Synthetic application of in situ generation of N-acyliminium ions from α-amido p-tolylsulfones for the synthesis of α-amino nitriles

Article abstract of DOI:10.1016/j.tet.2010.01.010

In the presence of catalytic amount of bismuth bromide (5 mol %) the α-amido p-tolylsulfones are converted into N-acyliminium ions, which undergo the nucleophilic addition of trimethylsilyl cyanide (TMSCN) to provide the N-protected α-amino nitriles in very good yield. A variety of α-amido p-tolylsulfones were prepared from aromatic as well as aliphatic aldehydes for the synthesis of α-amino nitriles.

Full text of DOI:10.1016/j.tet.2010.01.010

Tetrahedron 66 (2010) 1684–1688
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthetic application of in situ generation of N-acyliminium ions from a-amido
p-tolylsulfones for the synthesis of
a
-amino nitriles
*
Santosh T. Kadam, 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:
In the presence of catalytic amount of bismuth bromide (5 mol %) the a-amido p-tolylsulfones are con-
Received 16 November 2009
Received in revised form 24 December 2009
Accepted 4 January 2010
verted into N-acyliminium ions, which undergo the nucleophilic addition of trimethylsilyl cyanide
(TMSCN) to provide the N-protected -amino nitriles in very good yield. A variety of -amido p-tolylsulfones
were prepared from aromatic as well as aliphatic aldehydes for the synthesis of -amino nitriles.
a
a
a
Available online 11 January 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
a
-Amido p-tolylsulfones
TMSCN
-Amino nitriles
a
N-Acyliminum ions
Bismuth bromide
1. Introduction
presence of the catalyst. In addition to HCN and TMSCN, other
cyanating agents, such as tributyltin cyanide,4a diethyl phosphor-
ocyanidated (DEPC),4b acetyl cyanide,4c and diethyl aluminum
cyanide4d have been also reported under various reaction condi-
tions. TMSCN is a safe and easy to handle reagent, and more ef-
fective cyanide source for the Strecker reactions as compared to
hydrogen cyanide, sodium or potassium cyanides.
a-Amino nitriles have shown the broad interest in recent years
because of their synthetic utility when transferring their func-
tionality into the bioactive and natural products.1
a
-Amino nitriles
-amino acids and various nitrogen
containing heterocycles, such as imidazoles and thiadiazoles.2
-Amino acids manifest biological and economical significance due
to their use in chemistry and biology.3 One of the most important
reactions for the production of -amino nitriles is the catalytic
cyanation of imines (Scheme 1). Another method for the synthesis
of -amino nitriles is the one-pot three-component reaction of
carbonyl compounds, aromatic amines and HCN or TMSCN in the
can be readily converted into
a
a
a-Amino nitriles have been prepared with carbonyl compounds,
amines, and TMSCN by numerous catalytic systems5a,b using such
as vanadyl triflate,5c rhodium iodide,5d Fe(Cp)2PF6,5e ionic liquid,5f
a
b
-cyclodextrin,5g thallium chloride,5h and iodine.5i Along with the
a
catalytic systems, Strecker reactions are also reported without help
of the catalyst.6 Recently several authors demonstrate the use of
phase transfer catalysts for the asymmetric Strecker reactions of
amido p-tolylsulfones. Ooi et al. have reported the synthesis of N-
arylsulfonyl -amino nitriles from -amido p-tolylsulfones in
a-
Ar
Catalyst
Catalyst
O
a
a
HN
Ar-NH4 HCN
TMSCN / HCN
CN
H
aqueous potassium cyanide in presence of quaternary ammonium
R
H
R
salt.7a Herrera et al. describe the enantioselective Strecker reactions
of
a cyanating agent.7b The synthesis of recemic
-amido p-tolylsulfones in presence 10 mol % of indium chloride
has been also reported.8
-Amido p-tolylsulfones are considered stable precursor to
a
-amido p-tolylsulfones with the help of acetone cyanohydrin as
R3
R3
N
HN
a
-amino nitrile from
CN
R2
a
R1 R2
R1
a
Scheme 1. Synthesis of a-amino nitriles via Strecker reaction.
produce N-acyliminium ion 2 that can further react with various
types of nucleophiles (Scheme 2).9
The reaction of N-acyliminium ions has been employed for the syn-
thesis of N-homoallylic amines,10a
a
,
b
-dipeptides,10b
a
-amino phospho-
* Corresponding author. Fax: þ82 32 867 5604.
