L-Proline-catalyzed five-component domino reaction leading to multifunctionalized 1,2,3,4-tetrahydropyridines

Article abstract of DOI:10.1016/j.tet.2010.10.041

Multifunctionalized 1,2,3,4-tetrahydropyridines are concisely synthesized in good yields via l-proline-catalyzed or l-proline/FeCl₃-cocatalyzed one-pot multicomponent reactions (MCRs). The MCRs involve a domino hydroamination/prins reaction/Man

Full text of DOI:10.1016/j.tet.2010.10.041

Tetrahedron 66 (2010) 9721e9728
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L
-Proline-catalyzed five-component domino reaction leading to
multifunctionalized 1,2,3,4-tetrahydropyridines
*
Huan-Feng Jiang , Jing-Hao Li, Zheng-Wang Chen
School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 17 July 2010
Received in revised form 28 September 2010
Accepted 15 October 2010
Available online 11 November 2010
Multifunctionalized 1,2,3,4-tetrahydropyridines are concisely synthesized in good yields via L-proline-
catalyzed or L-proline/FeCl3-cocatalyzed one-pot multicomponent reactions (MCRs). The MCRs involve
a domino hydroamination/prins reaction/Mannich-type reaction/intramolecular dehydrationecycliza-
tion process. The molecular structure of 5baa, one of multifunctionalized 1,2,3,4-tetrahydropyridines,
was confirmed by single-crystal X-ray diffraction.
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
two-component prins reaction;11 (3) three-component Mannich-
type reaction; (4) intramolecular dehydration-cyclization.
Multicomponent reactions (MCRs) have emerged as a powerful
tool in synthetic organic chemistry. Compared with conventional
methods, MCRs exhibit high levels of efficiency and diversity, as
they offer rapid and convergent construction of complex molecular
skeletons from common starting materials in one-pot, and these
reactions are environmentally friendly and proceed with excellent
chemoselectivities.1,2 Therefore, designing novel MCRs for con-
structing valuable compounds remains the interest of synthetic
chemists.
Tetrahydropyridines are one of the fundamental heterocycles,
which have been the subject of intense research for their
outstanding biological properties and wide range of applications
to pharmaceutical compounds and synthetic intermediates.3
Although there are some reports for the synthesis of tetrahy-
dropyridines, these methods are notalways satisfactory with respect
to ease of operation, yield, applicability and the regioselectivity of
the products.4 Besides, very few efficient methods of formation
1,2,3,4-tetrahydropyridines are described in the literatures.4d,5
Over the past few years, we have developed a series of hetero-
cyclic compounds, such as tetrahydropyrimidines,6 3,6-dihydro-
2H-1,3-oxazines,7 1,3-oxazine-6-ones,8 1,4-dihydropyridines,9
1,2,3,4-tetrahydropyridines5g through the MCR methods. During
our ongoing research on the synthesis of other nitrogen-containing
heterocycles, we found a novel multicomponent coupling strategy
to synthesize multisubstituted 1,2,3,4-tetrahydropyridine de-
rivatives. Our approach could briefly comprise four sequential
processes (Scheme 1): (1) two-component hydroamination;10 (2)
Scheme 1. Thedomino processesleadingto multisubstituted1,2,3,4-tetrahydropyridine.
2. Results and discussion
On the basis of our previous work on the L-proline-catalyzed
synthesis of highly functionalized multisubstituted 1,4-dihy-
dropyridines,9,12 we initially examined the reaction in ethanol
solvent at room temperature, the reaction did not give target
product (Table 1, entry 1). To our delight, the reaction gave satis-
fying results in DMF at 100 ꢀC (Table 1, entry 2). Without any cat-
alysts, the reaction was carried out inefficiently, and the desired
product was obtained in a poor yield of 33% (Table 1, entry 3). Next,
* Corresponding author. E-mail address: jianghf@scut.edu.cn (H.-F. Jiang).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.10.041

9722
H.-F. Jiang et al. / Tetrahedron 66 (2010) 9721e9728
Table 1
the solvents were evaluated. Except ethanol, other solvents such as
toluene, CH3CN, THF, and DMSO proved to be appropriate (Table 1,
Optimization of reaction conditionsa
entries 4e8). The reaction also showed a significant dependence on
bases, and L-proline proved to be superior to other bases (Table 1,
entries 2 and 9e14). The lower temperature and the shortened
reaction time can reduce the product yield (Table 1, entries 15
and 16).
On the basis of these results, the optimal conditions involved the
following parameters: L-proline as catalyst, and DMF as solvent,
with reaction temperature at 100 ꢀC for 12 h. Under these opti-
mized conditions, a study on the substrate scope was carried out,
and the results are summarized in Table 2.
Entry
1c
2
3
4
5
6
7
8
Additive
Solvent
Yieldb (%)
L
-Proline
-Proline
EtOH
DMF
DMF
EtOH
Toluene
CH3CN
THF
DMSO
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
n.p.
87 (83)
33
Trace
65
64
56
77
75
77
46
35
36
39
68
75
L
None
In order to determine the structures of this series of compound
definitively, a single crystal of 5baa was obtained by slow crystal-
lization from ethyl acetate and its structure was established by
single-crystal X-ray analysis (Fig. 1).
L-Proline
L-Proline
L-Proline
L-Proline
L-Proline
Under the above optimized conditions, the scope of this new
MCR process was next examined using various readily available
starting materials (Table 2). It was pleasing to find that all the
reactions afforded the corresponding products in good yields. The
alkynones with different substituted groups on the benzene ring
had no obvious impact to the reaction. The heterocyclic alkynone
(Table 2, entry 9) and the cyclohexyl alkynone (Table 2, entry 10)
afforded the corresponding products in high yields. Unfortunately,
only the simple primary amines, such as methylamine and eth-
ylamine, were suitable for the reaction. Moreover, a series of active
methylene compounds were compatible for the reaction.13 When
9
Pyridine
DABCO
Et3N
NaOH
Na2CO3
CH3COONa
10
11
12
13
14
15d
16e
L
-Proline
-Proline
L
a
Reaction conditions: 1a (1 mmol), 2a (1 mmol), 3a (1.5 mmol), 4 (2 mmol), and
additive (0.1 mmol, 10 mol %) in solvent (3.0 mL) at 100 ꢀC for 12 h.
b
Determined by GC. Number in parenthesis is isolated yield.
Room temperature.
60 ꢀC.
c
d
the reaction substrates were switched from b-diketones to malo-
nonitrile, the reactions could be carried out smoothly to give the
e
6 h.
corresponding products with higher yields (Table 2, entries 1e11).
