3895
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G. Blay, R. M. Girón, M. Montesinos-Magraner, J. R. Pedro
FULL PAPER
ponent, the reaction did not give the expected 3-amino- (see Table 1, Entry 5). The amount of base could be reduced
alkylated indole 3 with the carbamoyl moiety. Instead, 3- to 2 equiv. with practically no detriment to the yield (see
substituted indole 5 that contained an arylsulfonyl group Table 1, Entry 6), but the use of other halogenated solvents
was obtained. The authors rationalized their results did not improve this result (see Table 1, Entries 8 and 9).
through the initial formation of the expected F-C alkylation
Table 1. Reaction between indole (1a) and α-amido sulfone 2a ac-
product 3, which was unstable under these reaction condi-
tions and rapidly eliminated the carbamoyl moiety to gener-
ate an alkylideneindolenium ion 4. This ion underwent ad-
dition with either ArSO2H or indole to afford product 5 or
the double addition product 6, respectively (see
Scheme 1).[11]
cording to Scheme 2. Optimization of the reaction conditions.[a]
Entry
Base
Solvent
T
t
Yield [%][b]
(equiv.)
[°C]
[h]
3aa 7aa 6aa
1
2
3
4
5
6
7
8
9
10
11
12[c]
13[d]
14[c]
15[c]
16[c]
17[c]
18[c]
CsF (3)
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CHCl3
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
48
72
96
72
3
43
70
60
70
–
–
12
–
–
–
–
14
3
–
2
–
–
–
–
–
15
–
–
–
–
–
–
–
–
Li2CO3 (3)
Na2CO3 (3)
K2CO3 (3)
Cs2CO3 (3)
Cs2CO3 (2)
Cs2CO3 (1)
Cs2CO3 (3)
Cs2CO3 (3)
Et2Zn (2)
We envisaged that these drawbacks could be avoided if
the reaction was carried out in a basic medium (see
Scheme 2). Under these conditions, deprotonation of the
carbamate and elimination of the sulfinate group of α-
amido sulfone 2 gives an N-carbamoyl imine that undergoes
reaction with the indole to lead to the corresponding ad-
duct 3, which should be stable under the basic conditions,
preventing the elimination of the carbamate. This overall
process represents a switch of the leaving group with regard
to the acidic conditions in the previously published results.
Still, we assume that N-H indoles are ambidentate nucleo-
philes under basic conditions and, therefore, the introduc-
tion of an aminoalkyl moiety at the nitrogen atom is also
possible to give the corresponding N-aminoalkylated prod-
uct 7, which involves a switch in the regioselectivity of the
reaction. This switch should closely depend upon the reac-
tion conditions.[12]
–
88
87
–
87
75
–
–
–
–
–
3
27
20
22
48
1.5
1.5
4
1.5
0.75
5
(ClCH2)2 r.t.
–
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
0
0
0
0
0
0
0
r.t.
r.t.
49
74
91
83
35
80
85
42
30
MeMgBr (1)
MeMgBr (1)
MeMgBr (1)
MeMgBr (0.5) CH2Cl2
MeMgBr (1)
MeMgBr (1)
MeMgBr (1)
MeMgBr (1)
CHCl3
(ClCH2)2
THF
–
–
–
–
20
4
Et2O
[a] Reagents and conditions: 1a (0.125 mmol) and 2a (0.125 mmol)
in solvent (1.5 mL). [b] Yield of isolated product. [c] MgBr2
(20 mol-%) was used as additive. [d] MgBr2 (10 mol-%) was used
as additive.
Inspired by our previous work with α-amido sulfones,[14]
we employed a stronger base such as diethylzinc, which led
to a decrease in the yield of 3aa and to the formation of
double addition product 6aa (see Table 1, Entry 10). On the
other hand, the use MeMgBr as a base accelerated the reac-
tion to give product 3aa in good yield and with high selec-
tivity (see Table 1, Entry 11). Next, we carried out the reac-
tion using MeMgBr in the presence of 20 mol-% of MgBr2,
as this salt had been used as a Lewis acid together with
MeMgBr to increase the reactivity of an electrophile.[15] To
our delight, product 3aa was obtained in excellent yield
(91%) and with total selectivity with regard to both attack
position and leaving group (see Table 1, Entry 12). A de-
crease of either the salt loading or the amount of base re-
sulted in a lower yield (see Table 1, Entries 13 and 14). The
use of different chlorinated or ether solvents did not show
Scheme 2. Addition of indole to α-amido sulfones under basic con-
ditions and the regioselectivity of the aminoalkylation reaction
(this work).
Results and Discussion
Initially, we investigated the use of different bases in the an improvement over the results that were obtained with
reaction of indole (1a) and α-amido sulfone 2a (R = Ph, RЈ CH2Cl2 (see Table 1, Entries 15–18). In summary, the opti-
= Bn, Ar = 4-MeC6H4). We first investigated the suitability mized reaction conditions were established, that is, the C-
of using CsF in dichloromethane for the deprotonation of 3-aminoalkylated products 3 were obtained by using the
the α-amido sulfone, as Sato had described for a stan- MeMgBr/MgBr2 system in CH2Cl2 at 0 °C (see Table 1, En-
nylation reaction.[13] However, low yields (43%) of the C-3- try 12), and the N-1-aminoalkylated products 7 were pro-
aminoalkylated product 3aa together with 14% of the di- duced by using Cs2CO3 in CH2Cl2 at room temperature (see
indolyl deriative 6aa were obtained by using this system. Table 1, Entry 6). Remarkably, in both cases we can use
Lithium, sodium, and potassium carbonates provided prod- equimolar amounts of the reactants.
uct 3aa with high selectivity, but there was incomplete con-
Once the optimized conditions for the regioselective ami-
version (see Table 1, Entries 2–4). Cesium carbonate was noalkylations were established, several indoles 1 were
also investigated, but this base did not afford compound treated with different α-amido sulfones 2 by using both
3aa. Instead, N-aminoalkylated product 7aa was obtained methods (see Tables 2 and 3). First, the scope of reaction at
in high yield with a complete switch in the regioselectivity C-3 was studied. The reactions between indole (1a) and α-
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Aminoalkylation of Indoles and Heterocycles with α-Amido Sulfones
amido sulfones 2a–2f, which contained either electron-do- Table 3. Regioselective N-1-aminoalkylation of indoles with α-
amido sulfones. Scope of the reaction.[a]
nating or -withdrawing groups at different positions of the
phenyl group, as well as α-amido sulfones 2g and 2h, with
heteroaromatic groups, afforded products 3 with excellent
selectivity and high yields (see Table 2, Entries 1–8).
Table 2. Regioselective C-3-aminoalkylation of indoles with α-
amido sulfones. Scope of the reaction.[a]
Entry
1
R
2
RЈ
t
[h]
7
Yield
[%][b]
1
2
3
4
5
6
7
8
9
10
11
12
13
14[c]
15[c]
16
17
18
19
20
21
22
23
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
2a
2b
Ph
4-MeC6H4
3
3.5
7aa
7ab
7ac
7ad
7ae
7af
7ag
7ah
7ai
87
89
91
84
96
86
90
86
89
92
93
88
99
87
88
72
2c 4-MeOC6H4 12
2d
2e
2f
2g
2h
2i
2j
2k
2l
4-ClC6H4
3-MeC6H4
2-ClC6H4
3-furanyl
2-thienyl
nBu
isobutyl
neopentyl
cyclohexyl
iPr
3
12
6
1
48
3
3
3
3
6
4
8
5
5
5
5
5
Entry
1
R
2
RЈ
t
[h]
3
Yield
[%][b]
1
2
3
4
5
1a
1a
1a
1a
1a
1a
1a
1a
1a
H
H
H
H
H
H
H
H
H
H
H
H
H
2a
2b
2c
2d
2e
2f
2g
2h
2i
Ph
4-MeC6H4
4-MeOC6H4
4-ClC6H4
3-MeC6H4
2-ClC6H4
3-furanyl
2-thienyl
nBu
isobutyl
neopentyl
cyclohexyl
iPr
3
3.5
1
3
3
3
1
2
1
3aa
3ab
3ac
3ad
3ae
3af
3ag
3ah
3ai
3aj
3ak
3al
3am
3an
3ao
3ba
3ca
3da
91
72
99
81
99
99
95
90
75
74
86
88
85
91
79
98
n.r.
39
7aj
7ak
7al
2m
2n
2o
7am
7an
7ao
7da
6
7
Ph
4-MeC6H4
Ph
8
1d 2-COOCH3 2a
1e
1f
1g
1h
1i
9[c]
2-CH3
3-CH3
4-CH3
5-CH3O
5-Cl
2a
2a
2a
2a
2a
2a
2a
Ph
Ph
Ph
Ph
Ph
Ph
Ph
7ea n.d.[d]
10[c] 1a
11[c] 1a
12[c] 1a
13[c] 1a
14[d] 1a
15[d] 1a
2j
2k
2l
1
7fa
7ga
7ha
7ia
7ja
7ka
80
92
86
91
94
51
0.5
1.5
2
3.5
1.5
1.5
24
24
4
1
3
3
3
2m
2n
2o
2a
2a
2a
2a
2a
2a
2a
2a
2a
3.5
21
3
H
H
Ph
4-MeC6H4
Ph
1j
1k
6-F
7-CH3
16
17
18
19
20
21
22
23
24
1b
1c
1-CH3
1-CH3OC
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
[a] Reagents and conditions: 1 (0.125 mmol), 2 (0.125 mmol) and
Cs2CO3 (2 equiv.) in CH2Cl2 (1.5 mL) at room temp., PG = Cbz
unless otherwise stated. [b] Isolated product. [c] PG = Boc. [d] A
complex mixture was obtained (n.d. = not detected).
1d 2-COOCH3
1e
1g
1h
1i
1j
1k
2-CH3
4-CH3
5-CH3O
5-Cl
6-F
7-CH3
3ea n.d.[e]
3ga
3ha
3ia
3ja
3ka
91
93
97
92
97
the benzyloxycarbonyl (Cbz) protecting group (see Table 2,
Entries 14 and 15).
3
The scope of the reaction was further studied by em-
ploying differently substituted indoles and α-amido sulfone
2a. Indoles that were substituted on the heterocyclic ring
gave variable results (see Table 2, Entries 16–19). 1-Acet-
ylindole (1c) did not react, and the starting material was
recovered unchanged (see Table 2, Entry 17). The presence
of a substituent at the C-2 position of the indole affected
[a] Reagents and conditions: 1 (0.125 mmol), 2 (0.125 mmol),
MeMgBr (1 equiv.), and MgBr2 (20 mol-%) in CH2Cl2 (1.5 mL) at
0 °C, PG = Cbz unless otherwise stated. [b] Isolated product. [c] 1a
(0.375 mmol), 2 (0.125 mmol), MeMgBr (1 equiv.), and MgBr2
(20 mol-%) in CHCl3 (1.5 mL) at room temp. [d] PG = Boc, n.r.
= no reaction. [e] A complex mixture was obtained (n.d. = not
detected).
The introduction of an alkyl moiety at the C-3 position the reactivity, but not the regioselectivity. Thus, 2-(meth-
was problematic because of the lower reactivity of the ali- oxycarbonyl)indole (1d) slowly underwent a reaction to give
phatic α-amido sulfone. It was possible, however, to find a the C-3-aminoalkylation product 3da in 39% yield after
compromise between the low reactivity of the α-amido sulf- 24 h (see Table 2, Entry 18), whereas 2-methylindole (1e)
one and the formation of the double addition product 6 by was very reactive and gave a complex reaction mixture (see
performing the reaction in CHCl3 at room temperature with Table 2, Entry 19). On the other hand, the presence of sub-
3 equiv. of indole (1a). By using these modified conditions, stituents on the homocyclic ring did not affect the yield or
the reaction also tolerated α-amido sulfones with alkyl the reactivity. Regardless of their nature or position, the
groups that were substituted at the α position by a hydrogen expected C-3-aminoalkylation products were obtained in
atom. Independently, these were primary, secondary, cyclic, excellent yields (see Table 2, Entries 20–24).
or highly branched alkyl substituents on the α-amido sulf-
Moreover, we studied the scope of the N-aminoalkyl-
one (see Table 2, Entries 9–13) to afford the C-3-amino- ation reaction. Indole (1a) was treated under the optimized
alkylated products 3 in good yields. This method was also conditions with several α-amido sulfones 2 that contained
applied to N-Boc-protected α-amido sulfones (Boc = tert- different phenyl-substituted moieties (see Table 3, En-
butoxycarbonyl) with results similar to those obtained with tries 1–6) or heteroaromatic groups (see Table 3, Entries 7
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G. Blay, R. M. Girón, M. Montesinos-Magraner, J. R. Pedro
FULL PAPER
and 8) to give compounds 7 in very high yields and with
total regioselectivity. The reaction also tolerated α-amido
sulfones with alkyl moieties (see Table 3, Entries 9–13) to
afford again excellent results in terms of yield and selectiv-
ity.
