Approach to synthesis of Β-enamino ketones and pyrroles catalyzed by gallium(III) triflate under solvent-free conditions

Article abstract of DOI:10.1080/00397910902898528

Metal triflates have been used to catalyze synthesis of-enamino ketones or pyrroles from amines and 1,3-dicarbonyl or 1,4-dicarbonyl compounds under solvent-free conditions, respectively. Among different metal triflates screened, 0.5mol% Ga(OTf)3 efficiently promoted the reactions to give excellent yields. In addition, the catalyst could be recovered easily after the reactions and reused without evident loss in activity.

Full text of DOI:10.1080/00397910902898528

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Approach to Synthesis of β-
Enamino Ketones and Pyrroles
Catalyzed by Gallium(III)
Triflate Under Solvent-Free
Conditions
Jiuxi Chen a , Xiaoliang Yang a , Miaochang Liu a ,
Huayue Wu a , Jinchang Ding a & Weike Su a b
a College of Chemistry and Materials Engineering,
Wenzhou University, Wenzhou, China
b College of Pharmaceutical Sciences, Zhejiang
University of Technology, Zhejiang Key Laboratory of
Pharmaceutical Engineering, Hangzhou, China
Published online: 29 Oct 2009.
To cite this article: Jiuxi Chen , Xiaoliang Yang , Miaochang Liu , Huayue Wu ,
Jinchang Ding & Weike Su (2009) Approach to Synthesis of β-Enamino Ketones and
Pyrroles Catalyzed by Gallium(III) Triflate Under Solvent-Free Conditions, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 39:23, 4180-4198, DOI: 10.1080/00397910902898528
To link to this article: http://dx.doi.org/10.1080/00397910902898528
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Synthetic Communications1, 39: 4180–4198, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902898528
Approach to Synthesis of b-Enamino Ketones and
Pyrroles Catalyzed by Gallium(III) Triflate
Under Solvent-Free Conditions
Jiuxi Chen,1 Xiaoliang Yang,1 Miaochang Liu,1 Huayue Wu,1
Jinchang Ding,1 and Weike Su1,2
1College of Chemistry and Materials Engineering, Wenzhou University,
Wenzhou, China
2College of Pharmaceutical Sciences, Zhejiang University of Technology,
Zhejiang Key Laboratory of Pharmaceutical Engineering,
Hangzhou, China
Abstract: Metal triflates have been used to catalyze synthesis of b-enamino
ketones or pyrroles from amines and 1,3-dicarbonyl or 1,4-dicarbonyl compounds
under solvent-free conditions, respectively. Among different metal triflates
screened, 0.5mol% Ga(OTf)3 efficiently promoted the reactions to give excellent
yields. In addition, the catalyst could be recovered easily after the reactions and
reused without evident loss in activity.
Keywords: b-Enamino ketones, gallium(III) triflate, pyrroles, solvent-free
conditions
INTRODUCTION
A variety of reactions using Lewis acids have been developed in organic
synthesis.[1] The majority of the strong and efficient Lewis acids such as
AlCl3, BF3, TiCl4, and SnCl4 used in various organic transformations are
prone to fast hydrolysis and deactivate readily in the presence of even a
Received March 9, 2008.
Address correspondence to Huayue Wu, College of Chemistry and Materials
Engineering, Wenzhou University, Wenzhou 325027, China. E-mail: huayuewu@
wzu.edu.cn
4180

b-Enamino Ketones and Pyrroles
4181
small amount of water. Generally, stoichiometric or even excess amounts
of conventional Lewis acids are needed, and the catalyst cannot be recov-
ered and reused after the reactions are completed. In recent decades, as
consciousness of protecting the environment has strengthened, methods
that are cheap or environmentally friendly have been advocated. Metal
triflates have advantages of being water tolerant, air stable, recoverable
from water, operationally simple (not requiring anhydrous treatment),
strongly tolerant of oxygen, nitrogen, phosphorus, and sulfur-containing
reaction substrates and functional groups, and reusable, showing their
significant potential as safe and environmentally benign catalysts.[2]
Thus, metal triflates as new versatile Lewis acids have been widely used
in organic synthesis, such as formation of the CꢀC bond or CꢀX
=
(X N, O, P, etc.) bond, oxidation and reduction, rearrangement, protec-
tion and deprotection, polymerization, and miscellaneous reactions.[2]
They can be easily synthesized by reacting metallic oxides with trifluoro-
methanesulfonic acid.[3]
b-Enamino ketones are the most important intermediates, having
become increasingly important in medicinal chemistry and organic synth-
esis.[4] Consequently, an enormous number of procedures have been
developed for the construction of b-enamino ketones.[5] The direct con-
densation of 1,3-dicarbonyl compounds with amines is the most straight-
forward method for the synthesis of b-enamino ketones in the presence of
various promoting agents.[6] Recently, this condensation reaction has also
been performed in water[6l,6o] and ionic liquid medium.[6i,6m]
Pyrroles are important heterocyclic compounds, having become
increasingly important in medicinal chemistry and organic synthesis.[7]
From the extensive work on the synthesis of pyrroles,[8] the Paal–Knorr
reaction is one of the most common approaches in which c-diketones are
converted to pyrroles from 1,4-ketones and primary amines (or ammo-
nia) in the presence of various promoting agents[9] and microwave
irradiation.[10]
Although these methods are suitable for certain synthetic conditions,
some of these methods often involve the use of stoichiometric and even
excess amounts of acids because they can be trapped by nitrogen in this
condensation, hazardous organic solvents, tedious workup, and unsatis-
factory yield. Thus, they may not be preferred choices in view of green
chemistry. Therefore, the development of facile and environmentally
friendly methods for the synthesis of b-enamino ketones and pyrroles
that can overcome the shortcomings of the previous methods is
necessary.
On the other hand, the absence of solvent in organic synthesis and
the employment of a small excess of reagent make procedures simpler,
saves energy, and prevents solvent waste, hazards, and toxicity. To the