E-mail address: sungsoo@inha.ac.kr (S.S. Kim).
nates,10c
b
-amino carbonyl compounds,10d and (1-alkyl-1-aryl)methyl
0040-4020/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.01.010

S.T. Kadam et al. / Tetrahedron 66 (2010) 1684–1688
1685
Table 1
O
Nu
O
R
O
Lewis acid
Nu-X
Cyanation of N-benzyloxycarbonylamino phenyl p-tolylsulfone with TMSCNa
R1
R
N
H
3
R1
p-TolO2S
N
H
1
R1
R
N
H
2
NHCbz
SO2Tol-p
Catalyst
Solvent
NHCbz
CN
TMSCN
2
Ph
Ph
Scheme 2. Nucleophilic substitution of
a-amido p-tolylsulfones through N-acylimi-
nium ions.
3
1
Cbz: benzyloxycarbonyl
phenylsulfones.10e Ballini et al. have reported that the Montmoril-
lonite K-10 could be an efficient catalyst for the Friedel–Crafts re-
Entry
Catalyst
Mol %
Solvent
Reaction
time (h)
Yieldb (%)
actions of
demonstrate that InBr3 is an effective catalyst for the synthesis of tri-
aryl methanes and 3-(1-arylsulfonylalkyl)indole from -amido
p-tolylsulfones.10g Gianelli et al. have utilized the amino catalyst
a
-amido p-tolylsulfones with indoles.10f Kim et al.
1
2
3
4
5
Nafion-SAC-13
Nafion-NR-50
BiBr3
B(C6F5)3
Montmorillonite
K-10
PMA
BiBr3
BiBr3
BiBr3
BiBr3
BiBr3
BiBr3
Bi(OTf)3
BiCl3
Bi(NO3)3$5H2O
FeCl3
FeBr3
RhI3$H2O
TICl3$4H2O
30 mg
30 mg
10
10
30 mg
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
10
10
3
6
10
NR
NR
90
30
NR
a
for the anti-Mannich reaction of aldehydes with
a-amido p-
tolylsulfones.10h
6
7
8
9
10
10
10
10
10
5
3
5
5
5
CH2Cl2
CH3CN
THF
CHCl3
DMF
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
10
5
6
10
10
3
8
5
5
5
NR
38
43
30
10
90
64
35
42
NR
48
33
NR
17
With increasing environmental concern, the need for envi-
ronmentally benign method has become of significant importance.
According to the principle of green chemistry, synthetic method
should be designed to use substances that exhibit little or no
toxicity to human health and environment.11 In this regard, bis-
muth salts have recently attracted considerable attention because
bismuth salts are remarkably nontoxic, stable, and cost less.12
Bismuth salts have been reported as the catalyst for various or-
ganic transformation, such as Friedel–Craft reactions,13a depro-
tection of ketoximes,13b coupling of carbonyl compounds with
alkoxysilane,13c synthesis of homoallylic amines,13d silylation of
alcohols,13e and allylation of aldehydes.13f
10
11
12
13
14
15
16
17
18
19
5
5
5
5
3
3
8
8
a
Reagent and conditions: 1 mmol of N-benzyloxycarbonylamino phenyl p-tol-
ylsulfone, 1 mmol of TMSCN, and 5 mol % of BiBr3 were employed at rt.
b
Isolated yield of the products.
