Synthesis of functionalized 2-vinyl-2,3-dihydropyrroles and 3-methylene-1,2,3,4-tetrahydropyridines by palladium-catalyzed cyclization of β-enaminocarbonyl compounds with allylic bisacetates

Article abstract of DOI:10.1039/c3ob42510j

A palladium-catalyzed cyclization of β-enaminocarbonyl compounds with allylic bisacetates is described. 2-Vinyl-2,3-dihydropyrroles and 3-methylene-1,2,3,4-tetrahydropyridines were produced from the reaction of β-enaminocarbonyl compounds with 1,4-diacetoxy-2-butene and 2-methylene-1,3-propanediol diacetate, respectively. the Partner Organisations 2014.

Full text of DOI:10.1039/c3ob42510j

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DOI: 10.1039/C3OB42510J
ARTICLE
Synthesis of Functionalized 2-Vinyl-2,3-
dihydropyrroles and 3-Methylene-1,2,3,4-
tetrahydropyridines by Palladium-Catalyzed
Cyclization of -Enaminocarbonyl Compounds with
Allylic Bisacetates
Cite this: DOI: 10.1039/x0xx00000x
Received 00th January 2012,
Accepted 00th January 2012
DOI: 10.1039/x0xx00000x
Masahiro Yoshida,* Kouki Kinoshita and Kosuke Namba
www.rsc.org/
A palladium-catalyzed cyclization of
described. 2-Vinyl-2,3-dihydropyrroles and 3-methylene-1,2,3,4-tetrahydropyridines were
produced from the reaction of -enaminocarbonyl compounds with 1,4-diacetoxy-2-butene and
2-methylene-1,3-propanediol diacetate, respectively.
-enaminocarbonyl compounds with allylic bisacetates is

Introduction
Substituted dihydropyrroles and tetrahydropyridines are an
important class of heteroaromatic molecules, which are
components in a variety of biologically active natural products
and pharmaceutical agents.1,2 Furthermore, some of their
derivatives serve as excellent intermediates for various
nitrogen-containing heterocyclic molecules of synthetic and
biological interest.3,4 For this reason, extensive studies have
been devoted toward finding syntheses of substituted
dihydropyrroles and tetrahydropyridines.5,6
Palladium-catalyzed allylic substitution reactions with
nucleophiles have received considerable attention because of
their versatile and specific reactivities. A large number of
transformations including cyclization reactions have been
developed by using various allylic substrates and nucleophiles.7
For example,
nucleophile that contains two nucleophilic parts within the
molecule, to afford a cyclized product via successive double
a 1,4-diacyloxy-2-butene reacts with bis-
A
allylic substitutions (Scheme 1). Similarly, reaction of a 2-
methylene-1,3-propanediol diester with bis-nucleophile
produces a cyclized compound B. A variety of classes of cyclic
molecules have been synthesized by the suitable design of bis-
nucleophiles.8,9 During the course of our studies on the
palladium-catalyzed reactions of propargylic esters with bis-
Scheme
1
Palladium-catalyzed cyclizations of allylic
bisacetates with bis-nucleophiles.
nucleophiles,10 we focused on the nucleophilic activity of
-
enaminocarbonyl compounds10h towards the 1,4-diacyloxybut-
2-ene and the 2-methylene-1,3-propanediol diester. Herein, we
describe palladium-catalyzed reactions of
compounds with 1,4-diacetoxybut-2-ene (
1,3-propanediol diacetate ), in which the 2-vinyl-2,3-
dihydropyrroles and 3-methylene-1,2,3,4-tetrahydropyridines
have been constructed in one step, respectively (Scheme 2).

-enaminocarbonyl
2) and 2-methylene-
1
(
4
3
5
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R2OC
R1
also proceeded to afford the corresponding product 3c in 96%
yield (entry 2). Similar results were obtained in the reaction of
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AcO
OAc
2
the substrates having
a
2-naphthalenesulfonyl, 2-
N
nitrobenzenesulfonyl (Ns) and 4-nitrobDenOzI:e1n0e.1s0u3l9f/oCn3yOlB4(2N5o10sJ)
group to afford the corresponding products 3d 3e and 3f in
COR2
EWG
,
3
cat. Pd
good yield, respectively (entries 3–5). Furthermore, the yield of
the corresponding product 3g was increased to 99% yield when
2,4,6-trimethylbenzenesulfonyl-substituted substrate 1g was
used (entry 6).11
R1
NH
EWG
R2OC
R1
AcO
OAc
4
1
N
EWG
5
Table 2. Reactions using various substrates 1b–1g with 2.
Scheme 2 Synthesis of 2-vinyl-2,3-dihydropyrroles
3 and 3-
methylene-1,2,3,4-tetrahydropyridines 5.
Results and discussion
Entry
EWG
Yield of 3 (%)
We began our studies using tosyl-substituted β-enamino ester
1a and ( )-1,4-diacetoxybut-2-ene ( ). When 1a and were
1
2
3
4
5
6
benzenesulfonyl (1b)
88
96
86
82
74
99
Z
2
2
methanesulfonyl (Ms) (1c)
2-naphthalenesulfonyl (1d)
2-nitrobenzensulfonyl (Ns) (1e)
4-nitrobenzensulfonyl (Nos) (1f)
2,4,6-trimethylbenzenesulfonyl (1g)
subjected to the reaction with 10 mol % of Pd(OAc)2, 20 mol %
of 1,3-Bis(diphenylphosphino)propane (DPPP) and 4 equiv
K2CO3 in THF under reflux conditions for 20 min, the 2-vinyl-
2,3-dihydropyrrole 3a was produced in 26% yield (entry 1 in
Table 1). Experimenting with reaction solvents (entries 2–5)
revealed that the yield was increased to 63% in the case of
dioxane (entry 5). After attempts employing various phosphine
ligands (entries 6–9), we found that 3a was produced in 95%
yield when the reaction was carried out in the presence of (±)-
2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP) (entry 9).
We next conducted the reactions using various
enaminocarbonyl compounds 1h–1p (Table 3). When
enamino isopropyl ester (1h) and


-
-
2 were exposed to the optimal
conditions, the 2-vinyl-2,3-dihydropyrrole 3h was obtained in
92% yield (entry 1). The propyl-substituted substrate 1i
uneventfully reacted to afford the corresponding product 3i in
90% yield (entry 2), but the yield of the corresponding product
3j was decreased in the case of isopropyl-substituted substrate
1j (entry 3), presumably because of the bulkiness of the
Table 1. Initial attempts using 1a with 2
isopropyl moiety. The phenyl-substituted
successfully reacted with to produce the corresponding
product 3k in 99% yield (entry 4). Similarly, the reactions of
the substrates 1l 1n having a various aryl group proceeded to
give the corresponding products 3l–3n in high yields (entries 5–
7). When the -enamino ketones 1o and 1p were subjected to
the reaction, the corresponding cyclized products 3o and 3p
were obtained in 91% and 89% yield, respectively (entries 8
and 9).
-enamino ester 1k
2
–
Entry
Solvent
Ligand
Temp (ºC)
Yield (%)

1
2
3
4
5
6
7
8
9
THF
DMF
NMP
MeCN
dioxane
dioxane
dioxane
dioxane
dioxane
DPPP
DPPP
DPPP
DPPP
DPPP
DPPB
DPPE
DPPF
(±)-BINAP
reflux
120
120
reflux
reflux
reflux
reflux
reflux
reflux
26
43
44
56
63
31
78
85
95
A plausible mechanism for the cyclization process is shown in
Scheme 3. In the presence of a palladium catalyst, 1,4-
diacetoxybut-2-ene
complex , which causes the nucleophilic attack of the
enaminocarbonyl compound to afford the substituted allylic
acetate . The compound is successively subjected to the
intramolecular nucleophilic attack of the enamino moiety by
palladium via the formation of -allylpalladium intermediate
to produce the dihydropyrrole
2 is transformed to the -allylpalladium
6
-
7
7

.
8
3
Having identified a useful set of reaction conditions, we next
carried out a study using β-enamino esters 1b–1g containing
various sulfonyl groups on the amino moiety (Table 2). When
substrate 1b having a benzenesulfonyl group was subjected to
the reaction with allylic bisacetate
2, the 2-vinyl-2,3-
dihydropyrrole 3b was produced in 88% yield (entry 1 in Table
1). The reaction using mesyl-substituted β-enamino ester 2c
2 | Org. Biomol. Chem., 2013, 00, 1‐3
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Table 3. Reactions using various substrates 1h–1p with 2
Entry
1
Product 3
Substrate 1
Yield (%)
92
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DOI: 10.1039/C3OB42510J
iPrO2C
i
CO2 Pr
NH
N
Ts
Ts
1h
3h
3i
MeO2C
MeO2C
CO2Me
2
3
4
5
6
7
8
9
90
36
99
96
98
93
91
89
NH
N
Ts
Ts
1i
CO2Me
Scheme 3 Proposed mechanism for the production of 3.
NH
N
Ts
Ts
1j
3j
We next examined the reactions using other allylic 1,4-
bisacetates (Scheme 4). When the palladium-catalyzed reaction
MeO2C
Ph
CO2Me
of (
carried out, the 2-vinyl-2,3-dihydropyrrole 3a, which was the
same product from the reaction of ( )-substrate , was obtained
in 84% yield. This result indicates that the reactions proceeded
via the formation of a common -allylpalladium intermediate
E)-1,4-diacetoxy-2-butene (9) with -enamino ester 1a was
Ph
NH
N
Ts
Ts
1k
3k
Z
2
MeO2C
MeO2C
MeO2C
CO2Me
NH

