Three components synthesis of homoallylic amines catalyzed by bismuth(III) nitrate pentahydrate

Article abstract of DOI:10.1016/j.tet.2009.05.010

Bismuth (III) nitrate pentahydrate catalyzes efficiently the three-component condensation of aldehydes, amines, and allyltributylstannane at rt to afford the corresponding homoallylic amines in excellent yield.

Full text of DOI:10.1016/j.tet.2009.05.010

Tetrahedron 65 (2009) 5168–5173
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Three components synthesis of homoallylic amines catalyzed
by bismuth(III) nitrate pentahydrate
*
Ponnaboina Thirupathi, Sung Soo Kim
Department of Chemistry, Inha University, Incheon 402-751, South Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 3 April 2009
Received in revised form 6 May 2009
Accepted 6 May 2009
Bismuth (III) nitrate pentahydrate catalyzes efficiently the three-component condensation of aldehydes,
amines, and allyltributylstannane at rt to afford the corresponding homoallylic amines in excellent yield.
Ó 2009 Elsevier Ltd. All rights reserved.
Available online 9 May 2009
Keywords:
Bismuth(III) nitrate pentahydrate
Aldehyde
Amine
Allyltributylstannane
Homoallylic amines
1. Introduction
as a very effective catalyst for various organic transformations7
because of inexpensive and oxygen/moisture tolerant nature. In
Homoallylic amines are important fundamental building blocks
for the synthesis of many nitrogen containing natural products1
and biologically or synthetically active compounds.2 Moreover, N-
aryl homoallylic amines show potent antifungal activity3 and hence
the syntheses of these compounds are highly useful. Nucleophilic
addition of allylic organometallic (Si, Sn, Ge) reagents4 to imines in
the presence of catalyst is straightforward method for the synthesis
of homoallylic amines. In recent years the Lewis acids such as
continuation of work on the development of useful synthetic
methodologies,8 we report herein a three-component synthesis of
homoallylic amines using Bi(NO3)3$5H2O as the catalyst (Eq. 1).
2. Results and discussions
Several parameters including catalyst and its amount, allylating
source, solvent, and temperature were optimized, which are sum-
marized in Table 1. Several Lewis acids (bismuth, rhodium, ruthe-
nium, and thallium salts) were screened and bismuth nitrate
pentahydrate [Bi(NO3)3$5H2O] and thallium nitrate trihydrate
[Tl(NO3)3$3H2O] were proved suitable catalysts (Table 1).
Bi(NO3)3$5H2O is the better catalyst because of non-toxicity. To
a mixture of benzaldehyde (1 mmol), p-anisidine (1 mmol), and
Bi(NO3)3$5H2O (10 mol % based on the amount of benzaldehyde) in
CH2Cl2 at rt the allyltributylstannane (1 mmol) was added. The
reaction was monitored by TLC. After 2 h of reaction time, the yield
of the homoallylic amine has been found to give 73% yield. The
remarkable improvement of the reaction yield (92%) was observed
by changing the ratio reactants, benzaldehyde (1 mmol), p-anisi-
dine (1.5 mmol), and allyltributylstannane (1.2 mmol).9a Allyl-
trimethylsilane and allyltributylstannane were also examined for
the allylation reaction as allylating source. The allyltributyl-
stannane is more effective allyl source compared to allyl-
trimethylsilane in terms of reaction time and yield. Furthermore
TiCl4,5a BF3$OEt2,5a PdCl2(Ph3P)2/PtCl2(Ph3P)2,5b bis-
p-allyl palla-
dium complex,5c Yb(OTf)3,5d Sc(OTf)3,5e LiClO4,5f TaCl5,5g
ZrOCl2$8H2O,5h and CuI5i have been employed for this purpose.5
The solid catalysts such as sulfamic acid and PMA$SiO2 were also
used.6
Some of the reactions were carried out in one-pot operation
with poor yields because water formed during the imine formation
can decompose or deactivate the Lewis acid.5a,b Other methods
have involved the use of strong acidic condition5a,d,e and extended
reaction time.5b,e,f,h,i Several lanthanide triflates were used as cat-
-
alysts that is however strongly acidic and highly expensive.5d,e
Therefore, the development of less expensive and high yielding
catalytic method is desired. Recently, Bi(NO3)3$5H2O has emerged
* Corresponding author. Tel.: þ82 32 860 7678; fax: þ82 32 867 5604.
E-mail address: sungsoo@inha.ac.kr (S.S. Kim).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.05.010

P. Thirupathi, S.S. Kim / Tetrahedron 65 (2009) 5168–5173
5169
OCH3
O
Catalyst
NH2
HN
H
+
X
+
Solvent
r. t.
H3CO
(1)
1
2
3A & 3B
4
X=SiMe3= A
X=SnBu3= B
Table 1
containing electron-donating substituents in the aromatic ring
afford the reaction products in excellent yield (entries 2–4).
The reactions of o, m, and p-chlorobenzaldehydes with p-
ansidine give corresponding homoallylic amines in 83, 91, and
87% yield, respectively (entries 6–8). o-Chloro isomer indicates
slight steric effect that is responsible for the less yield. The
reaction of aldehydes containing electron-withdrawing group
such as NO2, CN at m or p-position in aromatic ring with p-
ansidine gave no reaction products at all. This indicates that
strongly electron-withdrawing group hardly induces the re-
action at all (entries 10–12). The acid sensitive heteroaromatic
aldehydes such as 2-furaladehyde, 2-thiophenaldehyde, 2-pyr-
idinecarboxaldehyde, and cinnamaldehyde react with p-ansi-
dine to offer the corresponding homoallylic amines in
considerably good yield (entries 14–16). The reaction of
cyclohexane carboxaldehyde and butaraldehyde gives the cor-
responding products in 80 and 60%, respectively (entries 18
and 19).
