10.1002/ejoc.201801639
European Journal of Organic Chemistry
FULL PAPER
(S)-3-Isobutyl-3,4-dihydroquinoxalin-2(1H)-one (3d):[8b] 0.161 g, 98%
yield, 100% ee. Yellow viscous oil. Rf = 0.75 (hexane/EtOAc = 1:1, v/v).
(S)-3-(3,4-Dihydroxybenzyl)-3,4-dihydroquinoxalin-2(1H)-one (3h):[24]
16.7 mg, 68% yield , 99.2% ee (0.090 mmol of 2h used, 12 equiv. of Zn
used). White solid; m.p. 86–90 °C. Rf = 0.44 (CH2Cl2/MeOH = 10:1, v/v).
[α]D = –84.8 (c = 0.07, MeOH). IR: ṽ = 3330, 3067, 2960, 2919, 1673,
1604, 1507, 1425, 1367, 1288, 1230, 749 cm–1 1H NMR (400 MHz,
.
CD3COCD3) d = 9.31 (s, 1H), 7.85 (s, 2H), 6.88–6.63 (m, 6H), 6.54 (d, J
= 7.7 Hz, 1H), 5.04 (s, 1H), 3.97–3.86 (m, 1H), 2.96 (dd, J = 13.4, 3.4 Hz,
1H), 2.65 (dd, J = 13.4, 10.0 Hz, 1H) ppm. 13C NMR (101 MHz,
CD3COCD3) d = 167.40, 144.96, 143.71, 133.49, 128.86, 126.34, 122.95,
120.75, 118.34, 116.35, 115.26, 114.67, 114.27, 57.92, 36.88 ppm.
HRMS (ESI-TOF): m/z calcd for [C15H14N2O3+H]+ [M+H]+ 271.1077,
found 271.1079. Chiral HPLC conditions: Chiralcel® OJ–H column (4.6
mm´250 mm), hexane/iPrOH = 20:80, flow rate: 0.5 mL/min, detected
wavelength: 240 nm, retention time: 9.02 min ((R)-enantiomer), 9.46 min
((S)-enantiomer).
20
[α]D = +47.2 (c = 0.75, MeOH). IR: ṽ = 3333, 3211, 3066, 2956, 2870,
1677, 1605, 1507, 1377, 1303, 744 cm–1. 1H NMR (400 MHz, CDCl3) d =
8.68 (s, 1H), 6.99–6.86 (m, 1H), 6.80–6.72 (m, 2H), 6.68 (d, J = 7.8 Hz,
1H), 3.93–3.97 (m, 2H), 1.83–1.59 (m, 3H), 0.98 (d, J = 6.5 Hz, 3H), 0.96
(d, J = 6.5 Hz, 3H) ppm. 13C NMR (101 MHz, CDCl3) d = 169.40, 132.82,
125.43, 123.80, 119.44, 115.34, 114.26, 54.55, 40.16, 24.25, 23.29,
21.46 ppm. HRMS (ESI-TOF): m/z calcd for [C12H16N2O+H]+ [M+H]+
205.1335, found 205.1334. Chiral HPLC conditions: Chiralcel® OJ–H
column (4.6 mm´250 mm), hexane/iPrOH = 75:25, flow rate: 1 mL/min,
detected wavelength: 240 nm, retention time: 6.35 min ((S)-enantiomer).
20
(S)-1,2,3,3a-Tetrahydropyrrolo[1,2-a]quinoxalin-4(5H)-one
(3e):[8b]
0.116 g, 78% yield, 99.4% ee; Light yellow solid; m.p. 164–165 °C. Rf =
20
0.55 (hexane/EtOAc = 1:1, v/v). [α]D = –94.0 (c = 0.25, MeOH); IR: ṽ =
3198, 3075, 2979, 2927, 1679, 1612, 1509, 1405, 1365, 1321, 741 cm–1
.
(S)-3-(Hydroxymethyl)-3,4-dihydroquinoxalin-2(1H)-one (3i):[8b] 0.141
g, 99% yield, 100% ee; White solid; m.p. 123–125 °C. Rf = 0.10
(hexane/EtOAc = 1:1, v/v). [α]D20 = +34.3 (c = 0.25, MeOH). IR: ṽ = 3318,
1H NMR (400 MHz, CDCl3) d = 8.82 (s, 1H), 6.98 (t, J = 7.6 Hz, 1H), 6.82
(d, J = 7.6 Hz, 1H), 6.75 (t, J = 7.6 Hz, 1H), 6.59 (d, J = 7.6 Hz, 1H), 3.73
(dd, J = 9.0, 7.0 Hz, 1H), 3.49 (td, J = 8.6, 5.2 Hz, 1H), 3.19 (td, J = 9.2,
6.0 Hz, 1H), 2.37–2.27 (m, 1H), 2.22–1.98 (m, 3H) ppm. 13C NMR (101
MHz, CDCl3) d = 168.71, 135.16, 126.86, 123.98, 118.46, 115.12,
111.96, 60.07, 46.42, 26.75, 22.20 ppm. HRMS (ESI-TOF): m/z calcd for
[C11H12N2O+H]+ [M+H]+ 189.1022, found 189.1022. Chiral HPLC
conditions: Chiralcel® OJ–H column (4.6 mm´250 mm), hexane/iPrOH =
75:25, flow rate: 0.5 mL/min, detected wavelength: 240 nm, retention
time: 17.51 min ((S)-enantiomer), 19.68 min ((R)-enantiomer).