2. Results and discussions
reactivity toward cyanation reaction and produce the correspond-
ing product in good yield (entries 2 and 6). When electron-with-
drawing groups are located in the phenyl ring of R in 4 (entries
8–15), the yield shows somewhat lower than in case of para-
substituted electron-donating ones (entries 1–7). Comparing the
yield of entry 4 and entry 15, the lower yield of entry 15 (67%) may
be due to electron-withdrawing power of bromine atom. ortho-Me
displays 88% yield in entry 4 that can be considered to hardly exhibit
the steric hindrance. Van der Waals radius of CH3 and Br are 200 pm
and 185 pm, respectively.16 The electron-withdrawing power is
exemplified with p-NO2– and p-CN– that show no reactivity at all
toward the Strecker reaction even after 8 h reaction time (entries 16
and 17).
In light of the success in developing several catalytic systems for
the cyanosilylation of carbonyl compounds,14,15 we extend our
studies to cyanation of
wish to herein report a simple and mild method for the synthesis
N-protected -amino nitriles from -amido p-tolylsulfones.
a-amido p-tolylsulfones with TMSCN. We
a
a
The investigations involving the reaction of N-benzyloxy-
carbonylamino phenyl p-tolylsulfone with TMSCN in presence of
heterogeneous catalysts such as Nafion-SAC-13, Nafion-NR-50,
Montmorillonite K-10 (30 mg) and PMA (10 mol %) show no re-
activity for the cyanation reaction. Strong Lewis acid B(C6F5)3 is
enable to produce only 30% yield of the product within 6 h reaction
time. Among the other Lewis acid, rhodium iodide is unable to
produce the desired product but FeCl3, FeBr3, and thallium chloride
are able to yield 48, 33, and 17% of the products, respectively. For-
tunately,10 mol % BiBr3 gives 90% yield of desired product within 3 h
reaction time. The reduction of catalyst amount up to 5 mol % shows
similar effect on the reactivity. But further decrease in catalyst
loading up to3 mol % gives the lower yield (64%) in 8 h reaction time.
The reactivity of BiBr3 was studied in other polar solvents like
CH3CN, CHCl3, THF, and DMF that gives rise to lower yield (10–38%)
with longer reaction time (6–10 h). Among the bismuth salts stud-
ied, Bi(OTf)3 and BiCl3 demonstrate the moderate yield of N-pro-
a-Amido p-tolylsulfones derived from acid-sensitive heterocy-
clic 2-thiophenaldehyde and 2-pyridinecarboxyladehyde undergo
smoothly for the formation of the products (entries 18 and 19).
Similarly the sulfone containing naphthalene ring is also able to
provide the amino nitrile with good yield (entry 20). a-Amido p-
tolylsulfones prepared from aliphatic aldehydes is moderately re-
active toward the cyanation reaction under present condition
(entries 21–22). Cyclic aliphatic groups containing sulfone have
shown somewhat lower yield of products relative to aromatics.
Besides TMSCN, the catalytic system is also effectively utilized for
tected
a
-amino nitriles (35 and 42%) while Bi(NO3)3$5H2O fails to
the cyanation of
a-amido p-tolylsulfones with bulky silyl cyanide,
give the product. Accordingly 5 mol % of BiBr3 can be the optimum
amount in 3 h reaction time (entry 11, Table 1).
