790
M. Grazia Perrone et al. / Tetrahedron: Asymmetry 16 (2005) 783–792
(76 MHz, CDCl3): d 168.92 (1C, CO); 69.10 (1C,
CHOH); 62.47 (1C, CHCl); 61.26 (1C, CH2CH3);
19.35 (1C, CH3CHOH); 14.18 (1C, CH3CH2). GC–MS
(70 eV) (m/z) (rel. int.): 151 (M+ꢀ15, 2), 124 (19), 122
(56), 96 (33), 94 (100), 85 (17), 78 (10), 76 (28), 45
(32), 43 (12).
(m/z) (rel. int.): 260 [M(37Cl)+, 6], 258 [M(35Cl)+, 19],
214 (19), 168 (9), 167 (8), 143 (32), 142 (8), 141 (100),
139 (15), 130 (16), 129 (10), 128 (49), 111 (10), 99 (7),
75 (10), 45 (7), 43 (9).
20
D
4.2.3.3. (2S,3S)-2a. Yield 5%; ½aꢁ ¼ ꢀ29:0 (c 1.1
CHCl3). Dr = 89:11, de = 78%, ee = 99%. Analytical
and spectroscopic data were identical to those of its
enantiomer (2R,3R)-2a.
20
4.2.2.4. (2R,3R)-5.36 Yield 75%; ½aꢁ ¼ ꢀ4:9 (c 1.2,
D
CHCl3). Analytical and spectroscopic data were identi-
cal to those ones of its enantiomer (2S,3S)-5.
20
4.2.3.4. (2R,3S)-2a. ½aꢁ ¼ þ36:5 (c 1.4, CHCl3).
D
Ee = 97%. Analytical and spectroscopic data were iden-
tical to those of its enantiomer (2S,3R)-2a.
4.2.3. Preparation of ethyl 2-(4-chlorophenoxy)-3-
hydroxybutanoate 2a: general procedure. A mixture of
5 (51.9 mmol) and caesium 4-chlorophenate (57.1 mmol)
was stirred at 50 ꢁC for 5 days, monitoring the reaction
progress by GC analysis. Water was added and the reac-
tion mixture extracted three times with ethyl acetate.
The combined extracts were dried over anhydrous
Na2SO4 and the solvent was evaporated under reduced
pressure. A red oil was obtained. Products were sepa-
rated by flash chromatography (silica gel; mobile phase:
petroleum ether/ethyl acetate = 8:2).
4.2.4. Preparation of ethyl 3-(4-chlorophenoxy)-2-
hydroxybutanoate 6: general procedure. A mixture of
7 (3.86 mmol), 4-chlorophenol (3.86 mmol) and caesium
4-chlorophenate (0.39 mmol) was stirred at 50 ꢁC for
5 days. Reaction progress was monitored by GC analy-
sis. Then, water was added and the reaction mixture ex-
tracted three times with ethyl acetate. The extracts were
combined and dried over anhydrous Na2SO4. The sol-
vent was evaporated under reduced pressure and a col-
ourless oil was obtained. Products were isolated by
flash chromatography (silica gel; mobile phase: petro-
leum ether/ethyl acetate = 8:2).
20
D
4.2.3.1. (2R,3R)-2a. Yield 5%; ½aꢁ ¼ þ29:0 (c 1.1,
CHCl3). Dr = 88:12, de = 77%, ee >99%. IR (neat):
3700–3100, 3050, 2984, 2939, 1737, 1659, 1596, 1584,
1492, 1447, 1375, 1281, 1238, 1201, 1095, 1063, 1023,
20
826 cmꢀ1
.
1H NMR (300 MHz, CDCl3): d 7.23–7.17
4.2.4.1. (2S,3R)-6. ½aꢁ ¼ þ20:9 (c 1.0, CHCl3).
(m, 2H, aromatic protons); 6.84–6.79 (m, 2H, aromatic
protons); 4.55–4.53 (d, J = 4.39 Hz, 1H, CHOC6H4Cl);
4.32–4.17 (qd, J = 6.59 and 4.39 Hz, 1H, CHOH, par-
tially overlapped to a quartet of doublets, J = 7.14 and
1.38 Hz, 2H, CH2CH3); 3.80–3.00 (br s, 1H, OH: ex-
changes with D2O); 1.34–1.32 (d, J = 6.59 Hz, 3H,
CH3CHOH); 1.24–1.20 (t, J = 7.14 Hz, 3H, CH3CH2).
13C NMR (76 MHz, CDCl3): d 169.59 (1C, CO);
156.48 (1C, aromatic carbon); 129.68 (2C, aromatic car-
bons); 127.13 (1C, aromatic carbon); 116.91 (2C, aro-
matic carbons); 81.12 (1C, CHOC6H4Cl) 68.57 (1C,
CHOH); 61.86 (1C, CH2CH3); 18.58 (1C, CH3CHOH);
14.33 (1C, CH3CH2). GC–MS (70 eV) (m/z) (rel. int.):
260 [M(37Cl)+, 7], 258 [M(35Cl)+, 19], 216 (10), 214
(20), 168 (10), 167 (11), 143 (32), 142 (10), 141 (100),
139 (16), 130 (18), 129 (10), 128 (52), 111 (11), 99 (10),
75 (11), 45 (10), 43 (11).
