The Friedel-Crafts Reaction of Indoles with Michael Acceptors Catalyzed by Magnesium and Calcium Salts

Article abstract of DOI:10.1055/s-0036-1589068

Friedel-Crafts alylation of indole and its derivatives with a variety of electron-deficient alkenes catalyzed by Mg and Ca salts has been studied. The dependence of the results on the nature of the starting olefins, substituents on indole, and Michael acc

Full text of DOI:10.1055/s-0036-1589068

SYNTHESIS
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1
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© Georg Thieme Verlag Stuttgart · New York
2017, 49, A–N
paper
A
en
M. N. Feofanov et al.
Paper
Synthesis
The Friedel–Crafts Reaction of Indoles with Michael Acceptors
Catalyzed by Magnesium and Calcium Salts
O
Friedel–Crafts addition catalyzed by Mg and Ca salts
Mikhail N. Feofanov
Maxim V. Anokhin
Alexei D. Averin
COOMe
COOMe
EtO
Ph
NO2
Ph
N
H
Irina P. Beletskaya*
HN
N
H
Ca(NTf2)2, 90%
MeOOC
Ph
MgI2, 82%
CF3
Department of Chemistry, Lomonosov Moscow State
University, Leninskie Gory, 1-3, Moscow, 119991,
Russian Federation
O
NH
O
beletska@org.chem.msu.ru
Ph
COOMe
O
N
N
O
H
H
MgI2, 93%
MgI2, 85%
MgI2, 76%
Received: 29.04.2017
Accepted after revision: 12.06.2017
Published online: 02.08.2017
Catalysis by Mg salts and, more rarely, by Ca salts is al-
ready used in aldol condensation reactions,2 for transforma-
tions of cyclopropanes,3 epoxides4 or aziridines,5 in the
Diels–Alder reaction,6 ene-reaction,7 in addition to
imines,8,9 in various dipolar cycloaddition processes,10 and
in the ring-opening reactions of vinylcyclopropanes.11 The
favorable influence of MgX2 has been documented for many
reactions catalyzed by transition metal complexes9–12 or or-
ganocatalysts.13 Mg salts and complexes are known to have
been employed in the Michael addition reactions.3a–c,14 One
of the most interesting fields of asymmetric synthesis cata-
lyzed by Lewis acids is associated with Friedel–Crafts reac-
tions.15 Further to our study of the reactions of indole with
Michael acceptors catalyzed by copper salts and their com-
plexes,16a,b we studied Michael addition/Friedel–Crafts reac-
tions of indole using various Michael acceptors under catal-
ysis by chiral Cu(II) complexes.16c
DOI: 10.1055/s-0036-1589068; Art ID: ss-2017-t0285-op
Abstract Friedel–Crafts alkylation of indole and its derivatives with a
variety of electron-deficient alkenes catalyzed by Mg and Ca salts has
been studied. The dependence of the results on the nature of the start-
ing olefins, substituents on indole, and Michael acceptors, as well as on
the composition of the Lewis acid is discussed. High yields of the addi-
tion products were achieved in the addition of indole to β,γ-unsaturat-
ed α-keto esters and coumarin derivatives, some nitroolefins, and
arylidenemalonates. Reactions involving arylidenemalonates were
found to be the most versatile and smooth, the best yields reached
92%. Among the Mg and Ca salts tested, magnesium iodide (MgI2)
proved to be the most appropriate catalyst in the addition to various
unsaturated carbonyl compounds, while calcium triflimide [Ca(NTf2)2]
efficiently catalyzed the addition to nitroolefins.
Key words Friedel–Crafts reaction, Lewis acid catalysis, indole,
Michael addition, alkenes
In the present work we discuss the results obtained
during the investigation of the reactions of indoles 1 with
methyl (E)-2-oxo-4-phenylbut-3-enoate (2), arylidene-
malonates 3, methyl 2-oxo-2H-chromene-3-carboxylate
(4), α,β-unsaturated ketones 5, ethyl (Z)-3-nitro-2-phenyl-
acrylate (6), (E)-(2-nitrovinyl)benzene (7), methyl 2-nitro-
3-phenylacrylate (8), and 3-nitro-2H-chromen-2-one (9)
catalyzed by Mg and Ca salts. The influence of substituents
in the reagents, the solvent, and the nature of the counteri-
on on the results of these reactions was studied. In the first
step of our investigation we chose Mg and Ca triflates as
catalysts. Compounds 2, 3a, and 4 were taken as Michael ac-
ceptors and THF was used as a solvent (Table 1). The reac-
tions showed good chemoselectivity, but with triflates the
reaction rate was quite low, especially for less electrophilic
olefins 3a and 4. Mg salts were much more active as cata-
lysts than Ca salts, in particular with olefins 3a and 4 (Table
1, entries 3–8). The reactions accelerated dramatically
Catalysis with transition metal complexes has seriously
changed the situation in fine organic synthesis in the last 15
years. The proof of this is in the three Nobel Prizes granted
in the period of 2001–2010 and the rapidly proliferating
studies in this area. However, in comparison with this type
of catalysis, the results achieved by the application of Lewis
acids and, in particular, asymmetric catalysis with the use
of chiral complexes of scandium, indium, yttrium, and
some lanthanides salts1 have been, as yet, underdeveloped.
It is noted that recently the interest in the use of non-
transition metal salts (primarily magnesium and calcium)
has increased. Obviously these investigations are in a trend
of green chemistry considering high price and toxicity of
many transition metals. Ca and Mg as biogenic elements are
non-toxic even in large amounts; they are abundant in
Nature and rank 5th and 8th places, respectively, in abun-
dancy in the Earth’s core.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–N

B
M. N. Feofanov et al.
Paper
Synthesis
when changing Mg(OTf)2 for Mg(NTf2)2 (Table 1, entry 8).
For this reason further investigation was carried out only
with Mg salts.
chemoselectivity. Formation of only 1,4-addition product
10 was noted in the presence of MgI2 in THF (Table 2, entry
4). Insignificant amounts of the side product 13 were ob-
served with Mg(ClO4)2 (Table 2, entry 7) and MgI2 in CH2Cl2
(Table 2, entry 8).
Table 1 Indole (1a) Addition to Michael Acceptors 2, 3a, and 4 Cata-
lyzed by Mg and Ca Saltsa
Table 2 Indole (1a) Addition to Methyl 2-Oxo-3-phenylbut-3-enoate
(2) Catalyzed by Mg Saltsa
MeOOC
O
Ph
NH
O
N
H
COOMe
10
MgX2
(10 mol%)
O
O
10
+
+
Ph
COOMe
COOMe
MX2, THF
20 °C
20 °C
N
H
H
N
2
H
N
COOMe
COOMe
Ph
COOMe
2
Ph
1a
3a
COOMe
COOMe
MX2, THF
20 °C
N
H
N
H
1a
11aa
13
COOMe
O
MX2, THF
20 °C
Entry MgX2
Solvent
Conv.b (%) of 2
Ratiob 10/13
O
4
1
2
3
4
5
6
7
8
Mg(OTf)2
THF
100
65:35
55:45
55:45
100:0
20:80
66:34
94:6
NH
Mg(NTf2)2
Mg(ClO4)2
MgI2
THF
100
THF
100
THF
100 (92)c
100
COOMe
O
Mg(OTf)2
Mg(NTf2)2
Mg(ClO4)2
MgI2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
O
100
12
100
Entry
Michael
acceptor
MX2
Time
Product
100
95:5
[yieldb (%)]
a Reaction conditions: indole (1a, 0.5 mmol), methyl 2-oxo-3-phenylbut-3-
enoate (2, 0.25 mmol), catalyst (0.025 mmol), THF (0.5 mL), 20 °C, 24 h.
b Estimated by 1H NMR.
1
2
3
4
5
6
7
8
2
Ca(OTf)2
24 h
24 h
60 d
60 d
60 d
60 d
60 d
24 h
10 (52)
10 (65)
–
2
Mg(OTf)2
Ca(OTf)2
Mg(OTf)2
Ca(OTf)2
Mg(OTf)2
Сa(NTf2)2
Mg(NTf2)2
c Isolated yield (%) of compound 10.
3a
3a
4
11aa (68)
–
The reaction of dimethyl benzylidenemalonate (3a) (Ta-
ble 3) was found to be most sensitive to the nature of the
counterion. Mg(OTf)2 was not efficient enough (Table 3, en-
tries 1 and 5), whilst the activity of Mg(ClO4)2 and
Mg(NTf2)2 in THF was higher than in CH2Cl2 (Table 3, entries
2, 3, 6, and 7). The best catalytic activity was demonstrated
by MgI2. The reaction went to completion in THF in 6 hours
(Table 3, entry 4), and in CH2Cl2 in only 5 minutes (Table 3,
entry 8).
4
12 (20)
11aa (32)
11aa (93)
3a
3a
a Reaction conditions: indole (1a, 0.5 mmol), Michael acceptor (0.25
mmol), catalyst (0.025 mmol), THF (0.5 mL), 20 °C.
b Isolated yield.
In the reaction of indole (1a) with β,γ-unsaturated α-
keto ester 2 the addition can proceed not only with the C=C
bond but also with the C=O bond resulting in the formation
of a bisindole product 13 (Table 2).17 Investigation of the in-
fluence of X in MgX2 salts in the reactions of β,γ-unsaturat-
ed α-keto ester 2 showed that with all counterions (OTf–,
The lower yield of compound 11aa was due to the for-
mation of the symmetric bisindole derivative 14, the possi-
ble mechanism of its formation is shown in Scheme 1.
We studied the dependence of the products yield, reac-
tion time, and chemoselectivity on the nature of the sub-
stituents in the starting compounds (Table 4). 7-Nitroindole
(1b) was totally inert and even after 3 days no product was
detected in the reaction mixture (Table 4, entry 2). The re-
–
–
NTf2 , ClO4 , I–) in THF or CH2Cl2 at room temperature the
reaction went to completion in 24 hours (reaction time was
not optimized) with full conversion of 2 but with different
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–N

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M. N. Feofanov et al.
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Synthesis
Table 3 Indole (1a) Addition to Dimethyl Benzylidenemalonate (3a)
withdrawing substituents like 5-NO2 (Table 4, entry 4), 6-
COOMe (Table 4, entry 5), 5-CN (Table 4, entry 6), 4-CN (Ta-
ble 4, entry 7) gave the addition products in good yields (up
to 75%) after column chromatography isolation. No bisin-
dole side product was observed.
However, the reaction time increased up to 40 h due to a
decrease in nucleophilicity of C3 of the indoles containing
strong electron-withdrawing substituents. The introduc-
tion of halogens in positions 5 and 6 led to lower yields of
the Michael addition products and resulted in the forma-
tion of notable amounts of the bisindole side products (Ta-
ble 4, entries 8–12). Such bisindole derivatives became pre-
dominant for indoles with electron-donor substituents in
the benzene or pyrrole ring. The reaction with 5-methoxy-
indole (1m) at room temperature produced exclusively a
symmetric bisindole compound (Table 4, entry 13).
Catalyzed by Mg Saltsa
H
N
COOMe
MgX2 (10 mol%)
20 °C
COOMe
COOMe
COOMe
+
N
H
1a
11aa
3a
Entry
MgX2
Solvent
Time
Conv.b (%) of 3a
1
2
3
4
5
6
7
8
Mg(OTf)2
Mg(NTf2)2
Mg(ClO4)2
MgI2
THF
24 h
24 h
24 h
6 h
15
100
100
100
0
THF
THF
THF
Mg(OTf)2
Mg(NTf2)2
Mg(ClO4)2
MgI2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
24 h
24 h
24 h
5 min
77
Table 4 Indoles Addition to Substituted Dimethyl Arylidenemalonates
a
Catalyzed by MgI2
56
100 (82)c
COOMe
R2
a Reaction conditions: indole (1a, 0.5 mmol), dimethyl benzylidene-
malonate (3a, 0.25 mmol), catalyst (0.025 mmol), solvent (0.5 mL), 20 °C.
b Estimated by 1H NMR.