Table 2
L
-Proline-catalyzed synthesis of polysubstituted 1,2,3,4-tetrahydropyridines via the MCRsa
R1
R4
R5
O
O
L
-Proline
R4
R5
+
R2
R3NH2
+
+
2HCHO
R1
DMF, 100 oC, 12 h
R2
N
R3
5
1a-1f
2a-2b
3a-3e
4
Entry
Alkynone
Amine
Active methylene compound
Product
Yieldb (%)
O
O
O
O
NH2
O
1
83
O
2a
3a
N
1a
5aaa
O
O
O
2
2a
3a
84
O
N
1b
5baa
O
O
3
2a
3a
81
O
O
N
1c
5caa

H.-F. Jiang et al. / Tetrahedron 66 (2010) 9721e9728
9723
Table 2 (continued)
Entry
Alkynone
Amine
Active methylene compound
Product
Yieldb (%)
O
NH2
4
1c
3a
77
O
O
2b
N
5cba
CN
CN
NC
CN
O
5
6
7
1a
1c
1c
2a
86
82
82
N
3b
5aab
CN
CN
2a
3b
O
N
5cab
CN
CN
2b
3b
3b
3b
3b
3b
O
N
5cbb
O
CN
CN
8
2a
2a
2a
2a
O
89
78
83
N
1d
5dab
F
O
CN
CN
9
O
N
F
1e
5eab
O
O
O
CN
CN
10
O
N
1f
5fab
O
CN
CN
O
11
84
N
1g
(continued on next page)
5gab

9724
Table 2 (continued)
H.-F. Jiang et al. / Tetrahedron 66 (2010) 9721e9728
Entry
Alkynone
Amine
Active methylene compound
Product
Yieldb (%)
CO2Et
CO2Et
EtOOC
COOEt
O
12
1a
2a
68
3c
N
5aac
O
CO2Et
CO2Et
O
13
14
15
1f
1a
1c
2a
3c
64
78
83
N
5fac
O
O
OEt
O
CO2Et
2a
O
N
3d
5aad
O
OEt
2a
3d
O
O
N
5cad
O
O
Ph
OEt
O
CO2Et
16
1a
2a
74
Ph
O
N
3e
5aae
a
Reaction conditions: 1 (1 mmol), 2 (1 mmol), 3 (1.5 mmol), 4 (2 mmol), and L
-proline (10 mol %) in DMF (3.0 mL) at 100 ꢀC for 12 h.
Isolated yield.
b
For further exploration the scope of the MCRs,
L-proline/FeCl3-
cocatalyzed system was developed. Table 2 has showed an elegant
method for the synthesis of multifunctionalized 1,2,3,4-tetrahy-
dropyridines, but the substrates were limited to the aromatic
alkynones and aliphatic amines. Herein we got a series of 1,2,3,4-
tetrahydropyridines from ethyl acetoacetate, amines, malononitrile,
and formaldehyde via
domino reactions (Scheme 2).2b,14 The reaction did not proceed
without FeCl3, and gave a reduced yield without -proline. Aromatic
L-proline/FeCl3-cocatalyzed five-component
L
amines with electron-donating attached to the benzene rings
gave higher yields than the electron-withdrawing groups (Scheme
2, 5heb, 5hfb, and 5hgb).
3. Conclusions
In conclusion, we have developed a new strategy that provides
an efficient synthesis of multisubstituted 1,2,3,4-tetrahydropyr-
idines and is therefore complementary to the construction of small
heterocyclic molecules in our laboratory. Our method involves mild
reaction conditions, uses very simple and accessible starting ma-
terials and solvents, as well as an inexpensive and non-toxic cata-
lyst. It also has the additional advantage of proceeding with high
Fig. 1. X-ray structure of 5baa.
When b-diketones were replaced with diethyl malonate, the re-
action gave the products with lower yields (Table 2, entries
12e13). This meant that steric effect had much influence on the
reaction.

H.-F. Jiang et al. / Tetrahedron 66 (2010) 9721e9728
9725
ether layer was then washed with saturated salt water and dried
over anhydrous MgSO4. Solvent was removed in vacuo, and the
crude product was purified by preparative TLC (GF254) with pe-
troleum ether/ethyl acetate (10:1 to 4:1) as eluent to afford the
desired products 5aaae5aae.
O
CN
CN
L
-Proline / FeCl3
O
O
NC
CN
R3NH2
O
2HCHO
DMF
O
100 oC, 4 h
N
R3
2b
5
4
2c-2g
3b
1h
4.2.1. 1,10-(5-Benzoyl-1-methyl-6-phenyl-1,2,3,4-tetrahydropyridine-
3,3-diyl)diethanone (5aaa). Yellow viscous oil. IR (KBr): 2926, 1741,
1688, 1545, 1366, 1244, 1049, 761 cmꢂ1. 1H NMR (400 MHz, CDCl3):
O
O
O
O
CN
CN
CN
CN
CN
CN
d
¼7.10e7.08 (m, 2H), 7.02e6.89 (m, 8H), 3.72 (s, 2H), 3.26 (s, 2H),
O
O
2.68 (s, 3H), 2.27 (s, 6H). 13C NMR (100 MHz, CDCl3):
d
¼204.3, 196.5,
N
N
N
158.3, 142.2, 134.8, 130.1, 129.1, 128.5, 128.2, 127.8, 127.1, 105.9, 65.5,
53.8, 41.0, 29.9, 26.7. MS (EI) m/z: 361, 319, 118, 105, 77, 43, 28. Anal.
Calcd for C23H23NO3: C, 76.43; H, 6.41; N, 3.88. Found: C, 76.61; H,
6.33; N, 3.84.
5hcb, 76%
5hbb, 70%
5hdb, 85%
(67%)c
(0) d
4.2.2. 1,10-(5-Benzoyl-1-methyl-6-p-tolyl-1,2,3,4-tetrahydropyridine-
3,3-diyl)diethanone (5baa). Yellow crystal, mp: 177e178 ꢀC. IR
(KBr): 2921, 1743, 1693, 1547, 1367, 1243, 1048, 755 cmꢂ1. 1H NMR
O
O
O
CN
CN
CN
CN
CN
CN
O
O
O
(400 MHz, CDCl3):
3.23 (s, 2H), 2.69 (s, 3H), 2.25 (s, 6H), 2.10 (s, 3H). 13C NMR
(100 MHz, CDCl3):
d
¼7.05e6.90 (m, 5H), 6.74 (s, 4H), 3.69 (s, 2H),
N
N
N
d
¼204.4, 196.6, 158.7, 142.4, 138.7, 131.9, 130.1,
128.7, 128.4, 128.1, 127.0, 105.7, 65.5, 53.7, 41.0, 29.8, 26.7, 21.0. MS
(EI) m/z: 375, 333, 332, 105, 77, 32, 28. Anal. Calcd for C24H25NO3: C,
76.77; H, 6.71; N, 3.73. Found: C, 76.91; H, 6.64; N, 3.77.
