Indium triflate-catalyzed allylation reactions of N-sulfonyl aldimines or N-alkoxycarbonylamino p-tolylsulfones with allyltrimethylsilane: Synthesis of protected homoallylic amines

Article abstract of DOI:10.1016/j.tet.2010.09.038

Indium triflate-catalyzed allylation reactions of N-sulfonyl aldimines or N-alkoxyloxycarbonylamino p-tolylsulfone with allyltrimethylsilane have been successfully developed to produce protected homoallylic amines.

Full text of DOI:10.1016/j.tet.2010.09.038

Tetrahedron 66 (2010) 8623e8628
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Indium triflate-catalyzed allylation reactions of N-sulfonyl aldimines or
N-alkoxycarbonylamino p-tolylsulfones with allyltrimethylsilane: synthesis of
protected homoallylic amines
*
Ponnaboina Thirupathi, Sung Soo Kim
Department of Chemistry, Inha University, Incheons 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 13 August 2010
Received in revised form 10 September 2010
Accepted 11 September 2010
Available online 17 September 2010
Indium triflate-catalyzed allylation reactions of N-sulfonyl aldimines or N-alkoxyloxycarbonylamino
p-tolylsulfone with allyltrimethylsilane have been successfully developed to produce protected homo-
allylic amines.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
N-Sulfonyl aldimines
N-Alkoxycarbonylamino p-tolylsulfone
Allyltrimethylsilane
Allylation
Protected homoallylic amines
1. Introduction
2. Results and discussions
The allylation of carbonyl derivatives, such as aldehydes, ke-
tones, and imines is one of the important carbonecarbon bond
forming reactions because of the versatility of homoallylic alcohols
and amines as synthetic intermediates.1 In particular, Lewis acid-
catalyzed allylation of imines has attracted increasing attention
because of the significance for the preparation of nitrogen con-
taining molecules.1,2 The homoallylic amines are useful funda-
mental building blocks for the synthesis of many nitrogen
containing natural products and bioactive molecules.3,4 The de-
velopment of new methods for the synthesis of homoallylic amines
is a significant task for synthetic chemist. A number of methods
have been reported for the preparation of protected homoallylic
amines using various substrates.5,6
In continuation of the development of useful synthetic meth-
odologies for CeC bond forming reactions7 we report herein the
Indium triflate-catalyzed allylation reactions of N-sulfonyl aldi-
mines or N-alkoxycarbonylamino p-tolylsulfone with allyl-
trimethylsilane. In recent years the utility of indium salts as Lewis
acid in organic synthesis has received a great deal of attention due
to the relatively low toxicity, stability in air and water, strong tol-
erance to oxygen- and nitrogen-containing substrates.8
2.1. Allylation of N-sulfonyl aldimines
Recently, Bateyand Li reported the synthesis of protected homo-
allylic amines by palladium pincer complex.6f Szabo and co-workers
have demonstrated the preparation of protected homoallylic amines
with the reaction of N-sulfonyl aldimines with potassium trifluoro
(allyl)borate.6g The N-sulfonyl aldimines (3) were prepared from the
condensation of aldehydes (1), sulfonamides, and sodium salt of
arenesulfinic acid to produce the sulfonamidesulfone (2) followed by
the treatment with saturated aq NaHCO3 (Scheme 1).9
The reactions
of
N-tosyl(phenylbenzylidene)-4-methyl-
benzenesulfonamide (3a) with allyltrimethylsilane (4) were ex-
amined under reaction conditions employing various catalysts
(Table 1). The reaction of N-tosyl(phenylbenzylidene)-4-methyl-
benzenesulfonamide (3a) and allyltrimethylsilane (4) in the ab-
sence of the catalyst did not take place at all (entry 1). The reactions
have been screened in the presence of various Lewis acids. Among
the various iron and indium catalysts tested, In(OTf)3 was shown to
be the most effective one (entry 11). In(NO3)3$XH2O and In
(acac)3$XH2O did not allow the reaction to proceed at all (entries 6
and 7). Other metal triflates La(OTf)3, Ce(OTf)3, heteropoly acids
H3PO4$12WO3$XH2O, H3PMo12O40 (PMA), and heterogeneous cat-
alysts Amberlyst-15, PMA$SiO2 also catalyzed the reaction with
only decreased yields (entries 12e17).
* Corresponding author. Fax: þ82 32 867 5604; e-mail address: sungsoo@inha.
ac.kr (S.S. Kim).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.09.038

8624
P. Thirupathi, S.S. Kim / Tetrahedron 66 (2010) 8623e8628
p-TolSO2NH2
SiMe3
O
NHSO2Tol-p
ArSO2Na
NSO2Tol-p
NHSO2Tol-p
aq. NaHCO3
CH2Cl2, r. t.
4
aq. HCO2H
r. t.
R
H
R
SO2Ar
R
R
H
CH2Cl2
r. t.
1
2
3
5
R= Aryl or alkyl
Ar = p-Tolyl
Scheme 1. General preparation method for the synthesis of N-sulfonyl aldimines and synthesis of protected homoallyl amines.