COOMe
MgI2 (10 mol%)
CH2Cl2
COOMe
COOMe
R1
+
N
c Isolated yield (%) of 11aa.
R1
H
R2
1a–r
3a–v
N
H
MeO
O
MeO
O
MgI2
MgI2
11aa–av
–
O
O
+
– H+
Entry Indole,
R1
Malonate,
R2
Temp
(°C)
Timeb
Product
N
OMe
N
OMe
[yieldc (%)]
H
1
2
1a, H
3a, H
20
20
5 min 11aa (82)
1b, 7-NO2
1c, 1-Me
1d, 5-NO2
3a, H
72 h
11ba (–)
3
3a, H
20
18 h
8 h
11ca (<50)
11da (75)
4
3a, H
20
MeO
O
MgI2
5
1e, 6-COOMe
1f, 5-CN
1g, 4-CN
1h, 5-F
3a, H
20
40 min 11ea (70)
+
O
–
+
6
3a, H
20
40 h
20 h
11fa (73)
11ga (72)
N
OMe
H
7
3a, H
20
8
3a, H
20
30 min 11ha (70)
30 min 11ia (65d)
30 min 11ja (55d)
30 min 11ka (51d)
20 min 11la (67d)
2 min 11ma (0e)
+ H+ – MgI2
– H+
9
1i, 5-Cl
3a, H
20
N
H
10
11
12
13
14
15
16
17
18
19
20
21
1j, 5-Br
3a, H
20
MeO
O
1k, 5-I
3a, H
20
O
HN
1l, 6-Cl
3a, H
20
OMe
1m, 5-OMe
1m, 5-OMe
1n, 2-Me
1o, 5-Me
1p, 5-OBn
1q, 4-OMe
1r, 4-OBn
1a, H
3a, H
20
3a, H
–40
–40
–40
–40
–40
–40
3 h
4 h
4 h
4 h
6 h
8 h
11ma (80)
11na (86)
11oa (88)
11pa (85)
11qa (86)
11ra (80)
11ab (0)
N
3a, H
H
3a, H
14
3a, H
Scheme 1 Plausible mechanism of formation of bisindole derivative 14
3a, H
3a, H
3b, 4-NO2
3c, 4-COOMe
–40 to r.t. 72 h
20 3 h
action with 1-methylindole (1c) was also very slow as only
50% conversion was observed after 18 horus (Table 4, entry
3). The reactions of other indole derivatives with electron
1a, H
11ac (62)
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D
M. N. Feofanov et al.
Paper
Synthesis
Table 4 (continued)
3e (Table 4, entry 23) or halogen atoms in any position of
the benzene ring (Table 4, entries 24–32) afforded the prod-
ucts in 70–92% yields.
Entry Indole,
R1
Malonate,
R2
Temp
(°C)
Timeb
Product
[yieldc (%)]
We also found out that the introduction of trifluorometh-
oxy and methylthio substituents in the para-position did
not diminish the yields of the target products (entries 33
and 34) but the presence of alkyl or methoxy substituents
in the ortho- and para-positions led to an increase in the
yields of bisindole products (Table 4, entries 35–38). These
facts envisage high reactivity of starting compounds in the
presence of MgI2. Similar influence was noted for het-
eroarylidenemalonates. Thus dimethyl (thiophen-2-yl-
methylene)malonate (3u) formed the addition product in
90% yield at –40 °C (Table 4, entry 39) while with dimethyl
(pyridin-2-ylmethylene)malonate (3v) the reaction did not
occur even at room temperature (Table 4, entry 40).
One should stress that the observed influence of the
substituents is opposite to that assumed as typical for
Cu(II)-catalyzed reactions.18
Other electron-rich aromatic compounds also react
with dimethyl benzylidenemalonate (3a) in the presence of
MgI2 (Table 5). Pyrrole (15) forms the addition product 18
in a high yield (82%, Table 5, entry 1), but its N-Me analogue
16 reacts very slowly (Table 5, entry 2). In the case of 3,5-
dimethylpyrazole (17), full conversion of the starting ben-
zylidenemalonate 3a was observed (Table 5, entry 3), how-
ever, an attempt to purify the product using column chro-
matography was unsuccessful due to its complete decom-
position. It was impossible to carry out the reactions with
2-methylfuran and electron-enriched 1,3-dimethoxyben-
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
1a, H
1a, H
1a, H
1a, H
1a, H
1a, H
1a, H
1a, H
1a, H
1a, H
1a, H
1a, H
1a, H
1a, H
1a, H
1a, H
1a, H
1a, H
1a, H
3d, 4-CF3
3e, 3,5-(CF3)2
3f, 2-F
20
–40
–40
–40
–40
–40
–40
–40
–40
–40
–40
–40
–40
–40
–40
–40
–40
–40
–40
4 h
18 h
18 h
18 h
18 h
18 h
18 h
18 h
18 h
18 h
18 h
18 h
18 h
18 h
18 h
18 h
18 h
48 h
72 h
11ad (76)
11ae (87)
11af (70)
11ag (82)
11ah (76)
11ai (92)
11aj (75)
11ak (90)
11al (68)
11am (87)
11an (81)
11ao (83)
11ap (81)
11aq (62d)
11ar (60d)
11as (60d)
11at (51d)
11au (90)
11av (0)
3g, 3-F
3h, 4-F
3i, 2-Cl
3j, 3-Cl
3k, 4-Cl
3l, 2-Br
3m, 3-Br
3n, 4-Br
3o, 4-OCF3
3p, 4-SMe
3q, 2-Me
3r, 4-Et
3s, 2-OMe
3t, 4-OMe
3uf
3vg
a Reaction conditions: indole (0.5 mmol), Michael acceptor (0.25 mmol),
MgI2 (0.025 mmol), CH2Cl2 (0.5 mL).
b Estimated by TLC.
c Isolated yield.
d 100% conversion of the starting Michael acceptor.
e Bisindole adduct was isolated in 85% yield.
f Dimethyl (thiophen-2-ylmethylene)malonate.
g Dimethyl (pyridin-2-ylmethylene)malonate.
Table 5 Friedel–Crafts Reaction of the Aromatic Compounds with Di-
a
methyl Benzylidenemalonate (3a) Catalyzed by MgI2
Performing the reaction at –40 °C allowed the desired
addition product of 5-methoxyindole (1m) to be obtained
in 80% yield (Table 4, entry 14), and no bisindole derivative
was observed. Adducts with other indoles possessing elec-
tron-donor substituents were isolated in high yields under
low temperature conditions (Table 4, entries 15–19).
COOMe
MgI2 (10 mol%)
COOMe
COOMe
COOMe
ArH
+
CH2Cl2
Ar
15–17
18–20
3a
The studies of the influence of substituents in arylidene-
malonate revealed some interesting facts. It is known that
in the case of the catalysis by Cu(II) complexes the reaction
is rapid when electron-withdrawing substituents like the
para-nitro group are present in arylidenemalonates. In con-
trast, the introduction of electron-donor substituents like
the para-methoxy group decreases the reaction rate. When
the reaction is catalyzed by MgI2, 4-nitrobenzylidene-
malonate 3b does not react with indole (1a) (Table 4, entry
20). Weaker electron-withdrawing substituents like
COOMe and CF3 (Table 4, entries 21 and 22) provided the
products 11ac,ad in good yields, but the reactions needed
more time compared to the unsubstituted analogue 3a. The
introduction of two meta-CF3 groups in arylidenemalonate
N
N
H
N
N
H
Me
16
17
15
Entry
ArH
15, pyrrole
Timeb (h) Product [conv.c (%) of 3a]
1
2
3
2
24
2
18 (100, 82d)
19 (20)
16, N-methylpyrrole
17, 3,5-dimethylpyrazole
20 (100)
a Reaction conditions: aromatic compound (0.5 mmol), dimethyl ben-
zylidenemalonate (3a, 0.25 mmol), MgI2 (0.025 mmol), CH2Cl2 (0.5 mL),
–40 °C.
b Estimated by TLC.
c Estimated by 1H NMR.
d Isolated yield (%) for 18.
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M. N. Feofanov et al.
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Synthesis
zene, 1,3,5-trimethoxybenzene, and N,N-diethylaniline be-
cause these compounds were not sufficiently nucleophilic
to participate in this process.
products was formed among which no Michael adducts
were noted (Table 7, entry 3). In contrast, chalcone (24) re-
acted with indole (1a), however, the conversion of the un-
saturated ketone did not surpass 40% (Table 7, entry 4).
Methyl vinyl ketone (5a) and trifluorobenzylideneacetone
5b were the most active unsaturated carbonyl compounds.
The addition of indole (1a) to methyl vinyl ketone (5a) gave
26 in 75% isolated yield (Table 7, entry 5), the reaction with
trifluorobenzylideneacetone 5b resulted in 27 in 76% yield
(Table 7, entry 6).
The reaction of indole with methyl 2-oxo-2H-
chromene-3-carboxylate (4) (Table 6) was found to be very
sensitive to the nature of the solvent. Mg salts other than
MgI2 were not active in THF (Table 6, entries 1–3), and with
MgI2 the conversion reached only 32% after 72 hours (Table
6, entry 4). Similar poor results were observed in CH2Cl2
(entries 5–8). However, the yield could be increased up to
50–60% in 1,2-dichloroethane, acetone, acetonitrile (Table
6, entries 9–11). In chloroform it attained 85% (Table 6, en-
try 12). The synthesis of product 12 was fully diastereose-
Table 7 Indole (1a) Addition to α,β-Unsaturated Ketones Catalyzed by
a
MgI2
lective giving one isomer with the coupling constant 3JHH
=
H
N
7.1 Hz between H3 and H4 of the chromane.
O
H
MgI2 (10 mol%)
CH2Cl2, 20 °C
N
R2
+
Table 6 Indole (1a) Addition to Methyl 2-Oxo-2H-chromene-3-carbox-
ylate (4) Catalyzed by Mg Saltsa
R1
25–27
R1
5a,b, 21–24
O
R2
1a
NH
COOMe
Entry
1
Michael acceptor
Time (h)
Product [conv.b (%)]
MgX2 (10 mol%)
+
COOMe
20 °C
N
O
O
O
H
4
1a
O
O
96
96
0
12
21
Entry
MgX2
Solvent
Conv.b (%) of 4
O
1
2
Mg(OTf)2
Mg(NTf2)2
Mg(ClO4)2
MgI2
THF
0
2
3
0
0
THF
1
Ph
3
THF
2
22
4
THF
32
2
O
H
5
Mg(OTf)2
Mg(NTf2)2
Mg(ClO4)2
MgI2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
DCE
72
6
6
Ph
7
10
25
52
56
60
90 (85)c
23
8
O
9
MgI2
Ph
4
5
6
96
24
24
25 (40)
10
11
12
MgI2
MeCN
acetone
CHCl3
Ph
MgI2
24
MgI2
O
a Reaction conditions: indole (1a, 0.5 mmol), methyl 2-oxo-2H-chromene-
3-carboxylate (4, 0.25 mmol), Mg salt (0.025 mmol), solvent (0.5 mL),
20 °C, 24 h.
26 (100, 75c)
27 (100, 76c)
b Estimated by 1H NMR.
5a
c Isolated yield (%) of 12.
