Enantioselective Conjugate Addition of Pyrazolones to Nitroalkenes Catalyzed by Binaphthyl-modified Squaramide Organocatalyst

Full text of DOI:10.1002/bkcs.11241

Note
DOI: 10.1002/bkcs.11241
BULLETIN OF THE
Y. H. Kim et al.
KOREAN CHEMICAL SOCIETY
Enantioselective Conjugate Addition of Pyrazolones to Nitroalkenes
Catalyzed by Binaphthyl-modified Squaramide Organocatalyst
*
Yong Hwan Kim, Ji Hee Yoon, Min Young Lee, and Dae Young Kim
Department of Chemistry, Soonchunhyang University, Asan, Chungnam, 31538, Korea.
E-mail: dyoung@sch.ac.kr
*
Received July 13, 2017, Accepted August 3, 2017
Keywords: Pyrazolone, Conjugate addition, Nitroalkenes, Organocatalysis, Asymmetric catalysis
Pyrazolones have attracted much attention in synthetic
organic chemistry due to their popularity in many natural
and diverse ranges of biologically active compounds, such
as enzyme inhibitors and antibacterial, analgesic, antifungal,
7, 98% yield and 94% ee). Then DCE was selected as the
solvent to further study the effect of catalyst loading. This
process tolerates catalyst loading down to 2.5, or 1 mol %
without compromising the enantioselectivity, but yields
were slightly decreased (Table 1, entries 13–15). The abso-
lute configuration of 3 was established by comparison of
the specific rotation value and chiral HPLC analysis with
1
and antiplatelet drugs. Therefore, the asymmetric synthesis
of pyrazolone derivatives has become the subject of great
2
interest over the past decades. Among the general protocols
4
for the synthesis of chiral pyrazolone derivatives, catalytic
enantioselective conjugated reactions have been intensively
previously reported values.
With the optimized conditions in hand, we investigated
the scope of the enantioselective conjugate addition of
pyrazol-5-ones with various aromatic nitroalkenes 2 in the
presence of 1 mol % of binaphthyl-modified squaramide III
in DCE at room temperature (Table 2, entries 1–10). Various
3
studied with various Michael acceptors. Since the pioneer
work on the enantioselective conjugate addition of pyrazo-
lones to nitroalkenes using the thiourea catalyst disclosed
by Yuan and coworkers in 2010, Ma, Du, Trivedi, Zhou,
and Li groups reported successively the enantioselective
organocatalytic Michael addition of pyrazolones to nitroalk-
nitroalkenes
2
with electron-donating and electron-
withdrawing substituent in aryl groups furnished the corre-
sponding conjugate addition products 3 with excellent yields
4
enes using various types of organocatalysts. Although these
(91–97%) and excellent enantioselectivities (90–95%). The
are to some extent satisfied as synthetic process, new orga-
nocatalytic conjugate addition of pyrazolones to nitroalk-
enes is highly desired.
reaction of aliphatic nitroalkene also undergoes the addition
reaction in good yield, although with somewhat reduced
enantioselectivity relative to the aryl substrates (Table 2,
entry 11).
In summary, we have developed highly efficient cata-
lytic enantioselective conjugate addition reaction of
pyrazol-5-ones to nitroalkenes using binaphthyl-modified
squaramide. The desired Michael products were obtained
inexcellent yields and enantioselectivities (up to 95%
ee). We believe that this method provides a practical
entry to biologically useful chiral 4-substituted pyrazol
derivatives.
In connection with our continuing research program on
the development of new enantioselctieve synthetic
5
methods, we recently reported enantioselective conjugate
addition of active methylenes and methines using chiral
6
organocatalysts. Herein, we report the asymmetric conju-
gate addition of pyrazol-5-ones to nitroalkenes catalyzed by
binaphthyl-modified bifunctional organocatalysts bearing
both central and axial chiral elements (Figure 1).