CH3
Br
O
CH3
5hgb, 93%
5hfb, 64%
5heb, 88%
4.2.3. 1,10-(1-Methyl-5-(4-methylbenzoyl)-6-phenyl-1,2,3,4-tetrahy-
Scheme 2. L-Proline/FeCl3-cocatalyzed synthesis of polysubstituted 1,2,3,4-tetrahy-
b
a
dropyridines via the MCRsa,
;
Reaction conditions: ethyl acetoacetate (1 mmol),
dropyridine-3,3-diyl)diethanone (5caa). Yellow viscous oil. IR (KBr):
2929, 1742, 1688, 1534, 1357, 1242, 1048, 753 cmꢂ1 1H NMR
.
amines (1 mmol), malononitrile (1.5 mmol), formaldehyde (2 mmol), L-proline
b
c
(10 mol %) and FeCl3 (10 mol %) in DMF (3.0 mL) at 100 ꢀC for 4 h Isolated yield.
Without L-proline. Without FeCl3.
(400 MHz, CDCl3):
(d, 2H, J¼8.0 Hz), 3.68 (s, 2H), 3.20 (s, 2H), 2.65 (s, 3H), 2.24 (s, 6H),
2.14 (s, 3H). 13C NMR (100 MHz, CDCl3):
d¼7.03e6.95 (m, 5H), 6.88 (d, 2H, J¼8.0 Hz), 6.74
d
d
¼204.4, 196.5, 157.4, 142.4,
139.4, 135.1, 130.1, 129.1, 128.4, 127.8, 127.7, 105.9, 65.5, 53.7, 41.0,
29.8, 26.7, 21.2. MS (EI) m/z: 375, 333, 332, 119, 118, 91, 28. Anal.
Calcd for C24H25NO3: C, 76.77; H, 6.71; N, 3.73. Found: C, 76.92; H,
6.63; N, 3.80.
atom economy and having water as the only side product. Further
synthetic applications and studies of the mechanism of the MCRs
are underway.
4. Experimental
4.1. General
4.2.4. 1,10-(1-Ethyl-5-(4-methylbenzoyl)-6-phenyl-1,2,3,4-tetrahy-
dropyridine-3,3-diyl)diethanone (5cba). Yellow viscous oil. IR
(KBr): 2928, 1743, 1699, 1545, 1359, 1224, 1075, 755, cmꢂ1 1H
.
NMR (400 MHz, CDCl3):
d
¼7.01 (d, 2H, J¼8.0 Hz), 6.99e6.88 (m,
All the reactions were carried out under air atmosphere in
5H), 6.74 (d, 2H, J¼8.0 Hz), 3.68 (s, 2H), 3.18 (s, 2H), 2.92e2.86
a round bottom flask equipped with magnetic stir bar. Melting
(m, 2H), 2.25 (s, 6H), 2.14 (s, 3H), 1.01 (t, 3H, J¼6.8 Hz). 13C NMR
€
points were measured with a BUCHI B-545 melting point in-
(100 MHz, CDCl3):
d
¼204.7, 196.9, 157.0, 142.7, 139.4, 135.3, 129.8,
strument and were uncorrected. GCeMS was obtained using elec-
tron ionization (EI). IR spectra were obtained as potassium bromide
pellets or as liquid films between two potassium bromide pellets
with a Brucher Vector 22 spectrometer. 1H NMR and 13C NMR
spectra were recorded using a Bruker Avance 400 or 600 MHz NMR
spectrometer and, respectively, referenced to 7.27 and 77.0 ppm for
chloroform-d with TMS as internal standard. TLC was performed
using commercially prepared 100e400 mesh silica gel plates
(GF254), and visualization was effected at 254 nm. All the other
chemicals were purchased from Aldrich Chemicals.
128.6, 128.3, 127.8, 127.7, 105.9, 64.9, 50.7, 47.0, 30.3, 26.8,
21.2, 14.0. MS (EI) m/z: 389, 347, 346, 119, 91, 43. Anal. Calcd
for C25H27NO3: C, 77.09; H, 6.99; N, 3.60. Found: C, 77.26; H,
6.93; N, 3.67.
4.2.5. 5-Benzoyl-1-methyl-6-phenyl-1,2-dihydropyrid- ine-3,3(4H)-
dicarbonitrile (5aab). White crystal, mp: 225e226 ꢀC. IR (KBr):
2926, 2351, 1672, 1607, 1559, 1382, 1267, 738, 692 cmꢂ1 1H NMR
.
(400 MHz, CDCl3):
d
¼7.25e7.23 (m, 2H), 7.11e7.00 (m, 8H), 3.93
(s, 2H), 3.43 (s, 2H), 2.86 (s, 3H). 13C NMR (100 MHz, CDCl3):
d
¼195.9, 155.7, 140.3, 133.8, 129.9, 129.8, 129.2, 127.9, 127.8, 126.9,
4.2. General procedure for the synthesis of
multifunctionalized 1,2,3,4-tetrahydropyridines (5aaae5aae)
113.6, 106.6, 56.3, 41.3, 35.0, 28.3. MS (EI) m/z: 327, 223, 222, 207,
105, 77, 44. Anal. Calcd for C21H17N3O: C, 77.04; H, 5.23; N, 12.84.
Found: C, 77.28; H, 5.17; N, 12.79.
To a mixture of alkynone 1 (1 mmol) and amine 2 (1 mmol),
3 mL DMF was added successively. The mixture was stirred at room
temperature for 30 min. Subsequently, active methylene compound
4.2.6. 1-Methyl-5-(4-methylbenzoyl)-6-phenyl-1,2-di- hydropyridine-
3,3(4H)-dicarbonitrile (5cab). White crystal, mp: 186e187 ꢀC. IR
(KBr): 2926, 2370,1687,1609,1570,1385,1271, 827, 746, 701 cmꢂ1. 1H
3 (1.5 mmol), 38% formaldehyde 4 (160 mg, 2 mmol), and L-proline
(11.5 mg, 0.1 mmol) were added, and the stirring was continued in
a round bottom flask at 100 ꢀC for another 12 h. The progress of the
reaction was followed by TLC. After cooling, the reaction was di-
luted with water and extracted with diethyl ether (15 mLꢁ3). The
NMR (400 MHz, CDCl3):
6.80(d, 2H, J¼8.0 Hz), 3.90(s, 2H), 3.38(s, 2H), 2.83(s, 3H), 2.16 (s, 3H).
