Stereoselective Direct Asymmetric Aldol Reaction
A R T I C L E S
3.1. tert-Butyl (2S*,3S*)-2-Amino-3-hydroxy-5-phenylpentanoate
(anti-5a):11 1H NMR (400 MHz, CDCl3) δ 7.26-7.29 (2 H, m, Ph),
7.16-7.20 (3 H, m, Ph), 3.77 (1 H, ddd, J ) 7.6, 4.4, 3.2 Hz, CHOH),
3.47 (1 H, d, J ) 4.4 Hz, CHNH2), 2.84-2.91 (1 H, ddd, J ) 14.0,
9.2, 4.8 Hz, PhCH), 2.65-2.73 (1 H, dt, J ) 14.0, 8.0 Hz, PhCH),
1.85 (3 H, br, OH and NH2), 1.65-1.75 (1 H, m, PhCH2CH), 1.53-
1.62 (1 H, m, PhCH2CH), 1.41 (9 H, s, t-Bu); 13C NMR (100 MHz,
CDCl3) δ 172.8, 141.8, 128.4, 128.3, 125.7, 81.7, 71.0, 59.0, 33.8, 32.0,
28.1; IR (neat) 3373, 2977, 2934, 1730, 1602, 1456, 1367, 1252, 1153,
) 6.8 Hz, CHNH), 1.77-1.94 (2 H, m, CH2), 1.30-1.53 (8 H, m,
(CH2)4), 1.50 (9 H, s, t-Bu), 0.89 (3 H, t, J ) 6.8 Hz, CH3); 13C NMR
(100 MHz, CDCl3) δ 188.8, 167.0, 85.6, 84.2, 62.7, 34.9, 31.6, 28.7,
28.0, 24.3, 22.5, 14.1; IR (KBr) 3186, 2932, 2860, 1740, 1506, 1371,
1246, 1180, 1155, 914, 841, 733 cm-1; HPLC: DAICEL Chiralpak
AD-H, hexane/2-propanol ) 10:1, flow rate ) 0.5 mL/min, retention
time ) 14.0 and 23.4 min.
3.9. tert-Butyl (2S*,3S*)-2-Amino-3-hydroxy-4-triisopropylsiloxy-
butanoate (anti-5c): [R]D28 9.2° (c 0.46, CHCl3, 98% ee); H NMR
1
1051, 849, 748, 700 cm-1
.
(400 MHz, CDCl3) δ 3.76-3.85 (3 H, m, SiOCH2 and CHOH), 3.53
(1 H, br d, J ) 4.4 Hz, CHNH2), 1.83 (3 H, br, OH and NH2), 1.48 (9
H, s, t-Bu), 1.06-1.16 (21 H, m, i-Pr3SiO); IR (neat) 3369, 2943, 2868,
2360, 1734, 1464, 1393, 1367, 1250, 1157, 1121, 1067, 1015, 997,
920, 883, 849, 797, 683, 660 cm-1; HRMS (ESI-TOF) calcd for
C17H37NO4Si, 348.2565 ([M + H]+); found, 348.2565 ([M + H]+).
3.10. (4S*,5S*)-5-Triisopropylsiloxymethyl-2-thiooxooxazoline-
4-carboxylic Acid tert-Butyl Ester (cis-6c): [R]2D9 -36.9° (c 0.31,
3.2. (4S*,5S*)-5-(2′-Phenylethyl)-2-thiooxooxazoline-4-carboxylic
Acid tert-Butyl Ester (cis-6a):11 1H NMR (400 MHz, CDCl3) δ 7.19-
7.32 (6 H, m, Ph and NH), 4.96 (1 H, ddd, J ) 8.8, 8.0, 6.0 Hz,
CHOCdS), 4.43 (1 H, dd, J ) 8.8, 2.4 Hz, CHNH), 2.92-3.00 (1 H,
m, PhCH), 2.76-2.84 (1 H, m, PhCH), 2.01-2.11 (2 H, m, PhCH2CH2),
1.48 (9 H, s, t-Bu); 13C NMR (100 MHz, CDCl3) δ 189.7, 166.4, 139.7,
128.5, 128.3, 126.3, 84.4, 83.4, 61.3, 31.6, 31.4, 28.0; IR (KBr) 3171,
2988, 2939, 1732, 1522, 1369, 1231, 1182, 1158, 1088, 852, 700 cm-1
;
1
CHCl3, 98% ee); H NMR (400 MHz, CDCl3) δ 7.60 (1 H, br, NH),
HPLC: DAICEL Chiralpak AD-H, hexane/2-propanol ) 10:1, flow
rate ) 0.5 mL/min, retention time ) 18.9 (major) and 28.7 min (minor).