In an attempt to validate the feasibility of the asymmetric
conjugate addition of pyrazol-5-ones, we investigated a
reaction system with 3-methyl-1-phenyl-1H-pyrazol-5(4H)-
one (1) with β-nitrostyrene (2a) in the presence of 5 mol %
of catalyst in dichloromethane (DCM) at room temperature.
We examined the effect of catalysts I–VI on enantioselec-
tivity (Table 1, entries 1–6). High yields and excellent
enantioselectivities were observed using binaphthyl-
modified squaramide catalyst III (Table 1, entry 3, 94%
ee). A survey of the reaction media indicated that common
solvents (Table 1, entries 3 and 7–12), such as DCM, 1,2-
dichloroethane (DCE), chloroform, ether, THF, toluene,
and acetonitrile were well tolerated in this conjugate addi-
tion with slightly decrease in enantioselectivity. DCE led to
excellent yield and enantioselectivity (Table 1, entry
Experimental
Typical procedure for the Michael addition of 3-methyl-
1-phenyl-1H-pyrazol-5(4H)-one (1a) with β-nitrostyrene
(2a). To a stirred solution of 3-methyl-1-phenyl-1H-pyra-
zol-5(4H)-one (1a, 52.2 mg, 0.3 mmol) and catalyst III
(2.1 mg, 3 μmol) in DCE (3.0 mL) was added
β-nitrostyrene (2a, 44.7 mg, 0.3 mmol) at room tempera-
ture. The reaction mixture was stirred for 24 h at room tem-
perature. After completion of the reaction, the resulting
solution was concentrated in vacuo and the obtained resi-
due was purified by flash column chromatography (EtOAc:
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Hex, 1:2) to afford (R)-3-methyl-4-(2-nitro-1-phenylethyl)-
1
-phenyl-1H-pyrazol-5-ol (3a, 93 yield, 90 mg).
(
R)-3-methyl-4-(2-nitro-1-phenylethyl)-1-phenyl-1H-pyr-
H
ꢀ
4e
azol-5-ol (3a). A white solid; m.p. 58–59 C [lit.
m.p. 57–59 C]; [α]
NMR (400 MHz, CDCl ) δ = 7.17–7.31 (m, 7H), 7.08 (t,
ꢀ
27
1
= −322.9 (c = 0.9, CH Cl ). H
D
2 2
3
J = 8.0 Hz, 2H), 6.99 (t, J = 7.0 Hz, 1H), 5.22 (dd,
J = 9.6 Hz, 18.6 Hz, 1H), 4.78 (dd, J = 6.4 Hz, 12.8 Hz,
1
3
1
H), 4.42 (t, J = 7.8 Hz, 1H), 1.89 (s, 3H) ppm; C NMR
(
1
1
100 MHz, CDCl ) δ = 147.2, 139.2, 135.7, 130.9, 128.8,
3
27.5, 127.4, 125.9, 120.5, 119.3, 103.7, 75.1, 39.7,
0.7 ppm; The ee value was 94%, t (minor) = 9.00 min,
R
tR (major) = 10.84 min (Chiralpak IA, λ = 254 nm, 20% i-
PrOH/hexane, flow rate = 1.0 mL/min).
(
R)-4-(1-(4-chlorophenyl)-2-nitroethyl)-3-methyl-1-pheny-
ꢀ
4e
l-1H-pyrazol-5-ol (3b). A white solid; m.p. 61-63 C [lit.