Table 1
containing halogen groups, such as chlorine and bromine on the
phenyl ring proceeded smoothly to give the corresponding products
in good yields (entries 2e5). N-Tosyl(4-methylbenzylidene) (3f), N-
tosyl(4-methoxybenzylidene) (3g), and N-tosyl(3,4,5-trimethox-
ybenzylidene)-4-methylbenz-enesulfonamide (3h) react with allyl-
trimethylsilane (4) to give 5f, 5g, and 5h in 87, 88, and 91%,
respectively (entries 6e8). The reactions of N-sulfonyl aldimines
bearing an electron-withdrawing group on the phenyl ring took place
in slightly lower yields (entries 9e11).
The reaction conditions for allylation of N-tosyl(phenylbenzylidene)-4-methyl-
benzenesulfonamide with allyltrimethylsilanea
Entry
Catalyst (mol %)
Reaction time (h)
Isolated yield (%)b
1
2
3
4
5
6
7
8
d
16
10
10
10
8
10
10
6
8
6
6
16
8
NR
21
49
57
80
NR
NR
81
46
85
84
76
82
76
80
56
74
2.2. Allylation of N-alkoxycarbonylamino p-tolylsulfone
FeCl3$6H2O (10)
FeBr3 (10)
FeCl3 (10)
The acylatedhomoallylic amines are important synthonsformany
synthetic applications, notably for acyliminum chemistry.10The vari-
eties of synthetic methods have been reported for the synthesis of
homoallylic amines. The in situ generations of imines are highly at-
tractive, among which the three-component allylation reaction have
been introduced by Panek5aand developed by Veenstra.5bYet, many
Lewis acids cannot be used in this reaction because they decompose
or are deactivated in the presence of the amine or water produced
during imine formation. Thus the Sakurai reaction of N-alkoxy-
carbonylamino p-tolylsulfone (6) with allyltrimethylsilane (4) in the
presence of a suitable Lewis acid constitutes an important method for
the synthesis of N-alkoxycarbonyl-protected homoallylic amines.
This reactionproceeds through avery reactive N-acyliminium species
or N-alkoxycarbonyliminium derivative (7, Scheme 2).
InCl3 (10)
In(NO3)3$XH2O (10)
In(acac)3$XH2O (10)
InBr3 (10)
In(ClO4)3$XH2O (10)
In(OTf)3 (10)
In(OTf)3 (5)
La(OTf)2 (10)
Ce(OTf)3 (10)
H3PO4$12WO3$XH2O (1)
H3PMo12O40 (PMA) (1)
Amberlyst-15 (100 mg)
PMA.SiO2 (100 mg)
9
10
11
12
13
14
15
16
17
8
6
16
16
a
Reaction condition: N-Tosyl-(phenylbenzylidene)-4-methylbenzenesulfonamide
(1.0 mmol) and allyltrimethylsilane (1.5 mmol) are used.
b
Yield of isolated product after column chromatography.
Recently, very few Lewis acid catalysts, such as TiCl4, SnCl4, GaCl3,
InCl3, or Bi(OTf)3 have been employed for the preparation of alkox-
ycarbonyl-protected homoallylic amines.11 However, TiCl4 or SnCl4
is moisture sensitive and required in stoichiometric quantity or in
large excess. Some of these methods show longer reaction time and
lower yield. To overcome these limitations, we report herein In
(OTf)3-catalyzed Sakurai reaction of N-alkoxycarbonylamino p-tol-
ylsulfone with allyltrimethylsilane. Under optimized reaction con-
ditions as in Table 1, the scope of allylation reactions have been
studied using N-alkoxycarbonylamino p-tolylsulfone (6) and allyl-
trimethylsilane (4). The results are summarized in Table 3.
The In(OTf)3-catalyzed reactions of various N-sulfonyl aldimine
with allyltrimethylsilane that proceeded smoothly to give the corre-
sponding protected homoallylic amines (Table 2). The reaction of N-
tosyl(phenylbenzylidene)-4-methylbenzenesulfonamide (3a) with
allyltrimethylsilane (4) produces the protected homoallylic amine
(5a) in 84% yield (entry 1). The reaction of N-sulfonyl aldimines
Table 2
Allylation of various N-sulfonyl aldimines with allyltrimethylsilane catalyzed by In
a
(OTf)3
N-Alkoxycarbonylamino p-tolylsulfones (6) with electron-do-
nating group attached to the benzene ring react with allyl-
trimethylsilane (4) to produce the Cbz-protected homoallylic
amines in good yield (entries 2e6). The reactions of p-, m-, and o-
halogen containing N-alkoxycarbonylamino p-tolylsulfone gave
corresponding products in 90, 83, 89, 87, 84, and 83% yield, re-
spectively (entries 7e12). This shows no serious electron-with-
drawing effects of halogen atoms. o-Isomers exhibit a slight steric
and electron effect, that is responsible for the less yield and longer
reaction time (entries 8 and 11). The electron-withdrawing p-CN
group also (6k) proceeds smoothly to give the allylation product in
good yield (entry 13). 2-Furyl (6n) and 2-naphthyl N-alkox-
ycarbonylamino p-tolylsulfone (6o) react with allyltrimethylsilane
(4) to afford the corresponding products (entries 14 and 15). The
reactions of acyclic aliphatic N-alkoxycarbonylamino p-tolylsulfone
give the Cbz-protected homoallylic amines in comparatively low
yield (entries 16 and 17). Cyclohexyl and 2-cyclohexenyl N-alkoxy-
carbonylamino p-tolylsulfone bring about the corresponding ally-
lation derivatives (entry 18 and 19).