We extend our studies of synthesis of other homoallylic
amines by allylation of benzaldimines (benzaldehyde and
various amines) with allyltributylstannane (Eq. 3 and Table 3).
The results are summarized in Table 3, which show that ar-
omatic amines containing electron-donating substituents af-
ford the corresponding homoallylic amines in good yields
(entries 2–4). The reactions of 4-chloro- and 4-fluoroaniline
with benzaldehyde afford the corresponding homoallylic
amines in 85 and 87%, respectively (entries 5 and 6). Under
similar reaction condition the reaction of sterically hindered
2,6-diisopropyl aniline, 2-aminopyridine, cyclohexylamine,
benzylamine or benzyl carbamate rarely produce desired
products at all.
Synthesis of homoallylic amines from benzaldehyde and p-ansidine under various
reaction conditionsa
Entry Catalyst
Allyl sourceb Catalyst amountc Solvent Reaction Isolated
time (h) yieldd (%)
1
2
d
A
A
B
B
A
B
B
A
d
CH2Cl2
d
NR
<25
42
NR
75
Bi(OTf)3
10.0
10.0
10.0
10.0
10.0
10.0
10.0
10.0
10.0
5.0
10.0
10.0
10.0
10.0
10.0
5.0
CH2Cl2 6.0
CH2Cl2 5.0
CH2Cl2 7.0
CH2Cl2 3.0
3.0
CH2Cl2 3.5
5.0
CH2Cl2 2.0
1.5
3
4
Bi2O3
BiBr3
81
80
5
6
BiCl3
68
Bi(NO3)3$5H2O B
73e
90
B
B
1.5
87
7
RhI3$H2O
B
B
B
A
B
B
B
CH2Cl2 6.0
CH2Cl2 7.0
CH2Cl2 2.5
CH2Cl2 1.5
CH2Cl2 1.5
CH2Cl2 1.5
CH3CN 1.5
3.5
NRf
NR
80
8
Ru(acac)3
9
10
TlCl3$3H2O
Tl(NO3)3$3H2O
76
90
84
92
12
13
Bi(NO3)3$5H2O
5.0
2.0
68
Bi(NO3)3$5H2O B
3.0
4.0
CH3CN 3.0
1.5
82
90
CHCl3 5.0
MeOH 5.0
57
NRf
Trace
NRf
24
14
Bi(NO3)3$5H2O B
5.0
EtOH
H2O
6.0
6.0
3.0
Neat
a
Benzaldehyde (1 mmol), 1.5 mmol of p-anisidine, and 1.2 mmol of allyl-
tributylstannane were used.
b
The allyl source, A is allyltrimethylsilane and B is allyltributylstannane.
The amount of catalyst was used with respect to aldehyde.
Isolated yields after chromatography purification.
Benzaldehyde (1 mmol), 1.0 mmol of p-anisidine, and 1.0 mmol of allyl-
c
d
e
The generality and the excellence of Bi(NO3)3$5H2O in terms of
the catalyst loading, allylating source, reaction time, and yield can
be easily clarified from the comparison of the data with the liter-
ature results as is shown in Table 4.
tributylstannane were used.
f
Only formation of imines was observed.
the synthesis of homoallylic amines has also been reported with
allyltributylstannane.5,6 The effect of various solvents such as
CH2Cl2, CHCl3, MeOH, EtOH, H2O, CH3CN, and solvent-free condi-
tion has been studied. CH3CN is found to be the solvent of choice in
terms of yield and reaction time (Table 1).
A variety of aldehydes and p-ansidine were coupled with
allyltributylstannane in CH3CN at rt so as to give the desired
products in excellent yield (Eq. 2 and Table 2). The aldehydes
3. Summary
A convenient method for the synthesis of homoallylic amines
through three-component coupling reaction has been described.
The major advantages of the method are that operational simplicity
and low catalyst loading at rt.
OCH3
Bi(NO3)3.5H2O
5 mol%
NH2
HN
O
ð2Þ
+
SnBu3
+
CH3CN
R
R
H
H3CO
r.t.
3B
6
5
2

5170
P. Thirupathi, S.S. Kim / Tetrahedron 65 (2009) 5168–5173
Table 2
Table 2 (continued)
Bismuth(III) nitrate pentahydrate catalyzed synthesis of homoallylic amines with
different aldehydesa,b
Product
Reaction
time (h)
Entry
RCHO
Isolated
yieldsc (%)
Entry
RCHO
Product
Reaction Isolated
time (h) yieldsc (%)
O
10
d6j
3.0
NRd
OCH3
H
O
NC
1
1.5
1.5
92
90
HN
H
O
O
11
12
d6k
d6l
3.0
NRd
H
6a
OCH3
O2N
O
2
HN
3.0
1.5
NRd
H
H
O
H3C
H3C
6b
OCH3
NO2
OCH3
13
14
90
O
HN
HN
H
H
3
1.5
90
6m
OCH3
CH3
6c
CH3
2.0
2.0
85
88
OCH3
HN
H
H
O
O
O
HN
O
6n
H
O
4
5
6
1.5
1.5
1.5
83
87
87
OCH3
15
OPh
HN
6d
OPh
S
OCH3
O
O
S
6o
HN
H
OCH3
N
16
17
2.0
2.0
90
81
H
O
HN
6e
N
OCH3
6p
OCH3
O
HN
H
Cl
HN
H
6f
OCH3
Cl
6q
O
HN
OCH3
O
O
H
H
18
1.5
2.0
80
60
7
8
2.0
2.0
91
83
HN
HN
H
H
Cl
6g
Cl
6r
OCH3
OCH3
O
19
HN
6s
Cl
O
a
6h
Aldehyde (1 mmol), 1.5 mmol of p-anisidine, and 1.2 mmol of allyltributyl-
Cl
stannane were used.