6
N
as shown in Scheme 3, regardless of the stereochemistry of the
allylic bisacetates. The cis-cyclohexene diacetate 10 also
reacted with 1a to afford the cis-fused tetrahydroindole 3q in a
stereospecific manner. This result demonstrates that the
nucleophilic substitution process proceeded with the overall
retention of the stereochemistry.
Ts
Ts
1l
3l
CO2Me
NH
N
F
Ts
Ts
1m
3m
3n
F
CO2Me
NH
N
MeO
Ts
Ts
1n
MeO
O
O
NH
Ts
N
Ts
1o
1p
3o
3p
O
O
NH
Ts
N
Ts
aAll reactions were carried out with 2 in the presence of 10 mol %
Pd(OAc)2, 20 mol% (±)-BINAP and 4 equiv K2CO3 in dioxane under
reflux for 30 min.
Scheme 4 Reactions using allylic bisacetates
9 and 10 with 1a.
We next turned our attention to the reaction with the 2-
methylene-1,3-propanediol diester. When 2-methylene-1,3-
propanediol diacetate (4) and -enamino ester 1a were treated
with 10 mol % Pd(OAc)2, 20 mol % (±)-BINAP and 4 equiv
K2CO3 in dioxane under reflux conditions, the reaction
successfully proceeded to produce the 3-methylene-1,2,3,4-
tetrahydropyridine 5a in 98% yield (Scheme 5).
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Reactions of various
with

-enaminocarbonyl compounds 1h–1p
4 are summarized in Table 4. When 
-enamVinieow AisrtoicplerOonpliynel
DOI: 10.1039/C3OB42510J
ester (1h) was subjected to the reaction, the 3-methylene-
1,2,3,4-tetrahydropyridine 5h was produced in 99% yield (entry
1). The propyl- and isopropyl-substituted substrates 1i and 1j
were successfully transformed to the cyclized products 5i and
5j in 94% and 75% yield, respectively (entries 2 and 3). The
Scheme 5 Reaction of allylic bisacetate
4 with 1a.
reactions of
group also proceeded to give the corresponding products 5k–5n
in high yield, respectively (entries 4–7). Similarly, the
enamino ketones 1o and 1p were uneventfully converted to the
corresponding cyclized products 5o and 5p in 87% and 91%
yield, respectively (entries 8 and 9).
-enamino esters 1k–1n which have a various aryl
Table 4. Reactions using various substrates 1h–1p with 4
Entry
Product 5
Substrate 1
Yield (%)
99

-
i
iPrO2C
CO2 Pr
1
NH
N
A plausible mechanism for the production of 3-methylene-
5h
5i
Ts
Ts
1h
1,2,3,4-tetrahydropyridine
with a palladium catalyst, 2-methylene-1,3-propanediol diester
is converted to the -allylpalladium complex 11, which is
subjected to the nucleophilic attack of the -enaminocarbonyl
5 is shown in Scheme 6. By reacting
CO2Me
MeO2C
MeO2C
4

2
3
4
5
6
7
8
9
94
75
99
95
94
96
87
91

NH
N
Ts
1i
Ts
compound to afford the substituted allylic acetate 12. Then
intramolecular nucleophilic cyclization of 12 occurs via the
intermediate 13 by further reacting with palladium to produce
CO2Me
the 3-methylene-1,2,3,4-tetrahydropyridine 5.
NH
N
Ts
Ts 5j
1j
CO2Me
MeO2C
Ph
Ph
NH
N
Ts
1k
5k
Ts
CO2Me
NH
MeO2C
MeO2C
N
5l
Ts
Ts
1l
CO2Me
NH
N
Ts
5m
5n
1m
Ts
F
F
CO2Me
MeO2C
Scheme 6 Proposed mechanism for the production of 5.
NH
N
Ts
Ts
1n
MeO
MeO
Conclusions
O
O
In conclusion, the effort described above has led to the
development of palladium-catalyzed reaction of
a
-
N
NH
Ts
enaminocarbonyl compounds with allylic bisacetates. This
process affords 2-Vinyl-2,3-dihydropyrroles and 3-methylene-
1,2,3,4-tetrahydropyridines having a variety of substituents via
a successive nucleophilic cyclization. Since many biologically
active molecules containing a pyrrolidine and piperidine
component have been reported, our methodology could provide
a new protocol for the synthesis of these compounds.
5o
5p
Ts
1o
1p
O
O
NH
Ts
N
Ts
aAll reactions were carried out with 4 in the presence of 10 mol %
Pd(OAc)2, 20 mol% (±)-BINAP and 4 equiv K2CO3 in dioxane under
reflux for 30 min.
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1
1629, 1542, 1255, 1172 cm−1; H-NMR (400 MHz, CDCl3) δ 2.17
Experimental
(3H, s), 3.74 (3H, s), 5.01 (1H, s), 7.767.79 (2H, m), 7.897.91 (1H,
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13
General experimental
m), 8.168.18 (1H, m), 11.62 (1H, brs);DOCI: -1N0.M103R9/C(130O0B4M25H10zJ,
CDCl3) δ 20.0 (CH3), 51.4 (CH3), 97.4 (CH), 125.6 (CH), 130.5
(CH), 132.8 (CH), 134.2 (Cq), 134.3 (CH), 148.0 (Cq), 151.2 (Cq),
168.9 (Cq); HRMS (ESI) m/z calcd for C11H12N2O6SNa [M+Na]+
323.0314, found 323.0312.
(Z)-Methyl 3-(4-nitrophenylsulfonamido)but-2-enoate (1f). Yield
67%; pale yellow crystals (AcOEt, mp. 102.9−105.7 ºC); IR (neat):
1672, 1629, 1533, 1257, 1168 cm−1; H-NMR (400 MHz, CDCl3) δ
All nonaqueous reactions were carried out under a positive
atmosphere of argon in dried glassware unless otherwise
indicated. Materials were obtained from commercial suppliers
and used without further purification except when otherwise
noted. Solvents were dried and distilled according to standard
protocol.
1
General procedure for the synthesis of β-enamino esters 1
To a stirred solution of ethyl acetoacetate (1.0 mL, 9.31 mmol) in
benzene (40 mL) were added p-toluenesulfoneamide (1.67 g, 9.77
mmol), p-TsOH·H2O (89.0 mg, 465 μmol) at rt. After stirring was
continued for 13 h under reflux condition with a Dean-Stark trap, the
reaction mixture was concentrated. After filtration of the residue
using small amount of silica gel followed by concentration, the
residue was recrystallized by AcOEt to give the β-enamino ester 1a
