P. V. Podea et al. / Tetrahedron: Asymmetry 19 (2008) 1959–1964
1963
(M+, 3), 164 (9), 163 (41), 162 (29), 136 (22), 135 (100), 134 (57),
109 (9), 108 (37), 107 (12), 91 (10), 90 (30), 82 (17), 81 (8), 76
(9), 75 (11), 74 (9), 69 (41), 64 (20), 63 (41), 51 (14), 50 (27), 45
(22), 39 (32), 38 (16), 31 (94); 1H NMR (CDCl3): d = 3.08 (s, 1H),
5.18 (s, 2H), 7.55–7.65 (m, 2H), 8.02 (d, 1H), 8.20 (d, 1H); 13C
NMR (CDCl3): d = 66.5, 122.4, 125.5, 127.3, 128.1, 136.8, 153.3,
~
(27), 38 (12), 31 (75); 1H NMR (CD3OD): d = 3.84–4.04 (m, 2H),
4.06–5.09 (m, 1H), 7.38–7.53 (m, 2H), 7.92–7.99 (m, 2H); 13C
NMR (CD3OD): d = 65.8, 72.7, 121.6, 121.9, 124.7, 125.8, 134.5,
~
152.9, 176.2; IR:
m = 3262, 2929, 2360, 1508, 1436, 1324, 1317,
1182, 1112, 1074, 1054, 968, 759, 730, 615, 443.
162.4, 193.7; IR:
m = 3478, 3396, 1697, 1484, 1415, 1319, 1240,
4.3.4.2. rac-1-(Benzo[b]thiophen-2-yl)ethane-1,2-diol rac-5b.
Yield = 93%; mp 113 °C from CHCl3; HRMS: M+ found (M+ calcu-
lated for C10H10O2S): 194.04028 (194.04015); MS: m/z (%) = 196
(M+2, 2), 195 (M+1, 4), 194 (M+, 32), 176 (6), 165 (6), 164 (12),
163 (100), 147 (29), 136 (11), 135 (75), 134 (28), 115 (7), 102
(8), 92 (9), 91 (91), 90 (11), 89 (29), 77 (10), 69 (20), 63 (20), 51
(16), 50 (10), 45 (18), 39 (18), 32 (5), 31 (51); 1H NMR (CD3OD):
d = 3.80 (d, 2H), 4.99 (t, 1H), 7.25–7.35 (m, 3H), 7.71–7.74 (m,
1H), 7.80–7.82 (m, 1H); 13C NMR (CD3OD): d = 66.9; 70.9, 120.2,
~
1220, 1106, 1068, 916, 765, 734, 431.
4.3.3.2. 1-(Benzo[b]thiophen-2-yl)-2-hydroxyethanone
4b.
Yield = 97%; mp 151 °C from ethanol; HRMS: M+ found (M+ calcu-
lated for C10H8O2S): 192.02464 (192.0245); MS: m/z (%) = 192
(M+,2), 190 (15), 161 (85), 133 (35), 106 (4), 93 (10), 90 (9), 89
(100), 82 (7), 69 (18), 63 (44), 51 (7), 50 (14), 45 (9), 39 (29), 38
(12), 32 (5); 1H NMR (DMSO-d6): d = 3.41 (s, 1H), 4.82 (s, 2H),
7.44–7.55 (m, 2H), 8.01–8.07 (m, 2H), 8.35 (s, 1H); 13C NMR
(DMSO-d6): d = 65.9, 123.5, 125.7, 126.7, 128.1, 130.6, 139.5, 140.7,
~
121.8, 123.0, 123.6, 123.8, 139.3, 139.7, 146.6; IR:
m = 3253, 3052,
2927, 2873, 2406, 1683, 1455, 1443, 1361, 1348, 1249, 1159,
1089, 1052, 935, 871, 838, 742, 725, 674, 590, 576, 441.
141.5, 194.7. IR:
m = 3399, 3056, 2917, 2898, 2522, 2360, 2343,
1656, 1590, 1556, 1515, 1427, 1407, 1259, 1236, 1187, 1170, 1103,
1020, 910, 869, 840, 771, 746, 740, 725, 707, 607, 582, 460, 420.