In addition, it was possible to perform the reaction with
N-Boc-protected α-amido sulfones (see Table 3, Entries 14
and 15). Furthermore, α-amido sulfone 2a was treated with
several substituted indoles 1. The reaction afforded good
results when the substituent was located away from the re-
action center, and this occurred regardless of the nature or
position of the substitutent (see Table 3, Entries 18–22).
When the substituent was located close to the reaction cen-
ter, results were not as good (see Table 3, Entries 16, 17,
and 23). Again, the presence of substituents at the C-2 posi-
tion did not exert any effect on the regioselectivity. 2-(Meth-
oxycarbonyl)indole (1d) gave compound 7da in good yield
(72%, see Table 3, Entry 16), whereas 2-methylindole (1e)
produced a complex mixture (see Table 3, Entry 17), as in
the reaction with MeMgBr (Table 2, Entry 19).
Finally, an extension of these regioselective C- and N-
aminoalkylations by starting from pyrroles and 7-azaindole
was investigated. After optimizing the experimental condi-
tions (see Supporting Information), we found that pyrroles
underwent reaction at the C-2 position to afford the corre-
sponding aminoalkylated products 8 in good yields, even
when aliphatic α-amido sulfones were used. Moreover, the
less reactive 7-azaindole gave the desired product in a mod-
est yield, which is in agreement with previously reported
examples involving the Pictet–Spengler reaction.[16] On the
other hand, pyrrole showed a lower reactivity under the re-
action conditions for the N-substitution, but 7-azaindole af-
forded the desired products in good yields (see Figure 1).
Scheme 3. Deprotection of the product 3aa and acetylation of
amine 12aa. Reagents and conditions: (i) Na (20 equiv.), NH3/tetra-
hydrofuran (THF), –78 °C, 30 min, 100%; (ii) AcCl (3 equiv.),
NaOH (2.2 equiv.), CH2Cl2, room temp., 1 h, 70%.
Conclusions
We have developed two methods for the regioselective
aminoalkylation of indoles and related heterocycles with α-
amido sulfones. Both methods allowed the preparation C-
and N-aminoalkylated indoles, pyrroles, and 7-azaindole
with high selectivity, in excellent yields in most of the cases,
and with a wide structural diversity by using α-amido sulf-
ones that contained aromatic, heteroaromatic, and even ali-
phatic groups. The C-3 aminoalkylation (F-C) of indoles
involved an unprecedented switch of the leaving group of
the α-amido sulfone in comparison to previously reported
F-C reactions of indoles and α-amido sulfones, but the N-
1-aminoalkylation constituted a switch in the regioselectiv-
ity of the reaction.
Experimental Section
General Methods: Reactions were carried out under nitrogen in
round-bottomed flasks that were oven-dried at 120 °C overnight.
Commercial reagents were used as purchased. α-Amido sulfones
were synthesized as described in the literature.[9] Dichloromethane
was freshly distilled from CaH2. Chloroform was filtered through
basic alumina, distilled from P2O5, and stored over molecular sieves
(4 Å). Reactions were monitored by TLC analysis using Merck sil-
ica gel 60 F-254 thin layer plates. Flash column chromatography
was performed on Merck silica gel 60, 0.040–0.063 mm. Melting
points were determined with capillary tubes. The NMR spectro-
scopic data were recorded at 300 MHz for 1H NMR and at
75 MHz for 13C NMR by using the residual nondeuterated solvent
1
as the internal standard (CDCl3: δ = 7.26 ppm for H NMR and δ
= 77.0 ppm for 13C NMR; [D6]DMSO: δ = 2.50 ppm for 1H NMR
and δ = 39.52 ppm for 13C NMR; [D6]acetone: δ = 2.05 ppm for
1H NMR and δ = 29.84 ppm for 13C NMR). Chemical shifts are
given in ppm. The 13C assignments were determined by using
DEPT experiments. High resolution mass spectra (ESI) were re-
corded with a Q-TOF spectrometer equipped with an electrospray
source and a capillary voltage of 3.3 kV.
Figure 1. C- and N-aminoalkylations of pyrroles and 7-azaindole
with α-amido sulfones.
Compounds 3 and 7 are gramine and N-isogramine de-
rivatives, respectively, which are particularly interesting on
account of their biological activities and their use as start-
ing materials in further transformations. The cleavage of the
Cbz group in compound 3aa was carried out under re-
ductive conditions to afford 12aa in quantitative yield fol-
lowed by the transformation into monoacetyl derivative
13aa for comparative purposes (see Scheme 3).[17] However,
the deprotection of the N-aminoalkylated products 7 was
not possible by either reducing or acid methods, possibly
because of the instability of the aminal that would be
formed.
Procedures for the Synthesis of C-3-Aminoalkylated Indoles
(a) With Aromatic α-Amido Sulfones: Table 2. MeMgBr (1 m solu-
tion in THF, 125 μL, 0.125 mmol) was added to a cooled (ice bath)
solution of indole 1 (0.125 mmol) and MgBr2 (4.6 mg, 0.025 mmol)
in CH2Cl2 (0.5 mL). The mixture was stirred at 0 °C for 2 h. Then,
a suspension of α-amido sulfone (0.125 mmol) in CH2Cl2 (1 mL)
was added, and the mixture was stirred at 0 °C until the reaction
reached completion (TLC). Then, it was quenched with a saturated
aqueous solution of NH4Cl (1 mL), and the resulting mixture was
extracted with CH2Cl2 (3ϫ25 mL). The combined organic layers
were washed with brine (50 mL) and dried with anhydrous Na2SO4.
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Aminoalkylation of Indoles and Heterocycles with α-Amido Sulfones
Purification by flash chromatography on silica gel (hexane/EtOAc)
afforded compounds 3.
Benzyl [(1H-Indol-3-yl)(m-tolyl)methyl]carbamate (3ae): 45.8 mg,
99% yield; m.p. 117–118 °C. 1H NMR (300 MHz, CDCl3): δ = 8.15
(s, 1 H), 7.51 (d, JH,H = 8.0 Hz, 1 H), 7.44–7.15 (m, 10 H), 7.15–
7.05 (m, 2 H), 6.73 (s, 1 H), 6.26 (d, JH,H = 7.5 Hz, 1 H), 5.49 (d,
JH,H = 7.5 Hz, 1 H), 5.19 (d, JH,H = 12.5 Hz, 1 H), 5.14 (d, JH,H
= 12.5 Hz, 1 H), 2.35 (s, 3 H) ppm. 13C NMR (75.5 MHz, CDCl3).
δ = 155.7 (C), 141.5 (C), 138.0 (C), 136.6 (C), 136.5 (C), 128.4
(CH), 128.3 (CH), 128.0 (CH), 127.57 (CH), 125.82 (C), 123.86
(CH), 123.29 (CH), 122.42 (CH), 119.8 (CH), 119.4 (CH), 117.4
(C), 111.3 (CH), 66.8 (CH2), 52.3 (CH), 21.5 (CH3) ppm. HRMS
(b) With Aliphatic α-Amido Sulfones: Table 2. MeMgBr (1 m solu-
tion in THF, 125 μL, 0.125 mmol) was added to a cooled (ice bath)
solution of indole 1 (0.375 mmol) and MgBr2 (4.6 mg, 0.025 mmol)
in CHCl3 (0.5 mL). The mixture was stirred at 0 °C for 2 h. Then,
a suspension of α-amido sulfone (0.125 mmol) in CHCl3 (1 mL)
was added, and the reaction mixture was stirred at room tempera-
ture until it reached completion (TLC). Then, it was quenched with
a saturated aqueous solution of NH4Cl (1 mL), and the resulting
solution was extracted with CH2Cl2 (3ϫ25 mL). The combined
organic layers were washed with brine (50 mL) and dried with an-
hydrous Na2SO4. Purification by flash chromatography on silica
gel (hexane/EtOAc) afforded compounds 3.
(ESI): calcd. for C24H22KN2O2 [M
409.1329.
+
K]+ 409.1318; found
Benzyl [(2-Chlorophenyl)(1H-indol-3-yl)methyl]carbamate (3af):
1
48.2 mg, 99% yield; m.p. 57–60 °C. H NMR (300 MHz, CDCl3):
δ = 8.11 (s, 1 H), 7.51–7.44 (m, 1 H), 7.37 (dd, JH,H = 7.5, 2.0 Hz,
1 H), 7.31–7.05 (m, 10 H), 7.00 (ddd, JH,H = 8.0, 7.0, 1.0 Hz, 1 H),
Benzyl [(1H-Indol-3-yl)(phenyl)methyl]carbamate (3aa): 40.5 mg,
91% yield; m.p. 132–133 °C. 1H NMR (300 MHz, CDCl3): δ = 8.05
(s, 1 H), 7.48 (d, JH,H = 8.0 Hz, 1 H), 7.44–7.27 (m, 11 H), 7.21
(ddd, JH,H = 8.0, 7.0, 1.0 Hz, 1 H), 7.08 (ddd, JH,H = 8.0, 7.0,
1.0 Hz, 1 H), 6.76 (s, 1 H), 6.28 (d, JH,H = 7.5 Hz, 1 H), 5.45 (d,
JH,H = 6.5 Hz, 1 H), 5.17 (d, JH,H = 12.5 Hz, 1 H), 5.12 (d, JH,H
= 12.5 Hz, 1 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 155.7
(C), 141.5 (C), 136.6 (C), 136.3 (C), 128.41 (CH), 128.36 (CH),
128.0 (CH), 127.9 (CH), 127.2 (CH), 126.8 (CH), 125.7 (C), 123.4
(CH), 122.3 (CH), 119.7 (CH), 119.2 (CH), 116.9 (C), 111.4 (CH),
66.8 (CH2), 52.3 (CH) ppm. HRMS (ESI): calcd. for
C23H20N2NaO2 [M + Na]+ 379.1422; found 379.1410.
6.53–6.43 (m, 2 H), 5.45 (d, JH,H = 6.0 Hz, 1 H), 5.07 (d, JH,H
=
12.5 Hz, 1 H), 5.01 (d, JH,H = 12.5 Hz, 1 H) ppm. 13C NMR
(75.5 MHz, CDCl3): δ = 155.5 (C), 139.1 (C), 136.6 (C), 136.4 (C),
133.2 (C), 129.9 (CH), 128.5 (CH), 128.4 (CH), 128.0 (CH), 127.8
(CH), 126.9 (CH), 125.8 (C), 123.4 (CH), 122.5 (CH), 119.9 (CH),
119.1 (CH), 115.5 (C), 111.4 (CH), 66.8 (CH2), 50.0 (CH) ppm.
HRMS (ESI): calcd. for C23H19ClNaN2O2 [M + Na]+ 413.1033;
found 413.1037.
Benzyl [(Fur-3-yl)(1H-indol-3-yl)methyl]carbamate (3ag): 41.0 mg,
95% yield; m.p. 100–102 °C. 1H NMR (300 MHz, CDCl3): δ = 8.20
(s, 1 H), 7.55 (d, JH,H = 8.0 Hz, 1 H), 7.42–7.29 (m, 8 H), 7.25–
7.18 (m, 1 H), 7.14–7.05 (m, 1 H), 6.98 (s, 1 H), 6.37 (s, 1 H), 6.24
(d, JH,H = 8.5 Hz, 1 H), 5.39 (d, JH,H = 6.5 Hz, 1 H), 5.16 (s, 2 H)
ppm. 13C NMR (75.5 MHz, CDCl3). δ = 155.7 (C), 143.3 (CH),
139.9 (CH), 136.6 (C), 136.4 (C), 128.5 (CH), 128.1 (CH), 128.0
(CH), 126.7 (C), 125.6 (C), 122.8 (CH), 122.5 (CH), 119.8 (CH),
119.4 (CH), 116.3 (C), 111.4 (CH), 109.9 (CH), 66.9 (CH2), 45.0
(CH) ppm. HRMS (ESI): calcd. for C21H18NaN2O3 [M + Na]+
369.1220; found 369.1215.
Benzyl [(1H-Indol-3-yl)(p-tolyl)methyl]carbamate (3ab): 33.3 mg,
72% yield; m.p. 144–145 °C. 1H NMR (300 MHz, CDCl3): δ = 8.17
(s, 1 H), 7.53–7.45 (m, 1 H), 7.42–7.13 (m, 11 H), 7.08 (ddd, JH,H
= 8.0, 7.0, 1.0 Hz, 1 H), 6.73 (s, 1 H), 6.25 (d, JH,H = 8.0 Hz, 1 H),
5.49 (d, JH,H = 7.5 Hz, 1 H), 5.18 (d, JH,H = 12.5 Hz, 1 H), 5.13
(d, JH,H = 12.5 Hz, 1 H), 2.37 (s, 3 H) ppm. 13C NMR (75.5 MHz,
CDCl3): δ = 155.7 (C), 138.6 (C), 136.8 (C), 136.6 (C), 136.4 (C),
129.1 (CH), 128.5 (CH), 128.4 (CH), 128.0 (CH), 126.8 (CH), 125.7
(C), 123.2 (CH), 122.4 (CH), 119.8 (CH), 119.4 (CH), 117.4 (C),
111.3 (CH), 66.8 (CH2), 52.1 (CH), 21.1 (CH3) ppm. HRMS (ESI):
calcd. for C24H22N2NaO2 [M + Na]+ 393.1579; found 393.1586.