3069, 2918, 1674, 1606, 1507, 1428, 1383, 1309, 1060, 746 cm–1 1H
.
NMR (400 MHz, CD3SOCD3) d = 10.17 (s, 1H), 6.76 – 6.61 (m, 3H), 6.49
(dp, J = 7.8, 3.8 Hz, 1H), 5.87 (s, 1H), 4.84 (t, J = 5.2 Hz, 1H), 3.75 (dd, J
= 6.8, 3.1 Hz, 1H), 3.68–3.56 (m, 1H), 3.55–3.44 (m, 1H) ppm. 13C NMR
(101 MHz, CD3SOCD3) d = 166.57, 134.39, 125.82, 123.11, 117.62,
114.94, 113.71, 62.34, 58.09 ppm. HRMS (ESI-TOF): m/z calcd for
[C9H10N2O2+H]+ [M+H]+ 179.0815, found 179.0815. Chiral HPLC
conditions: Chiralcel® OJ–H column (4.6 mm´250 mm), hexane/iPrOH =
75:25, flow rate: 0.5 mL/min, detected wavelength: 240 nm, retention
time: 15.89 min ((S)-enantiomer).
(S)-3-Benzyl-3,4-dihydroquinoxalin-2(1H)-one (3f):[8b] 0.186 g, 97%
yield, 100% ee; Light yellow solid; m.p. 189–190 °C. Rf
=
0.67
22
(hexane/EtOAc = 1:1, v/v). [α]D20 = -45.34 (c = 0.5, CHCl3) (lit.,[8b] [α]D
=
(S)-3-((R)-1-Hydroxyethyl)-3,4-dihydroquinoxalin-2(1H)-one
(3j):
20
-45.90 (c = 0.5, CHCl3)). [α]D = -57.6 (c = 0.18, MeOH). IR: ṽ = 3371,
0.149 g, 95% yield, 99.4% ee. Yellow solid; m.p. 39–41 °C. Rf = 0.16
(hexane/EtOAc = 1:1, v/v). [α]D20 = +30.9 (c = 0.60, MeOH); IR: ṽ = 3333,
3220, 3065, 2973, 2932, 1673, 1606, 1507, 1425, 1378, 1300, 1075,
3208, 3062, 2961, 2923, 1680, 1604, 1506, 1376, 1307, 745, 700 cm–1
.
1H NMR (400 MHz, CDCl3) d = 8.88 (s, 1H), 7.43–7.27 (m, 3H), 7.22 (d, J
= 7.5 Hz, 2H), 6.97–6.87 (m, 1H), 6.85–6.73 (m, 2H), 6.59 (d, J = 7.6 Hz,
1H), 4.15–4.01 (m, 1H), 3.86 (s, 1H), 3.27 (dd, J = 13.0, 2.7 Hz, 1H), 2.86
(dd, J = 13.0, 11.8 Hz, 1H) ppm. 13C NMR (126 MHz, CDCl3) d = 168.66,
136.82, 132.41, 129.40 (d, JNC = 13.3 Hz), 128.96 (d, JNC = 11.2 Hz),
127.10, 125.38, 124.07, 119.58, 115.48, 114.61, 57.82 (d, JNC = 10.5
Hz), 37.52 (d, JNC = 6.7 Hz) ppm. HRMS (ESI-TOF): m/z calcd for
[C15H14N2O+H]+ [M+H]+ 239.1179, found 239.1178. Chiral HPLC
conditions: Chiralcel® OJ–H column (4.6 mm´250 mm), hexane/iPrOH =
75:25, flow rate: 1 mL/min, detected wavelength: 240 nm, retention time:
9.162 min ((S)-enantiomer);[8g] Chiralcel® OD–H column (4.6 mm´250
mm), hexane:iPrOH = 85:15, flow rate: 1 mL/min, detected wavelength:
240 nm, retention time: 11.78 min ((S)-enantiomer) (lit.,[7a] 17.717 min
((S)-enantiomer), 26.785 ((R)-enantiomer)).
919, 741 cm–1 1H NMR (400 MHz, CDCl3) d = 8.89 (s, 1H), 7.01–6.84
.
(m, 1H), 6.79–6.62 (m, 3H), 4.21 (s, 1H), 4.16–4.05 (m, 1H), 3.94 (d, J =
5.1 Hz, 1H), 2.92 (d, J = 6.1 Hz, 1H), 1.36 (d, J = 6.4 Hz, 3H) ppm. 13C
NMR (126 MHz, CDCl3) d = 167.55, 132.70, 124.51, 124.18, 119.39,
115.46, 114.20, 67.71, 61.05, 19.32 ppm. HRMS (ESI-TOF): m/z calcd
+
for [C10H12N2O2+H] [M+H]+ 193.0972, found 193.0974. Chiral HPLC
conditions: Chiralcel® OJ–H column (4.6 mm´250 mm), hexane/iPrOH =
75:25, flow rate: 1 mL/min, detected wavelength: 240 nm, retention time:
6.77 min ((S)-enantiomer), 9.66 min ((R)-enantiomer).
