Synthesis of 2,3-Ring Fused Pyrroles via Cu-Catalyzed 5- exo-dig Annulation of Alkyne-Tethered Enaminones

Article abstract of DOI:10.1021/acs.joc.9b02672

A copper-catalyzed annulation of alkyne-tethered enaminones for the synthesis of 2,3-ring fused pyrroles is reported. The 5-exo-dig cyclization/olefin migration reaction delivers the multisubstituted pyrroles in 59-99% yields with 16 examples. This strate

Full text of DOI:10.1021/acs.joc.9b02672

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Note
Synthesis of 2,3-Ring Fused Pyrroles via Cu-Catalyzed
5-exo-dig Annulation of Alkyne-tethered Enaminones
Weishuang Li, Muhammad Usman, Lin-Yang Wu, and Wen-Bo Liu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b02672 • Publication Date (Web): 07 Nov 2019
Downloaded from pubs.acs.org on November 8, 2019
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Synthesis of 2,3-Ring Fused Pyrroles via Cu-Catalyzed 5-exo-dig
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Annulation of Alkyne-tethered Enaminones
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Weishuang Li, Muhammad Usman, Lin-Yang Wu, and Wen-Bo Liu*
Engineering Research Center of Organosilicon Compounds & Materials, Ministry of
Education, College of Chemistry and Molecular Sciences, Wuhan University, Wuhan,
Hubei, 430072, China
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Sauvage Center for Molecular Sciences, Wuhan University, Wuhan, Hubei, 430072,
China
wenboliu@whu.edu.cn
O
O
CuI (10 mol %)
Cs2CO3 (1.5 equiv)
R2
R2
THF, 25 o
C
N
R1
NHR1
R1
R2
O
N
(5-exo-dig)
Cu(I)
5-exo-dig cyclization Mild reaction conditions
Ligand-free copper catalyst Ring-fused pyrrole derivatives
Readily available starting materials Good yields (up to 99%) with 16 examples
Abstract: A copper-catalyzed annulation of alkyne-tethered enaminones for the
synthesis of 2,3-ring fused pyrroles is reported. The 5-exo-dig cyclization/olefin
migration reaction delivers the multi-substituted pyrroles in 59–99% yields with 16
examples. This strategy features easily available starting materials, mild reaction
conditions, and cheap ligand-free copper catalyst. The atom-economic transformation
provides a simple access to a variety of synthetic useful pyrroles and their derivatives.
As one of the most abundant heterocycles, pyrroles are intensively used as building
blocks in the synthesis of natural products and as pharmacophores for drug design.1
Meanwhile, pyrrole structural cores are widely present in catalysts/ligands and
photoelectric materials.2 Correspondingly, many classical methods,3 such as Hantzsch,4
Paal-Knorr,5,6 and Piloty-Robinson7 reactions, have been developed for their syntheses.
Particularly, catalytic protocols employing transition metals have made significant
progress in last few decades.8,9,10 Yet there is still room for improvement, for instance,
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avoiding the use of precious metal catalysts and harsh reaction conditions, starting with
more accessible materials, etc. Therefore, searching for new synthetic routes to access
pyrroles, especially through novel cyclization models and with cheap metal catalyst,
continues to attract the interest of the community.
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Scheme 1. Transition-Metal-Catalyzed Pyrroles Synthesis Via Cyclization of
Nitrogen to Alkynes.
(a) Copper-catalyzed 5-endo-dig cyclization
R2
[Cu]
R2
(5-endo-dig)
(ref 10a, b, and 11)
N
R1
NHR1
(b) Transition-metal-catalyzed 5-exo-dig strategies
R3
R4
R3
[Ag, Au, Zn, In, Fe]
R4
(5-exo-dig)
(ref 12)
R2
N
R1
R2
NHR1
(c) Copper-catalyzed 5-exo-dig cyclization (this research)
R
O
O
[Cu]/base
Me
Me
N
Ar = 2-I-C6H4
NHAr
N
1k
2k
Ar
only product
B
O
R = CH2CCMe
N.D.
Cu(I)
Ar
isomerization
BH
B
BH
O
Ar
N
O
Ar
N
O
N
(5-exo-dig)
Me
Me
H
Cu(I)
Me
Cu(I)
II
Cu(I)
I
III
Copper-catalyzed 5-endo-dig cyclization of (Z)-but-1-en-3-yn-1-amines has been
widely used in the synthesis of pyrroles and their derivatives (Scheme 1a), for the
reason that the stability of the products increased by the formation of aromatic
pyrroles.9a,10a,b,11 In contrast, a few strategies employing (Z)-pent-1-en-4-yn-1-amines
as the substrates to construct simple polysubstituted pyrroles through 5-exo-dig
cyclization strategy (Scheme 1b), but mainly limited in precious silver and gold
catalysis.12a–c Notable examples with zinc , indium, and iron as the catalysts were
reported recently by the groups of Stevens12d, Nakamura12e, and Zhang12f, respectively.
During our studies toward DHPIs (dihydropyrido[1,2-a]indolones) synthesis,13 we
found that with alkyne-tethered enaminone 1k as a substrate, intramolecular addition
of nitrogen to the alkyne furnished 2,3-ring fused the pyrrole 2k exclusively (Scheme
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1c). Based on precedent reports of the pyrrole synthesis,10,12 we proposed that the
reaction is work through the coordination of alkyne of 1k to Cu(I) to generate the π-
alkyne copper intermediate I,14 followed by the attack of nitrogen to the activated
alkyne generates alkenyl copper intermediate II. Subsequently, protonolysis of II
results intermediate III and the 1,3-H shift of III leads to the formation of the desired
2,3-fused pyrrole 2k (Scheme 1c).15 Given the readily accessible starting materials,
cheap but efficient catalyst, and the high value of the pyrrole products, we set out to
investigate the generality of this transformation. Particularly, the presence of the ketone
functionality in the pyrroles provides a number of opportunities for diversity synthetic
applications. Herein, we report the detail studies of this copper-catalyzed 5-exo-dig
cyclization.
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Table 1. Reaction Condition Optimizations.
entrya
solvent
THF
[Cu] (n mol %)
CuI (10)
base
yield (%)b
1
2
KOAc
6c
32c
90
98
91
93
82
52
80
75
THF
CuI (10)
K2CO3
K3PO4
3
THF
CuI (10)
4
THF
CuI (10)
CuI (10)
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
5
dioxane
CH2Cl2
toluene
CH3CN
THF
6
CuI (10)
7
CuI (10)
8
CuI (10)
9
CuBr (10)
CuCl (10)
10
THF
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15d
THF
Cu(OTf)2 (10)
CuI (5)
CuI (2)
–
Cs2CO3
76c
88
THF
THF
THF
THF
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
86
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N.D.
CuI (10)
22
aReactions conducted with 0.2 mmol of 1a (0.2 mmol), 0.3 mmol of base (0.3 mmol) in 1 mL of
b
c
solvent under Ar for 7 h. Isolated yield. NMR yield (1,3,5-trimethoxybenzene as an internal
standard). dUnder air. N.D. = not detected.
The optimization of the reaction conditions was initiated with butynyl phenylamino
cyclohexenone 1a as a model substrate (Table 1). With 10 mol % of CuI alone as the
catalyst, KOAc as the base, and THF as the solvent, the desired pyrrole 2a was observed
in only 6% NMR yield at room temperature (entry 1). The effect of various bases was
then investigated (entries 2–4). A slightly increased yield was obtained with K2CO3 but
the use of K3PO4 dramatically increased the reactivity (entries 2 and 3). We were glad
to find that when Cs2CO3 was used as a base, the yield of 2a was increased to 98%
(entry 4). Further screen of organic solvents (dioxane, CH2Cl2, toluene, and CH3CN,
entries 5–8) and copper sources (CuBr, CuCl, and Cu(OTf)2, entries 9–11) resulted in
lower yields. Control experiment revealed that the catalytic efficiency decreased as the
loading of CuI reduced (entries 12–13) and no reaction occurred in the absence of CuI
(entry 14). When under an air atmosphere, the desired pyrrole 2a was obtained in 22%
yield (entry 15). Thus using 10 mol % CuI, 1.5 equiv of Cs2CO3 in THF at room
temperature (entry 4) were identified as the optimal reaction conditions.
Table 2. Scope for the Synthesis of Fused Pyrrolesa
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O
O
CuI (10 mol %)
R2
5
Cs2CO3 (1.5 equiv)
6
7
8
R2
THF, 25 ºC
N
R1
NHR1
1
2
9
O
O
O
O
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Et
Et
Et
Et
N
N
N
N
R3
2b: R3 = Me, 7 h, 97% yield
2c: R3 = OMe, 7 h, 97% yield
NH2
tBu
2d: 12 h, 93% yield
2e: 7 h, 99% yield
2a: 7 h, 98% yield
(7 h, 93% yieldb)
O
O
O
O
Et
N
Et
N
Et
N
Et
N
R4
R3
NO2
2f: R3 = Cl, 7 h, 99% yield
2g: R3 = Br, 7 h, 88% yield
2j: R4 = Me, 7 h, 93% yield
2k: R4 = I, 7 h, 98% yield
2h: 12 h, 64% yield
2i: 7 h, 96% yield
O
O
O
O
Et
N
Et
N
Et
N
Et
N
O
4
Me
2l: 24 h, 80% yieldc
O
2o: 24 h, 65% yieldc
2m: 24 h, 77% yield
2n: 24 h, 59% yield
O
O
Bn
N
Me
NH
Me
NH2
1r: 7 h, decomposed
2p: 12 h, 76% yield
1q: 7 h, n.r.
aReaction conducted under the conditions of entry 5, Table 1. bUsing the Schlenk line under argon.
c40 oC.