Entry R in 3
Reaction time (h) Product 5 Isolated yieldb (%)
1
3a, C6H4
6.0
5.0
6.0
6.0
6.0
5.0
4.0
5a
5b
5c
5d
5e
5f
5g
5h
5i
84
88
85
82
89
87
88
91
78
82
76
2
3
4
5
6
7
3b, 4-ClC6H4
3c, 3-ClC6H4
3d, 2-ClC6H4
3e, 4-BrC6H4
3f, 4-MeC6H4
3g, 4-MeOC6H4
8
3h, 3,4,5-(MeO)3C6H2 3.5
9
10
11
3i, 4-NO2C6H4
3j, 4-CNC6H4
3k, 3-CNC6H4
6.0
6.0
6.0
5j
5k
a
Reaction condition: N-sulfonyl aldimine (1.0 mmol), trimethylsilane (1.5 mmol),
and In(OTf)3 (5 mol % with respective to N-sulfonyl aldimine) are used.
b
Yield of isolated product after column chromatography.

P. Thirupathi, S.S. Kim / Tetrahedron 66 (2010) 8623e8628
8625
O
O
O
R1OC(O)NH2
ArSO2Na
SiMe3
O
HN
OR
HN
OR1
1 Lewis acid
HN
OR1
4
R
H
aq. HCO2H
R
SO2Ar
R
R
1
7
6
8
Scheme 2. General equation for Lewis acid-catalyzed allylation of N-benzyloxycarbonylamino p-tolylsulfone.
Table 3
Allylation of various N-alkoxycarbonylamino p-tolylsulfone with allyltrimethylsilane catalyzed by In(OTf)3
a
Entry
R in 6
Reaction time (h)
Product 8
Isolated yield (%)b
1
2
3
4
5
6
7
8
6a, C6H4
8.0
9.0
9.0
8.0
8.0
9.0
9.0
9.0
8.0
9.0
9.0
9.0
9.0
8a
8b
8c
8d
8e
8f
8g
8h
8i
87
89
85
91
91
87
92
83
89
87
84
83
80
6b, 4-MeC6H4
6c, 2-MeC6H4
6d, 4-MeOC6H4
6e, 3,4-(MeO)3C6H2
6f, 3-PhOC6H4
6g, 4-BrC6H4
6h, 2-BrC6H4
6i, 4-ClC6H4
9
10
11
12
13
6j, 3-ClC6H4
6k, 2-ClC6H4
6l, 3-FC6H4
8j
8k
8l
6m, 4-CNC6H4
8m
14
9.0
8n
8o
76
6 n,
6o,
O
15
9.0
84
16
17
6p, CH3(CH2)2
6q, CH3(CH2)6
10.0
10.0
8p
8q
70
76
18
10.0
8r
75
6r,
6s,
19
10.0
8s
78
a
Reaction condition: N-alkoxycarbonylamino p-tolylsulfone (6) (1.0 mmol), trimethylsilane (1.5 mmol), and In(OTf)3 (5 mol % with respective to N-sulfonyl aldimine) are used.
Yield of isolated product after column chromatography.
b
3. Conclusion
and monitored by TLC. After the completion, the reaction mixture is
filtered, and the residue is washed with CH2Cl2 (2ꢀ5 mL). The fil-
trate is dried over anhydrous Na2SO4 and concentrated under
vacuum. The crude product is subject to flash column chromatog-
raphy (silica gel, hexaneeEtOAc, 9:1) to obtain the pure product.
An effective Indium triflate-catalyzed allylation reaction of N-
sulfonyl aldimines or N-alkoxycarbonylamino p-tolylsulfone with
allyltrimethylsilane is described. The present method provides
a facile and convenient route for the synthesis of protected
homoallylic amines. The advantages of the present method include:
(1) low catalyst loading and (2) mild reaction conditions.
4.2. Experimental procedure for the allylation of N-
alkoxycarbonylamino p-tolylsulfone with allyltrimethylsilane
Allyltrimethylsilane (1.5 mmol) was added drop-wise to a stir-
red solution of N-alkoxycarbonylamino p-tolylsulfone (1 mmol)
and In(OTf)3 (5 mol %) in CH2Cl2 (3 mL) under nitrogen atmosphere
at rt, The mixture is stirred at rt and monitored by TLC. After the
completion, the reaction mixture is filtered, and the residue is
washed with CH2Cl2 (2ꢀ5 mL). The filtrate is dried over anhydrous
Na2SO4 and concentrated under vacuum. The crude product is
subject to flash column chromatography (silica gel, hexaneeEtOAc,
90:10 to 95:5) to obtain the pure product.
