Gold-Catalyzed Annulations of N-Propargyl Ynamides with Anthranils with Two Distinct Chemoselectivities

Article abstract of DOI:10.1002/chem.201806083

Gold-catalyzed annulation of N-propargyl ynamides with anthranils can proceed by two distinct mechanisms. In the case of a terminal N-propargyl ynamide, its resulting α-imino gold carbene reacts with a tethered alkyne to generate a vinyl cation to enable hydrolysis, which ultimately yields a pyrrolo[2,3-b]quinoline derivative after treatment with p-toluenesulfonic acid. For an internal alkyne, its α-imino gold carbene reacts with a tethered alkyne via either a vinyl cation or an alkenylgold carbene; both paths ultimately lead to a 4-ketone-2-aminopyrrole derivative. Our mechanistic analysis indicates that water is a better nucleophile than anthranil for terminal ynamides, whereas water and anthranils are equally reactive for internal ynamides.

Full text of DOI:10.1002/chem.201806083

A Journal of
Accepted Article
Title: Gold-catalyzed Annulations of N-Propargyl Ynamides with
Anthranils With Two Distinct Chemoselectivities
Authors: Rai-Shung Liu, Yu-Chen Hsu, and Shu-An Hsieh
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To be cited as: Chem. Eur. J. 10.1002/chem.201806083
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Gold-catalyzed Annulations of N-Propargyl Ynamides with
Anthranils With Two Distinct Chemoselectivities
Yu-Chen Hsu, Shu-An Hsieh and Rai-Shung Liu*
Abstract: Gold-catalyzed annulation of N-propargyl ynamides with
deliver compounds 7' (Scheme 1, eq 4).
anthranils can proceed via two distinct mechanisms. In the case of a
terminal N-propargyl ynamide, its resulting -imino gold carbene
reacts with a tethered alkyne to generate a vinyl cation to enable
hydrolysis, ultimately yielding a pyrrolo[2,3-b]quinoline derivative after
treatment with TsOH. For an internal alkyne, its -imino gold carbene
reacts with a tethered alkyne via either a vinyl cation or an alkenylgold
carbene; both paths lead to a 4-ketone-2-aminopyrrole derivative
ultimately. Our mechanistic analysis indicates that water is a better
nucleophile than anthranil for terminal ynamides whereas water and
anthranils are equally reactive for internal ynamides.
Introduction
Interest in the generation of gold carbenes from alkynes is
rapidly increasing in synthetic chemistry.1 -Oxo gold carbenes
generated from the alkyne oxidations are synthetically valuable
because of their versatility toward cyclopropanations,2 X-H
additions (X = C, N and O),3 annulations,4 cyclizations5 and
skeletal rearrangements.6 Hashmi reported that -oxo gold
carbenes could react with tethered alkynes to yield alkenyl metal
carbenes via a 1,6-carbene transfer (Scheme 1, eq 1).7 Such a
1,6-carbene transfer was noted also for rhodium catalysts8 and
several gold carbenes generated from 1,3-acyloxy shifts of
Scheme 1. The reactions of metal carbenes with alkynes
propargyl acetates.9 Although alkynes can also generate -imino
gold carbenes using various nitrogen-containing nucleophiles, in
most cases these -imino carbenes are transformed into pyrroles
and other azacycles via a rapid intramolecular cyclization.10-12
Elaboration of -imino gold carbenes for other synthetic
applications is less explored. Ye and coworkers reported that -
imino gold carbenes could react with alkynes to generate vinyl
cations (Scheme 1, eq 2)12a, in a path distinct from that of -oxo
gold carbenes (Scheme 1, eq 1). To gain insight into -imino gold
carbenes, we report two distinct reactions between N-propargyl
ynamides (1 and 6) and anthranils. Herein, the resulting -imino
gold carbenes In-5 can react with tethered terminal alkynes (R =
H) to form vinyl cations In-5 that is trapped by water to deliver
Pyrrolo[2,3-b]quinoline cores are found in several bioactive
and naturally occurring molecules13 including PGP-4008 (VIII-1),
neocryptofelepine (VIII-2) and perophoramidine (VIII-3).
Compound VIII-1 was effective to inhibit Pgb in vitro; the other two
species (VIII-2 and VIII-3) are natural alkaloids (see Figure 1).
pyrrolyl species 3, and pyrrolo[2,3-b]quinoline products
4
sequentially (Scheme 1, eq 3). For internal alkynes (R = Ar), the
corresponding gold carbenes In-5' might form vinyl cation or
alkenylgold carbenes In-6 that can be trapped by an anthranil to
Figure 1. Representative bioactive and natural products
Results and Discussion
[*]
Yu-Chen Hsu, Shu-An Hsieh and Prof. Dr. Rai-Shung Liu
Department of Chemistry, National Tsing-Hua University
Hsinchu (30013), Taiwan
Table 1 shows the reactions of N-tosyl propargyl ynamide14
(1a) with anthranil15 (2a) using various metallic catalysts. In
entries 1-10, the resulting DCE solution was washed with
aqueous HCl (1 M) solution to ensure a complete hydrolysis of its
ketone-derived imine 3a' (vide infra, Table 5). We tested the
catalytic efficiency with 5 mol % LAuCl/AgNTf2 (L = P(t-Bu)2(o-
biphenyl)), (PhO)3PAuCl/AgNTf2 and IPrAuCl/ AgNTf2) in DCE
E-mail: rsliu@mx.nthu.edu.tw .
Supporting information for this article is given via a link at the end of
the document.
o
near 23 C, affording pyrrole derivative 3a in yield 33-36 %. A
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change of silver salts as in IPrAuCl/AgX (X = SbF6 and OTf)
increased the yield of compound 3a to 50 % and 55 % (entries 4-
5). We switched to Zn(OTf)2 and PtCl2/CO, each at 5 mol %, giving
unreacted species 1a with 84-86 % recovery (entries 6-7). We
used 5 mol % AuCl to afford desired product 3a in yield 35 %
(entry 8). To our pleasure, AuBr3 and AuCl3, each at 5 mol %
loading, were reactive to deliver compound 3a in yields 72 % and
79 %, respectively (entries 9-10). When initial N-propargyl
ynamide (1a) was completely consumed in this AuCl3-catalyzed
reaction, we added p-toluenesulfonate acid (TsOH, 20 mol %) to
enable a further transformation of pyrrole product 3a into a new
pyrrolo[2,3-b]quinoline 4a in yield 82 % (entry 11). This
AuCl3/TsOH reaction sequence in dichloromethane (DCM) and
nitromethane delivered 4a in yields 81 % and 54 % respectively
(entries 12-13). AuCl3 alone failed to show a catalytic activity in
THF and CH3CN, with a large recovery of N-propargyl ynamide
1a. The molecular structure of compound 4a was determined with
X-ray diffraction (see Figure 2).16 We also performed the reaction
between N-tosyl propargyl ynamide (1a) with isoxazole (2 equiv)
using P(t-Bu)2(o-biphenyl)AuCl/AgNTf2 (10 mol %), and we
recovered starting 1a in 74% after heating the mixture in DCE (65
oC, 16 h).
Figure 2. Molecular structures of compounds 4a (left) and 4c (right)
o
dichloroethane (DCE) near 23 C; the results are summarized in
Table 2. In entries 1-5, various 1,5-diynes 1b-1f bearing para-
phenyl substituents were examined; electron-donating and -
withdrawing substituents (X = Me, OMe, F, Cl and Br) were
operable with 5 mol % AuCl3 and 20 mol % TsOH to afford
compounds 4b-4f and 4c in satisfactory yields (62-87 %); herein,
the donating groups (X = Me and OMe) seemed to be more
efficient because of their high reactivity in the attack of alkyne on
gold carbene In-5. We used also various meta-substituted
Table 2. Reactions with terminal N-propargyl ynamides.
Table 1. Optimization of Reaction Conditions.
[a]
[b]
entry
catalyst
(mol%)
solvent
TsOH
t1
t2
yields(%)[e]
(mol%)
(min)
(h)
1a
-
3a
33
36
36
50
55
-
4a
-
1
2
LAuCl(5)[c]/AgNTf2(5)
(PhO)3PAuCl(5)/AgNTf2(5)
IPrAuCl(5)[d]/AgNTf2(5)
IPrAuCl(5)[d]/AgSbF6(5)
IPrAuCl(5)[d]/AgOTf(5)
Zn(OTf)2(5)
DCE
DCE
-
-
40
40
40
30
30
6h
12h
1h
20
20
20
25
25
7h
7h
-
-
-
-
3
DCE
-
-
-
-
4
DCE
-
-
-
-
5
DCE
-
-
-
-
6
DCE
-
-
84
86
-
-
7
PtCl2(5)/CO
DCE
-
-
-
-
8
AuCl(5)
DCE
-
-
-
35
72
79
-
-
9
AuBr3(5)
DCE
-
-
-
10
11
12
13
14
15
AuCl3(5)
DCE
-
-
-
-
AuCl3(5)
DCE
20
20
20
-
2.5
2.5
4
-
82
81
54
-
AuCl3(5)
DCM
CH3NO2
THF
-
-
AuCl3(5)
-
-
AuCl3(5)
-
73
68
-
AuCl3(5)
CH3CN
-
-
-
-
[a] Period required for the first step. [b] Period required for the second step.
[c] L=P(t-Bu)2(o-biphenyl). [d] IPr = 1,3-bis(diisopropylphenyl)imidazol-2-
ylidene. [e] Product yields were obtained after purification from a silica
column.
1 (0.05 M, 1.0 equiv.) and 2a (1.3 equiv.).[a] Product yields were obtained
after purification from a silica column. [b] These values correspond to t1 (h)/t2
We assessed the scope of these pyrrolo[2,3-b]quinoline
syntheses using various N-substituted propargyl ynamides 1b-1s
bearing terminal alkynes at the ynamide moieties. The reactions
were performed with AuCl3 (5 mol %) and TsOH (20 mol %) in
(h).
propargyl ynamides (X = Me, OMe and Cl) to afford the desired
pyrrolo[2,3-b]quinolines in yields 43-55 % (entries 6-8). We
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prepared also ortho-substituted substrates 1j-1n (X = Me, OMe,
F, Cl and Br) that afforded desired products 4j-4n in yields 43-
66 % (entries 9-13). The reactions were extensible to 1-naphthyl-
substituted 1,5-diyne 1o, yielding desired product 4o in yield 84 %
(entry 14). For thienyl-substituted 1,5-diyne derivatives 1p and 1q,
their corresponding pyrrolo[2,3-b]quinoline products 4p and 4q
were produced in yields only 31-34 % (entries 15 and 16). For N-
mesyl propargyl ynamide 1r (R' = Ms), its corresponding
pyrrolo[2,3-b]quinoline 4r was produced in yield 64 %. This
annulation was unsucessful with cyclopropyl-substituted
parpargyl amine 1s, giving a complicated mixture of products
(entry 18). Among these products, the molecular structure of
pyrrolo[2,3-b]quinoline 4c was characterized with X-ray diffraction
(see Figure 2).16
Figure 3. Molecular structures of compounds 5i (left) and 7a’(right)
N-Propargyl ynamides bearing internal ynamides show a
distinct chemoselectivity. We selected aryl-substituted ynamides
as a target because alkyl-substituted ynamides will generate gold
carbenes that will undergo
a
1,2-hydrogen shift.10d,10g,11a
Treatment of species 6a with anthranil 2a (2.2 equiv) gave imine
derivative 7a' and its hydrolysis product 7a in molar ratio 1.2:1;
the combined yields were 82 % (Scheme 2). When 6a/2a was
used in molar ratio 1:1, the combined yields of 7a/7a' were 44 %.