Next, the efficiency of this annulation strategy was demonstrated by the construction
of an array of fused pyrroles (Table 2). Substituents at the para-position of anilines with
electron-donating (Me, OMe, NH2, tBu) and electron-withdrawing (Cl, Br) groups were
converted into the corresponding products 2b–2g smoothly in 88%–99% yields. It is
noteworthy that a free amine group was also tolerated (2d). The reaction of 1h was
sluggish and delivered product 2h in diminished yield (64%). Notably, the methodology
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allows for the synthesis of N-sterically hindered pyrroles (2i–2k). Naphthalen-1-amine
(1i), o-toluidine (1j), and 2-iodoaniline (1k) derived substrates all furnished the desired
products 2i–2k in excellent yields (93–98% yields). This reaction was not limited to
access the N-aryl substituted pyrroles, and alkyl amine substrates are also compatible
(2l–2o). The N-benzyl (2l) and N-furanylmethyl (2m) pyrroles were obtained in 80%
and 77% yields, respectively. Moreover, N-allyl (2n) and N-alkyl (2o) pyrroles were
also formed in moderate yields (59% and 65%). Interestingly, when phenylpropynyl
substituted cyclohexenone 1p was employed, the corresponding product 2p was
obtained in 76% yield. However, the reaction with unsubstituted enanminone 1q
synthesized from ammonia is failed to deliver the desired product. Decomposition of
the starting material was obtained when treatment of a terminal alkyne bearing substrate
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1r under the standard conditions.16
Scheme 2. Gram-Scale Reactions.
Scheme 3. Product Derivatizations.
O
O
OH
Et
HN
a
d
Et
N
N
Ph
Ph
6
3
Me
N
O
N
O
OH
b
e
Et
Et
Et
N
N
N
Ph
4
Ph
Ph
2a
7
8
O
O
Br
c
f
Et
Et
N
N
Ph
Ph
5
Reaction conditions: (a) 2a (0.2 mmol), polyformaldehyde (3 equiv), HCl (12 M), dioxane, 25 oC,
78% yield. (b) 2a (0.2 mmol), 1-methylpiperazine (3 equiv), polyformaldehyde (3 equiv), AcOH,
o
o
25 C, 79% yield. (c) 2a (0.2 mmol), oxone (1.1 equiv), NH4Br (1.1 equiv), MeOH, 35 C, 60%
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yield; (d) 2a (0.2 mmol), NaN3 (2 equiv), conc HCl, 0 oC, 57% yield. (e) i) 2a (0.1 mmol), CuBr2
(2 equiv), EtOAc, reflux; ii) LiBr (1.1 equiv), Li2CO3 (1.1 equiv), DMF, 150 oC, 52% yield of two
steps; (f) 2a (1 mmol), LDA (1 equiv), allyl bromide (4 equiv), THF, –78 – 25 oC, 83% yield.
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The utilities of the method were demonstrated by scale-up reactions and product
transformations. Gram-scale reactions with both substrates 1a and 1k under the
standard conditions provided the desired products 2a and 2k in 91% (1.09 g) and 99%
(1.82 g) yields, respectively (Scheme 2). The fused pyrrole products possess multiple
synthetic handles for further transformations as showcasing in Scheme 3. Friedel-Crafts
reactions of 2a with polyformaldehyde and imine under acidic conditions delivered the
alkylation products 3 and 4 in 78% and 79% yields, respectively.17 Bromination
reaction of 2a with NH4Br/oxone provided bromopyrrole 5, a useful cross-coupling
precursor, in 60% yield.18 Moreover, subjecting 2a to the Schmidt rearrangement
conditions provided lactam 6 in 57% yield.19 Additionally, 4-hydroxyindole 7 was
readily synthesized in 52% yield by a two-step procedure.20 Finally, an efficient α-
allylation of ketone moiety of 2a provided compound 8 in 83% yield.
Conclusions
We have reported a copper-catalyzed 5-exo-dig cyclization strategy for the synthesis of
2,3-ring fused pyrroles. With readily accessible alkyne-tethered enaminones as the
starting materials and cheap CuI as the catalyst, the annulation reactions operate under
mild reaction conditions in good to excellent yields. The diversely substituted pyrroles
provide resourceful entries to valuable synthetic intermediates. Further studies on the
application of the method in the synthesis of complex molecules are undergoing in our
laboratory.
Experimental Section:
General Methods: Unless otherwise stated, all experiments were carried out in flame-
dried glassware using argon manifolds or in a glovebox. Reactions were monitored by
thin-layer chromatography (TLC). TLC was performed using Huanghai 8±0.2 µm
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precoated glass plates (0.25 mm). Huanghai silica gel (particle size 300–400 mesh) was
used for chromatography. NMR spectra were recorded at room temperature on a Bruker
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ADVANCE III 400 MHz spectrometer. Data for H NMR were reported as chemical
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shift (δ ppm) (multiplicity, coupling constant (Hz), integration) using standard
abbreviations for multiplicities: s, singlet; d, doublet; t, triplet; q, quartet; quint, quintet,
m, multiplet; br s, broad signal. Data for 13C{1H}NMR was reported in terms of
chemical shifts (δ ppm). Melting points were obtained on a RY-1G Melting point meter
and were reported in range of temperature (oC). High-resolution mass spectra (HRMS)
were obtained by use of a Bruker Compact TOF mass spectrometer in electrospray
ionization mode (ESI+). Unless otherwise noted, all reagents were purchased
commercially and used without further purification. Petroleum ether (PE) (60–90 oC),
ethyl acetate (EA) were used as eluent for silica gel chromatography. Dry solvents were
purchased commercially or were dried by passage through an activated alumina column
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under argon.21
General Procedure for Synthesis of 2,3-Ring Fused Pyrroles (2a–2p)
To a screw capped vial equipped with a magnetic stirring bar were added CuI (3.6 mg,
0.02 mmol, 10 mol %), enaminone 1a (47.7 mg, 0.2 mmol), Cs2CO3 (100.3 mg, 0.3
mmol), and 1.0 mL of THF. The vial was removed from the glovebox, and the mixture
was stirred at room temperature for 7 h. The reaction was quenched with HCl aqueous
solution (2 mL, 1 M in THF) and the resulted mixture was continued to stir overnight
at room temperature. Then the mixture was diluted with DCM (10 mL), the organic
phase was separated, and dried over anhydrous Na2SO4, filtered through a short pad of
celite. Then the filtrate was concentrated under reduced pressure. The desired product
2a (46.7 mg, 98% yield) was obtained as a white solid after purification by silica gel
chromatography (PE/EA = 5:1). mp: 112−113 °C;1H NMR (400 MHz, CDCl3) δ 7.55–
7.42 (m, 3H), 7.27–7.19 (m, 2H), 6.41 (s, 1H), 2.57–2.43(m, 4H), 2.35 (q, J = 7.2 Hz,
2H), 2.08 (quint, J = 6.3 Hz, 2H), 1.11 (t, J = 7.5 Hz, 3H); 13C{1H}NMR (100 MHz,
CDCl3) δ 194.6, 144.7, 138.1, 137.2, 129.6, 128.8, 127.8, 120.2, 101.9, 38.0, 24.0, 22.7,
20.0, 12.7; HRMS (ESI+) calc’d for C16H17NNaO [M + Na]+: 262.1202, found
262.1204.
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2-Ethyl-1-(p-tolyl)-1,5,6,7-tetrahydro-4H-indol-4-one 2b. The general procedure
was followed. The reaction was performed with CuI (3.9 mg, 10 mol %), 1b (50.3 mg,
0.2 mmol), and Cs2CO3 (98.4 mg, 0.3 mmol) in 1.0 mL of THF at room temperature in
a heating mantle for 7 h. The desired product 2b (48.6 mg, 97% yield) was obtained as
a white solid after purification by silica gel chromatography (PE/EA = 5:1). mp:
90−92 °C; 1H NMR (400 MHz, CDCl3) δ 7.29 (t, J = 8.4 Hz, 2H), 7.11 (d, J = 8.4 Hz,
2H), 6.41 (s, 1H), 2.52–2.48 (m, 4H), 2.43 (s, 3H), 2.39–2.27 (m, 2H), 2.07 (quint, J =
6.4 Hz, 2H), 1.10 (t, J = 7.5 Hz, 3H); 13C{1H}NMR (100 MHz, CDCl3) δ 194.6, 145.1,
138.9, 138.4, 134.5, 130.2, 127.5, 120.0, 101.8, 37.9, 24.0, 22.7, 21.3, 20.0, 12.8;
HRMS (ESI+) calc’d for C17H19NNaO [M + Na]+: 276.1359, found 276.1357.
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2-Ethyl-1-(4-methoxyphenyl)-1,5,6,7-tetrahydro-4H-indol-4-one 2c. The general
procedure was followed. The reaction was performed with CuI (3.7 mg, 10 mol %), 1c
(53.8 mg, 0.2 mmol), and Cs2CO3 (97.9 mg, 0.3 mmol) in 1.0 mL of THF at room
temperature in a heating mantle for 7 h. The desired product 2c (52.2 mg, 97% yield)
was obtained as a white solid after purification by silica gel chromatography (PE/EA =
5:1). mp: 130−131 °C; 1H NMR (400 MHz, CDCl3) δ 7.15 (d, J = 8.8 Hz, 2H), 6.99 (d,
J = 8.9 Hz, 2H), 6.40 (s, 1H), 3.87 (s, 3H), 2.58–2.48 (m, 4H), 2.36–2.28 (m, 2H), 2.08
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(quint, J = 6.2 Hz, 2H), 1.11 (t, J = 7.4 Hz, 3H); C{1H}NMR (100 MHz, CDCl3) δ
194.6, 159.7, 145.5, 138.6, 129.8, 128.8, 119.9, 114.7, 101.7, 55.7, 37.9, 24.0, 22.7,
20.0, 12.8; HRMS (ESI+) calc’d for C17H19NNaO2 [M + Na]+: 292.1308, found
292.1306.