m.p. 60–63 C]; [α]
NMR (400 MHz, CDCl ) δ = 7.75 (dd, J = 0.8 Hz,
ꢀ
29
1
= −209.60 (c = 0.1, CH Cl ). H
D
2 2
3
8
7
1
1
1
1
.6 Hz, 2H), 7.63 (d, J = 8.0 Hz, 2H), 7.34–7.40 (m, 4H),
.17 (t, J = 7.6 Hz, 1H), 5.45 (dd, J = 8.8 Hz, 13.4 Hz,
H), 5.22–5.29 (m, 1H), 4.68 (t, J = 8.0 Hz, 1H), 2.27 (s,
13
H) ppm; C NMR (100 MHz, CD COCD ) δ = 149.5,
3
3
40.0, 138.3, 133.4, 130.6, 129.7, 129.5, 125.6, 119.6,
05.7, 77.2, 39.9, 39.8, 11.3 ppm; The ee value was 94%,
Figure 1. Structure of organocatalysts.
a
Table 1. Optimization of the reaction conditions.
b
c
Entry
Cat.
Solvent
Time (h)
Yield (%)
ee (%)
1
2
3
4
5
6
7
8
9
I
II
III
IV
V
VI
III
III
III
III
III
III
III
III
III
DCM
DCM
DCM
DCM
DCM
DCM
DCE
CHCl3
2
Et O
THF
PhMe
MeCN
DCE
DCE
DCE
10
10
11
24
24
21
11
13
17
15
18
36
17
24
36
89
86
95
84
82
87
98
87
79
85
97
97
97
94
88
81
70
94
42
51
59
94
94
76
80
87
55
94
94
92
10
11
12
13
14
15
a
d
e
f
Reaction conditions: 3-methyl-1-phenyl prazol-5-one (1, 0.3 mmol), β-nitrostyrene (2a, 0.3 mmol), solvent (3.0 mL) catalyst (0.015 mmol) at
room temperature.
Isolated yield.
b
c
d
e
f
Enantiopurity was determined by HPLC analysis using Chiralpak IA column.
.5 mol % catalyst loading.
mol % catalyst loading.
2
1
0
.5 mol % catalyst loading.
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KOREAN CHEMICAL SOCIETY
a
Table 2. Substrate scope.
1
b
c
Entry
R
Time (h)
Yield (%)
ee (%)
1
2
3
4
5
6
7
8
9
Ph
4-Cl-C H
4-OMe-C
4-Me-C
2-F-C H
2-Cl-C
3-NO -C H
1-naphthyl
2-furanyl
2-thienyl
24
18
16
23
18
24
24
21
24
24
18
3a, 94
3b, 95
3c, 93
3d, 97
3e, 97
3f, 97
3g, 92
3h, 91
3i, 97
3j, 93
3k, 77
94
94
92
92
95
90
92
92
94
94
80
6
4
6
H
4
6
H
4
6
4
6 4
H
2
6 4
1
1
a
0
1
d
PhCH CH
2
2
Reaction conditions: 3-methyl-1-phenyl prazol-5-one (1, 0.3 mmol), nitroalkene 2 (0.3 mmol), solvent (3.0 mL), catalyst III (0.003 mmol) at
room temperature.
Isolated yield.
b
c
d
Enantiopurity was determined by HPLC analysis using Chiralpak IA (for 3a–3h, and 3k), ID (for 3j), AS-H (for 3i) columns.
5
mol % catalyst loading.
t (minor) = 13.44 min, t (major) = 25.31 min (Chiralpak
IA, λ = 254 nm, 15% i-PrOH/hexanes, flow rate = 1.0
mL/min).
(S)-4-(1-(2-fluorophenyl)-2-nitroethyl)-3-methyl-1-pheny-
R
R
ꢀ
4e
l-1H-pyrazol-5-ol (3e). A white solid; m.p. 141–143 C [lit.