4. Experimental section
4.1. Experimental procedure for the allylation of N-sulfonyl
aldimines with allyltrimethylsilane
To a stirred solution of N-sulfonyl aldimines (1 mmol) and In
(OTf)3 (5 mol %) in CH2Cl2 (3 mL) under nitrogen atmosphere at rt,
allyltrimethylsilane (1.5 mmol) is added. The mixture is stirred at rt

8626
P. Thirupathi, S.S. Kim / Tetrahedron 66 (2010) 8623e8628
The products were characterized by 1H and 13C NMR data that
3H), 3.67 (s, 6H), 2.45e2.39 (m, 2H), 2.32 (s, 3H); 13C NMR
(100 MHz, CDCl3) 152.8, 142.9, 137.6, 136.8, 135.8, 133.2, 129.5,
are consistent with literature values. Melting point, HRMS-FAB, 1H,
and 13C NMR values for new products are given below.
d
129.0, 127.1, 126.3, 118.8, 103.5, 60.4, 57.7, 55.8, 41.7, 21.3; HRMS-FAB
(m/z) [MþH]þ calcd for C20H26NO5S 391.1453, found 391.1453.
4.2.1. Compound 5a. White solid, mp 75e76 ꢁC; IR (KBr): nmax 3261,
1458, 1314, 1159, 1088 cmꢂ1
;
1H NMR (400 MHz, CDCl3)
d
7.51 (d,
4.2.9. Compound 5i. White solid, mp 127 ꢁC; IR (KBr): nmax 3285,
J¼8.4 Hz, 2H), 7.14e7.01 (m, 7H), 5.50e5.43 (m, 1H), 5.11 (br s, 1H),
1518, 1362, 1148, 1064 cmꢂ1 1H NMR (400 MHz, CDCl3)
; d 8.00 (d,
4.99 (d, J¼14.0 Hz, 2H), 4.33 (q, J¼7.0 Hz, 1H), 2.46e2.36 (m, 2H),
J¼8.8 Hz, 2H), 7.55 (d, J¼8.4 Hz, 2H), 7.28 (d, J¼8.8 Hz, 2H), 7.14 (d,
J¼8.0 Hz, 2H), 5.60 (d, J¼6.2 Hz, 1H), 5.50e5.48 (m, 1H), 5.04 (d,
J¼5.5 Hz, 1H), 5.02 (d, J¼12.5 Hz, 1H), 4.44 (q, J¼7.0 Hz, 1H),
2.32 (s, 3H); 13C NMR (100 MHz, CDCl3)
d 143.0, 140.3, 137.4, 133.1,
129.2, 128.3, 127.3, 127.1, 126.5, 119.1, 57.2, 41.8, 21.4.5c,6g,l
2.44e2.39 (m, 2H), 2.35 (s, 3H); 13C NMR (100 MHz, CDCl3)
d: 147.9,
4.2.2. Compound 5b. White solid, mp 159e160 ꢁC; IR (KBr): nmax
146.9, 143.8, 131.9, 129.4, 127.5, 127.0, 123.4, 120.1, 56.6, 41.4, 21.3.6g
3261,1456,1314,1159,1076 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d 7.53 (d,
J¼8.4 Hz, 2H), 7.13e7.07 (m, 4H), 6.98 (d, J¼8.0 Hz, 2H), 5.51e5.44 (m,
4.2.10. Compound 5j. White solid, mp 148e149 ꢁC; IR (KBr): nmax
2H), 5.03 (s, 1H), 5.00e4.98 (m, 1H), 4.32 (q, J¼7.0 Hz,1H), 2.43e2.36
3297, 2210, 1338, 1135, 1064 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d 7.51
(m, 2H), 2.38 (s, 3H); 13C NMR (100 MHz, CDCl3)
d
143.2, 138.8, 137.2,
(d, J¼8.4 Hz, 2H), 7.39 (d, J¼7.8 Hz, 2H), 7.17 (d, J¼8.0 Hz, 2H), 7.10 (d,
J¼8.0 Hz, 2H), 5.65 (d, J¼6.6 Hz, 1H), 5.42e5.39 (m, 1H), 4.99 (d,
J¼4.7 Hz,1H), 4.97 (d, J¼11.7 Hz,1H), 4.35 (q, J¼7.0 Hz,1H), 2.37e2.33
132.9, 132.7, 129.2, 128.3, 128.0, 127.0, 119.2, 56.7, 41.5, 21.3.5c,6l
4.2.3. Compound 5c. Viscous mass; IR (KBr): nmax 3273, 1589, 1422,
(m, 2H), 2.34 (s, 3H); 13C NMR (100 MHz, CDCl3)
d: 145.9,143.5,136.9,
1291, 1148, 1088 cmꢂ1
;
1H NMR (400 MHz, CDCl3)
d
7.54 (d,
132.0, 129.3, 127.4, 127.0, 119.8, 118.5, 110.9, 56.8, 41.3, 21.3.