1-(4-Aminophenyl)-2-ethyl-1,5,6,7-tetrahydro-4H-indol-4-one 2d. The general
procedure was followed. The reaction was performed with CuI (3.4 mg, 10 mol%), 1d
(50.6 mg, 0.2 mmol), and Cs2CO3 (97.7 mg, 0.3 mmol) in 1.0 mL of THF at room
temperature in a heating mantle for 12 h. The desired product 2d (46.8 mg, 93% yield)
was obtained as a light yellow solid after purification by silica gel chromatography
(PE/EA = 3:1 to PE/EA = 1:1). mp: 164−166 °C; 1H NMR (400 MHz, CDCl3) δ 6.98
(d, J = 8.6 Hz, 2H), 6.77 (d, J = 8.8 Hz, 2H), 6.36 (s, 1H), 3.82 (br s, 2H), 2.56–2.39
(m, 4H), 2.37–2.27 (m, 2H), 2.06 (quint, J = 6.3 Hz, 2H), 1.09 (t, J = 7.5 Hz, 3H);
13C{1H}NMR (100 MHz, CDCl3) δ 194.6, 146.4, 145.3, 138.6, 128.6, 127.9, 119.8,
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115.7, 101.3, 38.0, 24.0, 22.6, 20.0, 12.8; HRMS (ESI+) calc’d for C16H19N2O [M +
H]+: 255.1492, found 255.1492.
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1-(4-(tert-Butyl)phenyl)-2-ethyl-1,5,6,7-tetrahydro-4H-indol-4-one 2e. The general
procedure was followed. The reaction was performed with CuI (3.6 mg, 10 mol %), 1e
(59.9 mg, 0.2 mmol), and Cs2CO3 (99.7 mg, 0.3 mmol) in 1.0 mL of THF at room
temperature in a heating mantle for 7 h. The desired product 2e (59.5 mg, 99% yield)
was obtained as a white solid after purification by silica gel chromatography (PE/EA =
5:1). mp: 202−203 °C; 1H NMR (400 MHz, CDCl3) δ 7.49 (d, J = 8.5 Hz, 2H), 7.14 (d,
J = 8.5 Hz, 2H), 6.43 (s, 1H), 2.56–2.46 (m, 4H), 2.40–2.28 (m, 2H), 2.08 (quint, J =
6.2 Hz, 2H), 1.37 (s, 9H), 1.12 (t, J = 7.5 Hz, 3H); 13C{1H}NMR (100 MHz, CDCl3) δ
194.5, 151.8, 144.9, 138.2, 134.4, 127.2, 126.4, 120.0, 101.6, 38.0, 34.9, 31.4, 24.0,
22.8, 20.0, 12.7; HRMS (ESI+) calc’d for C20H25NNaO [M + Na]+: 318.1828, found
318.1832.
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1-(4-Chlorophenyl)-2-ethyl-1,5,6,7-tetrahydro-4H-indol-4-one 2f. The general
procedure was followed. The reaction was performed with CuI (3.8 mg, 10 mol %), 1f
(54.7 mg, 0.2 mmol), and Cs2CO3 (97.3 mg, 0.3 mmol) in 1.0 mL of THF at room
temperature in a heating mantle for 7 h. The desired product 2f (54.4 mg, 99% yield)
was obtained as a white solid after purification by silica gel chromatography (PE/EA =
5:1). mp: 96−97 °C; 1H NMR (400 MHz, CDCl3) δ 7.48 (d, J = 9.3 Hz, 2H), 7.18 (d, J
= 9.4 Hz, 2H), 6.42 (s, 1H), 2.55–2.45 (m, 4H), 2.40–2.28 (m, 2H), 2.09 (quint, J = 6.3
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Hz, 2H), 1.11 (t, J = 7.5 Hz, 3H); C{1H}NMR (100 MHz, CDCl3) δ 194.5, 144.7,
138.0, 135.7, 134.9, 129.9, 129.1, 120.5, 102.3, 37.9, 24.0, 22.7, 20.0, 12.8; HRMS
(ESI+) calc’d for C16H16ClNNaO [M + Na]+: 296.0813, found 296.0809.
1-(4-Bromophenyl)-2-ethyl-1,5,6,7-tetrahydro-4H-indol-4-one 2g. The general
procedure was followed. The reaction was performed with CuI (3.8 mg, 10 mol %), 1g
(63.8 mg, 0.2 mmol), and Cs2CO3 (97.7 mg, 0.3 mmol) in 1.0 mL of THF at room
temperature in a heating mantle for 7 h. The desired product 2g (55.9 mg, 88% yield)
was obtained as a white solid after purification by silica gel chromatography (PE/EA =
5:1). mp: 146−147 °C; 1H NMR (400 MHz, CDCl3) δ 7.64 (d, J = 9.4 Hz, 2H), 7.12 (d,
J = 9.4 Hz, 2H), 6.42 (s, 1H), 2.55–2.44 (q, J = 5.8 Hz, 4H), 2.39 – 2.27 (m, 2H), 2.09
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(quint, J = 6.0 Hz, 2H), 1.11 (t, J = 7.5 Hz, 3H); C{1H}NMR (100 MHz, CDCl3) δ
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194.5, 144.5, 138.0, 136.3, 132.9, 129.4, 122.9, 120.5, 102.3, 37.9, 24.0, 22.7, 20.0,
12.8; HRMS (ESI+) calc’d for C16H16BrNNaO [M + Na]+: 340.0307, found 340.0306.
2-Ethyl-1-(4-nitrophenyl)-1,5,6,7-tetrahydro-4H-indol-4-one 2h. The general
procedure was followed. The reaction was performed with CuI (3.6 mg, 10 mol %), 1h
(56.2 mg, 0.2 mmol), and Cs2CO3 (97.7 mg, 0.3 mmol) in 1.0 mL of THF at room
temperature in a heating mantle for 12 h. The desired product 2h (36.1 mg, 64% yield)
was obtained as a yellow solid after purification by silica gel chromatography (PE/EA
= 5:1 to 3:1). mp: 146−147 °C; 1H NMR (400 MHz, CDCl3) δ 8.40 (d, J = 8.6 Hz, 2H),
7.45 (d, J = 8.6 Hz, 2H), 6.47 (s, 1H), 2.60–2.45 (m, 4H), 2.38 (q, J = 7.0 Hz, 2H), 2.11
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(quint, J = 6.1 Hz, 2H), 1.13 (t, J = 7.4 Hz, 3H); C{1H}NMR (100 MHz, CDCl3) δ
194.4, 147.6, 144.0, 142.9, 137.7, 128.7, 125.1, 121.2, 103.4, 38.0, 24.0, 22.9, 20.2,
12.8. HRMS (ESI+) calc’d for C16H17N2O3 [M + Na]+: 285.1234, found 285.1227.
2-Ethyl-1-(naphthalen-1-yl)-1,5,6,7-tetrahydro-4H-indol-4-one 2i. The general
procedure was followed. The reaction was performed with CuI (3.9 mg, 10 mol %), 1i
(57.7 mg, 0.2 mmol), and Cs2CO3 (98.0 mg, 0.3 mmol) in 1.0 mL of THF at room
temperature in a heating mantle for 7 h. The desired product 2i (55.6 mg, 96% yield)
was obtained as a yellow solid after purification by silica gel chromatography (PE/EA
= 5:1). mp: 92−93 °C; 1H NMR (400 MHz, CDCl3) δ 7.99 (d, J = 8.6 Hz, 2H), 7.96 (d,
J = 8.6 Hz, 2H), 7.62–7.54 (m, 2H), 7.53–7.47 (m, 1H), 7.44 (dd, J = 7.0, 1.2 Hz, 1H),
7.17 (d, J = 8.0 Hz, 1H), 6.53 (s, 1H), 2.53 (t, J = 6.3 Hz, 2H), 2.50–2.38 (m, 1H), 2.29–
2.18 (m, 2H), 2.17–2.10 (m, 1H), 2.08–1.99 (m, 2H), 1.05 (t, J = 7.5 Hz, 3H);
13C{1H}NMR (100 MHz, CDCl3) δ 194.8, 146.1, 139.3, 134.4, 133.7, 131.0, 129.7,
128.5, 127.9, 127.1, 126.1, 125.5, 122.5, 120.2, 101.8, 37.9, 24.0, 22.2, 19.7, 12.8;
HRMS (ESI+) calc’d for C20H20NO [M + H]+: 290.1539, found 290.1532.
2-Ethyl-1-(o-tolyl)-1,5,6,7-tetrahydro-4H-indol-4-one 2j. The general procedure was
followed. The reaction was performed with CuI (3.9 mg, 10 mol %), 1j (50.2 mg, 0.2
mmol), and Cs2CO3 (100.1 mg, 0.3 mmol) in 1.0 mL of THF at room temperature in a
heating mantle for 7 h. The desired product 2j (46.9 mg, 93% yield) was obtained as a
white solid after purification by silica gel chromatography (PE/EA= 3:1).mp: 93−94 °C;
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1H NMR (400 MHz, CDCl3) δ 7.42–7.28 (m, 3H), 7.16 (dd, J = 7.4, 1.5 Hz, 1H), 6.43
(s, 1H), 2.55–2.45 (m, 2H), 2.44–2.39 (m, 1H), 2.36–2.15 (m, 3H), 2.13–2.01 (m, 2H),
1.97 (s, 3H), 1.10 (t, J = 7.5 Hz, 3H); 13C{1H}NMR (100 MHz, CDCl3) δ 194.6, 144.5,
137.8, 136.4, 136.2, 131.2, 129.4, 128.4, 127.1, 120.2, 101.7, 38.0, 24.1, 22.3, 19.8,
17.3, 12.7; HRMS (ESI+) calc’d for C17H19NNaO [M + Na]+: 276.1359, found
276.1359.