4.3.4.3. rac-1-(Benzo[b]thiophen-3-yl)ethane-1,2-diol
rac-5c.
Yield = 93%; mp 103 °C from CHCl3; HRMS: M+ found (M+ calcu-
lated for C10H10O2S): 194.04034 (194.04015); MS: m/z (%) = 194
(M+, 27), 163 (82), 147 (26), 135 (78), 115 (12), 91 (100), 77 (15),
69 (27), 63 (29), 51 (8), 50 (15), 45 (34), 43 (11), 39 (28), 32 (63),
31 (98); 1H NMR (CD3OD): d = 3.75–3.90 (m, 2H), 5.12–5.16 (m,
1H), 7.31–7.41 (m, 2H), 7.53 (s, 1H), 7.85–7.94 (m, 2H); 13C NMR
(CD3OD): d = 65.9, 70.1, 121.8, 122.3, 122.6, 123.6, 124.0, 136.8,
~
4.3.3.3. 1-(Benzo[b]thiophen-3-yl)-2-hydroxyethanone
4c.
Yield = 95%; mp 84–85 °C from ethanol; HRMS: M+ found (M+ cal-
culated for C10H8O2S): 192.02471 (192.0245); MS: m/z (%) = 194
(M+2, 1), 193 (M+1, 3), 192 (M+, 20), 161 (100), 133 (34), 106
(2), 93 (7), 90 (8), 89 (77), 82 (5), 69 (12), 63 (25), 51 (5), 50 (8),
45 (9), 39 (12), 31 (38); 1H NMR (CDCl3): d = 3.87 (s, 1H), 4.78 (s,
2H), 7.33–7.45 (m, 2H), 7.77 (d, 1H), 8.10 (s, 1H), 8.64 (d, 1H);
13C NMR (CDCl3): d = 65.6, 122.3, 125.1, 125.7, 126.0, 131.3,
~
137.6, 140.7; IR:
m = 3291, 2923, 2454, 2375, 1457, 1427, 1371,
1251, 1141, 1114, 1076, 1062, 1031, 890, 792, 754, 728, 663, 428.
136.2, 137.0, 139.5, 193.3; IR:
m = 3482, 3407, 3070, 2360, 1668,
1492, 1457, 1423, 1309, 1228, 1211, 1168, 1091, 1056, 908, 867,
763, 752, 728, 709, 470.
4.3.4.4. rac-1-(Benzofuran-3-yl)ethane-1,2-diol rac-5d.
93%; mp 69 °C from CHCl3; HRMS: M+ found (M+ calculated for
10H10O3): 178.06316 (178.06299); MS: m/z (%) = 179 (M+1, 2), 178
Yield =
4.3.3.4. 1-(Benzofuran-3-yl)-2-hydroxyethanone 4d.
Yield =
C
97%; mp 98–99 °C from ethanol; HRMS: M+ found (M+ calculated
for C10H8O3): 176.04756 (176.04734); MS: m/z (%) = 176 (M+,2),
174 (12), 146 (10), 145 (100), 117 (8), 90 (9), 89 (96), 88 (9), 74
(6), 63 (75), 62 (36), 61 (13), 51 (7), 50 (14), 44 (3), 39 (46), 38
(12), 32 (5); 1H NMR (CDCl3): d = 3.20 (s, 1H), 4.77 (s, 2H), 7.39–
7.45 (m, 2H), 7.55–7.59 (m, 1H), 8.15–8.19 (m, 1H), 8.32 (s, 1H);
13C NMR (CDCl3): d = 66.1, 111.7, 118.7, 122.4, 123.5, 124.9, 126.0,
~
(M+, 15), 160 (2), 147 (52), 131 (10), 119 (5), 103 (6), 92 (9), 91
(100), 90 (8), 89 (20), 77 (12), 65 (26), 63 (22), 62 (10), 51 (16), 50
(10), 43 (4), 39 (24), 31 (49); 1H NMR (CD3OD): d = 3.83–3.86 (m,
2H), 4.95–4.99 (m 1H), 7.23–7.30 (m, 2H), 7.45–7.48 (m, 1H), 7.71–
7.74 (m, 2H); 13C NMR (CD3OD): d = 65.6, 67.4, 110.8, 120.2, 121.3,
~
122.1, 124.0, 126.3, 142.0, 155.6; IR:
m = 3351, 3228, 2935, 1452,
1373, 1191, 1105, 1027, 896, 750, 734, 630, 420.
