Visible Light Mediated Organocatalytic Activation of Ethyl Bromofluoroacetate: Coupling with Indoles and Anilines

Article abstract of DOI:10.1021/acs.joc.5b01736

The activation of ethyl bromofluoroacetate employing a visible light mediated, Eosin Y catalyzed photoredox transformation is reported. Using indoles and anilines as nucleophiles, the reaction leads to the formation of two C _sp²-C _sp³ bonds resulting in an efficient synthesis of bisindolyl and bisanilinoyl acetate derivatives. Application of this method to the direct synthesis of unsymmetrical diarylacetates featuring indoles and N-substituted anilines was also demonstrated.

Full text of DOI:10.1021/acs.joc.5b01736

Subscriber access provided by CMU Libraries - http://library.cmich.edu
Article
Visible Light Mediated Organocatalytic Activation of Ethyl
Bromofluoroacetate: Coupling with Indoles and Anilines
Santosh D Jadhav, Debanjan Bakshi, and Anand Singh
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 22 Sep 2015
Downloaded from http://pubs.acs.org on September 24, 2015
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
The Journal of Organic Chemistry is published by the American Chemical Society.
1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 27
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Visible Light Mediated Organocatalytic Activation
of Ethyl Bromofluoroacetate: Coupling with Indoles
and Anilines
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Santosh D. Jadhav, Debanjan Bakshi, and Anand Singh*
Department of Chemistry, Indian Institute of Technology Kanpur, Kanpurꢀ208016, India
email: anands@iitk.ac.in
KEYWORDS
Photocatalysis; Visible light; Radical Reactions; FreidelꢀCraft Alkylation; CarbonꢀCarbon Bond
Formation
ABSTRACT
The activation of ethyl bromofluoroacetate employing a visible light mediated, Eosin Y
catalysed photoredox transformation is reported. Using indoles and anilines as nucleophiles, the
reaction leads to the formation of two Csp
2
ꢀCsp bonds resulting in an efficient synthesis of
3
bisindolyl and bisanilinoyl acetate derivatives. Application of this method to the direct synthesis
of unsymmetrical diarylacetates featuring indoles and Nꢀsubstituted anilines was also
demonstrated.
ACS Paragon Plus Environment
1

The Journal of Organic Chemistry
Page 2 of 27
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
O
R
R
CO Et
R
2
O
N
H
Br
Br
N
H
CO Et
2
HO
O
OH
HN
NH
NHR
O
Br
Br
F
(Eosin Y)
OEt
CO2Et
i
i
HN
Pr NEt, DMF, rt
visible light
Eosin Y
Pr NEt, DMF, rt
visible light
2
2
NHR
Br
NHR
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
RHN
NHR
INTRODUCTION
The formation of carbonꢀcarbon bonds is a process of fundamental importance in organic
synthesis. There exists a wide array of elegant transformations that result in the formation of CꢀC
bonds but the quest continues for newer methods that offer advantages of improved selectivity,
milder conditions, environmental sustainability, and convenient access to starting materials. One
of the current challenges in this area is the development of catalytic processes, especially those
which do not rely on metals. Herein, we report the activation of CꢀBr and CꢀF bonds in ethyl
bromofluoroacetate initiated by an organoꢀphotocatalytic manifold employing visible light as the
1
energy source. This strategy represents a mild route toward bisindolylmethane derivatives which
2
are of interest due to their biological activities (Scheme 1) and also provides a convenient
3
synthesis for bisanilinoyl acetate derivatives that are otherwise difficult to access. Wu and
coworkers have recently published an elegant double FridelꢀCrafts alkylation of glycine
derivatives for the synthesis of bisindolylacetates employing CꢀN and CꢀH activation (Scheme
4
1
). Our strategy utilizes the commercially available and inexpensive ethylbromofluoroacetate to
construct Csp
2
ꢀCsp
3
bonds, via the activation of the CꢀBr and CꢀF bonds.
ACS Paragon Plus Environment
2

Page 3 of 27
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Scheme 1. Activation of C-Br and C-F Bonds in Ethyl bromofluoroacetate.
Wu et. al.
CO Et
2
O
H
N
TBPA+ SbCl6
R
Ar
X
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
N
HN
NH
H
H
1
3
This work
CO Et
2
N
H
O
HN
NH
O
Br
HO
Br
CO Et
2
O
OH
O
Br
Br
NHR
F
(
i
Eosin Y)
OEt
Pr NEt
green LED's
2
2
RHN
NHR
Br
CO Et
2
N
H
HN
NHR
NHR
Examples of bioactive bis-indolylmethane derivatives
CF3
HN
HN
NH
AcO
NH
HN
HN
NH
genotoxic agent
inhibition of renal cell
carcinoma
inhibition of lung cancer
cell growth
RESULTS AND DISCUSSION
Our initial studies (Table 1a) focused on employing ethylbromofluoroacetate as a
radical precursor which would react with nuleophiles such as arenes. Preliminary experiments
revealed that Eosin Y as a catalyst provided clean conversion to product (3), albeit with low
5
yield. While only one product was being formed, 2 was being completely consumed, and hence
ACS Paragon Plus Environment
3

The Journal of Organic Chemistry
Page 4 of 27
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
i
6
we reasoned that the radical generated from 2 might be getting reduced by the amine ( Pr NEt)
2
and hence the amount of ethyl bromofluoroacetate was increased. Under these conditions, 3 was
obtained as the sole product in high yield. Dimethylformamide (DMF) was found to be the ideal
solvent and it was observed that dimethylsulfoxide (DMSO) afforded diminished yields while no
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
product was obtained with acetonitrile (CH CN). Under the optimized conditions, only 2.5 mol%
3
of Eosin Y was necessary to afford the product efficiently. A comparative study into the
applicability of ethyl dibromoacetate and ethyl chlorofluoroacetate revealed that only ethyl
bromofluoroacetate could be activated by photocatalysis (Table 1b). The C3 substitution on
indole was established by NMR studies and further confirmed by Xꢀray diffraction of a single
crystal that was obtained for 7. The C3ꢀalkylation is an interesting contrast to the reported C2
6
selectivity provided by the malonyl radical.
Table 1. Preliminary Experiments and Reaction Optimization
Key control experiments were performed to establish that both visible light and catalyst are
necessary for the reaction, and that simply heating indole with 2 did not afford any product
(
Scheme 2). A test reaction in the presence of (2,2,6,6ꢀtetramethylpiperidinꢀ1ꢀyl)oxidanyl
ACS Paragon Plus Environment
4

Page 5 of 27
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
(
TEMPO) did not afford any bisindole product, indicating the involvement of a radical
mechanism.
Scheme 2. Control Experiments
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
This protocol for generating bisꢀindolyl acetates represents a milder alternative to the currently
7
8
known acid and metal mediated methods. Table 2 shows the derivatives that were synthesized
using the optimized procedure. Electron rich aromatics were found to be suitable substrates for
this reaction. Various substituted indoles and anilines afforded the corresponding diarylacetate
products efficiently. Free indole (NꢀH), Nꢀmethylindole and 2ꢀmethylindole reacted smoothly,
and a variety of substitutions on the carbocyclic ring of indole were tolerated well. It was
discovered that 3ꢀsubstituted indoles did not react under these conditions. Nꢀsubstituted anilines
(monoꢀ, and diꢀsubstituted) exhibited Cꢀalkylation at the 4ꢀposition to afford products in good
yields. The applicability of precursors with pendant olefin and acetylene as functionalities was
also possible (products 15, 16, 17, Table 2). While the N,Nꢀdimethylaniline derivative 18 was
obtained in low yield (probably due to the propensity of such tertiary amines to engage in
9
electron transfer) , the fluoro substituted derivative provided the product 20 in good yield. Nꢀ
Benzylꢀ1ꢀnaphthylamine also provided the product in good yield (22) but pyrrole afforded the
1
0
bisꢀcompound 23 in only 30% yield (a trisꢀpyrrole product was isolated in 65% yield). While
ACS Paragon Plus Environment
5

The Journal of Organic Chemistry
Page 6 of 27
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
our method works well for Nꢀsubstituted anilines, free anilines do not afford the desired product.
Such bisꢀaniline derivatives represent a less explored chemical space, presumably due to the
paucity of methods available to synthesize them, and this photocatalytic route fills a key gap in
this area by offering a convenient route to these molecules.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Table 2. Scope of the Reaction
Mechanistic possibilities for this reaction are outlined in Scheme 3, and although we have not
obtained direct evidence to support the existence of key intermediates, the analysis is based on
1
1
the products formed and related information available in the literature. We propose that the
ACS Paragon Plus Environment
6