ꢀ
27
1
m.p. 143–145 C]; [α] = −213.78 (c = 0.81, CH Cl ). H
D
2
2
(
R)-4-(1-(4-methoxyphenyl)-2-nitroethyl)-3-methyl-1-phe-
NMR (400 MHz, CDCl ) δ = 9.71 (s, 1H), 7.53 (t, J = 7.6 Hz,
3
ꢀ
nyl-1H-pyrazol-5-ol (3c). A white solid; m.p. 56–58 C
1H), 7.26–7.32 (m, 2H), 7.14–7.20 (m, 3H), 6.97–7.07 (m, 3H),
4e
ꢀ
28
D
[lit.
m.p1. 54–56 C]; [α]
= −181.47 (c = 0.19,
5.33 (dd, J = 8.8 Hz, 12.0 Hz, 1H), 4.79–4.87 (m, 2H), 2.03 (s,
13
CH Cl ). H NMR (400 MHz, CDCl ) δ = 7.60 (d,
3H) ppm; C NMR (100 MHz, CDCl ) δ = 159.8 (d, JC–
3
2
2
3
J = 8.4 Hz, 2H), 7.36 (d, J = 8.8 Hz, 2H), 7.23 (t,
J = 8.0 Hz, 2H), 7.01 (t, J = 7.6 Hz, 1H) 6.72 (d,
J = 8.8 Hz, 2H), 5.28 (dd, J = 8.6 Hz, 13.2 Hz, 1H), 5.04
F
= 245 Hz), 147.9, 135.8, 129.2 (d, JC–F = 2.8 Hz), 129.1,
128.9, 125.9, 125.6 (d, JC–F = 14.3 Hz), 124.5 (d, JC–
= 3.9 Hz), 120.2, 115.4 (d, JC–F = 21.9 Hz), 103.5, 75.1,
31.6, 10.7 ppm; The ee value was 95%, t (minor) = 10.15
min, t (major) = 16.62 min (Chiralpak IA, λ = 254 nm, 15%
i-PrOH/hexane, flow rate = 1.0 mL/min).
(S)-4-(1-(2-chlorophenyl)-2-nitroethyl)-3-methyl-1-pheny-
F
(
3
dd, J = 7.6 Hz, 13.2 Hz, 1H), 4.46 (t, J = 8.0 Hz, 1H),
.61 (s, 3H), 2.08 (s, 3H) ppm; C NMR (100 MHz,
R
1
3
R
CD COCD ) δ = 158.4, 147.9, 137.0, 131.6, 128.8, 128.4,
3
3
1
9
28.3, 128.1, 124.1, 118.2, 113.4, 105.1, 76.3, 54.1, 38.4,
ꢀ
4e
.9 ppm; The ee value was 92%, t (minor) = 18.06 min,
l-1H-pyrazol-5-ol (3f). A white solid; m.p. 152–154 C [lit.
R
ꢀ
22
1
tR (major) = 30.69 min (Chiralpak IA, λ = 254 nm, 15% i-
PrOH/hexane, flow rate = 1.0 mL/min).
m.p. 153–156 C]; [α]
= −193.96 (c = 1.00, CH Cl ). H
D 2 2
NMR (400 MHz, CDCl ) δ = 10.82 (s, 1H), 7.59 (d,
J = 7.2 Hz, 1H), 7.33 (d, J = 8.0 Hz, 1H), 6.99–7.21 (m, 7H),
3
(
R)-3-methyl-4-(2-nitro-1-(p-tolyl)ethyl)-1-phenyl-1H-py-
ꢀ
4e
razol-5-ol (3d). A white solid; m.p. 168–171 C [lit.
5.25 (t, J = 11.6 Hz, 1H), 4.95 (dd, J = 5.4 Hz, 9.8 Hz, 1H),
ꢀ
28
D
13
m.p. 168–170 C]; [α]
= −339.48 (c = 0.62, CH Cl ).
4.63 (dd, J = 5.2 Hz, 13.2 Hz, 1H), 1.97 (s, 3H) ppm;
C
2
2
1
H NMR (400 MHz, CD COCD ) δ = 7.75 (d, J = 8.0 Hz,
NMR (100 MHz, CDCl3) δ = 162.4, 147.7, 136.3, 135.6,
133.1, 129.9, 129.0, 127.4, 126.3, 120.8, 102.0, 75.3, 35.9,
11.0 ppm; The ee value was 90%, t (minor) = 9.65 min, t R
R R
(major) = 16.40 min (Chiralpak IA, λ = 254 nm, 15% i-PrOH/
hexane, flow rate = 1.0 mL/min).