Benzyl [(1H-Indol-3-yl)(thien-2-yl)methyl]carbamate (3ah): 40.7 mg,
90% yield; m.p. 125–126 °C. 1H NMR (300 MHz, CDCl3): δ = 8.25
(s, 1 H), 7.50 (d, JH,H = 8.0 Hz, 1 H), 7.36 (dd, JH,H = 4.54, 3.0 Hz,
6 H), 7.28–7.17 (m, 2 H), 7.09 (dd, JH,H = 11.0, 4.0 Hz, 1 H), 7.04–
6.92 (m, 3 H), 6.55 (d, JH,H = 8.0 Hz, 1 H), 5.60 (d, JH,H = 6.5 Hz,
1 H), 5.18 (s, 2 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 155.5
(C), 146.0 (C), 136.6 (C), 136.3 (C), 128.5 (CH), 128.1 (CH), 128.0
(CH), 126.7 (CH), 125.4 (C), 125.0 (CH), 124.5 (CH), 123.0 (CH),
122.5 (CH), 119.9 (CH), 119.3 (CH), 116.7 (C), 111.4 (CH), 67.0
(CH2), 48.6 (CH) ppm. HRMS (ESI): calcd. for C21H18NaN2O2S
[M + Na]+ 385.0987; found 385.09907.
Benzyl [(1H-Indol-3-yl)(4-methoxyphenyl)methyl]carbamate (3ac):
47.8 mg, 99% yield; m.p. 147–148 °C. 1H NMR (300 MHz,
CDCl3): δ = 8.04 (s, 1 H), 7.45 (d, JH,H = 7.5 Hz, 1 H), 7.40–7.26
(m, 8 H), 7.24–7.14 (m, 1 H), 7.07 (ddd, JH,H = 8.0, 7.0, 1.0 Hz, 1
H), 6.94–6.83 (m, 2 H), 6.80 (s, 1 H), 6.22 (d, JH,H = 8.0 Hz, 1 H),
5.41 (d, JH,H = 5.0 Hz, 1 H), 5.17 (d, JH,H = 12.5 Hz, 1 H), 5.11
(d, JH,H = 12.5 Hz, 1 H), 3.81 (s, 3 H) ppm. 13C NMR (75.5 MHz,
CDCl3): δ = 158.8 (C), 155.7 (C), 136.7 (C), 136.5 (C), 133.4 (C),
128.5 (CH), 128.0 (CH), 128.0 (CH), 125.8 (C), 123.1 (CH), 122.5
(CH), 119.8 (CH), 119.5 (CH), 117.7 (C), 113.8 (CH), 111.3 (CH),
66.8 (CH2), 55.3 (CH3), 51.8 (CH) ppm. HRMS (ESI): calcd. for
C24H22NaN2O2 [M + Na]+ 409.1528; found 409.1535.
Benzyl [1-(1H-Indol-3-yl)pentyl]carbamate (3ai): 31.5 mg, 75%
1
yield; m.p. 55–56 °C. H NMR (300 MHz, CDCl3): δ = 8.11 (s, 1
H), 7.67 (d, JH,H = 7.5 Hz, 1 H), 7.44–6.95 (m, 9 H), 5.23–4.89 (m,
4 H), 2.10–1.85 (m, 2 H), 1.48–1.19 (m, 4 H), 0.89 (t, JH,H = 7.0 Hz,
3 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 155.9 (C), 136.7 (C),
136.5 (C), 128.4 (CH), 128.0 (CH), 125.9 (C), 122.3 (CH), 121.4
(CH), 119.7 (CH), 119.3 (CH), 117.5 (C), 111.3 (CH), 66.6 (CH2),
48.6 (CH), 35.2 (CH2), 28.6 (CH2), 22.5 (CH2), 14.0 (CH3) ppm.
HRMS (ESI): calcd. for C21H24NaN2O2 [M + Na]+ 359.1743;
found 359.1735.
Benzyl [(4-Chlorophenyl)(1H-indol-3-yl)methyl]carbamate (3ad):
39.5 mg, 81% yield; m.p. 152–153 °C. 1H NMR (300 MHz,
CDCl3): δ = 8.18 (s, 1 H), 7.46 (d, JH,H = 8.0 Hz, 1 H), 7.44–7.28
(m, 10 H), 7.25–7.18 (m, 1 H), 7.14–7.05 (m, 1 H), 6.71 (s, 1 H),
6.23 (d, JH,H = 7.5 Hz, 1 H), 5.47 (d, JH,H = 6.5 Hz, 1 H), 5.18 (d,
JH,H = 12.5 Hz, 1 H), 5.12 ppm (d, JH,H = 12.5 Hz, 1 H) ppm. 13C
NMR (75.5 MHz, CDCl3): δ = 155.7 (C), 140.2 (C), 136.6 (C),
136.3 (C), 133.0 (C), 128.6 (CH), 128.5 (CH), 128.2 (CH), 128.1
Benzyl [1-(1H-Indol-3-yl)-3-methylbutyl]carbamate (3aj): 31.1 mg,
1
74% yield; m.p. 68–70 °C. H NMR (300 MHz, CDCl3): δ = 8.02
(CH), 128.1 (CH), 128.1 (CH), 125.6 (C), 123.3 (CH), 122.7 (CH), (s, 1 H), 7.58 (d, JH,H = 8.0 Hz, 1 H), 7.31–7.17 (m, 6 H), 7.11
120.1 (CH), 119.2 (CH), 116.9 (C), 111.4 (CH), 67.0 (CH2), 51.8 (ddd, JH,H = 8.0, 7.0, 1.0 Hz, 1 H), 7.06–6.92 (m, 2 H), 5.13–4.82
(CH) ppm. HRMS (ESI): calcd. for C23H19ClN2NaO2 [M + Na]+
413.1033; found 413.1016.
(m, 4 H), 1.86–1.49 (m, 3 H), 0.92–0.85 (m, 6 H) ppm. 13C NMR
(75.5 MHz, CDCl3): δ = 155.8 (C), 136.6 (C), 136.5 (C), 128.5
Eur. J. Org. Chem. 2013, 3885–3895
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3889

G. Blay, R. M. Girón, M. Montesinos-Magraner, J. R. Pedro
FULL PAPER
(CH), 128.0 (CH), 125.9 (C), 122.3 (CH), 121.4 (CH), 119.7 (CH), 13C NMR (75.5 MHz, CDCl3): δ = 155.6 (C), 141.7 (C), 137.4 (C),
119.4 (CH), 117.7 (C), 111.3 (CH), 66.6 (CH2), 46.6 (CH), 44.6 136.5 (C), 128.5 (CH), 128.4 (CH), 128.1 (CH), 128.0 (CH), 127.9
(CH2), 25.1 (CH), 22.6 (CH3), 22.6 (CH3) ppm. HRMS (ESI):
(CH), 127.2 (CH), 126.8 (CH), 126.2 (C), 122.0 (CH), 119.5 (CH),
119.4 (CH), 115.8 (C), 109.4 (CH), 66.7 (CH2), 52.2 (CH), 32.6
(CH3) ppm. HRMS (ESI): calcd. for C24H22N2NaO2 [M + Na]+
393.1579; found 393.1580.
calcd. for C21H24NaN2O2 [M + Na]+ 359.1743; found 359.1738.
Benzyl
[1-(1H-Indol-3-yl)-3,3-dimethylbutyl]carbamate
(3ak):
37.6 mg, 86% yield; m.p. 130–132 °C. 1H NMR (300 MHz,
CDCl3): δ = 8.01 (s, 1 H), 7.62 (d, JH,H = 7.0 Hz, 1 H), 7.34–6.87
(m, 9 H), 5.23–4.86 (m, 4 H), 1.96 (dd, JH,H = 14.0, 5.0 Hz, 1 H),
1.79 (dd, JH,H = 14.0, 8.0 Hz, 1 H), 0.92 (s, 9 H) ppm. 13C NMR
(75.5 MHz, CDCl3). δ = 155.4 (C), 136.7 (C), 136.6 (C), 129.0 (C),
128.4 (CH), 128.0 (CH), 125.6 (C), 122.3 (CH), 121.1 (CH), 119.6
(CH), 119.4 (CH), 111.3 (CH), 66.5 (CH2), 49.3 (CH2), 45.9 (CH),
30.7 (C), 29.9 (CH3) ppm. HRMS (ESI): calcd. for C22H26NaN2O2
[M + Na]+ 373.1892; found 373.1895.
Methyl 3-[{[(Benzyloxy)carbonyl]amino}(phenyl)methyl]-1H-indole-
2-carboxylate (3da): Oil (20.2 mg, 39% yield). 1H NMR (300 MHz,
CDCl3): δ = 9.02 (s, 1 H), 7.75 (d, JH,H = 8.0 Hz, 1 H), 7.46–7.08
(m, 11 H), 6.88 (s, 2 H), 5.18 (d, JH,H = 12.5 Hz, 1 H), 5.15–5.08
(m, 2 H), 4.72 (s, 1 H), 3.82 (s, 3 H) ppm. 13C NMR (75.5 MHz,
CDCl3): δ = 162.0 (C), 156.1 (C), 141.6 (C), 136.5 (C), 136.2 (C),
135.6 (C), 128.5 (CH), 128.4 (CH), 128.3 (CH), 128.1 (CH), 127.0
(CH), 126.3 (CH), 126.1 (CH), 124.2 (C), 122.8 (C), 121.1 (CH),
121.0 (CH), 112.0 (CH), 66.8 (CH2), 52.1 (CH), 50.2 (CH3) ppm.
HRMS (ESI): calcd. for C25H23N2O4 [M + H]+ 415.1658; found
415.1651.
Benzyl [Cyclohexyl(1H-indol-3-yl)methyl]carbamate (3al): 39.8 mg,
88% yield; m.p. 129–130 °C. 1H NMR (300 MHz, CDCl3): δ = 8.17
(s, 1 H), 7.64 (d, JH,H = 7.5 Hz, 1 H), 7.41–7.27 (m, 6 H), 7.25–
7.16 (m, 1 H), 7.16–7.07 (m, 1 H), 7.02 (s, 1 H), 5.21–4.98 (m, 3
H), 4.83 (t, JH,H = 8.5 Hz, 1 H), 2.03–1.54 (m, 7 H), 1.35–0.86 (m,
4 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 156.2 (C), 136.6 (C),
136.5 (C), 128.4 (CH), 128.1 (CH), 128.0 (CH), 125.9 (C), 122.1
(CH), 121.9 (CH), 119.6 (CH), 119.3 (CH), 116.4 (C), 111.4 (CH),
66.7 (CH2), 54.0 (CH), 42.5 (CH), 30.4 (CH2), 29.6 (CH2), 26.3
(CH2), 26.1 (CH2), 26.1 (CH2) ppm. HRMS (ESI): calcd. for
C23H27N2O2 [M + H]+ 363.2074; found 363.2073.
Benzyl [(4-Methyl-1H-indol-3-yl)(phenyl)methyl]carbamate (3ga):
42.1 mg, 91% yield; m.p. 145–146 °C. 1H NMR (300 MHz,
CDCl3): δ = 8.13 (s, 1 H), 7.55–7.22 (m, 10 H), 7.17 (d, JH,H
=
8.0 Hz, 1 H), 7.14–7.04 (m, 1 H), 6.93–6.80 (m, 1 H), 6.53 (s, 1 H),
6.45 (d, JH,H = 7.0 Hz, 1 H), 5.42 (d, JH,H = 6.5 Hz, 1 H), 5.19 (d,
JH,H = 12.5 Hz, 1 H), 5.09 (d, JH,H = 12.5 Hz, 1 H), 2.61 (s, 3 H)
ppm. 13C NMR (75.5 MHz, CDCl3): δ = 155.1 (C), 142.2 (C), 137.0
(C), 136.5 (C), 130.7 (C), 128.4 (CH), 128.3 (CH), 128.0 (CH),
127.2 (CH), 126.9 (CH), 124.8 (C), 124.4 (CH), 122.6 (CH), 121.7
(CH), 118.0 (C), 109.2 (CH), 66.7 (CH2), 52.9 (CH), 19.9 (CH3)
ppm. HRMS (ESI): calcd. for C24H23N2O2 [M + H]+ 371.1760;
found 371.1769.
Benzyl
[1-(1H-Indol-3-yl)-2-methylpropyl]carbamate
(3am):
1
34.2 mg, 85% yield; m.p. 79–81 °C. H NMR (300 MHz, CDCl3):
δ = 8.15 (s, 1 H), 7.64 (d, JH,H = 7.5 Hz, 1 H), 7.43–6.91 (m, 9 H),
5.19–5.02 (m, 3 H), 4.84 (t, JH,H = 9.0 Hz, 1 H), 2.39–2.21 (m, 1
H), 1.03 (d, JH,H = 6.5 Hz, 3 H), 0.94 (d, JH,H = 6.5 Hz, 3 H) ppm.