Page 7 of 27
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
reaction proceeds via the generation of the ethyl αꢀfluoroacetate radical which is formed by a
single electron transfer from the Eosin Y radical anion to 2. The intermediacy of the Eosin Y
radical anion has been postulated previously for reactions that contain an electron rich species,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
5,9,12
including amines.
The fluoroacetate radical is then intercepted by the indole motif via the C3
carbon, leading to the formation of 24 which on subsequent oxidation will provide the αꢀ
fluoroindole derivative 25. This oxidation can be brought about by the diisopropylethylamine
1
3
radical cation, Eosin Y*, or by 2 in a radicalꢀchain propagating manner. While compound 25 is
1
4
not known in the literature, the instability of analogous bromo derivatives and a related difluoro
15
compound indicate that CꢀX bonds benzylic to the indole motif are very reactive (and the
reactivity is expected to increase if an additional electron withdrawing group is present at the αꢀ
carbon). Hence, we postulate that the CꢀF bond in compound 25 is weakened (compared to other
ArꢀF and RꢀF bonds) due to the presence of the ester and indole moeities at the αꢀcarbon. In this
scenario, 25 can react either by generating the intermediate 26 via a baseꢀmediated extrusion of
fluoride, or by generating the radical intermediate 27 via photocatalysis. Both 26 and 27 can lead
to the observed products, and in the absence of any additional proof, it is not possible to ascertain
which pathway is operative for the second arylation.
ACS Paragon Plus Environment
7

The Journal of Organic Chemistry
Page 8 of 27
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Scheme 3. Plausible Reaction Pathways for the Formation of 3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
The installation of two different aryl groups using this reaction would be desirable because
accessing such unsymmetrical diarylated compounds without employing prefunctionalized
3
,16
substrates is a significant synthetic challenge.
As shown in Table 3, this method can be used
to synthesize unsymmetrical diarylacetates featuring indoles and anilines, albeit in moderate
yields owing to the inherent limitation on selectivity. While unsymmetrical bisꢀindole derivatives
29, 31, and 32 were obtained in low yields, subtle reactivity differences increase the yield of the
unsymmetrical diaryl product, as observed for compound 30. It was discovered that the
unsymmetrical indoleꢀaniline diaryl derivatives 33ꢀ40 could be accessed in improved yields (43ꢀ
74%). A variety of Nꢀsubstituted anilines underwent the reaction smoothly and as observed
before, the alkynyl (compound 33, Table 3) and allyl substituents (products 39 and 40) were
ACS Paragon Plus Environment
8

Page 9 of 27
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
tolerated well. Free anilines are not compatible in this reaction but the applicability of Nꢀ
benzylanilines (products 34 and 38) can provide a route to diarylacetates with a free aniline
moeity, if so desired. Although not a high yielding process, this method does offer rapid access
to these molecules without the need to prefunctionalize the substrates, and can be potentially
useful at the discovery stage.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ACS Paragon Plus Environment
9

The Journal of Organic Chemistry
Page 10 of 27
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Table 3. Synthesis of Unsymmetrical Diarylacetates
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
CONCLUSION
In summary, we have developed a visible light mediated method for the synthesis of bisindolyl
and bisanilinoyl acetate derivatives by activating ethyl bromofluoroacetate using Eosin Y as the
ACS Paragon Plus Environment
10

Page 11 of 27
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
photocatalyst. The reaction occurs under mild conditions and represents a convenient and
transition metal free method to construct C ꢀCsp3 bonds resulting in α,αꢀdiarylated acetate
sp2
derivatives. This method can also be applied to the direct synthesis of unsymmetrical
diarylacetates (indoleꢀindole, and indoleꢀaniline) in moderate yields. Explorations into
employing this method to establish a general route toward unsymmetrical diarylacetates are
underway.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
EXPERIMENTAL SECTION
General Information
All reactions were carried out under argon atmosphere with dry solvents under anhydrous
conditions. Reagents were purchased at the highest commercial quality and used without further
purification, unless otherwise stated. Yields refer to chromatographically pure material. Reaction
were monitored by thinꢀlayer chromatography (TLC) carried out on 0.25 mm Merck silica gel
plates (60Fꢀ254) using UV light as a visualizing agent and pꢀanisaldehyde or KMnO stain, and
4
heat as developing agents. Merck silica gel (particle size 100ꢀ200 and 230ꢀ400 mesh) was used
for flash column chromatography.
1
13
1
13
NMR spectra were recorded on 500 ( H: 500 MHz, C: 125 MHz) or 400 ( H: 400 MHz, C:
00 MHz) NMR spectrometers in CDCl having TMS 0.03% as internal standard. Mass
1
3
spectrometric data were obtained using QꢀTOF ESIꢀMS.
The following abbreviations were used to explain the multiplicities: s = singlet, d = doublet, t
=
triplet, q = quartet, dd = doublet of doublet, ddd = doublet of a doublet of doublet.
Crystal data for 7 has been deposited at the Cambridge Crystallographic Data Centre with the
deposition numbers CCDCꢀ1060893.
General Experimental Procedure (I) for the Synthesis of Symmetrical Diarylacetates
A dried vial equipped with a magnetic stir bar was charged with indole (1 equiv.), ethyl
bromofluoroacetate (2 equiv.), diisopropyl ethylamine (2 equiv.), Eosin Y (0.025 equiv.) and dry
DMF (2 mL). The mixture was sparged with argon for 10 minutes and then exposed to green
(530 nm) LED’s for 36 h (207 cm LED strip wrapped around a beaker; total power 18 W). After
ACS Paragon Plus Environment
11

The Journal of Organic Chemistry
Page 12 of 27
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
the completion of reaction (confirmed by TLC), the mixture was poured into separating funnel
containing 50 ml ethyl acetate/water (1:1). The layers were separated and the aqueous layer was
extracted with ethyl acetate (2 x 15 ml). The combined organic layers were dried over sodium
sulphate and concentrated in vacuo. The residue was purified by column chromatography on
silica gel (ethyl acetate/ petroleum ether)
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
General Procedure for the Synthesis of Unsymmetrical Diarylacetates (II) A dried vial
1
equipped with a magnetic stir bar was charged with indole (Ar , 1 equiv.), substituted indole
2
2
(
Ar , 2 equiv.)/Nꢀsubstituted aniline (Ar , 3 equiv.), ethyl bromofluoroacetate (2 equiv.),
diisopropyl ethylamine (2 equiv.), Eosin Y (0.025 equiv.) and dry DMF (3 mL). The mixture was
sparged with argon for 10 minutes and then exposed to green (530 nm) LED’s for 36 h (207 cm
LED strip wrapped around a beaker; total power 18 W). After the completion of reaction
(confirmed by TLC), the mixture was poured into separating funnel containing 50 ml ethyl
acetate/water (1:1). The layers were separated and the aqueous layer was extracted with ethyl
acetate (2 x 15 ml). The combined organic layers were dried over sodium sulphate and
concentrated in vacuo. The residue was purified by column chromatography on silica gel (ethyl
acetate/ petroleum ether)
4
Ethyl 2,2-di(1H-indol-3-yl)acetate (3) : According to the general
procedure (I), indole (200 mg, 1.71 mmol) provided 3 after flash
columnchromatography (15ꢀ25% ethyl acetate in petroleum ether) as a
flame red solid (226 mg, 83%). R = 0.3 (30% ethyl acetate in petroleum ether). IR (neat):
f
ꢀ1
1
νmax/cm 3413, 3051, 2928, 1734. mp = 69ꢀ71 °C. H NMR (400 MHz, Chloroformꢀd) δ 8.02 (s,
2H), 7.64 (d, J = 7.8 Hz, 2H), 7.26 (d, J = 8.1 Hz, 2H), 7.18 (t, J = 7.4 Hz, 2H), 7.10 (t, J = 7.3
1
3
Hz, 2H), 6.92 (s, 2H), 5.50 (s, 1H), 4.22 (q, J = 7.0 Hz, 2H), 1.26 (t, J = 7.1 Hz, 3H). C NMR
(125 MHz, Chloroformꢀd) δ 173.0, 135.2, 125.4, 122.5, 120.9, 118.4, 118.1, 112.1, 110.4, 60.2,
+
+
3
9.5, 13.1. Exact mass calculated for C H N O [M+H] : 319.1441; found: 319.1447.
20 19 2 2
ACS Paragon Plus Environment
12