13C NMR (100 MHz, CDCl3):
¼196.3, 155.6, 140.9, 137.6, 134.3, 130.3,
129.5,128.6,128.1,128.0,114.1,107.1, 56.6, 41.8, 35.4, 28.5, 21.3. MS (EI)
d
¼7.16 (d, 2H, J¼8.0 Hz), 7.06e7.03 (m, 5H),
d

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H.-F. Jiang et al. / Tetrahedron 66 (2010) 9721e9728
m/z: 341, 222, 207,119, 91, 32, 28. Anal. Calcd for C22H19N3O: C, 77.40;
H, 5.61; N, 12.31. Found: C, 77.18; H, 5.69; N, 12.26.
(KBr): 2981, 1732, 1599, 1547, 1360, 1263, 754, 702 cmꢂ1. 1H NMR
(400 MHz, CDCl3):
d¼7.14e7.09 (m, 5H), 7.07 (s, 1H), 6.44 (d, 1H,
J¼3.2 Hz), 6.04e6.03 (m, 1H), 4.21e4.16 (m, 4H), 3.73 (s, 2H), 3.17 (s,
4.2.7. 1-Ethyl-5-(4-methylbenzoyl)-6-phenyl-1,2-dihy- dropyridine-
3,3(4H)-dicarbonitrile (5cbb). White crystal, mp: 192e193 ꢀC. IR
(KBr): 2927, 2362, 1688, 1604, 1554, 1361, 1272, 751, 703 cmꢂ1. 1H
2H), 2.70 (s, 3H), 1.22 (t, 6H, J¼7.2 Hz). 13C NMR (100 MHz, CDCl3):
d
¼182.9, 169.6, 156.9, 153.9, 143.5, 135.7, 129.6, 128.6, 127.8, 115.0,
110.9, 106.6, 61.7, 54.5, 53.1, 40.9, 30.9, 14.0. MS (EI) m/z: 411, 339,
338, 214, 118, 95, 28. Anal. Calcd for C23H25NO6: C, 67.14; H, 6.12; N,
3.40. Found: C, 67.35; H, 5.99; N, 3.45.
NMR (400 MHz, CDCl3):
d
¼7.14 (d, 2H, J¼8.0 Hz), 7.08e7.03 (m, 5H),
6.81 (d, 2H, J¼8.0 Hz), 3.87 (s, 2H), 3.38 (s, 2H), 3.08e3.03 (m, 2H),
2.17 (s, 3H), 1.09 (t, 3H, J¼7.2 Hz). 13C NMR (100 MHz, CDCl3):
d
¼196.5, 155.3, 140.7, 138.0, 134.6, 130.1, 129.4, 128.5, 128.1, 128.1,
4.2.14. Ethyl 3-acetyl-5-benzoyl-1-methyl-6-phenyl-1,2,3,4-tetrahy-
114.2, 106.2, 53.3, 47.6, 35.6, 28.6, 21.3, 14.5. MS (EI) m/z: 355, 354,
237, 236, 119, 104, 91, 65, 28. Anal. Calcd for C23H21N3O: C, 77.72; H,
5.96; N, 11.82. Found: C, 77.98, H, 5.88; N, 11.78.
dropyridine-3-carboxylate (5aad). Reddish brown oil. IR (KBr):
2984, 1710, 1605, 1547, 1364, 1230, 730, 705 cmꢂ1 1H NMR
.
(600 MHz, CDCl3):
d
¼7.12e7.10 (m, 2H), 7.03e6.91 (m, 8H),
4.26e4.25 (m, 2H), 3.82e3.67 (m, 2H), 3.27e3.20 (m, 2H), 2.69 (s,
4.2.8. 1-Methyl-5-(4-methylbenzoyl)-6-p-tolyl-1,2-dihydropyridine-
3,3(4H)-dicarbonitrile (5dab). White crystal, mp: 208e209 ꢀC. IR
(KBr): 2921, 2312, 1689, 1605, 1541, 1357, 1274, 819 cmꢂ1. 1H NMR
3H), 2.33 (s, 3H), 1.29 (t, 3H, J¼7.2 Hz). 13C NMR (150 MHz, CDCl3):
d
¼203.3, 196.3, 170.0, 158.3, 142.4, 135.2, 129.0, 128.7, 128.1, 127.1,
106.0, 61.9, 58.5, 53.8, 40.9, 30.9, 26.3, 14.0. MS (EI) m/z: 391, 349,
348, 118, 105, 77, 28. Anal. Calcd for C24H25NO4: C, 73.64; H, 6.44; N,
3.58. Found: C, 73.81; H, 6.33; N, 3.44.
(400 MHz, CDCl3):
6.84e6.80 (m, 4H), 3.89 (s, 2H), 3.36 (s, 2H), 2.84 (s, 3H), 2.18 (s, 3H),
2.14 (s, 3H). 13C NMR (100 MHz, CDCl3):
d¼7.15 (d, 2H, J¼8.0 Hz), 6.93 (d, 2H, J¼8.0 Hz),
d¼196.4, 155.9, 140.7, 139.7,
137.7, 131.4, 130.2, 128.8, 128.6, 128.0, 114.2, 106.9, 56.6, 41.8, 35.5,
28.6, 21.3. MS(EI)m/z:355, 236,119,91, 28. Anal. CalcdforC23H21N3O:
C, 77.72; H, 5.96; N, 11.82. Found: C, 77.99; H, 5.88; N, 11.86.
4.2.15. Ethyl 3-acetyl-1-methyl-5-(4-methylbenzoyl)-6-phenyl-1,2,3,4-
tetrahydropyridine-3-carboxylate (5cad). Reddish brown oil. IR
(KBr): 2982, 1711, 1605, 1544, 1363, 1234, 822, 749, 705 cmꢂ1 1H
.