13C NMR (75.5 MHz, CDCl3): δ = 156.2 (C), 136.6 (C), 136.4 (C),
128.5 (CH), 128.1 (CH), 128.0 (CH), 125.9 (C), 122.2 (CH), 121.7
(CH), 119.6 (CH), 119.4 (CH), 116.7 (C), 111.3 (CH), 66.7 (CH2),
54.7 (CH), 32.8 (CH), 20.1 (CH3), 18.9 (CH3) ppm. HRMS (ESI):
calcd. for C20H22N2NaO2 [M + Na]+ 345.1579; found 345.1573.
Benzyl [(5-Methoxy-1H-indol-3-yl)(phenyl)methyl]carbamate (3ha):
44.9 mg, 93%; m.p. 121–123 °C. 1H NMR (300 MHz, CDCl3): δ =
8.06 (s, 1 H), 7.43–7.17 (m, 11 H), 6.94–6.77 (m, 2 H), 6.65 (s, 1
H), 6.24 (d, JH,H = 7.5 Hz, 1 H), 5.48 (d, JH,H = 7.0 Hz, 1 H), 5.19
(d, JH,H = 12.5 Hz, 1 H), 5.10 (d, JH,H = 12.5 Hz, 1 H), 3.72 (s, 3
H) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 155.7 (C), 154.1 (C),
141.5 (C), 136.5 (C), 131.7 (C), 128.4 (CH), 128.0 (CH), 127.3
(CH), 126.8 (CH), 126.2 (C), 124.0 (CH), 117.1 (C), 112.7 (CH),
112.1 (CH), 100.9 (CH), 66.8 (CH2), 55.7 (CH), 52.2 (CH3) ppm.
HRMS (ESI): calcd. for C24H22N2NaO3 [M + Na]+ 409.1530;
found 409.1520.
tert-Butyl [(1H-Indol-3-yl)(phenyl)methyl]carbamate (3an): 36.6 mg,
91% yield; m.p. 144–146 °C. 1H NMR (300 MHz, CDCl3): δ = 8.25
(s, 1 H), 7.53 (d, JH,H = 8.0 Hz, 1 H), 7.45–7.24 (m, 6 H), 7.24–
7.16 (m, 1 H), 7.10 (ddd, JH,H = 8.0, 7.0, 1.0 Hz, 1 H), 6.68 (s, 1
H), 6.22 (d, JH,H = 6.0 Hz, 1 H), 5.26 (d, JH,H = 4.0 Hz, 1 H), 1.48
(s, 9 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 155.3 (C), 142.0
(C), 136.7 (C), 128.3 (CH), 127.1 (CH), 126.8 (CH), 125.9 (C),
123.3 (CH), 122.3 (CH), 119.7 (CH), 119.3 (CH), 117.7 (C), 111.3
(CH), 79.6 (C), 51.7 (CH), 28.4 (CH3) ppm. HRMS (ESI): calcd.
for C20H22NaN2O2 [M + Na]+ 345.1579; found 345.1580.
Benzyl [(5-Chloro-1H-indol-3-yl)(phenyl)methyl]carbamate (3ia):
47.3 mg, 97% yield; m.p. 127–128 °C. 1H NMR (300 MHz,
CDCl3): δ = 8.32 (s, 1 H), 7.53–7.02 (m, 13 H), 6.70 (s, 1 H), 6.20
(d, JH,H = 8.0 Hz, 1 H), 5.48 (d, JH,H = 6.5 Hz, 1 H), 5.19 (d, JH,H
= 12.5 Hz, 1 H), 5.12 (d, JH,H = 12.5 Hz, 1 H) ppm. 13C NMR
(75.5 MHz, CDCl3): δ = 155.7 (C), 141.1 (C), 136.3 (C), 135.0 (C),
128.6 (CH), 128.5 (CH), 128.1 (CH), 128.0 (CH), 127.5 (CH), 126.8
(CH), 125.5 (C), 124.6 (CH), 122.8 (CH), 118.7 (CH), 116.9 (C),
112.4 (CH), 66.9 (CH2), 52.2 (CH) ppm. HRMS (ESI): calcd. for
C23H19ClN2NaO2 [M + Na]+ 413.1033; found 413.1035.
tert-Butyl [(1H-Indol-3-yl)(p-tolyl)methyl]carbamate (3ao): 33.2 mg,
79% yield; m.p. 137–139 °C. 1H NMR (300 MHz, CDCl3): δ = 8.23
(s, 1 H), 7.53 (d, JH,H = 8.0 Hz, 1 H), 7.39–7.04 (m, 7 H), 6.73 (d,
JH,H = 1.5 Hz, 1 H), 6.19 (d, JH,H = 7.5 Hz, 1 H), 5.24 (d, JH,H
=
7.5 Hz, 1 H), 2.36 (s, 3 H), 1.48 (s, 9 H) ppm. 13C NMR (75.5 MHz,
CDCl3): δ = 155.2 (C), 139.0 (C), 136.7 (C), 136.6 (C), 129.0 (CH),
126.7 (CH), 125.9 (C), 123.2 (CH), 122.3 (CH), 119.7 (CH), 119.4
(CH), 117.9 (C), 111.3 (CH), 79.5 (C), 51.4 (CH), 28.4 (CH3), 21.1
(CH3) ppm. HRMS (ESI): calcd. for C21H24N2NaO2 [M + Na]+
359.1735; found 359.1734.
Benzyl [(6-Fluoro-1H-indol-3-yl)(phenyl)methyl]carbamate (3ja):
43.0 mg, 92% yield; m.p. 131–133 °C. 1H NMR (300 MHz,
CDCl3): δ = 8.18 (s, 1 H), 7.46–7.21 (m, 11 H), 6.99 (dd, JH,H
=
9.5, 2.0 Hz, 1 H), 6.82 (dt, JH,H = 9.0, 2.0 Hz, 1 H), 6.69 (s, 1 H),
6.23 (d, JH,H = 8.0 Hz, 1 H), 5.47 (d, JH,H = 6.0 Hz, 1 H), 5.18 (d,
JH,H = 12.5 Hz, 1 H), 5.12 (d, JH,H = 12.5 Hz, 1 H) ppm. 13C NMR
(75.5 MHz, CDCl3): δ = 160.05 (d, JH,H = 238.5 Hz, C), 155.7 (C),
Benzyl [(1-Methyl-1H-indol-3-yl)(phenyl)methyl]carbamate (3ba):
45.3 mg, 98% yield; m.p. 142–143 °C. 1H NMR (300 MHz,
CDCl3): δ = 7.52 (d, JH,H = 8.0 Hz, 1 H), 7.47–7.23 (m, 12 H), 141.3 (C), 136.6 (d, JH,H = 12.5 Hz, C), 136.4 (C), 128.5 (CH),
7.11 (ddd, JH,H = 8.0, 6.5, 1.5 Hz, 1 H), 6.64 (s, 1 H), 6.31 (d, JH,H 128.1 (CH), 128.0 (CH), 127.4 (CH), 126.8 (CH), 123.6 (CH), 123.5
= 7.5 Hz, 1 H), 5.50 (d, JH,H = 7.0 Hz, 1 H), 5.20 (d, JH,H
12.0 Hz, 1 H), 5.14 (d, JH,H = 12.0 Hz, 1 H), 3.70 (s, 3 H) ppm.
=
(CH), 122.4 (C), 120.1 (d, JH,H = 10.0 Hz, CH), 117.4 (C), 108.6
(d, JH,H = 24.5 Hz, CH), 97.6 (d, JH,H = 26.0 Hz, CH), 66.9 (CH2),
3890
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© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 3885–3895

Aminoalkylation of Indoles and Heterocycles with α-Amido Sulfones
52.3 (CH) ppm. HRMS (ESI): calcd. for C23H20FN2O2 [M + H]+
375.1509; found 375.1510.
DMSO): δ = 9.12 (d, JH,H = 9.0 Hz, 1 H), 7.60–7.50 (m, 2 H),
7.45–6.96 (m, 13 H), 6.52 (d, JH,H = 3.0 Hz, 1 H), 5.13 (d, JH,H
=
12.5 Hz, 1 H), 5.06 (d, JH,H = 12.5 Hz, 1 H) ppm. 13C NMR
(75.5 MHz, [D6]DMSO): δ = 155.6 (C), 137.4 (C), 136.5 (C), 135.0
(C), 133.0 (C), 128.5 (CH), 128.4 (CH), 128.4 (CH), 128.0 (CH),
126.0 (CH), 125.1 (CH), 121.5 (CH), 120.6 (CH), 119.7 (CH), 110.6
(CH), 102.0 (CH), 66.1 (CH2), 64.3 (CH) ppm. HRMS (ESI):
calcd. for C23H19ClN2NaO2 [M + Na]+ 413.1033; found 413.1032.
Benzyl [(7-Methyl-1H-indol-3-yl)(phenyl)methyl]carbamate (3ka):
44.8 mg, 97% yield; m.p. 158–159 °C. 1H NMR (300 MHz,
CDCl3): δ = 8.12 (s, 1 H), 7.52–7.22 (m, 11 H), 7.08–6.95 (m, 2 H),
6.74 (s, 1 H), 6.29 (d, JH,H = 8.0 Hz, 1 H), 5.52 (d, JH,H = 7.0 Hz,
1 H), 5.19 (d, JH,H = 12.5 Hz, 1 H), 5.13 [d, JH,H = 12.5 Hz, 1 H),
2.46 (s, 3 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 155.7 (C),
141.6 (C), 136.4 (C), 136.2 (C), 128.4 (CH), 128.4 (CH), 128.0
(CH), 127.2 (CH), 126.8 (CH), 125.3 (C), 123.0 (CH), 122.9 (CH),
120.5 (C), 120.1 (CH), 117.7 (C), 117.0 (CH), 66.8 (CH2), 52.4
(CH), 16.5 (CH3) ppm. HRMS (ESI): calcd. for C24H23N2O2 [M
+ H]+ 371.1760; found 371.1762.
Benzyl [(1H-Indol-1-yl)(m-tolyl)methyl]carbamate (7ae): 44.4 mg,
96% yield; m.p. 123–124 °C. 1H NMR (300 MHz, CDCl3): δ =
7.75–7.59 (m, 1 H), 7.47–6.93 (m, 14 H), 6.57 (dd, JH,H = 3.5,
0.5 Hz, 1 H), 5.89 (d, JH,H = 8.0 Hz, 1 H), 5.18 (d, JH,H = 12.0 Hz,
1 H), 5.08 (d, JH,H = 12.0 Hz, 1 H), 2.34 (s, 3 H) ppm. 13C NMR
(75.5 MHz, CDCl3): δ = 155.3 (C), 138.7 (C), 137.3 (C), 135.7 (C),
135.5 (C), 129.5 (CH), 129.1 (C), 128.8 (CH), 128.5 (CH), 128.3
(CH), 128.2 (CH), 126.9 (CH), 125.8 (CH), 123.4 (CH), 122.0
(CH), 121.0 (CH), 120.1 (CH), 110.4 (CH), 102.7 (CH), 67.4 (CH2),
65.2 (CH), 21.4 (CH3) ppm. HRMS (ESI): calcd. for
C24H22N2NaO2 [M + Na]+ 393.1579; found 393.1577.
General Procedure for the Synthesis of N-1-Aminoalkylated Indoles:
Table 3. Cs2CO3 (84.4 mg, 0.25 mmol) was dried in a Schlenk tube
by using a heat gun under vacuum. α-Amido sulfone (0.125 mmol)
was added, and the system was purged with nitrogen. Then,
CH2Cl2 (0.7 mL) was added, and the mixture was stirred at room
temperature for 2 h. A solution of the indole 1 (0.125 mmol) in
CH2Cl2 (0.5 mL) was added. The mixture was stirred at room tem-
perature until it reached completion (TLC). Then, it was quenched
with water (1 mL), and the resulting solution was extracted with
CH2Cl2 (3ϫ25 mL). The combined organic layers were washed
with brine (50 mL) and dried with anhydrous Na2SO4. Purification
by flash chromatography on silica gel (hexane/EtOAc) afforded
compounds 7.
Benzyl [(2-Chlorophenyl)(1H-indol-1-yl)methyl]carbamate (7af):
41.9 mg, 86% yield; m.p. 108–110 °C. 1H NMR (300 MHz,
CDCl3): δ = 7.68–7.60 (m, 1 H), 7.54 (d, JH,H = 7.5 Hz, 1 H), 7.49–
7.40 (m, 2 H), 7.40–7.10 (m, 10 H), 7.01 (s, 1 H), 6.54 (d, JH,H
=
3.0 Hz, 1 H), 5.72 (s, 1 H), 5.18 (d, JH,H = 12.0 Hz, 1 H), 5.13 (d,
JH,H = 12.0 Hz, 1 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ =
154.9 (C), 135.7 (C), 135.5 (C), 135.2 (C), 133.6 (C), 130.4 (CH),
130.3 (CH), 129.1 (C), 128.5 (CH), 128.3 (CH), 128.1 (CH), 127.4
(CH), 127.2 (CH), 124.4 (CH), 122.2 (CH), 121.1 (CH), 120.3
(CH), 110.2 (CH), 102.8 (CH), 67.5 (CH2), 63.3 (CH) ppm. HRMS
(ESI): calcd. for C23H19ClKN2O2 [M + K]+ 429.0765; found
429.0775.