such as tert-butyldimethylsilyl cyanide (TBSCN). The reaction of a-
amido p-tolylsulfones with TBSCN gives 62% of the yield within
Various aliphatic and aromatic aldehydes were used for the
synthesis of N-benzyloxycarbonylamino phenyl p-tolylsulfones that
12 h reaction time. The lower yield with longer reaction time may
be due to the steric effects of TBSCN. The N-Boc-protected
p-tolylsulfones is also underwent the cyanation with TMSCN under
the present reaction condition (Scheme 3). -Amido p-tolylsulfones
with N-Boc-protection (79 and 67%) shows lower yield relative to
Cbz-protected -amido p-tolylsulfones (90 and 80%) toward the
a-amido
in turn react with TMSCN to give the N-protected
a-amino nitriles
(Table 2). The -amido p-tolylsulfone, 1 containing unsubstituted
a
a
benzene ring is able to give 90% yield (entry 1). N-benzyloxy-
carbonylamino phenyl p-tolylsulfones containing electron-donating
MeO- and Me- groups on p-, m-, and o- position of phenyl ring
a
cyanation reaction. Similar type of reaction has been reported with
indium chloride as the catalyst that indicates similar result with the
present one.8
provide quite good yield of the products (entry 3–9). Beside
a-
amido p-tolylsulfones, -amido phenylsulfones also show similar
a

1686
S.T. Kadam et al. / Tetrahedron 66 (2010) 1684–1688
Table 2
Table 2 (continued)
BiBr3 catalyzed cyanation of a
-amido p-tolylsulfones with TMSCNa
Entry
R in 4
5
Time (h)
8
Yieldb (%)
NR
NHCbz
NHCbz
CN
BiBr3, 5 mol %
rt, CH2Cl2
TMSCN
R
SO2Tol-p
R
17
5q
NC
4
2
5
S
18
5r
4
77
Cbz: benzyloxycarbonyl
Entry
R in 4
5
Time (h)
3
Yieldb (%)
19
20
21
5s
5t
4
3
8
9
80
91
65
62
N
1
2
3
5a
5b
5c
90
3
3
90c
88
5u
5v
22
Me
a
Reagent and conditions: 1 mmol of a-amido p-tolylsulfones, 1 mmol of TMSCN,
4
5
6
5d
5e
5f
3
3
3
88
and 5 mol % of BiBr3 were employed at rt.
b
Me
Isolated yield of products.
Instead of –SO2–Tol-p, –SO2–Ph was used.
c
90
O
O
MeO
MeO
MeO
HN
O
BiBr3, 5 mol %
rt, CH2Cl2
HN
O
TMSCN
90c
R
CN
R
SO2Tol-p
6
2
7
6a: Benzene
6b: 2-Pyridine
7a: 3 h, 79%
7b: 3 h, 67 %
7
5g
5h
5i
3
3
3
3
90
81
90
84
Scheme 3. Cyanation of N-Boc-protected
a
-amido p-tolylsulfones with TMSCN.
Me
3. Summary
8
MeO
A very simple and novel method has been developed for the
synthesis of N-protected -amino nitriles from -amino p-tol-
ylsulfones via the formation of N-acyliminium ions. The various
types of -amido p-tolylsulfones derived from aromatic and ali-
phatic aldehydes react with TMSCN to give the N-protected
F
a
a
MeO
MeO
a
9
a
-
OMe
amino nitriles in considerably good yield. In addition to TMSCN this
catalytic protocol is applicable for bulky silyl cyanide (TBSCN) as
cyanide source. The major advantage of the method is the lowest
catalyst quantity required among other reported works.
10
5j
OPh
4. Experimental section
4.1. General
11
12
5k
5l
3
5
82
78
F
In all cases the 1H NMR (200 MHz) spectra were recorded with
Varian Gemini 4000 spectrometer. Chemical shifts are reported in
parts per million in CDCl3 with tetramethylsilane as an internal
standard. 13C NMR data were collected on a Varian Gemini 2000
spectrometer (50 MHz).
Cl
13
14
5m
5n
3
4
85
80
4.2. General procedure for the synthesis of N-protected
Cl
Br
a-amino nitriles
To a mixture of
a-amido p-tolylsulfones (1 mmol) and BiBr3
(5 mol %), TMSCN (1.0 mmol) was added at rt. The completion of the
reaction was monitored with TLC. After the completion of reaction,
the reaction mixture was concentrated and the viscous mass was
subject to silica gel flash column chromatography to obtain the pure
compound.