4182
J. Chen et al.
Scheme 1. The model reaction of acetylacetone with aniline under difference
conditions.
best of our knowledge, Ga(OTf)3-promoted[11] syntheses of b-enamino
ketones and pyrroles have not been reported.
Recently, we have successfully applied metal triflates in several
reactions.[12a–13i] In continuation of our interest in solvent-free organic
synthesis,[12a,13d,12l] green chemistry, and Lewis acid–catalyzed organic
reactions,[12] we herein developed green, simple, and practical methods
for the synthesis of b-enamino ketones from 1,3-dicarbonyl compounds
with amines and the synthesis of pyrroles from 1,4-dicarbonyl com-
pounds with amines using a catalytic amount of Ga(OTf)3 under
solvent-free conditions.
Table 1. Condensation of acetylacetone with aniline under different reaction
conditionsa
Entry
Solvent
Catalyst (mol%)
Time (min)
Yields (%)b
1
2
3
4
5
6
7
8
9
10
11c
12
13
14
15
16
17
None
None
None
None
None
None
None
None
None
None
None
None
None
H2O
Cu(OTf)2 (5)
Mg(OTf)2 (5)
Bi(OTf)3 (5)
Yb(OTf)3 (5)
Sc(OTf)3 (5)
Y(OTf)3 (5)
La(OTf)3 (5)
Sm(OTf)3 (5)
Eu(OTf)3 (5)
Ga(OTf)3 (5)
Ga(OTf)3 (1)
Ga(OTf)3 (0.5)
Ga(OTf)3 (0.1)
Ga(OTf)3 (0.5)
Ga(OTf)3 (0.5)
Ga(OTf)3 (0.5)
None
60
80
60
60
60
60
60
60
60
25
30
30
35
40
30
30
100
78
47
79
76
83
81
77
82
84
93
92
92, 90, 89
82
72
82
86
14 (22)d
CH2Cl2
CH3NO2
None
a30ꢁC for 25 min.
bIsolated yield.
cCatalyst was reused three times.
dReaction was run at 50ꢁC for 12 h.

b-Enamino Ketones and Pyrroles
4183
RESULTS AND DISCUSSION
Initially, we investigated the model reaction from acetylacetone with
aniline using various metal triflates as catalysts (Scheme 1), and the
results are summarized in Table 1. Most of the metal triflates bring
out this reaction efficiently under solvent-free conditions. However,
Ga(OTf)3 was particularly effective for this reaction in the shortest
time (Table 1, entries 10–13). It was observed that 3a was obtained
in only poor yield in the absence of Ga(OTf)3 even after a long reac-
tion time in higher temperature, which also further proved that
Ga(OTf)3 does play an important role in the condensation reaction
(Table 1, entry 17). Moreover, we also examined the activity of the
recycled catalyst; Ga(OTf)3 could be reused three times without any
loss of activity (Table 1, entry 12). In addition, we studied the influ-
ence of solvent and the amount of catalyst on the catalytic property
of the reaction: 0.5 mol% of Ga(OTf)3 was enough, and excessive
amount of catalyst did not increase the yield (Table 1, entries
10–13). Obviously, the additional solvent does not make the reaction
rate faster. Therefore, we achieved an optimized condition using
0.5 mol% of Ga(OTf)3 as the catalyst under solvent-free conditions.
Because of the good results obtained, we expanded our methodology
to synthesize other b-enamino ketones (Scheme 2, Table 2). In all cases,
the condensation reactions proceeded smoothly and gave the correspond-
ing products in good to excellent yield in the present protocol.
As shown in Table 2, aromatic amines bearing either
electron-donating or electron-withdrawing groups on the aromatic ring
were investigated. The substitution groups on the aromatic ring have
no obvious effect on the yield and reaction time under the optimal
conditions. However, amines with strongly electron-withdrawing
groups on the aromatic ring such as p-nitroaniline gave the product
of 3e with good yield in a long reaction time (Table 2, entry 5). When
an unsymmetrical b-dicarbonyl compound such as benzoylacetone was
used as a substrate, the regiochemistry was controlled by the more
reactive carbonyl group, which underwent the attack by the amine
(Table 2, entries 11–13).
Scheme 2. The reaction of amines with acetylacetone under solvent-free
conditions.