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2-Ethyl-1-(2-iodophenyl)-1,5,6,7-tetrahydro-4H-indol-4-one 2k. The general
procedure was followed. The reaction was performed with CuI (3.8 mg, 10 mol %), 1k
(73.3 mg, 0.2 mmol), and Cs2CO3 (98.0 mg, 0.3 mmol) in 1.0 mL of THF at room
temperature in a heating mantle for 7 h. The desired product 2k (72.0 mg, 98% yield)
was obtained as a white solid after purification by silica gel chromatography (PE/EA =
5:1). mp: 150−151 °C; 1H NMR (400 MHz, CDCl3) δ 7.98 (dd, J = 7.8, 1.5 Hz, 1H),
7.50 (td, J = 7.7, 1.5 Hz, 1H), 7.30 (dd, J = 7.6, 1.5 Hz, 1H), 7.20 (td, J = 8.0, 1.5 Hz,
1H), 6.43 (s, 1H), 2.57–2.47 (m, 2H), 2.46–2.33 (m, 2H), 2.25–2.15 (m, 2H), 2.14–2.04
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(m, 2H), 1.14 (t, J = 7.5 Hz, 3H); C{1H}NMR (100 MHz, CDCl3) δ 194.7, 144.5,
140.3, 140.0, 137.5, 130.9, 129.6, 129.4, 120.6, 102.0, 99.5, 37.9, 24.0, 22.6, 20.0, 12.6;
HRMS (ESI+) calc’d for C16H16INNaO [M + Na]+: 388.0169, found 388.0168.
1-Benzyl-2-ethyl-1,5,6,7-tetrahydro-4H-indol-4-one 2l. The general procedure was
followed. The reaction was performed with CuI (4.1 mg, 10 mol %), 1l (50.6 mg, 0.2
mmol), and Cs2CO3 (98.5 mg, 0.3 mmol) in 1.0 mL of THF at 40 oC in a heating mantle
for 24 h. The desired product 2l (40.5 mg, 80% yield) was obtained as a brown oil after
purification by silica gel chromatography (PE/EA = 3:1). 1H NMR (400 MHz, CDCl3)
δ 7.38–7.22 (m, 3H), 6.90 (d, J = 6.8 Hz 2H), 6.40 (s, 1H), 5.04 (s, 2H), 2.64 (t, J = 6.1
Hz, 2H), 2.55–2.37 (m, 4H), 2.11 (quint, J = 6.1 Hz, 2H), 1.20 (t, J = 7.4 Hz, 3H);
13C{1H}NMR (100 MHz, CDCl3) δ 194.4, 144.5, 137.4, 136.8, 129.1, 127.8, 125.7,
120.0, 102.1, 47.2, 37.7, 23.9, 22.1, 19.5, 12.4; HRMS (ESI+) calc’d for C17H19NNaO
[M + Na]+: 276.1359, found 276.1358.
2-Ethyl-1-(furan-2-ylmethyl)-1,5,6,7-tetrahydro-4H-indol-4-one 2m. The general
procedure was followed. The reaction was performed with CuI (3.6 mg, 10 mol %), 1m
(48.6 mg, 0.2 mmol), and Cs2CO3 (97.9 mg, 0.3 mmol) in 1.0 mL of THF at room
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temperature in a heating mantle for 24 h. The desired product 2m (37.6 mg, 77% yield)
was obtained as a white solid after purification by silica gel chromatography (PE/EA =
3:1). mp: 133−134 °C; 1H NMR (400 MHz, CDCl3) δ 7.34 (d, J = 1.0 MHz,1H), 6.38–
6.25 (m, 2H), 6.10 (d, J = 2.4 Hz, 1H), 4.93 (s, 2H), 2.80 (t, J = 6.2 Hz, 2H), 2.58 (q, J
= 7.5 Hz, 2H), 2.45 (t, J = 6.0 Hz, 2H), 2.14 (quint, J = 6.3 Hz, 2H), 1.24 (t, J = 7.4 Hz,
3H); 13C{1H}NMR (100 MHz, CDCl3) δ 194.2, 149.8, 144.1, 142.9, 137.0, 120.0, 110.6,
107.9, 101.8, 40.8, 37.7, 23.8, 22.0, 19.4, 12.3; HRMS (ESI+) calc’d for C15H17NNaO2
[M + Na]+: 266.1151, found 266.1148.
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1-Allyl-2-ethyl-1,5,6,7-tetrahydro-4H-indol-4-one 2n. The general procedure was
followed. The reaction was performed with CuI (3.7 mg, 10 mol %), 1n (40.3 mg, 0.2
mmol), and Cs2CO3 (98.2 mg, 0.3 mmol) in 1.0 mL of THF at room temperature in a
heating mantle for 24 h. The desired product 2n (24.0 mg, 59% yield) was obtained as
a yellow solid after purification by silica gel chromatography (PE/EA = 3:1). mp:
59−60 °C; 1H NMR (400 MHz, CDCl3) δ 6.31 (s, 1H), 5.98–5.74 (m, 1H), 5.15 (d, J =
10.6 Hz, 1H), 4.75 (d, J = 16.9 Hz, 1H), 4.46–4.33 (m, 2H), 2.67 (t, J = 6.2 Hz, 2H),
2.56–2.35 (m, 4H), 2.11 (quint, J = 6.2 Hz, 2H), 1.23 (t, J = 7.4 Hz, 3H); 13C{1H}NMR
(100 MHz, CDCl3) δ 194.3, 144.1, 137.0, 132.8, 116.5, 101.6, 45.9, 37.7, 23.9, 21.8,
19.2, 12.4; HRMS (ESI+) calc’d for C13H17NNaO [M + Na]+: 226.1202, found
226.1203.
2-Ethyl-1-(n-hexyl)-1,5,6,7-tetrahydro-4H-indol-4-one 2o. The general procedure
was followed. The reaction was performed with CuI (4.0 mg, 10 mol %), 1o (49.4 mg,
0.2 mmol), and Cs2CO3 (100.5 mg, 0.3 mmol) in 1.0 mL of THF at 40 oC in a heating
mantle for 24 h. The desired product 2o (31.9 mg, 65% yield) was obtained as a yellow
oil after purification by silica gel chromatography (PE/EA = 3:1). 1H NMR (400 MHz,
CDCl3) δ 6.28 (s, 1H), 3.73 (t, J = 7.4 Hz, 2H), 2.71 (t, J = 6.1 Hz, 2H), 2.52 (q, J = 7.4
Hz, 2H), 2.44 (t, J = 6.3 Hz, 2H), 2.12 (quint, J = 6.2 Hz, 2H), 1.68–1.50 m, 2H), 1.39–
1.19 (m, 9H), 0.88 (t, J = 6.4 Hz, 3H); 13C{1H}NMR (100 MHz, CDCl3) δ 194.1, 143.6,
136.7, 119.6, 101.5, 44.1, 37.8, 31.5, 30.8, 26.6, 23.9, 22.6, 22.2, 19.4, 14.1, 12.4;
HRMS (ESI+) calc’d for C16H25NNaO [M + Na]+: 270.1828, found 270.1827.
2-Benzyl-1-phenyl-1,5,6,7-tetrahydro-4H-indol-4-one 2p. The general procedure
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was followed. The reaction was performed with CuI (3.6 mg, 10 mol %), 1p (60.2 mg,
0.2 mmol), and Cs2CO3 (96.8 mg, 0.3 mmol) in 1.0 mL of THF at room temperature in
a heating mantle for 12 h. The desired product 2p (45.6 mg, 76% yield) was obtained
as a light yellow solid after purification by silica gel chromatography (PE/EA = 3:1).
mp: 114−116 °C; 1H NMR (400 MHz, CDCl3) δ 7.47–7.35 (m, 3H), 7.21–7.12 (m, 3H),
7.11–7.04 (m, 2H), 6.93 (d, J = 7.3 Hz, 2H), 6.38 (s, 1H), 3.71 (s, 2H), 2.55 – 2.40 (m,
4H), 2.15–1.99 (m, 2H); 13C{1H}NMR (100 MHz, CDCl3) δ 194.6, 145.3, 138.5, 137.0,
135.1, 129.5, 128.9, 128.8, 128.4, 128.0, 126.4, 120.3, 104.8, 38.0, 33.2, 24.0, 22.7;
HRMS (ESI+) calc’d for C21H19NNaO [M + Na]+: 324.1359, found 324.1357.
Gram Scale Synthesis of 2a. To a 100 mL Schlenk flask equipped with a magnetic
stirring bar were added CuI (95.7 mg, 0.5 mmol, 10 mol %), substrate 1a (1.19 g, 5
mmol), Cs2CO3 (2.47 g, 7.5 mmol), and 25 mL of THF. The flask was removed from
the glovebox, and the reaction was stirred at room temperature for 12 h under argon.
After completion of the reaction, it was quenched with 50 mL of HCl aqueous solution
(1 M in THF). The resulted mixture was continued to stir overnight at room temperature.