NMR (600 MHz, CDCl3):
d
¼7.04 (d, 2H, J¼7.8 Hz), 7.00e6.91 (m, 5H),
4.2.9. 5-(4-Fluorobenzoyl)-1-methyl-6-phenyl-1,2-dihydropyridine-
3,3(4H)-dicarbonitrile (5eab). White crystal, mp: 190e191 ꢀC. IR
(KBr): 2926, 2365, 1687, 1608, 1375, 1271, 745, 701 cmꢂ1. 1H NMR
6.75 (d, 2H, J¼7.8 Hz), 4.25e4.21 (m, 2H), 3.78e3.64 (m, 2H),
3.23e3.15 (m, 2H), 2.66 (s, 3H), 2.29 (s, 3H), 2.14 (s, 3H), 1.27 (t, 3H,
J¼7.2 Hz). 13C NMR (150 MHz, CDCl3):
¼203.4, 196.4, 170.1, 157.7,
d
(400 MHz, CDCl3):
6.70e6.66 (m, 2H), 3.93 (s, 2H), 3.42 (s, 2H), 2.87 (s, 3H). 13C NMR
(100 MHz, CDCl3):
d¼7.27e7.23 (m, 2H), 7.14e7.05 (m, 5H),
139.4, 135.4, 128.5, 128.4, 127.8, 127.7, 106.2, 61.9, 58.6, 53.8, 40.9,
31.1, 26.4, 21.2, 14.1. MS (EI) m/z: 405, 363, 362, 170, 119, 118, 118, 91.
Anal. Calcd for C25H27NO4: C, 74.05; H, 6.71; N, 3.45. Found: C,
73.88; H, 6.82; N, 3.47.
d
¼195.0, 156.5, 136.9, 134.1, 130.8, 130.7, 130.4,
130.0, 128.4, 114.3, 106.8, 56.6, 42.0, 35.3, 28.8. MS (EI) m/z: 345,
223, 222, 122, 118, 94. Anal. Calcd for C21H16FN3O: C, 73.03; H, 4.67;
N, 12.17. Found: C, 73.21; H, 4.60; N, 12.21.
4.2.16. Ethyl 3,5-dibenzoyl-1-methyl-6-phenyl-1,2,3,4-tetrahydropyr-
idine-3-carboxylate (5aae). Yellow crystal, mp: 142e143 ꢀC. IR
(KBr): 2926, 1730, 1680, 1546, 1360, 1261, 1236, 699 cmꢂ1. 1H NMR
4.2.10. 5-(Furan-2-carbonyl)-1-methyl-6-phenyl-1,2-dihydropyr-
idine-3,3(4H)-dicarbonitrile (5fab). White crystal, mp: 229e230 ꢀC.
IR (KBr): 2376, 1688, 1592, 1545, 1383, 1272, 758, 702 cmꢂ1. 1H NMR
(400 MHz, CDCl3):
d
¼7.96e7.94 (m, 2H), 7.57e7.42 (m, 3H),
7.11e6.92 (m,10H), 4.20e4.17 (m, 2H), 3.95e3.86 (m, 2H), 3.63e3.03
(400 MHz, CDCl3):
J¼3.2 Hz), 6.10e6.09 (m, 1H), 3.90 (s, 2H), 3.38 (s, 2H), 2.89 (s, 3H).
13C NMR (100 MHz, CDCl3):
d¼7.22e7.19 (m, 5H), 7.09 (s, 1H), 6.57 (d, 1H,
(m, 2H), 2.69 (s, 3H), 1.27 (t, 3H, J¼7.2 Hz). 13C NMR (100 MHz,
CDCl3):
d¼196.6, 195.5, 171.2, 158.3, 142.4, 135.6, 135.4, 133.1, 129.0,
d
¼182.3, 155.1, 152.7,144.0,134.0, 129.4,
128.7,128.6,128.3,127.8,127.0,108.3, 61.8, 56.8, 55.9, 40.8, 32.3,13.8.
MS (ESI) m/z: 453. Anal. Calcd for C29H27NO4: C, 76.80; H, 6.00; N,
3.09. Found: C, 76.96; H, 5.51; N, 3.06.
129.2,127.8,115.9,113.6,111.0,106.1, 56.3, 41.5, 34.6, 28.2. MS (EI) m/
z: 317, 222, 207, 206, 32, 28. Anal. Calcd for C19H15N3O2: C, 71.91; H,
4.76; N, 13.24. Found: C, 72.14; H, 4.66; N, 13.29.
4.2.11. 5-(Cyclohexanecarbonyl)-1-methyl-6-phenyl-1,2-dihydropyr-
idine-3,3(4H)-dicarbonitrile (5gab). White crystal, mp: 163e164 ꢀC.
IR (KBr): 2926, 2361, 1698, 1616, 1547, 1378, 1260, 769, 703 cmꢂ1. 1H
4.3. General procedure for the synthesis of
multifunctionalized 1,2,3,4-tetrahydropyridines (5hbbe5hgb)
NMR (400 MHz, CDCl3):
3.78 (s, 2H), 3.19 (s, 2H), 2.80 (s, 3H), 1.50e0.95 (m, 9H), 0.57e0.52
(m, 2H). 13C NMR (100 MHz, CDCl3):
129.3, 129.0, 114.1, 107.6, 56.2, 47.9, 41.7, 34.8, 29.7, 29.1, 25.7, 25.6.
MS (EI) m/z: 333, 251, 250, 118, 55, 28. Anal. Calcd for C21H23N3O: C,
75.65; H, 6.95; N, 12.60. Found: C, 75.48; H, 7.12; N, 12.64.
d
¼7.49e7.42 (m, 3H), 7.30e7.28 (m, 2H),
A mixture of ethyl acetoacetate 1h (130 mg, 1 mmol), amines 2
(1 mmol), malononitrile 3b (66 mg, 1 mmol), 38% formaldehyde 4
(160 mg, 2 mmol), FeCl3 (16 mg, 0.1 mmol), and L-proline (11.5 mg,
d¼204.0, 155.0, 135.4, 130.1,
0.1 mmol) was heated in DMF (3 ml) with stirring in a round bottom
flask at 100 ꢀC for 4 h. The progress of the reaction was followed by
TLC. After cooling, the reaction was diluted with water and
extracted with diethyl ether (15 mLꢁ3). The ether layer was then
washed with saturated salt water and dried over anhydrous MgSO4.
Solvent was removed in vacuo, and the crude product was purified
by preparative TLC (GF254) with petroleum ether/ethyl acetate (10:1
to 4:1) as eluent to afford the desired products 5hbbe5hgb.
4.2.12. 5-Benzoyl-1-methyl-6-phenyl-1,2-dihydropyr-idine-3,3(4H)-
dicarboxylate (5aac). Yellow viscous oil. IR (KBr): 2928, 1613, 1553,
1382, 1256, 767, 706 cmꢂ1. 1H NMR (400 MHz, CDCl3):
d¼7.17e7.15
(m, 2H), 7.03e6.94 (m, 8H), 4.24e4.19 (m, 4H), 3.75 (s, 2H), 3.17 (s,
2H), 2.66 (s, 3H), 1.25 (t, 6H, J¼7.2 Hz). 13C NMR (100 MHz, CDCl3):
d
¼196.6, 169.8, 157.5, 142.4, 135.5, 130.2, 129.1, 128.6, 128.3, 127.8,
4.3.1. Ethyl 5,5-dicyano-1-ethyl-2-methyl-1,4,5,6-tetrahydropyridine-
127.1, 107.3, 61.8, 54.5, 53.1, 40.9, 31.2, 14.0. MS (EI) m/z: 421, 349,
348, 249,170,118,105, 77, 28. Anal. Calcd for C25H27NO5: C, 71.24; H,
6.46; N, 3.32. Found: C, 71.36, H, 6.38; N, 3.27.