These two compounds were not separable on a silica column, but
crystallization of this mixture in DCM afforded pure product 7a' in
yield 42 %. The molecular structure of imine derivative 7a' was
confirmed with X-ray diffraction (see Figure 3).16 Treatment of this
7a/7a' mixture with 37 % HCl (1 equiv) in the mother solution
yielded ketone 7a in overall yield 82 % (Scheme 2).
Table 3 shows the suitability of these reactions for various
anthranils using AuCl3/TsOH catalysts; the desired pyrrolo[2,3-
b]quinolines 5b-5k were obtained in yields satisfactory to
excellent, except pyrrole derivative 3l that failed to undergo a
Friedel-Craft reaction with TsOH. For 5-substituted anthranils 2b-
2f, (R1 = Cl, Br, Me, OMe and OCO2Et), their annulations with 1,5-
diyne 1a delivered pyrrolo[2,3-b]quinolines 5b-5f in yields 64-
91 % (entries 1-5). In the case of anthranils 2g-2i bearing R2 = Cl,
Br and Me, their corresponding products 5g-5i were obtained in
yields 67-90 % (entries 6-8). We tested the reaction also with
dimethoxyphenyl and dioxolo-substituted anthranils 2j-2k, further
affording compounds 5j and 5k in yields 77 % and 74 %
respectively (entries 9-10). The molecular structure of compound
5i was confirmed with X-ray diffraction (see Figure 3).16 We tested
the reaction of 3-methylanthranil 2l that afforded pyrrole derivative
3l without a further cyclization, because of the poor electrophilicity
of the ketone group.
Table 3. Reactions with various anthranils.
Scheme 2. Catalytic reactions on internal ynamide
Table 4 shows the scope of the reactions of various internal
ynamides 6b-6d and anthranils 2; in these cases, we first
estimated the ratios of crude mixtures of imine derivatives 7' and
ketone products 7, ranging from 7'/7 ratios 2.5-0.5. Because of
the difficulty of separating the two products, these crude products
were treated with aqueous HCl to deliver 4-ketonyl pyrroles 7
efficiently. For various 4-phenyl ynamides 6b-6c (X = Cl and Me)
and their thienyl analogue 6d, their resulting 4-ketonyl pyrroles
7b-7d were obtained in yields 47-76 % (entries 1-3). These gold-
catalyzed reactions were applicable also to 5- and 6-substituted
anthranils, yielding desired pyrrole products 7e-7g in yields 57-
85 % (entries 4-6).
We examine the effects of water and anthranil on the
chemoselectivity of ynamides 1a and 6a; the results are
summarized in Table 5. Initial ynamides were completely
consumed for all cases. In the presence of MS 4A, the reaction of
terminal ynamide 1a with anithranil 2a (2 equiv) in DCE (25 oC 20
min) gave a mixture of imine 3a' and ketone 3a with a ratio of
3a/3a' = 2.7/1, the combined yield was only 45% (entry 1).
1a (0.05 M, 1.0 equiv.) and 2 (1.3 equiv.).[a] Product yields were obtained
after purification from a silica column. [b] These values correspond to t1 (h)/t2
(h).
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whereas water and anthranil are equally competitive for internal
ynamides.
Table 4. Reactions with internal N-propargyl ynamides.
We conducted 18O-labeling experiments to elucidate the
annulation mechanism of terminal ynamide 1a and anthranil 2a.
In the presence of H218O (2 equiv), these two reactants yielded
desired 18O-3a with one 18O-atom enrichment ca. 42%, indicating
that H2O was the oxygen source of its ketone group (Scheme 3).
To support this argument, the resulting compound 18O-3a was
treated with TsOH in DCE to yield species 18O-4a that is highly
enriched with 18O; this information indicates that the initial 18O-
content is located on the ketone group of species 18O-3a. We also
performed additional expeiments to confirm that species 3a and
4a do not undergo 18O-exchange with external H218O in the
presence of AuCl3 or TsOH. In the presence of H2O (5 equiv), we
analyzed the compositions of crude products with 1H NMR
analysis; we found no NMR signal assignable to 2-
aminobenzaldehyde. In fact, this reaction was complete with a
ratio of reactants 1a/2a = 1/1.3; accordingly, pyrrole derivative 3a
could not arise from a facile hydration of imine derivative 3a'. For
one specific product 4n, a Pd-catalyzed intramolecular cyclization
delivered polycyclic azacyclic product 8a in yield 82 % (Scheme
3).
6 (0.05 M, 1.0 equiv.) and 2 (2.2 equiv.).[a] Product yields were obtained
after purification from a silica column. [b] These values correspond to t1 (h)/t2
(h).
Additional anthranil 2a (6 equiv) did not affect this product ratio
(3a/3a' = 2.5/1) and the yields (46%, entry 2). Although we were
unable to separate the two products because of a facile hydrolysis
of iminie species 3a' on a silica column; the quantitative analysis
could be estimated by 1H-NMR and HRMS. In the absence of MS
4A, ketone 3a will become dominant as long as suffient water was
present, the combined yields were high (59-82%) (entries 3-6).
For internal ynamide 6a, the yields of ketone 7a and its imino
derivative 7a' are proportional to the amount of water and
anthranil respectively. The data in Table 1 indicates that water is
better than anthranil as a nucleophile for terminal ynamide
Table 5. Competition of water and anthranil 2a
entry
1
alkynes
1a
n
2
m
0
additives
MS 4A
Product (yields)[b,c]
3a/3a‘ = 2.7/1 (45%)
2
3
4
5
6
7
8
1a
1a
1a
1a
6a
6a
6a
6
2
0
0
0
2
0
0
0
MS 4A
3a/3a‘ = 2.5/1 (46%)
3a/3a‘ = 3.3/1 (60%)
3a/3a‘ = 4.2/1 (82%)
3a/3a‘ = 3.3/1 (59%)
7a/7a‘ = 1/6 (80%)
7a/7a‘ = 1/3.3 (73%)
7a/7a‘ = 1/1.2 (83%)
Scheme 3. 18O-labeling experiment and application
-
We postulate plausible mechanisms as depicted in Scheme 4.
For terminal N-propargyl ynamide 1a, its gold -complex A is
attacked by anthranil 2a to generate imino gold carbene C, in
which the carbene functionality is attacked by a tethered terminal
alkyne to generate a vinyl cation as depicted by species D (path
a). A water attack of this vinyl cation species yields species E and
F sequentially. An auto-oxidation of species F forms the observed
pyrrole products 3a that undergo an intramolecular cyclization to
yield a final pyrrolo[2,3-b]quinoline derivative 4a. Notably, in this
process, water participates in the attack at the vinyl cation D, but
is released again in the formation of pyrrole product 3a.
Accordingly, water can be considered a catalyst to facilitate the
1.3
2
-
-
4
MS 4A
4
-
-
2.2
[a] Molarity = 0.05 M, [b] The ratios of 3a/3a', were deterimned by 1H NMR spectra
before hydrolysis. [c] Yields are reported based on the amount of 3a or 7a after the
hydrolysis of the mixtures
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reaction, and the presence of MS 4A is unable to inhibit this
reaction completely.
carbene reacted with a tethered alkyne via either a vinyl cation or
a alkenylgold carbene; both paths lead to the same 4-ketone-2-
aminopyrrole product after treatment with aqueous HCl solution.
For internal alkynes 6, we observe that anthranil 2a is as
efficient as water to attack at the propargyl alkyne; this information
suggests that the occurrence of vinyl cations D' is difficult because
its gold moiety is situated in a highly hindered quaternary carbon.
However, in the reactions of vinyl cations D' with anthranils, the
weak Au-C bond of resulting intermediate G might lead to a facile
cleavage of the oxazole ring. If this N-O cleavage is the rate
determining step, the attack of anthranil and water on cations D'
will have the same nucleophilicity.
An alternative mechanism is the formation of alkenylgold
carbenes D'' from a carbene/alkyne metathesis of -imino gold
carbenes C'; gold and rhodium carbenes were known to be very
active toward anthranil to generate 2-imino benzaldehydes.17
Gold carbene D'' is also responsible for formation of ketone
product 7a through carbene hydrolysis and aerobic oxidation
sequence.
Experimental Section
General
Unless otherwise noted, all the reaction for the preparation of the
substrates were performed in oven-dried glassware under nitrogen
atmosphere with freshly distilled solvents, toluene, tetrahydrofuran (THF)
and hexane were dried with sodium, benzophenone and distilled before
use. Dichloromethane (DCM), ether and 1,2-dichloroethane (DCE) were
dried over CaH2 and distilled before use. All other commercial reagents
were used without further purification, unless otherwise indicated.
Reactions were magnetically stirred and monitored by thin layer
chromatography carried out on 0.25 mm E. Merck silica gel plate (60f -254)
using UV light as visualizing agents. 1H NMR and 13C NMR spectra were
recorded on a Bruker 400 MHz, 500 MHz and 600MHz, Varian 400 MHz
and 500MHz. Spectrometers using chloroform-d (CDCl3) as the internal
standards. Melting points of solid compounds were recorded using Buchi
melting point B-540.
(1.1) Standard procedure for synthesis of compound (3a)
A single neck tube was charged with AuCl3 (2.45 mg, 0.0081 mmol), and
to this was added dry DCE (1mL). The resulting mixture was stirred at
room temperature for 5 minutes. To this mixture was added a dry DCE
(2.5mL)
solution
of
N-ethynyl-4-methyl-N-(3-phenylprop-2-yn-1-
yl)benzene sulfonamide 1a (50 mg, 0.1616 mmol) and anthranil 2a (25 mg,
0.2101 mmol). After stirring at room temperature for 20 minutes, the
reaction mixture was filter over a short celite bed, concentrated. The crude
compound was then added 1M HCl(aq) (3mL), and stirred at room
temperature for 1h. The reaction mixture extracted twice with 1M HCl(aq),
and the organic extract was dried (MgSO4), concentrated and eluted
through a silica column with ethyl acetate/hexane to afford 3a (56.8 mg ,
0.128 mmol, 79%) as yellow oil.