4184
J. Chen et al.
a
Table 2. Synthesis of b-enamino ketones by catalyzed Ga(OTf)3
Entry R1
R2
R3
Time (min) Product Yieldb(%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Me Me C6H5
30
30
30
35
35
30
30
45
50
45
30
40
30
35
35
3a
3b
3c
3d
3e
3f
92
94
91
90
Me Me p-(CH3)C6H4
Me Me p-(OCH3)C6H4
Me Me p-(Cl)C6H4
Me Me p-(NO2)C6H4
Me Me CH3CH2CH2CH2
Me Me C6H5CH2
65 (84)c
91
92
3g
3h
3i
Ph
Ph
Ph
Ph C6H5
Ph C6H5CH2
Ph o-(OCH3)C6H4
83
87
85
90
90
89
91
88
3 j
3k
3l
Me Ph C6H5
Me Ph C6H5CH2
Me Ph o-(OCH3)C6H4
Me Me R-(þ)-C6H5CH(CH3)
Me Me S-(ꢀ)-C6H5CH(CH3)
3m
3n
3o
aReaction conditions: amine (5 mmol), acetylacetone (5 mmol), and Ga(OTf)3
(0.5 mol%), 30ꢁC.
bIsolated total yield.
cReaction was run for 2 h.
Next, we investigated the reaction of diamines and acetylacetone
(Scheme 3). In this reaction, 2 equivalents of acetylacetone are required
in the presence of diamines. When diamines such as 1,3-propanediamine
and 1,4-butanediamine were examined, the products of 3p–3q with two
enaminone groups were obtained in excellent yields.
However, when 1,3-dicarbonyl compound was replaced with
1,4-dicarbonyl compound such as acetonylacetone, the Paal–knorr con-
densation product pyrrole was obtained under the same conditions
(Scheme 4). Therefore, we also investigated the synthesis of pyrroles in
the presence of Ga(OTf)3, and similar results are shown in Table 3.
Scheme 3. The reaction of diamines with acetylacetone under solvent-free
conditions.

b-Enamino Ketones and Pyrroles
4185
Scheme 4. The reaction of amines with acetonylacetone under solvent-free
conditions.
Table 3. Condensation of acetonylacetone with amines in the presence of
a
Ga(OTf)3
Entry
R
Time (min)
Product
Yield (%)b
1
2
3
4
5
6
7
8
C6H5
30
40
35
30
40
30
40
35
4a
4b
4c
4d
4e
4f
91
89
87
91
88
95
86
90
p-(CH3)C6H4
2,6-(iPr)2C6H3
p-(F)C6H4CH2
C6H5CH2CH2
p-(Cl)C6H4
p-(NO2)C6H4
p-(OCH3)C6H4CH2
4g
4h
aReaction conditions: amine (5 mmol), acetonylacetone (5 mmol), and
Ga(OTf)3 (0.5 mol%), 30ꢁC.
bIsolated total yield.
In addition, we also investigated the reaction from diamines with
acetonylacetone, and similar results were observed (Scheme 5).
A tentative mechanism for the formation of b-enamino ketones is
proposed in Scheme 6. Species 5 is very prone to react immediately with
amine by attack of the nitrogen nucleophile at the carbonyl carbon,
which is activated by Ga(OTf)3 to produce the product of 3. The catalyst
is regenerated for further reaction. The (Z)-selectivity in the product of 3
derived from 1,3-dicarbonyl compound was stabilized by intramolecular
Scheme 5. The reaction of diamines with acetonylacetone under solvent-free
conditions.