3-carboxylate (5hbb). Yellow viscous oil, IRmax (KBr): 2977, 2260,
1766, 1681, 1568, 1424, 1256, 1202, 1160, 1106 cmꢂ1 1H NMR
.
(400 MHz, CDCl3):
d
¼4.16e4.11 (m, 2H), 3.64 (s, 2H), 3.44e3.39
(m, 2H), 3.10 (s, 2H), 2.49 (s, 3H), 1.28 (t, 3H, J¼7.2), 1.21 (t, 3H,
4.2.13. Diethyl
5-(furan-2-carbonyl)-1-methyl-6-phenyl-1,2-dihy-
J¼7.2). 13C NMR (100 MHz, CDCl3):
¼167.1, 154.1, 114.3, 90.7, 59.7,
d
dropyridine-3,3(4H)-dicarboxylate (5fac). Yellow viscous oil. IR
53.5, 46.3, 34.2, 29.3, 15.9, 14.5, 14.1. MS (EI) m/z: 247, 202, 174, 135,

H.-F. Jiang et al. / Tetrahedron 66 (2010) 9721e9728
9727
42, 29, 28. Anal. Calcd for C13H17N3O2: C, 63.14; H, 6.93; N, 16.99.
Found: C, 63.25; H, 6.85; N, 17.04.
Research Program of China (973 Program) (No. 2011CB808603),
the Doctoral Fund of the Ministry of Education of China
(20090172110014) and Guangdong Natural Science Foundation
(No. 8451064101000236) for financial support.
4.3.2. Ethyl 1-benzyl-5,5-dicyano-2-methyl-1,4,5,6-tetrahydropyridine-
3-carboxylate (5hcb). Yellow viscous oil. IR (KBr): 2981, 2260, 1689,
1576, 1359, 1246, 1130, 734, 699 cmꢂ1. 1H NMR (400 MHz, CDCl3):
Supplementary data
d
¼7.41e7.20 (m, 5H), 4.60 (s, 2H), 4.19e4.14 (m, 2H), 3.59 (s, 2H),
3.15 (s, 2H), 2.56 (s, 3H), 1.30 (t, 3H, J¼7.2). 13C NMR (100 MHz,
Supplementary data associated with this article can be found in
the online version at doi:10.1016/j.tet.2010.10.041.
CDCl3):
d
¼167.0, 154.3, 135.9, 129.2, 128.2, 126.7, 114.2, 91.8, 59.9,
54.8, 53.6, 34.2, 29.2, 16.6, 14.5. MS (EI) m/z: 309, 264, 236, 230, 158,
132, 91, 28. Anal. Calcd for C18H19N3O2: C, 69.88; H, 6.19; N, 13.58.
Found: C, 69.71; H, 6.27; N, 13.52.
References and notes
€
1. For recent reviews of multicomponent reactions, see: (a) Domling, A. Chem.
4.3.3. Ethyl 5,5-dicyano-2-methyl-1-phenyl-1,4,5,6-tetrahydropyridine-
ꢁ
Rev. 2006, 106, 17; (b) Ramon, D. J.; Yus, M. Angew. Chem., Int. Ed. 2005, 44,
ꢁ
1602; (c) Toure, B. B.; Hall, D. G. Chem. Rev. 2009, 109, 4439; (d) Tietze, L. F.
3-carboxylate (5hdb). Reddish brown oil. IR (KBr): 2981, 2260,
1684, 1575, 1355, 1246, 1138, 734, 699 cmꢂ1 1H NMR (400 MHz,
.
Chem. Rev. 1996, 96, 115.
2. For recent examples on multicomponent reactions, see: (a) Brioche, J.;
Masson, G.; Zhu, J. Org. Lett. 2010, 12, 1432; (b) Maiti, S.; Biswas, S.; Jana, U. J.
Org. Chem. 2010, 75, 1674; (c) Scheffelaar, R.; Paravidino, M.; Muilwijk, D.;
Lutz, M.; Spek, A. L.; de Kanter, F. J. J.; Orru, R. V. A.; Ruijter, E. Org. Lett. 2009,
11, 125; (d) Yoo, E. J.; Park, S. H.; Lee, S. H.; Chang, S. Org. Lett. 2009, 11, 1155;
(e) Dou, G.; Shi, C.; Shi, D. J. Comb. Chem. 2008, 10, 810; (f) Bonne, D.; De-
khane, M.; Zhu, J. Angew. Chem., Int. Ed. 2007, 46, 2485; (g) Li, D.-M.; Song, L.-
P.; Li, X.-F.; Xing, C.-H.; Peng, W.-M.; Zhu, S.-Z. Eur. J. Org. Chem. 2007, 3520;
(h) Siamaki, A. R.; Arndtsen, B. A. J. Am. Chem. Soc. 2006, 128, 6050; (i) Duan,
X.-H.; Liu, X.-Y.; Guo, L.-N.; Liao, M.-C.; Liu, W.-M.; Liang, Y.-M. J. Org. Chem.
2005, 70, 6980.
3. (a) Aridoss, G.; Amirthaganesan, S.; Jeong, Y. T. Bioorg. Med. Chem. Lett.
2010, 20, 2242; (b) Malviya, M.; Sunil Kumar, Y. C.; Mythri, R. B.; Ven-
kateshappa, C.; Subhash, M. N.; Rangappa, K. S. Bioorg. Med. Chem. Lett.
2009, 17, 5526; (c) Ishida, J.; Hattori, K.; Yamamoto, H.; Iwashita, A.; Mi-
hara, K.; Matsuoka, N. Bioorg. Med. Chem. Lett. 2005, 15, 4221; (d) Suleman,
N. K.; Flores, J.; Tanko, J. M.; Isin, E. M.; Castagnoli, N., Jr. Bioorg. Med.
Chem. 2008, 16, 8557; (e) Wimalasena, D. S.; Perera, R. P.; Heyen, B. J.;
Balasooriya, I. S.; Wimalasena, K. J. Med. Chem. 2008, 51, 760; (f) Dunbar,
P. G.; Durant, G. J.; Rho, T.; Ojo, B.; Messer, W. S., Jr. J. Med. Chem. 1994, 37,
2774; (g) Chao, Y. X.; He, B. P.; Tay, S. S. W. J. Neuroimmunol. 2009, 216, 39;
(h) Roberts, E.; Sanc¸ on, J. P.; Sweeney, J. B.; Workman, J. A. Org. Lett. 2003,
5, 4775; (i) Rodinovskaya, L. A.; Shestopalov, A. M.; Chunikihn, K. S. Tet-
rahedron 2002, 58, 4273.