OCH3
The structures of the products were settled from spectral (1H, 13C NMR, MS) data.
b
The spectral data (1H, 13C NMR, and MS) of the compounds are compared with the
literature values.
HN
c
H
Isolated yields after chromatography purification.
9
1.5
88
d
In case of the imine containing electron-withdrawing substituents (p-NO2, m-
NO2, and p-CN), allyltributylstannane reacts with aldehyde to give homoallylic al-
cohol instead of forming the homoallylic amines between the reaction of the imine
and the allyltributylstannane.
F
6i
F

P. Thirupathi, S.S. Kim / Tetrahedron 65 (2009) 5168–5173
5171
Bi(NO3)3.5H2O
10 mol%
O
R
HN
NH2
H
ð3Þ
+
SnBu3
+
CH3CN
R
r.t.
1
7
8
3B
Table 3
Table 4
Bismuth(III) nitrate pentahydrate catalyzed synthesis of homoallylic amines with
different aminesa,b
Bi(NO3)3$5H2O catalyzed synthesis of N-(1-phenylbut-3-enyl)aniline (8a) in com-
parison with other literatures
Entry
Amine
Product
Reaction
time (h)
Isolated
Entry Catalyst/equiv
Allyltributyl Reaction
stannane
(equiv)
Reaction Isolated Reference
(%)
yieldsc (%)
temperature time (h) yielda,b
1
2
3
4
5
BF3$OEt2/1.0
TiCl4/1.0
PdCl2(PPh3)2/0.1
PtCl2(PPh3)2/0.1
Bis-allylpalladium 1.2
complex/0.05
Yb(OTf)3/0.2
Sc(OTf)3/0.2
and SDS/0.2
LiClO4/0.2
2.0
2.0
1.0
1.0
ꢀ78 ꢁ
ꢀ78 ꢁ
rt
rt
0
C
C
2.5
2.5
4 days
4 days
20
73
53
64
90
70
5a
5a
5b
5b
5c
HN
NH2
1
2.0
3.0
91
87
8a
6
7
1.0
1.5
ꢀ45 ꢁ
C
C
12
20
81
83
5d
5e
H3C
HN
rt
NH2
CH3
2
3
8
9
10
11
12
1.0
2.0
rt
3.0
3.0
5.0
1.0
2.0
90
92
87
90
91
5f
5g
5h
6a
Present
method
TaCl5/1.0
ꢀ78 ꢁ
ZrOCl2$8H2O/0.2 1.2
Sulfamic acid/0.05 1.2
Bi(NO3)3$5H2O/0.1 1.2
60 ꢁ
rt
C
8b
rt
HO
HN
a
Isolated yields after chromatography purification.
Other substrates have also shown similar trend of the yield.
b
3.0
90
NH2
OH
8c
4. Experimental
CH3
4.1. General methods
NH2
4
3.0
90
In all the cases the 1H NMR spectra were recorded with Varian
Gemini 200 or 400 MHz instrument. Chemical shifts are reported in
parts per million in CDCl3 with tetramethylsilane as an internal
standard. 13C NMR data were collected on Varian Gemini 200 or
400 MHz instrument (50 or 100 MHz). Compounds have been also
identified by HRMS (EI) with Jeol DMX 303.
HN
CH3
8d
Cl
5
6
3.0
3.0
85
87
NH2
HN
Cl
F
4.2. General experimental procedure
8e
To a mixture of aldehyde (1 mmol) and amine (1.5 mmol) in
acetonitrile (2 mL) was added bismuth(III) nitrate pentahydrate (5–
10 mol %) that was stirred for 5 min at rt. Then allyltributylstannane
(1.2 mmol) was added that was stirred at rt. The progress of the
reaction mixture was monitored by TLC. After completion of the
reaction, the mixture was filtered. The filtrate was concentrated
and the viscous mass was subjected to silica gel column chroma-
tography using 0.5% EtOAc in n-hexane as eluent.
F
NH2
HN
8f
NH2
7
3.0
89
4.3. The spectral data of the products
HN
4.3.1. 4-Methoxy-N-(1-phenylbut-3-enyl)aniline (6a)
8g
Yellow viscous mass; 1H NMR (CDCl3, 200 MHz):
d 7.38–7.16 (5H,
a
Benzaldehyde (1 mmol), 1.5 mmol of amines, and 1.2 mmols of allyltributyl-
stannane were used.
m), 6.67 (2H, d, J¼8.8 Hz), 6.44 (2H, d, J¼8.8 Hz), 5.82–5.71 (1H, m),
5.20–5.10 (2H, m), 4.28 (1H, dd, J¼8.0, 4.6 Hz), 3.91 (1H, br s), 3.66
b
The structures of the products were settled from spectral (1H, 13C NMR, MS) data.
(3H, s), 2.60–2.40 (2H, m); 13C NMR (CDCl3, 100 MHz)
d 151.9, 143.7,
The spectral data (1H, 13C NMR, and MS) of the compounds are compared with the
literature values.
141.5, 134.7, 128.5, 126.9, 126.3, 118.1, 114.6, 114.5, 57.9, 55.6, 43.3.
Isolated yields after chromatography purification.