4186
J. Chen et al.
Scheme 6. A tentative mechanism for the formation of b-enamino ketones.
hydrogen bonding. A tentative mechanism for the formation of pyrroles
is proposed in Scheme 7.
To sum up, a new catalytic protocol for the regioselectivity synthesis of
b-enamino ketones from 1,3-dicarbonyl compounds and amines and the
facile synthesis of pyrroles from 1,4-dicarbonyl compounds and amines
have been developed. Compared with previously reported methodologies,
the present method has the following noteworthy features: simple workup,
the shorter reaction times, environmental friendliness, recovery and reuse
of metal triflates, and mild reaction conditions with excellent yield. A wide
range of b-enamino ketones and pyrroles were synthesized successfully by
employing this present reaction system. Currently, studies on the extension
of this protocol are ongoing in our laboratory.
EXPERIMENTAL
All the melting points were uncorrected and determined on digital
melting-point apparatus WRS-1B. Infrared (IR) spectra were recorded
on an Avatar 370 FI-IR spectrophotometer. Mass spectra were measured
with a Thermo Finnigan LCQ-Advantage. 1H NMR and 13C NMR
spectra were recorded on a Varian Mercury Plus-400 or Bruer-300
Scheme 7. A tentative mechanism for the formation of pyrroles.

b-Enamino Ketones and Pyrroles
4187
instrument using CDCl3 as the solvent with tetramethylsilane (TMS) as
an internal standard at room temperature. Chemical shifts are given in
d relative to TMS; coupling constants (J) values are given in hertz. All
reagents used are commercially available. Silica gel 60 GF254 was used
for analytical and preparative thin-layer chromatography (TLC).
General Procedure for the Synthesis of b-Enamino Ketones
Ga(OTf)3 (0.025mmol, 0.5 mol%) was added to a mixture of 1,3-dicarbo-
nyl compound (5 mmol) and amines (5mmol) or diamines (10 mmol). The
mixture was stirred at 30ꢁC for the appropriate time. After completion of
the reaction as indicated by TLC, the reaction mixture was diluted with
water, and the product was extracted with ethyl acetate (3ꢂ 10mL). The
combined organic layer was dried (MgSO4) and evaporated; the crude pro-
duct was purified by flash-column chromatography to provide the desired
product. The catalyst in the aqueous phase was concentrated in vacuo to
give a crystalline residue, which was finally heated at 180ꢁC for 48h in
vacuo. The recovered Ga(OTf)3 could be reused in another reaction.
Characterization Data of All the Products
(Z)-4-(Phenylamino)pent-3-en-2-one (3a)
Yield: 92%; mp 47–48ꢁC (lit.[6o] 47ꢁC). IR (KBr), (n=cmꢀ1): 3439 (NH),
1
1625 (CO). H NMR (300 MHz, CDCl3) ppm d: 1.99 (s, 3H), 2.10 (s,
3H), 5.19 (s, 1H), 7.11 (d, J ¼ 8.4 Hz, 2H), 7.17–7.21 (m, 1H), 7.34 (t,
J ¼ 7.6 Hz, 2H), 12.48 (br s, 1H, NH). 13C NMR (75 MHz, CDCl3)
ppm d: 19.8, 29.1, 97.6, 124.7, 125.5, 129.1, 138.8, 160.2, 196.1.
(Z)-4-(p-Toluidino)pent-3-en-2-one (3b)
Yield: 94%; mp 67–68ꢁC (lit.[6n] 65–67ꢁC). IR (KBr), (nmax=cmꢀ1): 3414
1
(NH), 1631 (CO). H NMR (300 MHz, CDCl3) ppm d: 1.97 (s, 3H),
2.09 (s, 3H), 2.33 (s, 3H), 5.16 (s, 1H), 7.00 (d, J ¼ 8.4 Hz, 2H), 7.14 (d,
J ¼ 8.4 Hz, 2H), 12.37 (br s, 1H, NH).
(Z)-4-(4-Methoxyphenylamino)pent-3-en-2-one (3c)
Yield: 91%; mp 42ꢁC (lit.[6r] 40.5–42.1ꢁC). IR (KBr), nmax=cmꢀ1: 3430
1
(NH), 1621 (CO). H NMR (300 MHz, CDCl3) ppm d: 1.90 (s, 3H),

