H
Synthesis
J.-N. Yuan et al.
Paper
(S)-2-[1-(3-Methoxyphenyl)-2-nitroethyl]-malonic Acid Di-
HPLC: Chiralcel OD column, hexane/i-PrOH (70:30), 1.0 mL/min, tR
phenyldithioester (4da)
(major) = 18.4 min, t (minor) = 33.6 min; 95% ee.
R
Yield: 37.0 mg (80%); white solid; mp 127–130 °C; [α]D25 +72.4 (c
IR (KBr): 1701, 1685, 1568, 1550, 1488, 1477, 1261, 1072, 1010, 964,
825, 748, 686 cm .
–1
0
.25, CHCl3).
HPLC: Chiralcel OD column, hexane/i-PrOH (70:30), 1.0 mL/min, tR
major) = 18.4 min, t (minor) = 20.8 min; 88% ee.
1
H NMR (400 MHz, CDCl ): δ = 7.51–7.45 (m, 5 H), 7.44 –7.37 (m, 5 H),
3
(
7.19 (d, J = 1.6 Hz, 1 H), 7.17 (t, J = 2.2 Hz, 2 H), 7.15 (s, 1 H), 4.81 (d, J =
R
7.2 Hz, 2 H), 4.44 (d, J = 9.6 Hz, 1 H), 4.39–4.34 (m, 1 H).
IR (KBr): 1701, 1558, 1550, 1488, 1477, 1438, 1377, 1261, 1041, 960,
–1
748, 686 cm .
1
(S)-2-[1-(2-Bromophenyl)-2-nitroethyl]-malonic Acid Di-
phenyldithioester (4ia)
H NMR (400 MHz, CDCl ): δ = 7.47–7.44 (m, 3 H), 7.43–7.41 (m, 2 H),
.40–7.35 (m, 3 H), 7.29 (t, J = 16.0 Hz, 1 H), 7.19 (dd, J = 7.6, 1.2 Hz, 2
3
9
7
H), 6.88–6.85 (m, 2 H), 6.79 (t, J = 1.8 Hz, 1 H), 4.85 (t, J = 4.8 Hz, 2 H),
Yield: 43.8 mg (85%).
4
.47 (d, J = 9.2 Hz, 1 H), 4.39–4.33 (m, 1 H), 3.80 (s, 3 H).
HPLC: Chiralcel OD column, hexane/i-PrOH (70:30), 1.0 mL/min, tR
13
C NMR (100 MHz, CDCl ): δ = 190.52, 189.66, 160.06, 136.84,
(major) = 10.9 min, t (minor) = 16.9 min; 94% ee.
R
3
1
34.38, 134.34, 130.33, 130.25, 130.16, 129.63, 129.48, 126.18,
IR (KBr): 1716, 1558, 1550, 1473, 1438, 1377, 1261, 1095, 1022, 968,
120.41, 114.30, 114.13, 69.33, 55.41, 44.41.
–1
798, 748, 686 cm
.
+
HRMS (ESI): m/z [M + Na] calcd for C24H NNaO S : 490.0755; found:
1
21
5
2
H NMR (400 MHz, CDCl ): δ = 7.51 (dd, J = 8.0, 1.2 Hz, 1 H), 7.47–7.35
3
490.0753.
(m, 8 H), 7.33–7.27 (m, 3 H), 7.25–7.19 (m, 2 H), 5.14–5.09 (m, 1 H),
4.96 (d, J = 13.2 Hz, 1 H), 4.88–4.79 (m, 2 H).
(
S)-2-[1-(4-Methylphenyl)-2-nitroethyl]-malonic Acid Di-
9
phenyldithioester (4ea)
(S)-2-[1-(2-Chlorophenyl)-2-nitroethyl]-malonic Acid Di-
Yield: 21.7 mg (78%).
phenyldithioester (4ja)
25
HPLC: Chiralcel OD column, hexane/i-PrOH (70:30), 1.0 mL/min, tR
Yield: 42.4 mg (90%); white solid; 89–90 °C; [α]
D
+85.6 (c 0.5, CH-
(
major) = 13.9 min, t (minor) = 18.3 min; 73% ee.
Cl
HPLC: Chiralcel OD column, hexane/i-PrOH (70:30), 1.0 mL/min, t
(major) = 10.4 min, t (minor) = 16.5 min; 89% ee.
IR (KBr): 2923, 2854, 1701, 1558, 1477, 1438, 1377, 1261, 964, 748,
3
).
R
IR (KBr): 1701, 1685, 1620, 1550, 1477, 1431, 1377, 1261, 1022, 960,
9
R
10, 817, 748, 686 cm–
1
.
R
1
H NMR (400 MHz, CDCl ): δ = 7.47–7.41 (m, 5 H), 7.40–7.34 (m, 3 H),
3
–1
7
.18–7.14 (m, 6 H), 4.85–4.80 (m, 2 H), 4.46 (d, J = 9.2 Hz, 1 H), 4.38–
686 cm .