Then the mixture was diluted with DCM (100 mL) and the organic phase was separated,
dried over anhydrous Na2SO4, and filtered with a pad of celite. The solvents were
removed under reduced pressure and the desired product 2a (1.09 g, 91% yield) was
obtained as a white solid after purification by silica gel chromatography (PE/EA = 3:1).
Gram Scale Synthesis of 2k. Followed the procedure of the gram scale synthesis of
2a, the reaction was carried out with substrate 1k (1.83 g, 5 mmol) for 12 h. The desired
product 2k (1.82 g, 99% yield) was obtained as a white solid after purification by silica
gel chromatography (PE/EA = 1:1).
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Synthesis of 2-Ethyl-3-(hydroxymethyl)-1-phenyl-1,5,6,7-tetrahydro-4H-indol -4-
one 3. To a solution of 2a (48.1 mg, 0.2 mmol) in 1 mL of dioxane were added
polyformaldehyde (19.4 mg, 0.6 mmol) and HCl (1 mL, 12 M). The mixture was stirred
at room temperature and monitored by TLC. After completion of the reaction, the
solvents were removed under reduced pressure. The desired product 3 (42.1 mg, 78%
yield) was obtained as a white solid after purification by silica gel chromatography
(PE/EA = 1:1). mp: 136−137 °C; 1H NMR (400 MHz, CDCl3) δ 7.55–7.44 (m, 3H),
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J = 6.6 Hz, 2H), 0.88 (t, J = 7.5 Hz, 3H); C{1H}NMR (100 MHz, CDCl3) δ 196.6,
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145.9, 136.9, 133.6, 129.7, 129.1, 127.9, 119.2, 119.0, 56.4, 37.9, 23.8, 22.6, 17.5, 15.4;
HRMS (ESI+) calc’d for C17H19NNaO2 [M + Na]+: 292.1308, found 292.1308.
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Synthesis
of
2-Ethyl-3-((4-methylpiperazin-1-yl)methyl)-1-phenyl-1,5,6,7-
tetrahydro-4H- indol-4-one 4. Compound 2a (47.6 mg, 0.2 mmol) and
polyformaldehyde (18.8 mg, 0.6 mmol) were dissolved in acetic acid (0.4 mL), then N-
methyl piperazine (60.5 mg, 0.6 mmol) was added to the mixture. The reaction was
stirred at room temperature and monitored by TLC. After completion of the reaction,
the mixture was diluted with water (5 mL), and the pH was adjusted to 8–9 by the
addition of NH3•H2O carefully. The mixture was then extracted with DCM (5 mL×3).
The combined organic layers were washed with brine and dried over anhydrous MgSO4,
filtered and the filtrate was concentrated under reduced pressure. The desired product
4 (55.4 mg, 79% yield) was obtained as a brown oil without further purification. mp:
1
103−104 °C; H NMR (400 MHz, CDCl3) δ 7.52–7.36 (m, 3H), 7.24–7.14 (m, 2H),
3.84 (s, 2H), 2.65 (br s, 4H), 2.54–2.44 (m, 4H), 2.45–2.33 (m, 6H), 2.23 (s, 3H), 1.97
(quint, J = 6.3 Hz, 2H), 0.77 (t, J = 7.4 Hz, 3H); C{1H}NMR (100 MHz, CDCl3) δ
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194.9, 143.9, 137.3, 136.6, 129.5, 128.7, 127.8, 118.9, 113.0, 54.8, 52.0, 51.0, 45.9,
38.9, 23.6, 22.8, 17.6, 14.3; HRMS (ESI+) calc’d for C22H30N3O [M + H]+: 352.2383,
found 352.2383.
Synthesis of 3-Bromo-2-ethyl-1-phenyl-1,5,6,7-tetrahydro-4H-indol-4-one 5.
Compound 2a (47.4 mg, 0.2 mmol) and NH4Br (22.1 mg, 0.22 mmol) were dissolved
in MeOH (1 mL), then oxone (35.5 mg, 0.22 mmol) was added to the mixture. The
o
reaction was stirred at 35 C in a heating mantle and monitored by TLC. After
completion of the reaction, saturated Na2S2O3 aqueous solution was added to quench
the reaction. The aqueous layer was extracted with EA (5 mL × 3). The combined
organic layers were washed with water and dried over anhydrous Na2SO4, filtered and
the filtrate was concentrated under reduced pressure. The desired product 5 (38.3 mg,
60% yield) was obtained as a brown solid after purification by silica gel
1
chromatography (PE/EA = 5:1). mp: 120−121 °C; H NMR (400 MHz, CDCl3) δ
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7.58–7.46 (m, 3H), 7.25–7.18 (m, 2H), 2.59–2.40 (m, 6H), 2.06 (t, J = 6.2 Hz, 2H),
0.92 (t, J = 7.5 Hz, 3H); 13C{1H}NMR (100 MHz, CDCl3) δ 193.3, 144.1, 136.8, 135.5,
129.8, 129.4, 127.9, 117.2, 93.0, 38.6, 23.4, 23.1, 18.3, 13.6; HRMS (ESI+) calc’d for
C16H16BrNNaO [M + Na]+: 340.0307, found 340.0304.
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Synthesis of 2-Ethyl-1-phenyl-5,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4(1H)-one 6.
Compound 2a (47.4 mg, 0.2 mmol) was dissolved in concentrated HCl (0.35 mL) at 0
oC, and NaN3 (25.5 mg, 0.4 mmol) was then added to the mixture carefully. The reaction
was stirred at 50 oC in a heating mantle and monitored by TLC until the full conversion
of the starting material. The mixture was poured into ice water, and the pH was adjusted
to 10 by the addition of aqueous K2CO3 (1 M). The mixture was then extracted with
DCM (5 mL×3), and the combined organic layers were washed with brine and dried
over anhydrous MgSO4, filtered and the filtrate was concentrated under reduced
pressure. The desired product 6 (28.8 mg, 57% yield) was obtained as a white solid
1
after purification by silica gel chromatography (PE/EA = 5:1). mp: 120−121 °C; H
NMR (400 MHz, CDCl3) δ 7.55–7.41 (m, 3H), 7.24–7.16 (m, 2H), 6.34 (s, 1H), 3.81–
3.73 (m, 2H), 2.57 (t, J = 6.5 Hz, 2H), 2.28 (q, J = 7.5 Hz, 2H), 1.96–1.80 (m, 2H), 1.10
13
(t, J = 7.5 Hz, 3H); C{1H}NMR (100 MHz, CDCl3) δ 151.5, 137.5, 136.8, 136.1,
129.7, 129.1, 128.2, 116.0, 107.7, 52.1, 29.0, 23.6, 20.0, 12.8; HRMS (ESI+) calc’d for
C16H19N2O [M + H]+: 255.1492, found 255.1489.
Synthesis of 2-Ethyl-1-phenyl-1H-indol-4-ol 7. To a Schlenk flask were added prrrole
2a (24.0 mg, 0.1 mmol), CuBr2 (44.5 mg, 0.2 mmol) and EA (1 mL) under argon. The
flask was then connected with a condenser and the mixture was reflux in a heating
mantle until the completion of the starting material as monitored by TLC. Then the
mixture was filtered while it was hot. The filtrate was diluted with DCM, and washed
with brine and dried over anhydrous MgSO4, filtered and concentrated under reduced
pressure. The resulted crude product was directly carried out into the next step without
further purification.
To a solution of above prepared crude product in DMF (1 mL), LiBr (9.3 mg, 0.1 mmol),
and Li2CO3 (9.0 mg) were added. The mixture was stirred at 150 oC in a heating mantle
under argon for 1.5 h. Then the mixture was poured into saturated NH4Cl aqueous
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solution and the aqueous phase was extracted with DCM (5 mL × 3). The combined
organic phase was washed with water, dried over anhydrous MgSO4, filtered and
concentrated under reduced pressure. The desired product 7 (12.3 mg, 52% yield of two
steps) was obtained as a yellow oil after purification by silica gel chromatography
(PE/EA = 5:1). 1H NMR (400 MHz, CDCl3) δ7.58–7.50 (m, 2H), 7.49–7.42 (m, 1H),
7.39–7.31 (m, 2H), 6.94 (t, J = 7.6 Hz, 1H), 6.68 (d, J = 7.6 Hz, 1H), 6.54 (d, J = 7.6
Hz, 1H), 6.47 (br s, 1H), 2.62 (q, J = 7.5 Hz, 2H), 1.22 (t, J = 7.5 Hz, 3H); 13C{1H}NMR
(100 MHz, CDCl3) δ 148.2, 142.5, 140.3, 138.1, 129.6, 128.3, 128.0, 122.0, 117.4,
104.6, 103.5, 95.4, 20.7, 13.0; HRMS (ESI+) calc’d for C16H16NO [M + H]+: 238.1226,
found 238.1220.
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Synthesis of 5-Allyl-2-ethyl-1-phenyl-1,5,6,7-tetrahydro-4H-indol-4-one 8. To a
solution of 2a (239.5 mg, 1 mmol) in THF (5 mL) was added LDA (5 mL, 1 mmol, 0.2
M in THF) dropwise at –78 oC under argon. After the mixture was stirred at –78 oC for
2 h, a solution of allyl bromide (476.9 mg, 4 mmol) in THF (5 mL) was added slowly
by syringe. The reaction was stirred at room temperature until the completion of 2a.