3
3
2
7
5
1
H), 7.45 (d, J = 8.0 Hz, 2H), 7.38(t, J = 7.8 Hz, 2H),
.17–7.11 (m, 3H), 5.43 (dd, J = 8.6 Hz, 13.6 Hz, 1H),
.23 (dd, J = 7.8 Hz, 12.8 Hz, 1H), 4.62 (t, J = 7.8 Hz,
1
3
H), 2.27 (s, 3H), 2.23 (s, 3H) ppm; C NMR (100 MHz,
CD COCD ) δ = 148.1, 137.1, 136.7, 136.1, 128.7, 128.3,
(R)-3-methyl-4-(2-nitro-1-(3-nitrophenyl)ethyl)-1-phenyl-
3
3
ꢀ
1
27.2, 118.1, 105.1, 76.1, 38.8, 19.6, 9.9 ppm; The ee
1H-pyrazol-5-ol (3g). A white solid; m.p. 176–179 C
4
e
ꢀ
24
value was 92%, t (minor) = 12.10 min, t (major) = 17.15
[lit.
m.p. 180–182 C]; [α]
2
= −188.80 (c = 0.50,
R
R
D
1
min (Chiralpak IA, λ = 254 nm, 15% i-PrOH/hexane, flow
rate = 1.0 mL/min).
CH Cl ); H NMR (400 MHz, CD COCD ) δ = 8.55 (s,
2
3
3
1H), 8.12 (dd, J = 8.4 Hz, 12.8 Hz, 2H), 7.73 (d,
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BULLETIN OF THE
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KOREAN CHEMICAL SOCIETY
J = 7.6 Hz, 2H), 7.63 (t, J = 8.0 Hz, 1H), 7.37 (t,
J = 8.0 Hz, 2H), 7.16 (t, J = 7.2 Hz, 1H), 5.49 (dd,
J = 8.4 Hz, 13.2 Hz, 1H), 5.38 (dd, J = 7.2 Hz, 13.4 Hz,
J = 5.4 Hz, 12.6 Hz, 1H), 3.18–3.26 (m, 1H), 2.12–2.56
13
(m, 2H), 2.16–2.23 (m, 1H), 1.92 (m, 4H) ppm; C NMR
(100 MHz, CD COCD ) δ = 148.9, 141.0, 137.3, 128.3,
3
3
1
3
1H), 4.87 (t, J = 7.6 Hz, 1H), 2.32 (s, 3H) ppm; C NMR
128.0, 127.8, 127.7, 125.2, 123.9, 117.8, 103.6, 76.8, 33.4,
(
1
7
100 MHz, CD COCD ) δ = 150.8, 150.7, 144.7, 139.5,
32.6, 30.3, 9.8 ppm; The ee value was 80%, t (minor) =
10.21 min, tR (major) = 14.43 min (Chiralpak IA, λ =
254 nm, 15% i-PrOH/hexane, flow rate = 1.0 mL/min).
3
3
R
36.8, 132.2, 131.1, 127.1, 125.1, 124.4, 120.9, 105.9,
8.4, 40.4, 12.6 ppm; The ee value was 92%, t (minor) =
R
14.19 min, tR (major) = 27.40 min (Chiralpak IA,
λ = 254 nm, 15% i-PrOH/hexane, flow rate = 1.0 mL/min).
Acknowledgment. This research was supported by Soon-
chunhyang University Research Fund.