O
Having investigated the regularities of the reactions of
unsaturated compounds 2–4 with indoles, at the next step
we studied several enones in this process (Table 7). We
found out that cyclohex-2-enone (21) (Table 7, entry 1) and
benzylideneacetone (22) (Table 7, entry 2) did not partici-
pate in the reaction with indole (1a) in the presence of
MgI2, and with cinnamaldehyde (23) a complex mixture of
CF3
Ph
5b
a Reaction conditions: indole (1a, 0.5 mmol), ketone (0.25 mmol), MgI2
(0.025 mmol), CH2Cl2 (0.5 mL), 20 °C.
b Estimated by 1H NMR.
c Isolated yield (%).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–N

F
M. N. Feofanov et al.
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Synthesis
The application of other catalysts can lead to much bet-
ter yields of the addition products of this series, e.g.
FeCl3/PdCl2 was shown to provide excellent yields of the in-
dole adduct with chalcone.20
a
Table 9 Indole (1a) Addition to Nitroolefins Catalyzed by Ca(NTf2)2
Entry Michael acceptor
Product
Conv.b (%)
[yieldc (%)]
100 (90)
The influence of Mg and Ca salts on the addition to ni-
troolefins was studied using compound 6 as an example
(Table 8). Magnesium triflate and iodide did not catalyze
the reactions in THF at all (Table 8, entries 1 and 3), and the
conversion with Mg(NTf2)2 was also low (Table 8, entry 2).
In the case of Ca salts in THF the influence of the counterion
was notable as triflate was inactive and iodide provided a
good yield of the addition product (Table 8, entries 4 and 6).
A better result was achieved with Ca(NTf2)2 (Table 8, entry
5). The variations in the nature of the solvent allowed a sub-
stantial increase in the conversion: 67% in THF, 90% in tolu-
ene, and 100% in chloroform (Table 8, entries 5, 7, and 8).
O2N
Ph
NO2
Ph
1
7
N
H
29
30
NO2
COOMe
Ph
NO2
Ph
2
3
100 (78)
COOMe
N
H
8
HN
Table 8 Indole (1a) Addition to Ethyl (Z)-3-Nitro-2-phenylacrylate (6)
Catalyzed by Ca and Mg Salts
NO2
O
100 (55)d
NO2
O
O
9
O
O
NO2
O
O
O
NO2
MX2 (10 mol%)
20 °C
31
+
N
a Reaction conditions: indole (0.5 mmol), nitroolefin (0.25 mmol),
Ca(NTf2)2 (0.025 mmol), CHCl3 (0.5 mL), –30 °C, 18 h.
b Yield estimated by 1H NMR.
H
HN
c Isolated yield.
1a
28
6
d The addition of indole to 9 with full conversion into 31 in i-PrOH catalyzed
by Mg(OTf)2 was described in the literature.19
Entrya
MX2
Solvent
Conv.b (%) of 6
1
2
3
4
5
6
7
8
Mg(OTf)2
Mg(NTf2)2
MgI2
THF
0
THF
30
acceptors 2–5, while Ca(NTf2)2 was found to be the best cat-
alyst for the reactions with nitroolefins. The reactions of
substituted indoles and arylidenemalonates were shown to
tolerate various substituents giving addition products in
good to high yields.
THF
0
Ca(OTf)2
Ca(NTf2)2
CaI2
THF
0
THF
67
THF
55
Ca(NTf2)2
Ca(NTf2)2
toluene
CHCl3
90 (75)c
100 (90)c
All commercially available reagents were used without further purifi-
cation. Solvents were purified using known procedures. Compounds
2,21 3a–v,22 4,23 5,24 6,25 7,26 8,27 and 928 were prepared according to
reported methods. All reactions were performed under an air atmo-
sphere. 1H, 13C, and 19F NMR spectra were recorded in CDCl3 with
a Reaction conditions: indole (1a, 0.5 mmol), nitroolefin 6 (0.25 mmol), cat-
alyst (0.025 mmol), solvent (0.5 mL), 20 °C, 18 h.
b Estimated by 1H NMR.
c Isolated yield (%) of 28.
Bruker Avance-400 and Agilent 400-MR spectrometers at r.t. (13
C
Other nitroolefins 7, 8, and 9 reacted much better and
even at –30 °C produced adducts 29–31 in yields from good
to high (Table 9, entries 1–3). According to TLC and 1H NMR
the conversion of the nitroolefins 7–9 was quantitative in
each case, but due to the difficulties of the chromatographic
isolation the preparative yields varied from 55% (Table 9,
entry 3) to 90% (Table 9, entry 1). The formation of product
31 was fully diastereoselective affording a single isomer
with the coupling constant between H3 and H4 of the chro-
manone moiety 3JHH = 9.8 Hz.
spectra were 1H decoupled) relative to the residual solvent peak
(CHCl3: δ = 7.26 for 1H) or to solvent (CDCl3: δ = 77.00 for 13C) as inter-
nal standards or to an external standard (CF3COOH: δ = –78.5 for 19F).
Accurate-mass measurements (HRMS) were performed by ESI-TOF
with a Thermo Scientific Orbitrap Elite mass spectrometer or by
MALDI-TOF with poly(ethylene glycols) as internal standards with
Bruker Autoflex II spectrometer. Analytical TLC was carried out using
Macherey-Nagel silica gel 60 F254 plates, the spots were visualized by
UF. Preparative column chromatography was performed using
Macherey-Nagel silica gel 60 (0.040–0.063 mm, 230–400 mesh). Pe-
troleum ether
= PE. Melting points were measured with an
Electrothermal IA 9200 apparatus and are uncorrected.
To sum up, the present investigation revealed that MgI2
was the best catalyst for the addition of indole to Michael
Compounds 3e,m,o,p were obtained according to a known proce-
dure22 using 2 mmol of the starting material.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–N

G
M. N. Feofanov et al.
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Synthesis
Dimethyl 2-[3,5-Bis(trifluoromethyl)benzylidene]malonate (3e)
Methyl 4-(1H-Indol-3-yl)-2-oxo-4-phenylbutanoate (10)29
Purified by column chromatography (PE/EtOAc, 5:1); white solid;
yield: 427 mg (60%); mp 71–72 °C.
1H NMR (400 MHz, CDCl3): δ = 7.90 (s, 1 H), 7.86 (s, 2 H), 7.79 (s, 1 H),
Following the GP using indole (1a, 58 mg, 0.5 mmol) and 2 (47 mg,
0.25 mmol) in THF using MgI2 (6.9 mg, 0.025 mmol) as the catalyst at
r.t. After purification by gradient column chromatography (CH2Cl2/PE,
4:1, then CH2Cl2), the product was obtained as a yellow solid; yield:
70 mg (92%).
1H NMR (400 MHz, CDCl3): δ = 8.02 (s, 1 Н), 7.43 (d, J = 8.0 Hz, 1 Н),
7.33 (m, 3 Н), 7.27 (t, J = 7.5 Hz, 2 Н), 7.14–7.20 (m, 2 Н), 7.01–7.04
(m, 2 Н), 4.93 (t, J = 7.6 Hz, 1 Н), 3.77 (s, 3 Н), 3.70 (dd, J = 17.1, 7.6 Hz,
1 Н), 3.62 (dd, J = 17.1 Hz, 7.6 Hz, 1 Н).
3.88 (s, 3 H), 3.84 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 165.7, 163.5, 139.1, 134.9, 132.4 (q, J =
33.8 Hz, 2 C), 129.4, 128.8–128.9 (m), 123.6 (septet, J = 3.6 Hz), 122.8
(q, J = 273.5 Hz, 2 C), 53.1, 52.8.
19F NMR (376 MHz, CDCl3): δ = –63.24 (s, 6 F).
HRMS (ESI): m/z [M + Na]+ calcd for C14H10F6NaO4: 379.0381; found:
13C NMR (101 MHz, CDCl3): δ = 192.6, 161.2, 143.1, 136.5, 128.4 (2 C),
127.7 (2 C), 126.6, 126.3, 122.2, 121.5, 119.4, 119.3, 118.2, 111.2, 52.9,
45.7, 37.7.
379.0360.
Dimethyl 2-(3-Bromobenzylidene]malonate (3m)
Recrystallized (hot MeOH); white solid; yield: 328 mg (55%); mp 72–
73 °C.
1H NMR (400 MHz, CDCl3): δ = 7.68 (s, 1 H), 7.54 (s, 1 H), 7.51 (d, J =
8.0 Hz, 1 H), 7.34 (d, J = 7.8 Hz, 1 H), 7.26 (t, J = 7.8 Hz, 1 H), 3.84 (s, 3
H), 3.84 (s, 3 H).
Dimethyl 2-[(1H-Indol-3-yl)(phenyl)methyl]malonate (11aa)
Following the GP using indole (1a, 58 mg, 0.5 mmol) and 3a (55 mg,
0.25 mmol) in CH2Cl2 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at r.t. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 69 mg (82%); mp 153–154 °C.
13C NMR (101 MHz, CDCl3): δ = 166.5, 164.0, 141.0, 134.8, 133.4,
1H NMR (400 MHz, CDCl3): δ = 8.08 (s, 1 Н), 7.52 (d, J = 8.1 Hz, 1 Н),
7.34 (d, J = 7.7 Hz, 2 Н), 7.29 (d, J = 8.1 Hz, 1 H), 7.24 (t, J = 7.8 Hz, 2 Н),
7.17–7.12 (m, 3 Н), 7.03 (t, J = 7.8 Hz, 1 Н), 5.11 (d, J = 11.9 Hz, 1 Н),
4.33 (d, J = 11.9 Hz, 1 Н), 3.56 (s, 3 H), 3.52 (s, 3 Н).
132.0, 130.3, 127.7, 127.0, 122.9, 52.8, 52.7.
HRMS (MALDI, dithranol, PEG-300): m/z [M]+ calcd for C12H11BrO4:
297.9842; found: 297.9781.
13C NMR (101 MHz, CDCl3): δ = 166.4, 166.2, 141.2, 136.2, 128.4 (2 C),
128.0 (2 C), 126.8, 126.6, 122.3, 120.1, 119.5, 119.3, 116.7, 111.0, 56.2,
52.6, 52.4, 42.9.
HRMS (MALDI, dithranol, PEG-300): m/z [M]+ calcd for C20H19NO4:
337.1314; found: 337.1295.
Dimethyl 2-[4-(Trifluoromethoxy)benzylidene]malonate (3o)
Purified by column chromatography (PE/EtOAc, 5:1); yellow liquid;
yield: 426 mg (70%).
1H NMR (400 MHz, CDCl3): δ = 7.72 (s, 1 H), 7.43–7.46 (m, 2 H), 7.19–
7.22 (m, 2 H), 3.84 (s, 3 H), 3.83 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 166.7, 164.1, 150.5 (q, J = 1.9 Hz),
141.0, 131.2, 130.9, 126.3, 120.9 (q, J = 1.1 Hz), 120.2 (q, J = 258.4 Hz),
52.6 (2 C).
19F NMR (376 MHz, CDCl3): δ = –57.73 (s, 3 F).
HRMS (ESI): m/z [M + Na]+ calcd for C13H11F3NaO5: 327.0456; found:
Dimethyl 2-[(5-Nitro-1H-indol-3-yl)(phenyl)methyl]malonate
(11da)
Following the GP using indole 1d (81 mg, 0.5 mmol) and 3a (55 mg,
0.25 mmol) in CH2Cl2 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at r.t. After purification by column chromatography (CH2Cl2), the
product was obtained as a yellow solid; yield: 72 mg (75%); mp 174–
176 °C.
327.0452.
Dimethyl 2-[4-(Methylthio)benzylidene]malonate (3p)
1H NMR (400 MHz, CDCl3): δ = 8.83 (s, 1 Н), 8.50 (s, 1 Н), 8.02 (d, J =
8.8 Hz, 1 Н), 7.25–7.36 (m, 6 Н), 7.17–7.20 (t, J = 7.3 Hz 1 Н), 5.13 (d,
J = 11.6 Hz, 1 Н), 4.29 (d, J = 11.6 Hz, 1 Н), 3.58 (s, 3 H), 3.55 (s, 3 Н).