White solid, mp 47–50 ꢁDC. De >99%, ee >99%. IR
(KBr): 3750–3250, 3030, 2985, 2936, 1740, 1594, 1580,
1491, 1409, 1393, 1378, 1281, 1241, 1157, 1120, 1092,
1062, 1008, 968, 882, 867, 823, 648 cmꢀ1 1H NMR
.
(300 MHz, CDCl3): d 7.23–7.18 (m, 2H, aromatic pro-
tons); 6.84–6.79 (m, 2H, aromatic protons); 4.73–4.66
(qd, J = 6.33 and 2.20 Hz, 1H, CHCH3); 4.19–4.12 (m,
3H, CHOH and CH2CH3); 3.20–3.00 (br s, 1H, OH: ex-
changes with D2O); 1.42–1.40 (d, J = 6.33 Hz, 3H,
CH3CH); 1.17–1.12 (t, J = 7.15 Hz, 3H, CH3CH2). 13C
NMR (76 MHz, CDCl3): d 172.59 (1C, CO); 156.23
(1C, aromatic carbon); 129.65 (2C, aromatic carbons);
126.58 (1C, aromatic carbon); 117.73 (2C, aromatic car-
bons); 75.76 (1C, CHCH3); 73.88 (1C, CHOH); 62.19
(1C, CH2CH3); 15.73 (1C, CH3CH); 14.37 (1C
CH3CH2). GC–MS (70 eV) (m/z) (rel. int.): 260
[M(37Cl)+, 10], 258 [M(35Cl)+, 29], 214 (5), 167 (5), 157
(25), 155 (69), 141 (19), 130 (38), 129 (12), 128 (100),
111 (10), 75 (8), 57 (12).
20
4.2.3.2. (2S,3R)-2a. ½aꢁ ¼ ꢀ36:0 (c 1.4, CHCl3).
D
Ee >99%. IR (neat): 3600–3200, 3056, 2985, 2932,
2855, 1748, 1596, 1491, 1376, 1266, 1236, 1199, 1137,
20
D
4.2.4.2. (2R,3S)-6. ½aꢁ ¼ ꢀ15:9 (c 0.74, CHCl3).
1095, 1076, 1025, 1009, 826, 738 cmꢀ1
.
1H NMR
White solid, mp 57–58 ꢁC. De >99%, ee >99%. Analyti-
cal and spectroscopic data were identical to those of its
enantiomer (2S,3R)-6.
(500 MHz, CDCl3): d 7.25–7.20 (m, 2H, aromatic pro-
tons); 6.86–6.83 (m, 2H, aromatic protons); 4.43–4.42
(d, J = 4.94 Hz, 1H, CHOC6H4Cl); 4.32–4.17 (qd,
J = 7.15 and 1.64 Hz, 2H of CH2CH3 completely over-
lapped to the signal of CHOH); 2.60–2.20 (br s, 1H,
OH: exchanges with D2O); 1.35–1.34 (d, J = 6.45 Hz,
3H, CH3CHOH); 1.27–1.24 (t, J = 7.15 Hz, 3H,
CH3CH2). 13C NMR (76 MHz, CDCl3): d 169.74 (1C,
CO); 156.44 (1C, aromatic carbon); 129.68 (2C, aro-
matic carbons); 127.13 (1C, aromatic carbon); 116.91
(2C, aromatic carbons); 81.12 (1C, CHOC6H4Cl) 68.57
(1C, CHOH); 61.86 (1C, CH2CH3); 18.58 (1C,
CH3CHOH); 14.33 (1C, CH3CH2). GC–MS (70 eV)
20
D
4.2.4.3. (2R,3R)-6. Oil; ½aꢁ ¼ ꢀ19:9 (c 1.0, CHCl3).
De = 73%, ee(2R,3R) = 82%, ee(2S,3R) = 93%. IR (neat):
3700–3200, 3099, 3073, 2983, 2937, 2874, 1736, 1595,
1582, 1490, 1447, 1381, 1282, 1239, 1150, 1093, 1076,
1
1022, 940, 826 cmꢀ1. H NMR (500 MHz, CDCl3): d
7.22–7.20 (m, 2H, aromatic protons); 6.87–6.85 (m, 2H,
aromatic protons); 4.64–4.59 (qd, J = 6.42 and 3.01 Hz,
1H, CHCH3); 4.40–4.39 (d, J = 3.01 Hz, 1H, CHOH);
4.33–4.24 (m, 2H, CH2CH3); 3.30–3.15 (br s, 1H, OH:
exchanges with D2O); 1.32–1.31 (d, J = 6.41 Hz, 3H,