J¼8.4 Hz, 2H), 7.14 (d, J¼8.4 Hz, 2H), 7.09 (d, J¼6.0 Hz, 2H),
7.02e6.98 (m, 1H), 6.94 (s, 1H), 5.54e5.44 (m, 2H), 5.06 (s, 1H), 5.02
(d, J¼5.8 Hz, 1H), 4.34 (q, J¼7.0 Hz, 1H), 2.44e2.38 (m, 2H), 2.36 (s,
4.2.11. Compound 5k. White solid, mp 84e85 ꢁC; IR (KBr): nmax
3249, 2210, 1327, 1159, 1052 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d 7.49
3H); 13C NMR (100 MHz, CDCl3)
d
143.2, 142.3, 137.1, 134.0, 132.6,
(d, J¼8.4 Hz, 2H), 7.39e7.34 (m, 2H), 7.27e7.22 (m, 2H), 7.10 (d,
J¼8.4 Hz, 2H), 5.60 (br s, 1H), 5.47e5.39 (m, 1H), 5.03e4.96 (m, 2H),
4.35 (q, J¼6.7 Hz, 1H), 2.40e2.35 (m, 2H), 2.36 (s, 3H); 13C NMR
129.5, 129.2, 127.3, 127.0, 126.8, 124.8, 119.4, 56.8, 41.5, 21.3; HRMS-
FAB (m/z) [MþH]þ calcd for C17H19ClNO2S 336.0825, found
336.0825.
(100 MHz, CDCl3)
d 143.5, 141.9, 137.0, 132.1, 131.2, 130.7, 130.2,
129.4, 129.0,126.9, 119.8,118.3,112.1, 56.6, 41.4, 21.3; HRMS-FAB (m/
4.2.4. Compound 5d. White solid, mp 113e114 ꢁC; IR (KBr): nmax
z): [MþH]þ calcd for C18H19N2O2S: 327.1167, found: 327.1165.
3261, 1446, 1327, 1159, 1086 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d 7.60
(d, J¼8.4 Hz, 2H), 7.21e7.17 (m, 2H), 7.12 (d, J¼7.0 Hz, 2H), 7.08e7.05
(m, 2H), 5.58e5.44 (m, 2H), 5.03 (d, J¼15 Hz, 2H), 4.83 (q, J¼7.0 Hz,
1H), 2.48e2.38 (m, 2H), 2.34 (s, 3H); 13C NMR (100 MHz, CDCl3)
4.2.12. Compound 8a. White solid, mp 67 ꢁC; IR (KBr): nmax 3367,
1685, 1530, 1257, 1028 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d
7.31e7.22
(m, 10H), 5.70e5.59 (m, 1H), 5.20 (br s, 1H), 5.10e5.01 (m, 4H), 4.79
d
143.1, 137.8, 136.8, 132.7, 131.9, 129.4, 129.2, 128.3, 128.2, 127.1,
(br s, 1H), 2.51 (s, 2H); 13C NMR (100 MHz, CDCl3)
d 155.7, 142.0,
126.7, 119.3, 54.0, 40.3, 21.4; HRMS-FAB (m/z) [MþH]þ calcd for
136.5, 133.8, 128.6, 128.5, 128.1, 127.3, 126.3, 118.4, 66.8, 54.6, 41.1.5g
C17H19ClNO2S 336.0825, found 336.0826.
4.2.13. Compound 8b. White solid, mp 63e64 ꢁC; IR (KBr): nmax
4.2.5. Compound 5e. White solid, mp 129e130 ꢁC; IR (KBr): nmax
3357, 1697, 1518, 1267, 1040 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d 7.27
3249, 1446, 1327, 1159, 1064 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d
7.52
(s, 5H), 7.11e7.07 (m, 5H), 5.68e5.58 (m, 1H), 5.32 (br s, 1H),
(d, J¼8.4 Hz, 2H), 7.25 (d, J¼8.4 Hz, 2H), 7.13 (d, J¼8.4 Hz, 2H), 6.93
(d, J¼8.4 Hz, 2H), 5.54e5.45 (m, 1H), 5.34 (d, J¼6.6 Hz, 1H), 5.05 (s,
1H), 5.02 (d, J¼8.4 Hz,1H), 4.32 (q, J¼7.0 Hz,1H), 2.43e2.38 (m, 2H),
5.07e4.98 (m, 4H), 4.74 (br s, 1H), 2.46 (s, 2H), 2.28 (s, 3H); 13C NMR
(100 MHz, CDCl3)
d 155.6, 138.9, 136.7, 136.4, 133.8, 129.1, 128.3,
127.9, 126.1, 118.1, 66.5, 54.2, 40.9, 20.9.11f
2.39 (s, 3H); 13C NMR (100 MHz, CDCl3)
d: 143.3, 139.3, 137.2, 132.6,
131.3, 129.3, 128.3, 127.0, 121.1, 119.4, 56.6, 41.5, 21.4; HRMS-FAB
4.2.14. Compound 8c. White solid, mp 51e52 ꢁC; IR (KBr): nmax
(m/z) [MþH]þ calcd for C17H19BrNO2S 380.0143, found 380.0137.