Purified by column chromatography (PE/EtOAc, 4:1); dark-brown oil;
yield: 425 mg (80%).
1H NMR (400 MHz, CDCl3): δ = 7.68 (s, 1 H), 7.32 (d, J = 8.4 Hz, 2 H),
7.18 (d, J = 8.4 Hz, 2 H), 3.84 (s, 3 H), 3.82 (s, 3 H), 2.47 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 167.2, 164.5, 142.9, 142.2, 129.8,
13C NMR (101 MHz, CDCl3): δ = 168.2, 167.4, 141.6, 140.2, 139.2,
128.7 (2 C), 127.9 (2 C), 127.3, 126.0, 124.2, 119.2, 118.0, 116.5, 111.3,
57.9, 52.8, 52.6, 42.4.
HRMS (ESI): m/z [M]+ calcd for C20H18N2O6: 382.1165; found:
128.8, 125.6, 124.1, 52.6, 52.5, 14.8.
HRMS (ESI): m/z [M + Na]+ calcd for C13H14NaO4S: 289.0510; found:
382.1109.
289.0505.
Dimethyl 2-{[6-(Methoxycarbonyl)-1H-indol-3-yl](phenyl)meth-
yl}malonate (11ea)
Friedel–Crafts Alkylation Reaction; General Procedure
Following the GP using indole 1e (88 mg, 0.5 mmol) and 3a (55 mg,
0.25 mmol) in CH2Cl2 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at r.t. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 69 mg (70%); mp 196–198 °C.
1H NMR (400 MHz, CDCl3): δ = 8.55 (s, 1 H), 8.06 (s, 1 H), 7.72 (dd, J =
8.5, 0.56 Hz, 1 H), 7.54 (d, J = 8.5 Hz, 1 H), 7.32–7.34 (m, 3 H), 7.25 (t,
J = 7.4 Hz, 2 H), 7.16 (t, J = 7.3 Hz, 1 H), 5.10 (d, J = 11.8 Hz, 1 H), 4.32
(d, J = 11.8 Hz, 1 H), 3.90 (s, 3 H), 3.53 (s, 3 H), 3.53 (s, 3 H).
The calcium or magnesium salt (0.025 mmol, 10 mol%) and Michael
acceptor (0.25 mmol) were dissolved in solvent (0.5 mL), and the mix-
ture was stirred at r.t. for 30 min in a glass vial. The aromatic com-
pound (0.5 mmol) was added and the reaction was stirred at the tem-
perature indicated in Tables 2–9; reaction progress was monitored by
TLC. When the reaction was complete, the solvent was evaporated
under reduced pressure. The crude residue was purified by column
chromatography to afford the product.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–N

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M. N. Feofanov et al.
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Synthesis
13C NMR (101 MHz, CDCl3): δ = 168.1, 167.9, 167.9, 140.9, 135.5,
129.8 (2 C), 128.2 (2 C), 127.3, 126.6, 124.6, 123.2, 119.9, 118.4, 116.3,
113.6, 57.8, 52.4, 52.2, 51.6, 42.5.
HRMS (MALDI, dithranol, PEG-300): m/z [M]+ calcd for C22H21NO6:
395.1369; found: 395.1361.
Dimethyl 2-[(5-Chloro-1H-indol-3-yl)(phenyl)methyl]malonate
(11ia)
Following the GP using indole 1i (76 mg, 0.5 mmol) and 3a (55 mg,
0.25 mmol) in CH2Cl2 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at r.t. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 60 mg (65%); mp 146–147 °C.
Dimethyl 2-[(5-Cyano-1H-indol-3-yl)(phenyl)methyl]malonate
(11fa)
1H NMR (400 MHz, CDCl3): δ = 8.11 (s, 1 H), 7.48 (d, J = 1.5 Hz, 1 H),
7.32 (d, J = 7.7 Hz, 2 H), 7.25 (t, J = 7.4 Hz, 2 H), 7.15–7.21 (m, 3 H),
7.08 (dd, J = 6.8, 1.9 Hz, 1 H), 5.03 (d, J = 11.8 Hz, 1 H), 4.29 (d, J = 11.8
Hz, 1 H), 3.56 (s, 3 H), 3.53 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 168.3, 168.0, 140.7, 134.5, 128.5 (2 C),
127.88 (2 C), 127.5, 127.0, 125.2, 122.6, 122.2, 118.6, 116.4, 112.1,
58.1, 52.7, 52.5, 42.6.
Following the GP using indole 1f (88 mg, 0.5 mmol) and 3a (55 mg,
0.25 mmol) in CH2Cl2 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at r.t. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 69 mg (73%); mp 142–143 °C.
1H NMR (400 MHz, CDCl3): δ = 8.60 (s, 1 Н), 7.84 (s, 1 Н), 7.34 (d, J =
0.6 Hz, 2 H), 7.24–7.32 (m, 5 Н), 7.18 (t, J = 7.1 Hz, 1 H), 5.05 (d, J =
11.6 Hz, 1 Н), 4.29 (d, J = 11.6 Hz, 1 Н), 3.58 (s, 3 H), 3.53 (s, 3 Н).
HRMS (ESI): m/z [M + Na]+ calcd for C20H18ClNNaO4: 394.0822; found:
394.0819.
13C NMR (101 MHz, CDCl3): δ = 168.2, 167.8, 140.3, 137.8, 128.6 (2 C),
127.9 (2 C), 127.2, 126.4, 125.2, 124.9, 123.1, 120.6, 117.6, 112.1,
102.4, 57.9, 52.7, 52.5, 42.6.
Dimethyl 2-[(5-Bromo-1H-indol-3-yl)(phenyl)methyl]malonate
(11ja)
+
H]+ calcd for
Following the GP using indole 1j (98 mg, 0.5 mmol) and 3a (55 mg,
0.25 mmol) in CH2Cl2 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at r.t. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 67 mg (55%); mp 146–148 °C.
HRMS (MALDI, dithranol, PEG-300): m/z [M
21H19N2O4: 363.1267; found: 363.1345.
C
Dimethyl 2-[(4-Cyano-1H-indol-3-yl)(phenyl)methyl]malonate
(11ga)
1H NMR (400 MHz, CDCl3): δ = 8.12 (s, 1 H), 7.63 (d, J = 1.7 Hz, 1 H),
7.30–7.32 (m, 2 H), 7.24 (dt, J = 7.6, 0.6 Hz, 2 H), 7.12–7.21 (m, 4 H),
5.01 (d, J = 11.7 Hz, 1 H), 4.27 (d, J = 11.7 Hz, 1 H), 3.54 (s, 3 H), 3.51 (s,
3 H).
13C NMR (101 MHz, CDCl3): δ = 168.2, 167.9, 140.7, 134.8, 128.5 (2 C),
128.18 (2 C), 127.9, 127.0, 125.2, 122.1, 121.8, 116.4, 112.9, 112.5,
58.2, 52.7, 52.5, 42.5.
Following the GP using indole 1g (88 mg, 0.5 mmol) and 3a (55 mg,
0.25 mmol) in CH2Cl2 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at r.t. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 68 mg (72%); mp 171–172 °C.
1H NMR (400 MHz, CDCl3): δ = 9.16 (s, 1 H), 7.50–7.52 (m, 2 H), 7.46
(d, J = 7.6 Hz, 2 H), 7.37 (d, J = 7.3 Hz, 1 H), 7.22 (t, J = 7.5 Hz, 2 H),
7.08–7.16 (m, 2 H), 5.77 (d, J = 11.8 Hz, 1 H), 4.33 (d, J = 11.8 Hz, 1 H),
3.54 (s, 3 H), 3.49 (s, 3 H).
HRMS (ESI): m/z [M + Na]+ calcd for C20H18BrNNaO4: 438.0317; found:
438.0312.
13C NMR (101 MHz, CDCl3): δ = 168.2, 167.9, 140.5, 136.3, 128.6 (2 C),
128.3 (2 C), 126.9, 126.8, 125.6, 124.4, 121.5, 119.5, 116.4, 101.7, 59.1,
52.7, 52.4, 41.0 (one aromatic quaternary carbon atom was not un-
ambiguously assigned).
Dimethyl 2-[(5-Iodo-1H-indol-3-yl)(phenyl)methyl]malonate
(11ka)
Following the GP using indole 1k (122 mg, 0.5 mmol) and 3a (55 mg,
0.25 mmol) in CH2Cl2 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at r.t. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 59 mg (51%); mp 170–172 °C.
HRMS (MALDI, dithranol, PEG-300): m/z [M
21H19N2O4: 363.1267; found: 363.1245.
+
H]+ calcd for
C
Dimethyl 2-[(5-Fluoro-1H-indol-3-yl)(phenyl)methyl]malonate
(11ha)
1H NMR (400 MHz, CDCl3): δ = 8.12 (s, 1 H), 7.86 (d, J = 1.4 Hz, 1 H),
7.38 (dd, J = 8.5, 1.5 Hz, 1 H), 7.32 (d, J = 7.2 Hz, 2 H), 7.26 (t, J = 7.5 Hz,
2 H), 7.17 (t, J = 7.2 Hz, 1 H), 7.10 (s, 1 H), 7.07 (d, J = 8.5 Hz, 1 H), 5.01
(d, J = 11.8 Hz, 1 H), 4.27 (d, J = 11.8 Hz, 1 H), 3.56 (s, 3 H), 3.53 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 168.2, 168.0, 140.8, 135.2, 130.6,
129.1, 128.5 (2 C), 128.0 (2 C), 127.9, 127.0, 121.8, 116.1, 113.1, 83.1,
58.2, 52.7, 52.5, 42.45.
Following the GP using indole 1h (68 mg, 0.5 mmol) and 3a (55 mg,
0.25 mmol) in CH2Cl2 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at r.t. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 62 mg (70%); mp 164–166 °C.
1H NMR (400 MHz, CDCl3): δ = 8.08 (s, 1 H), 7.32 (d, J = 7.3 Hz, 2 H),
7.12–7.27 (m, 6 H), 6.87 (t, J = 8.3 Hz, 1 H), 5.01 (d, J = 12.3 Hz, 1 H),
4.29 (d, J = 12.3 Hz, 1 H), 3.57 (s, 3 H), 3.52 (s, 3 H).
HRMS (ESI): m/z [M + Na]+ calcd for C20H18INNaO4: 486.0178; found:
486.0174.
13C NMR (101 MHz, CDCl3): δ = 168.3, 168.0, 158.70 (d, J = 234.6 Hz),
140.8, 132.7, 128.5 (2 C), 128.0 (2 C), 127.0, 126.9, 122.5, 116.9 (d, J =
5.0 Hz), 111.7 (d, J = 9.5 Hz), 110.7 (d, J = 26.7 Hz), 104.2 (d, J = 24.0
Hz), 58.0, 52.7, 52.5, 42.8.
19F NMR (376 MHz, CDCl3): δ = –124.26 (dt, J = 9.8, 4.1 Hz, 1 F).
HRMS (ESI): m/z [M + Na]+ calcd for C20H18FNNaO4: 378.1118; found:
Dimethyl 2-[(6-Chloro-1H-indol-3-yl)(phenyl)methyl]malonate
(11la)
Following the GP using indole 1l (76 mg, 0.5 mmol) and 3a (55 mg,
0.25 mmol) in CH2Cl2 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at r.t. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 62 mg (67%); mp 146–147 °C.
378.1114.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–N

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M. N. Feofanov et al.