4. For some examples on the synthesis of multiplysubstituted tetrahydropyr-
idines, see: (a) Tsukamoto, H.; Kondo, Y. Angew. Chem., Int. Ed. 2008, 47,
4851; (b) Spiegel, D. A.; Schroeder, F. C.; Duvall, J. R.; Schreiber, S. L. J. Am.
Chem. Soc. 2006, 128, 14766; (c) Ramachandran, P. V.; Burghardt, T. E.;
Bland-Berry, L. J. Org. Chem. 2005, 70, 7911; (d) Zhu, X.-F.; Lan, J.; Kwon, O.
J. Am. Chem. Soc. 2003, 125, 4716; (e) Legault, C.; Charette, A. B. J. Am. Chem.
Soc. 2003, 125, 6360; (f) Buonora, P.; Olsen, J.-C.; Oh, T. Tetrahedron 2001,
57, 6099; (g) Kita, Y.; Maekawa, H.; Yamasak, Y.; Nishiguchi, I. Tetrahedron
2001, 57, 2095; (h) Rutjes, F. P. J. T.; Tjen, K. C. M. F.; Wolf, L. B.; Karstens,
W. F. J.; Schoemaker, H. E.; Hiemstra, H. Org. Lett. 1999, 1, 717; (i) Abell, A.
D.; Gardiner, J.; Phillips, A. J.; Robinson, W. T. Tetrahedron Lett. 1998, 39,
CDCl3):
d
¼7.41e7.15 (m, 5H), 4.19e4.14 (m, 2H), 3.98 (s, 2H), 3.20 (s,
2H), 2.19 (s, 3H), 1.29 (t, 3H, J¼7.2 Hz). 13C NMR (100 MHz, CDCl3):
d¼166.7, 153.1, 143.8, 129.9, 127.8, 127.4, 114.1, 93.9, 59.9, 55.8, 34.2,
29.2, 19.2, 14.4. MS (EI) m/z: 295, 266, 250, 223, 222, 144, 118, 77.
Anal. Calcd for C17H17N3O2: C, 69.14; H, 5.80; N, 14.23. Found: C,
69.30; H, 5.72; N, 14.18.
4.3.4. Ethyl 5,5-dicyano-2-methyl-1-p-tolyl-1,4,5,6-tetrahydropyr-
idine-3-carboxylate (5heb). Reddish brown oil. IR (KBr): 2982, 2260,
1691,1579,1514,1452,1383,1246,1140, 823 cmꢂ1.1H NMR(400 MHz,
CDCl3):
d
¼7.18 (d, 2H, J¼8.0 Hz), 7.03 (d, 2H, J¼8.0 Hz), 4.18e4.12 (m,
2H), 3.95 (s, 2H), 3.19 (s, 2H), 2.34 (s, 3H), 2.17 (s, 3H), 1.28 (t, 3H,
J¼7.2 Hz). 13C NMR (150 MHz, CDCl3):
¼166.8, 153.4, 141.3, 137.9,
d
130.5, 127.3, 114.2, 93.4, 59.9, 55.9, 34.3, 29.2, 21.0, 19.1, 14.4. MS (EI)
m/z: 309, 264, 236, 230, 158, 132, 91, 28. Anal. Calcd for C18H19N3O2:
C, 69.88; H, 6.19; N, 13.58. Found: C, 69.62; H, 6.25; N, 13.62.
4.3.5. Ethyl 1-(4-bromophenyl)-5,5-dicyano-2-methyl-1,4,5,6-tetra-
hydropyridine-3-carboxylate (5hfb). Reddish brown oil. IR (KBr):
2981, 2260, 1694, 1577, 1513, 1487, 1383, 1244, 1145, 823 cmꢂ1. 1H
NMR (400 MHz, CDCl3):
d
¼7.54 (d, 2H, J¼8.4 Hz), 7.06 (d, 2H,
J¼8.4 Hz), 4.22e4.16 (m, 2H), 3.98 (s, 2H), 3.21 (s, 2H), 2.21 (s, 3H),
1.31 (t, 3H, J¼7.2 Hz). 13C NMR (100 MHz, CDCl3):
¼166.6, 152.3,
d
142.9, 133.1, 129.0, 121.4, 114.0, 95.4, 60.1, 55.7, 34.2, 29.2, 19.3, 14.4.
MS (EI) m/z: 373, 328, 300, 296, 222, 220, 196, 155, 143, 75. Anal.
Calcd for C17H16BrN3O2: C, 54.56; H, 4.31; Br, 21.35; N, 11.23. Found:
C, 54.71; H, 4.26; Br, 21.38; N, 11.20.
~
ꢁ
ꢁ
9563; (j) Brana, M. F.; Moran, M.; Perez de Vega, M. J.; Pita-Romero, I. J.
Org. Chem. 1996, 61, 1369; (k) Norman, M. H.; Heathcock, C. H. J. Org. Chem.
1988, 53, 3370.
4.3.6. Ethyl 5,5-dicyano-1-(4-methoxyphenyl)-2-methyl-1,4,5,6-tet-
rahydropyridine-3-carboxylate (5hgb). Reddish brown oil. IR (KBr):
2980, 2850, 2261, 1691, 1579, 1511, 1457, 1383, 1245, 1139, 831 cmꢂ1. 1H
5. For some examples on the synthesis of multiplysubstituted 1,2,3,4-tetrahy-
dropyridines, see: (a) Caplan, J. F.; Sutherland, A.; Vederas, J. C. J. Chem. Soc.,
Perkin Trans. 1 2001, 2217; (b) Harrison, T. J.; Dake, G. R. J. Org. Chem. 2005, 70,
10872; (c) Li, X.; Song, L.; Xing, C.; Zhao, J.; Zhu, S. Tetrahedron 2006, 62,
2255; (d) Han, R.-G.; Wang, Y.; Li, Y. Y.; Xu, P. F. Adv. Synth. Catal. 2008, 350,
1474; (e) Zanatta, N.; da Fernandes, L. S.; Nachtigall, F. M.; Ceolho, H. S. Eur. J.