(1.44 g, 57%) as colorless crystals.
2.06 (3H, s), 3.82 (3H, s), 5.01 (1H, s), 8.09 (2H, dt, J = 8.8 and 2.0
Hz), 8.39 (2H, dt, J = 8.8 and 2.0 Hz), 11.35 (1H, brs); 13C-NMR
(100 MHz, CDCl3) δ 19.8 (CH3), 51.5 (CH3), 97.7 (CH), 124.7 (CH),
128.4 (CH), 146.0 (Cq), 150.3 (Cq), 151.7 (Cq), 169.4 (Cq); HRMS
(ESI) m/z calcd for C11H12N2O6SNa [M+Na]+ 323.0314, found
323.0314.
(Z)-Methyl
3-(2,4,6-trimethylphenylsulfonamido)but-2-enoate
(1g). Yield 66%; colorless crystals (AcOEt/hexane, mp. 113.1−116.7
1
ºC); IR (neat): 1669, 1624, 1345, 1277, 1159 cm−1; H-NMR (400
MHz, CDCl3) δ 1.93 (3H, s), 2.31 (3H, s), 2.65 (6H, s), 3.70 (3H, s),
4.85 (1H, s), 6.97 (2H, s), 11.20 (1H, brs); 13C-NMR (100 MHz,
CDCl3) δ 18.9 (CH3), 21.0 (CH3), 22.5 (CH3), 51.1 (CH3), 94.3
(CH), 132.2 (CH), 134.7 (Cq), 139.0 (Cq), 143.1 (Cq), 153.0 (Cq),
169.5 (Cq); HRMS (ESI) m/z calcd for C14H20NO4S [M+H]+
298.1113, found 298.1112
(Z)-Methyl 3-(4-methylphenylsulfonamido)but-2-enoate (1a).
Yield 57%; colorless crystals (AcOEt, mp. 75.2−76.8 ºC); IR (neat):
1
1672, 1626, 1256, 1164 cm−1; H-NMR (400 MHz, CDCl3) δ 2.03
(3H, s), 2.43 (3H, s), 3.70 (3H, s), 4.90 (1H, s), 7.32 (2H, d, J = 8.2
Hz), 7.78 (2H, d, J = 8.2 Hz), 11.10 (1H, brs); 13C-NMR (100 MHz,
CDCl3) δ 19.7 (CH3), 21.5 (CH3), 51.2 (CH3), 95.9 (CH), 127.1
(CH), 129.9 (CH), 137.6 (Cq), 144.2 (Cq), 152.9 (Cq), 169.4 (Cq);
HRMS (ESI) m/z calcd for C12H16NO4S [M+H]+ 270.0800, found
270.0800.
(Z)-Isopropyl 3-(4-methylphenylsulfonamido)but-2-enoate (1h).
Yield 31%; colorless crystals (AcOEt, mp. 65.7−67.8 ºC); IR (neat):
1
1665, 1626, 1258, 1165 cm−1; H-NMR (400 MHz, CDCl3) δ 1.24
(6H, d, J = 6.4 Hz), 2.02 (3H, s), 2.43 (3H, s), 4.87 (1H, s), 5.03 (1H,
septet, J = 6.4 Hz) 7.32 (2H, d, J = 8.4 Hz), 7.78 (2H, d, J = 8.4 Hz),
11.20 (1H, brs); 13C-NMR (100 MHz, CDCl3) δ 19.6 (CH3),
21.5(CH3), 21.8 (CH3), 67.4(CH), 96.9 (CH), 127.1 (CH), 129.9
(CH), 137.7 (Cq), 144.1 (Cq), 152.4 (Cq), 168.6 (Cq); HRMS (ESI)
m/z calcd for C14H20NO4S [M+H]+ 298.1113, found 298.1114.
(Z)-Methyl 3-(4-methylphenylsulfonamido)hex-2-enoate (1i).
Yield 45%; colorless crystals (AcOEt, mp. 84.5−86.1 ºC); IR (neat):
(Z)-Methyl 3-(phenylsulfonamido)but-2-enoate (1b). Yield 69%;
colorless crystals (AcOEt, mp. 40.0−42.2 ºC); IR (neat): 1672, 1627,
1
1257, 1168 cm−1; H-NMR (400 MHz, CDCl3) δ 2.04 (3H, s), 3.71
(3H, s), 4.93 (1H, s), 7.527.56 (2H, m), 7.607.62 (1H, m),
7.897.92 (2H, m), 11.16 (1H, brs); 13C-NMR (100 MHz, CDCl3) δ
19.7 (CH3), 51.2 (CH3), 96.1 (CH), 127.0 (CH), 129.3 (CH), 133.3
(CH), 140.4 (Cq), 152.7 (Cq), 169.4 (Cq); HRMS (ESI) m/z calcd
for C11H13NO4SNa [M+Na]+ 278.0463, found 278.0460.
1
1674, 1623, 1236, 1160 cm−1; H-NMR (400 MHz, CDCl3) δ 0.87
(Z)-Methyl 3-(methylsulfonamido)but-2-enoate (1c). Yield 49%;
colorless crystals (AcOEt, mp. 40.7−44.3 ºC); IR (neat): 1673, 1626,
(3H, t, J = 7.4 Hz), 1.48 (2H, sextet, J = 7.4 Hz), 1.54 (3H, s), 2.34
(2H, t, J = 7.4 Hz), 3.70 (3H, s), 4.95 (1H, s), 7.31 (2H, d, J = 7.6
Hz), 7.76 (2H, d, J = 7.6 Hz), 11.02 (1H, brs); 13C-NMR (100 MHz,
CDCl3) δ 13.5 (CH3), 21.0 (CH2), 21.5 (CH3), 34.1 (CH2), 51.2
(CH3), 95.8 (CH), 127.1 (CH), 129.9 (CH), 137.5 (Cq), 144.1 (Cq),
157.4 (Cq), 169.6 (Cq); HRMS (ESI) m/z calcd for C14H20NO4S
[M+H]+ 298.1113, found 298.1114.
1
1257, 1154 cm−1; H-NMR (400 MHz, CDCl3) δ 2.24 (3H, s), 3.14
(3H, s), 3.71 (3H, s), 5.03 (1H, s), 10.90 (1H, brs); 13C-NMR (100
MHz, CDCl3) δ 19.7 (CH3), 43.0 (CH3), 51.3 (CH3), 96.2 (CH),
152.5 (Cq), 169.4 (Cq); HRMS (ESI) m/z calcd for C6H12NO4S
[M+H]+ 194.0487, found 194.0488.
(Z)-Methyl 3-(naphthalene-2-sulfonamido)but-2-enoate (1d).
Yield 53%; colorless crystals (AcOEt, mp. 63.4−66.3 ºC); IR (neat):
(Z)-Methyl
4-methyl-3-(4-methylphenylsulfonamido)pent-2-
enoate (1j). Yield 39%; colorless crystals (AcOEt, mp. 64.9−68.6
ºC); IR (neat): 1673, 1621, 1240, 1165 cm−1; H-NMR (400 MHz,
1
1671, 1626, 1256, 1164 cm−1; H-NMR (400 MHz, CDCl3) δ 2.07
1
(3H, s), 3.71 (3H, s), 4.91 (1H, s), 7.617.69 (2H, m), 7.85 (1H, dd,
J = 2.0 and 8.4 Hz), 7.92 (1H, d, J = 8.4 Hz), 7.98 (2H, d, J = 8.4
Hz), 8.48 (1H, d, J = 2.0 Hz), 11.24 (1H, brs); 13C-NMR (100 MHz,
CDCl3) δ 19.7 (CH3), 51.2 (CH3), 96.1 (CH), 122.1 (CH), 127.8
(CH), 127.9 (CH), 128.5 (CH), 129.2 (CH), 129.3 (CH), 129.8 (CH),
132.0 (Cq), 135.0 (Cq), 137.3 (Cq), 152.7 (Cq), 169.4 (Cq); HRMS
(ESI) m/z calcd for C15H16NO4S [M+H]+ 306.0800, found 306.0804.
(Z)-Methyl 3-(2-nitrophenylsulfonamido)but-2-enoate (1e). Yield
59%; pale green crystals (AcOEt, mp. 90.1−91.6 ºC); IR (neat): 1676,
CDCl3) δ 1.00 (6H, d, J = 6.8 Hz), 2.43 (3H, s), 3.11 (1H, septet, J =
6.8 Hz), 3.70 (3H, s), 5.02 (1H, s), 7.31 (2H, d, J = 8.0 Hz), 7.75 (2H,
d, J = 8.0 Hz), 11.01 (1H, brs); 13C-NMR (100 MHz, CDCl3) δ 21.5
(CH3), 21.8 (CH3), 29.4 (CH), 51.3 (CH3), 94.0 (CH), 127.1 (CH),
129.8 (CH), 137.5 (Cq), 144.1 (Cq), 164.4 (Cq), 169.9 (Cq); HRMS
(ESI) m/z calcd for C14H20NO4S [M+H]+ 298.1113, found 298.1110.
(Z)-Methyl
3-(4-methylphenylsulfonamido)-3-phenylacrylate
(1k). Yield 30%; colorless crystals (AcOEt/hexane, mp.
1
130.9−132.0 ºC); IR (neat): 1667, 1621, 1282, 1166 cm−1; H-NMR
This journal is © The Royal Society of Chemistry 2013
Org. Biomol. Chem., 2013, 00, 1‐3 | 5