Then saturated NH4Cl aqueous solution was added to quench the reaction. THF was
removed under reduced pressure, and the aqueous layer was extracted with DCM (5
mL × 3). The combined organic phase was dried over anhydrous Na2SO4, filtered and
concentrated under reduced pressure. The desired product 8 (231.0 mg, 83% yield) was
obtained as a yellow solid after purification by silica gel chromatography (PE/EA =
3:1). mp: 69−70 °C; 1H NMR (400 MHz, CDCl3) δ 7.56–7.41 (m, 3H), 7.25–7.21 (m,
2H), 6.41 (t, J = 1.1 Hz, 1H), 5.93–5.73 (m, 1H), 5.11–4.98 (m, 2H), 2.79–2.66 (m, 1H),
2.55–2.49 (m, 2H), 2.49–2.40 (m, 1H), 2.39–2.30 (m, 2H), 2.30–2.19 (m, 1H), 2.16–
13
2.09 (m, 1H), 1.92–1.79 (m, 1H), 1.11 (t, J = 7.4 Hz, 3H); C{1H}NMR (100 MHz,
CDCl3) δ 195.5, 144.0, 138.3, 137.2, 137.1, 129.6, 128.8, 127.8, 119.8, 116.6, 102.2,
45.9, 34.2, 28.4, 21.5, 20.1, 12.8; HRMS (ESI+) calc’d for C19H21NNaO [M + Na]+:
302.1515, found 302.1514.
General Procedure for the Synthesis of Enaminones 1 (see Table S1 in SI for
structures). To a 100 mL two-neck round-bottomed flask equipped with a Dean-Stark
apparatus were added aniline (1.49 g, 15 mmol), 2-(but-2-yn-1-yl)cyclohexane-1,3-
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dione (1.65 g, 10 mmol), p-TsOH•H2O (125.5 mg, 0.66 mmol) and 50 mL of toluene.
The mixture was refluxed and monitored by TLC. After completion of the reaction, it
was cooled to room temperature and neutralized with solid K2CO3. The mixture was
diluted with DCM (100 mL), washed with brine and dried over anhydrous Na2SO4. The
desired product 2-(but-2-yn-1-yl)-3-(phenylamino)cyclohex-2-en-1-one 1a (1.73 g, 72%
yield) was obtained as a white solid after purification by silica gel chromatography
(PE/EA = 10:1 to PE/EA = 1:1). mp: 127−128 °C; 1H NMR (400 MHz, CDCl3) δ 7.37
(t, J = 7.8 Hz, 2H), 7.33 (br s, 1H), 7.21 (t, J = 7.4 Hz, 1H), 7.09 (d, J = 7.9 Hz, 2H),
3.38 (q, J = 2.8 Hz, 2H), 2.51 (t, J = 6.1 Hz, 2H), 2.39 (t, J = 6.5 Hz, 2H), 1.92 (quint,
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J = 6.3 Hz, 2H), 1.83 (t, J = 2.5 Hz, 3H); C{1H}NMR (100 MHz, CDCl3) δ 194.3,
160.1, 138.8, 129.4, 125.6, 124.9, 107.8, 77.4, 76.5, 36.5, 27.2, 22.0, 12.3, 3.8; HRMS
(ESI+) calc’d for C16H17NNaO [M + Na]+: 262.1202, found 262.1202.
2-(But-2-yn-1-yl)-3-(p-tolylamino)cyclohex-2-en-1-one 1b. The general procedure
was followed. The reaction was conducted with 4-methylaniline (322.6 mg, 3.0 mmol),
2-(but-2-yn-1-yl)cyclohexane-1,3-dione (332.2 mg, 2.0 mmol), p-TsOH•H2O (21.6 mg,
0.11 mmol) in toluene (20 mL). The desired product 1b (386.2 mg, 76% yield) was
obtained as a white solid after purification by silica gel chromatography (PE/EA = 5:1
to PE/EA = 1:1). mp: 119−120 °C; 1H NMR (400 MHz, CDCl3) δ 7.25 (br s, 1H), 7.17
(d, J = 8.0 Hz, 2H), 6.99 (d, J = 8.0 Hz, 2H), 3.37 (q, J = 2.7 Hz, 2H), 2.45 (t, J = 6.2
Hz, 2H), 2.38 (t, J = 5.9 Hz, 2H), 2.36 (s, 3H), 1.89 (quint, J = 6.4 Hz, 2H), 1.81 (t, J =
13
2.7 Hz, 3H); C{1H}NMR (100 MHz, CDCl3) δ 194.1, 160.6, 136.1, 135.8, 130.0,
125.2, 107.2, 77.2, 76.6, 36.5, 27.2, 21.9, 21.1, 12.2, 3.8; HRMS (ESI+) calc’d for
C17H19NNaO [M + Na]+: 276.1359, found 276.1358.
2-(But-2-yn-1-yl)-3-((4-methoxyphenyl)amino)cyclohex-2-en-1-one 1c. The general
procedure was followed. The reaction was conducted with 4-methoxyaniline (930.4 mg,
7.5 mmol), 2-(but-2-yn-1-yl)cyclohexane-1,3-dione (820.4 mg, 5.0 mmol), p-
TsOH•H2O (58.6 mg, 0.31 mmol) in toluene (30 mL). The desired product 1c (953.8
mg, 71% yield) was obtained as a light yellow solid after purification by silica gel
chromatography (PE/EA= 10:1 to PE/EA= 1:1). mp: 102−103 °C; 1H NMR (400 MHz,
CDCl3) δ 7.14 (br s, 1H), 7.05 (d, J = 9.0 Hz, 2H), 6.89 (d, J = 9.0 Hz, 2H), 3.82 (s,
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3H), 3.36 (q, J = 2.7 Hz, 2H), 2.43–2.31 (m, 4H), 1.88 (quint, J = 6.4 Hz, 2H), 1.80 (t,
J = 2.6 Hz, 3H); 13C{1H}NMR (100 MHz, CDCl3) δ 194.0, 161.1, 158.0, 131.5, 127.3,
114.6, 106.7, 77.1, 76.6, 55.7, 36.4, 27.1, 21.7, 12.2, 3.8; HRMS (ESI+) calc’d for
C17H20NO2 [M + H]+: 270.1489, found 270.1496.
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3-((4-Aminophenyl)amino)-2-(but-2-yn-1-yl)cyclohex-2-en-1-one 1d. The general
procedure was followed. The reaction was conducted with benzene-1,4-diamine (435.4
mg, 4.0 mmol), 2-(but-2-yn-1-yl)cyclohexane-1,3-dione (824.7 mg, 5.0 mmol), p-
TsOH•H2O (59.5 mg, 0.31 mmol) in toluene (30 mL). The desired product 1d (947.2
mg, 93% yield) was obtained as a yellow solid after purification by silica gel
chromatography (PE/EA = 1:1 to PE/EA = 1:2). mp: 114−115 °C; 1H NMR (400 MHz,
CDCl3) δ 7.08 (br s, 1H), 6.92 (d, J = 8.7 Hz, 2H), 6.69 (d, J = 8.8 Hz, 2H), 3.72 (br s,
2H), 3.35 (q, J = 2.7 Hz, 2H), 2.49–2.22 (m, 4H), 1.87 (quint, J = 6.3 Hz, 2H), 1.79 (t,
J = 2.7 Hz, 3H); 13C{1H}NMR (100 MHz, CDCl3) δ 193.9, 161.6, 144.7, 129.6, 127.5,
115.7, 106.3, 76.9, 76.7, 36.4, 27.0, 21.7, 12.2, 3.8; HRMS (ESI+) calc’d for C16H19N2O
[M + H]+: 255.1492, found 255.1488.
2-(But-2-yn-1-yl)-3-((4-(tert-butyl)phenyl)amino)cyclohex-2-en-1-one 1e. The
general procedure was followed. The reaction was conducted with 4-tert-butylaniline
(448.3 mg, 3.0 mmol), 2-(but-2-yn-1-yl)cyclohexane-1,3-dione (329.3 mg, 2.0 mmol),
p-TsOH•H2O (21.4 mg, 0.11 mmol) in toluene (20 mL). The desired product 1e (469.2
mg, 80% yield) was obtained as an orange solid after purification by silica gel
chromatography (PE/EA = 3:1 to PE/EA = 1:1). mp: 152−154 °C; 1H NMR (400 MHz,
CDCl3) δ 7.37 (d, J = 8.6 Hz, 2H), 7.29 (br s, 1H), 7.02 (d, J = 8.6 Hz, 2H), 3.37 (q, J
= 2.7 Hz, 2H), 2.49 (t, J = 6.1 Hz, 2H), 2.38 (t, J = 6.1 Hz, 2H), 1.90 (quint, J = 6.0 Hz,
2H), 1.81 (t, J = 2.7 Hz, 3H), 1.32 (s, 9H); 13C{1H}NMR (100 MHz, CDCl3) δ 194.1,
160.6, 149.0, 136.1, 126.3, 124.8, 107.1, 77.2, 76.6, 36.5, 34.6, 31.5, 27.2, 21.9, 12.2,
3.8. HRMS (ESI+) calc’d for C20H25NNaO [M + Na]+: 318.1828, found 318.1829.
2-(But-2-yn-1-yl)-3-((4-chlorophenyl)amino)cyclohex-2-en-1-one 1f. The general
procedure was followed. The reaction was conducted with 4-chloroaniline (384.9 mg,
3.0 mmol), 2-(but-2-yn-1-yl)cyclohexane-1,3-dione (328.7 mg, 2.0 mmol), p-
TsOH•H2O (21.4 mg, 0.11 mmol) in toluene (20 mL). The desired product 1f (337.3
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mg, 62% yield) was obtained as a yellow solid after purification by silica gel
chromatography (PE/EA = 3:1 to PE/EA = 1:1). mp: 130−131 °C; 1H NMR (400 MHz,
CDCl3) δ 7.33 (d, J = 8.8 Hz, 2H), 7.31 (br s, 1H), 7.02 (d, J = 8.8 Hz, 2H), 3.36 (q, J
= 2.7 Hz, 2H), 2.47 (t, J = 6.1 Hz, 2H), 2.40 (t, J = 6.1 Hz, 2H), 1.92 (quint, J = 6.3 Hz,
2H), 1.82 (t, J = 2.7 Hz, 3H); 13C{1H}NMR (100 MHz, CDCl3) δ 194.3, 159.7, 137.4,
131.2, 129.6, 126.0, 108.4, 77.5, 76.3, 36.4, 27.2, 21.9, 12.3, 3.8; HRMS (ESI+) calc’d
for C16H16ClNNaO [M + Na]+: 296.0813, found 296.0814.