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Synthesis
1H NMR (400 MHz, CDCl3): δ = 8.13 (s, 1 H), 7.40 (d, J = 8.5 Hz, 1 H),
7.32 (d, J = 7.3 Hz, 2 H), 7.23–7.27 (m, 3 H), 7.17 (t, J = 7.1 Hz, 1 H),
7.12 (d, J = 2.0 Hz, 1 H), 6.99 (dd, J = 8.5, 1.7 Hz, 1 H), 5.06 (d, J = 11.8
Hz, 1 H), 4.30 (d, J = 11.8 Hz, 1 H), 3.56 (s, 3 H), 3.53 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 168.4, 168.2, 141.3, 134.1, 128.7,
128.3 (2 C), 128.0 (2 C), 126.7, 123.8, 120.9, 118.8, 116.1, 110.6, 58.2,
52.6, 52.4, 42.9, 21.5; (one aromatic quaternary carbon atom was not
unambiguously assigned).
13C NMR (101 MHz, CDCl3): δ = 168.4, 168.1, 140.8, 136.5, 128.5 (2 C),
128.2, 127.9 (2 C), 127.0, 125.1, 121.4, 120.3, 120.1, 116.9, 111.0, 58.0,
52.7, 52.5, 42.7.
HRMS (MALDI, dithranol, PEG-300): m/z [M]+ calcd for C21H21NO4:
351.1471; found: 351.1418.
HRMS (ESI): m/z [M + Na]+ calcd for C20H18ClNNaO4: 394.0822; found:
Dimethyl 2-{[5-(Benzyloxy)-1H-indol-3-yl](phenyl)meth-
yl}malonate (11pa)
394.0817.
Following the GP using indole 1p (112 mg, 0.5 mmol) and 3a (55 mg,
0.25 mmol) in CH2Cl2 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at –40 °C. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 94 mg (85%); mp 157–158 °C.
1H NMR (400 MHz, CDCl3): δ = 7.94 (s, 1 H), 7.44 (d, J = 7.0 Hz, 2 H),
7.28 (t, J = 7.2 Hz, 2 H), 7.32 (d, J = 8.3 Hz, 3 H), 7.23 (t, J = 7.4 Hz, 2 H),
7.15–7.18 (m, 2 H), 7.13 (d, J = 1.8 Hz, 1 H), 7.03 (d, J = 2.2 Hz, 1 H),
6.87 (dd, J = 8.8, 2.2 Hz, 1 H), 4.98–5.05 (m, 3 H), 4.30 (d, J = 11.8 Hz, 1
H), 3.56 (s, 3 H), 3.52 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 168.4, 168.2, 153.1, 141.1, 131.5,
128.5 (2 C), 128.4 (2 C), 128.0 (2 C), 127.7 (2 C), 127.6, 127.0, 126.8,
121.4, 116.6, 113.3, 111.7, 102.8, 100.0, 70.8, 58.0, 52.7, 52.5, 42.9.
HRMS (MALDI, dithranol, PEG-300): m/z [M]+ calcd for C27H25NO5:
443.173; found: 443.137.
Dimethyl 2-[(5-Methoxy-1H-indol-3-yl)(phenyl)methyl]malonate
(11ma)
Following the GP using indole 1m (73 mg, 0.5 mmol) and 3a (55 mg,
0.25 mmol) in CH2Cl2 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at –40 °C. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 73 mg (80%); mp 120–122 °C.
1H NMR (400 MHz, CDCl3): δ = 7.94 (s, 1 H), 7.32–7.34 (m, 2 H), 7.20–
7.24 (m, 2 H), 7.11–7.16 (m, 3 H), 6.91 (d, J = 2.3 Hz, 1 H), 6.78 (dd, J =
9.0, 2.4 Hz, 1 H), 5.03 (d, J = 11.8 Hz, 1 H), 5.01, 4.27 (d, J = 11.8 Hz, 1
H), 3.75 (s, 3 H), 3.55 (s, 3 H), 3.50 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 168.5, 168.2, 153.9, 141.1, 131.3,
128.4 (2 C), 128.1 (2 C), 127.0, 126.8, 121.53, 116.5, 112.5, 111.7,
101.1, 58.1, 55.7, 52.8, 52.5, 42.8.
HRMS (MALDI, dithranol, PEG-300): m/z [M]+ calcd for C21H21NO5:
367.1420; found: 367.1397.
Dimethyl 2-[(4-Methoxy-1H-indol-3-yl)(phenyl)methyl]malonate
(11qa)
Following the GP using indole 1q (73 mg, 0.5 mmol) and 3a (55 mg,
0.25 mmol) in CH2Cl2 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at –40 °C. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 79 mg (86%); mp 157–159 °C.
1H NMR (400 MHz, CDCl3): δ = 8.04 (s, 1 H), 7.32 (d, J = 7.4 Hz, 2 H),
7.21 (t, J = 7.2 Hz, 2 H), 7.09–7.13 (m, 2 H), 7.03 (t, J = 7.8 Hz, 1 H), 6.90
(d, J = 8.2 Hz, 1 H), 6.41 (d, J = 7.4 Hz, 1 H), 5.51 (d, J = 12.1 Hz, 1 H),
4.31 (d, J = 12.1 Hz, 1 H), 3.84 (s, 3 H), 3.58 (s, 3 H), 3.51 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 168.6, 168.5, 154.7, 142.2, 137.9,
128.6 (2 C), 127.9 (2 C), 126.3, 123.1, 119.3, 117.3, 116.8, 104.2, 99.7,
58.6, 54.8, 52.53, 52.3, 43.4.
HRMS (MALDI, dithranol, PEG-300): m/z [M]+ calcd for C21H21NO5:
367.1420; found: 367.1438.
Dimethyl 2-[(2-Methyl-1H-indol-3-yl)(phenyl)methyl]malonate
(11na)
Following the GP using indole 1n (66 mg, 0.5 mmol) and 3a (55 mg,
0.25 mmol) in CH2Cl2 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at –40 °C. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 76 mg (86%); mp 128–129 °C.
1H NMR (400 MHz, CDCl3): δ = 7.77 (s, 1 H), 7.63 (dd, J = 6.4, 2.5 Hz, 1
H), 7.35 (m, 2 H), 7.22–7.24 (m, 2 H), 7.16–7.20 (m, 1 H), 7.09–7.12
(m, 1 H), 7.00–7.06 (m, 2 H), 5.07 (d, J = 12.2 Hz, 1 H), 4.71 (d, J = 12.20
Hz, 1 H), 3.62 (s, 3 H), 3.37 (s, 3 H), 2.42 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 168.2, 168.3, 141.6, 135.2, 132.1,
128.4 (2 C), 127.3 (2 C), 127.1, 126.4, 120.8, 119.3, 118.9, 111.1, 110.4,
55.5, 52.6, 52.3, 42.3, 12.2.
HRMS (MALDI, dithranol, PEG-300): m/z [M]+ calcd for C21H21NO4:
351.1471; found: 367.1427.
Dimethyl 2-{[4-(Benzyloxy)-1H-indol-3-yl](phenyl)meth-
yl}malonate (11ra)
Following the GP using indole 1r (112 mg, 0.5 mmol) and 3a (55 mg,
0.25 mmol) in CH2Cl2 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at –40 °C. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 89 mg (80%); mp 180–181 °C.
1H NMR (400 MHz, CDCl3): δ = 8.07 (s, 1 H), 7.34–7.41 (m, 5 H), 7.07–
7.09 (m, 6 H), 6.98 (t, J = 7.98 Hz, 1 H), 6.89 (d, J = 8.08 Hz, 1 H), 6.43
(d, J = 7.58 Hz, 1 H), 5.58 (d, J = 12.1 Hz, 1 H), 5.21 (d, J = 11.9 Hz, 1 H),
5.19 (d, J = 11.9 Hz, 1 H), 4.29 (d, J = 12.1 Hz, 1 H), 3.57 (s, 3 H), 3.46 (s,
3 H).
Dimethyl 2-[(5-Methyl-1H-indol-3-yl)(phenyl)methyl]malonate
(11oa)
Following the GP using indole 1o (66 mg, 0.5 mmol) and 3a (55 mg,
0.25 mmol) in CH2Cl2 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at –40 °C. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 77 mg (88%); mp 145–146 °C.
1H NMR (400 MHz, CDCl3): δ = 7.94 (s, 1 H), 7.35 (d, 2 H), 7.31 (s, 1 H),
7.24 (t, J = 7.8 Hz, 2 H), 7.17 (t, J = 8.3 Hz, 2 H), 7.12 (s, 1 H), 6.96 (d, J =
8.1 Hz, 1 H), 5.07 (d, J = 11.9 Hz, 1 H), 4.29 (d, J = 11.9 Hz, 1 H), 3.55 (s,
3 H), 3.52 (s, 3 H), 2.38 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 168.0, 167.8, 153.0, 141.8, 137.8,
136.9, 128.1 (2 C), 127.9 (2 C), 127.4 (2 C), 127.3 (2 C), 127.2, 125.6,
121.9, 119.4, 116.26, 116.0, 104.3, 100.0, 69.3, 58.1, 51.9, 51.6, 42.7,
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–N

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M. N. Feofanov et al.
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Synthesis
HRMS (MALDI, dithranol, PEG-300): m/z [M]+ calcd for C27H25NO5:
Dimethyl 2-[(2-Fluorophenyl)(1H-indol-3-yl)methyl]malonate
443.173; found: 443.138.
(11af)
Following the GP using indole (1a, 58 mg, 0.5 mmol) and 3f (60 mg,
0.25 mmol) in CH2Cl2 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at –40 °C. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 62 mg (70%); mp 114–116 °C.
1H NMR (400 MHz, CDCl3): δ = 8.14 (s, 1 H), 7.62 (d, J = 8.0 Hz, 1 H),
7.34 (t, J = 7.5 Hz, 1 H), 7.26 (d, J = 8.0 Hz, 1 H), 6.95–7.15 (m, 6 H),
5.39 (d, J = 11.9 Hz, 1 H), 4.51 (d, J = 11.9 Hz, 1 H), 3.55 (s, 3 H), 3.52 (s,
3 H).
13C NMR (101 MHz, CDCl3): δ = 168.2, 168.0, 160.5 (d, J = 246.6 Hz),
135.9, 129.6 (d, J = 4.2 Hz), 128.4 (d, J = 8.4 Hz), 128.3, 126.3, 124.1 (d,
J = 3.4 Hz), 122.2, 121.3, 119.6, 118.7, 115.7 (d, J = 22.5 Hz), 115.3,
111.1, 56.6 (d, J = 1.5 Hz), 52.7, 52.6, 36.3 (d, J = 2.3 Hz).
Dimethyl 2-{(1H-Indol-3-yl)[4-(methoxycarbonyl)phenyl]meth-
yl}malonate (11ac)
Following the GP using indole (1a, 58 mg, 0.5 mmol) and 3c (70 mg,
0.25 mmol) in CH2Cl2 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at r.t. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 61 mg (62%); mp 156–157 °C.
1H NMR (400 MHz, CDCl3): δ = 8.44 (s, 1 H), 7.96 (d, J = 8.3 Hz, 2 H),
7.51 (d, J = 7.8 Hz, 1 H), 7.46 (d, J = 8.3 Hz, 2 H), 7.30 (d, J = 8.1 Hz, 1 H),
7.14–7.17 (m, 2 H), 7.08 (t, J = 7.5 Hz, 1 H), 5.21 (d, J = 11.6 Hz, 1 H),
4.40 (d, J = 11.6 Hz, 1 H), 3.89 (s, 3 H), 3.57 (s, 3 H), 3.56 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 168.1, 167.9, 166.8, 146.6, 136.2,
129.7 (2 C), 128.6, 128.1 (2 C), 126.2, 122.3, 121.0, 119.5, 118.9, 115.6,
111.2, 57.6, 52.7, 52.5, 52.1, 42.7.