Organic & Biomolecular Chemistry
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(400 MHz, CDCl3) δ 2.40 (3H, s), 3.71 (3H, s), 5.19 (1H, s), 7.18 then extracted with AcOEt followed by concentration. The residue
(2H, d, J = 8.0 Hz), 7.25−7.34 (4H, m), 7.37−7.45 (3H, m), 10.65 was recrystallized by AcOEt to give cyclic β-enamino ketone 1p
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(1H, brs); 13C-NMR (100 MHz, CDCl3) δ 21.6 (CH3), 51.5 (CH3), (4.05 g, 61%). Colorless crystals (AcOEt, mp. 212.4−215.9 ºC); IR
DOI: 10.1039/C3OB42510J
1
101.5 (CH), 127.5 (CH), 127.8 (CH), 128.8 (CH), 129.3 (CH), 130.5 (neat): 1600, 1345, 1160 cm−1; H-NMR (400 MHz, CDCl3) δ 1.95
(CH), 133.8 (Cq), 136.4 (Cq), 144.0 (Cq), 155.1 (Cq), 168.7 (Cq); (2H, quint, J = 6.3 Hz), 2.27 (2H, t, J = 6.3 Hz), 2.32 (2H, t, J = 6.3
HRMS (ESI) m/z calcd for C17H18NO4S [M+H]+ 332.0957, found Hz), 2.45 (3H, s), 5.81 (1H, s), 6.76 (1H, brs), 7.33−7.37 (2H, m),
332.0953.
7.80−7.84 (2H, m); 13C-NMR (100 MHz, CDCl3) δ 21.2 (CH2), 21.7
(Z)-Methyl
3-(4-methylphenylsulfonamido)-3-(p-tolyl)acrylate (CH3), 28.2 (CH2), 36.2 (CH2), 108.9 (CH), 127.7 (CH), 130.1 (CH),
(1l). Yield 32%; colorless crystals (Et2O/hexane, mp. 110.6−114.3 135.3 (Cq), 145.2 (Cq), 154.3 (Cq), 198.2 (Cq); HRMS (ESI) m/z
1
ºC); IR (neat): 1673, 1618, 1285, 1166 cm−1; H-NMR (400 MHz, calcd for C13H15NO3SNa [M+Na]+ 288.0670, found 288.0668.
CDCl3) δ 2.38 (3H, s), 2.41 (3H, s), 3.70 (3H, s), 5.18 (1H, s), 7.12
(2H, d, J = 8.0 Hz), 7.16−7.23 (4H, m), 7.42 (2H, d, J = 7.6 Hz) General procedure for the synthesis of 2-vinyl-2,3-
10.60 (1H, brs); 13C-NMR (100 MHz, CDCl3) δ 21.4 (CH3), 21.5 dihydropyrroles 3 (Table 1, entry 9)
(CH3), 51.4 (CH3), 101.2 (CH), 127.5 (CH), 128.6 (CH), 128.8 (CH),
To a stirred solution of β-enamino ester (80.8 mg, 300 μmol) in
129.3 (CH), 131.1 (Cq), 136.4 (Cq), 140.9 (Cq), 144.0 (Cq), 155.2 dioxane (3.0 mL) were added (Z)-1,4-diacetoxybut-2-ene (2) (62.0
(Cq), 168.8 (Cq); HRMS (ESI) m/z calcd for C18H19NO4SNa mg, 360 μmol), Pd(OAc)2 (6.7 mg, 30.0 μmol), (±)-BINAP (37.4 mg,
[M+Na]+ 368.0932, found 368.0935.
60.0 μmol) and K2CO3 (166 mg, 1.20 mmol) at rt, and stirring was
(Z)-Methyl
3-(4-fluorophenyl)-3-(4- continued for 30 min at the same temperature under argon
methylphenylsulfonamido)acrylate (1m). Yield 32%; colorless atmosphere. The reaction mixture was then allowed to heat to 120 ºC,
crystals (Et2O/hexane, mp. 128.0−129.4 ºC); IR (neat): 1683, 1622, and stirring was continued for 30 min. After filtration of the reaction
1507, 1284, 1167 cm−1; 1H-NMR (400 MHz, CDCl3) δ 2.41 (3H, s), mixture using small amount of silica gel followed by concentration,
3.71 (3H, s), 5.17 (1H, s), 6.97−7.04 (2H, m), 7.20 (2H, d, J = 7.2 the residue was chromatographed on silica gel with AcOEt–hexane
Hz), 7.26−7.33 (2H, m), 7.41 (2H, d, J = 7.8 Hz), 10.63 (1H, brs); (1:6 v/v) as eluent to give the 2-vinyl-2,3-dihydropyrrole 3a (91.3
13C-NMR (100 MHz, CDCl3) δ 21.6 (CH3), 51.6 (CH3), 101.6 (CH), mg, 284 μmol, 95%) as colorless needles.
115.0 (CH, d, J = 22.3 Hz), 127.5 (CH), 129.4 (CH), 129.9 (Cq, d, J
= 3.3 Hz), 130.9 (CH, d, J = 8.2 Hz), 136.3 (Cq), 144.2(Cq), 154.0 Methyl
(Cq), 164.1 (Cq, d, J = 249.4 Hz), 168.6 (Cq); HRMS (ESI) m/z carboxylate (3a). Yield 95%; colorless needles (AcOEt, mp.
calcd for C17H17NO4FS [M+H]+ 350.0862, found 350.0865. 91.993.2 ºC); IR (neat) 1705, 1635, 1167, 1103 cm−1; 1H-NMR
(Z)-Methyl 3-(4-methoxyphenyl)-3-(4- (400 MHz, CDCl3) δ 2.392.45 (1H, m), 2.43 (3H, s) 2.47 (3H, t, J =
2-methyl-1-tosyl-5-vinyl-4,5-dihydro-1H-pyrrole-3-
methylphenylsulfonamido)acrylate (1n). Yield 34%; colorless 1.8 Hz), 2.792.87 (1H, m), 3.67 (3H, m), 4.70 m),
crystals (AcOEt, mp. 128.2−131.2 ºC); IR (neat): 1671, 1616, 1285, 5.18d, J = 10.0 Hz5.33 (1H, d, J = 16.8 Hz), 5.88 (1H, ddd, J
1167 cm−1; 1H-NMR (400 MHz, CDCl3) δ 2.40 (3H, s), 3.69 (3H, s), = 6.4, 10.0 and 16.8 Hz), 7.31 (2H, d, J = 8.4 Hz), 7.70 (2H, d, J =
3.84 (3H, s), 5.16 (1H, s), 6.83 (2H, d, J = 8.4 Hz), 7.18 (2H, d, J = 8.4 Hz); 13C-NMR (100 MHz, CDCl3) δ 14.3 (CH3), 21.5 (CH3),
8.4 Hz), 7.27 (2H, d, J = 8.4 Hz), 7.41 (2H, d, J = 8.4 Hz), 10.58 (1H, 34.4 (CH2), 51.1 (CH3), 63.0 (CH), 110.0 (Cq), 115.8 (CH2), 127.1
brs); 13C-NMR (100 MHz, CDCl3) δ 21.6 (CH3), 51.4 (CH3), 55.3 (CH), 129.9 (CH), 136.7 (Cq), 137.5 (CH), 144.2 (Cq), 151.0 (Cq),
(CH3), 100.7 (CH), 113.3 (CH), 126.1 (Cq), 127.5 (CH), 129.3 (CH), 166.0 (Cq); HRMS (ESI) m/z calcd for C16H19NO4S [M]+ 321.1035,
130.5 (CH), 136.2 (Cq), 144.0 (Cq), 154.9 (Cq), 161.6 (Cq), 168.9 found 321.1032.
(Cq); HRMS (ESI) m/z calcd for C18H19NO5S [M]+ 361.0984, found Methyl
2-methyl-1-(phenylsulfonyl)-5-vinyl-4,5-dihydro-1H-
361.0986.
pyrrole-3-carboxylate (3b). Yield 88%; yellow oil; IR (neat) 1706,
1
(Z)-4-Methyl-N-(4-oxopent-2-en-2-yl)benzenesulfonamide (1o).
Yield 35%; colorless crystals (AcOEt, mp. 71.8−74.3 ºC); IR (neat):
1643, 1586, 1254, 1163 cm−1; 1H-NMR (400 MHz, CDCl3) δ 2.04
(3H, s), 2.11 (3H, s), 2.43 (3H, s), 5.32 (1H, s), 7.32 (2H, d, J = 8.4
Hz), 7.78 (2H, d, J = 8.4 Hz), 12.74 (1H, brs); 13C-NMR (100 MHz,
CDCl3) δ 19.5 (CH3), 21.5 (CH3), 30.0 (CH3), 104.5 (CH), 127.2
(CH), 129.9 (CH), 137.6 (Cq), 144.3 (Cq), 153.8 (Cq), 199.5 (Cq);
HRMS (ESI) m/z calcd for C12H15NO3S [M+Na]+ 276.0670, found
276.0671.
1636, 1170, 1105 cm1; H-NMR (400 MHz, CDCl3) δ 2.402.45
(1H, m), 2.48 (3H, t, J = 1.8 Hz), 2.792.87 (1H, m), 3.68 (3H, s),
4.724.77 (1H, m), 5.19 (1H, d, J = 10.0 Hz), 5.34 (1H, d, J = 17.2
Hz), 5.88 (1H, ddd, J = 6.4, 10.0 and 16.8 Hz), 7.517.55 (2H, m),
7.597.64 (1H, m), 7.827.84 (2H, m); 13C-NMR (100 MHz,
CDCl3) δ 14.3 (CH3), 34.5 (CH2), 51.2 (CH3), 63.1 (CH), 110.7 (Cq),
116.0 (CH2), 127.1 (CH), 129.3 (CH), 133.2 (CH), 137.3 (CH),
139.7 (Cq), 150.9 (Cq), 165.9 (Cq); HRMS (ESI) m/z calcd for
C15H18NO4S [M+H]+ 308.0957, found 308.0960.
Methyl
2-methyl-1-(methylsulfonyl)-5-vinyl-4,5-dihydro-1H-
4-Methyl-N-(3-oxocyclohex-1-en-1-yl)benzenesulfonamide (1p). pyrrole-3-carboxylate (3c). Yield 96%; pale yellow oil; IR (neat)
To a stirred solution of 3-aminocyclohex-2-enone (2.78 g, 25.0 1703, 1634, 1161, 1107 cm1; 1H-NMR (400 MHz, CDCl3) δ
mmol) in THF (200 mL) were added NaH (60% in oil) (3.00 g, 75.0 2.492.54 (1H, m), 2.51 (3H, s), 3.01 (3H, s), 3.073.15 (1H, m),
mmol) at rt. After stirring was continued for 1 h under reflux 3.73 (3H, s), 4.754.80 (1H, m), 5.21 (1H, d, J = 10.4 Hz), 5.34 (1H,
condition, TsCl (4.77 g, 25.0 mmol) in THF (50 mL) was added d, J = 17.2 Hz), 5.86 (1H, ddd, J = 7.6, 10.4 and 17.6 Hz); 13C-NMR
dropwise, and further stirring was continued for 4 h under reflux (100 MHz, CDCl3) δ 13.8 (CH3), 34.5 (CH2), 42.0 (CH3), 51.2 (CH3),
condition. The reaction mixture was quenched with 2 N HCl aq, and 63.2 (CH), 109.2 (Cq), 117.2 (CH2), 136.3 (CH), 150.6 (Cq), 166.0
6 | Org. Biomol. Chem., 2013, 00, 1‐3
This journal is © The Royal Society of Chemistry 2013