Analytical data are consistent with reported literature values.9a
c

5172
P. Thirupathi, S.S. Kim / Tetrahedron 65 (2009) 5168–5173
4.3.2. 4-Methoxy-N-(1-p-tolylbut-3-enyl)aniline (6b)
114.0, 113.7, 55.0, 53.4, 40.1; HRMS-EI (m/z): [M]þ calcd for
C17H18NClO: 287.1076, found: 287.1078.
Light yellow viscous mass; 1H NMR (CDCl3, 400 MHz):
d
7.21
(2H, d, J¼8.4 Hz), 7.07 (2H, d, J¼8.4 Hz), 6.65 (2H, d, J¼8.9 Hz), 6.41
(2H, d, J¼8.9 Hz), 5.79–5.69 (1H, m), 5.18–5.09 (2H, m), 4.24 (1H, dd,
J¼8.2, 4.8 Hz), 3.94 (1H, br s), 3.67 (3H, s), 2.59–2.55 (1H, m), 2.53–
4.3.9. N-(1-(3-Fluorophenyl)but-3-enyl)-4-methoxyaniline (6i)
Brown viscous mass; 1H NMR (CDCl3, 400 MHz):
d 7.28–7.22
2.41 (1H, m), 2.29 (3H, s); 13C NMR (CDCl3, 100 MHz)
d
152.0, 141.5,
(1H, m), 7.12 (1H, d, J¼8.0 Hz), 7.06 (1H, dd, J¼8.0, 1.2 Hz), 6.89 (1H,
td, J¼8.5, 4.5 Hz), 6.66 (2H, d, J¼8.8 Hz), 6.42 (2H, d, J¼8.8 Hz),
5.78–5.68 (1H, m), 5.19–5.10 (2H, m), 4.26 (1H, dd, J¼8.4, 4.1 Hz),
3.67 (3H, s), 2.58–2.51 (1H, m), 2.49–2.41 (1H, m); 13C NMR (CDCl3,
140.7, 136.1, 134.9, 129.2, 126.2, 118.0, 114.7, 114.6, 96.2, 57.7, 43.4,
21.1; HRMS-EI (m/z): [M]þ calcd for C18H21NO: 267.1623, found:
267.1624.
100 MHz) d 165.6, 152.1, 146.9, 146.8, 141.2, 134.3, 130.1, 129.9, 121.9,
4.3.3. 4-Methoxy-N-(1-m-tolylbut-3-enyl)aniline (6c)
118.6, 114.7, 114.6, 57.5, 55.7, 43.2; HRMS-EI (m/z): [M]þ calcd for
C17H18NFO: 271.1372, found: 271.1378.
Light yellow viscous mass; 1H NMR (CDCl3, 400 MHz):
d
7.23–7.16 (3H, m), 7.05 (1H, d, J¼8.5 Hz), 6.70 (2H, d, J¼8.7 Hz),
6.48 (2H, d, J¼8.7 Hz), 5.74–5.72 (1H, m), 5.21–5.13 (2H, m), 4.28
(1H, dd, J¼8.0, 4.5 Hz), 3.97 (1H, br s), 3.85 (3H, s), 2.63–2.58 (1H,
m), 2.54–2.42 (1H, m), 2.38 (3H, s); 13C NMR (CDCl3, 100 MHz)
4.3.10. 4-Methoxy-N-(1-(naphthalene-2-yl)but-3-enyl)aniline (6m)
Brown viscous mass; 1H NMR (CDCl3, 200 MHz):
d 7.82–7.64
(4H, m), 7.52–7.37 (3H, m), 6.64 (2H, d, J¼8.6 Hz), 6.44 (2H, d,
J¼8.6 Hz), 5.82–5.65 (1H, m), 5.22–5.11 (2H, m), 4.40 (1H, dd, J¼8.0,
5.0 Hz), 3.99 (1H, br s), 3.62 (3H, s), 2.72–239 (2H, m); 13C NMR
d
151.9, 143.8, 141.7, 138.1, 134.9, 128.4, 127.7, 126.9, 123.4, 118.1,
114.7, 114.6, 57.9, 55.7, 43.4, 21.5; HRMS-EI (m/z): [M]þ calcd for
C18H21NO: 267.1623, found: 267.1624.
(CDCl3, 100 MHz) d 152.0, 141.6, 141.3, 134.7, 133.5, 132.7, 128.3,
127.8, 127.6, 125.9, 125.4, 124.9, 124.7, 118.3, 114.7, 114.6, 58.1, 55.6,
43.3. Analytical data are consistent with reported literature
values.9a
4.3.4. 4-Methoxy-N-(1-(3-phenoxyphenyl)but-3-enyl)aniline (6d)
Colorless viscous mass; 1H NMR (CDCl3, 400 MHz):
d 7.33–7.21
(3H, m), 7.12–7.04 (3H, m), 6.95 (2H, d, J¼8.4 Hz), 6.85 (1H, dd,
J¼8.4, 1.5 Hz), 6.67 (2H, d, J¼8.7 Hz), 6.43 (2H, d, J¼8.7 Hz),
5.81–5.68 (1H, m), 5.20–5.10 (2H, m), 4.27 (1H, dd, J¼8.0, 4.0 Hz),
3.68 (3H, s), 2.60–2.52 (1H, m), 2.47–2.42 (1H, m); 13C NMR (CDCl3,
4.3.11. N-(1-(Furan-2-yl)but-3-enyl)-4-methoxyaniline (6n)
Yellow viscous mass; 1H NMR (CDCl3, 200 MHz):
d 7.34–7.32
(1H, m), 6.73 (2H, d, J¼9.0 Hz), 6.56 (2H, d, J¼9.0 Hz), 6.26 (1H, dd,
J¼3.5, 2.0 Hz), 6.15 (1H, dd, J¼3.5, 2.0 Hz), 5.81–5.68 (1H, m), 5.18–
5.07 (2H, m), 4.41 (1H, dd, J¼8.0, 4.5 Hz), 3.71 (3H, s), 2.63–2.46 (2H,
100 MHz) d 175.9,157.2,152.0,146.0,141.2,134.5,129.8,129.6,123.0,
121.3, 118.5, 118.3, 117.3, 117.0, 114.7, 114.6, 57.7, 55.7, 43.1; HRMS-EI
(m/z): [M]þ calcd for C23H23NO2: 345.1728, found: 345.1721.