19F NMR (376 MHz, CDCl3): δ = –116.50 (ddd, J = 11.9, 7.6, 5.6 Hz, 1 F).
HRMS (MALDI, dithranol, PEG-300): m/z [M]+ calcd for C20H18FNO4:
HRMS (MALDI, dithranol, PEG-300): m/z [M]+ calcd for C22H21NO6:
355.1220; found: 355.1178.
395.1314; found: 395.1422.
Dimethyl 2-[(3-Fluorophenyl)(1H-indol-3-yl)methyl]malonate
(11ag)
Dimethyl 2-{(1H-Indol-3-yl)[4-(trifluoromethyl)phenyl]meth-
yl}malonate (11ad)
Following the GP using indole (1a, 58 mg, 0.5 mmol) and 3g (60 mg,
0.25 mmol) in CH2Cl2 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at –40 °C. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 73 mg (82%); mp 140–141 °C.
1H NMR (400 MHz, CDCl3): δ = 8.13 (s, 1 H), 7.49 (d, J = 7.9 Hz, 1 H),
7.29 (d, J = 8.3 Hz, 1 H), 7.12–7.25 (m, 4 H), 7.00–7.06 (m, 2 H), 6.82–
6.86 (m, 1 H), 5.10 (d, J = 11.7 Hz, 1 H), 4.29 (d, J = 11.7 Hz, 1 H), 3.55
(s, 3 H), 3.55 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 168.2, 168.0, 162.7 (d, J = 245.9 Hz),
143.9 (d, J = 6.6 Hz), 136.2, 129.8 (d, J = 8.1 Hz), 126.4, 123.8 (d, J = 2.2
Hz), 122.4, 120.9, 119.6, 119.1, 116.1, 115.0 (d, J = 22.0 Hz), 113.8 (d,
J = 21.2 Hz), 111.1, 57.9, 52.7, 52.6, 42.5.
Following the GP using indole (1a, 58 mg, 0.5 mmol) and 3d (72 mg,
0.25 mmol) in CH2Cl2 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at r.t. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 77 mg (76%); mp 145–147 °C.
1H NMR (400 MHz, CDCl3): δ = 8.09 (s, 1 H), 7.47–7.51 (m, 5 H), 7.32
(d, J = 8.1 Hz, 1 H), 7.20 (d, J = 2.2 Hz, 1 H), 7.16 (t, J = 7.6 Hz, 1 H), 7.05
(t, J = 7.5 Hz, 1 H), 5.17 (d, J = 11.6 Hz, 1 H), 4.33 (d, J = 11.6 Hz, 1 H),
3.57 (s, 3 H), 3.55 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 168.1, 167.9, 145.4, 136.2, 128.83 (q,
J = 32.4 Hz), 128.4 (2 C), 126.2 (2 C), 125.4 (q, J = 3.6 Hz), 124.2 (q, J =
271.7 Hz), 122.5, 121.0, 119.7, 119.0, 115.8, 111.2, 57.6, 52.8, 52.6,
42.6.
19F NMR (376 MHz, CDCl3): δ = –112.98 (dt, J = 9.5, 6.0 Hz, 1 F).
HRMS (MALDI, dithranol, PEG-300): m/z [M]+ calcd for C20H18FNO4:
19F NMR (376 MHz, CDCl3): δ = –62.48 (s, 3 F).
HRMS (MALDI, dithranol, PEG-300): m/z [M]+ calcd for C21H18F3NO4:
355.1220; found: 355.1164.
405.1188; found: 405.1264.
Dimethyl 2-[(4-Fluorophenyl)(1H-indol-3-yl)methyl]malonate
(11ah)
Dimethyl 2-{[3,5-Bis(trifluoromethyl)phenyl](1H-indol-3-
yl)methyl}malonate (11ae)
Following the GP using indole (1a, 58 mg, 0.5 mmol) and 3h (60 mg,
0.25 mmol) in CH2Cl2 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at –40 °C. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 68 mg (76%); mp 183–185 °C.
1H NMR (400 MHz, CDCl3): δ = 8.03 (s, 1 H), 7.45 (d, J = 7.8 Hz, 1 H),
7.26–7.32 (m, 3 H), 7.13–7.18 (m, 2 H), 7.03 (t, J = 7.5 Hz, 1 H), 6.92 (t,
J = 5.6 Hz, 2 H), 5.09 (d, J = 11.8 Hz, 1 H), 4.26 (d, J = 11.8 Hz, 1 H), 3.57
(s, 3 H), 3.54 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 168.3, 168.1, 161.4 (d, J = 246.16 Hz),
136.6, 136.2, 129.6 (d, J = 7.59 Hz, 2 C), 126.4, 122.4, 120.7, 119.6,
119.2, 116.4, 115.2 (d, J = 21.05 Hz, 2 C), 111.1, 58.0, 52.7, 52.5, 42.13.
19F NMR (376 MHz, CDCl3): δ = –115.96 (tt, J = 8.5, 5.1 Hz, 1 F).
HRMS (MALDI, dithranol, PEG-300): m/z [M]+ calcd for C20H18FNO4:
Following the GP using indole (1a, 58 mg, 0.5 mmol) and 3e (89 mg,
0.25 mmol) in CH2Cl2 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at –40 °C. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 103 mg (87%); mp 155–156 °C.
1H NMR (400 MHz, CDCl3): δ = 8.16 (s, 1 H), 7.82 (s, 2 H), 7.70 (s, 1 H),
7.46 (d, J = 8.0 Hz, 1 H), 7.35 (d, J = 8.1 Hz, 1 H), 7.24 (d, J = 2.4 Hz, 1 H),
7.19 (dt, J = 7.5, 0.6 Hz, 1 H), 7.08 (t, J = 7.5 Hz, 1 H), 5.25 (d, J = 11.8
Hz, 1 H), 4.33 (d, J = 11.8 Hz, 1 H), 3.58 (s, 3 H), 3.57 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 167.7, 167.7, 143.9, 136.2, 131.7 (q, J =
32.9 Hz, 2 C), 128.7 (2 C), 126.0, 123.2 (q, J = 272.97 Hz, 2 C), 122.8,
121.3, 121.1–120.9 (m), 120.0, 118.6, 114.7, 111.4, 57.5, 52.9, 52.6,
42.3.
19 F NMR (376 MHz, CDCl3): δ = –62.82 (s, 6 F).
HRMS (MALDI, dithranol, PEG-300): m/z [M]+ calcd for C22H17F6NO4:
355.1220; found: 355.1138.
473.1062; found: 473.0981.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–N

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M. N. Feofanov et al.
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Synthesis
Dimethyl 2-[(2-Chlorophenyl)(1H-indol-3-yl)methyl]malonate
(11ai)
1H NMR (400 MHz, CDCl3): δ = 8.08 (s, 1 H), 7.68 (d, J = 8.0 Hz, 1 H),
7.54 (dd, J = 8.1, 1.2 Hz, 1 H), 7.36 (dd, J = 7.7, 1.67 Hz, 1 H), 7.29 (d, J =
8.0 Hz, 1 H), 7.18–7.22 (m, 2 H), 7.15 (dt, J = 7.5, 1.0 Hz, 1 H), 7.07 (dd,
J = 7.5, 1.0 Hz, 1 H), 7.02 (dd, J = 7.5, 1.8 Hz, 1 H), 5.67 (d, J = 11.5 Hz, 1
H), 4.40 (d, J = 11.5 Hz, 1 H), 3.57 (s, 3 H), 3.53 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 168.2, 167.8, 140.4, 136.0, 133.2,
128.9, 128.4, 127.5, 126.5, 124.8, 122.2, 121.90, 119.6 (2 C), 115.7,
111.0, 57.5, 52.6, 52.6, 41.2.
Following the GP using indole (1a, 58 mg, 0.5 mmol) and 3i (63 mg,
0.25 mmol) in CH2Cl2 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at –40 °C. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 85 mg (92%); mp 130–131 °C.
1H NMR (400 MHz, CDCl3): δ = 8.08 (s, 1 H), 7.65 (d, J = 8.1 Hz, 1 H),
7.35 (dt, J = 8.1, 1.5 Hz, 2 H), 7.29 (d, J = 8.1 Hz, 1 H), 7.04–7.19 (m, 5
H), 5.68 (d, J = 11.6 Hz, 1 H), 4.43 (d, J = 11.6 Hz, 1 H), 3.57 (s, 3 H),
3.54 (s, 3 H).
HRMS (MALDI, dithranol, PEG-300): m/z [M]+ calcd for C20H18BrNO4:
415.042; found: 415.020.
13C NMR (101 MHz, CDCl3): δ = 168.3, 167.9, 138.7, 135.9, 133.8,
129.9, 128.8, 127.9, 126.9, 126.4, 122.1, 121.8, 119.5, 119.2, 115.3,
111.1, 57.3, 52.6, 52.5, 38.5.
HRMS (MALDI, dithranol, PEG-300): m/z [M]+ calcd for C20H18ClNO4:
371.0924; found: 371.1007.
Dimethyl 2-[(3-Bromophenyl)(1H-indol-3-yl)methyl]malonate
(11am)
Following the GP using indole (1a, 58 mg, 0.5 mmol) and 3m (75 mg,
0.25 mmol) in CH2Cl2 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at –40 °C. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 91 mg (87%); mp 123–124 °C.
Dimethyl 2-[(3-Chlorophenyl)(1H-indol-3-yl)methyl]malonate
(11aj)
1H NMR (400 MHz, CDCl3): δ = 8.11 (s, 1 H), 7.47–7.51 (m, 2 H), 7.28–
7.32 (m, 3 H), 7.14–7.18 (m, 2 H), 7.11 (t, J = 7.9 Hz, 1 H), 7.06 (dt, J =
7.0, 1.0 Hz, 1 H), 5.07 (d, J = 11.7 Hz, 1 H), 4.27 (d, J = 11.7 Hz, 1 H),
3.57 (s, 3 H), 3.56 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 168.1, 168.0, 143.6, 136.1, 131.0,
130.0, 129.9, 126.8, 126.2, 122.4 (2 C), 121.0, 119.6, 119.0, 115.7,
111.2, 57.8, 52.7, 52.6, 42.3.
Following the GP using indole (1a, 58 mg, 0.5 mmol) and 3j (63 mg,
0.25 mmol) in CH2Cl2 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at –40 °C. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 69 mg (75%); mp 112–114 °C.
1H NMR (400 MHz, CDCl3): δ = 8.14 (s, 1 H), 7.52 (d, J = 7.8 Hz, 1 H),
7.28–7.34 (m, 3 H), 7.14–7.22 (m, 4 H), 7.08 (dt, J = 7.6, 1.0 Hz, 1 H),
5.11 (d, J = 11.9 Hz, 1 H), 4.31 (d, J = 11.9 Hz, 1 H), 3.59 (s, 3 H), 3.58 (s,
3 H).
HRMS (ESI): m/z [M]+ calcd for C20H18BrNO4: 415.0419; found:
415.0414.
13C NMR (101 MHz, CDCl3): δ = 168.2, 168.0, 143.3, 136.2, 134.1,
129.6, 128.1, 127.0, 126.3, 122.3, 120.9, 119.6, 119.0, 115.8, 111.2,
57.8, 52.7, 52.6, 42.4 (one aromatic quaternary carbon atom was not
unambiguously assigned).
HRMS (MALDI, dithranol, PEG-300): m/z [M]+ calcd for C20H18ClNO4:
371.0924; found: 371.0965.
Dimethyl 2-[(4-Bromophenyl) (1H-indol-3-yl)methyl]malonate
(11an)
Following the GP using indole (1a, 58 mg, 0.5 mmol) and 3n (75 mg,
0.25 mmol) in CH2Cl2 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at –40 °C. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 84 mg (81%); mp 135–137 °C.