4188
J. Chen et al.
2.09 (s, 3H), 3.80 (s, 3H), 5.16 (s, 1H), 6.86 (d, J ¼ 7.6 Hz, 2H), 7.04 (d,
J ¼ 7.6 Hz, 2H), 12.30 (br s, 1H, NH). 13C NMR (75 MHz, CDCl3)
ppm d: 119.5, 28.9, 55.3, 96.7, 114.1, 126.5, 131.3, 157.6, 161.1, 195.6.
(Z)-4-(4-Chlorophenylamino)pent-3-en-2-one (3d)
Yield: 90%; mp 60–61ꢁC (lit.[6n] 60–62ꢁC). IR (KBr), (nmax=cmꢀ1): 3456
1
(NH), 1619 (CO). H NMR (300 MHz, CDCl3) ppm d: 1.97 (s, 3H),
2.11 (s, 3H), 5.20 (s, 1H), 7.03 (d, J ¼ 8.4 Hz, 2H), 7.30 (d, J ¼ 8.4 Hz,
2H), 12.41 (br s, 1H, NH).
(Z)-4-(4-Nitrophenylamino)pent-3-en-2-one (3e)
Yield: 84%; mp 142–143ꢁC (lit.[13] 143.6–144.1ꢁC). IR (KBr), (nmax=cmꢀ1):
1
3405 (NH) 1634 (CO). H NMR (300MHz, CDCl3) ppm d: 2.06 (s, 3H),
2.19 (s, 3H), 5.34 (s, 1H), 7.18 (d, J ¼ 8.8 Hz, 2H), 8.21 (d, J ¼ 8.8 Hz, 2H),
12.72 (br s, 1H, NH).
(Z)-4-(Butylamino)pent-3-en-2-one (3f)
Yield: 91%; oil (lit.[6r]). IR (neat), (nmax=cmꢀ1): 3378 (NH), 1617 (CO).
1H NMR (300 MHz, CDCl3) ppm d: 0.96 (t, J ¼ 7.2 Hz, 3H), 1.36–1.46
(m, 2H), 1.54–1.61 (m, 2H), 1.92 (s, 3H), 2.07 (s, 3H), 3.18–3.26 (m,
2H), 4.94 (s, 1H), 11.03 (br s, 1H, NH).
(Z)-4-(Benzylamino)pent-3-en-2-one (3g)
Yield: 92%; oil (lit.[6r]). IR (KBr), (nmax=cmꢀ1): 3431 (NH), 1622 (CO).
1H NMR (300 MHz, CDCl3) ppm d: 1.90 (s, 3H), 2.04 (s, 3H), 4.45 (d,
J ¼ 6.4 Hz, 2H), 5.02 (s, 1H), 7.29–7.33 (m, 5H), 11.13 (br s, 1H, NH).
(Z)-1,3-Diphenyl-3-(phenylamino)prop-2-en-1-one (3h)
Yield: 83%; mp 96–97ꢁC (lit.[14] 103ꢁC). IR (KBr), (nmax=cmꢀ1): 3353
1
(NH), 1617 (CO). H NMR (300 MHz, CDCl3) ppm d: 6.11 (s, 1H),
6.76 (d, J ¼ 7.6 Hz, 2H), 6.96–7.01 (m, 1H), 7.08–7.12 (m, 2H),
7.24–7.49 (m, 8H), 7.96 (d, J ¼ 6.9 Hz, 2H), 12.87 (br s, 1H, NH). 13C
NMR (75 MHz, CDCl3) ppm d: 97.0, 123.1, 124.2, 127.2, 127.9, 128.5,
128.6, 128.9, 131.4, 135.8, 139.4, 140.1, 161.3, 189.5.

b-Enamino Ketones and Pyrroles
4189
(Z)-3-(Benzylamino)-1,3-diphenylprop-2-en-1-one (3i)
Yield: 87%; mp 100–101ꢁC (lit.[14] 100ꢁC). IR (KBr), (nmax=cmꢀ1): 3351
(NH), 1624 (CO). 1H NMR (300 MHz, CDCl3) ppm d: 4.41 (d,
J ¼ 6.8 Hz, 2H), 5.83 (s, 1H), 7.21–7.26 (m, 3H), 7.27–7.45 (m, 10H),
7.90 (t, J ¼ 7.6, 2H), 11.68 (br s, 1H, NH). 13C NMR (75 MHz, CDCl3)
ppm d: 48.3, 93.9, 127.0, 127.2, 127.5, 127.9, 128.4, 128.7, 129.1, 129.6,
130.8, 135.4, 138.4, 140.2, 166.8, 188.6.
(Z)-3-(4-Methoxyphenylamino)-1,3-diphenylprop-2-en-1-one (3j)
Yield: 85%; mp 102ꢁC (lit.[6r] 100–101ꢁC). IR (KBr), (nmax=cmꢀ1): 3452
1
(NH), 1626 (CO). H NMR (300 MHz, CDCl3) ppm d: 3.90 (s, 3H),
6.07 (s, 1H), 6.37 (t, J ¼ 8.4 Hz, 1H), 6.53–6.56 (m, 1H), 6.86 (t,
J ¼ 8.4 Hz, 1H), 6.91–6.94 (m, 1H), 7.30–7.51 (m, 8H), 7.99 (dd,
J ¼ 7.8, 1.5 Hz, 2H), 12.72 (br s, 1H, NH).
(Z)-1-Phenyl-3-(phenylamino)but-2-en-1-one (3k)
Yield: 90%; mp 111–112ꢁC (lit.[15] 110.5–111.5ꢁC). IR (KBr), (nmax=cmꢀ1):
3418 (NH), 1620 (CO). 1H NMR (300MHz, CDCl3) ppm d: 2.14 (s, 3H),
5.91 (s, 1H), 7.16–7.23 (m, 3H), 7.35–7.47 (m, 5H), 7.91–7.94 (m, 2H),
12.98 (br s, 1H, NH).
(Z)-3-(Benzylamino)-1-phenylbut-2-en-1-one (3l)
Yield: 90%; mp 61–62ꢁC (lit.[6m]). IR (KBr), (nmax=cmꢀ1): 3428 (NH),
1
1618 (CO). H NMR (300 MHz, CDCl3) ppm d: 1.97 (s, 3H), 4.45 (d,
J ¼ 6.4 Hz, 2H), 5.71 (s, 1H), 7.28–7.41 (m, 3H), 7.81–7.94 (m, 2H),
11.70 (br, 1H). 13C NMR (75 MHz, CDCl3) ppm d: 19.2, 46.8, 92.4,
126.6, 127.3, 128.1, 128.7, 130.4, 137.6, 140.2, 164.6, 187.7.
(Z)-3-(4-Methoxyphenylamino)-1-phenylbut-2-en-1-one (3m)
Yield: 89%; mp 92ꢁC (lit.[15] 92–93ꢁC). IR (KBr), (nmax=cmꢀ1): 3356
1
(NH), 1607 (CO). H NMR (300 MHz, CDCl3) ppm d: 2.12 (s, 3H),
3.89 (s, 3H), 5.92 (s, 1H), 6.90–6.96 (m, 2H), 7.17–7.23 (m, 2H),
7.40–7.45 (m, 3H), 7.91–7.94 (m, 2H), 12.86 (br s, 1H, NH). 13C NMR
(75 MHz, CDCl3) ppm d: 20.3, 55.6, 94.3, 111.5, 120.6, 125.2, 126.8,
127.0, 128.0, 130.7, 140.2, 153.0, 162.5, 188.6.