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3-((4-Bromophenyl)amino)-2-(but-2-yn-1-yl)cyclohex-2-en-1-one 1g. The general
procedure was followed. The reaction was conducted with 4-bromoaniline (516.3 mg,
3.0 mmol), 2-(but-2-yn-1-yl)cyclohexane-1,3-dione (329.9 mg, 2.0 mmol), p-
TsOH•H2O (22.4 mg, 0.12 mmol) in toluene (20 mL). The desired product 1g (470.9
mg, 74% yield) was obtained as a light yellow solid after purification by silica gel
chromatography (PE/EA = 3:1). mp: 140−141 °C; 1H NMR (400 MHz, CDCl3) δ 7.47
(d, J = 8.7 Hz, 2H), 7.27 (br s, 1H), 6.95 (d, J = 8.7 Hz, 2H), 3.34 (q, J = 2.7 Hz, 2H),
2.47 (t, J = 6.1 Hz, 2H), 2.38 (t, J = 6.4 Hz, 2H), 1.92 (quint, J = 6.3 Hz, 2H), 1.81 (t,
J = 2.7 Hz, 3H); 13C{1H}NMR (100 MHz, CDCl3) δ 194.3, 159.3, 138.0, 132.5, 126.2,
118.7, 108.6, 77.5, 76.3, 36.5, 27.2, 21.9, 12.3, 3.8; HRMS (ESI+) calc’d for
C16H16BrNNaO [M + Na]+: 340.0307, found 340.0304.
2-(But-2-yn-1-yl)-3-((4-nitrophenyl)amino)cyclohex-2-en-1-one 1h. The general
procedure was followed. The reaction was conducted with 4-nitroaniline (1.0530 g, 7.5
mmol), 2-(but-2-yn-1-yl)cyclohexane-1,3-dione (818.0 mg, 5.0 mmol), p-TsOH•H2O
(51.3 mg, 0.27 mmol) in toluene (30 mL). The desired product 1h (847.4 mg, 60% yield)
was obtained as a dark yellow solid after purification by silica gel chromatography
(PE/EA = 10:1 to PE/EA = 1:1). mp: 159−160 °C; 1H NMR (400 MHz, CDCl3) δ 8.22
(d, J = 8.8 Hz, 2H), 7.80 (br s, 1H), 7.07 (d, J = 8.8 Hz, 2H), 3.35 (q, J = 2.7 Hz, 2H),
2.68 (t, J = 6.0 Hz, 2H), 2.45 (t, J = 6.6 Hz, 2H), 2.02 (quint, J = 6.3 Hz, 2H), 1.84 (t,
J = 2.6 Hz, 3H); 13C{1H}NMR (100 MHz, CDCl3) δ 194.9, 157.0, 145.3, 143.2, 125.5,
121.2, 112.6, 78.3, 75.8, 36.6, 27.8, 22.4, 12.6, 3.8; HRMS (ESI+) calc’d for
C16H17N2O3 [M + H]+: 285.1234, found 285.1233.
2-(But-2-yn-1-yl)-3-(naphthalen-1-ylamino)cyclohex-2-en-1-one 1i. The general
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procedure was followed. The reaction was conducted with naphthalen-1-amine (2.1527
g, 15 mmol), 2-(but-2-yn-1-yl)cyclohexane-1,3-dione (1.6485 g, 10.0 mmol), p-
TsOH•H2O (53.8 mg, 0.28 mmol) in toluene (50 mL). The desired product 1i (2.11 g,
70% yield) was obtained as a brown solid after purification by silica gel
chromatography (PE/EA= 10:1 to PE/EA= 1:1). mp: 169−170 °C; 1H NMR (400 MHz,
CDCl3) δ 8.12–8.03 (m, 1H), 7.96–7.89 (m, 1H), 7.83 (d, J = 8.3 Hz, 1H), 7.60–7.53
(m, 2H), 7.52–7.46 (m, 2H), 7.33 (d, J = 7.2 Hz, 1H), 3.51 (q, J = 2.7 Hz, 2H), 2.41 (t,
J = 6.6 Hz, 2H), 2.31 (t, J = 6.2 Hz, 2H), 1.92–1.80 (m, 5H); 13C{1H}NMR (100 MHz,
CDCl3) δ 194.2, 162.1, 134.6, 134.5, 130.8, 128.7, 127.6, 127.2, 126.8, 125.6, 124.6,
122.5, 107.4, 77.6, 77.4, 36.3, 26.9, 21.7, 12.3, 3.9; HRMS (ESI+) calc’d for
C20H19NONa [M + Na]+: 312.1359, found 312.1364.
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2-(But-2-yn-1-yl)-3-(o-tolylamino)cyclohex-2-en-1-one 1j. The general procedure
was followed. The reaction was conducted with o-toluidine (804.4 mg, 7.5 mmol), 2-
(but-2-yn-1-yl)cyclohexane-1,3-dione (839.5 mg, 5.0 mmol), p-TsOH•H2O (54.2 mg,
0.28 mmol) in toluene (30 mL). The desired product 1j (896.8 mg, 71% yield) was
obtained as a white solid after purification by silica gel chromatography (PE/EA = 5:1
to PE/EA = 1:1). mp: 82−84°C; 1H NMR (400 MHz, CDCl3) δ 7.40–7.24 (m, 3H), 7.18
(dd, J = 7.3, 1.8 Hz, 1H), 7.09 (br s, 1H), 3.49 (q, J = 2.7 Hz, 2H), 2.47 (t, J = 6.5 Hz,
2H), 2.44–2.35 (m, 2H), 2.41 (s, 3H), 1.98 (quint, J = 6.4 Hz, 2H), 1.88 (t, J = 2.7 Hz,
3H); 13C{1H}NMR (100 MHz, CDCl3) δ 194.0, 161.0, 137.4, 134.2, 131.1, 127.0, 126.8,
107.4, 77.4, 77.0, 36.5, 27.0, 21.8, 18.1, 12.2, 3.9; HRMS (ESI+) calc’d for C17H20NO
[M + H]+: 254.1539, found 254.1543.
2-(But-2-yn-1-yl)-3-((2-iodophenyl)amino)cyclohex-2-en-1-one 1k. The general
procedure was followed. The reaction was conducted with 2-iodoaniline (3.3052 g, 15
mmol), 2-(but-2-yn-1-yl)cyclohexane-1,3-dione (1.6450 g, 10.0 mmol), p-TsOH•H2O
(51.7 mg, 0.27 mmol) in toluene (50 mL). The desired product 1k (2.2152 g, 61% yield)
was obtained as a brown solid after purification by silica gel chromatography (PE/EA
= 10:1 to PE/EA = 1:1). mp: 134−135 °C; 1H NMR (400 MHz, CDCl3) δ 7.89 (d, J =
7.9 Hz, 1H), 7.36 (t, J = 7.4 Hz, 1H), 7.16 (d, J = 7.8 Hz, 1H), 7.09 (br s, 1H), 6.95 (t,
J = 7.8, 1.5 Hz, 1H), 3.38 (q, J = 2.8 Hz, 2H), 2.39 (t, J = 6.5 Hz, 2H), 2.33 (t, J = 6.1
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Hz, 2H), 1.91 (quint, J = 6.3 Hz, 2H), 1.79 (t, J = 2.6 Hz, 3H); 13C{1H}NMR (100 MHz,
CDCl3) δ 194.6, 159.6, 140.7, 139.7, 129.2, 127.8, 126.9, 109.4, 97.4, 77.5, 76.4, 36.6,
27.3, 21.7, 12.5, 4.4; HRMS (ESI+) calc’d for C16H17INO [M + H]+: 366.0349, found
366.0347.
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3-(Benzylamino)-2-(but-2-yn-1-yl)cyclohex-2-en-1-one 1l. The general procedure
was followed. The reaction was conducted with phenylmethanamine (857.4 mg, 7.5
mmol), 2-(but-2-yn-1-yl)cyclohexane-1,3-dione (821.6 mg, 5.0 mmol), p-TsOH•H2O
(31.0 mg, 0.16 mmol) in toluene (30 mL). The desired product 1l (987.1 mg, 78% yield)
was obtained as a light brown solid after purification by silica gel chromatography
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(PE/EA = 1:1). mp: 105−106 °C; H NMR (400 MHz, CDCl3) δ 7.42–7.35 (m, 2H),
7.34–7.28 (m, 3H), 5.84 (br s, 1H), 4.51 (d, J = 6.0 Hz, 2H), 3.30 (q, J = 2.7 Hz, 2H),
2.47 (t, J = 6.2 Hz, 2H), 2.33 (t, J = 6.5 Hz, 2H), 1.91 (quint, J = 6.3 Hz, 2H), 1.68 (t,
J = 2.6 Hz, 3H); 13C{1H}NMR (100 MHz, CDCl3) δ 193.2, 162.4, 138.1, 129.1, 127.9,
126.8, 76.84, 76.81, 47.3, 35.9, 25.6, 21.2, 12.0, 3.7; HRMS (ESI+) calc’d for
C17H19NNaO [M + Na]+: 276.1359, found 276.1363.