(1.2) Standard procedure for synthesis of compound (4a)
A single neck tube was charged with AuCl3 (2.45 mg, 0.0081 mmol), and
to this was added dry DCE (1mL). The resulting mixture was stirred at
room temperature for 5 minutes. To this mixture was added a dry DCE
(2.5mL)
solution
of
N-ethynyl-4-methyl-N-(3-phenylprop-2-yn-1-
yl)benzene sulfonamide 1a (50 mg, 0.1616 mmol) and anthranil 2a (25 mg,
0.2101 mmol). After stirring at room temperature for 20 minutes, we
monitored with TLC analysis. After 1a was finished, to this solution was
added TsOH (6.2 mg, 0.0323 mmol), and the mixture was stirred at room
temperature for 2.5 hours. The reaction mixture was filter over a short
celite bed. The solvent was evaporated under reduced pressure, and
eluted through a silica column with ethyl acetate/hexane to afford 4a (56.5
mg, 0.133 mmol, 82%) as yellow solid.
Scheme 4. Plausible mechanisms.
Conclusions
(1.3) Standard procedure for synthesis of compound (7a)
In summary, gold-catalyzed annulations of N-propargyl
ynamides with anithranils were examined. In the case of a
terminal alkyne, the resulting -imino gold carbene reacted with a
tethered alkyne to generate a vinyl cation that was trapped with
A single neck tube was charged with AuCl3 (1.97 mg, 0.0065 mmol), and
to this was added dry DCE (1mL). The resulting mixture was stirred at
room temperature for 5 minutes. To this mixture was added a dry DCE
(1.6mL) solution of 4-methyl-N-(phenylethynyl)-N-(3-phenylprop-2-yn-1-
yl)benzenesulfonamide 6a (50 mg, 0.1297 mmol) and anthranil 2a (34 mg,
0.285 mmol). After stirring at room temperature for 20 minutes, we
water to yield
a pyrrolo[2,3-b]quinoline via acid-catalyzed
intramolecular cyclization. For an internal alkyne, its -imino gold
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monitored with TLC analysis. After 6a was finished, to this solution was
added 37% HCl (11 µL, 0.1297 mmol), and the mixture was stirred at room
temperature for 1.0 hour. The reaction mixture was filter over a short celite
bed. The solvent was evaporated under reduced pressure, and eluted
through a silica column with ethyl acetate/hexane to afford 7a (55.4 mg,
0.106 mmol, 82%) as yellow oil.
(4-fluorophenyl)(1-tosyl-1H-pyrrolo[2,3-b]quinolin-3-yl) methanone
(4d): Yellow solid; mp: 215.2~215.6℃;(30% ethylacetate/hexane, Rf =
0.32, 42.1 mg, 0.095 mmol, 62%); 1H NMR (500 MHz, CDCl3): δ 9.05 (s,
1H), 8.33 (s, 1H), 8.25 (d, J = 7.5Hz, 2H), 8.19 (d, J = 8.5Hz, 1H),
7.97~7.92 (m, 3H), 7.74 (t, J = 8.0Hz, 1H), 7.52 (t, J = 7.5Hz, 1H), 7.29 (d,
J = 8.0Hz, 2H), 7.24 (t, J = 8.0Hz, 2H), 2.34 (s, 3H); 13C NMR (125 MHz,
CDCl3): δ 188.7, 166.4 (d: JC-F = 252.8Hz), 164.4 (d: JC-F = 252.8Hz), 147.4,
146.1, 145.9, 136.2, 134.8, 134.8, 134.1, 131.4 (d: JC-F = 6.26Hz), 131.4
(d: JC-F = 6.26Hz), 131.3, 129.7, 129.6, 128.9, 128.6, 126.4, 125.5, 120.7,
116.9, 116.1 (d: JC-F = 21.8Hz), 115.9 (d: JC-F = 21.8Hz), 21.7; ESI-MS
(M+H) calcd. for C25H18FN2O3S:445.1022; Found: 445.10210.
2-((4-benzoyl-1-tosyl-1H-pyrrol-2-yl)amino)benzaldehyde (3a): Yellow
oil;(30% ethylacetate/hexane, Rf = 0.17, 56.8 mg , 0.128 mmol, 79%); 1H
NMR (600 MHz, CDCl3): δ 9.94 (s, 1H), 9.90 (s, 1H), 7.85~7.84 (m, 2H),
7.71 (d, J = 1.2Hz, 1H), 7.62 (d, J = 7.2Hz, 2H), 7.61~7.58 (m, 1H),
7.56~7.55 (m, 1H), 7.50 (t, J = 7.8Hz, 2H), 7.18 (td, J = 7.2Hz & 1.2Hz,
1H), 7.12~7.08 (m, 2H), 6..84 (t, J = 7.2Hz, 1H), 6.65 (d, J = 8.4Hz, 1H),
6.60 (s, 1H), 2.29 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 194.4, 189.9,
147.1, 145.8, 138.3, 135.9, 135.6, 134.1, 132.3, 130.2, 129.9, 129.0, 128.6,
127.9, 124.6, 124.5, 119.6, 118.4, 113.3, 107.5, 21.6; ESI-MS (M+Na)
calcd. for C25H20N2NaO4S:467.1041; Found: 467.10231.
(4-chlorophenyl)(1-tosyl-1H-pyrrolo[2,3-b]quinolin-3-yl) methanone
(4e): Yellow solid; mp: 195.2~196.1℃;(30% ethylacetate/hexane, Rf = 0.26,
1
45.6 mg, 0.099 mmol, 68%); H NMR (600 MHz, CDCl3): δ 9.06 (s, 1H),
8.31 (s, 1H), 8.24 (d, J = 8.5Hz, 2H), 8.19 (d, J = 8.4Hz, 1H), 7.97 (dd, J =
8.2Hz & 0.7Hz, 1H), 7.84 (dt, J = 8.9Hz & 1.9Hz, 2H), 7.76~7.73 (m, 1H),
7.56~7.52 (m, 3H), 7.29 (d, J = 8.3Hz, 2H), 2.35 (s, 3H); 13C NMR (150
MHz, CDCl3): δ 189.0, 147.4, 146.2, 145.9, 139.0, 136.9, 136.4, 134.1,
131.5, 130.2, 129.7, 129.7, 129.2, 129.0, 128.7, 126.4, 125.5, 120.6, 116.8,
21.7; ESI-MS (M+H) calcd. for C25H18ClN2O3S:461.0727; Found:
461.07197.
1-(2-((4-benzoyl-1-tosyl-1H-pyrrol-2-yl)amino)phenyl)ethan-1-one
(3b) : Yellow oil;(30% ethylacetate/hexane, Rf = 0.20, 62.3 mg, 0.136 mmol,
84%); 1H NMR (600 MHz, CDCl3): δ 10.55 (s, 1H), 7.85~7.83 (m, 2H), 7.78
(dd, J = 8.0Hz & 1.4Hz, 1H), 7.68 (d, J = 1.9Hz, 1H), 7.64 (dd, J = 8.7Hz
& 2.0Hz, 2H), 7.58 (tt, J = 6.9Hz & 1.3Hz, 1H), 7.49 (t, J = 7.9Hz, 2H), 7.13
(td, J = 7.2Hz & 1.6Hz, 1H), 7.09 (d, J = 8.0Hz, 2H), 6.74 (td, J = 7.1Hz &
1.1Hz, 1H), 6.70 (dd, J = 8.5Hz & 0.7Hz, 1H), 6.54 (q, J = 1.0Hz, 1H), 2.67
(s, 3H), 2.29 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 201.5, 190.0, 147.3,
145.7, 138.4, 134.6, 134.2, 132.3, 131.9, 131.3, 129.9, 129.0, 128.5, 127.9,
124.6, 124.3, 119.3, 117.8, 114.4, 106.3, 28.0, 21.6; ESI-MS (M+H) calcd.
for C26H23N2NaO4S:459.1379; Found: 459.13786.
(4-bromophenyl)(1-tosyl-1H-pyrrolo[2,3-b]quinolin-3-yl) methanone
(4f): White solid; mp: 203.4~204.2℃;(30% ethylacetate/hexane, Rf = 0.40,
1
46.9 mg, 0.093 mmol, 72%); H NMR (600 MHz, CDCl3): δ 9.06 (s, 1H),
8.31 (s, 1H), 8.24 (dt, J = 8.8Hz & 2.0Hz, 2H), 8.19 (d, J = 8.2Hz, 1H), 7.97
(dd, J = 8.2Hz & 0.7Hz, 1H), 7.77~7.73 (m, 3H), 7.71 (dt, J = 8.6Hz & 2.0Hz,
2H), 7.55~7.52 (m, 1H), 7.29 (d, J = 8.5Hz, 2H), 2.35 (s, 3H); 13C NMR
(150 MHz, CDCl3): δ 189.2, 147.5, 146.2, 145.9, 137.4, 136.5, 134.1,
132.1, 131.5, 130.3, 129.7, 129.7, 129.0, 128.7, 127.5, 126.5, 125.6, 120.6,
116.8, 21.7; ESI-MS (M+H) calcd. for C25H18BrN2O3S:505.0222; Found:
505.02326.
phenyl(1-tosyl-1H-pyrrolo[2,3-b]quinolin-3-yl)methanone (4a) : White
solid; mp: 171.4~173.8℃;(30% ethylacetate/hexane, Rf = 0.32, 56.5 mg,
0.133 mmol, 82%); 1H NMR (600 MHz, CDCl3): δ 9.10 (s, 1H), 8.24 (dd, J
= 6.8Hz & 1.7Hz, 2H), 8.19 (dd, J = 8.6Hz & 0.4Hz, 1H), 7.98 (dt, J = 8.2Hz
& 0.7Hz, 1H), 7.89 (dt, J = 6.2Hz & 0.5Hz, 2H), 7.74 (t, J = 8.4Hz, 1H),
7.65 (t, J = 7.5Hz, 1H), 7.57 (t, J = 7.9Hz, 2H), 7.53 (t, J = 8.1Hz, 1H), 7.29
(d, J = 8.1Hz, 2H), 2.34 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 190.4, 147.5,
146.1, 145.9, 138.6, 136.6, 134.1, 132.5, 131.5, 129.7, 129.5, 129.0, 128.9,
128.9, 128.8, 128.7, 126.5, 125.5, 120.8, 117.1, 21.7; ESI-MS (M+H) calcd.
for C25H19N2O3S:427.1116; Found: 427.11146.