m); 13C NMR (CDCl3, 100 MHz)
d 156.5, 152.9, 142.0, 141.7, 134.7,
118.9, 115.7, 115.3, 110.7, 106.7, 56.3, 52.9, 39.9. Analytical data are
4.3.5. N-(1-(4-tert-Butylphenyl)but-3-enyl)-4-methoxyaniline (6e)
consistent with reported literature values.9a
Colorless viscous mass; 1H NMR (CDCl3, 400 MHz):
d 7.36 (2H, d,
J¼8.0 Hz), 7. 29 (2H, d, J¼8.0 Hz), 6.71 (2H, d, J¼8.7 Hz), 6.50 (2H, d,
J¼8.7 Hz), 5.83–5.76 (1H, m), 5.21–5.14 (2H, m), 4.31 (1H, dd, J¼8.4,
4.8 Hz), 3.84 (1H, br s), 3.71 (3H, s), 2.65–2.58 (1H, m), 2.53–2.47
4.3.12. 4-Methoxy-N-(1-(thiophen-2-yl)but-3-enyl)aniline (6o)
Brown viscous mass; 1H NMR (CDCl3, 400 MHz):
d 7.17 (1H, d,
J¼5.0 Hz), 6.98–6.93 (2H, m), 6.73 (2H, d, J¼8.8 Hz), 6.57 (2H, d,
J¼8.8 Hz), 5.86–5.78 (1H, m), 5.24–5.16 (2H, m), 4.64 (1H, dd, J¼8.0,
4.5 Hz), 3.87 (1H, br s), 3.76 (3H, s), 2.76–2.60 (2H, m); 13C NMR
(1H, m), 1.37 (9H, s); 13C NMR (CDCl3, 100 MHz)
d 151.8, 149.6, 141.8,
140.6, 135.0, 125.9, 125.4, 118.0, 114.7, 114.6, 57.5, 55.7, 43.3, 31.4,
15.3; HRMS-EI (m/z): [M]þ calcd for C21H27NO: 309.2092, found:
309.2092.
(CDCl3, 100 MHz)
d 152.4, 149.0, 141.2, 134.1, 126.7, 123.7, 123.3,
118.6, 115.0, 114.6, 55.6, 54.3, 43.2; HRMS-EI (m/z): [M]þ calcd for
C15H17NOS: 259.1030, found: 259.1027.
4.3.6. N-(1-(4-Chlorophenyl)but-3-enyl)-4-methoxyaniline (6f)
Yellow viscous mass; 1H NMR (CDCl3, 200 MHz):
d
7.30–7.21
4.3.13. 4-Methoxy-N-(1-(pyridine-2-yl)but-3-enyl)aniline (6p)
(4H, m), 6.67 (2H, d, J¼9.0 Hz), 6.41 (2H, d, J¼9.0 Hz), 5.80–5.63 (1H,
Yellow viscous mass; 1H NMR (CDCl3, 400 MHz):
d 8.59 (1H, d,
m), 5.20–5.11 (2H, m), 4.23 (1H, dd, J¼8.2, 5.0 Hz), 3.87 (1H, br s),
J¼6.5 Hz), 7.60 (1H, m), 7.35 (1H, d, J¼8.0 Hz), 7.12 (1H, m), 6.70 (2H,
d, J¼8.9 Hz), 6.50 (2H, d, J¼8.9 Hz), 5.82–5.69 (1H, m), 5.18–5.09
(2H, m), 4.46 (1H, dd, J¼8.2, 4.6 Hz), 4.20 (1H, br s), 3.68 (3H, s),
2.73–2.66 (1H, m), 2.56–2.50 (1H, m); 13C NMR (CDCl3, 100 MHz)
3.67 (3H, s), 2.60–2.33 (2H, m); 13C NMR (CDCl3, 100 MHz)
d 152.1,
142.3, 141.2, 134.3, 132.4, 128.7, 127.7, 118.5, 114.7, 114.6, 57.3, 55.6,
43.2. Analytical data are consistent with reported literature
values.9a
d
162.7, 152.0, 149.3, 141.3, 136.6, 134.6, 121.9, 120.9, 118.2, 114.7,
114.6, 59.3, 55.6, 41.3; HRMS-EI (m/z): [M]þ calcd for C16H18N2O:
4.3.7. N-(1-(3-Chlorophenyl)but-3-enyl)-4-methoxyaniline (6g)
254.1419, found: 254.1401.