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ARTICLE
(Cq); HRMS (ESI) m/z calcd for C10H15NNaO4S [M+Na]+ 268.0619, J = 17.2 Hz), 5.89 (1H, ddd, J = 6.8, 9.6 and 16.4 Hz) 7.31 (2H, d, J
found 268.0617.
Methyl
= 8.4 Hz), 7.71 (2H, d, J = 8.4 Hz); 13C-NMR (100 MHz, CDCl3) δ
2-methyl-1-(naphthalen-2-ylsulfonyl)-5-vinyl-4,5- 14.2 (CH3), 21.6 (CH3), 22.0 (CH3), 34.6 (CH2), 62.9 (CH), 67.3
DOI: 10.1039/C3OB42510J
View Article Online
dihydro-1H-pyrrole-3-carboxylate (3d). Yield 86%; colorless (CH), 110.0 (Cq), 115.8 (CH2), 127.2 (CH), 129.9 (CH), 136.8 (Cq),
needles (AcOEt/Hexane, mp. 71.373.4 ºC); IR (neat) 1703, 1634, 137.6 (CH), 144.1 (Cq), 150.3 (Cq), 165.2 (Cq); HRMS (ESI) m/z
1
1351, 1161, 1107 cm1; H-NMR (400 MHz, CDCl3) δ 2.412.45 calcd for C18H23NO4S [M+]+ 349.1348, found 349.1347.
(1H, m), 2.53 (3H, s), 2.802.87 (1H, m), 3.65 (3H, s), 4.804.85 Methyl
2-propyl-1-tosyl-5-vinyl-4,5-dihydro-1H-pyrrole-3-
(1H, m), 5.21 (1H, d, J = 10.4 Hz), 5.37 (1H, d, J = 16.8 Hz), 5.91 carboxylate (3i). Yield 90%; colorless needles (AcOEt, mp.
(1H, ddd, J = 6.8, 10.4 and 16.8 Hz), 7.627.69 (2H, m), 7.757.78 57.058.6 ºC); IR (neat) 1709, 1628, 1168, 1114 cm1; 1H-NMR
(1H, m), 7.92 (1H, d, J = 8.0 Hz), 7.967.99 (2H, m), 8.43 (1H, s); (400 MHz, CDCl3) δ 0.94 (3H, t, J = 7.2 Hz), 1.511.60 (1H, m),
13C-NMR (100 MHz, CDCl3) δ 14.3 (CH3), 34.5 (CH2), 51.1 (CH3), 1.651.74 (1H, m), 2.35 (1H, dd, J = 2.8 and 15.6 Hz), 2.43 (3H, s),
63.2 (CH), 110.6 (Cq), 116.0 (CH2), 121.9 (CH), 127.8 (CH), 128.0 2.672.79 (2H, m), 3.203.27 (1H, m), 3.67 (3H, s), 4.654.70 (1H,
(CH), 128.8 (CH), 129.2 (CH), 129.3 (CH), 129.7 (CH), 132.1 (Cq), m), 5.18 (1H, dt, J = 1.2 and 10.4 Hz), 5.35 (1H, dt, J = 1.2 and 16.8
135.0 (Cq), 136.6 (Cq), 137.5 (CH), 150.9 (Cq), 165.9 (Cq); HRMS Hz), 5.86 (1H, ddd, J = 6.0, 10.4 and 16.4 Hz), 7.31 (2H, d, J = 8.4
(ESI) m/z calcd for C19H20NO4S [M+H]+ 358.1113, found 358.1111.
Hz), 7.68 (2H, d, J = 8.4 Hz); 13C-NMR (100 MHz, CDCl3) δ 13.8
Methyl 2-methyl-1-((2-nitrophenyl)sulfonyl)-5-vinyl-4,5- (CH3), 21.5 (CH3), 22.2 (CH2), 29.1 (CH2), 34.3 (CH2), 51.1 (CH3),
dihydro-1H-pyrrole-3-carboxylate (3e). Yield 82%; yellow oil; IR 62.5 (CH), 111.8 (Cq), 115.5 (CH2), 126.9 (CH), 129.9 (CH), 136.4
(neat) 1706, 1637, 1544, 1173, 1109 cm1; 1H-NMR (400 MHz, (Cq), 137.5 (CH), 144.1 (Cq), 155.6 (Cq), 165.7 (Cq); HRMS (ESI)
CDCl3) δ 2.43 (3H, t, J = 2.0 Hz), 2.482.53 (1H, m), 3.073.15 (1H, m/z calcd for C18H23NO4S [M]+ 349.1348, found 349.1346.
m), 3.70 (3H, s), 4.844.88 (1H, m), 5.17 (1H, d, J = 10.4 Hz), 5.33 Methyl
2-isopropyl-1-tosyl-5-vinyl-4,5-dihydro-1H-pyrrole-3-
(1H, d, J = 17.2 Hz), 5.88 (1H, ddd, J = 6.8, 10.4 and 17.2 Hz), carboxylate (3j). Yield 36%; colorless needles (AcOEt/Hexane, mp.
7.707.79 (3H, m), 8.058.07 (1H, m); 13C-NMR (100 MHz, 48.850.3 ºC); IR (neat) 1715, 1615, 1167, 1105 cm1; 1H-NMR
CDCl3) δ 13.9 (CH3), 34.2 (CH2), 51.3 (CH3), 64.1 (CH), 110.6 (Cq), (400 MHz, CDCl3) δ 1.24 (3H, d, J = 7.2 Hz), 1.30 (3H, d, J = 7.2
116.2 (CH2), 124.8 (CH), 131.0 (CH), 132.0 (CH), 133.6 (Cq), 134.3 Hz), 2.28 (1H, dd, J = 1.8 and 15.8 Hz), 2.44 (3H, s), 2.61 (1H, dd, J
(CH), 136.7 (CH), 148.2 (Cq), 149.7 (Cq), 165.8 (Cq); HRMS (ESI) = 9.8 and 15.8 Hz), 3.58 (1H, septet, J = 7.20 Hz), 3.68 (3H, s),
m/z calcd for C15H16N2NaO6S [M+Na]+ 375.0627, found 375.0623.
Methyl
4.717.47 (1H, m), 5.17 (1H, d, J = 10.4 Hz), 5.38 (1H, d, J = 17.2
2-methyl-1-((4-nitrophenyl)sulfonyl)-5-vinyl-4,5- Hz), 5.80 (1H, ddd, J = 5.6, 10.4 and 16.4 Hz), 7.32 (2H, d, J = 8.6
dihydro-1H-pyrrole-3-carboxylate (3f). Yield 74%; yellow plates Hz), 7.72 (2H, d, J = 8.6 Hz); 13C-NMR (100 MHz, CDCl3) δ 18.2
(AcOEt, mp. 104.8105.9 ºC); IR (neat) 1735, 1704, 1532, 1171, (CH3), 19.9 (CH3), 21.5 (CH3), 28.2 (CH), 34.9 (CH2), 51.2 (CH3),
1
1107 cm1; H-NMR (400 MHz, CDCl3) δ 2.442.49 (1H, m), 2.49 62.8 (CH), 112.9 (Cq), 115.7 (CH2), 127.1 (CH), 129.8 (CH), 136.9
(3H, t, J = 1.6 Hz), 2.842.92 (1H, m), 3.69 (3H, s), 4.764.81 (1H, (Cq), 136.9 (CH), 144.1 (Cq), 160.3 (Cq), 165.3 (Cq); HRMS (ESI)
m), 5.22 (1H, d, J = 10.4 Hz), 5.35 (1H, d, J = 17.2 Hz), 5.84 (1H, m/z calcd for C18H23NNaO4S [M+Na]+ 372.1245, found 372.1248.
ddd, J = 6.8, 10.0 and 16.8 Hz), 8.02 (2H, d, J = 8.8 Hz), 8.38 (2H, d, Methyl
2-phenyl-1-tosyl-5-vinyl-4,5-dihydro-1H-pyrrole-3-
J = 8.8 Hz); 13C-NMR (100 MHz, CDCl3) δ 14.2 (CH3), 34.5 (CH2), carboxylate (3k). Yield 99%; colorless oil; IR (neat) 1717, 1697,
51.4 (CH3), 63.4 (CH), 111.8 (Cq), 116.8 (CH2), 124.6 (CH), 128.5 1171, 1189 cm1; H-NMR (400 MHz, CDCl3) δ 2.42 (3H, s), 2.53
1
(CH), 136.7 (CH), 145.4 (Cq), 149.7 (Cq), 150.3 (Cq), 165.5 (Cq); (1H, dd, J = 2.6 and 16.2 Hz), 2.95 (1H, dd, J = 10.4 and 16.2 Hz),
HRMS (ESI) m/z calcd for C15H16N2NaO6S [M+Na]+ 375.0627, 3.50 (3H, s), 4.964.99 (1H, m), 5.28 (1H, d, J = 10.0 Hz), 5.51 (1H,
found 375.0631.
d, J = 17.2 Hz), 5.99 (1H, ddd, J = 6.0, 10.0 and 16.8 Hz), 7.21 (2H,
Methyl
1-(mesitylsulfonyl)-2-methyl-5-vinyl-4,5-dihydro-1H- d, J = 8.2 Hz), 7.287.33 (4H, m), 7.367.41 (1H, m), 7.40 (2H, d, J
pyrrole-3-carboxylate (3g). Yield 99%; colorless needles = 8.2 Hz); 13C-NMR (100 MHz, CDCl3) δ 21.5 (CH3), 35.4 (CH2),
(AcOEt/Hexane, mp. 51.953.2 ºC); IR (neat) 1700, 1627, 1159, 51.1 (CH3), 62.5 (CH), 113.7 (Cq), 115.8 (CH2), 127.1 (CH), 127.4
1110 cm1; H-NMR (400 MHz, CDCl3) δ 2.24 (3H, t, J = 1.8 Hz), (CH), 129.5 (CH), 129.5 (CH), 130.1 (CH), 130.6 (Cq), 136.2 (Cq),
1
2.31 (3H, s), 2.462.51 (1H, m), 2.61 (6H, s), 2.993.07 (1H, m), 137.3 (CH), 144.0 (Cq), 151.0 (Cq), 165.0 (Cq); HRMS (ESI) m/z
3.68 (3H, s), 4.744.79 (1H, m), 5.10 (1H, d, J = 10.0 Hz), 5.25 (1H, calcd for C21H21NO4S [M]+ 383.1191, found 383.1189.
d, J = 17.2 Hz), 5.88 (1H, ddd, J = 6.8, 10.4 and 17.2 Hz), 6.96 (2H, Methyl
2-(p-tolyl)-1-tosyl-5-vinyl-4,5-dihydro-1H-pyrrole-3-
s); 13C-NMR (100 MHz, CDCl3) δ 13.1 (CH3), 21.0 (CH3), 22.5 carboxylate (3l). Yield 96%; colorless needles (AcOEt/Hexane, mp.
(CH3), 34.2 (CH2), 51.0 (CH3), 63.5 (CH), 107.1 (Cq), 115.8 (CH2), 90.091.2 ºC); IR (neat) 1717, 1626, 1171, 1090 cm1; 1H-NMR
132.3 (CH), 134.4 (Cq), 136.8 (CH), 139.8 (Cq×2), 143.4 (Cq), (400 MHz, CDCl3) δ 2.38 (3H, s), 2.41 (3H, s), 2.50 (1H, dd, J = 2.4
151.9 (Cq), 166.3 (Cq); HRMS (ESI) m/z calcd for C18H23NNaO4S and 16.2 Hz), 2.88 (1H, dd, J = 10.0 and 16.2 Hz), 3.51 (3H, s),
[M+Na]+ 372.1245, found 372.1243.
Isopropyl 2-methyl-1-tosyl-5-vinyl-4,5-dihydro-1H-pyrrole-3- Hz), 5.97 (1H, ddd, J = 6.0, 10.8 and 16.8 Hz), 7.13 (2H, d, J =
4.904.94 (1H, m), 5.26 (1H, d, J = 10.0 Hz), 5.51 (1H, d, J = 16.8
carboxylate (3h). Yield 92%; colorless plates (AcOEt, mp. 8.2Hz), 7.20 (2H, d, 3.2 Hz), 7.22 (2H, d, J = 3.2 Hz), 7.43 (2H, d, J
72.774.2 ºC); IR (neat) 1698, 1635, 1168, 1092 cm1; 1H-NMR = 8.2 Hz); 13C-NMR (100 MHz, CDCl3) δ 21.5 (CH3×2), 35.3 (CH2),
(400 MHz, CDCl3) δ 1.22 (6H, t, J = 5.8 Hz), 2.382.45 (1H, m), 51.1 (CH3), 62.3 (CH), 113.3 (Cq), 115.7 (CH2), 127.4 (CH), 127.5
2.43 (3H, s), 2.46 (3H, S), 2.802.87 (1H, m), 4.694.74 (1H, m), (Cq), 127.9 (CH), 129.5 (CH), 130.0 (CH), 136.1 (Cq), 137.3 (CH),