m-tolyl(1-tosyl-1H-pyrrolo[2,3-b]quinolin-3-yl)methanone (4g): White
solid; mp: 175.5~176.1℃;(30% ethylacetate/hexane, Rf = 0.34, 29.3 mg,
0.067 mmol, 43%); 1H NMR (600 MHz, CDCl3): δ 9.08 (s, 1H), 8.33 (s, 1H),
8.23 (d, J = 8.5Hz, 2H), 8.19 (d, J = 8.6Hz, 1H), 7.98 (d, J = 7.7Hz, 1H),
7.75~7.72 (m, 1H), 7.68~7.66 (m, 2H), 7.54~7.52 (m, 1H), 7.45 ( d, J =
7.0Hz, 2H), 7.28 (d, J = 8.2Hz, 2H), 2.48 (s, 3H), 2.34 (s, 3H); 13C NMR
(150 MHz, CDCl3): δ 190.6, 147.6, 146.1, 145.9, 138.8, 138.7, 136.6,
134.2, 133.3, 131.5, 129.7, 129.5, 129.3, 129.0, 128.9, 128.7, 128.6, 128.2,
126.5, 126.1, 125.4, 120.8, 117.2, 21.7, 21.5; ESI-MS (M+H) calcd. for
C26H21N2O3S:441.1273; Found: 441.12776.
p-tolyl(1-tosyl-1H-pyrrolo[2,3-b]quinolin-3-yl)methanone (4b): White
solid; mp: 170.2~171.3℃;(30% ethylacetate/hexane, Rf = 0.37, 51.8 mg,
0.117 mmol, 76%); 1H NMR (400 MHz, CDCl3): δ 9.07 (s, 1H), 8.34 (s, 1H),
8.23 (d, J = 8.4Hz, 2H), 8.19 (d, J = 8.5Hz, 1H), 7.97 (d, J = 8.1Hz, 1H),
7.81 (d, J = 8.1Hz, 2H), 7.73 (t, J = 7.2Hz, 1H), 7.52 (t, J = 7.6Hz, 1H),
7.36 (d, J = 8.0Hz, 2H), 7.28 (d, J = 8.4Hz, 2H), 2.48 (s, 3H), 2.34 (s, 3H);
13C NMR (100 MHz, CDCl3): δ 190.0, 147.5, 146.0, 145.8, 143.3, 136.2,
136.0, 134.2, 131.4, 129.7, 129.5, 129.0, 129.0, 128.9, 128.6, 126.4, 125.4,
120.9, 117.2, 21.6; ESI-MS (M+H) calcd. for C26H21N2O3S:441.1273;
Found: 441.12850.
(3-methoxyphenyl)(1-tosyl-1H-pyrrolo[2,3-b]quinolin-3-yl)methanone
(4h): White solid; mp: 148.0~150.1℃;(40% ethylacetate/hexane, Rf = 0.30,
1
37.0 mg, 0.081 mmol, 55%); H NMR (600 MHz, CDCl3): δ 9.08 (s, 1H),
8.37 (s, 1H), 8.24 (d, J = 8.2Hz, 2H), 8.19 (d, J = 8.6Hz, 1H), 7.97 (d, J =
8.2Hz, 1H), 7.74 (t, J = 7.1Hz, 1H), 7.53 (t, J = 7.4Hz, 1H), 7.48~7.46 (m,
2H), 7.39 (s, 1H), 7.28 (d, J = 8.2Hz, 2H), 7.18 (d, J = 6.7Hz, 1H), 3.89 (s,
3H), 2.34 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 190.1, 159.9, 147.5, 146.1,
145.9, 139.9, 136.7, 134.2, 131.5, 129.8, 129.7, 129.5, 129.0, 128.9, 128.6,
126.4, 125.4, 121.3, 120.7, 118.7, 117.1, 113.5, 55.5, 21.7; ESI-MS (M+H)
calcd. for C26H21N2O4S:457.1222; Found: 457.12243.
(4-methoxyphenyl)(1-tosyl-1H-pyrrolo[2,3-b]quinolin-3-yl)
methanone (4c): Yellow solid; mp: 175.0~176.5
℃ ;(40%
ethylacetate/hexane, Rf = 0.31, 58.5 mg, 0.128 mmol, 87%); 1H NMR (400
MHz, CDCl3): δ 9.02 (s, 1H), 8.34 (s, 1H), 8.24 (d, J = 8.4Hz, 2H), 8.19 (d,
J = 8.6Hz, 1H), 7.96~7.90 (m, 3H), 7.74~7.70 (m, 1H), 7.51 (t, J = 7.2Hz,
1H), 7.27 (d, J = 8.3Hz, 2H), 7.03 (dd, J = 8.8Hz & 1.8Hz, 2H), 3.90 (s, 3H),
2.32 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 188.8, 163.3, 147.5, 146.0,
145.8, 135.6, 134.2, 131.3, 129.7, 129.4, 128.9, 128.8, 128.6, 126.4, 125.3,
121.0, 117.2, 55.5, 21.6; ESI-MS (M+H) calcd. for C25H21N2O4S:457.1222;
Found: 457.12242.
(3-chlorophenyl)(1-tosyl-1H-pyrrolo[2,3-b]quinolin-3-yl) methanone
(4i): Yellow solid; mp: 163.1~165.3℃;(30% ethylacetate/hexane, Rf = 0.37,
1
36.2 mg, 0.079 mmol, 54%); H NMR (400 MHz, CDCl3): δ 9.07 (s, 1H),
8.32 (s, 1H), 8.25 (d, J = 8.4Hz, 2H), 8.19 (d, J = 8.6Hz, 1H), 7.98 (d, J =
8.0Hz, 1H), 7.84 (s, 1H), 7.77~7.74 (m, 2H), 7.62 (d, J = 8.1Hz, 1H),
7.56~7.49 (m, 2H), 7.30 (d, J = 8.2Hz, 2H), 2.35 (s, 3H); 13C NMR (100
MHz, CDCl3): δ 188.8, 147.5, 146.2, 146.0, 140.2, 136.7, 135.2, 134.1,
132.4, 131.5, 130.1, 129.8, 129.7, 129.0, 128.8, 128.7, 126.9, 126.5, 125.6,
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10.1002/chem.201806083
Chemistry - A European Journal
FULL PAPER
120.5, 116.8, 21.7; ESI-MS (M+H) calcd. for C25H18ClN2O3S:461.0727;
Found: 461.07328.
1H), 8.22~8.18 (m, 4H), 8.16 (s, 1H), 8.06 (d, J = 8.3Hz, 1H), 8.01 (d, J =
8.2Hz, 1H), 7.95 (d, J = 7.8Hz, 1H), 7.76 (t, J = 7.0Hz, 2H), 7.61 (d, J =
8.0Hz, 1H), 7.58~7.50 (m, 3H), 7.27 (d, J = 8.1Hz, 2H), 2.34 (s, 3H); 13
C
NMR (100 MHz, CDCl3): δ 191.9, 147.7, 146.1, 145.9, 137.7, 136.4, 134.1,
134.0, 131.7, 131.6, 130.5, 129.7, 129.6, 128.7, 128.5, 127.4, 127.0, 126.7,
126.6, 125.5, 125.3, 124.5, 120.4, 119.0, 21.7; ESI-MS (M+H) calcd. for
C29H21N2O3S:477.1273; Found: 477.12733.
o-tolyl(1-tosyl-1H-pyrrolo[2,3-b]quinolin-3-yl)methanone (4j): Yellow
solid; mp: 157.1~158.2℃;(30% ethylacetate/hexane, Rf = 0.41, 44.9 mg,
0.102 mmol, 66%); 1H NMR (400 MHz, CDCl3): δ 9.13 (s, 1H), 8.24 (d, J =
8.3Hz, 2H), 8.19 (d, J = 8.5Hz, 1H), 8.11 (s, 1H), 7.97 (d, J = 8.1Hz, 1H),
7.74 (t, J = 7.2Hz, 1H), 7.53 (t, J = 7.8Hz, 1H), 7.49~7.43 (m, 2H), 7.34 (d,
J = 8.8Hz, 2H), 7.30 (d, J = 8.3Hz, 2H), 2.42 (s, 3H), 2.35 (s, 3H); 13C NMR
(100 MHz, CDCl3): δ 192.7, 147.6, 146.1, 145.8, 138.6, 137.5, 136.6,
134.1, 131.5, 131.4, 130.6, 129.7, 129.5, 129.0, 128.6, 128.0, 126.5, 125.5,
125.5, 120.2, 118.5, 21.7, 19.7; ESI-MS (M+H) calcd. for
C26H21N2O3S:441.1273; Found: 441.12800.
thiophen-2-yl(1-tosyl-1H-pyrrolo[2,3-b]quinolin-3-yl) methanone (4p):
Yellow solid; mp: 203.4~204.4℃;(30% ethylacetate/hexane, Rf = 0.33,
1
21.3 mg, 0.049 mmol, 31%); H NMR (600 MHz, CDCl3): δ 9.03 (s, 1H),
8.60 (s, 1H), 8.25 (dd, J = 6.8Hz & 1.8Hz, 2H), 8.19 (d, J = 8.6Hz, 1H),
7.96 (dt, J = 8.2Hz & 0.7Hz, 1H), 7.89 (dd, J = 3.7Hz & 1.1Hz, 1H),
7.75~7.72 (m, 2H), 7.53~7.51 (m, 1H), 7.29 (d, J = 8.2Hz, 2H), 7.25 (d, J
= 3.7Hz, 1H), 2.34 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 180.9, 147.4,
146.1, 145.9, 143.5, 134.7, 134.2, 133.5, 132.5, 131.4, 129.7, 129.6, 129.0,
128.9, 128.7, 128.2, 126.4, 125.5, 120.7, 117.2, 21.7; ESI-MS (M+H) calcd.
for C23H17N2O3S2:433.0681; Found: 433.06849.
(2-methoxyphenyl)(1-tosyl-1H-pyrrolo[2,3-b]quinolin-3-yl)
methanone (4k): Yellow sticky solid;(30% ethylacetate/hexane, Rf = 0.25,
1
28.9 mg, 0.063 mmol, 43%); H NMR (400 MHz, CDCl3): δ 9.11, (s, 1H),
8.22 (d, J= 8.3Hz, 2H), 8.17 (d, J = 9.8Hz, 1H), 8.16 (s, 1H), 7.96 (d, J =
8.1Hz, 1H), 7.72 (t, J = 8.2Hz, 1H), 7.52 (t, J = 7.7Hz, 2H), 7.45 (dd, J =
7.4Hz & 1.4Hz, 1H), 7.28 (d, J = 8.3Hz, 2H), 7.11~7.04 (m, 2H), 3.81 (s,
3H), 2.33 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 190.2, 157.0, 147.6, 146.0,
145.7, 137.7, 134.2, 132.1, 131.4, 129.6, 129.4, 129.3, 128.9, 128.6, 126.5,
125.4, 120.7, 120.4, 120.2, 118.5, 111.8, 55.7, 21.6; ESI-MS (M+H) calcd.
for C26H21N2O4S:457.1222; Found: 457.12278.
thiophen-3-yl(1-tosyl-1H-pyrrolo[2,3-b]quinolin-3-yl) methanone (4q):
Yellow solid; mp: 207.9~211.2℃;(30% ethylacetate/hexane, Rf = 0.33,
1
23.3 mg, 0.054 mmol, 34%); H NMR (600 MHz, CDCl3): δ 9.05 (s, 1H),
8.48 (s, 1H), 8.25 (d, J = 8.3Hz, 2H), 8.19 (d, J = 8.6Hz, 1H), 8.09 (t, J =
1.5Hz, 1H), 7.96 (d, J = 8.2Hz, 1H), 7.73 (t, J = 7.3Hz, 1H), 7.64 (d, J =
5.0Hz, 1H), 7.52 (t, J = 7.3Hz, 1H), 7.47 (q, J = 2.9Hz, 1H), 7.29 (d, J =
8.4Hz, 2H), 2.34 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 183.4, 147.5, 146.1,
145.9, 141.8, 135.3, 134.2, 131.7, 131.4, 129.7, 129.5, 129.0, 128.9, 128.6,
127.8, 127.0, 126.4, 125.4, 120.7, 117.9, 21.7; ESI-MS (M+H) calcd. for
C23H17N2O3S2:433.0681; Found: 433.06867.