Page 13 of 27
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
17
Ethyl 2,2-bis(5-methoxy-1H-indol-3-yl)acetate (4) : According
to the general procedure (I), 5ꢀmethoxy indole (100 mg, 0.679
mmol) provided 4 after flash chromatography (15ꢀ25% ethyl acetate
in petroleum ether) as a dark brown solid (96 mg, 75%). R = 0.4
f
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ꢀ
1
(
30% ethyl acetate in petroleum ether). IR (neat): νmax/cm 3405, 2959, 2925, 2853, 1720. mp =
1
1
75ꢀ178 °C. H NMR (400 MHz, Chloroformꢀd) δ 7.96 (s, 2H), 7.23 (d, J = 8.8 Hz, 2H), 7.08
(
s, 4H), 6.84 (dd, J = 8.8, 2.2 Hz, 2H), 5.39 (s, 1H), 4.22 (q, J = 7.1 Hz, 2H), 3.79 (s, 6H), 1.28
1
3
(d, J = 7.1 Hz, 3H). C NMR (125 MHz, Chloroformꢀd) δ 172.6, 136.0, 126.9, 126.0, 120.6,
+
118.3, 118.0, 111.2, 108.2, 60.0, 39.3, 31.7, 13.2. Exact mass calculated for C H N O
4
2
2
23
2
+
[
M+H] : 379.1652; found: 379.1658.
1
8
Ethyl 2,2-bis(2-methyl-1H-indol-3-yl)acetate (5) : According to the
general procedure (I), 2ꢀmethyl indole (100 mg, 0.762 mmol) provided
5
after flash chromatography (15ꢀ25% ethyl acetate in pet ether) as a
brick red solid (103 mg, 78%). R = 0.3 (30% ethyl acetate in petroleum ether). IR (neat):
f
ꢀ1
1
νmax/cm 3396, 3048, 2924, 2854, 1720. mp = 196ꢀ198 °C. H NMR (400 MHz, Chloroformꢀd)
δ 7.69 (s, 2H), 7.32 – 7.29 (m, 2H), 7.12 (dt, J = 8.1, 0.9 Hz, 2H), 6.99 (ddd, J = 8.1, 7.1, 1.2 Hz,
2
H), 6.90 (ddd, J = 8.0, 7.1, 1.1 Hz, 2H), 5.37 (s, 1H), 4.18 (q, J = 7.1 Hz, 2H), 2.07 (s, 6H), 1.15
1
3
(
d, J = 7.1 Hz, 3H). C NMR (125 MHz, Chloroformꢀd) δ 173.8, 135.0, 132.3, 128.4, 121.0,
+
1
19.5, 118.8, 110.3, 108.8, 61.1, 40.2, 14.4, 12.4. Exact mass calculated for C H N NaO
22 22 2 2
+
[
M+Na] : 369.1573; found: 369.1576.
Ethyl 2,2-bis(1-allyl-1H-indol-3-yl)acetate (6): According to the
general procedure (I), Nꢀallyl indole indole (100 mg, 0.636 mmol)
provided 6 after flash chromatography (15ꢀ25% ethyl acetate in
petroleum ether) as a reddish brown paste (102 mg, 80%). R = 0.4
f
ꢀ1
1
(
NMR (400 MHz, Chloroformꢀd) δ 7.56 (d, J = 7.9 Hz, 2H), 7.20 (d, J = 8.2 Hz, 2H), 7.13 – 7.08
m, 2H), 7.03 – 6.95 (m, 4H), 5.85 (ddt, J = 16.9, 10.5, 5.4 Hz, 2H), 5.41(s, 1H), 5.10 – 5.03 (m,
30% ethyl acetate in petroleum ether). IR (neat): νmax/cm 3052, 2981, 2925, 1733, 1644. H
(
2H), 5.01 – 4.92 (m, 2H), 4.58 – 4.51 (m, 4H), 4.12 (q, J = 7.1 Hz, 2H), 1.17 (t, J = 7.1 Hz, 3H).
ACS Paragon Plus Environment
13

The Journal of Organic Chemistry
Page 14 of 27
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
13
C NMR (125 MHz, Chloroformꢀd) δ 173.6, 136.7, 133.6, 127.5, 127.2, 121.8, 119.7, 119.3,
+
+
117.3, 112.7, 109.8, 61.1, 49.0, 40.7, 14.4. Exact mass calculated for C H N NaO [M+Na] :
26 26 2 2
421.1886; found: 421.1894.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
19
Ethyl 2,2-bis(1-methyl-1H-indol-3-yl)acetate (7) : According to the
general procedure (I), Nꢀmethyl indole (100 mg, 0.762 mmol) provided
7 after flash chromatography (15ꢀ25% ethyl acetate in petroleum ether)
as a pink solid (93 mg, 70%). R = 0.4 (30% ethyl acetate in petroleum
f
ꢀ1
1
ether). IR (neat): νmax/cm 3051, 2927, 2855, 1733. mp = 138ꢀ141 °C. H NMR (500 MHz,
Chloroformꢀd) δ 7.57 (d, J = 8.0 Hz, 2H), 7.21 (d, J = 8.3 Hz, 2H), 7.18 – 7.11 (m, 2H), 7.05 –
6.98 (m, 2H), 6.94 (s, 2H), 5.42 (s, 1H), 4.13 (q, J = 7.0 Hz, 2H), 3.64 (s, 6H), 1.19 (t, J = 7.1
13
Hz, 3H). C NMR (125 MHz, Chloroformꢀd) δ 172.6, 136.0, 126.9, 126.0, 120.6, 118.3, 118.0,
+
+
111.2, 108.2, 60.0, 39.3, 31.7, 13.2. Exact mass calculated for C H N O [M+H] : 347.1754;
22 23 2 2
found: 347.1766.
CO Et
2
Ethyl
2,2-bis(6-methoxy-1H-indol-3-yl)acetate
(8):
O
O
According to the general procedure (I), 6ꢀmethoxyindole (100
mg, 0.68 mmol) provided 8 after flash chromatography (15ꢀ
HN
NH
25% ethyl acetate in petroleum ether) as a dark brown solid (93 mg, 72%). R = 0.4 (30% ethyl
f
ꢀ1
acetate in petroleum ether). IR (neat): νmax/cm 3406, 2960, 2929, 2835, 1720. mp = 59ꢀ62 °C.
1
H NMR (400 MHz, Chloroformꢀd) δ 7.91 (s, 2H), 7.48 (d, J = 8.6 Hz, 2H), 6.92 (d, J = 2.0 Hz,
2H), 6.79 – 6.72 (m, 4H), 5.39 (s, 1H), 4.19 (q, J = 7.1 Hz, 2H), 3.80 (s, 6H), 1.24 (t, J = 7.1 Hz,
13
3H). C NMR (100 MHz, Chloroformꢀd) δ 173.5, 154.1, 131.6, 127.2, 124.1, 113.4, 112.5,
+
+
112.0, 101.2, 61.2, 55.9, 40.9, 14.5. Exact mass calculated C H N NaO [M+Na] : 401.1472;
22 22 2 4
found: 401.1472.
Ethyl 2,2-bis(6-chloro-1H-indol-3-yl)acetate (9): According
to the general procedure (I), 6ꢀchloroindole (100 mg, 0.66
mmol) provided 9 after flash chromatography (15ꢀ25% ethyl
acetate in petroleum ether) as a yellowish paste (104 mg, 81%). R = 0.6 (30% ethyl acetate in
f
ACS Paragon Plus Environment
14

Page 15 of 27
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
ꢀ1
1
petroleum ether). IR (neat): νmax/cm 3414, 2925, 1714, 1619, 1455. H NMR (400 MHz,
DMSOꢀd ) δ 11.07 (s, 2H), 7.45 (d, J = 8.5 Hz, 2H), 7.35 (d, J = 1.9 Hz, 2H), 7.23 (d, J = 2.1
6
Hz, 2H), 6.92 (dd, J = 8.5, 1.9 Hz, 2H), 5.40 (s, 1H), 4.07 (t, J = 7.1 Hz, 2H), 1.12 (t, J = 7.1 Hz,
1
3
3H). C NMR (100 MHz, DMSOꢀD ) δ 172.9, 137.2, 126.4, 125.6, 125.4, 120.8, 119.4, 112.9,
6
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
+
+
1
11.7, 61.0, 14.6. Exact mass calculated for C H Cl N O [M] : 386.0583, found 386.0584.
20 16 2 2 2
Ethyl 2,2-bis(7-(benzyloxy)-1H-indol-3-yl)acetate (10):
According to the general procedure (I), 7ꢀbenzyloxy indole
(
100 mg, 0.448 mmol) provided 10 after flash chromatography
(
15ꢀ25% ethyl acetate in petroleum ether) as a yellowish paste (64 mg, 54%). R = 0.6 (30%
f
ꢀ1
1
ethyl acetate in petroleum ether). IR (neat): νmax/cm 3393, 2934, 1719, 1489, 1455. H NMR
(400 MHz, Chloroformꢀd) δ 8.25 (s, 2H), 7.44 (d, J = 7.0 Hz, 4H), 7.40 – 7.30 (m, 6H), 7.24 (d,
J = 8.0 Hz, 2H), 7.04 (d, J = 2.3 Hz, 2H), 6.97 (t, J = 7.9 Hz, 2H), 6.68 (d, J = 7.7 Hz, 2H), 5.44
1
3
(
s, 1H), 5.16 (s, 4H), 4.18 (q, J = 7.1 Hz, 2H), 1.23 (t, J = 7.1 Hz, 3H). C NMR (100 MHz,
Chloroformꢀd) δ 173.4, 145.5, 137.2, 128.7, 128.3, 128.2, 127.9, 127.1, 123.0, 120.0, 114.3,
+
+
1
12.5, 103.3, 70.3, 61.1, 41.0, 14.4. Exact mass calculated for C H N NaO [M+Na] :
34 30 2 4
553.2098, found 553.2092.
Ethyl 2,2-bis(2-phenyl-1H-indol-3-yl)acetate (11): According to the
general procedure (I), 2ꢀphenyl indole (100 mg, 0.517 mmol) provided
1
1 after flash chromatography (15ꢀ25% ethyl acetate in petroleum ether)
as a blue solid (96 mg, 79%). R = 0.5 (30% ethyl acetate in petroleum
f
ꢀ1
ether). IR (neat): νmax/cm 3392, 3058, 2985, 2924, 1719. Mp = 186ꢀ189
C. H NMR (400 MHz, Chloroformꢀd) δ 7.95 (s, 2H), 7.30 (s, 4H), 7.24 – 7.17 (m, 10H), 7.02
(t, J = 7.5 Hz, 2H), 6.84 (t, J = 7.5 Hz, 2H), 5.63 (s, 1H), 3.91 (q, J = 7.1 Hz, 2H), 1.00 (t, J = 7.1
1
°
13
Hz, 3H). C NMR (100 MHz, Chloroformꢀd) δ 172.2, 135.1, 134.6, 131.9, 127.5, 127.3, 126.7,
20.9, 119.9, 118.7, 109.5, 109.0, 98.9, 59.9, 40.6, 13.0. Exact mass calculated for
1
+
+
C H NaN O [M+Na] : 493.1886; found: 493.1892.
32
26
2
2
ACS Paragon Plus Environment
15