3344, 1673, 1541, 1267, 1028 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d 7.35
(s, 5H), 7.25e7.18 (m, 5H), 5.80e5.70 (m, 1H), 5.23 (br s, 1H),
4.2.6. Compound 5f. White solid, mp 118e119 ꢁC; IR (KBr): nmax
5.17e5.04 (m, 5H), 2.52 (s, 2H), 2.43 (s, 3H); 13C NMR (100 MHz,
3261, 1446, 1314, 1159, 1088 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d
7.55
CDCl3) d 155.7, 140.3, 136.5, 135.4, 134.0, 130.7, 128.5, 128.1, 127.2,
(d, J¼8.4 Hz, 2H), 7.14 (d, J¼8.7 Hz, 2H), 7.01e6.93 (m, 4H),
5.55e5.45 (m, 1H), 5.02 (dd, J¼12.0, 2.0 Hz, 3H), 4.31 (q, J¼7.0 Hz,
1H), 2.49e2.39 (m, 2H), 2.37 (s, 3H), 2.26 (s, 3H); 13C NMR
126.3, 125.1, 118.3, 66.8, 50.8, 40.3, 19.3.11h
4.2.15. Compound 8d. White solid, mp 69e70 ꢁC; IR (KBr): nmax
(100 MHz, CDCl3)
d
142.9, 137.5, 137.3, 137.0, 129.6, 129.2, 128.9,
3309, 1684, 1541, 1255, 1028 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d 7.30
127.1, 126.4, 119.0, 56.9, 41.7, 21.4, 20.9.5c,6g,l
(s, 5H), 7.16 (d, J¼7.8 Hz, 2H), 6.83 (d, J¼8.4 Hz, 2H), 5.70e5.59 (m,
1H), 5.14 (br s, 1H), 5.10e5.00 (m, 4H), 4.72 (br s, 1H), 3.76 (s, 3H),
4.2.7. Compound 5g. White solid, mp 86e87 ꢁC; IR (KBr): nmax
2.49 (s, 2H); 13C NMR (100 MHz, CDCl3)
d 158.7, 155.6, 136.4, 133.8,
3261, 1530, 1314, 1159, 1028 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d
7.52
128.4, 128.0, 127.3, 118.2, 113.8, 66.6, 55.1, 54.0, 40.9.5g
(d, J¼7.8 Hz, 2H), 7.09 (d, J¼8.0 Hz, 2H), 6.94 (d, J¼8.8 Hz, 2H), 6.64
(d, J¼8.4 Hz, 2H), 5.49e5.43 (m, 1H), 5.24 (br s, 1H), 4.99 (d,
J¼6.6 Hz, 2H), 4.27 (q, J¼7.0 Hz, 1H), 3.69 (s, 3H), 2.44e2.36 (m, 2H),
4.2.16. Compound 8e. White solid, mp 70 ꢁC; IR (KBr): nmax 3344,
1697, 1530, 1243, 1124 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d
7.35e7.25
(m, 5H), 6.46 (s, 2H), 5.73e5.62 (m, 1H), 5.18e5.08 (m, 6H), 4.75 (br
s, 1H), 3.81 (s, 9H), 2.51 (s, 2H); 13C NMR (100 MHz, CDCl3)
156.3,
2.32 (s, 3H); 13C NMR (100 MHz, CDCl3)
d: 158.7, 142.8, 137.5, 133.3,
132.4, 131.9, 129.2, 127.7, 127.0, 118.7, 113.6, 56.8, 55.1, 41.7, 21.3.5c
d
153.8, 138.3, 137.6, 136.9, 134.3, 129.0, 128.6, 119.0, 103.7, 67.4, 61.3,
4.2.8. Compound 5h. White solid, mp 67e68 ꢁC; IR (KBr): nmax
56.6, 55.3, 41.7.11f
3257, 1458, 1314, 1159, 1111 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d 7.50
(d, J¼7.8 Hz, 2H), 7.08 (d, J¼7.8 Hz, 2H), 6.21 (s, 2H), 5.58e5.52 (m,
4.2.17. Compound 8f. White solid, mp 45e46 ꢁC; IR (KBr): nmax
2H), 5.05 (d, J¼8.4 Hz,1H), 5.02 (s,1H), 4.30 (q, J¼7.0 Hz,1H), 3.72 (s,
3311, 1679, 1534, 1255, 1056 cmꢂ1 1H NMR (400 MHz, CDCl3)
;

P. Thirupathi, S.S. Kim / Tetrahedron 66 (2010) 8623e8628
8627
d
7.36e7.28 (m, 7H), 7.14e7.10 (m, 1H), 7.03e6.97 (m, 4H), 6.90 (d,
(100 MHz, CDCl3)
d
154.9, 153.4, 141.2, 135.7, 132.6, 127.8, 127.4,
J¼8.0 Hz, 2H), 5.73e5.64 (m, 1H), 5.19 (br s, 1H), 5.14e5.05 (m, 4H),
117.9, 109.5, 105.5, 66.2, 48.0, 37.8.5g
4.82 (br s,1H), 2.48 (s, 2H); 13C NMR (100 MHz, CDCl3)
d 157.3,157.0,
155.6, 144.1, 136.3, 133.4, 129.8, 129.7, 128.4, 128.0, 123.2, 121.0,
118.8, 118.5, 117.4, 116.6, 66.7, 54.1, 40.9; HRMS-FAB (m/z) [MþH]þ
calcd for C24H24NO3 373.1756, found 374.1755.