5.01 (1H, septet, J = 5.8 Hz), 5.18 (1H, d, J = 10.4 Hz), 5.33 (1H, d,
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Organic & Biomolecular Chemistry
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139.7 (Cq), 144.0 (Cq), 151.3 (Cq), 165.0 (Cq); HRMS (ESI) m/z (400 MHz, CDCl3) δ 1.631.72 (1H, m), 1.791.91 (2H, m),
calcd for C22H23NNaO4S [M+Na]+ 420.1245, found 420.1247.
1.962.04 (1H, m), 2.43 (3H, s), 2.44 (3H, s), 3.003.06 (1H, m),
View Article Online
DOI: 10.1039/C3OB42510J
Methyl
2-(4-fluorophenyl)-1-tosyl-5-vinyl-4,5-dihydro-1H- 3.70 (3H, s), 4.47 (1H, dd, J = 2.2 and 9.0 Hz), 6.016.10 (2H, m),
pyrrole-3-carboxylate (3m). Yield 98%; colorless plates (AcOEt, 7.31 (2H, d, J = 8.6 Hz), 7.70 (2H, d, J = 8.6 Hz); 13C-NMR (100
mp. 110.2111.4 ºC); IR (neat) 1716, 1628, 1171, 1090 cm1; H- MHz, CDCl3) δ 14.6 (CH3), 21.5 (CH3), 22.2 (CH2), 23.8 (CH2),
1
NMR (400 MHz, CDCl3) δ 2.43 (3H, s), 2.54 (1H, dd, J = 2.4 and 39.5 (CH), 51.0 (CH3), 60.2 (CH), 114.9 (Cq), 125.2 (CH), 127.1
16.4 Hz), 2.94 (1H, dd, J = 10.2 and 16.4 Hz), 3.52 (3H, s), (CH), 129.9 (CH), 132.7 (CH), 136.5 (Cq), 144.1 (Cq), 151.9 (Cq),
4.954.99 (1H, m), 5.28 (1H, d, J = 10.4 Hz), 5.50 (1H, d, J = 17.2 166.1 (Cq); HRMS (ESI) m/z calcd for C18H21NO4S [M]+ 347.1191,
Hz), 5.98 (1H, ddd, J = 6.0, 10.4 and 16.4 Hz), 6.987.03 (2H, m), found 347.1194.
7.227.29 (4H, m), 7.407.42 (2H, m); 13C-NMR (100 MHz,
CDCl3) δ 21.5 (CH3), 35.3 (CH2), 51.2 (CH3), 62.4 (CH), 113.9 (Cq), General procedure for the synthesis of 3-methylene-1,2,3,4-
114.3 (CH, d, J = 22.4 Hz), 115.9 (CH2), 126.5 (Cq), 127.4 (CH), tetrahydropyridines 5 (Scheme 6)
129.6 (CH), 132.2 (CH, d, J = 9.1 Hz), 136.2 (Cq), 137.3 (CH),
To a stirred solution of β-enamino ester 1a (53.9 mg, 200 μmol)
144.2 (Cq), 150.0 (Cq), 163.4 (Cq, d, J = 247.8 Hz), 164.8 (Cq); in dioxane (2.0 mL) were added 2-methylenepropane-1,3-diyl
HRMS (ESI) m/z calcd for C21H21NO4FS [M+H]+ 402.1175, found diacetate (4) (41.3 mg, 240 μmol), Pd(OAc)2 (4.5 mg, 20.0 μmol),
402.1171.
(±)-BINAP (24.9 mg, 40.0 μmol) and K2CO3 (111 mg, 800 μmol) at
Methyl
2-(4-methoxyphenyl)-1-tosyl-5-vinyl-4,5-dihydro-1H- rt, and stirring was continued for 30 min at the same temperature
pyrrole-3-carboxylate (3n). Yield 93%; colorless needles under argon atmosphere. The reaction mixture was then allowed to
(AcOEt/Hexane, mp. 117.6119.0 ºC); IR (neat) 1715, 1606, 1171, heat to 120 ºC, and further stirring was continued for 20 min. After
1089 cm1; 1H-NMR (400 MHz, CDCl3) δ 2.42 (3H, s), 2.50 (1H, dd, filtration of the reaction mixture using small amount of silica gel
J = 2.6 and 16.0 Hz), 2.87 (1H, dd, J = 10.0 and 16.0 Hz), 3.52 (3H, followed by concentration, the residue was chromatographed on
s), 3.85 (3H, s), 4.914.95 (1H, m), 5.27 (1H, dt, J = 1.2 and 10.4 silica gel with AcOEt–hexane (1:6 v/v) as eluent to give the 3-
Hz), 5.51 (1H, dt, J = 1.2 and 16.8 Hz), 5.97 (1H, ddd, J = 5.6, 10.4 methylene-1,2,3,4-tetrahydropyridine 5a (63.1 mg, 196 μmol, 98%)
and 16.0 Hz), 6.84 (2H, d, J = 8.6 Hz), 7.227.30 (4H, m), 7.43 (2H, as a pale yellow oil.
d, J = 8.6 Hz); 13C-NMR (100 MHz, CDCl3) δ 21.6 (CH3), 35.3
(CH2), 51.1 (CH3), 55.2 (CH3), 62.3 (CH), 112.6 (CH), 112.9 (Cq), Methyl
2-methyl-5-methylene-1-tosyl-1,4,5,6-
115.7 (CH2), 122.6 (Cq), 127.5 (CH), 129.5 (CH), 131.8 (CH), 136.3 tetrahydropyridine-3-carboxylate (5a). Yield 98%; pale yellow
1
(Cq), 137.4 (CH), 144.0 (Cq), 151.1 (Cq), 160.8 (Cq), 165.2 (Cq); oil; IR (neat) 1715, 1354, 1235, 1164, 1091 cm1; H-NMR (400
HRMS (ESI) m/z calcd for C22H23NO5S [M]+ 413.1297, found MHz, CDCl3) δ 2.41 (3H, s), 2.50 (3H, t, J = 2.0 Hz), 2.79 (2H, d, J
413.1301.
= 2.0 Hz), 3.72 (3H, s), 4.10 (2H, s), 4.73 (1H, s), 4.80 (1H, s), 7.24
1-(2-Methyl-1-tosyl-5-vinyl-4,5-dihydro-1H-pyrrol-3-yl)ethanone (2H, d, J = 8.4 Hz), 7.62 (2H, d, J = 8.4 Hz); 13C-NMR (100 MHz,
(3o). Yield 91%; pale yellow needles (AcOEt, mp. 95.697.1 ºC); IR CDCl3) δ 21.1 (CH3), 21.5 (CH3), 31.4 (CH2), 51.6 (CH3), 52.2
(neat) 1671, 1595, 1168, 1093 cm1; H-NMR (400 MHz, CDCl3) δ (CH2), 111.1 (CH2), 118.0 (Cq), 127.4 (CH), 129.4 (CH), 136.6 (Cq),
1
2.14 (3H, s), 2.44 (3H, s), 2.46 (3H, s), 2.442.48 (1H, m), 137.8 (Cq), 143.9 (Cq), 147.0 (Cq), 167.8 (Cq); HRMS (ESI) m/z
2.913.01 (1H, m), 4.777.82 (1H, m), 5.20 (1H, d, J = 10.4 Hz), calcd for C16H19NO4S [M]+ 321.1035, found 321.1036.
5.34 (1H, d, J = 17.2 Hz), 5.88 (1H, ddd, J = 6.8, 10.4 and 17.2 Hz), Isopropyl
2-methyl-5-methylene-1-tosyl-1,4,5,6-
7.31 (2H, J = 8.4 Hz), 7.71 (2H, d, J = 8.4 Hz); 13C-NMR (100 MHz, tetrahydropyridine-3-carboxylate (5h). Yield 99%; colorless
CDCl3) δ 14.6 (CH3), 21.5 (CH3), 30.1 (CH3), 35.5 (CH2), 63.1 (CH), plates (AcOEt, mp. 95.096.1 ºC); IR (neat) 1706, 1355, 1165 cm1;
116.2 (CH2), 118.3 (Cq), 127.2 (CH), 129.9 (CH), 136.8 (Cq), 137.3 1H-NMR (400 MHz, CDCl3) δ 1.27 (6H, d, J = 9.6 Hz), 2.41 (3H, s),
(CH), 144.3 (Cq), 150.1 (Cq), 195.8 (Cq); HRMS (ESI) m/z calcd 2.47 (3H, t, J = 2.0 Hz), 2.76 (2H, d, J = 2.0 Hz), 4.09 (2H, s), 4.73
for C16H19NNaO3S [M+Na]+ 328.0983, found 328.0979.
1-Tosyl-2-vinyl-2,3,6,7-tetrahydro-1H-indol-4(5H)-one
(1H, s), 4.79 (1H, s), 5.05 (1H, septet., J = 2.4 Hz), 7.24 (2H, d, J =
(3p). 8.0 Hz), 7.62 (2H, d, J = 8.0 Hz); 13C-NMR (100 MHz, CDCl3) δ
Yield 89%; pale yellow oil; IR (neat) 1654, 1620, 1395, 1361, 1166 21.1 (CH3), 21.5 (CH3), 21.9 (CH3), 31.5 (CH2), 52.2 (CH2), 68.0
1
cm1; H-NMR (400 MHz, CDCl3) δ 2.03 (2H, quint., J = 6.4 Hz), (CH), 111.0 (CH2), 118.9 (Cq), 127.4 (CH), 129.4 (CH), 136.7 (Cq),
2.33 (2H, t, J = 6.4 Hz), 2.412.45 (1H, m), 2.45 (3H, s), 2.682.76 138.0 (Cq), 143.8 (Cq), 145.8 (Cq), 167.0 (Cq); HRMS (ESI) m/z
(1H, m), 2.792.89 (2H, m), 4.734.78 (1H, m), 5.19 (1H, d, J = calcd for C18H23NO4S [M]+ 349.1348, found 349.1351.
10.4 Hz), 5.32 (1H, d, J = 17.2 Hz), 5.85 (1H, ddd, J = 6.8, 10.0 and Methyl 5-methylene-2-propyl-1-tosyl-1,4,5,6-tetrahydropyridine-
16.8 Hz), 7.34 (2H, d, J = 8.2 Hz), 7.71 (2H, d, J = 8.2 Hz); 13C- 3-carboxylate (5i). Yield 94%; colorless plates (AcOEt, mp.
NMR (100 MHz, CDCl3) δ 21.5 (CH3), 22.6 (CH2), 24.7 (CH2), 31.6 85.486.1 ºC); IR (neat) 1710, 1351, 1239, 1090 cm1; 1H-NMR
(CH2), 36.4 (CH2), 64.7 (CH), 116.4 (CH2), 119.4 (Cq), 127.1 (CH), (400 MHz, CDCl3) δ 0.90 (3H, t, J = 7.4 Hz), 1.58 (2H, sextet, J =
130.0 (CH), 136.2 (Cq), 137.0 (CH), 144.6 (Cq), 158.8 (Cq), 195.7 7.4 Hz), 2.41 (3H, s), 2.69 (2H, s), 2.95 (2H, t, J = 7.4 Hz), 3.72 (3H,
(Cq); HRMS (ESI) m/z calcd for C17H19NNaO3S [M+Na]+ 340.0983, s), 4.07 (2H, s), 4.70 (1H, s), 4.81 (1H, s), 7.23 (2H, d, J = 8.6 Hz),
found 340.0987.
7.62 (2H, d, J = 8.6 Hz); 13C-NMR (100 MHz, CDCl3) δ 13.9 (CH3),
(3aS*,7aS*)-Methyl 2-methyl-1-tosyl-3a,4,5,7a-tetrahydro-1H- 21.5 (CH3), 21.9 (CH2), 31.2 (CH2), 34.9 (CH2), 51.7 (CH3), 52.7
indole-3-carboxylate (3q). Yield 81%; colorless plates (AcOEt, mp. (CH2), 110.9 (CH2), 120.4 (Cq), 127.5 (CH), 129.4 (CH), 136.5 (Cq),
1
112.2113.9 ºC); IR (neat) 1701, 1626, 1169, 1106 cm1; H-NMR
8 | Org. Biomol. Chem., 2013, 00, 1‐3
This journal is © The Royal Society of Chemistry 2013