Benzyl [(1H-Indol-1-yl)(phenyl)methyl]carbamate (7aa): 38.7 mg,
87% yield; m.p. 118–120 °C. 1H NMR (300 MHz, CDCl3): δ =
7.72–7.63 (m, 1 H), 7.47–7.12 (m, 14 H), 7.10 (d, JH,H = 3.5 Hz, 1
H), 6.57 (dd, JH,H = 3.5, 0.5 Hz, 1 H), 5.90 (d, JH,H = 8.5 Hz, 1
H), 5.18 (d, JH,H = 12.0 Hz, 1 H), 5.07 (d, JH,H = 12.0 Hz, 1 H)
ppm. 13C NMR (75.5 MHz, CDCl3): δ = 155.3 (C), 137.4 (C), 135.7
(C), 135.5 (C), 129.2 (C), 128.9 (CH), 128.8 (CH), 128.5 (CH),
128.3 (CH), 128.2 (CH), 126.3 (CH), 125.8 (CH), 122.0 (CH), 121.1
(CH), 120.2 (CH), 110.4 (CH), 102.8 (CH), 67.5 (CH2), 65.3 (CH)
ppm. HRMS (ESI): calcd. for C23H20N2NaO2 [M + Na]+ 379.1422;
found 379.1424.
Benzyl [(Fur-3-yl)(1H-indol-1-yl)methyl]carbamate (7ag): Oil
1
(38.9 mg, 90% yield). H NMR (300 MHz, CDCl3): δ = 7.71–7.61
(m, 1 H), 7.55–7.05 (m, 12 H), 6.55 (dd, JH,H = 3.5, 0.5 Hz, 1 H),
6.24 (s, 1 H), 5.83 (d, JH,H = 9.0 Hz, 1 H), 5.16 (d, JH,H = 12.0 Hz,
1 H), 5.04 (d, JH,H = 12.0 Hz, 1 H) ppm. 13C NMR (75.5 MHz,
CDCl3): δ = 155.2 (C), 144.3 (CH), 140.4 (CH), 135.6 (C), 135.3
(C), 129.2 (C), 128.5 (CH), 128.4 (CH), 128.2 (CH), 125.5 (CH),
124.1 (C), 122.0 (CH), 121.1 (CH), 120.2 (CH), 110.5 (CH), 109.3
(CH), 102.9 (CH), 67.5 (CH2), 59.8 (CH) ppm. HRMS (ESI):
calcd. for C21H18N2NaO3 [M + Na]+ 369.1215; found 369.1201.
Benzyl [(1H-Indol-1-yl)(p-tolyl)methyl]carbamate (7ab): 41.2 mg,
89% yield; m.p. 119–120 °C. 1H NMR (300 MHz, CDCl3): δ =
7.72–7.60 (m, 1 H), 7.48–6.99 (m, 14 H), 6.56 (dd, JH,H = 3.5,
0.5 Hz, 1 H), 5.87 (d, JH,H = 7.0 Hz, 1 H), 5.18 (d, JH,H = 12.0 Hz,
1 H), 5.07 (d, JH,H = 12.0 Hz, 1 H), 2.37 (s, 3 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 155.3 (C), 138.6 (C), 135.7 (C), 135.4 (C),
134.4 (C), 129.5 (CH), 129.1 (C), 128.5 (CH), 128.3 (CH), 128.2
(CH), 126.2 (CH), 125.8 (CH), 121.9 (CH), 121.0 (CH), 120.1
(CH), 110.5 (CH), 102.6 (CH), 67.4 (CH2), 65.2 (CH), 21.0 (CH3)
ppm. HRMS (ESI): calcd. for C24H22N2NaO2 [M + Na]+ 393.1579;
found 393.1573.
Benzyl [(1H-Indol-1-yl)(thien-2-yl)methyl]carbamate (7ah): 38.9 mg,
1
86% yield; m.p. 86–87 °C. H NMR (300 MHz, CDCl3): δ = 7.72–
7.61 (m, 1 H), 7.60–7.06 (m, 11 H), 7.03–6.94 (m, 1 H), 6.90 (s, 1
H), 6.58 (d, JH,H = 3.5 Hz, 1 H), 6.03 (d, JH,H = 7.0 Hz, 1 H), 5.17
(d, JH,H = 12.0 Hz, 1 H), 5.06 (d, JH,H = 12.0 Hz, 1 H) ppm. 13C
NMR (75.5 MHz, CDCl3): δ = 155.0 (C), 141.2 (C), 135.5 (C),
135.3 (C), 129.2 (C), 128.5 (CH), 128.3 (CH), 128.2 (CH), 127.3
(CH), 126.4 (CH), 126.2 (CH), 125.6 (CH), 122.1 (CH), 121.1
(CH), 120.3 (CH), 110.4 (CH), 103.2 (CH), 67.6 (CH2), 62.5 (CH)
ppm. HRMS (ESI): calcd. for C21H19N2O2S [M + H]+ 363.1167;
found 363.1167.
Benzyl [(1H-Indol-1-yl)(4-methoxyphenyl)methyl]carbamate (7ac):
43.9 mg, 91% yield; m.p. 142–144 °C. 1H NMR (300 MHz,
CDCl3): δ = 7.67–7.63 (m, 1 H), 7.43–7.23 (m, 7 H), 7.22–7.06 (m,
5 H), 6.92–6.80 (m, 2 H), 6.55 (d, JH,H = 3.0 Hz, 1 H), 5.83 (d,
JH,H = 8.5 Hz, 1 H), 5.17 (d, JH,H = 12.0 Hz, 1 H), 5.06 (d, JH,H
= 12.0 Hz, 1 H), 3.80 (s, 3 H) ppm. 13C NMR (75.5 MHz, CDCl3):
δ = 159.8 (C), 155.3 (C), 135.7 (C), 135.4 (C), 129.3 (C), 129.2 (C),
128.5 (CH), 128.3 (CH), 128.2 (CH), 127.6 (CH), 125.8 (CH), 122.0
(CH), 121.1 (CH), 120.1 (CH), 114.2 (CH), 110.5 (CH), 102.6
(CH), 67.4 (CH2), 65.0 (CH), 55.2 (CH3) ppm. HRMS (ESI): calcd.
for C24H22N2NaO3 [M + Na]+ 409.1528; found 409.1535.
Benzyl [1-(1H-Indol-1-yl)pentyl]carbamate (7ai): Oil (37.4 mg,
1
89%). H NMR (300 MHz, CDCl3): δ = 7.53 (m, 2 H), 7.28–6.97
(m, 8 H), 6.45 (d, JH,H = 3.0 Hz, 1 H), 6.01 (d, JH,H = 7.5 Hz, 1
H), 5.35 (d, JH,H = 8.5 Hz, 1 H), 5.02 (d, JH,H = 12.0 Hz, 1 H),
4.88 (d, JH,H = 12.0 Hz, 1 H), 1.80–2.12 (m, 2 H), 1.37–1.05 (m, 4
H), 0.77 (t, JH,H = 7.0 Hz, 3 H) ppm. 13C NMR (75.5 MHz,
CDCl3): δ = 155.3 (C), 135.8 (C), 135.5 (C), 128.7 (CH), 128.5
Benzyl [(4-Chlorophenyl)(1H-indol-1-yl)methyl]carbamate (7ad): (CH), 128.2 (CH), 128.1 (C), 123.7 (CH), 121.9 (CH), 120.9 (CH),
40.9 mg, 84% yield; m.p. 175–177 °C. 1H NMR (300 MHz, [D6]- 119.9 (CH), 110.2 (CH), 102.6 (CH), 67.1 (CH2), 63.0 (CH), 34.7
Eur. J. Org. Chem. 2013, 3885–3895
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3891

G. Blay, R. M. Girón, M. Montesinos-Magraner, J. R. Pedro
FULL PAPER
(CH2), 27.6 (CH2), 22.1 (CH2), 13.8 (CH3) ppm. HRMS (ESI): 13C NMR (75.5 MHz, CDCl3): δ = 154.5 (C), 138.5 (C), 135.5 (C),
calcd. for C21H24N2NaO2 [M + Na]+ 359.1735; found 359.1730.
134.9 (CH), 129.5 (CH), 129.1 (C), 126.2 (CH), 125.7 (CH), 121.8
(CH), 121.0 (CH), 119.9 (CH), 110.5 (CH), 102.3 (CH), 80.7 (C),
64.8 (CH), 28.2 (CH3), 21.1 (CH3) ppm. HRMS (ESI): calcd. for
C21H24N2NaO2 [M + Na]+ 359.1735; found 359.1737.
Benzyl [1-(1H-Indol-1-yl)-3-methylbutyl]carbamate (7aj): 38.6 mg,
1
92% yield; m.p. 68–70 °C. H NMR (300 MHz, CDCl3): δ = 7.72–
7.59 (m, 2 H), 7.44–7.05 (m, 8 H), 6.56 (d, JH,H = 3.0 Hz, 1 H),
6.33–6.11 (m, 1 H), 5.45 (d, JH,H = 8.5 Hz, 1 H), 5.13 (d, JH,H
Methyl 1-[{[(Benzyloxy)carbonyl]amino}(phenyl)methyl]-1H-indole-
=
1
2-carboxylate (7da): 37.3 mg, 72% yield; m.p. 87–88 °C. H NMR
12.0 Hz, 1 H), 4.98 (d, JH,H = 12.0 Hz, 1 H), 2.10–1.84 (m, 2 H),
1.63–1.40 (m, 1 H), 0.97 (d, JH,H = 6.0 Hz, 6 H) ppm. 13C NMR
(75.5 MHz, CDCl3): δ = 155.3 (C), 135.8 (C), 135.5 (C), 128.6 (C),
128.5 (CH), 128.2 (CH), 128.1 (CH), 123.7 (CH), 122.0 (CH), 120.9
(CH), 119.9 (CH), 110.2 (CH), 102.7 (CH), 67.1 (CH2), 61.3 (CH),
43.8 (CH2), 24.6 (CH), 22.4 (CH3), 22.2 (CH3) ppm. HRMS (ESI):
calcd. for C21H24N2NaO2 [M + Na]+ 359.1735; found 359.1733.
(300 MHz, CDCl3): δ = 7.91–7.68 (m, 3 H), 7.61–7.15 (m, 12 H),
7.05–6.87 (m, 2 H), 5.27 (d, JH,H = 12.0 Hz, 1 H), 5.08 (d, JH,H
=
12.0 Hz, 1 H), 3.70 (s, 3 H) ppm. 13C NMR (75.5 MHz, CDCl3):
δ = 162.6 (C), 156.4 (C), 140.0 (C), 138.8 (C), 136.0 (C), 128.5
(CH), 128.4 (CH), 128.2 (CH), 128.2 (CH), 127.8 (CH), 126.7 (C),
126.2 (CH), 125.5 (C), 125.0 (CH), 122.7 (CH), 121.5 (CH), 113.7
(CH), 111.0 (CH), 67.3 (CH2), 63.7 (CH), 52.0 (CH3) ppm. HRMS
(ESI): calcd. for C25H22N2NaO4 [M + Na]+ 437.1477; found
437.1477.
Benzyl
[1-(1H-Indol-1-yl)-3,3-dimethylbutyl]carbamate
(7ak):
1
40.6 mg, 93% yield; m.p. 97–98 °C. H NMR (300 MHz, CDCl3):
δ = 7.75–7.57 (m, 2 H), 7.47–7.00 (m, 8 H), 6.55 (d, JH,H = 3.0 Hz,
1 H), 6.27 (d, JH,H = 6.5 Hz, 1 H), 5.53 (d, JH,H = 8.0 Hz, 1 H),
5.12 (d, JH,H = 12.0 Hz, 1 H), 4.96 (d, JH,H = 12.5 Hz, 1 H), 2.21–
1.85 (m, 2 H), 0.94 (s, 9 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ
= 155.0 (C), 135.8 (C), 135.0 (C), 128.7 (C), 128.5 (CH), 128.2
(CH), 128.1 (CH), 124.2 (CH), 121.9 (CH), 121.0 (CH), 119.8
(CH), 110.3 (CH), 102.6 (CH), 67.1 (CH2), 60.9 (CH), 48.5 (CH2),
30.3 (C), 29.5 (CH3) ppm. HRMS (ESI): calcd. for C22H26N2NaO2
[M + Na]+ 373.1892; found 373.1886.
Benzyl [(3-Methyl-1H-indol-1-yl)(phenyl)methyl]carbamate (7fa):
37.0 mg, 80% yield; m.p. 104–105 °C. 1H NMR (300 MHz,
CDCl3): δ = 7.68–7.54 (m, 1 H), 7.46–7.09 (m, 14 H), 6.84 (d, JH,H
= 0.8 Hz, 1 H), 5.81 (d, JH,H = 7.5 Hz, 1 H), 5.18 (d, JH,H
=
12.0 Hz, 1 H), 5.07 (d, JH,H = 12.0 Hz, 1 H), 2.32 (d, JH,H = 1.0 Hz,
3 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 155.4 (C), 137.6 (C),
135.9 (C), 135.8 (C), 129.5 (C), 128.8 (CH), 128.7 (CH), 128.5
(CH), 128.3 (CH), 128.2 (CH), 126.4 (CH), 123.2 (CH), 122.0
(CH), 119.5 (CH), 119.1 (CH), 112.0 (C), 110.3 (CH), 67.4 (CH2),
65.1 (CH), 9.7 (CH3) ppm. HRMS (ESI): calcd. for C24H22N2NaO2
[M + Na]+ 393.1579; found 393.1574.