4.2.26. Compound 8o. White solid, mp 66e67 ꢁC; IR (KBr): nmax
3368, 1673, 1518, 1243, 1028 cmꢂ1 1H NMR (400 MHz, CDCl3)
;
d
7.75e7.66 (m, 3H), 7.42e7.28 (m, 6H), 5.68e5.59 (m, 1H), 5.41 (br
s, 1H), 5.09e4.95 (m, 5H), 2.54 (s, 2H); 13C NMR (100 MHz, CDCl3)
4.2.18. Compound 8g. White solid, mp 87e88 ꢁC; IR (KBr): nmax
d 155.7, 139.3, 136.3, 133.6, 133.2, 132.6, 128.4, 128.3, 128.0, 127.8,
3344, 1684, 1541, 1267, 1040 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d
7.45
127.5, 126.1, 125.7, 124.8, 124.4, 118.4, 66.7, 54.6, 40.8.11f
(d, J¼8.4 Hz, 2H), 7.33 (s, 5H), 7.14 (d, J¼7.0 Hz, 2H), 5.68e5.60 (m,
1H), 5.20 (br s, 1H), 5.13e5.06 (m, 4H), 4.75 (br s, 1H), 2.49 (s, 2H);
4.2.27. Compound 8p. Viscous mass; IR (KBr): nmax 3320, 1697,
13C NMR (100 MHz, CDCl3)
d
155.6, 141.0, 136.2, 133.2, 131.6, 128.5,
1530, 1219, 1088 cmꢂ1 1H NMR (400 MHz, CDCl3)
; d 7.32 (s, 5H),
128.1, 127.9, 121.0, 118.8, 66.8, 53.9, 40.8; HRMS-FAB (m/z) [MþH]þ
5.82e5.74 (m, 1H), 5.17e5.06 (m, 4H), 4.78 (br s, 1H), 3.64e3.59 (m,
1H), 2.36e2.23 (m, 1H), 2.18e2.13 (m, 1H), 1.42e1.38 (m, 2H),
calcd for C18H19BrNO2 360.0599, found 360.0597.
0.99e0.93 (m, 5H); 13C NMR (100 MHz, CDCl3)
d 156.3, 136.8, 134.8,
4.2.19. Compound 8h. White solid, mp 73 ꢁC; IR (KBr): nmax 3311,
128.5, 128.0, 117.4, 66.5, 55.2, 41.4, 36.7, 29.7, 28.3, 26.4, 26.2, 26.1.5d
1693, 1547, 1268, 1030 cmꢂ1 1H NMR (400 MHz, CDCl3)
; d 7.55 (d,
J¼8.0 Hz, 2H), 7.34e7.24 (m, 6H), 7.14e7.09 (m, 1H), 5.75e5.64 (m,
4.2.28. Compound 8q. Viscous mass; IR (KBr): nmax 3320, 1684,
1H), 5.31 (br s, 1H), 5.16e5.03 (m, 5H), 2.56 (s, 2H); 13C NMR
1541, 1267, 1064 cmꢂ1 1H NMR (400 MHz, CDCl3)
; d 7.33 (s, 5H),
(100 MHz, CDCl3)
d
155.5, 141.0, 136.3, 133.5, 133.2, 128.7, 128.5,
5.82e5.74 (m, 1H), 5.66 (s, 2H), 5.14e5.05 (m, 4H), 4.67 (br s, 1H),
3.68e3.64 (m, 1H), 2.43e2.30 (m, 1H), 2.22e2.14 (m, 1H),
2.08e2.00 (m, 3H), 1.85e1.75 (m, 2H), 1.67e1.63 (m, 1H), 1.48e1.20
128.2, 127.6, 127.3, 122.7, 118.7, 66.8, 54.0, 39.4; HRMS-FAB (m/z)
[MþH]þ calcd for C18H19BrNO2 360.0599, found 360.0597.