The Journal of Organic Chemistry
Page 16 of 27
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Ethyl 2,2-bis(4-(benzyl(methyl)amino)phenyl)acetate (12):
According to the general procedure (I), NꢀbenzylꢀNꢀmethyl
aniline (100 mg, 0.507 mmol) provided 12 after flash
chromatography (15ꢀ25% ethyl acetate in petroleum ether) as a
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
yellowish paste (84 mg, 69%). R = 0.4 (20% ethyl acetate in petroleum ether). IR (neat):
f
ꢀ1
1
νmax/cm 2956, 2924, 2854, 1730. H NMR (400 MHz, Chloroformꢀd) δ 7.20 (d, J = 7.1 Hz,
4
H), 7.14 (t, J = 6.6 Hz, 6H), 7.07 (d, J = 8.6 Hz, 4H), 6.60 (d, J = 8.4 Hz, 4H), 4.72 (s, 1H),
1
3
4.39 (s, 4H), 4.07 (q, J = 7.1 Hz, 2H), 2.89 (s, 6H), 1.15 (t, J = 7.1 Hz, 3H). C NMR (100 MHz,
Chloroformꢀd) δ 173.7, 148.8, 139.1, 129.4, 128.7, 127.6, 127.0, 126.9, 112.5, 60.9, 56.9, 55.5,
+
+
3
8.7, 14.3. Exact mass calculated for C H N O [M+H] : 479.2693; found: 479.2692.
32 34 2 2
CO Et
Ethyl 2,2-bis(4-(benzylamino)phenyl)acetate (13): According
Ph to the general procedure (I), Nꢀbenzylaniline (100 mg, 0.546
N
mmol) provided 13 after flash chromatography (15ꢀ25% ethyl
2
Ph
N
H
H
acetate in petroleum ether) as a brown paste (73 mg, 59%). R =
f
ꢀ1
0.4 (20% ethyl acetate in petroleum ether). IR (neat): νmax/cm 3414, 3027, 2923, 2853, 1725.
1
H NMR (400 MHz, Chloroformꢀd) δ 7.36 – 7.26 (m, 10H), 7.10 (d, J = 8.5 Hz, 4H), 6.57 (d, J =
13
8
.5 Hz, 4H), 4.78 (s, 1H), 4.29 (s, 4H), 4.16 (q, J = 7.1 Hz, 2H), 1.23 (t, J = 7.1 Hz, 3H). C
NMR (125 MHz, Chloroformꢀd) δ 172.5, 146.0, 138.3, 128.3, 127.6, 127.5, 126.5, 126.2, 111.9,
+
+
5
9.8, 54.5, 47.5, 13.2. Exact mass calculated for C H N O [M+H] : 451.2380; found:
30 30 2 2
451.2383.
Ethyl 2,2-bis(4-(benzylamino)-2-bromophenyl)acetate (14):
According to the general procedure (I), Nꢀbenzylꢀ2ꢀ
bromoaniline (100 mg, 0.381 mmol) provided 14 after flash
chromatography (15ꢀ25% ethyl acetate in petroleum ether) as a
yellowish paste (68 mg, 59%). R = 0.4 (20% ethyl acetate in petroleum ether). IR (neat):
f
ꢀ1
1
νmax/cm 3413, 3061, 3029, 2961, 2924, 2851, 1730. H NMR (400 MHz, Chloroformꢀd) δ 7.32
–
7.24 (m, 10H), 7.18 (d, J = 0.5 Hz, 2H), 6.97 (dd, J = 8.4, 2.1 Hz, 2H), 6.51 (d, J = 8.4 Hz,
1
3
2H), 4.62 (s, 1H), 4.31 (s, 4H), 4.09 (q, J = 7.1 Hz, 2H), 1.16 (t, J = 7.1 Hz, 3H). C NMR (100
ACS Paragon Plus Environment
16

Page 17 of 27
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
MHz, Chloroformꢀd) δ 171.5, 142.4, 137.1, 131.2, 127.7 (Cꢀ2), 127.5, 126.4, 126.4, 111.1,
+
+
1
08.9, 60.2, 53.6, 47.3, 13.1. Exact mass calculated for C H Br N O [M+H] : 607.0590;
30 28 2 2 2
found: 607.0594.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Ethyl
2,2-bis(4-(prop-2-ynylamino)phenyl)acetate
(15):
According to the general procedure (I), Nꢀpropargyl aniline (100
mg, 0.762 mmol) provided 15 after flash chromatography (15ꢀ25%
ethyl acetate in petroleum ether) as an orangeꢀred solid (65 mg,
ꢀ1
4
2
8
9%). R = 0.4 (20% ethyl acetate in petroleum ether). IR (neat): ν /cm 3397, 3284, 2957,
f
max
1
924, 2853, 2120, 1721. mp = 132ꢀ134 °C. H NMR (400 MHz, Chloroformꢀd) δ 7.08 (d, J =
.5 Hz, 4H), 6.55 (d, J = 8.6 Hz, 4H), 4.74 (s, 1H), 4.13 – 4.07 (m, 2H), 3.83 (d, J = 2.4 Hz, 4H),
1
3
2.13 (t, J = 2.4 Hz, 2H), 1.19 (t, J = 7.6 Hz, 3H) (NH proton not observed). C NMR (100 MHz,
Chloroformꢀd) δ 172.3, 144.8, 128.3, 128.3, 112.4, 80.0, 70.3, 59.9, 54.5, 28.7, 13.2. Exact mass
+
+
calculated for C H N O [M+H] : 347.1754; found: 347.1761.
2
2
22
2
2
Ethyl 2,2-bis(4-(allylamino)phenyl)acetate (16): According
to the general procedure (I), Nꢀallyl aniline (100 mg, 0.751
mmol) provided 16 after flash chromatography (15ꢀ25% ethyl
acetate in petroleum ether) as a light yellow liquid (74 mg,
ꢀ1
5
6%). R = 0.4 (20% ethyl acetate in petroleum ether). IR (neat): ν /cm 3405, 2979, 2925,
f
max
1
2854, 1727, 1644. H NMR (400 MHz, Chloroformꢀd) δ 7.03 (d, J = 8.6 Hz, 4H), 6.50 (d, J = 8.5
Hz, 4H), 5.86 (ddt, J = 17.0, 10.7, 5.4 Hz, 2H), 5.19 (dd, J = 17.2, 1.6 Hz, 2H), 5.08 (dd, J =
1
0.3, 1.5 Hz, 2H), 4.71 (s, 1H), 4.09 (d, J = 7.1 Hz, 2H), 3.67 (d, J = 5.4 Hz, 4H), 1.16 (t, J = 7.1
1
3
Hz, 3H) (NH proton not observed). C NMR (100 MHz, Chloroformꢀd) δ 172.5, 145.9, 134.4,
+
128.3, 127.4, 115.2, 111.9, 59.8, 54.5, 45.6, 13.2. Exact mass calculated for C H N O
2
2
2
27
2
+
[M+H] : 351.2067; found: 351.2070.
Ethyl 2,2-bis(4-(allyl(methyl)amino)phenyl)acetate (17):
According to the general procedure (I), NꢀallylꢀNꢀmethyl
ACS Paragon Plus Environment
17