3.3. tert-Butyl (2S*,3R*)-2-Amino-3-hydroxy-5-phenylpentanoate
(syn-5a):11 1H NMR (400 MHz, CDCl3) δ 7.26-7.29 (2 H, m, Ph),
7.16-7.22 (3 H, m, Ph), 3.70 (1 H, ddd, J ) 7.6, 5.2, 4.8 Hz, CHOH),
3.24 (1 H, d, J ) 5.2 Hz, CHNH2), 2.82-2.90 (1 H, ddd, J ) 13.6,
9.0, 6.2 Hz, PhCH), 2.67-2.74 (1 H, ddd, J ) 13.6, 8.8, 7.2 Hz, PhCH),
2.17 (3 H, br, OH and NH2), 1.78-1.85 (2 H, m, PhCCH2), 1.46 (9 H,
s, t-Bu); 13C NMR (100 MHz, CDCl3) δ 173.2, 141.9, 128.3, 128.2,
125.7, 81.8, 71.4, 58.8, 36.0, 32.0, 28.1; IR (neat) 3377, 2977, 2934,
5.08 (1 H, ddd, J ) 10.0, 4.0, 2.8 Hz, CHOCdS), 4.63 (1 H, d, J )
10.0 Hz, CHNH), 4.11 (1 H, dd, J ) 12.0, 4.0 Hz, SiOCH), 4.06 (1 H,
dd, J ) 12.0, 2.8 Hz, SiOCH), 1.50 (9 H, s, t-Bu), 1.05-1.16 (21 H,
m, i-Pr3SiO); 13C NMR (100 MHz, CDCl3) δ 189.0, 165.6, 84.2, 84.1,
61.8, 59.0, 28.1, 18.0, 12.0; IR (KBr) 3184, 2945, 2868, 1738, 1520,
1464, 1369, 1244, 1178, 1155, 1111, 1067, 1032, 923, 883, 845, 683
cm-1; HRMS (ESI-TOF) calcd for C18H35NNaO4SSi, 412.1948 ([M +
Na]+); found, 412.1948 ([M + Na]+); HPLC: DAICEL Chiralpak AD-
H, hexane/2-propanol ) 20:1, flow rate ) 0.5 mL/min, retention time
) 12.0 (major) and 18.5 min (minor).
1730, 1603, 1456, 1393, 1369, 1250, 1155, 847, 750, 700 cm-1
.
3.11. tert-Butyl (2S*,3R*)-2-Amino-3-hydroxy-4-triisopropyl-
1
3.4. (4S*,5R*)-5-(2′-Phenylethyl)-2-thiooxooxazoline-4-carboxylic
Acid tert-Butyl Ester (trans-6a):11 1H NMR (400 MHz, CDCl3) δ
7.20-7.33 (6 H, m, Ph and NH), 4.87 (1 H, ddd, J ) 8.0, 7.2, 4.8 Hz,
CHOCdS), 4.10 (1 H, d, J ) 7.2 Hz, CHNH), 2.88-2.95 (1 H, m,
PhCH), 2.76-2.83 (1 H, m, PhCH), 2.10-2.27 (2 H, m, PhCCH2),
1.45 (9 H, s, t-Bu); 13C NMR (100 MHz, CDCl3) δ 188.8, 166.7, 139.7,
128.5, 128.3, 126.3, 84.5, 84.4, 62.6, 36.6, 30.8, 27.9; IR (KBr) 3188,
2980, 2932, 1744, 1497, 1371, 1242, 1182, 1155, 1097, 1016, 840,
750, 700 cm-1; HPLC: DAICEL Chiralpak AD-H, hexane/2-propanol
) 10:1, flow rate ) 0.5 mL/min, retention time ) 19.9 and 32.9 min.