(R)-3-methyl-4-(1-(naphthalen-1-yl)-2-nitroethyl)-1-phen-
ꢀ
yl-1H-pyrazol-5-ol (3h). A white solid; m.p. 94–95 C
4e
ꢀ
24
[lit.
m.p. 94–96 C]; [α]
= −250.03 (c = 0.75,
CH Cl ); H NMR (400 MHz, CDCl ) δ = 9.77 (s, 1H),
.14 (d, J = 8.8 Hz, 1H), 7.86 (d, J = 8.0 Hz, 1H), 7.73 (d,
J = 8.4 Hz, 1H), 7.61 (d, J = 7.2 Hz, 1H), 7.49–7.54 (m,
H), 7.28–7.36 (m, 3H), 7.11 (t, J = 8.0 Hz, 2H), 7.00 (t,
J = 7.6Hz, 1H), 5.39–5.49 (m, 2H), 4.75 (dd, J = 4.8 Hz,
D
1
References
2
2
3
8
1
2
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3
1
2.8 Hz, 1H), 1.89 (s, 3H) ppm; C NMR (100 MHz,
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CDCl ) δ = 146.9, 132.9, 132.8, 129.6, 128.2, 127.9,
3
3. (a) Z.-L. Tao, W.-Q. Zhang, D.-F. Chen, A. Adele, L.-Z. Gong,
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1
27.2, 125.7, 124.8, 124.8, 124.7, 124.3, 121.2, 119.2,
03.4, 74.8, 34.0, 10.1 ppm; The ee value was 92%, tR
(minor) = 24.24 min, tR (major) = 28.12 min (Chiralpak
3
58, 1713.
ID, λ = 254 nm, 15% i-PrOH/hexane, flow rate = 1.0
mL/min).
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(
R)-4-(1-(furan-2-yl)-2-nitroethyl)-3-methyl-1-phenyl-1H-
ꢀ
4e
pyrazol-5-ol (3i). A white solid; m.p. 42–44 C [lit.
ꢀ
24
1
m.p. 42–44 C]; [α]
= −89.10 (c = 0.58, CH Cl ); H
D
2 2
NMR (400 MHz, CDCl ) δ = 7.30 (d, J = 7.6 Hz, 2H),
3
4
844; (d) J.-H. Li, D.-M. Du, Org. Biomol. Chem. 2013, 11,
7
.25 (d, J = 4.8 Hz, 1H), 7.16–7.05 (m, 3H), 6.20 (t,
6
215; (e) K. S. Rao, P. Ramesh, R. Trivedi, M. L. Kantam,
J = 2.2 Hz, 1H), 5.99 (d, J = 3.2 Hz, 1H), 4.92 (dd,
Tetrahedron Lett. 2016, 57, 1227.
1
1
= 8.8 Hz, 12.8 Hz, 1H), 4.77 (dd, J = 6.8 Hz, 13.2 Hz,
H), 4.60 (t, J = 7.2 Hz, 1H), 1.92 (s, 3H) ppm; C NMR
5. (a) S. B. Woo, C. W. Suh, K. O. Koh, D. Y. Kim, Tetrahe-
dron Lett. 2013, 54, 3359; (b) J. H. Lee, D. Y. Kim, Bull.
Korean Chem. Soc. 2013, 34, 1619; (c) C. W. Suh,
T. H. Han, D. Y. Kim, Bull. Korean Chem. Soc. 2013, 34,
1
3
(100 MHz, CDCl ): δ = 151.1, 147.0, 141.8, 135.6, 128.8,
3
1
1
26.0, 120.5, 119.2, 110.5, 106.9, 100.4, 74.7, 33.0,
1
623; (d) C. W. Suh, C. W. Chang, K. W. Choi, Y. J. Lim,
0.5 ppm; The ee value was 94%, t (minor) = 14.57 min,
R
D. Y. Kim, Tetrahedron Lett. 2013, 54, 3651; (e) Y. K. Kang,
H. J. Lee, H. W. Moon, D. Y. Kim, RSC Adv. 2013, 3, 1332;
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PrOH/hexane, flow rate = 1.0 mL/min).