Dimethyl 2-[(4-Chlorophenyl)(1H-indol-3-yl)methyl]malonate
(11ak)
1H NMR (400 MHz, CDCl3): δ = 8.06 (s, 1 H), 7.46 (d, J = 7.4 Hz, 1 H),
7.34–7.38 (m, 2 H), 7.31 (d, J = 8.2 Hz, 1 H), 7.21–7.26 (m, 2 H), 7.13–
7.17 (m, 2 H), 7.04 (dt, J = 8.0, 1.0 Hz, 1 H), 5.07 (d, J = 11.7 Hz, 1 H),
4.27 (d, J = 11.7 Hz, 1 H), 3.57 (s, 3 H), 3.56 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 168.1, 168.0, 140.2, 136.2, 131.5 (2 C),
129.8 (2 C), 126.3, 122.4, 120.8, 120.6, 119.5, 119.0, 116.0, 111.1, 57.7,
52.7, 52.5, 42.3.
Following the GP using indole (1a, 58 mg, 0.5 mmol) and 3k (63 mg,
0.25 mmol) in CH2Cl2 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at –40 °C. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 83 mg (90%); mp 148–149 °C.
1H NMR (400 MHz, CDCl3): δ = 8.09 (s, 1 H), 7.48 (d, J = 7.8 Hz, 1 H),
7.15–7.34 (m, 7 H), 7.06 (dt, J = 7.6, 1.0 Hz, 1 H), 5.10 (d, J = 11.9 Hz, 1
H), 4.30 (d, J = 11.6 Hz, 1 H), 3.59 (s, 3 H), 3.58 (s, 3 H).
HRMS (ESI): m/z [M]+ calcd for C20H18BrNO4: 415.0419; found:
415.0414.
13C NMR (101 MHz, CDCl3): δ = 168.2, 168.0, 139.8, 136.2, 132.5,
129.4 (2 C), 128.5 (2 C), 126.3, 122.4, 120.8, 119.6, 119.0, 116.1, 111.1,
57.9, 52.7, 52.6, 42.2.
HRMS (MALDI, dithranol, PEG-300): m/z [M]+ calcd for C20H18ClNO4:
371.0924; found: 371.0916.
Dimethyl 2-{(1H-Indol-3-yl)[4-(trifluoromethoxy)phenyl]meth-
yl}malonate (11ao)
Following the GP using indole (1a, 58 mg, 0.5 mmol) and 3o (76 mg,
0.25 mmol) in CH2Cl2 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at –40 °C. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 87 mg (83%); mp 180–181 °C.
Dimethyl 2-[(2-Bromophenyl)(1H-indol-3-yl)methyl]malonate
(11al)
1H NMR (400 MHz, CDCl3): δ = 8.17 (s, 1 H), 7.47 (d, J = 8.1 Hz, 1 H),
7.36 (d, J = 8.6 Hz, 2 H), 7.29 (d, J = 8.1 Hz, 1 H), 7.13–7.17 (m, 2 H),
7.02–7.09 (m, 3 H), 5.12 (d, J = 11.6 Hz, 1 H), 4.29 (d, J = 11.6 Hz, 1 H),
3.55 (s, 3 H), 3.52 (s, 3 H).
Following the GP using indole (1a, 58 mg, 0.5 mmol) and 3l (75 mg,
0.25 mmol) in CH2Cl2 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at –40 °C. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 71 mg (68%); mp 138–139 °C.
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M. N. Feofanov et al.
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13C NMR (101 MHz, CDCl3): δ = 168.2, 168.0, 147.9 (q, J = 1.9 Hz, 2 C),
140.0, 136.2, 129.5, 126.3, 122.5, 121.6, 120.8 (q, J = 0.8 Hz, 2 C), 120.3
(q, J = 256.9 Hz), 119.7, 119.1, 116.1, 111.2, 58.0, 52.7, 52.5, 42.2.
19F NMR (376 MHz, CDCl3): δ = –57.90 (s, 3 F).
HRMS (ESI): m/z [M]+ calcd for C21H18FNO5: 421.1137; found:
Dimethyl 2-[(1H-Indol-3-yl)(2-methoxyphenyl)methyl]malonate
(11as)
Following the GP using indole (1a, 58 mg, 0.5 mmol) and 3s (63 mg,
0.25 mmol) in CH2Cl2 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at –40 °C. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 56 mg (60%); mp 141–142 °C.
421.1132.
1H NMR (400 MHz, CDCl3): δ = 8.06 (s, 1 H), 7.67 (d, J = 7.7 Hz, 1 H),
7.30 (dd, J = 7.6, 1.4 Hz, 1 H), 7.26–7.28 (m, 1 H), 7.20 (d, J = 2.4 Hz, 1
H), 7.11–7.16 (m, 2 H), 7.04–7.08 (m, 1 H), 6.86 (d, J = 7.5 Hz, 1 H), 6.8
(d, J = 8.0 Hz, 1 H), 5.50 (d, J = 11.8 Hz, 1 H), 4.59 (d, J = 11.8 Hz, 1 H),
3.85 (s, 3 H), 3.53 (s, 3 H), 3.51 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 168.8, 168.5, 157.0, 135.8, 129.5,
128.9, 127.8, 126.9, 121.9, 121.7, 120.5, 119.3 (2 C), 116.3, 111.0,
110.9, 56.7, 55.5, 52.5, 52.3, 36.6.
Dimethyl 2-{(1H-Indol-3-yl)[4-(methylthio)phenyl]meth-
yl}malonate (11ap)
Following the GP using indole (1a, 58 mg, 0.5 mmol) and 3p (67 mg,
0.25 mmol) in CH2Cl2 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at –40 °C. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 78 mg (81%); mp 142–144 °C.
1H NMR (400 MHz, CDCl3): δ = 8.07 (s, 1 H), 7.51 (d, J = 7.8 Hz, 1 H),
7.28–7.33 (m, 3 H), 7.13–7.18 (m, 4 H), 7.05 (dt, J = 7.1, 0.8 Hz, 1 H),
5.09 (d, J = 11.8 Hz, 1 H), 4.30 (d, J = 11.9 Hz, 1 H), 3.58 (s, 3 H), 3.57 (s,
3 H), 2.43 (s, 3 H).
HRMS (MALDI, dithranol, PEG-300): m/z [M]+ calcd for C21H21NO5:
367.1420; found: 367.1428.
Dimethyl 2-[(1H-Indol-3-yl)(4-methoxyphenyl)methyl]malonate
(11at)
13C NMR (101 MHz, CDCl3): δ = 168.3, 168.1, 138.2, 136.6, 136.2,
128.5 (2 C), 126.6 (2 C), 126.4, 122.2, 120.8, 119.5, 119.2, 116.4, 111.1,
58.0, 52.5, 52.5, 42.3, 15.7.
HRMS (ESI): m/z [M]+ calcd for C21H21NO4S: 383.1191; found:
383.1184.
Following the GP using indole (1a, 58 mg, 0.5 mmol) and 3t (63 mg,
0.25 mmol) in CH2Cl2 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at –40 °C. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 47 mg (51%); mp 141–142 °C.
1H NMR (400 MHz, CDCl3): δ = 8.05 (s, 1 H), 7.49 (d, J = 7.8 Hz, 1 H),
7.24–7.30 (m, 3 H), 7.11–7.14 (m, 2 H), 7.02 (t, J = 7.7 Hz, 1 H), 6.77 (d,
J = 8.6 Hz, 2 H), 5.05 (d, J = 11.8 Hz, 1 H), 4.27 (d, J = 11.8 Hz, 1 H), 3.73
(s, 3 H), 3.56 (s, 3 H), 3.54 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 168.5, 168.2, 158.2, 136.2, 133.2,
129.0 (2 C), 126.5, 122.2, 120.6, 119.4, 119.3, 116.9, 113.6 (2 C), 111.0,
58.2, 55.2, 52.6, 52.5, 42.0.
HRMS (MALDI, dithranol, PEG-300): m/z [M]+ calcd for C21H21NO5:
367.1420; found: 367.1397.
Dimethyl 2-[(1H-Indol-3-yl)(o-tolyl)methyl]malonate (11aq)
Following the GP using indole (1a, 58 mg, 0.5 mmol) and 3q (59 mg,
0.25 mmol) in CH2Cl2 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at –40 °C. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 55 mg (62%); mp 116–120 °C.
1H NMR (400 MHz, CDCl3): δ = 8.12 (s, 1 H), 7.61 (d, J = 7.8 Hz, 1 H),
7.36 (d, J = 7.6 Hz, 1 H), 7.27 (d, J = 7.6 Hz, 1 H), 7.06–7.18 (m, 5 H),
6.97 (s, 1 H), 5.36 (d, J = 11.8 Hz, 1 H), 4.41 (d, J = 11.8 Hz, 1 H), 3.55 (s,
3 H), 3.46 (s, 3 H), 2.48 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 168.7, 168.3, 139.9, 136.2, 135.9,
130.8, 126.5, 126.5, 126.0, 126.0, 122.3, 121.9, 119.5, 119.1, 116.1,
111.1, 58.2, 52.5, 52.4, 38.0, 19.8.
HRMS (MALDI, dithranol, PEG-300): m/z [M]+ calcd for C21H21NO4:
351.1471; found: 351.1446.
Dimethyl 2-[(1H-Indol-3-yl)(thiophen-2-yl)methyl]malonate
(11au)
Following the GP using indole (1a, 58 mg, 0.5 mmol) and 3u (57 mg,
0.25 mmol) in CH2Cl2 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at –40 °C. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 77 mg (90%); mp 136–138 °C.
1H NMR (400 MHz, CDCl3): δ = 8.12 (s, 1 H), 7.60 (d, J = 7.8 Hz, 1 H),
7.31 (d, J = 8.3 Hz, 1 H), 7.17 (t, J = 7.3 Hz, 2 H), 7.06–7.10 (m, 2 H),
6.98 (d, J = 3.0 Hz, 1 H), 6.87 (t, J = 4.4 Hz, 1 H), 5.42 (d, J = 11.6 Hz, 1
H), 4.35 (d, J = 11.6 Hz, 1 H), 3.66 (s, 3 H), 3.50 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 168.1, 167.8, 145.5, 136.1, 126.5,
126.2, 125.1, 124.4, 122.3, 121.4, 119.7, 119.2, 116.3, 111.1, 59.1, 52.7,
52.6, 37.9.
HRMS (ESI): m/z [M]+ calcd for C18H17NO4S: 343.0878; found:
343.0873.
Dimethyl 2-[(4-Ethylphenyl)(1H-indol-3-yl)methyl]malonate
(11ar)
Following the GP using indole (1a, 58 mg, 0.5 mmol) and 3r (62 mg,
0.25 mmol) in CH2Cl2 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at –40 °C. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 55 mg (60%); mp 116–120 °C.
1H NMR (400 MHz, CDCl3): δ = 8.16 (s, 1 H), 7.59 (d, J = 7.8 Hz, 1 H),
7.30 (m, 3 H), 7.05–7.18 (m, 5 H), 5.12 (d, J = 11.9 Hz, 1 H), 4.37 (d, J =
11.9 Hz, 1 H), 3.57 (s, 6 H), 2.59 (q, J = 7.6 Hz, 2 H), 1.20 (t, J = 7.6 Hz, 3
H).
13C NMR (101 MHz, CDCl3): δ = 168.5, 168.3, 142.5, 138.3, 136.2,
127.8 (4 C), 126.5, 122.1, 120.8, 119.4, 119.3, 116.8, 111.0, 58.2, 52.6,
52.4, 42.5, 28.4, 15.2.
HRMS (MALDI, dithranol, PEG-300): m/z [M]+ calcd for C22H23NO4:
365.1627; found: 365.1575.