4190
J. Chen et al.
(R, Z)-4-(1-Phenylethylamino)pent-3-en-2-one (3n)
Yield: 91%; oil (lit.[6r]); ½aꢃ2D0:8, ꢀ847.55 (c 0.70, EtOH). IR (neat),
1
(nmax=cmꢀ1): 3443 (NH), 1613 (CO). H NMR (300 MHz, CDCl3) ppm
d: 1.52 (d, J ¼ 6.9 Hz, 3H), 1.77 (s, 3H), 2.03 (s, 3H), 4.60–4.68 (m,
1H), 4.98 (s, 1H), 7.23–7.35 (m, 5H), 11.22 (br s, 1H, NH). 13C NMR
(75 MHz, CDCl3) ppm d: 18.7, 24.3, 28.5, 52.5, 95.6, 125.2, 127.1,
128.6, 143.9, 162.1, 194.5.
(S, Z)-4-(1-Phenylethylamino)pent-3-en-2-one (3o)
Yield: 88%; oil (lit.[6r]); ½aꢃ2D0:4: þ848.02 (c 0.70, EtOH). 1H NMR
(300 MHz, CDCl3) ppm d: 1.52 (d, J ¼ 6.9 Hz, 3H), 1.77 (s, 3H), 2.03
(s, 3H), 4.60–4.68 (m, 1H), 4.98 (s, 1H), 7.23–7.35 (m, 5H), 11.22 (br s,
1H, NH). 13C NMR (75 MHz, CDCl3) ppm d: 18.7, 24.3, 28.5, 52.5,
95.6, 125.2, 127.1, 128.6, 143.9, 162.1, 194.5; IR (neat), (nmax=cmꢀ1):
3443 (NH), 1613 (CO).
(3Z, 30Z)-4,40-(Propane-1,3-diylbis(azanediyl))dipent-3-en-2-one (3p)
Yield: 92%; mp 50–51ꢁC (lit.[16], 51ꢁC). IR (KBr), (nmax=cmꢀ1): 3442
1
(NH), 1606 (CO). H NMR (300 MHz, CDCl3): d ¼ 1.86 (t, J ¼ 6.4 Hz,
2H), 1.92 (s, 6H), 1.99 (s, 6H), 3.32–3.38 (m, 4H), 4.98 (s, 2H), 10.87
(br s, 2H, NH). 13C NMR (75 MHz, CDCl3) ppm d: 18.8, 28.8, 30.2,
39.6, 95.6, 163.2, 195.2.
(3Z, 30Z)-4,40-(Propane-1,3-diylbis(azanediyl))dipent-3-en-2-one (3q)
Yield: 94%; mp 61–62ꢁC (lit.[17] not reported). IR (KBr), (nmax=cmꢀ1):
1
3272 (NH), 1622 (CO). H NMR (300 MHz, CDCl3) ppm d: 1.57–1.61
(m, 4H), 1.85 (s, 6H), 1.97 (s, 6H), 3.18–3.23 (m, 4H), 4.96 (s, 2H),
10.75 (br, 2H). 13C NMR (75 MHz, CDCl3) ppm d: 18.9, 28.6 29.8,
40.3, 95.6, 163.2, 195.1.
General Procedure for the Synthesis of Pyrroles
Ga(OTf)3 (0.025 mmol, 0.5 mol%) was added to a mixture of 1,3-dicarbo-
nyl compound (5 mmol) and amines (5 mmol) or diamines (10 mmol). The
mixture was stirred at 30ꢁC for the appropriate time. After completion of
the reaction as indicated by TLC, water was added, and the product was