NMR (400 MHz, CDCl3):
d
¼7.08 (d, 2H, J¼8.8 Hz), 6.89 (d, 2H, J¼8.8 Hz),
4.17e4.12 (m, 2H), 3.93 (s, 2H), 3.80 (s, 3H), 3.19 (s, 2H), 2.16 (s, 3H),1.28
(t, 3H, J¼7.2 Hz). 13CNMR(150MHz,CDCl3):
d¼166.8,159.0,153.7,136.6,
Org. Chem. 2009, 1435; (f) Sridharan, V.; Maiti, S.; Menendez, J. C. Chem.dEur.
ꢁ
J. 2009, 15, 4565; (g) Liu, W.-B.; Jiang, H.-F.; Zhu, S.-F.; Wang, W. Tetrahedron
2009, 65, 7985; (h) Sperger, C. A.; Mayer, P.; Wanner, K. T. Tetrahedron 2009,
65, 10463.
6. (a) Zhang, M.; Jiang, H.; Liu, H.; Zhu, Q. Org. Lett. 2007, 9, 4111; (b) Cao, H.;
Wang, X.; Jiang, H.; Zhu, Q.; Zhang, M.; Liu, H. Chem.dEur. J. 2008, 14, 11623; (c)
Zhu, Q.; Jiang, H.; Li, J.; Zhang, M.; Wang, X.; Qi, C. Tetrahedron 2009, 65, 4604.
7. Cao, H.; Jiang, H.-F.; Qi, C.-R.; Yao, W.-J.; Chen, H.-J. Tetrahedron Lett. 2009, 50,
1209.
128.8, 115.0, 114.2, 92.9, 59.8, 56.1, 55.5, 34.2, 29.2, 19.0, 14.4. MS (EI)
m/z: 325, 280, 252, 247, 232, 174, 148, 28. Anal. Calcd for C18H19N3O3:
C, 66.45; H, 5.89; N, 12.91. Found: C, 66.61; H, 5.81; N, 12.85.
4.4. X-ray data
8. Zhang, M.; Jiang, H. F.; Wang, A. Z. Synlett 2007, 20, 3214.
9. Jiang, H.; Mai, R.; Cao, H.; Zhu, Q.; Liu, X. Org. Biomol. Chem. 2009, 7, 4943.
10. Muller, T. E.; Hultzsch, K. C.; Yus, M.; Foubelo, F.; Tada, M. Chem. Rev. 2008, 108,
Crystal data for 5baa. C24H25NO3, M¼375.45, monoclinic,
3
ꢀ
ꢀ
a¼6.1835 (12), b¼26.950 (5) A, c¼12.243 (2) A, U¼1983.6 (7) A ,
T¼293 (2) K, space group P21/n, 15,703 reflections measured, 3577
independent reflections (Rint¼0.0506). The final wR (F2) was 0.1799
(all data) and R1 was 0.0541 for I>2s (I). CCDC No. 779617.
€
3795.
€
€
€
ꢁ
ꢁ
11. (a) Tomoskozi, I.; Gruber, L.; Kovacs, G.; Szekely, I.; Simonidesz, V. Tetrahedron
Lett. 1976, 17, 4639; (b) Snider, B. B.; Rodini, D. J.; Kirk, T. C.; Cordova, R. J. Am.
Chem. Soc. 1982, 104, 555; (c) Tian, X.; Jaber, J. J.; Rychnovsky, S. D. J. Org. Chem.
2006, 71, 3176.
12. For representative recent examples of proline-catalyzed reactions, see: (a)
List, B.; Lerner, R. A.; Barbas, C. F., III. J. Am. Chem. Soc. 2000, 122, 2395; (b)
Sakthivel, K.; Notz, W.; Bui, T.; Barbas, C. F., III. J. Am. Chem. Soc. 2001, 123,
5260; (c) Zhou, Y.; Shan, Z. J. Org. Chem. 2006, 71, 9510; (d) Davies, H. J.;
Ruda, A. M.; Tomkinson, N. C. O. Tetrahedron Lett. 2007, 48, 1461; (e)
Acknowledgements
The authors thank the National Natural Science Foundation of
China (Nos. 20625205, 20772034 and 20932002), National Basic

9728
H.-F. Jiang et al. / Tetrahedron 66 (2010) 9721e9728
Chandrasekhar, S.; Vijeender, K.; Sridhar, C. Tetrahedron Lett. 2007, 48,
Zhang, J.; Sarma, K. D.; Curran, T. T.; Belmont, D. T.; Davidson, J. G. J. Org.
Chem. 2005, 70, 5890; (e) Zhang, Y.; Li, C.-J. Angew. Chem., Int. Ed. 2006, 45,
1949; (f) Basheer, A.; Rappoport, Z. J. Org. Chem. 2006, 71, 9743; (g) Ranu, B.
C.; Chattopadhyay, K.; Adak, L. Org. Lett. 2007, 9, 4595; (h) Fotouhi, L.;
Heravi, M. M.; Fatehi, A.; Bakhtiari, K. Tetrahedron Lett. 2007, 48, 5379; (i)
Saeedi, M.; Heravi, M. M.; Beheshtiha, Y. S.; Oskooie, H. A. Tetrahedron 2010,
66, 5345.
4935; (f) Sengupta, S.; Duan, H.; Lu, W.; Petersen, J. L.; Shi, X. Org. Lett.
€
2008, 10, 1493; (g) Hahn, B. T.; Frohlich, R.; Harms, K.; Glorius, F. Angew.
Chem., Int. Ed. 2008, 47, 9985; (h) Zhong, C.; Chen, Y.; Petersen, J. L.;
Akhmedov, N. G.; Shi, X. Angew. Chem., Int. Ed. 2009, 48, 1279; (i) Chandler,
C.; Galzerano, P.; Michrowska, A.; List, B. Angew. Chem., Int. Ed. 2009, 48,
1978; (j) Mukhopadhyay, C.; Tapaswi, P. K.; Butcher, R. J. Tetrahedron Lett.
2010, 51, 1797.
14. FeCl3-catalyzed formation of
b-enamino carbonyl compounds has been
13. (a) Lu, C.; Lu, X. Tetrahedron 2004, 60, 6575; (b) Li, Z.; Li, C.-J. Eur. J. Org.
Chem. 2005, 3173; (c) Ranu, B. C.; Banerjee, S. Org. Lett. 2005, 7, 3049; (d)
reported already, see: Hebbache, H.; Hank, Z.; Boutamine, S.; Meklati, M.;
Bruneau, C.; Renaud, J.-L. C.R. Chim. 2008, 11, 612.