Benzyl
[(Cyclohexyl)(1H-indol-1-yl)methyl]carbamate
(7al):
1
39.8 mg, 88% yield; m.p. 55–58 °C. H NMR (300 MHz, CDCl3):
δ = 7.65 (dd, JH,H = 9.0, 0.5 Hz, 1 H), 7.58 (d, JH,H = 7.5 Hz, 1
H), 7.44–6.97 (m, 8 H), 6.56 (d, JH,H = 3.0 Hz, 1 H), 5.81 (t, JH,H
Benzyl [(4-Methyl-1H-indol-1-yl)(phenyl)methyl]carbamate (7ga):
42.6 mg, 92% yield; m.p. 108–109 °C. 1H NMR (300 MHz,
CDCl3): δ = 7.49–7.01 (m, 14 H), 6.96 (dd, JH,H = 8.0, 1.0 Hz, 1
H), 6.59 (dd, JH,H = 3.5, 0.5 Hz, 1 H), 5.88 (d, JH,H = 7.0 Hz, 1
H), 5.18 (d, JH,H = 12.0 Hz, 1 H), 5.07 (d, JH,H = 12.0 Hz, 1 H),
2.59 (s, 3 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 155.8 (C),
137.9 (C), 136.2 (C), 135.6 (C), 131.0 (C), 129.5 (C), 129.3 (CH),
129.2 (CH), 129.0 (CH), 128.8 (CH), 128.7 (CH), 126.8 (CH), 125.7
(CH), 122.6 (CH), 120.8 (CH), 108.5 (CH), 101.7 (CH), 67.9 (CH2),
66.0 (CH), 19.1 (CH3) ppm. HRMS (ESI): calcd. for
C24H22N2NaO2 [M + Na]+ 393.1579; found 393.1567.
= 9.0 Hz, 1 H), 5.56 (d, JH,H = 8.5 Hz, 1 H), 5.12 (d, JH,H
=
12.5 Hz, 1 H), 4.97 (d, JH,H = 12.5 Hz, 1 H), 2.14–1.91 (m, 2 H),
1.82 (s, 1 H), 1.66 (s, 2 H), 1.43–0.74 (m, 6 H) ppm. 13C NMR
(75.5 MHz, CDCl3): δ = 155.6 (C), 135.8 (C), 135.7 (C), 128.5
(CH), 128.2 (CH), 128.1 (CH), 124.4 (CH), 121.9 (CH), 120.9
(CH), 119.7 (CH), 119.7 (C), 110.1 (CH), 102.5 (CH), 67.8 (CH),
67.1 (CH2), 42.1 (CH), 29.7 (CH2), 28.9 (CH2), 25.9 (CH2), 25.5
(CH2), 25.4 (CH2) ppm. HRMS (ESI): calcd. for C23H27N2O2 [M
+ H]+ 363.2073; found 363.2070.
Benzyl [1-(1H-Indol-1-yl)-2-methylpropyl]carbamate (7am): Oil
(39.8 mg, 99%). H NMR (300 MHz, CDCl3): δ = 7.68–7.50 (m, 2
Benzyl [(5-Methoxy-1H-indol-1-yl)(phenyl)methyl]carbamate (7ha):
43.2 mg, 86% yield; m.p. 112–114 °C. 1H NMR (300 MHz,
CDCl3): δ = 7.40–7.15 (m, 12 H), 7.12 (d, JH,H = 2.5 Hz, 1 H),
7.07 (d, JH,H = 3.0 Hz, 1 H), 6.82 (d, JH,H = 8.0 Hz, 1 H), 6.48 (d,
1
H), 7.41–6.95 (m, 8 H), 6.55 (d, JH,H = 3.0 Hz, 1 H), 5.90–5.36 (m,
2 H), 5.11 (d, JH,H = 12.5 Hz, 1 H), 4.98 (d, JH,H = 12.5 Hz, 1 H),
2.38 (s, 1 H), 1.15 (d, JH,H = 6.5 Hz, 3 H), 0.77 (d, JH,H = 6.0 Hz,
3 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 155.6 (C), 135.8 (C),
135.7 (C), 128.5 (CH), 128.2 (CH), 128.1 (CH), 124.3 (CH), 121.9
(CH), 120.9 (CH), 119.8 (CH), 119.7 (C), 110.1 (CH), 102.6 (CH),
68.9 (CH), 67.2 (CH2), 33.2 (CH), 19.3 (CH3), 18.8 (CH3) ppm.
HRMS (ESI): calcd. for C20H22N2NaO2 [M + Na]+ 345.1579;
found 345.1580.
JH,H = 3.0 Hz, 1 H), 5.90 (d, JH,H = 7.5 Hz, 1 H), 5.17 (d, JH,H
=
12.0 Hz, 1 H), 5.07 (d, JH,H = 12.0 Hz, 1 H), 3.85 (s, 3 H) ppm.
13C NMR (75.5 MHz, CDCl3): δ = 155.4 (C), 154.4 (C), 137.4 (C),
135.7 (C), 130.7 (C), 129.7 (C), 128.9 (CH), 128.8 (CH), 128.5
(CH), 128.3 (CH), 128.2 (CH), 126.5 (CH), 126.3 (CH), 112.1
(CH), 111.2 (CH), 102.8 (CH), 102.3 (CH), 67.4 (CH2), 65.5 (CH),
55.8 (CH3) ppm. HRMS (ESI): calcd. for C24H22KN2O3
[M + K]+ 425.1267; found 425.1260.
tert-Butyl [(1H-Indol-yl)(phenyl)methyl]carbamate (7an): 35.0 mg,
87% yield; m.p. 127–128 °C. 1H NMR (300 MHz, CDCl3): δ =
7.71–7.63 (m, 1 H), 7.45–7.06 (m, 11 H), 6.57 (d, JH,H = 3.0 Hz, 1
H), 5.60 (d, JH,H = 8.5 Hz, 1 H), 1.46 (s, 9 H) ppm. 13C NMR
(75.5 MHz, CDCl3): δ = 154.5 (C), 137.9 (C), 135.5 (C), 129.1 (C),
128.8 (CH), 128.6 (CH), 126.3 (CH), 125.7 (CH), 121.9 (CH), 121.0
(CH), 120.0 (CH), 110.5 (CH), 102.4 (CH), 80.7 (C), 64.9 (CH),
28.2 (CH3) ppm. HRMS (ESI): calcd. for C20H22N2NaO2 [M +
Na]+ 345.1579; found 345.1569.
Benzyl [(5-Chloro-1H-indol-1-yl)(phenyl)methyl]carbamate (7ia):
46.2 mg, 91% yield; m.p. 112–113 °C. 1H NMR (300 MHz,
CDCl3): δ = 7.61 (d, JH,H = 2.0 Hz, 1 H), 7.44–7.01 (m, 14 H),
6.49 (d, JH,H = 3.5 Hz, 1 H), 5.91 (d, JH,H = 7.5 Hz, 1 H), 5.16 (d,
JH,H = 12.0 Hz, 1 H), 5.06 (d, JH,H = 12.0 Hz, 1 H) ppm. 13C NMR
(75.5 MHz, CDCl3): δ = 155.3 (C), 137.0 (C), 135.6 (C), 133.9 (C),
130.2 (C), 129.0 (CH), 128.6 (CH), 128.4 (CH), 128.2 (CH), 127.0
(CH), 126.2 (CH), 125.9 (C), 122.3 (CH), 120.5 (CH), 111.4 (CH),
102.4 (CH), 67.6 (CH2), 65.5 (CH) ppm. HRMS (ESI): calcd. for
C23H19ClKN2O2 [M + K]+ 429.0772; found 429.0763.
tert-Butyl [(1H-Indol-1-yl)(p-tolyl)methyl]carbamate (7ao): 37.0 mg,
88% yield; m.p. 130–131 °C. 1H NMR (300 MHz, CDCl3): δ =
7.73–7.60 (m, 1 H), 7.43–7.04 (m, 9 H), 6.56 (d, JH,H = 3.0 Hz, 1
H), 5.58 (d, JH,H = 8.5 Hz, 1 H), 2.36 (s, 3 H), 1.46 (s, 9 H) ppm.
Benzyl [(6-Fluoro-1H-indol-1-yl)(phenyl)methyl]carbamate (7ja):
43.9 mg, 94% yield; m.p. 142–143 °C. 1H NMR (300 MHz,
3892
www.eurjoc.org
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 3885–3895

Aminoalkylation of Indoles and Heterocycles with α-Amido Sulfones
CDCl3): δ = 7.55 (dd, JH,H = 8.5, 5.5 Hz, 1 H), 7.44–7.15 (m, 11
H), 7.09 (d, JH,H = 3.5 Hz, 1 H), 7.00 (d, JH,H = 9.5 Hz, 1 H), 6.90
(ddd, JH,H = 9.5, 8.5, 2.5 Hz, 1 H), 6.53 (d, JH,H = 3.5 Hz, 1 H),
5.86 (d, JH,H = 7.5 Hz, 1 H), 5.17 (d, JH,H = 12.0 Hz, 1 H), 5.09
(d, JH,H = 12.0 Hz, 1 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ =
159.73 (d, JH,H = 238.5 Hz, C), 155.3 (C), 137.0 (C), 135.6 (C),
135.48 (d, JH,H = 12.0 Hz, C), 129.0 (CH), 129.0 (CH), 128.6 (CH),
JH,H = 12.0 Hz, 1 H), 4.95 (d, JH,H = 8.0 Hz, 1 H), 4.70 (td, JH,H
= 8.0, 6.5 Hz, 1 H), 2.16–1.70 (m, 2 H), 1.54–1.20 (m, 4 H), 0.92
(t, JH,H = 7.0 Hz, 3 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ =
157.0 (C), 136.2 (C), 133.7 (C), 128.5 (CH), 128.2 (CH), 128.0
(CH), 117.5 (CH), 107.6 (CH), 104.1 (CH), 66.9 (CH2), 48.6 (CH),
32.7 (CH2), 28.5 (CH2), 22.4 (CH2), 13.9 (CH3) ppm. HRMS (ESI):
calcd. for C19H27N2O2 [M + H]+ 315.2073; found 315.2077.
128.4 (CH), 128.2 (CH), 126.2 (CH), 125.5 (C), 121.76 (d, JH,H
=
Benzyl [(Phenyl)(1H-pyrrol-1-yl)methyl]carbamate (9aa): Cs2CO3
(84.4 mg, 0.25 mmol) was dried in a Schlenk tube by using a heat
gun under vacuum. α-Amido sulfone 2a (0.125 mmol) was added,
and the system was purged with nitrogen. Then, CH2Cl2 (0.7 mL)
was added, and the mixture was stirred at room temperature for
2 h. A solution of pyrrole (8.7 μL, 0.125 mmol) in CH2Cl2 (0.5 mL)
was added. The mixture was stirred at room temperature for 3 h
and then quenched with water (1 mL). The resulting solution was
extracted with CH2Cl2 (3ϫ25 mL), and the combined organic lay-
ers were washed with brine and dried with anhydrous Na2SO4. Pu-
rification by flash chromatography on silica gel (hexane/EtOAc)
afforded compound 9aa (13.2 mg, 32%); m.p. 114–116 °C. 1H
NMR (300 MHz, CDCl3): δ = 7.47–7.27 (m, 8 H), 7.21–7.10 (m, 2
H), 6.90 [d, JH,H = 7.5 Hz, 1 H), 6.77 [t, JH,H = 2.0 Hz, 2 H), 6.22
[t, JH,H = 2.0 Hz, 2 H), 5.73 [d, JH,H = 4.5 Hz, 1 H), 5.19 [d, JH,H
= 12.0 Hz, 1 H), 5.11 [d, JH,H = 12.0 Hz, 1 H) ppm. 13C NMR
(75.5 MHz, CDCl3): δ = 155.6 (C), 138.6 (C), 136.2 (C), 129.3
(CH), 129.0 (CH), 128.8 (CH), 128.7 (CH), 126.6 (CH), 119.8
(CH), 109.4 (CH), 67.9 (CH2), 30.1 (CH) ppm. HRMS (ESI):
calcd. for C19H18N3NaO2 [M + Na]+ 329.1266; found 329.1258.
10.0 Hz, CH), 108.93 (d, JH,H = 24.5 Hz, CH), 102.8 (CH), 97.09
(d, JH,H = 27.0 Hz, CH), 67.6 (CH2), 65.6 (CH) ppm. HRMS
(ESI): calcd. for C23H19FKN2O2 [M + K]+ 413.1068; found
413.1056.