15
16
5o
5p
3
8
67
Br
All products were characterized by 1H and 13C NMR data that are
consistent with literature values.7b,8,17 HRMS–FAB, melting point
and IR values for new products are given below.
NR
O2N

S.T. Kadam et al. / Tetrahedron 66 (2010) 1684–1688
1687
4.2.1. Compound (5a). 1H NMR (200 MHz, CDCl3)
d
: 7.42–7.33 (m,
CDCl3)
d
: 7.38 (d, J¼8.8 Hz, 2H), 7.31–7.23 (m, 7H), 5.78 (d,
10H), 5.79 (d, J¼8.2 Hz, 1H), 5.20 (d, J¼6.2 Hz, 1H), 5.14 (s, 2H); 13C
J¼7.8 Hz, 1H), 5.09 (s, 2H); 13C NMR (50 MHz, CDCl3)
d: 45.8, 68.0,
NMR (50 MHz, CDCl3)
d: 47.0, 68.4, 118.0, 127.4, 128.7, 129.0, 129.1,
116.8, 125.0, 127.0, 128.1, 128.5, 129.6, 130.5, 135.0, 135.1, 155.0;
HRMS–FAB: [MH]þ calcd for C16H14O2N2Cl: 301.0744, found:
301.0746.
130.0, 130.1, 130.3, 133.5, 136.0, 155.6.
4.2.2. Compound (5c). 1H NMR (200 MHz, CDCl3)
d: 7.42–7.34 (m,
5H), 7.25 (d, J¼7.2 Hz, 2H), 7.20 (d, J¼7.6 Hz, 2H), 5.70 (d, J¼8.0 Hz,
4.2.11. Compound (5m). White solid; mp 108–109 ꢀC; IR (KBr):
2H), 5.30 (d, J¼8.0 Hz, 1H), 5.10 (s, 2H), 2.35 (s, 3H); 13C NMR
3319, 3032, 2733, 2246, 1693, 1515, 874 cmꢁ1 1H NMR (400 MHz,
;
(50 MHz, CDCl3)
d: 21.6, 46.8, 68.3, 118.1, 127.3, 128.7, 129.0, 129.1,
CDCl3)
d
: 7.36 (d, J¼8.4 Hz, 2H), 7.32–7.29 (m, 5H), 6.91 (d, J¼8.4 Hz,
130.4, 136.0, 140.1, 155.6.
2H), 5.80 (d, J¼8.0 Hz, 1H), 5.65 (d, J¼8.0 Hz, 1H), 5.14 (s, 2H); 13C
NMR (50 MHz, CDCl3) d: 46.0, 68.0, 117.0, 128.3, 128.6, 128.5, 129.5,
4.2.3. Compound (5d). White solid; mp 108–109 ꢀC; IR (KBr): 3311,
131.5, 135.8, 156.2; HRMS–FAB: [MH]þ calcd for C16H14O2N2Cl:
301.0744, found: 301.0743.
3032, 2235,1602,1275, 738 cmꢁ1; 1H NMR (200 MHz, CDCl3)
d: 7.62
(d, J¼8.2 Hz, 1H), 7.31–7.42 (m, 8H), 5.75 (d, J¼8.0 Hz, 1H), 5.35 (d,
J¼8.0 Hz, 1H), 5.12 (s, 2H), 2.32 (s, 3H); 13C NMR (50 MHz, CDCl3)
d:
4.2.12. Compound (5n). White solid; mp 135–136 ꢀC; IR (KBr):
18.0, 44.8, 68.0, 118.0, 127.0, 127.5, 128.2, 128.4, 128.6, 130.0, 131.0,
131.4, 136.0, 136.2, 155.0; HRMS–FAB: [MH]þ calcd for C17H17O2N2:
281.1290, found: 281.1292.