Yellow viscous mass; 1H NMR (CDCl3, 400 MHz):
d 7.40 (1H, d,
J¼1.5 Hz), 7.28 (1H, dd, J¼8.0, 1.5 Hz), 7.26–7.20 (2H, m), 6.71 (2H, d,
J¼8.8 Hz), 6.45 (2H, d, J¼8.8 Hz), 5.80–5.62 (1H, m), 5.23–5.15 (2H,
m), 4.29 (1H, dd, J¼8.6, 4.8 Hz), 3.90 (1H, br s), 3.69 (3H, s),
2.62–2.57 (1H, m), 2.55–2.44 (1H, m); 13C NMR (CDCl3, 100 MHz)
4.3.14. (E)-4-Methoxy-N-(1-phenylhexa-1,5-dien-3yl)aniline (6q)
Light yellowviscous mass; 1H NMR (CDCl3, 400 MHz):
d 7.38–7.16
(5H, m), 6.75 (1H, d, J¼9.0 Hz), 6.65–6.53 (3H, m), 6.18 (1H, dd,
J¼15.8, 6.0 Hz), 5.91–5.78 (1H, m), 5.22–5.10 (2H, m), 4.26 (1H, dd,
J¼8.2, 4.6 Hz), 3.72 (3H, s), 2.58–2.51 (1H, m), 2.48–2.41 (1H, m).
Analytical data are consistent with reported literature values.9a
d
152.0, 146.3, 141.2, 134.3, 134.2, 129.8, 127.1, 126.4, 124.5, 118.6,
114.6, 114.5, 57.5, 55.6, 43.2; HRMS-EI (m/z): [M]þ calcd for
C17H18NClO: 287.1076, found: 287.1080.
4.3.15. N-(1-Cyclohexylbut-3-enyl)-4-methoxyaniline (6r)
4.3.8. N-(1-(2-Chlorophenyl)but-3-enyl)-4-methoxyaniline (6h)
Colorless viscous mass; 1H NMR (CDCl3, 200 MHz):
d 6.75 (2H, d,
Yellow viscous mass; 1H NMR (CDCl3, 400 MHz):
d
7.46 (1H, d,
J¼9.0 Hz), 6.53 (2H, d, J¼9.0 Hz), 5.86–5.75 (1H, m), 5.10–4.99 (2H,
m), 3.80–3.69 (1H, m), 3.74 (3H, s), 3.26 (1H, br s), 3.20 (1H, dd,
J¼8.0, 4.0 Hz), 2.37–2.10 (2H, m), 1.87–1.60 (5H, m), 1.55–1.43 (1H,
J¼8.0 Hz), 7.39 (1H, d, J¼8.0 Hz), 7.21–7.17 (2H, m), 6.70 (2H, d,
J¼9.0 Hz), 6.41 (2H, d, J¼9.0 Hz), 5.86–5.76 (1H, m), 5.26–5.15 (2H,
m), 4.81 (1H, dd, J¼8.4, 4.5 Hz), 3.99 (1H, br s), 3.67 (3H, s),
2.78–2.69 (1H, m), 2.43–2.38 (1H, m); 13C NMR (CDCl3, 100 MHz)
m), 1.29–0.97 (5H, m); 13C NMR (CDCl3, 100 MHz)
d 151.4, 142.6,
135.7, 116.9, 114.8, 114.3, 58.4, 55.7, 41.1, 35.7, 29.3, 29.0, 26.6, 26.4.
d
151.3, 140.4, 139.8, 133.8, 131.9, 129.0, 127.4, 126.9, 126.5, 117.8,
Analytical data are consistent with reported literature values.9a

P. Thirupathi, S.S. Kim / Tetrahedron 65 (2009) 5168–5173
5173
4.3.16. N-(1-Hept-1-en-4-yl)-4-methoxyaniline (6s)
Yellow viscous mass; 1H NMR (CDCl3, 400 MHz):
4.3.23. 4-Isopropyl-N-(1-phenylbut-3-enyl)aniline (8f)
Light yellow viscous mass; 1H NMR (CDCl3, 400 MHz):
d
6.71 (2H, d,
d
7.44–
J¼8.8 Hz), 6.50 (2H, d, J¼8.8 Hz), 5.83–5.76 (1H, m), 5.09–4.98 (2H,
m), 3.71 (3H, s), 3.22 (1H, br s), 3.14 (1H, J¼8.4, 4.0 Hz), 2.30–2.25
(2H, m), 2.18–2.10 (1H, m), 1.86–1.80 (2H, m), 0.87 (3H, t, J¼6.5 Hz);
7.36 (4H, m), 7.31–7.23 (1H, m), 6.99 (2H, d, J¼7.8 Hz), 6.50 (2H, d,
J¼7.8 Hz), 5.86–5.78 (1H, m), 5.22–5.16 (2H, m), 4.38 (1H, dd, J¼7.6,
4.0 Hz), 4.11 (1H, br s), 2.81–2.76 (1H, m), 2.66–2.60 (1H, m), 2.51–
2.45 (1H, m), 1.20 (6H, d, J¼6.5 Hz); 13C NMR (CDCl3, 100 MHz)
13C NMR (CDCl3, 100 MHz)
d 149.7, 135.8, 117.1, 117.0, 114.9, 114.5,
59.0, 55.8, 35.4, 30.6, 18.6, 15.1; HRMS-EI (m/z): [M]þ calcd for
C14H21NO: 219.1623, found: 219.1609.
d 145.3, 143.9, 137.7, 134.8, 128.5, 126.9, 126.8, 126.3, 118.2, 113.4,
57.4, 43.4, 33.0, 24.2; HRMS-EI (m/z): [M]þ calcd for C19H23N:
265.1830, found: 265.1837.