The Journal of Organic Chemistry
Page 18 of 27
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
aniline (100 mg, 0.679 mmol) provided 17 after flash chromatography (15ꢀ25% ethyl acetate in
petroleum ether) as a brown liquid (85 mg, 66%). R = 0.4 (20% ethyl acetate in petroleum
f
ꢀ1
1
ether). IR (neat): νmax/cm 2973, 2925, 2854, 1732, 1677. H NMR (400 MHz, Chloroformꢀd) δ
7.11 – 7.07 (m, 4H), 6.59 (d, J = 8.6 Hz, 4H), 5.75 (ddd, J = 12.0, 10.3, 5.1 Hz, 2H), 5.11 – 5.04
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(m, 4H), 4.73 (s, 1H), 4.10 (q, J = 7.1 Hz, 2H), 3.80 (dt, J = 5.0, 1.5 Hz, 4H), 2.83 (s, 6H), 1.16
13
(
d, J = 7.1 Hz, 3H) (NH proton not observed). C NMR (100 MHz, Chloroformꢀd) δ 172.6,
147.4, 132.9, 128.1, 126.2, 115.1, 111.3, 98.9, 59.8, 54.3, 37.0, 28.7, 13.2. Exact mass calculated
+
+
for C H N O [M+H] : 379.2380; found: 379.2382.
2
4
30
2
2
20
Ethyl
2,2-bis(4-(dimethylamino)phenyl)acetate
(18) :
According to the general procedure (I), N,Nꢀdimethyl aniline
(100 mg, 0.825 mmol) provided 18 after flash chromatography
(15ꢀ25% ethyl acetate in petroleum ether) as a green solid (46
ꢀ1
mg, 34%). R = 0.4 (20% ethyl acetate in petroleum ether). IR (neat): νmax/cm 3051, 2928,
f
1
2
852, 1733. mp = 186ꢀ188 °C. H NMR (400 MHz, Chloroformꢀd) δ 7.10 (d, J = 8.7 Hz, 4H),
6.61 (d, J = 8.8 Hz, 4H), 4.76 (s, 1H), 4.10 (q, J = 7.1 Hz, 2H), 2.83 (s, 12H), 1.17 (t, J = 7.1 Hz,
1
3
3H). C NMR (125 MHz, Chloroformꢀd) δ 172.5, 148.4, 128.1, 126.6, 111.7, 59.8, 54.3, 39.7,
+
+
1
3.2. Exact mass calculated for C H N O [M+H] : 327.2067; found: 327.2071.
20 26 2 2
Ethyl
2,2-bis(4-(benzylamino)-2,5-
dimethylphenyl)acetate (19): According to the general
procedure (I), Nꢀbenzylꢀ2,5ꢀdimethylaniline (100 mg,
0.473 mmol) provided 19 after flash chromatography (15ꢀ
25% ethyl acetate in petroleum ether) as a yellowish solid (82 mg, 68%). R = 0.4 (20% ethyl
f
ꢀ1
acetate in petroleum ether). IR (neat): νmax/cm 3434, 3026, 2924, 2856, 1729. mp = 64ꢀ67 °C.
1
H NMR (400 MHz, Chloroformꢀd) δ 7.35 – 7.20 (m, 10H), 6.73 (s, 2H), 6.40 (s, 2H), 5.00 (s,
1H), 4.26 (s, 4H), 4.12 (q, J = 7.1 Hz, 2H), 3.65 (s, 2H), 2.09 (s, 6H), 1.99 (s, 6H), 1.18 – 1.15
13
(
m, 3H). C NMR (100 MHz, Chloroformꢀd) δ 173.1, 143.8, 138.6, 133.8, 129.0, 127.6 (Cꢀ2),
ACS Paragon Plus Environment
18

Page 19 of 27
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
1
26.7, 126.2, 124.7, 118.4, 111.2, 59.7, 48.5, 47.5, 18.7, 16.3, 13.3. Exact mass calculated for
+
+
C H N O [M+H] : 507.3006; found: 507.3019.
34
38
2
2
Ethyl 2,2-bis(4-(benzylamino)-3-fluorophenyl)acetate (20):
According to the general procedure (I), Nꢀbenzylꢀ2ꢀ
fluoroaniline (100 mg, 0.497 mmol) provided 20 after flash
chromatography (15ꢀ25% ethyl acetate in petroleum ether) as a
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ꢀ1
brown paste (79 mg, 65%). R = 0.4 (20% ethyl acetate in petroleum ether). IR (neat): νmax/cm
f
1
3429, 3029, 2925, 2851, 1730. H NMR (400 MHz, Chloroformꢀd) δ 7.29 – 7.17 (m, 10H), 6.88
(dd, J = 12.6, 1.9 Hz, 2H), 6.79 (d, J = 8.3 Hz, 2H), 6.53 (t, J = 8.6 Hz, 2H), 4.66 (s, 1H), 4.27 (s,
1
3
4
H), 4.09 (t, J = 7.1 Hz, 2H), 1.17 (d, J = 7.1 Hz, 3H) (NH proton not observed). C NMR (100
MHz, Chloroformꢀd) δ 171.7, 150.2 (d, J = 239 Hz, 1C), 137.8, 134.6 (d, J = 11.8, 2C), 127.7,
26.6 (d, J = 6.5 Hz, 1C), 126.3, 123.4 (d, J = 3.14 Hz, 1C), 113.6 (d, J = 19.5 Hz, 1C), 110.9 (d,
1
+
+
J = 3.8 Hz, 1C), 60.1, 54.0, 46.8, 13.1. Exact mass calculated for C H F N O [M+H] :
3
0
28
2
2
2
4
87.2192; found: 487.2191.
Ethyl 2,2-bis(4-(benzylamino)-2-methylphenyl)acetate (21):
According to the general procedure (I), Nꢀbenzylꢀ3ꢀtoluidine
(100 mg, 0.5 mmol) provided 21 after flash chromatography
(15ꢀ25% ethyl acetate in petroleum ether) as an orange paste
ꢀ1
(62 mg, 53%). R = 0.4 (20% ethyl acetate in petroleum ether). IR (neat): νmax/cm 3411, 3054,
f
1
2924, 2854, 1727. H NMR (400 MHz, Chloroformꢀd) δ 7.37 – 7.27 (m, 10H), 6.88 (d, J = 8.3
Hz, 2H), 6.48 (d, J = 2.2 Hz, 2H), 6.43 (dd, J = 8.4, 2.4 Hz, 2H), 5.06 (s, 1H), 4.28 (s, 4H), 4.18
13
(
d, J = 7.1 Hz, 2H), 2.15 (s, 6H), 1.23 (t, J = 7.1 Hz, 3H) (NH proton not observed). C NMR
125 MHz, Chloroformꢀd) δ 172.7, 145.8, 138.4, 136.2, 128.1, 127.6, 126.6, 126.2, 125.5, 114.1,
(
+
+
109.4, 59.8, 48.6, 47.5, 18.8, 13.2. Exact mass calculated for C H N O [M+H] : 479.2693;
3
2
34
2
2
found: 479.2692.
ACS Paragon Plus Environment
19

The Journal of Organic Chemistry
Page 20 of 27
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
NH
Ethyl
2,2-bis(4-(benzylamino)naphthalen-1-yl)acetate
(22):
According to the general procedure (I), Nꢀbenzylnaphthalenꢀ1ꢀamine
(100 mg, 0.854 mmol) provided 22 after flash chromatography (10ꢀ
CO Et
2
2
8
0% ethyl acetate in petroleum ether) as a yellowish solid (87 mg,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
0%). R = 0.5 (10ꢀ20% ethyl acetate in petroleum ether). IR (neat):
f
NH
ꢀ1
1
νmax/cm 3442, 2977, 2924, 2851, 1728. mp = 82ꢀ84 °C. H NMR
400 MHz, Chloroformꢀd) δ 7.37 – 7.27 (m, 10H), 6.88 (d, J = 8.3 Hz, 2H), 6.48 (d, J = 2.2 Hz,
2H), 6.43 (dd, J = 8.4, 2.4 Hz, 2H), 5.06 (s, 1H), 4.28 (s, 4H), 4.18 (d, J = 7.1 Hz, 2H), 2.15 (s,
(
1
3
6
1
4
H), 1.24 (s, 3H) (NH proton not observed). C NMR (100 MHz, Chloroformꢀd) δ 174.1, 142.9,
39.1, 132.5, 129.1, 128.8, 127.9, 127.5, 127.5, 126.4, 124.7, 124.1, 124.1, 120.8, 104.6, 61.2,
+
+
9.7, 48.8, 14.4. Exact mass calculated for C H N O [M+H] : 551.2693, found 551.2691.
3
8
35
2
2
2
1
Ethyl 2,2-di(1H-pyrrol-2-yl)acetate (23) : According to the general
procedure (I), pyrrole (100 mg, 1.49 mmol) provided 23 after flash
chromatography (15ꢀ25% ethyl acetate in petroleum ether) as a dark blue solid
ꢀ1
(
49 mg, 30%). R = 0.5 (15ꢀ20% ethyl acetate in petroleum ether). IR (neat): νmax/cm 3388,
f
1
3
103, 2980, 2926, 1724. mp = 60ꢀ62 °C. H NMR (400 MHz, Chloroformꢀd) δ 8.39 (s, 2H),
6.65 – 6.62 (m, 2H), 6.08 (d, J = 2.9 Hz, 2H), 6.03 – 5.99 (m, 2H), 5.02 (s, 1H), 4.16 (q, J = 7.2
13
Hz, 2H), 1.23 (t, J = 7.2 Hz, 3H). C NMR (100 MHz, Chloroformꢀd) δ 170.6, 125.7, 117.0,
+
+
1
07.4, 106.0, 60.7, 42.7, 13.1. Exact mass calculated for C H N O [M+H] : 219.1128; found:
12 15 2 2
2
19.1139.
22
Ethyl 2-(1H-indol-3-yl)-2-(1-methyl-1H-indol-3-yl)acetate (29) :
According to the general procedure (II), indole (100 mg, 0.854 mmol) ,
Nꢀmethyl indole (224 mg, 1.71mmol) provided 29 after flash
chromatography (10ꢀ20% ethyl acetate in petroleum ether) as a brown
ꢀ1
paste (109 mg, 38%). R = 0.6 (10ꢀ25% EtOAc/pet ether). IR (neat): νmax/cm 3406, 3054, 2979,
f
1
2
929, 1730. H NMR (400 MHz, Chloroformꢀd) δ 8.02 (s, 1H), 7.63 (dq, J = 7.8, 1.1 Hz, 2H),
.30 – 7.25 (m, 2H), 7.24 – 7.19 (m, 1H), 7.16 (ddd, J = 8.1, 7.0, 1.2 Hz, 1H), 7.08 (ddd, J = 8.1,
7
6.9, 1.3 Hz, 2H), 7.06 – 7.02 (m, 1H), 6.96 (s, 1H), 5.52 – 5.46 (m, 1H), 4.20 (q, J = 7.1 Hz, 2H),
13
3
.65 (s, 3H), 1.25 (t, J = 7.1 Hz, 3H). C NMR (100 MHz, Chloroformꢀd) δ 173.7, 137.3, 136.5,
ACS Paragon Plus Environment
20