3280, 2246, 1693, 1528, 1075, 760 cmꢁ1; 1H NMR (200 MHz, CDCl3)
d
: 7.54 (d, J¼8 Hz, 2H), 7.44–7.37 (m, 5H), 7.29 (d, J¼6.6 Hz, 2H), 5.80
(d, J¼8.0 Hz, 1H), 5.65 (d, J¼8.0 Hz, 1H), 5.14 (s, 2H); 13C NMR
(50 MHz, CDCl3) d: 46.0, 68.6, 117.5, 124.4, 129.0, 129.1, 129.2, 132.7,
4.2.4. Compound (5e). White solid; mp 116–117 ꢀC; IR (KBr): 3296,
133.1, 135.8, 155.5; HRMS–FAB: [MH]þ calcd for C16H14O2N2Br:
345.0239, found: 345.0239.
3016, 2235, 1686, 1316, 1030, 823 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
: 7.38–7.36 (m, 5H), 7.30 (d, J¼7.6 Hz, 2H), 6.90 (d, J¼7.6 Hz, 2H),
5.74 (d, J¼8.0 Hz, 1H), 5.52 (d, J¼8.0 Hz, 1H) 3.80 (s, 3H); 13C NMR
4.2.13. Compound (5o). White solid; mp 126–127 ꢀC; IR (KBr):
(50 MHz, CDCl3)
d
: 46.0, 55.4, 67.8, 114.6, 117.6, 128.3, 128.4, 128.5,
3322, 2737, 2256, 1682, 1236, 745 cmꢁ1; 1H NMR (200 MHz, CDCl3)
128.6, 135.5, 156.4, 160.4; HRMS–FAB: [MH]þ calcd for C17H17O3N2:
297.1239, found: 297.1237.
d
: 7.65–7.59 (m, 2H), 7.39–7.31 (m, 7H), 6.03 (d, J¼8.2 Hz, 1H), 5.80
(d, J¼8.0 Hz, 1H), 5.65 (d, J¼8.0 Hz, 1H), 5.13 (s, 2H); 13C NMR
(50 MHz, CDCl3) d: 46.0, 68.0, 117.0, 128.2, 128.6, 129.6, 131.4, 132.2,
4.2.5. Compound (5g). White solid; mp 132–133 ꢀC; IR (KBr): 3417,
133.8, 135.8, 156.5; HRMS–FAB: [MH]þ calcd for C16H14O2N2Br:
345.0239, found: 345.0239.
3332, 2233, 1952, 1690, 1071, 735 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
: 7.44–7.34 (m, 5H), 7.28 (d, J¼7.2 Hz, 1H), 6.80 (d, J¼8.0 Hz, 1H),
7.20 (s, 1H), 5.70 (d, J¼8.0 Hz, 1H), 5.20 (s, 1H), 5.34 (d, J¼8.0 Hz,
4.2.14. Compound (5r). Brown solid; mp 127–128 ꢀC; IR (KBr):
1H), 5.1 (s, 2H), 3.82 (s, 3H), 2.20 (s, 3H); 13C NMR (50 MHz, CDCl3)
3273, 2924, 2242, 1689, 1282, 960 cmꢁ1; 1H NMR (200 MHz, CDCl3)
d
: 16.7, 46.72, 56.00, 110.7, 118.3, 126.2, 128.5, 128.8, 129.1, 129.7,
d
: 7.30 (d, J¼4.0 Hz, 1H), 7.20 (d, J¼4.2 Hz, 1H), 7.19–7.16 (m, 5H),
159.2; GC–MS: m/z: 310 [Mþ], 219, 175, 160, 148, 107, 91, 79.
6.94 (dd, J¼5.1, 4.4 Hz, 1H), 5.95 (s, 1H), 5.4 (s, 1H), 5.10 (s, 2H); 13C
NMR (50 MHz, CDCl3) d: 45.2, 68.6, 117.9, 127.8, 128.2, 128.9, 129.2,
4.2.6. Compound (5h). White solid; mp 118–119 ꢀC; IR (KBr): 3332,
136.0, 156.2; HRMS–FAB: [MH]þ calcd for C14H14O2NS: 273.0698,
found: 273.0698.