(2-fluorophenyl)(1-tosyl-1H-pyrrolo[2,3-b]quinolin-3-yl) methanone
(4l): Yellow solid; mp: 189.7~190.1℃;(30% ethylacetate/hexane, Rf = 0.32,
1
36.0 mg, 0.081 mmol, 53%); H NMR (600 MHz, CDCl3): δ 9.13 (s, 1H),
8.26 (s, 1H), 8.23 (d, J = 8.5Hz, 2H), 8.18 (d, J = 8.6Hz, 1H), 7.98 (d, J =
8.2Hz, 1H), 7.74 (td, J = 7.0Hz & 1.3Hz, 1H), 7.62 (t, J = 7.2Hz, 1H),
7.59~7.58 (m, 1H), 7.53 (td, J = 7.1Hz & 1.1Hz, 1H), 7.32 (td, J = 7.4Hz &
0.8Hz, 1H), 7.29 (d, J = 8.4Hz, 2H), 7.24 (t, J = 9.2Hz, 1H), 2.34 (s, 3H);
13C NMR (150 MHz, CDCl3): δ 186.9, 160.4 (d: JC-F = 251.1Hz), 158.8 (d:
(1-(methylsulfonyl)-1H-pyrrolo[2,3-b]quinolin-3-yl)(phenyl)
methanone (4r): Yellow solid; mp: 176.4~178.1
℃ ;(30%
ethylacetate/hexane, Rf = 0.21, 48.1 mg, 0.137 mmol, 64%); 1H NMR (600
MHz, CDCl3): δ 9.21 (s, 1H), 8.24 (s, 1H), 8.19 (d, J = 8.5Hz, 1H), 8.06 (dd,
J = 8.2Hz & 0.6Hz, 1H), 7.89~7.87 (m, 2H), 7.79~7.76 (m, 1H), 7.63 (t, J
= 7.3Hz, 1H), 7.59 (td, J = 8.0Hz & 0.8Hz, 1H), 7.55 (t, J = 7.9Hz, 2H), 3.81
(s, 3H); 13C NMR (150 MHz, CDCl3): δ 190.4, 147.8, 145.9, 138.5, 135.7,
132.6, 132.2, 129.9, 128.8, 126.6, 125.7, 120.9, 116.9, 42.3; ESI-MS
(M+H) calcd. for C19H15N2O3S:351.0803; Found: 351.07987.
JC-F = 251.1Hz), 147.5, 146.2, 145.9, 137.8, 137.8, 134.0, 133.2 (d: JC-F
=
8.2Hz), 133.1 (d: JC-F = 8.2Hz), 131.5, 130.2, 129.7, 129.6, 129.0, 128.7,
126.6, 125.5, 124.6, 120.0, 118.0, 116.8 (d: JC-F = 21.7Hz), 116.6 (d: JC-F
= 21.7Hz), 21.7; ESI-MS (M+H) calcd. for C25H18FN2O3S:445.1022;
Found: 445.10235.
(2-chlorophenyl)(1-tosyl-1H-pyrrolo[2,3-b]quinolin-3-yl) methanone
(4m): Yellow solid; mp: 158.9~160.0℃;(30% ethylacetate/hexane, Rf =
0.32, 31.5 mg, 0.068 mmol, 47%); 1H NMR (600 MHz, CDCl3): δ 9.13 (s,
1H), 8.23 (d, J = 8.5Hz, 2H), 8.18 (d, J = 8.5Hz, 1H), 8.09 (s, 1H), 7.98 (dt,
J = 8.2Hz & 0.7Hz, 1H), 7.76~7.73 (m, 1H), 7.55~7.52 (m, 2H), 7.51~7.49
(m, 2H), 7.45~7.42 (m, 1H), 7.30 (d, J = 8.2Hz, 2H), 2.35 (s, 3H); 13C NMR
(150 MHz, CDCl3): δ 189.3, 147.6, 146.2, 145.9, 138.4, 138.1, 134.0,
131.6, 131.2, 130.6, 129.8, 129.6, 129.1, 129.0, 129.0, 128.7, 128.2, 127.0,
126.6, 125.6, 119.8, 117.8, 21.7; ESI-MS (M+H) calcd. for
C25H18ClN2O3S:461.0727; Found: 461.07320.
(6-chloro-1-tosyl-1H-pyrrolo[2,3-b]quinolin-3-yl)(phenyl) methanone
(5b): Yellow solid; mp: 225.1~226.5℃;(30% ethylacetate/hexane, Rf =
0.26, 52.1 mg, 0.113 mmol, 70%); 1H NMR (400 MHz, CDCl3): δ 8.99 (s,
1H), 8.36 (s, 1H), 8.22 (d, J = 8.4Hz, 2H), 8.12 (d, J = 9.1Hz, 1H), 7.92 (d,
J = 2.2Hz, 1H), 7.87 (d, J = 8.5Hz, 1H), 7.87 (s, 1H), 7.67~7.63 (m, 2H),
7.57 (t, J = 7.7Hz, 2H), 7.30 (d, J = 8.2Hz, 2H), 2.35 (s, 3H); 13C NMR (100
MHz, CDCl3): δ 190.2, 147.6, 146.3, 144.1, 138.5, 137.0, 134.0, 132.6,
131.1, 130.5, 129.8, 128.9, 128.9, 128.8, 127.0, 126.9, 121.5, 116.9, 21.7;
ESI-MS (M+H) calcd. for C25H18ClN2O3S:461.0727; Found: 461.07253.
(2-bromophenyl)(1-tosyl-1H-pyrrolo[2,3-b]quinolin-3-yl) methanone
(4n): Yellow solid; mp: 171.2~173.5℃;(30% ethylacetate/hexane, Rf =
0.34, 43.0 mg, 0.085 mmol, 66%); 1H NMR (500 MHz, CDCl3): δ 9.13 (s,
1H), 8.23 (d, J = 7.5Hz, 2H), 8.18 (d, J = 8.0Hz, 1H), 8.08 (s, 1H), 7.98 (d,
J = 8.0Hz, 1H), 7.72 (t, J = 8.5Hz, 2H), 7.55~7.42 (m, 4H), 7.30 (d, J =
7.5Hz, 2H), 2.34 (s, 3H); 13C NMR (125 MHz, CDCl3): δ 190.0, 147.6, 146.2,
145.9, 140.3, 138.2, 133.9, 133.7, 131.6, 131.5, 129.7, 129.6, 129.1, 129.0,
128.8, 128.6, 127.5, 126.5, 125.6, 119.8, 119.5, 117.5, 21.7; ESI-MS
(M+H) calcd. for C25H18BrN2O3S:505.0222; Found: 505.02186.
(6-bromo-1-tosyl-1H-pyrrolo[2,3-b]quinolin-3-yl)(phenyl) methanone
(5c): Yellow solid; mp: 223.0~224.0℃;(20% ethylacetate/hexane, Rf = 0.29,
74.3 mg, 0.147 mmol, 91%); H NMR (400 MHz, CDCl3): δ 8.96 (s, 1H),
8.37 (s, 1H), 8.22 (d, J = 8.4Hz, 2H), 8.07 (d, J = 2.0Hz, 1H), 8.04 (d, J =
9.0Hz, 1H), 7.87 (d, J = 8.5Hz, 1H), 7.87 (s, 1H), 7.76 (dd, J = 9.1Hz &
2.2Hz, 1H), 7.67~7.63 (m, 1H), 7.56 (t, J = 7.8Hz, 2H), 7.30 (d, J = 8.3Hz,
2H), 2.35 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 190.1, 147.5, 146.3, 144.3,
138.5, 137.0, 134.0, 132.9, 132.6, 130.6, 130.4, 130.3, 129.8, 128.9, 128.8,
127.4, 121.4, 119.1, 116.9, 21.7; ESI-MS (M+H) calcd. for
C25H18BrN2O3S:505.0222; Found: 505.02324.
1
naphthalen-1-yl(1-tosyl-1H-pyrrolo[2,3-b]quinolin-3-yl)
methanone
(4o): Orange solid; mp: 174.2~174.6℃;(30% ethylacetate/hexane, Rf =
0.40, 55.7 mg, 0.117 mmol, 84%); 1H NMR (400 MHz, CDCl3): δ 9.23 (s,
(6-methyl-1-tosyl-1H-pyrrolo[2,3-b]quinolin-3-yl)(phenyl) methanone
(5d): Yellow solid; mp: 253.3~254.2℃;(30% ethylacetate/hexane, Rf =
This article is protected by copyright. All rights reserved.

10.1002/chem.201806083
Chemistry - A European Journal
FULL PAPER
0.30, 45.6 mg, 0.103 mmol, 64%); 1H NMR (600 MHz, CDCl3): δ 8.99 (s,
1H), 8.31 (s, 1H), 8.22 (d, J = 8.5Hz, 2H), 8.08 (d, J = 8.7Hz, 1H),
7.88~7.87 (m, 2H), 7.72 (s, 1H), 7.64 (t, J = 7.4Hz, 1H), 7.58~7.55 (m, 3H),
7.28 (d, J = 8.6Hz, 2H), 2.54 (s, 3H), 2.34 (s, 3H); 13C NMR (150 MHz,
CDCl3): δ 190.4, 147.6, 146.2, 146.0, 140.1, 138.7, 136.1, 134.3, 132.4,
131.2, 129.7, 128.9, 128.8, 128.8, 128.3, 127.9, 127.9, 124.6, 120.1, 117.2,
22.0, 21.7; ESI-MS (M+H) calcd. for C26H21N2O3S:441.1273; Found:
441.12704.