Dimethyl 2-[Phenyl(1H-pyrrol-2-yl)methyl]malonate (18)
Following the GP using pyrrole (15, 33 mg, 0.5 mmol) and 3a (55 mg,
0.25 mmol) in CH2Cl2 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at –40 °C. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 59 mg (82%); mp 112–114 °C.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–N

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M. N. Feofanov et al.
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1H NMR (400 MHz, CDCl3): δ = 8.39 (s, 1 H), 7.21–7.32 (m, 5 H), 6.66
(dd, J = 2.7, 1.6 Hz, 1 H), 6.09 (q, J = 2.9, 1.7 Hz, 1 H), 5.95–5.97 (m, 1
H), 4.81 (d, J = 10.74 Hz, 1 H), 4.20 (d, J = 10.74 Hz, 1 H), 3.70 (s, 3 H),
3.48 (s, 3 H).
1H NMR (400 MHz, CDCl3): δ = 8.28 (s, 1 Н), 7.49 (d, J = 2.5 Hz, 1 Н),
7.30–7.38 (m, 6 Н), 7.11 (t, J = 7.6 Hz, 1 Н), 6.87 (t, J = 7.6 Hz, 1 Н), 6.77
(d, J = 8.21 Hz, 1 Н), 5.66 (d, J = 13.6 Hz, 1 Н), 5.45 (d, J = 13.6 Hz, 1 Н),
4.20–4.33 (m, 2 Н), 1.21 (t, J = 7.07 Hz, 3 Н).
13C NMR (101 MHz, CDCl3): δ = 169.0, 167.8, 139.6, 130.8, 128.6 (2 C),
128.1 (2 C), 127.3, 117.6, 108.1, 106.4, 57.7, 52.9, 52.5, 44.3.
HRMS (ESI): m/z [M + H]+ calcd for C16H18NO4: 288.1236; found:
288.1231.
13C NMR (101 MHz, CDCl3): δ = 170.7, 137.8, 136.4, 128.2 (2 C), 127.7
(2 C), 127.7, 125.1, 124.9, 121.5, 120.2, 119.1, 111.4, 80.6, 61.8, 54.5,
13.6; (one aromatic quaternary carbon atom was not unambiguously
assigned).
3-(2-Nitro-1-phenylethyl)-1H-indole (29)33
Methyl 4-(1H-Indol-3-yl)-2-oxochromane-3-carboxylate (12)
Following the GP using indole (1a, 58 mg, 0.5 mmol) and 7 (37 mg,
0.25 mmol) in CHCl3 using Ca(NTf2)2 (15 mg, 0.025 mmol) as the cata-
lyst at –30 °C. After purification by gradient column chromatography
(CH2Cl2/PE, 1:1, then CH2Cl2/PE, 3:1), the product was obtained as a
grey solid; yield: 59 mg (90%).
Following the GP using indole (1a, 58 mg, 0.5 mmol) and 4 (51 mg,
0.25 mmol) in CHCl3 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at r.t. After purification by column chromatography (CH2Cl2), the
product was obtained as a white solid; yield: 68 mg (85%); mp 180–
182 °C.
1H NMR (400 MHz, CDCl3): δ = 8.07 (s, 1 Н), 7.47 (d, J = 8.0 Hz, 1 Н),
7.20–7.35 (m, 6 Н), 7.22 (t, J = 7.5 Hz, 1 H), 7.08 (t, J = 7.5 Hz, 1 Н), 6.99
(d, J = 1.8 Hz, 1 Н), 5.20 (t, J = 8.2 Hz, 1 Н), 5.07 (dd, J = 12.5, 8.2 Hz, 1
Н), 4.95 (dd, J = 12.5, 8.2 Hz, 1 Н).
13C NMR (101 MHz, CDCl3): δ = 139.1, 136.4, 128.9 (2 C), 127.7 (2 C),
127.50, 126.0, 122.6, 121.6, 119.9, 118.8, 114.3, 111.4, 76.7, 41.5.
1H NMR (400 MHz, CDCl3): δ = 8.28 (s, 1 Н), 7.49 (d, J = 8.0 Hz, 1 Н),
7.40 (d, J = 8.3 Hz, 1 Н), 7.31–7.35 (m, 1 Н), 7.21–7.25 (m, 1 Н), 7.08–
7.18 (m, 4 Н), 6.83 (s, 1 Н), 5.05 (d, J = 7.1 Hz, 1 Н), 4.23 (d, J = 7.1 Hz, 1
Н), 3.65 (s, 3 Н).
13C NMR (101 MHz, CDCl3): δ = 167.6, 164.6, 136.7, 129.0, 128.9,
125.3, 125.1, 123.7, 123.2, 122.6, 119.9, 118.6, 116.9, 112.8, 111.7,
53.0, 36.4, 25.8. (one aromatic quaternary carbon atom was not un-
ambiguously assigned).
Methyl 3-(1H-Indol-3-yl)-2-nitro-3-phenylpropanoate (30)
HRMS (MALDI, dithranol, PEG-300): m/z [M]+ calcd for C19H15NO4:
321.0933; found: 321.1001.
Following the GP using indole (1a, 58 mg, 0.5 mmol) and 8 (52 mg,
0.25 mmol) in CHCl3 using Ca(NTf2)2 (15 mg, 0.025 mmol) as the cata-
lyst at –30 °C. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 64 mg (78%); mp 70–74 °C.
1H NMR (400 MHz, CDCl3): δ (1:1 diastereomers) = 8.15 (s, 1 Н), 8.11
(s, 1 Н), 7.59 (d, J = 7.7 Hz, 1 Н), 7.47 (d, J = 7.8 Hz, 1 Н), 7.04–7.48 (m,
18 Н), 5.95 (d, J = 11.0 Hz, 1 Н), 5.92 (d, J = 11.0 Hz, 1 Н), 5.39 (d, J =
11.0 Hz, 1 Н), 5.38 (d, J = 11.0 Hz, 1 Н), 3.57 (s, 3 Н), 3.54 (s, 3 Н).
13C NMR (101 MHz, CDCl3): δ (1:1 diastereomers) = 163.81 (2 C),
138.4, 137.3, 136.2, 136.0, 128.9 (2 C), 128.8 (2 C), 128.4 (2 C), 127.8,
127.7 (3 C), 126.1, 122.7, 121.7, 120.6, 120.0, 119.9, 118.9, 118.8,
113.7, 112.8, 111.7 (2 C), 91.6, 91.5, 53.6, 53.4, 44.5, 43.8.
4-(1H-Indol-3-yl)butan-2-one (26)30
Following the GP using indole (1a, 58 mg, 0.5 mmol) and 5a (18 mg,
0.25 mmol) in CHCl3 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at r.t. After purification by column chromatography (CH2Cl2), the
product was obtained as a white solid; yield: 35 mg (75%).
1H NMR (400 MHz, CDCl3): δ = 7.98 (s, 1 Н), 7.60 (d, J = 8.0 Hz, 1 Н),
7.36 (d, J = 8.1 Hz, 1 Н), 7.18–7.22 (m, 1 Н), 7.11–7.15 (m, 1 Н), 6.98
(d, J = 1.9 Hz, 1 Н), 3.06 (t, J = 7.6 Hz, 2 Н), 2.86 (t, J = 7.5 Hz, 2 Н), 2.15
(s, 3 Н).
13C NMR (101 MHz, CDCl3): δ = 208.8, 136.3, 127.1, 122.0, 121.4,
119.3, 118.6, 115.1, 111.1, 44.1, 30.0, 19.3.
HRMS (ESI): m/z [M – H]+ calcd for C18H15N2O4: 323.1032; found:
323.1037.
1,1,1-Trifluoro-4-(1H-indol-3-yl)-4-phenylbutan-2-one (27)31
4-(1H-Indol-3-yl)-3-nitrochroman-2-one (31)
Following the GP using indole (1a, 58 mg, 0.5 mmol) and 5b (50 mg,
0.25 mmol) in CHCl3 using MgI2 (6.9 mg, 0.025 mmol) as the catalyst
at r.t. After purification by column chromatography (CH2Cl2), the
product was obtained as a white solid; yield: 60 mg (76%).
1H NMR (400 MHz, CDCl3): δ = 7.99 (s, 1 Н), 7.40 (d, J = 8.0 Hz, 1 Н),
7.23–7.33 (m, 5 Н), 7.13–7.19 (m, 2 Н), 7.02 (t, J = 7.9 Hz, 1 Н), 6.95 (d,
J = 2.2 Hz, 1 Н), 4.91 (t, J = 7.9 Hz, 1 Н), 3.56 (dd, J = 18.5, 7.9 Hz, 1 Н),
3.45 (dd, J = 18.5, 7.9 Hz, 1 Н).
Following the GP using indole (1a, 58 mg, 0.5 mmol) and 9 (47 mg,
0.25 mmol) in CHCl3 using Ca(NTf2)2 (15 mg, 0.025 mmol) as the cata-
lyst at –30 °C. After purification by column chromatography (CH2Cl2),
the product was obtained as a white solid; yield: 42 mg (55%); mp
90–92 °C.
1H NMR (400 MHz, CDCl3): δ = 8.25 (s, 1 Н), 7.36–7.42 (m, 2 Н), 7.32
(d, J = 8.2 Hz, 1 Н), 7.20–7.27 (m, 2 Н), 7.07–7.14 (m, 3 Н), 7.00 (d, J =
2.7 Hz, 1 Н), 5.82 (d, J = 9.8 Hz, 1 Н), 5.37 (d, J = 9.8 Hz, 1 Н).
19F NMR (376 MHz, CDCl3): δ = –79.36 (s, 3 F).
13C NMR (101 MHz, CDCl3): δ = 159.2, 149.8, 136.8, 129.9, 129.1,
125.9, 124.6, 124.6, 123.1, 120.9, 120.5, 118.6, 117.2, 112.0, 108.5,
86.3, 39.0.
Ethyl 2-(1H-Indol-3-yl)-3-nitro-2-phenylpropanoate (28)32
Following the GP using indole (1a, 58 mg, 0.5 mmol) and 6 (55 mg,
0.25 mmol) in CHCl3 using Ca(NTf2)2 (15 mg, 0.025 mmol) as the cata-
lyst at r.t. After purification by gradient column chromatography
(CH2Cl2/PE, 4:1, then CH2Cl2), the product was obtained as a white
solid; yield: 76 mg (90%).
HRMS (ESI): m/z [M – H]+ calcd for C17H11N2O4: 307.0719; found:
307.0723.
Funding Information
This work was financially supported by the RSF grant 14-23-00186.
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–N

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M. N. Feofanov et al.
Paper
Synthesis
Supporting Information
(14) (a) Palomo, C.; Pazos, R.; Oiarbide, M.; Garcia, J. M. Adv. Synth.
Catal. 2006, 348, 1161. (b) Vázquez, J.; Prieto, A.; Fernández, R.;
Enders, D.; Lassaletta, J. M. Chem. Commun. 2002, 498. (c) van
Lingen, H. L.; Zhuang, W.; Hansen, T.; Rutjes, F. P. J. T.; Jorgensen,
K. A. Org. Biomol. Chem. 2003, 1, 1953. (d) Wales, S. M.; Walker,
M. M.; Johnson, J. S. Org. Lett. 2013, 15, 2558.
(15) Catalytic Asymmetric Friedel–Crafts Alkylations; Bandini, M.;
Umani-Ronchi, A., Eds.; Wiley–VCH: Weinheim, 2009.
(16) (a) Beletskaya, I.; Tarasenko, E. Synthesis 2017, 49, 1689.
(b) Beletskaya, I. P.; Averin, A. D. Curr. Organocatal. 2015, 3, 60.
(c) Desyatkin, V. G.; Anokhin, M. V.; Rodionov, V. O.; Beletskaya,
I. P. Russ. J. Org. Chem. 2016, 52, 1719.
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1589068.
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