3032, 2254, 2042, 1693, 745 cmꢁ1 1H NMR (200 MHz, CDCl3)
; d:
7.45 (s, 1H), 7.35–7.25 (m, 4H), 7.19 (d, J¼7.6 Hz, 2H), 6.97 (t,
J¼7.6 Hz, 1H), 5.76 (d, J¼8.0 Hz, 1H), 5.43 (d, J¼8.0 Hz, 1H), 5.61 (s,
4.2.15. Compound (5s). Yellow oil; IR (KBr): 3436, 3274, 2246,
2H), 3.89 (s, 3H); 13C NMR (50 MHz, CDCl3)
d: 46.2, 56.8, 68.5,
1703, 1236, 1660, 1048, 708 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d:
114.23, 114.2, 115.2, 115.6, 117.7, 123.5, 123.6, 126.2, 126.3, 128.8,
129.0, 129.1, 135.9, 150.4, 155.6; HRMS–FAB: [MH]þ calcd for
C17H16O3N2F: 315.1145, found: 315.1143.
8.60 (s, 1H), 7.82 (t, J¼7.7 Hz, 2H), 7.45 (d, J¼5.8 Hz, 1H), 7.38–
7.32 (m, 5H), 6.18 (d, J¼8.0 Hz, 1H), 5.7 (d, J¼8.0 Hz, 1H), 5.12 (s,
2H); 13C NMR (50 MHz, CDCl3)
d: 47.5, 66.8, 118.1, 122.5, 124.8,
138.1, 150.3, 125.0; GC–MS: m/z: 267 [Mþ], 233, 178, 160, 131,
4.2.7. Compound (5i). 1H NMR (400 MHz, CDCl3)
5H), 6.61 (s, 2H), 6.12 (d, J¼8.0 Hz,1H), 5.72 (d, J¼8.0 Hz,1H), 5.16 (s,
2H), 3.79 (s, 9H); 13C NMR (50 MHz, CDCl3)
: 46.7,56.1, 60.8, 66.8,
d
: 7.34–7.32 (m,
107, 56.
d
4.2.16. Compound (5t). 1H NMR (200 MHz, CDCl3)
5H), 7.62–7.32 (m, 7H), 5.92 (d, J¼8.0 Hz, 1H), 5.55 (d, J¼8.0 Hz, 1H),
5.15 (s, 2H); 13C NMR (50 MHz, CDCl3)
: 46.1, 67.4, 117.0, 123.3,
d: 7.94–7.82 (m,
103.9, 117.6, 128.0, 128.2, 128.5, 128.6, 136.1, 138.4, 153.3, 156.9.
d
4.2.8. Compound (5j). White solid; mp 71–72 ꢀC; IR (KBr): 3432,
125.8, 126.5, 126.7, 127.2, 127.7, 128.0, 128.1, 129.0, 129.6, 132.4,
132.8, 134.9, 154.5.
3283, 2251, 1693, 1247, 785 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d:
7.38–7.27 (m, 8H), 7.20–6.98 (m, 4H), 6.95 (d, J¼7.6 Hz, 2H), 5.7 (d,
J¼8.0 Hz, 1H), 5.4 (d, J¼8.0 Hz, 1H), 5.1 (s, 2H); 13C NMR (50 MHz,
4.2.17. Compound (5u). White solid; mp 89–90 ꢀC; IR (KBr): 3286,
CDCl3)
d
: 46.0, 67.8, 117.0, 117.1, 119.1, 121.1, 123.8, 128.1, 128.3, 128.4,
3032, 2237, 1692, 1249, 745 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d:
129.8, 130.5, 134.8, 135.2, 156.0; HRMS–FAB: [MH]þ calcd for
C22H19O3N2: 359.1396, found: 359.1396.