4.3.17. N-(1-Phenylbut-3-enyl)aniline (8a)
Light yellow viscous mass; 1H NMR (CDCl3, 200 MHz):
(5H, m), 7.07 (2H, t, J¼8.8 Hz), 6.66 (1H, t, J¼7.2 Hz), 6.50 (2H, m),
5.75 (1H, m), 5.15 (2H, m), 4.40 (1H, m), 2.55 (2H, m). Analytical
data are consistent with reported literature values.9b
d 7.30
Acknowledgements
Authors thank the Centre for Biological Modulators of the KRICT
for the financial support. BK21 has been provided from Korea Re-
search Council.
4.3.18. 2-Methyl-N-(1-phenylbut-3-enyl)aniline (8b)
Yellow viscous mass; 1H NMR (CDCl3, 400 MHz):
d 7.40–7.34
(4H, m), 7.28–7.23 (1H, m), 7.12 (1H, d, J¼7.6 Hz), 6.89 (1H, t,
J¼7.6 Hz), 6.61 (1H, t, J¼7.6 Hz), 6.31 (1H, d, J¼7.6 Hz), 5.86–5.78
(1H, m), 5.27–5.18 (2H, m), 4.43 (1H, dd, J¼8.0, 4.0 Hz), 4.11 (1H, br
s), 2.72–2.66 (1H, m), 2.58–2.50 (1H, m), 2.23 (3H, s); 13C NMR
References and notes
1. (a) Yamaguchi, R.; Moriyasu, M.; Kawanisi, M. J. Org. Chem. 1985, 50, 287–
288; (b) Yamamoto, Y.; Schmid, M. J. Chem. Soc., Chem. Commun. 1989, 1310–
1312; (c) Ovaa, H.; Stragies, R.; Van der Marel, G. A.; Van Boom, J. H.; Ble-
chert, S. Chem. Commun. 2000, 1501–1502; (d) Hunt, J. C. A.; Laurent, P.;
Moody, C. J. Chem. Commun. 2000, 1771–1772; (e) Felpin, F.-X.; Girard, S.; Vo-
Thanh, G.; Robins, R. J.; Villieras, J.; Lebreton, J. J. Org. Chem. 2001, 66, 6305–
6312.
(CDCl3, 100 MHz)
d 145.8, 144.3, 135.6, 130.5, 129.2, 127.5, 126.8,
122.6, 119.0, 117.5, 111.8, 57.5, 44.3, 18.1; HRMS-EI (m/z): [M]þ calcd
for C17H19N: 237.1517, found: 237.1514.
2. (a) Enders, D.; Reinhold, U. Tetrahedron: Asymmetry 1997, 8, 1895–1946; (b)
Bloch, R. Chem. Rev. 1998, 98, 1407–1438; (c) Wright, D. L.; Schulte, J. P., II;
Page, M. A. Org. Lett. 2000, 2, 1847–1850; (d) Jain, R. P.; Williams, R. M. J. Org.
Chem. 2002, 67, 6361–6365; (e) Ramachandran, P. V.; Burghardt, T. E.; Bland-
Berry, L. J. Org. Chem. 2005, 70, 7911–7918; (f) Besada, P.; Mamedova, L.;
Thomas, C. J.; Costanzi, S.; Jacobson, K. A. Org. Biomol. Chem. 2005, 3, 2016–
2025.
3. Vargas, M. L. Y.; Castelli, M. V.; Kouznetsov, V. V.; Urbina, G. J. M.; Lopez, S. N.;
Sortino, M.; Enriz, R. D.; Ribas, J. C.; Zacchino, S. Bioorg. Med. Chem. 2003, 11,
1531–1550.
4.3.19. 2-(1-Phenylbut-3-enylamino)phenol (8c)
Black viscous mass; 1H NMR (CDCl3, 400 MHz):
d 7.38–7.21 (6H,
m), 6.60 (2H, d, J¼9.0 Hz), 6.42–6.37 (1H, m), 5.83–5.78 (1H, m),
5.25–5.16 (2H, m), 4.64 (1H, br s), 4.38 (1H, br s), 2.62–2.53 (2H, m);
13C NMR (CDCl3, 100 MHz)
d 143.5, 135.9, 134.6, 128.5, 126.9, 126.3,
121.4, 118.2, 117.6, 114.1, 113.6, 57.7, 43.0; HRMS-EI (m/z): [M]þ calcd
for C19H23N: 239.1310, found: 239.1310.
4. (a) Giammaruco, M.; Taddei, M.; Ulivi, P. Tetrahedron Lett. 1993, 34, 3635–3638;
(b) Akiyama, T.; Iwai, J. Synlett 1998, 273–274; (c) Aspinall, H. C.; Bissett, J. S.;
Greeves, N.; Levin, D. Tetrahedron Lett. 2002, 43, 323–326; (d) Choudary, B. M.;
Chidara, S.; Sekhar, C. V. R. Synlett 2002, 1694–1696.
4.3.20. 3-Methyl-N-(1-phenylbut-3-enyl)aniline (8d)
Yellow viscous mass; 1H NMR (CDCl3, 400 MHz):
d 7.38–7.31
5. (a) Keck, G. E.; Enholm, E. J. J. Org. Chem. 1985, 50, 146–147; (b) Nakamura, H.;
Iwama, H.; Yamamoto, Y. J. Am. Chem. Soc. 1996, 118, 6641–6647; (c) Nakamura,
H.; Nakamura, K.; Yamamoto, Y. J. Am. Chem. Soc. 1998, 120, 4242–4243; (d)
Kobayashi, S.; Nagayama, S. J. Am. Chem. Soc. 1997, 119, 10049–10053; (e) Ko-
bayashi, S.; Busujina, T.; Nagayama, S. Chem. Commun. 1998, 19–20; (f) Yadav, J.