3.5. tert-Butyl (2S*,3S*)-2-Amino-3-hydroxynonanoate (anti-5b):
11 1H NMR (400 MHz, CDCl3) δ 3.75-3.79 (1 H, m, CHOH), 3.46 (1
H, d, J ) 4.4 Hz, CHNH2), 1.97 (3 H, br, OH and NH2), 1.48 (9 H, s,
t-Bu), 1.28-1.53 (10 H, m, (CH2)5), 0.88 (3 H, t, J ) 6.8 Hz, CH3);
13C NMR (100 MHz, CDCl3) δ 173.0, 81.6, 72.2, 59.0, 32.2, 31.8,
29.2, 28.1, 25.8, 22.7, 14.2; IR (neat) 3368, 2930, 2858, 1732, 1592,
siloxybutanoate (syn-5c): H NMR (400 MHz, CDCl3) δ 3.95 (1 H,
ddd, J ) 6.0, 6.0, 2.8 Hz, CHOH), 3.78 (1 H, dd, J ) 10.0, 6.0 Hz,
SiOCH2), 3.70 (1 H, dd, J ) 10.0, 6.0 Hz, SiOCH2), 3.56 (1 H, d, J )
2.8 Hz, CHNH2), 1.64 (3 H, br, OH and NH2), 1.48 (9 H, s, t-Bu),
1.05-1.17 (21 H, m, i-Pr3SiO); IR (neat) 3385, 2943, 2893, 2866, 2370,
1734, 1464, 1393, 1369, 1279, 1250, 1157, 1121, 1067, 1013, 995,
918, 883, 847, 795, 681 cm-1; HRMS (ESI-TOF) calcd for C17H37NO4Si,
348.2565 ([M + H]+); found, 348.2572 ([M + H]+).
3.12. (4S*,5R*)-5-Triisopropylsiloxymethyl-2-thiooxooxazoline-
1
4-carboxylic Acid tert-Butyl Ester (trans-6c): H NMR (400 MHz,
CDCl3) δ 7.47 (1 H, br, NH), 4.98 (1 H, ddd, J ) 6.0, 3.6, 3.2 Hz,
CHOCdS), 4.54 (1 H, d, J ) 6.0 Hz, CHNH), 4.09 (1 H, dd, J )
11.6, 3.6 Hz, SiOCH), 3.90 (1 H, dd, J ) 11.6, 3.2 Hz, SiOCH), 1.50
(9 H, s, t-Bu), 1.05-1.17 (21 H, m, i-Pr3SiO); 13C NMR (100 MHz,
CDCl3) δ 189.9, 167.3, 85.1, 84.2, 62.8, 58.5, 28.0, 18.0, 12.0; IR (KBr)
3173, 2943, 2868, 1742, 1506, 1369, 1242, 1182, 1155, 883, 683 cm-1
;
1458, 1367, 1250, 1157, 851 cm-1
.
HRMS (ESI-TOF) calcd for C18H35NNaO4SSi, 412.1948 ([M + Na]+);
found, 412.1948 ([M + Na]+); HPLC: DAICEL Chiralpak AD-H,
hexane/2-propanol ) 20:1, flow rate ) 0.5 mL/min, retention time )
19.8 and 22.9 min.