(
f) C. W. Suh, D. Y. Kim, Bull. Korean Chem. Soc. 2014, 35,
(
1
R)-3-methyl-4-(2-nitro-1-(thiophen-2-yl)ethyl)-1-phenyl-
9
2
8; (g) S. B. Woo, D. Y. Kim, J. Fluorine Chem. 2015, 178,
14; (h) C. W. Suh, D. Y. Kim, Tetrahedron Lett. 2015, 56,
ꢀ
H-pyrazol-5-ol (3j). A white solid; m.p. 54–55 C [lit.
4e
ꢀ
22
1
m.p. 52–54 C]; [α]
= −303.07 (c = 0.65, CH Cl ); H
D
2 2
5661; (i) S. J. Kwon, Y. J. Kim, D. Y. Kim, Tetrahedron Lett.
2016, 57, 4371; (j) S. J. Kwon, D. Y. Kim, Org. Lett. 2016,
18, 4562; (k) S. J. Kwon, M. K. Gil, D. Y. Kim, Tetrahedron
Lett. 2017, 58, 1592.
NMR (400 MHz, CDCl ) δ = 7.29 (d, J = 7.6 Hz, 2H),
3
7
.14–7.02 (m, 4H), 6.82–6.89 (m, 2H) 5.15 (t,
J = 10.4 Hz, 1H), 4.69–4.78 (m, 2H) 1.94 (s, 3H) ppm;
1
3
C NMR (100 MHz, CDCl ) δ = 146.7, 141.5, 135.6,
6. (a) Y. K. Kang, S. M. Kim, D. Y. Kim, J. Am. Chem. Soc.
3
2
010, 132, 11847; (b) Y. K. Kwon, Y. K. Kang, D. Y. Kim,
1
7
1
28.8, 127.0, 126.0, 125.0, 124.6, 120.5, 119.2, 102.8,
Bull. Korean Chem. Soc. 2011, 32, 1773; (c) D. Y. Kim, Bull.
Korean Chem. Soc. 2013, 34, 3463; (d) Y. K. Kang, D. Y. Kim,
Adv. Synth. Catal. 2013, 355, 3131; (e) Y. K. Kang, D. Y. Kim,
Chem. Commun. 2014, 50, 222; (f ) C. W. Suh, D. Y. Kim,
Org. Lett. 2014, 16, 5374; (g) C. W. Suh, S. B. Woo,
D. Y. Kim, Asian J. Org. Chem. 2014, 3, 399; (h) C. W. Suh,
H. J. Jeong, D. Y. Kim, Bull. Korean Chem. Soc. 2015, 36, 406;
(i) M. H. Kim, H. J. Jeong, D. Y. Kim, Bull. Korean Chem.
Soc. 2015, 36, 1155; (j) C. W. Suh, S. J. Kwon, D. Y. Kim,
Org. Lett. 2017, 19, 1334.
5.5, 34.5, 10.5 ppm; The ee value was 94%, t (minor) =
R
6.52 min, tR (major) = 24.32 min (Chiralpak AS-H,
λ = 254 nm, 15% i-PrOH/hexane, flow rate = 1.0 mL/min).
(R)-3-methyl-4-(1-nitro-4-phenylbutan-2-yl)-1-phenyl-1H-
ꢀ
pyrazol-5-ol (3k).
A white solid; m.p. 93–96 C;
2
5
1
[
α]
= −116.29 (c = 0.82, CH Cl ); H NMR (400 MHz,
D 2 2
CD COCD ) δ = 7.67 (dd, J = 1.2 Hz, 8.8 Hz, 2H), 7.27
3
3
(t, J = 8.0 Hz, 2H), 7.13 (t, J = 7.2 Hz, 2H), 7.01–7.06 (m,
4
H), 4.85 (dd, J = 9.6 Hz, 12.4 Hz, 1H), 4.64 (dd,
Bull. Korean Chem. Soc. 2017
© 2017 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.bkcs.wiley-vch.de
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