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ARTICLE
138.6 (Cq), 143.8 (Cq), 151.0 (Cq), 167.8 (Cq); HRMS (ESI) m/z (Cq), 127.7 (CH), 128.8 (Cq), 129.1 (CH), 130.6 (CH), 136.6 (Cq),
calcd for C18H24NO4S [M+H]+ 350.1426, found 350.1424.
138.2 (Cq), 143.7 (Cq), 146.0 (Cq), 160.3 (Cq), 169.0 (Cq); HRMS
Methyl
2-isopropyl-5-methylene-1-tosyl-1,4,5,6- (ESI) m/z calcd for C22H23NNaO5S [M+Na]+ 436.1195, found
View Article Online
DOI: 10.1039/C3OB42510J
tetrahydropyridine-3-carboxylate (5j). Yield 75%; colorless plates 436.1194.
1
(AcOEt, mp. 81.983.2 ºC); IR (neat) 1718, 1352, 1165 cm1; H- 1-(2-Methyl-5-methylene-1-tosyl-1,4,5,6-tetrahydropyridin-3-
NMR (400 MHz, CDCl3) δ 1.26 (6H, d, J = 7.2 Hz), 2.402.41 (2H, yl)ethanone (5o). Yield 87%; pale yellow oil; IR (neat) 1684, 1351,
1
m), 2.46 (3H, s), 3.45 (1H, septet, J = 7.2 Hz), 3.74 (3H, s), 4.05 (2H, 1163 cm1; H-NMR (400 MHz, CDCl3) δ 2.23 (3H, s), 2.36 (3H, t,
s), 4.61 (1H, s), 4.79 (1H, s), 7.23 (2H, d, J = 8.0 Hz), 7.64 (2H, d, J J = 2.0 Hz), 2.42 (3H, s), 2.74 (2H, d, J = 2.0 Hz), 4.11 (2H, s), 4.77
= 8.0 Hz); 13C-NMR (100 MHz, CDCl3) δ 20.0 (CH3), 21.5 (CH3), (1H, s), 4.85 (1H, s), 7.25 (2H, d, J = 8.8 Hz), 7.62 (2H, d, J = 8.8
31.3 (CH2), 33.6 (CH), 51.8 (CH3), 53.3 (CH2), 110.4 (CH2), 124.7 Hz); 13C-NMR (100 MHz, CDCl3) δ 20.9 (CH3), 21.5 (CH3), 30.0
(Cq), 127.8 (CH), 129.3 (CH), 136.3 (Cq), 139.7 (Cq), 143.8 (Cq), (CH3), 31.7 (CH2), 52.0 (CH2), 111.3 (CH2), 126.9 (Cq), 127.3 (CH),
152.1 (Cq), 168.5 (Cq); HRMS (ESI) m/z calcd for C18H23NNaO4S 129.4 (CH), 136.6 (Cq), 137.6 (Cq), 142.7 (Cq), 143.9 (Cq), 201.0
[M+Na]+ 372.1245, found 372.1246.
(Cq); HRMS (ESI) m/z calcd for C16H19NO3S [M]+ 305.1086, found
Methyl 5-methylene-2-phenyl-1-tosyl-1,4,5,6- 305.1087.
tetrahydropyridine-3-carboxylate (5k). Yield 99%; colorless 3-Methylene-1-tosyl-1,2,3,4,7,8-hexahydroquinolin-5(6H)-one
plates (AcOEt, mp. 110.7111.1 ºC); IR (neat) 1707, 1360, 1168 (5p). Yield 91%; colorless plates (AcOEt, mp. 127.3129.5 ºC); IR
cm1; 1H-NMR (400 MHz, CDCl3) δ 2.40 (3H, s), 2.96 (2H, s), 3.40 (neat) 1659, 1361, 1164 cm1; 1H-NMR (400 MHz, CDCl3) δ
(3H, s), 4.30 (2H, s), 4.85 (1H, s), 4.93 (1H, s), 7.16 (2H, d, J = 8.2 1.901.96 (2H, m), 2.372.42 (5H, m), 2.852.88 (4H, m), 4.17 (2H,
Hz), 7.237.35 (5H, m), 7.39 (2H, d, J = 8.2 Hz); 13C-NMR (100 s), 4.87 (2H, s), 7.27 (2H, d, J = 8.2 Hz), 7.62 (2H, d, J = 8.2 Hz);
MHz, CDCl3) δ 21.5 (CH3), 31.8 (CH2), 51.5 (CH3), 52.7 (CH2), 13C-NMR (100 MHz, CDCl3) δ 21.6 (CH3), 22.1 (CH2), 28.4 (CH2),
112.0 (CH2), 120.5 (Cq), 127.5 (CH), 127.6 (CH), 129.0 (CH), 129.1 29.7 (CH2), 37.0 (CH2), 52.6 (CH2), 112.3 (CH2), 122.0 (Cq), 127.1
(CH), 129.2 (CH), 136.5 (Cq), 136.6 (Cq), 137.8 (Cq), 143.7 (Cq), (CH), 129.8 (CH), 136.5 (Cq), 144.4 (Cq), 154.2 (Cq), 197.6 (Cq);
146.0 (Cq), 168.8 (Cq); HRMS (ESI) m/z calcd for C21H21NNaO4S HRMS (ESI) m/z calcd for C17H19NNaO3S [M+Na]+ 340.0983,
[M+Na]+ 406.1089, found 406.1092.
found 340.0983.
Methyl
5-methylene-2-(p-tolyl)-1-tosyl-1,4,5,6-
tetrahydropyridine-3-carboxylate (5l). Yield 95%; colorless
needles (AcOEt, mp. 94.896.0 ºC); IR (neat) 1707, 1360, 1168
cm1; 1H-NMR (400 MHz, CDCl3) δ 2.36 (3H, s), 2.40 (3H, s), 2.92
(2H, s), 3.44 (3H, s), 4.28 (2H, s), 4.83 (1H, s), 4.92 (1H, s), 7.08
(2H, d, J = 8.2 Hz), 7.14 (2H, d, J = 8.4 Hz), 7.16 (2H, d, J = 8.4 Hz),
7.40 (2H, d, J = 8.2 Hz); 13C-NMR (100 MHz, CDCl3) δ 21.4 (CH3),
21.5 (CH3), 31.7 (CH2), 51.5 (CH3), 52.7 (CH2), 111.8 (CH2), 120.0
(Cq), 127.7 (CH), 128.3 (CH), 129.1 (CH), 129.1 (CH), 133.7 (Cq),
136.5 (Cq), 138.1 (Cq), 139.0 (Cq), 143.7 (Cq), 146.2 (Cq), 169.0
(Cq); HRMS (ESI) m/z calcd for C22H23NO4S [M]+ 397.1348, found
397.1350.
Acknowledgements
This study was supported in part by a Grant-in-Aid for
Scientific Technique Research Promotion Program for
Agriculture, Forestry, Fisheries and Food Industry from the
Ministry of Agriculture, Forestry and Fisheries.
Notes and references
Graduate School of Pharmaceutical Sciences, The University of
Tokushima, 1-78-1 Sho-machi, Tokushima 770-8505, Japan. E-mail:
yoshi@tokushima-u.ac.jp
1
†
Electronic Supplementary Information (ESI) available: Copies of H
Methyl
2-(4-fluorophenyl)-5-methylene-1-tosyl-1,4,5,6-
and 13C NMR spectra for all new compounds. See DOI:
tetrahydropyridine-3-carboxylate (5m). Yield 94%.; colorless
needles (AcOEt/Hexane, mp. 87.088.7 ºC); IR (neat) 1716, 1507,
10.1039/b000000x/
1
1361, 1168 cm1; H-NMR (400 MHz, CDCl3) δ 2.41 (3H, s), 2.97
1
(a) L. H. J. Hurley, Antibiot., 1977, 30, 349; (b) L. H. Hurley and D.
E. Thurston, Pharm. Res., 1984, 52; (c) J. D. Leber, J. R. E. Hoover,
K. G. Holden, R. K. Johnson, S. M. Hecht, J. Am. Chem. Soc., 1988,
110, 2992; (d) W. Li, A. Khullar, S. Chou, A. Sacramo, B.
Gerratana, Appl. Environ. Microbiol., 2009, 75, 2869; (e) I. V.
Magedov, G. Luchetti, N. M. Evdokimov, M. Manpadi, W. F. A.
Steelant, S. Van slambrouk, P. Tongwa, M. Y. Antipin, A.
Kornienko, Bioorg. Med. Chem. Lett., 2008, 18, 1392.
(2H, s), 3.44 (3H, s), 4.29 (2H, s), 4.87 (1H, s), 4.95 (1H, s),
6.936.98 (2H, m), 7.177.22 (4H, m), 7.38 (2H, d, J = 8.4 Hz); 13C-
NMR (100 MHz, CDCl3) δ 21.5 (CH3), 31.8 (CH2), 51.6 (CH3), 52.6
(CH2), 112.1 (CH2), 114.6 (CH, d, J = 21.7 Hz), 120.3 (Cq), 127.6
(CH), 129.3 (CH), 131.0 (CH, d, J = 8.3 Hz), 132.5 (Cq), 136.6 (Cq),
137.7 (Cq), 143.9 (Cq), 145.1 (Cq), 163.1 (Cq, d, J = 247.0 Hz),
168.6 (Cq); HRMS (ESI) m/z calcd for C21H20NO4FNaS [M+Na]+
424.0995, found 424.0998.
2
(a) J. W. Daly
2005 68 1556; (b) J. P. Michael, Nat. Prod. Rep., 2008
M. W. Whitehouse, Curr. Med. Chem., 2005 12 2931; (d) J. P.
Michael in The Alkaloids, Vol. 55 (Ed.: G. A. Cordell), Academic
Press, San Diego 2001; (e) D. L. Comins and S. P. Joseph in
Advances in Nitrogen Heterocycles, Vol. 2 (Ed.: C. J. Moody), JAI,
Greenwich 1996, pp. 251 294
,
T. F. Spande, and H. M. Garraffo, J. Nat. Prod.
,
Methyl
2-(4-methoxyphenyl)-5-methylene-1-tosyl-1,4,5,6-
,
,
,
25, 139; (c)
tetrahydropyridine-3-carboxylate (5n). Yield 96%; colorless
needles (AcOEt, mp. 135.9138.3 ºC); IR (neat) 1704, 1358, 1251,
1168 cm1; 1H-NMR (400 MHz, CDCl3) δ 3.40 (3H, s), 2.93 (2H, s),
3.44 (3H, s), 3.82 (3H, s), 4.29 (2H, s), 4.85 (1H, s), 4.94 (1H, s),
6.79 (2H, d, J = 8.8 Hz), 7.17 (4H, d, J = 8.8 Hz), 7.39 (2H, d, J =
8.0 Hz); 13C-NMR (100 MHz, CDCl3) δ 21.5 (CH3), 31.7 (CH2),
51.5 (CH3), 52.7 (CH2), 55.1 (CH3), 111.8 (CH2), 113.0 (CH), 119.3
,
,
,
,
–
.
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Org. Biomol. Chem., 2013, 00, 1‐3 | 9