3.6. (4S*,5S*)-5-Hexyl-2-thiooxooxazoline-4-carboxylic Acid tert-
Butyl Ester (cis-6b):11 1H NMR (400 MHz, CDCl3) δ 7.77 (1 H, br,
NH), 5.00 (1 H, ddd, J ) 8.8, 8.0, 6.4 Hz, CHOCdS), 4.48 (1 H, d,
J ) 8.8 Hz, CHNH), 1.29-1.77 (10 H, m, (CH2)5), 1.50 (9 H, s, t-Bu),
0.88 (3 H, t, J ) 6.8 Hz, CH3); 13C NMR (100 MHz, CDCl3) δ 189.9,
166.5, 84.8, 84.2, 61.4, 31.6, 30.3, 28.9, 28.0, 25.5, 22.5, 14.1; IR (KBr)
3167, 2926, 2853, 1734, 1524, 1393, 1369, 1227, 1186, 1153, 1082,
856, 704 cm-1; HPLC: DAICEL Chiralpak AD-H, hexane/2-propanol
) 10:1, flow rate ) 0.5 mL/min, retention time ) 13.1 (major) and
19.8 min (minor).
3.13. tert-Butyl (2S*,3S*)-2-Amino-3-hydroxy-6-benzyloxyhex-
anoate (anti-5d): [R]2D9 0.9° (c 0.50, CHCl3, 96% ee); H NMR (400
1
MHz, CDCl3) δ 7.26-7.35 (5 H, m, Ph), 4.50 (2H, s, PhCH2O), 3.78
(1 H, m, CHOH), 3.51 (2 H, t, J ) 6.0 Hz, BnOCH2), 3.46 (1 H, d, J
) 3.6 Hz, CHNH2), 2.04 (3 H, br, OH and NH2), 1.81-1.88 (1 H, m,
CHCOH), 1.71-1.76 (1 H, m, CHCOH), 1.45-1.52 (2 H, m,
BnOCCH2), 1.45 (9 H, s, t-Bu); 13C NMR (100 MHz, CDCl3) δ 172.9,
138.2, 128.2, 127.5, 127.4, 81.6, 72.9, 72.2, 70.2, 59.1, 29.2, 28.1, 26.3;
IR (KBr) 3369, 2934, 2858, 1730, 1587, 1454, 1367, 1252, 1153, 1101,
849, 737, 698 cm-1; HRMS (ESI-TOF) calcd for C17H28NO4, 310.2013
([M + H]+); found, 310.2013 ([M + H]+).
3.7. tert-Butyl (2S*,3R*)-2-Amino-3-hydroxynonanoate (syn-5b):
11 1H NMR (400 MHz, CDCl3) δ 3.65-3.69 (1 H, m, CHOH), 3.23 (1
H, d, J ) 4.8 Hz, CHNH2), 2.09 (3 H, br, OH and NH2), 1.48 (9 H, s,
t-Bu), 1.29-1.52 (10 H, m, (CH2)5), 0.88 (3 H, t, J ) 6.8 Hz, CH3);
13C NMR (100 MHz, CDCl3) δ 173.4, 81.6, 72.2, 58.8, 34.1, 31.8,
29.4, 28.1, 25.7, 22.7, 14.2; IR (neat) 3373, 2930, 2858, 1732, 1593,
3.14. (4S*,5S*)-5-(3′-Benzyloxypropyl)-2-thiooxooxazoline-4-car-
boxylic Acid tert-Butyl Ester (cis-6d): [R]2D9 -2.9° (c 0.41, CHCl3,
1458, 1367, 1251, 1157, 849 cm-1
.
1
96% ee); H NMR (400 MHz, CDCl3) δ 7.88 (1 H, br, NH), 7.26-
3.8. (4S*,5R*)-5-Hexyl-2-thiooxooxazoline-4-carboxylic Acid tert-
Butyl Ester (trans-6b):11 1H NMR (400 MHz, CDCl3) δ 8.10 (1 H,
br, NH), 4.89 (1 H, dd, J ) 12.8, 6.8 Hz, CHOCdS), 4.13 (1 H, d, J
7.36 (5 H, m, Ph), 5.02 (1 H, ddd, J ) 10.0, 9.2, 3.6 Hz, CHOCdS),
4.49 (2 H, s, PhCH2O), 4.45 (1 H, d, J ) 9.2 Hz, CHNH), 3.46-3.58
(2 H, m, BnOCH2), 1.52-2.05 (4 H, m, (CH2)2), 1.48 (9 H, s, t-Bu);
9
J. AM. CHEM. SOC. VOL. 126, NO. 31, 2004 9691