b-Enamino Ketones and Pyrroles
4191
extracted with diethyl ether (3 ꢂ 10 mL). The organic layer was dried
(MgSO4) and evaporated; the crude product was purified by flash column
chormatography to provide the corresponding product. The catalyst in
the aqueous phase was concentrated in vacuo to give a crystalline residue,
which was finally heated at 180ꢁC for 48 h in vacuo. The recovered
Ga(OTf)3 could be reused in another reaction.
Data
2,5-Dimethyl-1-phenyl-1H-pyrrole (4a)
Yield: 91%; mp 50–51ꢁC (lit.[9k]). IR (KBr), (nmax=cmꢀ1): 3060, 2922,
1
1599, 1520, 1498, 1403, 1321. H NMR (400 MHz, CDCl3) ppm d: 2.04
(s, 6H), 5.92 (s, 2H), 7.22–7.27 (m, 2H),7.41–7.49 (m, 3H). 13C NMR
(100 MHz, CDCl3) ppm d: 139.9, 129.0, 128.8, 127.6, 105.6, 13.0.
2,5-Dimethyl-1-p-tolyl-1H-pyrrole (4b)
Yield: 89%; mp 45–46ꢁC (lit.[9k]). IR (KBr), (nmax=cmꢀ1): 3033, 2923,
1
1549, 1515, 1409, 1384. H NMR (400 MHz, CDCl3) ppm d: 2.02 (s,
6H), 2.41 (s, 3H), 5.89 (s, 2H), 7.09 (d, J ¼ 7.6 Hz, 2H), 7.24 (d,
J ¼ 7.6 Hz, 2H). 13C NMR (100 MHz, CDCl3) ppm d: 137.4, 136.3,
128.8, 127.9, 105.4, 21.1, 13.0.
1-(2,6-Diisopropylphenyl)-2,5-dimethyl-1H-pyrrole (4c)
Yield: 87%; mp 55–56ꢁC. IR (KBr): 3070, 2965, 2927, 1580, 1473, 1459,
1398, 1382 cmꢀ1. 1H NMR (400 MHz, CDCl3) ppm d: 1.11 (d, J ¼ 6.8 Hz,
12H, CHCH3), 1.91 (s, 6H, CH3), 2.39–2.32 (m, 2H, CHCH3), 5.94 (s,
2H, pyrrole), 7.25 (d, J ¼ 8.0 Hz, 2H, ArH), 7.41 (t, J ¼ 7.2 Hz, 1H,
ArH). 13C NMR (100 MHz, CDCl3) ppm d: 12.7, 24.1, 27.8, 105.1,
123.8, 128.6, 128.9, 133.8, 147.5. MS (EI): m=z (%) ¼ 256 (22) [M þ 1]þ,
255 (100), [Mþ], 240 (50). Anal. calcd. for C18H25N: C, 84.65; H, 9.87.
Found: C, 84.73; H, 9.69.
1-(4-Fluorobenzyl)-2,5-dimethyl-1H-pyrrole (4d)
Yield: 91%; mp 56–57ꢁC. IR (KBr): 3067, 2932, 1509, 1444, 1409, 1347,
1224, 1157 cmꢀ1. 1H NMR (400 MHz, CDCl3) ppm d: 2.13 (s, 6H, CH3),
4.97 (s, 2H, CH2), 5.85 (s, 2H, pyrrole), 6.98 (t, J ¼ 8.8 Hz, 2H, ArH),