Page 21 of 27
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
1
28.1, 127.2, 126.8, 123.4, 122.2, 121.8, 119.6, 119.6, 119.4, 119.2, 113.9, 112.2, 111.4, 109.5,
+
+
61.2, 40.7, 32.9, 14.4. Exact mass calculated for C H N O [M+H] :333.1598; found:
21 21 2 2
333.1608.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
CO Et
2
Ethyl 2-(1-methyl-1H-indol-3-yl)-2-(2-methyl-1H-indol-3-yl)acetate
(
30): According to the general procedure (II), 2ꢀmethyl indole (100 mg,
0.763 mmol), Nꢀmethyl indole (200 mg, 1.52 mmol) provided 30 after
flash chromatography (10ꢀ20% ethyl acetate in petroleum ether) as a
HN
N
Me
Me
dark brown paste (174 mg, 66%). R = 0.6 (10ꢀ20% ethyl acetate in petroleum ether). IR (neat):
f
ꢀ1
1
νmax/cm 3397, 3054, 2974, 2927, 1730. H NMR (400 MHz, Chloroformꢀd) δ 7.86 (s, 1H), 7.71
d, J = 7.9 Hz, 1H), 7.44 (dt, J = 8.0, 0.9 Hz, 1H), 7.26 – 7.16 (m, 3H), 7.10 – 7.01 (m, 3H), 6.92
(d, J = 1.1 Hz, 1H), 5.42 (d, J = 1.1 Hz, 1H), 4.24 – 4.10 (m, 2H), 3.64 (s, 3H), 2.33 (s, 3H), 1.20
(
1
3
(
t, J = 7.1 Hz, 3H. C NMR (100 MHz, Chloroformꢀd) δ 173.4, 137.2, 135.2, 132.7, 128.1,
1
28.0, 127.5, 121.7, 121.0, 119.8, 119.4, 119.1, 119.1, 112.1, 110.3, 109.4, 108.6, 61.1, 40.3,
+
+
3
2.8, 14.4, 12.2. Exact mass calculated for C H N O [M] 346.1681, found 346.1687.
2
2
22
2
2
Ethyl
2-(5-methoxy-1H-indol-3-yl)-2-(1-methyl-1H-indol-3-
yl)acetate (31): According to the general procedure (II), 5ꢀmethoxy
indole (100 mg, 679.47 µmol), Nꢀmethyl indole (179 mg, 1.36 mmol),
provided 31 after flash chromatography (10ꢀ20% ethyl acetate in
petroleum ether) as a yellowish paste (89 mg, 36%). R = 0.5 (30% ethyl acetate in petroleum
f
ꢀ1
1
ether). IR (neat): νmax/cm 3408, 3052, 2981, 2936, 2829, 1733. H NMR (400 MHz,
Chloroformꢀd) δ 7.87 (s, 1H), 7.57 (d, J = 7.9 Hz, 1H), 7.21 (s, 1H), 7.18 – 7.12 (m, 3H), 7.02
(
dd, J = 9.1, 2.4 Hz, 2H), 6.92 (s, 1H), 6.77 (dd, J = 8.8, 2.4 Hz, 1H), 5.37 (s, 1H), 4.15 (d, J =
13
7.1 Hz, 2H), 3.73 (s, 3H), 3.63 (s, 3H), 1.21 (d, J = 7.1 Hz, 3H). C NMR (100 MHz,
Chloroformꢀd) δ 173.6, 154.1, 137.2, 131.5, 128.1, 127.2, 127.2, 124.1, 121.8, 119.5, 119.1,
1
13.7, 112.5, 112.1, 112.0, 109.4, 101.2, 61.1, 56.0, 40.7, 32.8, 14.4. Exact mass calculated for
+
+
C H N O [M] 362.1630, found 362.1634.
22
22
2
3
ACS Paragon Plus Environment
21

The Journal of Organic Chemistry
Page 22 of 27
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Ethyl
32):According to the general procedure (II), indole (100 mg, 0.854
mmol) , 3ꢀmethyl indole (280 mg, 2.13 mmol) provided 32 after flash
chromatography (10ꢀ20% ethyl acetate in petroleum ether) as a brown solid (72 mg, 25%). R =
2-(1H-indol-3-yl)-2-(3-methyl-1H-indol-2-yl)acetate
(
f
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
ꢀ
1
0
2
7
.4 (10ꢀ20% ethyl acetate in petroleum ether). IR (neat): νmax/cm 3407, 3048, 2972, 2919,
1
853, 1720. mp = 112ꢀ115°C. H NMR (400 MHz, Chloroformꢀd) δ 8.51 (s, 1H), 8.01 (s, 1H),
.48 (t, J = 7.4 Hz, 2H), 7.27 (d, J = 8.1 Hz, 1H), 7.21 – 7.14 (m, 2H), 7.17 – 7.06 (m, 2H), 7.02
(dd, J = 2.7, 1.1 Hz, 2H), 5.44 (d, J = 0.8 Hz, 1H), 4.16 (tt, J = 7.1, 3.5 Hz, 2H), 2.28 (s, 3H),
1
3
1.22 (d, J = 7.1 Hz, 3H). C NMR (125 MHz, Chloroformꢀd) δ 171.4, 135.2, 134.3, 129.1,
127.8, 125.2, 122.0, 121.5, 120.6, 119.0, 118.0, 117.8, 117.5, 111.6, 110.3, 109.8, 107.4, 60.6,
+
2
+
3
9.4, 13.2, 7.5. Exact mass calculated for C H N O [M+H] : 333.1598; found: 333.1600.
2
1
20
2
Ethyl
2-(1H-indol-3-yl)-2-(4-(prop-2-ynylamino)phenyl)acetate
(33): According to the general procedure (II), indole (100 mg, 0.853
mmol) and Nꢀpropargylaniline (336 mg, 2.56 mmol) provided 33
after flash chromatography (15ꢀ25% ethyl acetate in petroleum ether)
as a brown solid (211 mg, 74%). R = 0.3 (30% ethyl acetate in petroleum ether). IR (neat):
f
ꢀ1
1
νmax/cm 3410, 3286, 2980, 2925, 2853, 1721. mp = 109ꢀ111 °C. H NMR (400MHz,
Chloroformꢀd) δ 8.08 (s, 1H), 7.46 (d, J = 8.4 Hz, 1H), 7.31 (d, J = 8.1 Hz, 2H), 7.26 (d, J = 8.7
Hz, 2H), 7.18 – 7.13 (m, 2H), 7.05 (t, J = 7.9 Hz, 1H), 6.62 (d, J = 8.6 Hz, 2H), 5.14 (s, 1H),
4.27 – 4.13 (m, 2H), 3.89 (d, J = 2.5 Hz, 2H), 2.20 (t, J = 2.4 Hz, 1H), 1.25 (t, J = 7.1 Hz, 3H).
1
3
C NMR (100 MHz, Chloroformꢀd) δ 173.5, 146.1, 136.4, 129.4, 128.7, 126.8, 123.2, 122.2,
119.7, 119.2, 114.4, 113.6, 111.3, 81.1, 71.4, 61.1, 48.3, 33.8, 14.3. Exact mass calculated for
+
+
C H N O [M] : 332.1519; found: 332.1520.
21
20
2
2
Ethyl 2-(4-(benzylamino)phenyl)-2-(1H-indol-3-yl)acetate (34):
According to the general procedure (II), indole (100 mg, 0.853
mmol ) and Nꢀbenzylaniline (470 mg, 2.56 mmol) provided 34
after flash chromatography (15ꢀ25% ethyl acetate in petroleum
ACS Paragon Plus Environment
22