(6,7-dimethoxy-1-tosyl-1H-pyrrolo[2,3-b]quinolin-3-yl)(phenyl)
methanone (5j): Orange sticky solid;(50% ethylacetate/hexane, Rf = 0.15,
1
60.5 mg, 0.124 mmol, 77%); H NMR (600 MHz, CDCl3): δ 8.91 (s, 1H),
8.21 (s, 1H), 8.20 (d, J = 8.5Hz, 2H), 7.87 (dt, J = 8.1Hz & 0.6Hz, 2H), 7.63
(t, J = 7.4Hz, 1H), 7.55 (t, J = 7.7Hz, 2H), 7.48 (s, 1H), 7.28 (d, J = 8.2Hz,
2H), 7.18 (s, 1H), 4.09 (s, 3H), 4.01 (s, 3H), 2.35 (s, 3H); 13C NMR (150
MHz, CDCl3): δ 190.6, 153.0, 149.3, 146.6, 145.9, 143.3, 138.8, 135.0,
134.5, 132.4, 129.8, 129.4, 128.9, 128.8, 128.6, 122.3, 119.1, 117.3, 107.4,
105.5, 56.3, 56.1, 21.7; ESI-MS (M+H) calcd. for C27H23N2O5S:487.1328;
Found: 487.13505.
(6-methoxy-1-tosyl-1H-pyrrolo[2,3-b]quinolin-3-yl)(phenyl)
methanone (5e): Orange sticky solid;(40% ethylacetate/hexane, Rf = 0.21,
1
62.7 mg, 0.137 mmol, 85%); H NMR (400 MHz, CDCl3): δ 9.05 (s, 1H),
phenyl(6-tosyl-6H-[1,3]dioxolo[4,5-g]pyrrolo[2,3-b]quinolin-8-yl)
8.36 (s, 1H), 8.22~8.19 (m, 3H), 7.88 (d, J = 7.3Hz, 2H), 7.76 (d, J = 2.0Hz,
1H), 7.64 (t, J = 7.3Hz, 1H), 7.56 (t, J = 7.4Hz, 3H), 7.28 (d, J = 8.0Hz, 2H),
3.93 (s, 3H), 2.34 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 190.2, 154.2,
148.0, 147.5, 146.2, 143.8, 138.5, 136.9, 134.0, 132.5, 131.2, 130.5, 129.7,
128.9, 128.8, 126.4, 124.3, 121.3, 118.4, 116.8, 55.6, 21.6; EI-MS (M)
calcd. for C26H20N2O4S:456.1144; Found: 456.1143
methanone (5k): Yellow solid; mp: 242.9~243.7 ℃ ;(30%
ethylacetate/hexane, Rf = 0.19, 56.3 mg, 0.120 mmol, 74%); 1H NMR (600
MHz, CDCl3): δ 8.86 (s, 1H), 8.22 (s, 1H), 8.20 (d, J = 8.4Hz, 2H), 7.86 (dd,
J = 7.5Hz & 0.5Hz, 2H), 7.63 (t, J = 8.0Hz, 1H), 7.55 (t, J = 7.7Hz, 2H),
7.43 (s, 1H), 7.28 (d, J = 8.0Hz, 1H), 7.16 (s, 1H), 6.10 (s, 2H), 2.34 (s,
3H); 13C NMR (150 MHz, CDCl3): δ 190.5, 151.1, 147.3, 146.4, 146.0,
144.4, 138.7, 135.0, 134.3, 132.4, 129.9, 129.7, 128.9, 128.8, 128.8, 123.6,
119.1, 117.0, 105.1, 103.1, 101.9, 21.7; ESI-MS (M+H) calcd. for
C26H19N2O5S:471.1015; Found: 471.10234.
3-benzoyl-1-tosyl-1H-pyrrolo[2,3-b]quinolin-6-yl ethyl carbonate (5f):
Yellow solid; mp: 170.1~170.8℃;(40% ethylacetate/hexane, Rf = 0.27,
1
69.0 mg, 0.134 mmol, 83%); H NMR (600 MHz, CDCl3): δ 9.06 (s, 1H),
8.36 (s, 1H), 8.21~8.19 (m, 3H), 7.88 (d, J = 7.0Hz, 2H), 7.78 (d, J = 2.6Hz,
1H), 7.65 (t, J = 7.5Hz, 1H), 7.59~7.55 (m, 3H), 7.28 (d, J = 8.4Hz, 2H),
4.35 (q, J = 7.1Hz, 2H), 2.35 (s, 3H), 1.41 (t, J = 7.1Hz, 3H); 13C NMR (150
MHz, CDCl3): δ 190.3, 153.6, 148.0, 147.5, 146.2, 143.8, 138.5, 136.9,
134.0, 132.6, 131.2, 130.5, 129.8, 128.9, 128.9, 126.5, 124.5, 121.3, 118.5,
116.9, 65.1, 21.7, 14.2; ESI-MS (M+H) calcd. for C28H23N2O6S:515.1277;
Found: 515.13024.
2-((4-benzoyl-3-phenyl-1-tosyl-1H-pyrrol-2-yl)amino) benzaldehyde
(7a): Yellow oil;(30% ethylacetate/hexane, Rf = 0.41, 55.4 mg, 0.106 mmol,
82%); 1H NMR (600 MHz, CDCl3): δ 9.87 (s, 1H), 9.50 (s, 1H), 7.81~7.80
(m, 3H), 7.61 (dd, J = 6.7Hz & 1.7Hz, 2H), 7.50 (tt, J = 7.4Hz & 1.3Hz, 1H),
7.42 (dd, J = 7.7Hz & 1.5Hz, 1H), 7.39 (t, J = 7.6Hz, 2H), 7.13~7.11 (m,
2H), 7.08 (d, J = 8.0Hz, 2H), 7.05~7.01 (m, 3H), 6.95~6.92 (m, 1H), 6.69
(t, J = 7.9Hz, 1H), 6.05 (d, J = 8.5Hz, 1H), 2.30 (s, 3H); 13C NMR (150 MHz,
CDCl3): δ 194.5, 190.6, 148.1, 145.8, 138.1, 135.4, 135.1, 134.1, 132.6,
131.2, 129.9, 129.6, 129.0, 128.3, 128.1, 127.9, 127.1, 125.6, 125.3, 125.1,
123.5, 119.1, 117.9, 113.5, 21.6; ESI-MS (M+H) calcd. for
C31H25N2O4S:521.1535; Found: 521.15265.
(7-chloro-1-tosyl-1H-pyrrolo[2,3-b]quinolin-3-yl)(phenyl) methanone
(5g): Yellow solid; mp: 252.4~253.6℃;(30% ethylacetate/hexane, Rf =
0.31, 67.0 mg, 0.134 mmol, 90%); 1H NMR (400 MHz, CDCl3): δ 9.07 (s,
1H), 8.35 (s, 1H), 8.24~8.21 (m, 2H), 8.18 (d, J = 2.0Hz, 1H), 7.91~7.86
(m, 3H), 7.65 (tt, J = 6.4Hz & 1.2Hz, 1H), 7.56 (tt, J = 6.7Hz & 1.2Hz, 2H),
7.47 (dd, J = 8.7Hz & 2.0Hz, 1H), 7.32 (dd, J = 8.5Hz & 0.5Hz, 2H), 2.36
(s, 3H); 13C NMR (100 MHz, CDCl3): δ 190.2, 147.9, 146.3, 146.0, 138.5,
136.7, 135.5, 134.0, 132.6, 131.5, 129.8, 129., 128.9, 127.8, 126.6, 124.8,
12.10, 116.9, 21.7; ESI-MS (M+H) calcd. for C25H18ClN2O3S:461.0727;
Found: 461.07395.
2-((4-benzoyl-3-(4-methoxyphenyl)-1-tosyl-1H-pyrrol-2-
yl)amino)benzaldehyde (7b): Brown oil;(40% ethylacetate/hexane, Rf =
0.24, 50.4 mg, 0.092 mmol, 76%); 1H NMR (600 MHz, CDCl3): δ 9.88 (s,
1H), 9.48 (s, 1H), 7.81 (d, J = 8.0Hz, 2H), 7.77 (s, 1H), 7.60 (d, J = 8.1Hz,
2h), 7.51 (t, J = 7.3Hz, 1H), 7.43~7.39 (m, 3H), 7.06 (d, J = 8.9Hz, 4H),
6.95 (t, J = 7.8Hz, 1H), 6.69 (t, J = 7.6Hz, 1H), 6.59 (d, J = 8.4Hz, 2H),
6.05 (d, J = 8.5Hz, 1H), 3.63 (s, 3H), 2.30 (s, 3H); 13C NMR (150 MHz,
CDCl3): δ 194.5, 190.7, 158.6, 148.1, 145.7, 138.2, 135.4, 135.1, 134.2,
132.6, 130.2, 129.9, 128.3, 125.3, 125.1, 123.5, 119.1, 117.8, 113.6, 113.5,
55.0, 21.6; ESI-MS (M+H) calcd. for C32H27N2O5S:551.1641; Found:
551.16499.
(7-bromo-1-tosyl-1H-pyrrolo[2,3-b]quinolin-3-yl)(phenyl) methanone
(5h): Yellow solid; mp: 233.4~234.0℃;(30% ethylacetate/hexane, Rf =
0.37, 54.7 mg, 0.108 mmol, 67%); 1H NMR (400 MHz, CDCl3): δ 9.07 (s,
1H), 8.38~8.36 (m, 2H), 8.22 (d, J = 7.4Hz, 2H), 7.88~7.86 (m, 2H), 7.84
(d, J = 8.8Hz, 1H), 7.65 (t, J = 7.4Hz, 1H), 7.60 (dd, J = 8.8Hz & 1.9Hz,
1H), 7.57 (t, J = 7.8Hz, 2H), 7.32 (d, J = 8.3Hz, 2H), 2.37 (s, 3H); 13C NMR
(100 MHz, CDCl3): δ 190.2, 147.8, 146.3, 146.2, 138.5, 136.8, 134.0,
132.6, 131.6, 131.1, 129.8, 129.0, 129.0, 128.9, 128.8, 125.0, 123.8, 121.1,
116.9, 21.7; ESI-MS (M+H) calcd. for C25H18BrN2O3S:505.0222; Found:
505.02037.