4192
J. Chen et al.
6.98 (m, 2H, ArH). 13C NMR (100 MHz, CDCl3) ppm d: 12.4, 46.0,
2
3
105.5, 115.6 (d, JCCF ¼ 21.2 Hz), 127.2 (d, JCCCF ¼ 7.5 Hz), 127.8,
134.1, 161.9 (d, JCF ¼ 243.4 Hz). MS (EI): m=z (%) ¼ 203 (55) [Mþ],
1
109 (100), 83 (40). Anal. calcd. for C13H14FN: C, 76.82; H, 6.94. Found:
C, 76.90; H, 7.03.
2,5-Dimethyl-1-phenethyl-1H-pyrrole (4e)
Yield: 88%; oil (lit.[18]). IR (neat): 3063, 2928, 1604, 1518, 1496, 1454,
1
1407, 1359, 1299 cmꢀ1. H NMR (400 MHz, CDCl3) ppm d: 2.15 (s,
6H, CH3), 2.88 (t, J ¼ 7.8 Hz, 2H, CH2CH2Ph), 3.94 (t, J ¼ 7.8 Hz, 2H,
CH2CH2Ph), 5.77 (s, 2H, pyrrole), 7.10 (d, J ¼ 7.2 Hz, 2H, ArH),
7.26–7.22 (m, 1H, ArH), 7.30 (t, J ¼ 7.2 Hz, 2H, ArH). 13C NMR
(100 MHz, CDCl3) ppm d: 12.3, 37.5, 45.2, 105.2, 127.3, 128.6, 128.8,
138.5. MS (ESI): m=z (%) ¼ 200.2 (100) [M þ 1]þ.
1-(4-Chlorophenyl)-2,5-dimethyl-1H-pyrrole (4f)
Yield: 95%; mp 62–63ꢁC (lit.[19]). IR (KBr), (nmax=cmꢀ1): 3045, 2923,
1596, 1493, 1406. 1H NMR (400 MHz, CDCl3) ppm d: 2.02 (s, 6H)
5.90 (s, 2H), 7.15 (d, J ¼ 8.4 Hz, 2H), 7.43 (d, J ¼ 8.4 Hz, 2H). 13C
NMR (100 MHz, CDCl3) ppm d: 13.0, 106.0, 128.7, 129.3, 129.5, 133.5,
137.5.
2,5-Dimethyl-1-(4-nitrophenyl)-1H-pyrrole (4g)
Yield: 86%; mp 143–144ꢁC (lit.[9c]). IR (KBr), (nmax=cmꢀ1): 3106, 3075,
2920, 1604, 1595, 1518, 1492, 1398, 1337, 1311. H NMR (400 MHz,
1
CDCl3) ppm d: 2.08 (s, 6H), 5.96 (s, 2H), 7.39 (d, J ¼ 8.8 Hz, 2H), 8.35
(d, J ¼ 8.8 Hz, 2H). 13C NMR (100 MHz, CDCl3) ppm d: 146.8, 144.7,
128.8, 128.6, 124.6, 107.4, 13.1.
1-(4-Methoxybenzyl)-2,5-dimethyl-1H-pyrrole (4h)
Yield: 90%; mp 76–77ꢁC. IR (KBr), (nmax=cmꢀ1): 3028, 2958, 2931, 1584,
1513, 1443, 1409, 1353, 1304, 1291, 1250, 1170. H NMR (400 MHz,
1
CDCl3) ppm d: 2.14 (s, 6H), 3.77 (s, 3H), 4.94 (s, 2H), 5.84 (s, 2H),
6.82 (s, 4H). 13C NMR (100 MHz, CDCl3) ppm d: 158.5, 130.5, 127.9,
126.7, 114.0, 105.3, 55.2, 46.1, 12.4. MS (EI): m=z (%) ¼ 215 (10) [Mþ],

b-Enamino Ketones and Pyrroles
4193
121 (100). Anal. calcd. for C14H17NO: C, 78.10; H, 7.96. Found: C, 77.86;
H, 8.02.
1,2-Bis(2,5-dimethyl-1H-pyrrol-1-yl)ethane (4i)
Yield: 92%; mp 136–137ꢁC (lit.[20]). IR (KBr): 3101, 2970, 1607, 1575,
1
1520, 1474, 1405, 1301, 1224 cmꢀ1. H NMR (400 MHz, CDCl3) ppm
d: 2.01 (s, 6H, CH3), 3.93 (s, 4H, CH2CH2), 5.75 (s, 4H, pyrrole). 13C
NMR (100 MHz, CDCl3) ppm d: 127.9, 106.0, 44.1, 12.2. MS (EI): m=z
(%) ¼ 216 (100) [Mþ], 201 (21), 122 (33), 108 (95), 106 (47), 94 (10), 79
(24), 67 (27).
1,6-Bis(2,5-dimethyl-1H-pyrrol-1-yl)hexane (4j)
Yield: 94%; mp 103–105ꢁC (lit.[18]). IR (KBr): 3103, 3093, 2969, 2924,
1
1518, 1475, 1410, 1373, 1301 cmꢀ1. H NMR (400 MHz, CDCl3) ppm
d: 1.38–1.34 (m, 4H), 1.65–1.58 (m, 4H), 2.20 (s, 12H, CH3), 3.70 (t,
J ¼ 7.6 Hz, 4H), 5.76 (s, 4H, pyrrole). 13C NMR (100 MHz, CDCl3)
ppm d: 127.2, 105.0, 43.5, 30.9, 26.7, 12.5. MS (EI): m=z (%) ¼ 272
(100) [Mþ], 257 (8), 164 (38), 108 (30), 94 (18).
ACKNOWLEDGMENTS
We are grateful to the National Natural Science Foundation of China
(No. 20676123 and 20476098) and Natural Science Foundation of
Zhejiang Province (No. Y405015) for financial support.
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