(m, 1H); 13C NMR (100 MHz, CDCl3)
d 156.2, 136.5, 134.3, 128.4,
4.2.20. Compound 8i. White solid, mp 63 ꢁC; IR (KBr): nmax 3347,
127.9, 126.9, 125.9, 117.7, 66.5, 54.4, 37.4, 36.7, 28.6, 26.9, 25.6, 25.2,
24.3; HRMS-FAB (m/z) [MþH]þ calcd for C18H24NO2 290.2120,
found 290.2120.
1675, 1543, 1267, 1040 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d 7.40e7.27
(m, 6H), 7.17 (d, J¼7.0 Hz, 2H), 5.68e5.60 (m, 1H), 5.23 (br s, 1H),
5.17e5.01 (m, 4H), 4.78 (br s, 1H), 2.51 (s, 2H); 13C NMR (100 MHz,
CDCl3)
d
156.2, 141.3, 136.9, 133.8, 133.6, 129.2, 129.1, 121.0, 128.9,
4.2.29. Compound 8r. White solid, mp 64e65 ꢁC; IR (KBr): nmax
128.7, 128.2, 128.1, 119.4, 67.4, 54.5, 41.4.11h
3309, 1673, 1541, 1255 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d 7.39e7.28
(s, 5H), 5.82e5.76 (m, 1H), 5.09e5.05 (m, 4H), 4.67 (br s, 1H),
3.68e3.58 (m, 1H), 2.31e2.13 (m, 3H), 1.80e1.76 (m, 1H), 0.87e0.77
4.2.21. Compound 8j. White solid, mp 61e62 ꢁC; IR (KBr): nmax
3344, 1673, 1530, 1255, 1028 cmꢂ1
;
1H NMR (400 MHz, CDCl3)
(m, 5H); 13C NMR (100 MHz, CDCl3)
d 156.0, 136.7, 134.8, 134.3,
d
7.34e7.24 (m, 8H), 7.15 (d, J¼2.0 Hz, 1H), 5.73e5.60 (m, 1H), 5.26
(br s, 1H), 5.14e5.04 (m, 4H), 4.89 (br s, 1H), 2.50 (s, 2H); 13C NMR
(100 MHz, CDCl3) 155.6, 144.2, 136.2, 134.3, 133.1, 129.7, 128.4,
128.5, 128.0, 117.8, 66.5, 50.4, 39.5, 36.8, 19.1, 13.9.3e,5h
d
4.2.30. Compound 8s. Viscous mass; IR (KBr): nmax 3320, 1684,
128.1, 127.4, 126.3, 124.4, 118.8, 66.8, 54.0, 40.8; HRMS-FAB (m/z)
[MþH]þ calcd for C18H19ClNO2 316.1104, found 316.1105.
1518, 1243, 1040 cmꢂ1 1H NMR (400 MHz, CDCl3)
; d 7.36e7.28 (m,
5H), 5.82e5.73 (m, 1H), 5.10e5.04 (m, 4H), 4.74 (br s, 1H), 3.71 (br s,
1H), 2.28e2.16 (m, 2H), 1.47 (br s, 1H), 1.44e1.26 (m, 9H), 0.89 (t,
4.2.22. Compound 8k. White solid, mp 65e66 ꢁC; IR (KBr): nmax
J¼7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 155.9, 136.6, 134.2,
3309, 1673, 1541, 1267, 1028 cmꢂ1
;
1H NMR (400 MHz, CDCl3)
128.3, 128.0, 127.8, 117.6, 66.3, 50.6, 39.3, 34.5, 31.6, 29.0, 25.7, 22.4,
13.9; HRMS-FAB (m/z) [MþH]þ calcd for C18H28NO2 286.1807, found
286.1806.
d
7.37e7.17 (m, 8H), 5.75e5.63 (m, 1H), 5.33 (br s, 1H), 5.21e5.03
(m, 5H), 2.54 (s, 2H); 13C NMR (100 MHz, CDCl3)
d
156.1,140.1, 136.9,
134.0, 133.7, 130.5, 129.0, 128.7, 127.9, 127.5, 119.4, 67.4, 52.6,
39.8.5g,h
Acknowledgements
4.2.23. Compound 8l. Viscous mass; IR (KBr): nmax 3320, 1684,
Authors thank the Centre for Biological Modulators of the KRICT
for the financial support. We also acknowledge the assistance by
BK21 provided by Korea Research Council.
1530, 1243, 1028 cmꢂ1 1H NMR (400 MHz, CDCl3)
; d 7.31e7.22 (m,
6H), 7.03 (d, J¼7.0 Hz, 1H), 6.97e6.90 (m, 2H), 5.68e5.90 (m, 1H),
5.26 (d, J¼5.4 Hz,1H), 5.11e5.02 (m, 4H), 4.79 (br s,1H), 2.48 (s, 2H);
13C NMR (100 MHz, CDCl3)
d 164.1, 161.6, 155.6, 144.7, 136.2, 133.2,
References and notes
130.0, 129.9, 128.4, 128.1, 121.8, 118.7, 114.2, 113.9, 113.2, 113.0, 66.8,
54.0, 40.8; HRMS-FAB (m/z) [MþH]þ calcd for C18H19FNO2
300.1400, found 300.1398.
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