2-((4-benzoyl-3-(4-chlorophenyl)-1-tosyl-1H-pyrrol-2-
yl)amino)benzaldehyde (7c): Red oil;(30% ethylacetate/hexane, Rf =
0.25, 44.9 mg, 0.081 mmol, 68%); 1H NMR (600 MHz, CDCl3): δ 9.88 (s,
1H), 9.50 (s, 1H), 7.81 (d, J = 8.1Hz, 2H), 7.79 (s, 1H), 7.60 (d, J = 7.9Hz,
2H), 7.54 (t, J = 8.4Hz, 1H), 7.43 (q, J = 7.6Hz, 3H), 7.08 (t, J = 8.6Hz, 4H),
7.03 (d, J = 8.0Hz, 2H), 6.95 (t, J = 8.2Hz, 1H), 6.71 (t, J = 7.4Hz, 1H),
6.00 (d, J = 8.5Hz, 1H), 2.30 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 194.6,
190.4, 147.8, 145.9, 138.1, 135.5, 135.2, 134.0, 133.1, 132.8, 130.4, 129.9,
129.8, 129.5, 128.4, 128.1, 125.9, 125.4, 124.1, 123.1, 119.2, 118.1, 113.3,
21.6; ESI-MS (M+H) calcd. for C31H24ClN2O4S:555.1145; Found:
555.11502.
(7-methyl-1-tosyl-1H-pyrrolo[2,3-b]quinolin-3-yl)(phenyl) methanone
(5i): Yellow solid; mp: 254.5~255.4℃;(30% ethylacetate/hexane, Rf = 0.30,
1
55.5 mg, 0.126 mmol, 78%); H NMR (600 MHz, CDCl3): δ 9.03 (s, 1H),
8.30 (s, 1H), 8.24 (d, J = 8.3Hz, 2H), 7.97 (s, 1H), 7.89~7.85 (m, 3H), 7.64
(t, J = 7.1Hz, 1H), 7.56 (t, J = 7.6Hz, 2H), 7.36 (d, J = 8.3Hz, 1H), 7.29 (d,
J = 8.3Hz, 2H), 2.60 (s, 3H), 2.34 (s, 3H); 13C NMR (150 MHz, CDCl3): δ
190.4, 147.6, 146.2, 146.0, 140.0, 138.7, 136.1, 134.3, 132.4, 131.2, 129.7,
128.9, 128.8, 128.8, 128.3, 127.9, 127.9, 124.6, 120.1, 117.2, 22.0, 21.7;
ESI-MS (M+H) calcd. for C26H21N2O3S:441.1273; Found: 441.12704.
2-((4-benzoyl-3-(thiophen-2-yl)-1-tosyl-1H-pyrrol-2-
yl)amino)benzaldehyde (7d): Green oil;(30% ethylacetate/hexane, Rf =
0.24, 31.6 mg, 0.060 mmol, 47%); 1H NMR (600 MHz, CDCl3): δ 9.95 (s,
1H), 9.56 (s, 1H), 7.87 (d, J = 7.8Hz, 2H), 7.71 (s, 1H), 7.58~7.55 (m, 3H),
7.51 (d, J = 7.7Hz, 1H), 7.45 (t, J = 7.6Hz, 2H), 7.07~7.06 (m, 3H), 7.02 (d,
J = 5.2Hz, 1H), 6.99 (t, J = 7.3Hz, 1H), 6.76 (t, J = 7.7Hz, 1H), 6.74~6.72
This article is protected by copyright. All rights reserved.

10.1002/chem.201806083
Chemistry - A European Journal
FULL PAPER
(m, 1H), 6.09 (d, J = 8.5Hz, 1H), 2.29 (s, 3H); 13C NMR (150 MHz, CDCl3):
δ 194.6, 190.8, 147.7, 145.9, 138.1, 135.5, 135.2, 133.9, 132.9, 131.4,
129.9, 129.8, 128.4, 128.1, 127.9, 126.5, 125.9, 125.4, 125.0, 123.1, 119.4,
Chem. Int. Ed., 2011, 50, 3236-3239; e) G. Henrion, T. E. J. Chavas, X.
L. Goff, F. Gagosz, Angew. Chem. Int. Ed., 2013, 52, 6277-6282; f) R. K.
Kawade, R. S. Liu, Org. Lett., 2013, 15, 4094-4097; g) B. D. Mokar, D.
B. Huple, R. S. Liu, Angew. Chem. Int. Ed., 2016, 55, 11892-11896; h)
G. Li, L. Zhang, Angew. Chem. Int. Ed., 2007, 46, 5156-5159; i) Z. Zheng,
L. Zhang, Org. Chem. Front., 2015, 2, 1556-1560; j) Y. Wang, Z. Zheng,
L. Zhang, J. Am. Chem. Soc., 2015, 137, 5316−5319; k) F. Sánchez-
Cantalejo, J. D. Priest, P. W. Davies, Chem. Eur. J., 2018, 24, 17215-
17219; l) L. Li, C. Shu, B. Zhou, Y. F. Yu, X. Y. Xiao, L. W. Ye, Chem.
Sci., 2014, 5, 4057-4064; m) C. Shu, L. Li, X. Y. Xiao, Y. F. Yu, Y. F. Ping,
J. M. Zhou, L. W. Ye, Chem. Commun., 2014, 50, 8689-8692; n); C. Shu,
L. Li, Y. F. Yu, S. Jiang, L. W. Ye, Chem. Commun., 2014, 50, 2522-
2525; o) F. Pan, S. Liu, C. Shu, R. K. Lin, Y. F. Yu, J. M. Zhou, L. W. Ye,
Chem. Commun., 2014, 50, 10726-10729.
118.6,
118.2,
113.5,
21.6;
ESI-MS
(M+H)
calcd.
for
C29H23N2O4S2:527.1099; Found: 527.10895.
2-((4-benzoyl-3-phenyl-1-tosyl-1H-pyrrol-2-yl)amino)-5-
chlorobenzaldehyde (7e): Yellow oil;(30% ethylacetate/hexane, Rf = 0.31,
1
55.4 mg, 0.100 mmol, 77%); H NMR (400 MHz, CDCl3): δ 9.81 (s, 1H),
9.45 (s, 1H), 7.81~7.79 (m, 3H), 7.58 (d, J = 8.4Hz, 2H), 7.51 (t, J = 7.4Hz,
1H), 7.40~7.37 (m, 3H), 7.12~7.02 (m, 7H), 6.84 (dd, J = 9.0Hz & 2.5Hz,
1H), 5.96 (d, J = 9.0Hz, 1H), 2.33 (s, 3H); 13C NMR (100 MHz, CDCl3): δ
193.3, 190.5, 146.6, 146.1, 138.0, 135.0, 134.0, 133.9, 132.7, 130.9, 129.9,
129.6, 128.9, 128.3, 128.0, 127.4, 125.6, 125.2, 124.9, 123.4, 122.7, 119.7,
115.1, 21.6; ESI-MS (M+H) calcd. for C31H24ClN2O4S:555.1145; Found:
555.11545.
[4]
a) R. B. Dateer, K. Pati, R. S. Liu, Chem. Commun., 2012, 48, 7200-7202;
b) D. B. Huple, S. Ghorpade, R. S. Liu, Chem. Eur. J., 2013, 19, 12965-
12969; c) Y. Luo, K. Ji, Y. Li, L. Zhang, J. Am. Chem. Soc., 2012, 134,
17412-17415; d) W. He, C. Li, L. Zhang, J. Am. Chem. Soc., 2011, 133,
8482-8485; e) L. Wang, X. Xie, Y. Liu, Angew. Chem. Int. Ed., 2013, 52,
13302-13306.
2-((4-benzoyl-3-phenyl-1-tosyl-1H-pyrrol-2-yl)amino)-5-
methylbenzaldehyde (7f): Orange oil;(30% ethylacetate/hexane, Rf =
0.24, 58.9 mg, 0.110 mmol, 85%); 1H NMR (400 MHz, CDCl3): δ 9.84 (s,
1H), 7.81 (dd, J = 7.8Hz & 0.8Hz, 2H), 7.79 (s, 1H), 7.59 (d, J = 8.4Hz, 2H),
7.54 (td, J = 7.4Hz & 1.1Hz, 1H), 7.42 (t, J = 7.8Hz, 2H), 7.23 (s, 1H), 7.08
(d, J = 8.4Hz, 5H), 7.03 (dt, J = 8.5Hz & 1.9Hz, 2H), 6.78 (dd, J = 8.5Hz &
1.9Hz, 1H), 5.94 (d, J = 8.5Hz, 1H), 2.31 (s, 3H), 2.20 (s, 3H); 13C NMR
(100 MHz, CDCl3): δ 194.6, 190.4, 145.8, 138.1, 136.3, 135.3, 133.9,
133.1, 132.8, 130.4, 129.9, 129.5, 128.4, 128.1, 127.4, 126.2, 125.4, 124.1,
123.0, 119.0, 113.4, 21.6, 20.0; ESI-MS (M+H) calcd. for
C32H27N2O4S:535.1692; Found: 535.16656.
[5]
[6]
a) A. M. Jadhav, S. Bhunia, H. Y. Liao, R. S. Liu, J. Am. Chem. Soc.,
2011, 133, 1769-1771; b) H. S. Yeom, J. E. Lee, S. Shin, Angew. Chem.
Int. Ed., 2008, 47, 7040-7043.
a) B. Lu, Y. Li, Y. Wang, D. H. Aue, Y. Luo, L. Zhang, J. Am. Chem. Soc.,
2013, 135, 8512-8524; b) Shapiro, N. D.; F. D. Toste, J. Am. Chem. Soc.,
2007, 129, 4160-4161; c) X. Yao, T. Wang, X. Zhang, P. Wang, B. Zhang,
J. Wei, Z. Zhang, Adv. Synth. Catal., 2016, 358, 1534-1539; d) K. Jia, L.
Zhang, Adv. Synth. Catal., 2018, 360, 647-651; e) S. K. Pawar, C. D.
Wang, S. Bhunia, A. M. Jadhav, R. S. Liu, Angew. Chem. Int. Ed., 2013,
52, 7559-7563; f) A. S. K. Hashmi, T. Wang, S. Shi, M. J .Rudolph, Org.
Chem., 2012, 7, 7761-7767; g) M. Xu, T. T. Ren, C. Y. Li, Org. Lett., 2012,
14, 4902-49005; h) S. Ghorpade, M. D. Su, R. S. Liu, Angew. Chem. Int.
Ed., 2013, 52, 4229-4234; i) C. W. Li, K. Pati, G. Y. Lin, S. M. A. Sohel,
H. H. Hung, R. S. Liu, Angew. Chem. Int. Ed., 2010, 49, 9891-9894.
a) P. Nꢀsel, L. N. d. S. Comprido, T. Lauterbach, M. Rudolph, F.
Rominger, A. S. K. Hashmi, J. Am. Chem. Soc., 2013, 135, 15662-15666;
b) Z. Zheng, L. Zhang, Org. Chem. Front., 2015, 2, 1556-1560.