150.7, 155.4, 193.8; IR:
m = 3399 3338, 3120, 3068, 2913, 2360,
2341, 1668, 1548, 1477, 1448, 1411, 1317, 1290, 1143, 1132,
1105, 1083, 935, 858, 740, 647, 624, 424.
4.4. Asymmetric reduction of 2-(heteroaryl)-2-oxo-ethyl-
acetates 3a–d and 1-(heteroaryl)-2-hydroxy-ethanones 4a–d by
baker’s yeast
4.3.4. Synthesis of rac-1-(heteroaryl)-ethane-1,2-diols rac-5a–d
To a stirred solution of ketone 4a–d (100 mg) in methanol
(4 mL), NaBH4 (38 mg, 1 mmol) was added in small portions at
room temperature, until the entire amount of the ketone was trans-
formed. The progress of the reaction was followed by thin layer
chromatography, using CH2Cl2 as eluent. Then the reaction mixture
4.4.1. Analytical scale reduction of the prochiral ketones 3,4a–d
4.4.1.1. Analytical scale non-fermenting reduction of 2-(hetero-
aryl)-2-oxo-ethyl-acetates 3a–d and 1-(hetero-aryl)-2-hydroxy-
ethanones 4a–d by baker’s yeast.
Baker’s yeast (1.5 g) was
suspended in water (3 mL). After stirring for 15 min, 2-(hetero-
aryl)-2-oxo-ethyl-acetates 3a–d and 1-(heteroaryl)-2-hydroxy-
ethanones 4a–d (10 mg) dissolved in methanol (0.2 mL) was added
was treated with 1 M HCl (400 lL) and the methanol was removed
in vacuo. The crude product was treated with a mixture of CH2Cl2–
water = 1:1 (v/v), the organic layer was separated, dried over anhy-
drous MgSO4 and the CH2Cl2 was removed in vacuo. The crude
product was purified by column chromatography, using CH2Cl2–
acetone = 9:1 (v/v) as eluent. The pure racemic alcohols rac-5a–d
were used as reference for the chiral HPLC separation.
into the resulting cell suspension. Samples (100
periodically every 6 h over 48 h and extracted with ethyl acetate
(300 L). The organic layer was dried over anhydrous MgSO4 and
lL) were taken
l
was used for HPLC analysis without further purification.
4.3.4.1. rac-1-(Benzo[d]thiazol-2-yl)-ethane-1,2-diol
rac-5a.
4.4.1.2. Analytical scale reduction of heteroaryl-oxo-ethyl-ace-
tates 3a–d and heteroaryl-hydroxyethanones 4a–d with fer-
Yield = 93%; mp 142 °C from CHCl3; HRMS: M+ found (M+ calcu-
lated for C9H9NO2S): 195.03563 (195.0354); MS: m/z (%) = 196
(M+1, 2), 195 (M+, 6), 178 (3), 167 (4), 166 (14), 165 (94), 164
(100), 163 (6), 136 (74), 135 (16), 134 (6), 109 (70), 108 (33),
107 (4), 91 (9), 90 (6), 82 (21), 77 (13), 75 (9), 69 (51), 65 (47),
64 (10), 63 (29), 58 (12), 51 (16), 50 (17), 45 (25), 43 (13), 39
menting baker’s yeast.
A fresh wet cake of baker’s yeast
(1.5 g) and sucrose (0.5 g) was added to water (3 mL) and the
resulting suspension was stirred for 30 min. 2-(Heteroaryl)-2-
oxo-ethyl-acetates 3a–d or 1-(heteroaryl)-2-hydroxyethanones
4a–d (10 mg) dissolved in methanol (0.2 mL) were added into