2-(But-2-yn-1-yl)-3-((furan-2-ylmethyl)amino)cyclohex-2-en-1-one
1m.
The
general procedure was followed. The reaction was conducted with furan-2-
ylmethanamine (729.4 mg, 7.5 mmol), 2-(but-2-yn-1-yl)cyclohexane-1,3-dione (823.6
mg, 5.0 mmol), p-TsOH•H2O (53.7 mg, 0.28 mmol) in toluene (30 mL). The desired
product 1m (701.8 mg, 58% yield) was obtained as a yellow solid after purification by
silica gel chromatography (PE/EA= 1:1). mp: 137−138 °C; 1H NMR (400 MHz, CDCl3)
δ 7.37 (dd, J = 1.8, 0.8 Hz, 1H), 6.33 (dd, J = 3.3, 1.8 Hz, 1H), 6.24 (dd, J = 3.3, 0.9
Hz, 1H), 5.75 (br s, 1H), 4.44 (d, J = 6.1 Hz, 2H), 3.24 (q, J = 2.7 Hz, 2H), 2.53 (t, J =
6.2 Hz, 2H), 2.31 (t, J = 6.1 Hz, 2H), 1.93 (quint, J = 6.5 Hz, 2H), 1.68 (t, J = 2.7 Hz,
3H); 13C{1H}NMR (100 MHz, CDCl3) δ 193.3, 161.7, 151.4, 142.7, 110.6, 107.3, 106.0,
76.8, 76.6, 40.5, 36.0, 25.4, 21.1, 11.9, 3.6; HRMS (ESI+) calc’d for C15H18NO2 [M +
H]+: 244.1332, found 244.1330.
3-(Allylamino)-2-(but-2-yn-1-yl)cyclohex-2-en-1-one 1n. The general procedure was
followed. The reaction was conducted with prop-2-en-1-amine (424.8 mg, 7.5 mmol),
2-(but-2-yn-1-yl)cyclohexane-1,3-dione (821.2 mg, 5.0 mmol), p-TsOH•H2O (97.3 mg,
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0.51 mmol) in toluene (30 mL). The desired product 1n (616.6 mg, 61% yield) was
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obtained as a light yellow solid after purification by silica gel chromatography (PE/EA
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= 1:1). mp: 81−82 °C; H NMR (400 MHz, CDCl3) δ 5.99–5.78 (m, 1H), 5.52 (br s,
9
1H), 5.31–5.214 (m, 1H), 5.246–5.17 (m, 1H), 3.99–3.81 (m, 2H), 3.26 (q, J = 2.7 Hz,
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2H), 2.45 (t, J = 6.2 Hz, 2H), 2.31 (t, J = 6.0 Hz, 2H), 1.91 (quint, J = 6.4 Hz, 2H), 1.72
13
(t, J = 2.6 Hz, 3H); C{1H}NMR (100 MHz, CDCl3) δ 193.1, 162.4, 134.5, 116.4,
105.4, 76.7, 76.5, 45.4, 36.0, 25.2, 21.2, 11.9, 3.7; HRMS (ESI+) calc’d for C13H18NO
[M + H]+: 204.1383, found 204.1383.
2-(But-2-yn-1-yl)-3-(n-nexylamino)cyclohex-2-en-1-one 1o. The general procedure
was followed. The reaction was conducted with hexan-1-amine (795.7 mg, 7.5 mmol),
2-(but-2-yn-1-yl)cyclohexane-1,3-dione (824.6 mg, 5.0 mmol), p-TsOH•H2O (59.3 mg,
0.31 mmol) in toluene (30 mL). The desired product 1o (781.8 mg, 63% yield) was
obtained as a light yellow oil after purification by silica gel chromatography (PE/EA =
5:1 to PE/EA = 1:1). 1H NMR (400 MHz, CDCl3) δ 5.41 (br s, 1H), 3.34–3.16 (m, 4H),
2.47 (t, J = 6.2 Hz, 2H), 2.32 (t, J = 6.5 Hz, 2H), 1.93 (quint, J = 6.4 Hz, 2H), 1.75 (t,
J = 2.7 Hz, 3H), 1.60 (quint, J = 7.2 Hz, 2H), 1.46–1.36 (m, 2H), 1.36–1.26 (m, 4H),
0.90 (t, J = 6.8 Hz, 3H); 13C{1H}NMR (100 MHz, CDCl3) δ 192.8, 162.5, 104.5, 77.0,
76.3, 43.4, 36.0, 31.6, 30.5, 26.6, 25.7, 22.7, 21.2, 14.1, 11.9, 3.8; HRMS (ESI+) calc’d
for C16H26NO [M + H]+: 248.2009, found 248.2015.
3-(Phenylamino)-2-(3-phenylprop-2-yn-1-yl)cyclohex-2-en-1-one 1p. The general
procedure was followed. The reaction was conducted with aniline (118.6 mg, 1.26
mmol), 2-(3-phenylprop-2-yn-1-yl)cyclohexane-1,3-dione (190.2 mg, 0.84 mmol), p-
TsOH•H2O (13.9 mg, 0.07 mmol) in toluene (10 mL). The desired product 1p (166.9
mg, 66% yield) was obtained as a yellow solid after purification by silica gel
chromatography (PE/EA = 3:1). mp: 147−148 °C; 1H NMR (400 MHz, CDCl3) δ 7.42–
7.37 (m, 2H), 7.35 (d, J = 7.3 Hz, 2H), 7.32–7.27 (m, 3H), 7.22 (t, J = 7.4 Hz, 1H), 7.10
(d, J = 7.7 Hz, 2H), 3.68 (s, 2H), 2.53 (t, J = 6.1 Hz, 2H), 2.43 (t, J = 6.4 Hz, 2H), 1.95
(quint, J = 6.2 Hz, 2H); 13C{1H}NMR (100 MHz, CDCl3) δ 194.3, 160.4, 138.6, 131.7,
129.5, 128.4, 128.1, 125.9, 125.0, 123.4, 107.2, 87.2, 81.9, 36.5, 27.3, 21.9, 13.0;
HRMS (ESI+) calc’d for C21H20NO [M + H]+: 302.1539, found 302.1538.
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2-(But-2-yn-1-yl)-3-(prop-2-yn-1-ylamino)cyclohex-2-en-1-one 1r. The general
procedure was followed. The reaction was conducted with prop-2-yn-1-amine (416.9
mg, 7.5 mmol), 2-(but-2-yn-1-yl)cyclohexane-1,3-dione (822.9 mg, 5.0 mmol), p-
TsOH•H2O (67.7 mg, 0.36 mmol) in toluene (30 mL). The desired product 1r (574.6
mg, 57% yield) was obtained as a white solid after purification by silica gel
chromatography (PE/EA = 1:1). mp: 132−133 °C; 1H NMR (400 MHz, CDCl3) δ 5.60
(br s, 1H), 4.04 (dd, J = 5.9, 2.5 Hz, 2H), 3.23 (q, J = 2.7 Hz, 2H), 2.56 (t, J = 6.2 Hz,
2H), 2.38–2.28 (m, 3H), 1.96 (quint, J = 6.5 Hz, 2H), 1.75 (t, J = 2.7 Hz, 3H);
13C{1H}NMR (100 MHz, CDCl3) δ 193.6, 161.4, 106.8, 79.5, 76.9, 76.4, 72.7, 36.0,
33.0, 25.4, 21.1, 12.0, 3.8; HRMS (ESI+) calc’d for C13H16NO [M + H]+: 202.1226,
found 202.1229.
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3-Amino-2-(but-2-yn-1-yl)cyclohex-2-en-1-one 1q. To a 50 mL two-neck round-
bottomed flask equipped with a Dean-Stark apparatus were added NH4OAc (2.05 g, 25
mmol) and 2-(prop-2-yn-1-yl)cyclohexane-1,3-dione (820.2 mg, 5.0 mmol) in toluene
(30 mL). The mixture was refluxed and monitored by TLC. After completion of the
starting materials, it was cooled to room temperature and diluted with DCM (100 mL),
dried over anhydrous Na2SO4. The desired product 3-amino-2-(but-2-yn-1-
yl)cyclohex-2-en-1-one 1q (750.8 mg, 87% yield) was obtained as a white solid after
purification by silica gel chromatography (PE/EA = 1:1 to EA). mp: 169−170 °C; 1H
NMR (400 MHz, CDCl3) δ 5.04 (br s, 2H), 3.22 (q, J = 2.7 Hz, 2H), 2.43 (t, J = 6.2 Hz,
2H), 2.33 (t, J = 6.5 Hz, 2H), 1.93 (quint, J = 6.4 Hz, 2H), 1.75 (t, J = 2.7 Hz, 3H);
13C{1H}NMR (100 MHz, CDCl3) δ 194.3, 161.3 , 106.0 , 76.6, 76.2, 36.2, 30.0, 21.3,
12.0, 3.7; HRMS (ESI+) calc’d for C10H14NO [M + H]+: 164.1070, found 164.1068.
Associated Content
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website
1H NMR and 13C NMR spectra of new compounds (PDF).
Author Information
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Corresponding Author
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*E-mail: wenboliu@whu.edu.cn
Notes
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The authors declare no competing financial interest.
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Acknowledgements
We gratefully acknowledge the NSFC (21772148, 21971198) and Wuhan University
for financial support.
Notes and References
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dicarbonyl compounds with amines: a new one-pot approach to functionalized pyrroles.
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