Page 23 of 27
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
ether) as an yellowish paste (143 mg, 43%). R = 0.3 (30% ethyl acetate in petroleum ether). IR
f
ꢀ1
1
(
neat): νmax/cm 3407, 3057, 2981, 2926, 1719, 1621. H NMR (400 MHz, Chloroformꢀd) δ 8.05
(s, 1H), 7.46 (d, J = 7.9 Hz, 1H), 7.37 – 7.29 (m, 5H), 7.27 (dd, J = 6.0, 2.8 Hz, 1H), 7.23 (s,
2H), 7.18 – 7.11 (m, 2H), 7.05 (t, J = 7.5 Hz, 1H), 6.61 – 6.54 (m, 2H), 5.12 (s, 1H), 4.31 – 4.26
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
3
(
m, 2H), 4.24 – 4.14 (m, 2H), 4.02 (s, 1H), 1.25 (t, J = 7.1 Hz, 3H). C NMR (100 MHz
Chloroformꢀd) δ 173.6, 147.4, 139.5, 136.4, 129.4, 128.8, 127.7, 127.7, 127.4, 126.8, 123.2,
22.3, 119.7, 119.3, 114.6, 113.0, 111.2, 61.1, 48.6, 48.3, 14.4. Exact mass calculated for
1
+
+
C H N O [M] : 384.1832; found: 384.1834.
25
24
2
2
Ethyl
2-(4-(benzyl(methyl)amino)phenyl)-2-(1H-indol-3-
CO Et
2
yl)acetate (35): According to the general procedure (II), indole
(100 mg, 0.853 mmol ) and Nꢀbenzylꢀ2,6ꢀdimethylaniline (541.13
mg, 2.56 mmol) provided 35 after flash chromatography (15ꢀ25%
HN
N
ethyl acetate in petroleum ether) as a brown paste (157 mg, 52%). R = 0.4 (30% ethyl acetate in
f
1
petroleum ether). H NMR (400 MHz, Chloroformꢀd) δ = 8.09 (s, 1H), 7.51 (d, J=8.0, 1H), 7.37
– 7.29 (m, 4H), 7.28 (d, J=5.9, 1H), 7.27 – 7.21 (m, 3H), 7.20 – 7.15 (m, 2H), 7.08 (t, J=7.0,
1
H), 6.72 (d, J=8.8, 2H), 5.17 (s, 1H), 4.51 (s, 2H), 4.29 – 4.16 (m, 2H), 3.00 (s, 3H), 1.28 (t,
13
J=7.1, 3H). C NMR (100 MHz, Chloroformꢀd) δ 173.7, 149.0, 139.2, 136.4, 129.3, 128.7,
1
27.0, 126.9, 126.8, 126.6, 123.2, 122.2, 119.6, 119.2, 114.6, 112.5, 111.3, 77.5, 77.2, 76.8, 61.0,
+
+
5
6.8, 48.2, 38.6, 14.3. Exact mass calculated forC H NaN O [M+Na] : 421.1886; found:
26 26 2 2
421.1886.
CO Et
Ethyl 2-(4-(benzylamino)-3,5-dimethylphenyl)-2-(1H-indol-
2
Me
3-yl)acetate (36): According to the general procedure (II),
HN
indole (100 mg, 0.853 mmol ) and
Nꢀbenzylꢀ2,6ꢀ
N
H
Me
dimethylaniline (541.13 mg, 2.56 mmol) provided 36 after
flash chromatography (15ꢀ25% ethyl acetate in petroleum ether) as an yellowish paste (168 mg,
1
4
8%). R = 0.4 (30% ethyl acetate in petroleum ether). H NMR (400 MHz, Chloroformꢀd) δ =
f
8.20 (s, 1H), 7.53 (d, J=7.8, 1H), 7.41 – 7.27 (m, 6H), 7.22 – 7.16 (m, 2H), 7.11 (d, J=7.8, 3H),
5
.17 (s, 1H), 4.25 (dddd, J=17.8, 10.8, 7.1, 3.7, 2H), 4.10 (s, 2H), 2.75 (s, 1H), 2.26 (s, 6H), 1.30
ACS Paragon Plus Environment
23

The Journal of Organic Chemistry
Page 24 of 27
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
13
(
t, J=7.1, 5H). C NMR (126 MHz, Chloroformꢀd) δ 173.6, 145.0, 140.5, 136.4, 132.2, 129.9,
1
28.9, 128.7, 128.1, 127.4, 126.8, 123.3, 122.2, 119.6, 119.1, 114.3, 111.3, 61.1, 52.9, 48.4, 18.7,
+
+
14.3. Exact mass calculated forC H NaN O [M+Na] : 435.2043; found: 435.2042.
2
7
28
2
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
CO Et
Ethyl
2-(4-(benzylamino)-2,5-dimethylphenyl)-2-(1H-
2
Me
indol-3-yl)acetate (37): According to the general procedure
(II), indole (100 mg, 0.853 mmol ) and Nꢀbenzylꢀ2,6ꢀ
dimethylaniline (541.13 mg, 2.56 mmol) provided 37 after
HN
Me
N
H
flash chromatography (15ꢀ25% ethyl acetate in petroleum ether) as an yellowish paste (185 mg,
1
5
3%). R = 0.4 (30% ethyl acetate in petroleum ether). H NMR (400 MHz, Chloroformꢀd) δ =
f
8.12 (s, 1H), 7.48 (d, J=7.9, 1H), 7.45 – 7.37 (m, 4H), 7.32 (d, J=7.5, 2H), 7.22 – 7.16 (m, 1H),
7
7
1
1
.09 (d, J=5.2, 2H), 7.03 (d, J=2.3, 1H), 6.53 (s, 1H), 5.37 (s, 1H), 4.38 (s, 2H), 4.25 (qq, J=11.0,
1
3
.2, 2H), 2.40 (s, 3H), 2.06 (s, 3H), 1.30 (t, J=7.1, 3H). C NMR (100 MHz, Chloroformꢀd) δ
73.9, 145.1, 139.7, 136.4, 134.8, 129.9, 128.8, 127.8, 127.4, 127.0, 125.4, 123.7, 122.1, 119.8,
19.6, 119.0, 114.4, 112.2, 111.3, 61.0, 48.6, 44.6, 20.0, 17.3, 14.4. Exact mass calculated for
+
+
C H NaN O [M+Na] : 435.2043; found: 435.2043.
27
28
2
2
CO Et
Ethyl 2-(4-(benzylamino)-3,5-dimethylphenyl)-2-(1H-indol-3-
yl)acetate (38):- According to the general procedure (II), indole
(100 mg, 0.853 mmol ) and Nꢀbenzylꢀnapthylamine (598 mg, 2.56
mmol) provided 38 after flash chromatography (15ꢀ25% ethyl
2
HN
N
H
acetate in petroleum ether) as an yellowish paste (208 mg, 56%). R = 0.4 (30% ethyl acetate in
f
1
petroleum ether). H NMR (400 MHz, Chloroformꢀd) δ = 8.18 (d, J=8.1, 1H), 8.08 (s, 1H), 7.88
(d, J=8.9, 1H), 7.53 – 7.42 (m, 5H), 7.37 (t, J=7.8, 2H), 7.31 (d, J=16.5, 3H), 7.18 (t, J=7.6, 1H),
7
2
1
.07 (t, J=7.9, 1H), 7.00 (d, J=2.3, 1H), 6.55 (d, J=8.0, 1H), 5.91 (s, 1H), 4.73 (s, 1H), 4.44 (s,
13
H), 4.24 (q, J=7.1, 2H), 1.26 (t, J=7.1, 3H). C NMR (125 MHz, Chloroformꢀd) δ 173.8, 143.0,
39.2, 136.5, 132.5, 128.8, 127.9, 127.5, 127.1, 127.0, 126.3, 124.6, 124.3, 124.1, 124.0, 123.6,
122.3, 120.8, 119.7, 119.2, 114.0, 111.4, 104.6, 61.2, 48.7, 45.1, 14.4. Exact mass calculated for
+
+
C H N O [M+H] : 435.2067; found: 435.2068.
29 27
2
2
ACS Paragon Plus Environment
24

Page 25 of 27
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
CO Et
Ethyl
2-(4-(allyl(methyl)amino)phenyl)-2-(1H-indol-3-
2
yl)acetate (39): According to the general procedure (II), indole
(100 mg, 0.853 mmol ) and NꢀallylꢀN-methylaniline (377 mg, 2.56
mmol) provided 39 after flash chromatography (15ꢀ25% ethyl
HN
N
Me
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
acetate in petroleum ether) as a pink paste (172 mg, 58%). R = 0.4 (30% ethyl acetate in
f
1
petroleum ether). H NMR (400 MHz, Chloroformꢀd) δ = 8.20 (s, 1H), 7.55 (d, J=7.8, 1H), 7.32
(dd, J=16.3, 8.4, 3H), 7.20 (t, J=7.1, 1H), 7.14 – 7.08 (m, 2H), 6.72 (d, J=8.8, 2H), 5.88 (ddt,
J=17.1, 10.2, 5.1, 1H), 5.20 (dt, J=8.6, 6.5, 3H), 4.33 – 4.18 (m, 2H), 3.93 (d, J=5.3, 2H), 2.95
1
3
(
s, 3H), 1.31 (t, J=7.1, 3H). C NMR (125 MHz, Chloroformꢀd) δ 173.7, 148.8, 136.4, 134.0,
129.2, 126.8, 126.5, 123.2, 122.2, 119.6, 119.2, 116.3, 114.6, 112.6, 111.3, 61.0, 55.4, 48.2, 38.1,
+
+
1
4.3. Exact mass calculated for C H NaN O [M+Na] : 371.1730; found: 371.1724.
2
2
24
2
2
CO Et
2
Ethyl 2-(4-(diallylamino)phenyl)-2-(1H-indol-3-yl)acetate (40):
According to the general procedure (II), indole (100 mg, 0.853
mmol ) and N,Nꢀallylaniline (444 mg, 2.56 mmol) provided 40
HN
N
after flash chromatography (15ꢀ25% ethyl acetate in petroleum
1
ether) as an yellowish paste (197 mg, 62%). R = 0.4 (30% ethyl acetate in petroleum ether). H
f
NMR (400 MHz, Chloroformꢀd) δ = 8.16 (s, 1H), 7.55 (d, J=7.8, 1H), 7.30 (d, J=8.6, 3H), 7.18
(d, J=8.0, 1H), 7.14 (d, J=2.4, 1H), 7.11 (t, J=7.5, 1H), 6.70 (d, J=8.8, 2H), 5.88 (ddt, J=17.2,
10.0, 4.9, 2H), 5.26 – 5.15 (m, 5H), 4.25 (qq, J=10.8, 7.1, 2H), 3.93 (d, J=5.0, 4H), 1.30 (t,
1
3
J=7.1, 3H). C NMR (100 MHz, Chloroformꢀd) δ 173.8, 147.9, 136.4, 134.1, 129.1, 126.8,
26.3, 123.3, 122.1, 119.5, 119.1, 116.1, 114.4, 112.4, 111.3, 61.0, 52.8, 48.1, 14.3. Exact mass
1
+
+
calculated for C H KN O [M+K] : 413.1626; found: 413.1652.
2
4
26
2
2
Diethyl 2,2'-(1H-pyrrole-2,5-diyl)bis(2-(1H-pyrrol-2-yl)acetate):
According to the general procedure (I), pyrrole (100 mg, 1.49 mmol)
provided trimer after flash chromatography (15ꢀ25% ethyl acetate in pet ether) as a dark blue
ꢀ1
solid (103 mg, 65%). R = 0.3 (20% EtOAc/Hexanes). IR (neat): νmax/cm 3383, 2974, 2919,
f
1
2
846, 1725. mp = 112ꢀ115°C. H NMR (400 MHz, Chloroformꢀd) δ 8.63 (s, 1H), 8.47 (s, 2H),
ACS Paragon Plus Environment
25