4.32 (m, 1 H), 2.34 (s, 3 H).
1
H NMR (400 MHz, CDCl ): δ = 7.44–7.36 (m, 9 H), 7.31–7.22 (m, 5 H),
3
5.13–5.07 (m, 1 H), 4.94–4.85 (m, 2 H), 4.79 (d, J = 8.4 Hz, 1 H).
(
S)-2-[1-(4-Fluorophenyl)-2-nitroethyl]-malonic Acid Di-
13
C NMR (100 MHz, CDCl ): δ = 190.11, 189.31, 137.21, 134.84,
3
9
phenyldithioester (4fa)
134.14, 134.11, 130.27, 130.21, 130.07, 129.45, 129.33, 128.78,
Yield: 41.0 mg (90%).
128.38, 126.37, 125.71, 125.66, 68.74, 43.68.
HRMS (ESI): m/z [M + Na]+ calcd for C23H18ClNNaO S : 494.0251;
HPLC: Chiralcel OD column, hexane/i-PrOH (70:30), 1.0 mL/min, tR
4
2
(
major) = 15.9 min, t (minor) = 22.0 min; 77% ee.
found: 494.0258.
R
IR (KBr): 1701, 1620, 1550, 1508, 1442, 1377, 1234, 1161, 964, 879,
–1
837, 748, 667 cm
.
(S)-2-[1-(3-Chlorophenyl)-2-nitroethyl]-malonic Acid Di-
1
phenyldithioester (4ka)
H NMR (400 MHz, CDCl ): δ = 7.48–7.45 (m, 3 H), 7.44–7.40 (m, 2 H),
3
25
7
7
4
.39–7.35 (m, 3 H), 7.28–7.24 (m, 2 H), 7.17 (dd, J = 7.6, 1.2 Hz, 2 H),
.07 (t, J = 8.6 Hz, 2 H), 4.81 (d, J = 6.4 Hz, 2 H), 4.45 (d, J = 9.6 Hz, 1 H),
.46–4.36 (m, 1 H).
Yield: 42.0 mg (90%); white solid; mp 99–103 °C; [α]
CHCl ).
HPLC: Chiralcel OD column, hexane/i-PrOH (70:30), 1.0 mL/min, tR
major) = 16.8 min, t (minor) = 20.8 min; 89% ee.
D
+70.2 (c 0.25,
3
(
R
(
S)-2-[1-(2-Fluorophenyl)-2-nitroethyl]-malonic Acid Di-
IR (KBr): 1701, 1558, 1550, 1477, 1438, 1377, 1276, 1261, 964, 748,
9
phenyldithioester (4ga)
–1
690 cm
.
Yield: 40.8 mg (90%).
1
H NMR (400 MHz, CDCl ): δ = 7.48–7.45 (m, 3 H), 7.44–7.42 (m, 2 H),
3
HPLC: Chiralcel OD column, hexane/i-PrOH (70:30), 1.0 mL/min, tR
7.40 (d, J = 8.0 Hz, 2 H), 7.33–7.31 (m, 2 H), 7.28–7.26 (m, 2 H), 7.22–
7.16 (m, 3 H), 4.85 (d, J = 6.8 Hz, 2 H), 4.43 (d, J = 9.2 Hz, 1 H), 4.40–
(
major) = 10.0 min, t (minor) = 14.6 min; 99% ee.
R
4
13
.34 (m, 1 H).
IR (KBr): 1701, 1620, 1550, 1477, 1438, 1377, 1261, 1157, 1022, 964,
–1
794, 748, 686 cm
.
C NMR (100 MHz, CDCl ): δ = 189.23, 188.44, 136.34, 133.96,
3
1
133.27, 133.23, 129.39, 129.33, 129.19, 128.58, 128.46, 127.90,
27.51, 125.50, 124.84, 124.79, 67.86, 42.81.
HRMS (ESI): m/z [M + Na]+ calcd for C23H18ClNNaO S : 494.0247;
H NMR (400 MHz, CDCl ): δ = 7.47–7.43 (m, 5 H), 7.39–7.32 (m, 4 H),
.24–7.21 (m, 1 H), 7.15–7.10 (m, 4 H), 4.94 (dd, J = 13.6, 10.0 Hz, 1 H),
.80 (dd, J = 13.6, 4.4 Hz, 1 H), 4.65 (d, J = 10.0 Hz, 1 H), 4.61–4.55 (m,
3
1
7
4
4
2
1
H).
found: 494.0247.
(
S)-2-[1-(4-Bromophenyl)-2-nitroethyl]-malonic Acid Di-
(S)-2-[1-(4-Trifluoromethylphenyl)-2-nitroethyl]-malonic Acid
Diphenyldithioester (4la)
9
9
phenyldithioester (4ha)
Yield: 41.2 mg (80%).
Yield: 42.9 mg (85%).
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–J