Benzyl [(7-Methyl-1H-indol-1-yl)(phenyl)methyl]carbamate (7ka):
Oil (23.8 mg, 51%). 1H NMR (300 MHz, CDCl3): δ = 7.80 (d, JH,H
= 7.5 Hz, 1 H), 7.52 (d, JH,H = 7.5 Hz, 1 H), 7.44–7.27 (m, 7 H),
7.17–6.94 (m, 6 H), 6.60 (d, JH,H = 3.5 Hz, 1 H), 5.76 (d, JH,H
=
8.0 Hz, 1 H), 5.19 (d, JH,H = 12.5 Hz, 1 H), 5.10 (d, JH,H = 12.0 Hz,
1 H), 2.72 (s, 3 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 155.0
(C), 139.3 (C), 135.7 (C), 135.3 (C), 129.6 (C), 128.9 (CH), 128.7
(CH), 128.6 (CH), 128.4 (CH), 128.2 (CH), 126.0 (CH), 125.5
(CH), 125.0 (CH), 121.2 (C), 120.3 (CH), 119.2 (CH), 104.0 (CH),
67.5 (CH2), 66.2 (CH), 20.2 (CH3) ppm. HRMS (ESI): calcd. for
C24H22KN2O2 [M + K]+ 409.1318; found 409.1315.
Procedure for the Synthesis of C-2-Aminoalkylated Pyrroles 8:
MeMgBr (1 m solution in THF, 125 μL, 0.125 mmol) was added to
a solution of pyrrole (26.0 μL, 0.375 mmol) and MgBr2 (4.6 mg,
0.025 mmol) in CH2Cl2 (0.5 mL) at 0 °C under nitrogen. The mix-
ture was stirred at 0 °C for 2 h. Then, a suspension of α-amido
sulfone (0.125 mmol) in CH2Cl2 (1 mL) was added, and the mixture
was stirred (0 °C for aromatic α-amido sulfones, room temperature
for aliphatic α-amido sulfones) until it reached completion (TLC).
The reaction was quenched with NH4Cl (1 m saturated aqueous
solution, 1 mL), and the resulting solution was extracted with
CH2Cl2 (3ϫ25 mL). The combined organic layers were washed
with brine (5 mL) and dried with anhydrous Na2SO4. Purification
by flash chromatography on silica gel (hexane/EtOAc) afforded
compound 8.
Benzyl
[(Phenyl)(1H-pyrrolo[2,3-b]pyridin-3-yl)methyl]carbamate
(10aa): MeMgBr (1 m solution in THF, 125 μL, 0.125 mmol) was
added to a solution of 7-azaindole (14.8 mg, 0.125 mmol) and
MgBr2 (4.6 mg, 0.025 mmol) in CH2Cl2 (0.5 mL) at 0 °C under ni-
trogen. The mixture was stirred at 0 °C for 2 h. Then, a suspension
of α-amido sulfone 2a (0.125 mmol) in CH2Cl2 (1 mL) was added,
and the mixture was stirred at room temp. for 7 h and then
quenched with NH4Cl (1 m saturated aqueous solution, 1 mL). The
resulting solution was extracted with CH2Cl2 (3ϫ25 mL). The
combined organic layers were washed with brine and dried with
anhydrous Na2SO4. Purification by flash chromatography on silica
gel (hexane/EtOAc) afforded compound 10aa (17.9 mg, 40%); m.p.
Benzyl [(Phenyl)(1H-pyrrol-2-yl)methyl]carbamate (8aa): 33.3 mg,
1
87% yield; m.p. 93–94 °C. H NMR (300 MHz, CDCl3): δ = 8.58
1
210–212 °C. H NMR (300 MHz, [D6]DMSO): δ = 11.47 (s, 1 H),
(s, 1 H), 7.49–7.13 (m, 10 H), 6.71 (s, 1 H), 6.11 (dd, JH,H = 6.0,
3.0 Hz, 1 H), 5.96 (d, JH,H = 8.0 Hz, 1 H), 5.83 (s, 1 H), 5.56 (d,
JH,H = 5.5 Hz, 1 H), 5.19–5.05 (m, 2 H) ppm. 13C NMR
(75.5 MHz, CDCl3): δ = 156.2 (C), 139.7 (C), 136.1 (C), 132.2 (C),
128.7 (CH), 128.5 (CH), 128.2 (CH), 128.1 (CH), 127.9 (CH), 127.1
(CH), 118.1 (CH), 108.1 (CH), 107.3 (CH), 67.1 (CH2), 53.4 (CH)
ppm. HRMS (ESI): calcd. for C19H19N2O2 [M + H]+ 307.1442;
found 307.1447.
8.31 (d, JH,H = 9.0 Hz, 1 H), 8.18 (dd, JH,H = 4.5, 1.5 Hz, 1 H),
7.76 (dd, JH,H = 8.0, 1.5 Hz, 1 H), 7.48–7.40 (m, 2 H), 7.40–7.20
(m, 8 H), 7.07 (d, JH,H = 2.0 Hz, 1 H), 6.98 (dd, JH,H = 8.0, 4.5 Hz,
1 H), 6.11 (d, JH,H = 9.0 Hz, 1 H), 5.10 (d, JH,H = 12.5 Hz, 1 H),
5.04 (d, JH,H = 12.5 Hz, 1 H) ppm. 13C NMR (75.5 MHz, [D6]-
DMSO): δ = 155.7 (C), 148.7 (C), 142.7 (CH), 142.6 (C), 137.1 (C),
128.3 (CH), 128.2 (CH), 127.8 (CH), 127.1 (CH), 127.0 (CH), 126.9
(CH), 123.5 (CH), 117.9 (C), 115.4 (C), 115.1 (CH), 65.4 (CH2),
51.7 (CH) ppm. HRMS (ESI): calcd. for C22H20N3O2 [M + H]+
358.1555; found 358.1556.
Benzyl [(5-Ethyl-1H-pyrrol-2-yl)(phenyl)methyl]carbamate (8ba):
1
33.0 mg, 79% yield; m.p. 85–87 °C. H NMR (300 MHz, CDCl3):
δ = 8.33 (s, 1 H), 7.50–7.12 (m, 10 H), 5.92 (d, JH,H = 8.0 Hz, 1
Procedure for the Synthesis N-1-Aminoalkylated Azaindoles 11:
Cs2CO3 (84.4 mg, 0.25 mmol) was dried in a Schlenk tube by using
a heat gun under vacuum. α-Amido sulfone (0.125 mmol) was
added, and the system was purged with nitrogen. Then, CH2Cl2
(0.7 mL) was added, and the mixture was stirred at room tempera-
ture for 2 h. A solution of 7-azaindole (14.8 mg, 0.125 mmol) in
CH2Cl2 (0.5 mL) was added. The mixture was stirred at room tem-
perature until it reached completion (TLC), and then it was
quenched with water (1 mL). The resulting solution was extracted
with CH2Cl2 (3ϫ25 mL). The combined organic layers were
H), 5.78 (t, JH,H = 3.0 Hz, 1 H), 5.65 (s, 1 H), 5.51 (d, JH,H
=
8.0 Hz, 1 H), 5.24–5.04 (m, 2 H), 2.57 (q, JH,H = 7.5 Hz, 2 H), 1.22
(t, JH,H = 7.5 Hz, 3 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ =
156.2 (C), 139.8 (C), 136.2 (C), 134.8 (C), 130.7 (C), 128.7 (CH),
128.5 (CH), 128.2 (CH), 128.1 (CH), 127.8 (CH), 127.1 (CH), 107.4
(CH), 103.9 (CH), 67.0 (CH2), 53.5 (CH), 20.8 (CH2), 13.4 (CH3)
ppm. HRMS (ESI): calcd. for C21H23N2O2 [M + H]+ 335.1760;
found 335.1758.
Benzyl [1-(1H-Pyrrol-2-yl)pentyl]carbamate (8ai): 22.8 mg, 58%
1
yield; m.p. 123–124 °C. H NMR (300 MHz, CDCl3): δ = 8.89 (s, washed with brine and dried with anhydrous Na2SO4. Purification
1 H), 7.44–7.29 (m, 5 H), 6.71 (s, 1 H), 6.12 (dd, JH,H = 6.0, 3.0 Hz,
1 H), 6.05–5.99 (m, 1 H), 5.14 (d, JH,H = 12.0 Hz, 1 H), 5.08 (d,
by flash chromatography on silica gel (hexane/EtOAc) afforded
compounds 11.
Eur. J. Org. Chem. 2013, 3885–3895
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3893

G. Blay, R. M. Girón, M. Montesinos-Magraner, J. R. Pedro
FULL PAPER
Benzyl
[(Phenyl)(1H-pyrrolo[2,3-b]pyridin-1-yl)methyl]carbamate
N-[(1H-Indol-3-yl)(phenyl)methyl]acetamide (13aa):[17] Acetyl chlor-
ide (21 μL, 0.3 mmol) was added dropwise to a stirred suspension
of compound 12aa (23.6 mg, 0.1 mmol) and NaOH (8.8 mg,
(11aa): 37.0 mg, 83% yield; m.p. 94–96 °C. 1H NMR (300 MHz,
CDCl3): δ = 8.25 (dd, JH,H = 4.5, 1.5 Hz, 1 H), 7.93 (dd, JH,H
=
8.0, 1.5 Hz, 1 H), 7.63–6.98 (m, 14 H), 6.52 (d, JH,H = 3.5 Hz, 1 0.22 mmol) in CH2Cl2 (10 mL) at room temperature. The reaction
H), 5.20 (d, JH,H = 12.0 Hz, 1 H), 5.08 (d, JH,H = 12.0 Hz, 1 H)
progress was monitored by TLC, and H2O (1 mL) was added when
the starting material was consumed. The mixture was extracted
ppm. 13C NMR (75.5 MHz, CDCl3): δ = 155.5 (C), 147.3 (C), 143.0
(CH), 138.6 (C), 135.9 (C), 129.0 (CH), 128.6 (CH), 128.5 (CH), with EtOAc (3ϫ25 mL). The combined organic layers were dried
128.3 (CH), 128.2 (CH), 128.1 (CH), 127.1 (CH), 125.8 (CH), 121.2 with Na2SO4. Purification by flash chromatography on silica gel
(C), 116.3 (CH), 100.4 (CH), 67.2 (CH2), 66.1 (CH) ppm. HRMS
(hexane/EtOAc) afforded compound 13aa (18.5 mg, 70%); m.p.
169–172 °C. H NMR (300 MHz, [D6]acetone): δ = 10.13 (s, 1 H),
1
(ESI): calcd. for C22H20N3O2 [M + H]+ 358.1556; found 358.1548.
7.75 (d, JH,H = 8.0 Hz, 1 H), 7.48–7.28 (m, 6 H), 7.28–7.20 (m, 1
H), 7.10 (ddd, JH,H = 8.0, 7.0, 1.0 Hz, 1 H), 6.97 (ddd, JH,H = 8.0,
7.0, 1.0 Hz, 1 H), 6.90 (dd, JH,H = 2.5, 1.0 Hz, 1 H), 6.52 (d, JH,H
= 8.5 Hz, 1 H), 1.98 (s, 3 H) ppm. 13C NMR (75.5 MHz, [D6]-
acetone): δ = 169.1 (C), 144.0 (C), 138.0 (C), 129.0 (CH), 128.0
(CH), 127.6 (CH), 127.3 (C), 124.4 (CH), 122.5 (CH), 120.0 (CH),
119.8 (CH), 118.2 (C), 112.3 (CH), 50.6 (CH), 22.9 (CH3) ppm.
HRMS (ESI): calcd. for C17H16N2NaO [M + Na]+ 287.1160; found
287.1162.
Benzyl [(4-Methoxyphenyl)(1H-pyrrolo[2,3-b]pyridin-1-yl)methyl]-
carbamate (11ac): Oil (42.6 mg, 88% yield). H NMR (300 MHz,
1
CDCl3): δ = 8.24 (dd, JH,H = 4.5, 1.5 Hz, 1 H), 7.92 (dd, JH,H
=
8.0, 1.5 Hz, 1 H), 7.45–7.26 (m, 5 H), 7.06 (td, JH,H = 9.0, 4.5 Hz,
4 H), 6.84–6.75 (m, 2 H), 6.50 (d, JH,H = 3.5 Hz, 1 H), 5.18 (d,
JH,H = 12.0 Hz, 1 H), 5.06 (d, JH,H = 12.0 Hz, 1 H), 3.75 (s, 3 H)
ppm. 13C NMR (75 MHz, CDCl3): δ = 159.5 (C), 155.6 (C), 147.2
(C), 143.0 (CH), 135.9 (C), 130.7 (C), 129.0 (CH), 128.5 (CH),
128.2 (CH), 128.1 (CH), 127.1 (CH), 127.0 (CH), 121.3 (C), 116.2
(CH), 113.9 (CH), 100.3 (CH), 67.2 (CH2), 65.9 (CH), 55.2 (CH3)
ppm. HRMS (ESI): calcd. for C23H22N3O3 [M + H]+ 388.1661;
found 388.1664.