S.; Reddy, B. V. S.; Reddy, P. S. R.; Rao, M. S. Tetrahedron Lett. 2002, 43, 6245–
6247; (g) Shibata, I.; Nose, K.; Sakamoto, K.; Yasuda, M.; Baba, A. J. Org. Chem.
2004, 69, 2185–2187; (h) Shen, W.; Wang, L.- M.; Feng, J.- J.; Tian, H. Tetrahedron
Lett. 2008, 49, 4047–4049; (i) Pabitra Kumar, K.; Prodeep, P. Tetrahedron Lett.
2008, 49, 5495–5497.
(4H, m), 7.29–7.25 (1H, m), 6.98–6.95 (1H, m), 6.48 (1H, d, J¼7.8 Hz),
6.39 (1H, s), 6.36 (1H, d, J¼7.8 Hz), 5.82–5.74 (1H, m), 5.21–5.17 (2H,
m), 4.40 (1H, dd, J¼8.0, 4.2 Hz), 4.12 (1H, br s), 2.67–2.59 (1H, m),
2.57–2.48 (1H, m), 2.23 (3H, s); 13C NMR (CDCl3, 100 MHz)
d 148.0,
144.3,139.4,135.3,129.6,129.2,127.5,126.9,118.9,118.8,114.9,111.0,
57.7, 43.9, 22.2; HRMS-EI (m/z): [M]þ calcd for C17H19N: 237.1517,
found: 237.1514.
6. (a) Yadav, J. S.; Hassina, A.; Rao, P. P.; Rao, R. S.; Nagaiah, K.; Prasad, A. R. Catal.
Commun. 2006, 7, 797–801; (b) Das, B.; Aravind Kumar, R.; Thirupathi, P.; Suneel,
K. Can. J. Chem. 2008, 86, 709–713.
4.3.21. 4-Chloro-N-(1-phenylbut-3-enyl)aniline (8e)
Yellow viscous mass; 1H NMR (CDCl3, 200 MHz):
d 7.38–7.10 (5H,
7. (a) Srivastava, N.; Banik, B. J. Org. Chem. 2003, 68, 2109–2114; (b) Srivastava, N.;
Dasgupta, S. K.; Banik, B. K. Tetrahedron Lett. 2003, 44, 1191–1193; (c) Aggen, D.
H.; Arnold, J. N.; Hayes, P. D.; Smoter, N. J.; Mohan, R. S. Tetrahedron 2004, 60,
3675–3679; (d) Banik, B. K.; Reddy, A. T.; Datta, A.; Mukhopadhyay, C. Tetrahe-
dron Lett. 2007, 48, 7392–7394; (f) Mukhopadhyay, C.; Datta, A. Catal. Commun.
2008, 9, 2588–2592.
m), 6.97 (2H, d, J¼8.5 Hz), 6.35 (2H, d, J¼8.5 Hz), 5.82–5.71 (1H, m),
5.25–5.10 (2H, m), 4.32 (1H, dd, J¼8.2, 4.6 Hz), 4.08 (1H, br s), 2.69–
2.38 (2H, m), 1.87–1.60 (5H, m), 1.55–1.43 (1H, m), 1.29–0.97 (5H,
m). Analytical data are consistent with reported literature values.9c
8. (a) Kim, S. S.; Nehru, K. Synlett 2002, 616–619; (b) Kim, S. S.; Jung, H. C. Synthesis
2003, 14, 2135–2137; (c) Kim, S. S.; Rajagopal, G. Synthesis 2003, 16, 2461–2463;
(d) Kim, S. S.; Lee, S. H.; Kwak, J. M. Tetrahedron: Asymmetry 2006, 17, 1165–1169;
(e) Kim, S. S.; Kwak, J. M. Tetrahedron 2006, 62, 49–53; (f) Kim, S. S.; George, S. C.;
Rajagopal, G. Appl. Organomet. Chem. 2007, 21, 798–803; (g) Kim, S. S.; Anjoy, M.;
Kim, H. S. Appl. Organomet. Chem. 2008, 22, 407–411; (h) Kim, S. S.; Kadam, S. T.
Appl. Organomet. Chem. 2009, 23, 119–123.
9. (a) Grote, R. E.; Jarvo, E. R. Org. Lett. 2009, 11, 485–488; (b) Wang, D. K.; Zhou,
Y.-G.; Tang, Y.; Hou, X.-L.; Dai, L.-X. J. Org. Chem. 1999, 64, 4233–4237; (c) Das,
B.; Ravikanth, B.; Thirupathi, P.; Rao, B. V. Tetrahedron Lett. 2006, 47, 5041–
5044.
4.3.22. 4-Fluoro-N-(1-phenylbut-3-enyl)aniline (8f)
Brown viscous mass; 1H NMR (CDCl3, 400 MHz):
d 7.34–7.21
(3H, m), 7.27–7.21 (1H, m), 6.78 (2H, t, J¼8.6 Hz), 6.23 (2H, d,
J¼8.6 Hz), 6.39 (1H, s), 5.78–5.71 (1H, m), 5.20–5.11 (2H, m), 4.29
(1H, dd, J¼8.0, 4.2 Hz), 4.14 (1H, br s), 2.64–2.58 (1H, m), 2.51–2.42
(1H, m); 13C NMR (CDCl3, 100 MHz)
d 153.3, 143.8, 143.7, 134.6,
128.6, 127.1, 126.2, 118.4, 115.7, 115.2, 114.3, 114.1, 57.6, 43.4; HRMS-
EI (m/z): [M]þ calcd for C16H16FN: 241.1266, found: 241.1265.