R. Liu, G. N. W. Mcperson, Z. Y. Yang, X. Zhou, W. Song, Ilia. A. Guzei,
X. Xu, W. Tang, J. Am. Chem. Soc., 2013, 135, 8201-8204.
2-((4-benzoyl-3-phenyl-1-tosyl-1H-pyrrol-2-yl)amino)-4,5-
dimethoxybenzaldehyde (7g): Red oil;(50% ethylacetate/hexane, Rf =
0.40, 42.9 mg, 0.074 mmol, 57%); 1H NMR (600 MHz, CDCl3): δ 9.83 (s,
1H), 9.70 (s, 1H), 7.80 (s, 1H), 7.77 (dd, J = 8.3Hz & 1.3Hz, 2H), 7.62 (d,
J = 8.4Hz, 2H), 7.48 (tt, J = 7.5Hz & 1.2Hz, 1H), 7.35 (td, J = 7.6Hz &
1.7Hz, 2H), 7.14~7.12 (m, 2H), 7.07 (d, J = 7.9Hz, 2H), 7.05~6.99 (m, 3H),
6.80 (s, 1H), 5.37 (s, 1H), 3.78 (s, 3H), 3.41 (s, 3H), 2.30 (s, 3H); 13C NMR
(150 MHz, CDCl3): δ 191.8, 190.9, 155.7, 145.8, 144.6, 141.8, 138.1,
134.2, 132.7, 131.3, 129.8, 129.6, 129.0, 128.3, 128.2, 128.0, 127.3, 125.9,
124.8, 124.4, 123.5, 115.7, 111.6, 96.0, 56.3, 55.7, 21.5; ESI-MS (M+H)
calcd. for C33H29N2O6S:581.1746; Found: 581.17413.
[7]
[8]
[9]
a) J. Yan, G. L. Tay, C. Neo, B. R. Lee, P. W. H. Chan, Org. Lett., 2015,
17, 4176-4179; b) W. Rao, P. W. H. Chan, Chem. Eur. J., 2014, 20, 713-
718; c) W. Rao, M. J. Koh, D. Li, H. Hirao, P. W. H. Chan, J. Am. Chem.
Soc., 2013, 135, 7926-7932.
Keywords: Gold catalysis • Ynamides •Anthranil •Annulation •
[10] Selected examples: a) R. J. Reddy, M. P. B. Jones, P. W. Davies, Angew.
Chem. Int. Ed., 2017, 56, 13310-13313; b) P. W. Davies, A. Cremonesi,
L. Dumitrescu, Angew. Chem. Int. Ed., 2011, 50, 8931-8935; c) E.
Chatzopoulou, P. W. Davies, Chem. Commun., 2013, 49, 8617-8619; d)
A. H. Zhou, Q. He, C. Shu, Y. F. Yu, S. Liu, T. Zhao, W. Zhang, X. Lu, L.
W. Ye, Chem. Sci., 2015, 6, 1265-1271; e) L. Zhu, Y. Yu, Z. Mao, X.
Huang, Org. Lett., 2015, 17, 30-33; f) S. K. Pawar, R. L. Sahani, R. S.
Liu, Chem. Eur. J., 2015, 21, 10843-10850; g) H. Jin, L. Huang, J. Xie,
M. Rudolpb, F. Rominger, A. S. K. Hashmi, Angew. Chem. Int. Ed., 2016,
55, 794-797; h) C. Shu, Y. H. Wang, B. Zhou, X. L. Li, Y. F. Ping, X. Lu,
L. W. Ye, J. Am. Chem. Soc., 2015, 137, 9567-9570; i) C. Shu, Y. H.
Wong, C. H. Shen, P. P. Ruan, X. Lu, L. W. Ye, Org. Lett., 2016, 18,
3254-3257.
Chemoselectivity
[1]
For reviews of α-oxo gold carbene; see a) L. Zhang, Acc. Chem. Res.,
2014, 47, 877-888; b) H. Yeom, S. Shin, Acc. Chem. Res., 2014, 47, 966-
977; c) D. Qian, J. Zhang, Chem. Soc. Rev., 2015, 44, 677-698; d) L. Liu,
J. Zhang, Chem. Soc. Rev., 2016, 45, 506-516; e) J. Xiao, X. Li, Angew.
Chem. Int. Ed., 2011, 50, 7226-7236; f) Z. Zheng, Z. Wang, Y. Wang. L.
Zhang, Chem. Soc. Rev., 2016, 45, 4448-4458; g) J. Schießl, P. M. Stein,
J. Stirn, K. Emler, M. Rudolph, F. Rominger, A. S. K. Hashmi, Adv. Synth.
Catal., DOI : 10.1002/adsc.201801007.
[2]
[3]
a) D. Vasu, H. H. Hung, S. Bhunia, S. A. Gawade, A. Das, R. S. Liu,
Angew. Chem. Int., Ed. 2011, 50, 6911-6914; b) D. Qian, J. Zhang, Chem.
Commun., 2011, 47, 11152-11154; c) K. Ji, L. Zhang, Org. Chem. Front.,
2014, 1, 34-38; d) K. Ji, Z. Zheng, Z. Wang, L. Zhang, Angew. Chem. Int.
Ed., 2015, 54, 1245-1249; e) D. Qian, H. Hu, F. Liu, B. Tang, W. Ye, Y.
Wang, J. Zhang, Angew. Chem. Int. Ed., 2014, 53, 13751-13755; f) K.-
B. Wang, R. Q. Ran, S. D. Xiu, C. Y. Li, Org. Lett., 2013, 15, 2374-2377.
a) L. Ye, L. Cui, G. Zhang, L. Zhang, J. Am. Chem. Soc., 2010, 132,
3258-3259; b) L. Ye, W. He, L. Zhang, J. Am. Chem. Soc., 2010, 132,
8550-8551; c) S. Bhunia, S. Ghorpade, D. B. Huple, R. S .Liu, Angew.
Chem. Int. Ed., 2012, 51, 2939-2942; d) L. Ye, W. He, L. Zhang, Angew.
[11] a) M. S. H. Jin, M. S. B. Tian, M. S. X. Song, J. Xie, M. Rudolph, F.
Rominger, A. S. K. Hashmi, Angew. Chem. Int. Ed., 2016, 55, 12688-
12692; b) W. B. Shen, X. Y. Xiao, Q. Sun, B. Zhou, X. Q. Zhu, J. Z. Yan,
X. Lu, L. W. Ye, Angew. Chem. Int. Ed., 2017, 56, 605-609; c) R. L.
Sahani, R. S. Liu, Angew. Chem. Int. Ed., 2017, 56, 1026-1030.
[12] a) W. B. Shen, Q. Sun, L. Li, X. Liu, B. Zhou, J. Z. Yan, X. Lu, L. W. Ye,
Nat. Commun., 2017, 8, 1748; b) Z. Y. Yan, Y. Xiao, L. Zhang, Angew.
Chem. Int. Ed., 2012, 51, 8624-8627; c) B. Lu, Y. Luo, L. Liu, L. Ye, Y.
Wang, L. Zhang, Angew. Chem. Int. Ed., 2011, 50, 8358-8362.
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[13] a) D. Wong, J. Hu, J. Zhao, M. Shen, Y. Wang, P. Yu, Tetrahedron, 2018,
74, 4100-4110; b) K. Chen, X. Y. Tang, M. Shi, Chem. Commun., 2016,
52, 1967-1970; c) H. Zhao, Y. Xing, P. Lu and Y. Wang, Chem. Eur. J.
2016, 22, 15144-15150; d) B. D. Lee, Z. Li, K. J. French, Y. Zhuang, Z.
Xia and C. D. Smith, J. Med. Chem., 2004, 47, 1413-1422; e) L. Fan, M.
Liu, Y. Ye and G. Yin, Org. Lett., 2017, 19, 186-189; f) P. T. Parvatkar
and M. S. Majik, RSC Adv., 2014, 4, 22481-22486; g) C. Challa, J.
Ravindran, M. M. Konai, S. Varughese, J. Jacob, B. S. D. Kumar, J.
Haldar and R. S. Lankalapalli, ACS Omega, 2017, 2, 5187-5195.
[14]
For metal-catalyzed reactions of N-propargyl ynamides; see ref 8 and
selected examples: a) Q. Zhao, D. F. L. Rayo, D. Campeau, M. Daenen,
F. Gagosz, Angew. Chem. Int. Ed., 2018, 57, 13603-13607; b) C. M.
Wang, L. J. Qi, Q. Sun, B. Zhou, Z. X. Zhang, Z. F. Shi, S. C. Lin, X. Lu,
L. Gong, L. W. Ye, Green Chem., 2018, 20, 3271-3278; c) W. B. Shen,
B. Zhou, Z. X. Zhang, H. Yuan, W. Fang, L. W. Ye, Org. Chem. Front.,
2018, 5, 2468-2472; d) Y. Tokimizu, M. Wieteck, M. Rudolph, S. Oishi,
N. Fujii, A. S. K. Hashmi, H. Ohno, Org. Lett., 2015, 17, 604-607.
[15] For gold-catalyzed reactions of anthranils with alkynes; see ref 10g and
selected examples: a) R. D. Kardile, B. S. Kale, P. Sharma, R. S. Liu,
Org. Lett., 2018, 20, 3806-3809; b) M. H. Tsai, C. Y. Wang, A. S. K. Raj,
R. S. Liu, Chem. Commun., 2018, 54, 10866-10869; c) R. R. Singh, M.
Skaria, L. Y. Chen, M. J. Cheng, R. S. Liu, Chem. Sci., DOI:
10.1039/c8sc03619e; d) Z. Zeng, H. Jin, M. Rudolph, F. Rominger, A. S.
K. Hashmi, Angew. Chem. Int. Ed., 2018, 57, 16549-16553; e) R. L.
Sahani, R. S. Liu, Angew. Chem. Int. Ed., 2017, 56, 12736-12740; f) H.
Jin, B. Tian, X. Song, J. Xie, M. Rudolph, F. Rominger, A. S. K. Hashmi,
Angew. Chem. Int. Ed., 2016, 55, 12688-12692.
[16] Crystallographic data of compounds 4a, 4c, 5i and 7a' were deposited at
the Cambridge Crystallographic Data Centre: CCDC 1859503 (4a),
1859504 (4c), 1859505 (5i) and 1859510 (7a').
[17] Gold and rhodium carbenes have high reactivity toward anthranils or
isoxazoles; see ref 15a, 15c and selected examples : a) B. D. Mokar, P.
D. Jadhav, Y. B. Pandit, R. S. Liu, Chem. Sci., 2018, 9, 4488-4492; b) J.
R. Manning, H. M. L. Davices, Tetrahedron, 2008, 64, 6901-6908; c) J.
R. Manning, H. M. L. Davices, J. Am. Chem. Soc., 2008, 130, 8602-8603.
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Gold-catalyzed annulation of
N-propargyl ynamides with
anthranils can proceed via
two distinct mechanisms.
Yu-Chen Hsu, Shu-An Hsieh,
and Rai-Shung Liu*
Page No. – Page No.
Gold-catalyzed Annulations of
N-Propargyl Ynamides with
Anthranils With Two Distinct
Chemoselectivities
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