Supporting Information (see footnote on the first page of this arti-
cle): Synthetic procedures and characterization data for α-amido
sulfones 2. Copies of 1H and 13C NMR spectra of compounds 3
and 7–13.
Benzyl [(2-Chlorophenyl)(1H-pyrrolo[2,3-b]pyridin-1-yl)methyl]carb-
1
amate (11af): Oil (30.8 mg, 63%). H NMR (300 MHz, CDCl3): δ
Acknowledgments
= 8.19 (dd, JH,H = 4.7, 1.5 Hz, 1 H), 7.81 (dd, JH,H = 8.0, 1.5 Hz,
1 H), 7.59 (d, JH,H = 9.0 Hz, 1 H), 7.41–6.90 (m, 13 H), 6.38 (d,
JH,H = 3.5 Hz, 1 H), 5.08 (d, JH,H = 12.5 Hz, 1 H), 4.99 (d, JH,H
= 12.5 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 155.1 (C),
147.3 (C), 143.0 (CH), 138.6 (C), 136.0 (C), 135.9 (CH), 133.0 (C),
130.1 (CH), 129.9 (CH), 129.85 (CH), 129.0 (CH), 128.5 (CH),
128.1 (CH), 127.9 (CH), 126.9 (CH), 121.3 (C), 116.4 (CH), 100.4
(CH), 67.3 (CH2), 64.1 (CH) ppm. HRMS (ESI): calcd. for
C22H19ClN3O2 [M + H]+ 392.1166; found 392.1160.
Financial support from the MINECO (Gobierno de España) and
FEDER (European Union) (CTQ2009-13083) and from Genera-
litat Valenciana (ACOMP2012-212 and ISIC2012/001) is gratefully
acknowledged. M. M. thanks the Universitat de València for a pre-
doctoral grant.
[1] a) U. Huber, R. E. Moore, G. M. L. Patterson, J. Nat. Prod.
1998, 61, 1304–1306; b) I. Mancini, G. Guella, H. Zibrowius,
F. Pietra, Tetrahedron 2003, 59, 8757–8762; c) A. C. Kinsman,
M. A. Kerr, J. Am. Chem. Soc. 2003, 125, 14120–14125.
[2] a) K. A. Jørgensen, Synthesis 2003, 1117–1125; b) M. Bandini,
A. Eichholzer, Angew. Chem. 2009, 121, 9786; Angew. Chem.
Int. Ed. 2009, 48, 9608–9644; c) M. Zeng, S.-L. You, Synlett
2010, 1289–1301.
[3] a) V. Wittenau, M. Schach, E. Hans, J. Am. Chem. Soc. 1963,
85, 3425–3431; b) H. Kotsuki, M. Teraguchi, N. Shimomoto,
M. Ochi, Tetrahedron Lett. 1996, 37, 3727–3730; c) M. Bandini,
M. Fagioli, A. Melloni, A. Umani-Ronchi, Adv. Synth. Catal.
2004, 346, 573–578; d) M. Boudou, C. Ogawa, S. Kobayashi,
Adv. Synth. Catal. 2006, 348, 2585–2589.
[4] a) J. Szmuszkovicz, J. Am. Chem. Soc. 1957, 79, 2819–2821;
b) K. B. Jensen, J. Thorbauge, R. G. Hazell, K. A. Jørgensen,
Angew. Chem. 2001, 113, 164; Angew. Chem. Int. Ed. 2001, 40,
160–163; c) C. Palomo, M. Oiarbide, B. G. Kardak, J. M. Gar-
cia, A. Linden, J. Am. Chem. Soc. 2005, 127, 4154–4155; d)
D. A. Evans, K. R. Fandrick, H.-J. Song, J. Am. Chem. Soc.
2005, 127, 8942–8943; e) G. Bartoli, M. Bosco, A. Carlone, F.
Pesciaioli, L. Sambri, P. Melchiorre, Org. Lett. 2007, 9, 1403–
1405; f) G. Blay, I. Fernandez, J. R. Pedro, C. Vila, Org. Lett.
2007, 9, 2601–2604.
[5] a) D. Ranganathan, C. B. Rao, S. Ranganathan, A. K. Mehro-
tra, R. Iyengar, J. Org. Chem. 1980, 45, 1185–1189; b) J. Wu,
X.-C. Li, F. Wu, B.-S. Wan, Org. Lett. 2011, 13, 4834–4837; c)
H. Y. Kim, S. Kim, K. Oh, Angew. Chem. 2010, 122, 4578;
Angew. Chem. Int. Ed. 2010, 49, 4476–4478; d) F. Guo, G. Lai,
S. Xiong, S. Wang, Z. Wang, Chem. Eur. J. 2010, 16, 6438–
6441; e) J. Itoh, K. Fuchibe, T. Akiyama, Angew. Chem. 2008,
120, 4080; Angew. Chem. Int. Ed. 2008, 47, 4016–4018; f) S.-F.
Lu, D.-M. Du, J. Xu, Org. Lett. 2006, 8, 2115–2118; g) R. P.
Benzyl [2-Methyl-1-(1H-pyrrolo[2,3-b]pyridin-1-yl)propyl)carbamate
(11am): Oil (29.9 mg, 74%). 1H NMR (300 MHz, CDCl3): δ = 8.15
(dd, JH,H = 4.5, 1.5 Hz, 1 H), 7.81 (dd, JH,H = 8.0, 1.5 Hz, 1 H),
7.36–7.12 (m, 6 H), 6.97 (dd, JH,H = 8.0, 4.5 Hz, 1 H), 6.66 (d, JH,H
= 9.5 Hz, 1 H), 6.31 (d, JH,H = 3.5 Hz, 1 H), 5.53 (t, JH,H
10.0 Hz, 1 H), 5.05 (d, JH,H = 12.0 Hz, 2 H), 4.90 (d, JH,H
12.0 Hz, 1 H), 2.74 (qd, JH,H = 13.5, 6.5 Hz, 1 H), 1.05 (d, JH,H
=
=
=
6.5 Hz, 3 H), 0.57 (d, JH,H = 6.5 Hz, 3 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 155.9 (C), 146.9 (C), 142.4 (CH), 136.1 (C),
128.9 (CH), 128.4 (CH), 128.3 (CH), 128.1 (CH) 128.0 (CH), 121.5
(C), 116.0 (CH), 99.1 (CH), 71.6 (CH), 67.0 (CH2), 32.7 (CH), 19.3
(CH3), 19.0 (CH3) ppm. HRMS (ESI): calcd. for C19H22N3O2 [M
+ H]+ 324.1712; found 324.1711.
(1H-Indol-3-yl)(phenyl)methanamine (12aa):[7e] Na (46 mg, 2 mmol)
was dissolved in liquid NH3 (approximately 10 mL) under nitrogen
at –78 °C. Then, a solution of 3aa (33 mg, 0.1 mmol) in THF
(1 mL) was added dropwise. The mixture was stirred at –78 °C for
30 min. Then, NH4Cl (150 mg) was added with caution at –78 °C.
EtOAc (10 mL) and water (30 mL) were added. The resulting mix-
ture was extracted with EtOAc (50 mL) and dried with Na2SO4.
The solvent was removed under reduced pressure to afford product
12aa (23.6 mg, 100%). 1H NMR (300 MHz, [D6]DMSO): δ = 10.85
(s, 1 H), 7.50–7.39 (m, 3 H), 7.35–7.19 (m, 4 H), 7.19–7.11 (m, 1
H), 7.01 (ddd, JH,H = 8.0, 7.0, 1.0 Hz, 1 H), 6.86 (ddd, JH,H = 8.0,
7.0, 1.0 Hz, 1 H), 5.31 (s, 1 H) ppm. 13C NMR (75.5 MHz, [D6]-
DMSO): δ = 147.3 (C), 136.5 (C), 127.9 (CH), 126.9 (CH), 126.2
(CH), 125.7 (C), 122.0 (CH), 120.9 (CH), 120.6 (C), 119.3 (CH),
118.1 (CH), 111.4 (CH), 52.7 (CH) ppm.
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Eur. J. Org. Chem. 2013, 3885–3895

Aminoalkylation of Indoles and Heterocycles with α-Amido Sulfones
Herrera, V. Sgarzani, L. Bernardi, A. Ricci, Angew. Chem.
2005, 117, 6734; Angew. Chem. Int. Ed. 2005, 44, 6576–6579.
[6] a) X. Mi, S. Luo, J. Hea, J.-P. Chen, Tetrahedron Lett. 2004,
45, 4567–4570; b) W. Xie, K. M. Bloomfield, Y. Jin, N. Dolney,
P. G. Wan g, Synlett 1999, 498–500.
[7] a) D.-M. Jia, M.-H. Xu, Chem. Commun. 2010, 46, 1550–1552;
b) J. Esquivias, R. Gómez-Arrayás, J. C. Carretero, Angew.
Chem. 2006, 118, 645; Angew. Chem. Int. Ed. 2006, 45, 629–
633; c) Y.-X. Jia, J.-H. Xie, H.-F. Duan, L.-X. Wang, Q.-L.
Zhou, Org. Lett. 2006, 8, 1621–1684; d) B.-L. Wang, N.-K. Li,
J.-X. Zhang, G.-G. Liu, T. Liu, Q. Shen, X.-W. Wang, Org.
Biomol. Chem. 2011, 9, 2614–2617; e) Y.-Q. Wang, J. Song, R.
Hong, H. Li, L. Deng, J. Am. Chem. Soc. 2006, 128, 8156–
8157; f) Y.-X. Jia, J. Zhong, S.-F. Zhu, C.-M. Zhang, Q.-L.
Zhou, Angew. Chem. 2007, 119, 5661; Angew. Chem. Int. Ed.
2007, 46, 5565–5567; g) Q. Kang, Z.-A. Zhao, S.-L. You, J.
Am. Chem. Soc. 2007, 129, 1484–1485.
[8] a) M. Hatano, Y. Sugiura, M. Akakura, K. Ishihara, Synlett
2011, 9, 1247–1250; b) D. Uraguchi, K. Sorimachi, M. Terada,
J. Am. Chem. Soc. 2004, 126, 11804–11805; c) M. Terada, S.
Yokoyama, K. Sorimachi, D. Uraguchi, Adv. Synth. Catal.
2007, 349, 1863–1867; d) A. G. Wenzel, E. N. Jacobsen, J. Am.
Chem. Soc. 2002, 124, 12964–12965; e) T. P. Yoon, E. N. Ja-
cobsen, Angew. Chem. 2005, 117, 470; Angew. Chem. Int. Ed.
2005, 44, 466–468.
[11]
[12]
a) R. Ballini, A. Palmieri, M. Petrini, E. Torregiani, Org. Lett.
2006, 8, 4093–4096; b) C. Kuhakarm, K. Tandenpaisal, P.
Kongsaeree, S. Prapai, P. Tuchinda, M. Pohmakotr, V. Re-
utrakul, Tetrahedron Lett. 2007, 48, 2467–2470; c) S. T. Kadam,
P. Thirupathi, S. S. Kim, Tetrahedron 2009, 65, 10383–10398;
d) P. Thirupathi, S. S. Kim, J. Org. Chem. 2009, 74, 7755–7761;
e) P. Thirupathi, S. S. Kim, Eur. J. Org. Chem. 2010, 1798–
1808; f) P. Thirupathi, L. N. Neupane, K.-H. Lee, Tetrahedron
2011, 67, 7301–7310.
a) S. Nunomoto, Y. Kawakami, Y. Yamashita, H. Takeuchi, S.
Eguichi, J. Chem. Soc. Perkin Trans. 1 1990, 111–114; b) M. J.
Earle, P. B. McCormac, K. R. Seddon, Chem. Commun. 1998,
2245–2246; c) B. E. Love, B. T. Nguyen, Synlett 1998, 1123–
1125.
[13]
[14]
T. Mita, Y. Higuchi, Y. Sato, Org. Lett. 2011, 13, 2354–2357.
G. Blay, A. Brines, A. Monleón, J. R. Pedro, Chem. Eur. J.
2012, 18, 2440–2444.
[15] a) D. L. Cottle, L. S. Powell, J. Am. Chem. Soc. 1936, 58, 2267–
2272; b) M. Anteunis, J. Org. Chem. 1962, 27, 596–598; c) J.
Thomas, Bull. Soc. Chim. Fr. 1973, 4, 1300–1304; d) J. Thomas,
Bull. Soc. Chim. Fr. 1975, 209–214.
[16] D.-J. Cheng, H.-B. Wu, S.-K. Tian, Org. Lett. 2011, 13, 5636–
5639.
[17] H. Mao, X. Wang, W. Wang, L. He, L. Kong, J. Liu, Synthesis
2008, 16, 2582–2588.
[9] J. B. F. N. Engberts, J. Strating, Recl. Trav. Chim. Pays-Bas
1964, 83, 733–736.
[10] a) T. Mecozzi, M. Petrini, R. Profeta, Tetrahedron: Asymmetry
2003, 14, 1171–1178; b) M. Petrini, E. Torregiani, Tetrahedron
Lett. 2005, 46, 5999–6003.
Received: March 11, 2013
Published Online: May 5, 2013
Eur. J. Org. Chem. 2013, 3885–3895
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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