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9
Representative examples about the reactions using 2-methylene-1,3-
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696; (h) N. Gigant and I. Gillaizeau, Org. Lett., 2012, 14, 4622.
,
propanediol diester, see: (a) Y. Huang and X. Lu, Tetrahedron Lett.
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29 5663; (c) D. Gravel, S. Benoit, S. Kumanovîc and H.
,
4
5
(a) D. L. Comins, J. Heterocycl. Chem., 1999
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6793
,
36
,
1491; (b) M. J.
,
,
,
75
,
Sivaramakrishnan, Tetrahedron Lett., 1992, 33, 1403; (d) D. Gravel,
S. Benoit, S. Kumanovîc and H. Sivaramakrishnan, Tetrahedron
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Aagaard and M. McKinney, J. Chem. Soc., Chem. Commun., 1993,
860; (f) G. Campiani, L. Q. Sun, A. P. Kozikowski, P. Aagaard and
M. McKinney, J. Org. Chem., 1993, 58, 7660; (g) C. Jorand-Lebrun,
L. Fensterbank and M. Malacria, Tetrahedron Lett., 1995, 36, 1407;
(h) S. Kaneko, T. Yoshino, T. Katoh and S. Terashima, Tetrahedron
.
For selected examples of dihydropyrrole synthesis, see: (a) P. A.
Wender and D. Strand, J. Am. Chem. Soc., 2009, 131, 7528; (b) R.
A. Brawn and J. S. Panel, Org. Lett., 2009, 11, 473; (c) D. Monge,
K. L. Jensen, P. T. Franke, L. Lykke and K. A. Jørgensen, Chem.–
Eur. J., 2010, 16, 9478; (d) G. Zhang, Y. Zhang, X. Jiang, W. Yan
and R. Wang, Org. Lett., 2011, 13, 3806; (e) C.-R. Liu, B.-H. Zhu,
J.-C. Zheng, X.-L. Sun, Z. Xie and Y. Tang, Chem. Commun., 2011,
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Catal., 2011, 353, 1676; (g) J. Tian, R. Zhou, H. Sun, H. Song, Z.
He, J. Org. Chem., 2011, 76, 2374; (h) L. A. Polindara-García, L. D.
Asym., 1997, 8, 829; (i) X.-C. He, B. Wang and D. Bai, Tetrahedron
Lett., 1998, 39, 411; (j) F. Buono, A. Tenaglia, J. Org. Chem., 2000,
65, 3869; (k) C. Damez, J.-R. Labrosse, P. Lhoste, D. Sinou,
Synthesis, 2001, 1456.
Miranda, Org. Lett., 2012, 14, 5408; (i) M. K. Ghorai, D. P. Tiwari, 10 (a) M. Yoshida, M. Higuchi and K. Shishido, Tetrahedron Lett.
,
J. Org. Chem., 2013, 78, 2617; (j) T. Miura, T. Tanaka, K. Hiraga, S.
G. Stewart, M. Murakami, J. Am. Chem. Soc., 2013, 135, 13652.
For reviews, see: (a) J.-C. Quirion, in Science of Synthesis, Georg
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Lett., 2009, 11, 4752; (c) M. Yoshida, M. Higuchi and K. Shishido,
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Shishido, Chem. Eur. J., 2012, 18, 1604; (f) M. Yoshida, Chem.
Pharm. Bull. 2012, 60, 285; (g) M. Yoshida, T. Nakagawa, K.
Kinoshita, K. Shishido, J. Org. Chem., 2013, 78, 1687; (h) M.
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6
Thieme Verlag. 2006, pp, 629
–656; (b) J. P. Wan and Y. Liu, RSC
Adv., 2012, , 9763. For selected examples of tetrahydropyridine
2
synthesis, see: (c) M. Rueping and A. P. Antonchick, Angew. Chem.
Int. Ed., 2008, 47, 5836; (d) H. Guo, Q. Xu, O. Kwon, J. Am. Chem.
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Bergman and J. A. Ellman, J. Am. Chem. Soc., 2012, 134, 4064; (g)
D. M. Barber, H. J. Sanganee and D. J. Dixon, Org. Lett., 2012, 14
enamino esters, but no reactions proceeded in these cases.
,
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and M.-X. Wang, Chem. Eur. J., 2013, 19, 16981.
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(a) J. Tsuji, Palladium Reagents and Catalysts: New Perspectives
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8
Recent examples about the reactions using 1,4-diacyloxy-2-butene,
see: (a) M. Massacret, R. Lakhmiri, P. Lhoste, C. Nguefack, F. B. B.
Abdelouahab, R. Fadel and D. Sinou, Tetrahedron Asymm., 2000,
11, 3561; (b) S. Tanimori and M. Kirihata, Tetrahedron Lett., 2000,
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Int. Ed., 2001, 40, 1932; (d) H. Nakano, J. Yokoyama, R. Fujita and
H. Hongo, Tetrahedron Lett., 2002, 43, 7761; (e) S.-C. Yang, Y.-J.
Shue and P.-C. Liu, Organometallics, 2002, 21, 2013; (f) K. Ito, Y.
Imahayashi, T. Kuroda, S. Eno, B. Saito and T. Katsuki,
10 | Org. Biomol. Chem., 2013, 00, 1‐3
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