(S)-3-(2-(Methylthio)ethyl)-3,4-dihydroquinoxalin-2(1H)-one (3k):[8m]
0.173 g, 97% yield, 100% ee. Yellow viscous oil. Rf
(hexane/EtOAc = 1:1, v/v). [α]D20 = +34.2 (c = 0.71, MeOH). IR: ṽ = 3326,
3213, 3066, 2965, 2915, 1677, 1605, 1507, 1426, 1376, 1309, 745 cm–1
= 0.51
.
(S)-3-((1H-Indol-3-yl)methyl)-3,4-dihydroquinoxalin-2(1H)-one (3g):[8b]
0.167 g, 100% yield, 99.6% ee (0.60 mmol of 2g used); Yellow solid; m.p.
1H NMR (400 MHz, CDCl3) d = 8.97 (s, 1H), 6.95–6.84 (m, 1H), 6.79–
6.72 (m, 2H), 6.70 (d, J = 7.8 Hz, 1H), 4.26 (s, 1H), 4.16–4.05 (m, 1H),
2.81–2.56 (m, 2H), 2.24–2.13 (m, 1H), 2.13 (s, 3H), 2.09–1.97 (m, 1H)
ppm. 13C NMR (101 MHz, CDCl3) d = 168.73, 132.85, 125.25, 123.95,
119.53, 115.46, 114.27, 55.66 (d, JNC = 4.9 Hz), 30.39, 30.35, 15.35 ppm.
HRMS (ESI-TOF): m/z calcd for [C11H14N2OS+H]+ [M+H]+ 223.0900,
found 223.0900. Chiral HPLC conditions: Chiralcel® OJ–H column (4.6
mm´250 mm), hexane/iPrOH = 75:25, flow rate: 1 mL/min, detected
wavelength: 240 nm, retention time: 11.65 min ((S)-enantiomer).
20
89–90 °C. Rf = 0.34 (hexane/EtOAc = 1:1, v/v); [α]D = +3.0 (c = 0.25,
MeOH). IR: ṽ = 3366, 3056, 2957, 2927, 1674, 1604, 1506, 1422, 1376,
1307, 1234, 1119, 741 cm–1. 1H NMR (400 MHz, CDCl3) d = 8.80 (s, 1H),
8.23 (s, 1H), 7.63 (d, J = 8.0 Hz, 1H), 7.42 (d, J = 8.0 Hz, 1H), 7.25 (t, J =
8.0,1H), 7.15 (t, J = 8.0 Hz, 1H), 7.09 (d, J = 1.8 Hz, 1H), 6.92–6.84 (m,
1H), 6.83–6.72 (m, 2H), 6.52 (d, J = 7.7 Hz, 1H), 4.18 (dd, J = 11.2, 2.7
Hz, 1H), 3.98 (s, 1H), 3.48 (dd, J = 14.4, 2.7 Hz, 1H), 3.07 (dd, J = 14.4,
11.2 Hz, 1H) ppm. 13C NMR (101 MHz, CDCl3) d = 169.03, 136.45,
132.70, 127.17, 125.34, 123.92, 123.30, 122.50, 119.80, 119.35, 118.87,
115.38, 114.55, 111.35, 110.84, 56.71, 27.60 ppm. HRMS (ESI-TOF):
m/z calcd for [C17H15N3O+H]+ [M+H]+ 278.1288, found 278.1287. Chiral
HPLC conditions: Chiralcel® OJ–H column (4.6 mm´250 mm),
hexane/iPrOH = 75:25, flow rate: 0.5 mL/min, detected wavelength: 240
nm, retention time: 9.74 min ((S)-enantiomer), 11.83 min ((R)-
enantiomer).
Methyl
(S)-3-(3-oxo-1,2,3,4-tetrahydroquinoxalin-2-yl)-propanoate
(3l): 0.179 g, 95% yield, 100% ee. Light yellow solid; m.p. 73–74 °C. Rf =
0.39 (hexane/EtOAc = 1:1, v/v). [α]D20 = +42.8 (c = 0.25, MeOH). IR: ṽ =
3334, 3067, 2952, 1723, 1678, 1606, 1507, 1436, 1375, 1307, 746 cm–1
.
1H NMR (400 MHz, CDCl3) d = 9.09 (s, 1H), 6.93–6.85 (m, 1H), 6.78–
6.71 (m, 2H), 6.67 (d, J = 7.9 Hz, 1H), 4.16 (s, 1H), 4.02 (t, J = 5.6 Hz,
1H), 3.67 (s, 3H), 2.66–2.45 (m, 2H), 2.30–2.09 (m, 2H) ppm. 13C NMR
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