7.34–7.31 (m, 5H), 5.52 (s, 2H), 5.12 (d, J¼8.0 Hz, 1H), 4.49 (t,
J¼7.8 Hz, 1H), 1.86–1.78 (m, 4H), 1.70–1.67 (m, 1H), 1.26–1.06 (m,
6H); 13C NMR (50 MHz, CDCl3)
d: 25.2, 25.3, 25.6, 28.4, 28.7, 40.5,
4.2.9. Compound (5k). White solid; mp 103–104 ꢀC; IR (KBr): 3343,
48.1, 67.5, 117.8, 128.1, 128.3, 128.5, 135.5, 155.3; HRMS–FAB: [MH]þ
calcd for C17H21O2N2: 273.1603, found: 273.1602.
2919, 3032, 2246, 1679, 1266, 951 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
: 7.40–7.04 (m, 8H), 5.84 (d, J¼8.0 Hz, 1H), 5.67 (d, J¼8.0 Hz, 1H),
5.14 (s, 2H); 13C NMR (50 MHz, CDCl3)
d
: 45.2, 67.3, 113.2, 113.6,
4.2.18. Compound (5v). White solid; mp 78–79 ꢀC; IR (KBr): 3280,
115.7, 116.1, 16.2, 121.8, 127.5, 127.8, 127.9, 130.2, 134.5, 156; HRMS–
FAB: [MH]þ calcd for C16H14O2N2F: 285.1039, found: 285.1040.
2904, 2246, 1686, 1251, 1048, 688 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
: 7.37–7.32 (m, 5H), 5.71–5.68 (m, 1H), 5.64–5.31 (m, 1H), 5.39–
5.33 (m, 1H), 5.12 (s, 1H), 4.55 (d, J¼7.8 Hz, 1H), 2.18–2.04 (m, 3H),
1.94–1.75 (m, 3H), 1.51–1.39 (m, 1H); 13C NMR (50 MHz, CDCl3)
24.3, 27.4, 37.0, 47.5, 67.8, 117.8, 124.4, 127.1, 128.2, 128.6, 135.2,
4.2.10. Compound (5l). White solid; mp 98–99 ꢀC; IR (KBr): 3291,
d:
3032, 2746, 2244, 1691, 1290, 708 cmꢁ1 1H NMR (200 MHz,
;

1688
S.T. Kadam et al. / Tetrahedron 66 (2010) 1684–1688
155.2; HRMS–FAB: [MH]þ calcd for C17H19O2N: 271.1447, found:
271.1445.
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4.2.19. Compound (7a). 1H NMR (400 MHz, CDCl3)
d: 7.49–7.39 (m,
5H), 5.77 (d, J¼8 Hz,1H), 5.27 (s, 1H), 1.47 (s, 1H); 13C NMR (50 MHz,
CDCl3)
133.5.
d: 28.2, 46.0, 81.5, 117.80, 124.85, 126.9, 129.3, 129.4, 129.6,
4.2.20. Compound (7b). 1H NMR (400 MHz, CDCl3)
d: 8.62 (s, 1H),
7.72 (t, J¼7.7 Hz, 2H), 7.41 (d, J¼5.8 Hz, 1H), 6.12 (d, J¼8.0 Hz, 1H),
5.70 (d, J¼8.0 Hz, 1H), 1.28 (s, 9H); 13C NMR (50 MHz, CDCl3)
d: 28.2,
47.0, 81.4, 117.5, 121.8, 122.0, 124.3, 127.8, 137.0, 37.7, 149.8, 150.2,
153.7; HRMS–FAB: [MH]þ calcd for C12H16O2N3: 234.1243, found:
134.1242.
Acknowledgements
The authors thank The Center for Biological Modulators of the
KRICT for the financial support. Thanks are also due to BK 21 ad-
ministrated by Korea Research Council.
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