The Journal of Organic Chemistry
Page 26 of 27
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
6
2
1
.64 (d, J = 1.6 Hz, 2H), 6.06 (d, J = 3.0 Hz, 2H), 5.98 (s, 2H), 5.88 (t, J = 2.4 Hz, 2H), 4.96 (s,
1
3
H), 4.13 (d, J = 7.2 Hz, 4H), 1.22 – 1.19 (m, 6H). C NMR (100 MHz, Chloroformꢀd) δ 171.4,
+
27.3, 126.5, 118.1, 108.5, 107.5, 107.2, 61.8, 44.0, 14.2. Exact mass calculated for C H N O
4
2
0
24
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
+
[
M+H] : 370.1761; found: 370.1762.
ASSOCIATED CONTENT
Supporting Information.
1
13
H and C spectra for all compounds and Xꢀray data for compound 7. This material is available
free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*Eꢀmail: anands@iitk.ac.in
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
AS gratefully acknowledges IIT Kanpur (IITK/CHM/20130024) and BRNS
(BRNS/CHM/2014118) for funding. The authors thank Ms. Sonam Mehrotra for solving the
crystal structure of 7. SDJ and DB thank UGC, New Delhi and IIT Kanpur respectively for
research fellowships. AS thanks Professor Vinod K. Singh for the use of his laboratory during
the execution of this work.
REFERENCES
ACS Paragon Plus Environment
26

Page 27 of 27
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
(
1) a) Nguyen, J. D.; Tucker, J. W.; Konieczynska, M. D.; Stephenson, C. R. J. J. Am. Chem.
Soc. 2011, 133, 4160; b) Sun, X.; Yu, S. Org. Lett. 2014, 16, 2938; c) Wallentin, C.ꢀJ.; Nguyen,
J. D.; Finkbeiner, P.; Stephenson, C. R. J. J. Am. Chem. Soc. 2012, 134, 8875; d) Wei, X.ꢀJ.;
Yang, D.ꢀT.; Wang, L.; Song, T.; Wu, L.ꢀZ.; Liu, Q. Org. Lett. 2013, 15, 6054.
(2) a) Shiri, M.; Zolfigol, M. A.; Kruger, H. G.; Tanbakouchian, Z. Chem. Rev. 2009, 110,
2250; b) York, M.; Abdelrahim, M.; Chintharlapalli, S.; Lucero, S. D.; Safe, S. Clin. Cancer
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Res. 2007, 13, 6743; c) Lee, C.ꢀH.; Yao, C.ꢀF.; Huang, S.ꢀM.; Ko, S.; Tan, Y.ꢀH.; LeeꢀChen, G.ꢀ
J.; Wang, Y.ꢀC. Cancer 2008, 113, 815.
(3) Auvil, T. J.; So, S. S.; Mattson, A. E. Angew. Chem. Int. Ed. Engl. 2013, 52, 11317.
(4) Huo, C.; Wang, C.; Sun, C.; Jia, X.; Wang, X.; Chang, W.; Wu, M. Adv. Synth. Catal. 2013,
355, 1911.
(5) Hari, D. P.; Konig, B. Chem. Commun. 2014, 50, 6688.
(6) Furst, L.; Matsuura, B. S.; Narayanam, J. M. R.; Tucker, J. W.; Stephenson, C. R. J. Org.
Lett. 2010, 12, 3104.
(7) a) Peng, Y.ꢀY.; Zhang, Q.ꢀL.; Yuan, J.ꢀJ.; Cheng, J.ꢀP. Chin. J. Chem . 2008, 26, 2228; b)
Xu, H.ꢀY.; Zi, Y.; Xu, X.ꢀP.; Wang, S.ꢀY.; Ji, S.ꢀJ. Tetrahedron 2013, 69, 1600; c) Ramesh, C.;
Banerjee, J.; Pal, R.; Das, B. Adv. Synth. Catal. 2003, 345, 557.
(8) a) Ji, S.ꢀJ.; Zhou, M.ꢀF.; Gu, D.ꢀG.; Jiang, Z.ꢀQ.; Loh, T.ꢀP. Eur. J. Org. Chem. 2004, 2004,
1584; b) Lakshmi Kantam, M.; Aziz, K.; Likhar, P. R. Catal. Lett. 2004, 98, 117; c) Silveira, C.
C.; Mendes, S. R.; Líbero, F. M.; Lenardão, E. J.; Perin, G. Tetrahedron Lett. 2009, 50, 6060; d)
Soueidan, M.; Collin, J.; Gil, R. Tetrahedron Lett. 2006, 47, 5467.
(
(
(
9) Liang, Z.; Xu, S.; Tian, W.; Zhang, R. Beilstein J. Org. Chem. 2015, 11, 425.
10) Please see supporting information for details
11) a) Neumann, M.; Füldner, S.; König, B.; Zeitler, K. Angew. Chem. Int. Ed. 2011, 50, 951;
b) Xie, J.; Jin, H.; Xu, P.; Zhu, C. Tetrahedron Lett. 2014, 55, 36; c) Nishino, M.; Hirano, K.;
Satoh, T.; Miura, M. J. Org. Chem. 2011, 76, 6447; d) Ju, X.; Li, D.; Li, W.; Yu, W.; Bian, F.
Adv. Synth. Catal. 2012, 354, 3561.
(12) a) Yadav, A. K.; Srivastava, V. P.; Yadav, L. D. S. New J. Chem. 2013, 37, 4119; b)
Huang, L.; Zhao, J. RSC Adv. 2013, 3, 23377; c) Hari, D. P.; König, B. Org. Lett. 2011, 13,
3852.
(13) At this time, it is not possible to rule out participation of adventitious oxygen.
(14) a) Gai, S.; Zhang, Q.; Hu, X. J. Org. Chem. 2014, 79, 2111; b) SuarezꢀCastillo, O. R.;
MelendezꢀRodriguez, M.; CanoꢀEscudero, I. C.; Luz De ItaꢀGutierrez, S.; SanchezꢀZavala, M.;
MoralesꢀRios, M. S.; JosephꢀNathan, P. Heterocycles 2010, 81, 1169.
(15) Deng, W.ꢀP.; Nam, G.; Fan, J.; Kirk, K. L. J. Org. Chem. 2003, 68, 2798.
(16) Barluenga, J.; TomasꢀGamasa, M.; Aznar, F.; Valdes, C. Nat. Chem. 2009, 1, 494.
(17) So, S. S.; Mattson, A. E. Asian J. Org. Chem. 2014, 3, 425.
(18) Ballini, R.; Palmieri, A.; Petrini, M.; Torregiani, E. Org. Lett. 2006, 8, 4093.
(19) Dong, H.ꢀM.; Lu, H.ꢀH.; Lu, L.ꢀQ.; Chen, C.ꢀB.; Xiao, W.ꢀJ. Adv. Synth. Catal. 2007, 349,
1
(
597.
20) Song, B.; Himmler, T.; Gooßen, L. J. Adv. Synth. Catal. 2011, 353, 1688.
(21) Terazono, Y.; North, E. J.; Moore, A. L.; Moore, T. A.; Gust, D. Org. Lett. 2012, 14, 1776.
(22) Auvil, T. J.; So, S. S.; Mattson, A. E. Angew. Chem. Int. Ed. 2013, 52, 11317.
ACS Paragon Plus Environment
27