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4.16. Ethyl (S)-2,2-difluoro-3-propionyloxy-3-(4-fluoro-
phenyl)propanoate (2g)
[
a
]
35.1 (c 1.0, CH3Cl); HPLC (Chiralcel OJ-H, hexane/i-PrOH¼70:
D
30, 1.0 ml/min): (S)-enantiomer: 7.3 min, (R)-enantiomer: 10.7 min.
1H NMR (400 Hz, CDCl3): 7.36 (2H, dd, J¼5.2, 8.8 Hz), 7.01 (2H, t,
J¼8.4 Hz), 6.16 (1H, dd, J¼9.2, 16.0 Hz), 4.23 (2H, m), 2.35 (2H, m),
1.23 (3H, t, J¼7.2 Hz), 1.08 (3H, t, J¼7.2 Hz); 19F NMR (376 MHz,
CDCl3): ꢀ111.41 (1F, m), ꢀ113.34 (1F, dd, J¼7.5, 263.2 Hz), ꢀ117.45
(1F, dd, J¼15.0, 263.2 Hz); MS (EI, 70 eV): m/z 304 (MþHþ, 0.55),
247 (14.92), 228 (11.35), 97 (10.61), 71 (15.15), 69 (10.52), 57 (100),
43 (14.95); ESI-HRMS: m/z 304.0916 (Mþ, C14H15O4F3þ required
304.0911); IR (KBr): 2986.1, 2945.3, 1608.2, 1766.4, 1513.6, 1464.1,
4.21. Ethyl (R)-2,2-difluoro-3-hydroxy-3-(1-naphthyl)-
propanoate (3j)
1H NMR (400 MHz, CDCl3): 8.16 (1H, d, J¼8.8 Hz), 7.94 (2H, m),
7.83 (1H, d, J¼7.2 Hz), 7.58 (3H, m), 6.11 (1H, dd, J¼7.03, 15.6 Hz),
4.32 (2H, q, J¼7.14 Hz), 1.28 (3H, t, J¼7.14 Hz); 19F NMR (376 MHz,
CDCl3): ꢀ112.25 (1F, dd, J¼7.5, 259.4 Hz), ꢀ119.54 (1F, dd, J¼16.9,
263.2 Hz); ESI-MS: m/z 303.1 (MþNaþ), 335.1 (Mþ2Naþ); ESI-
HRMS: m/z 303.0816 (MþNaþ, C15H14O3F2Naþ1 required 303.0813);
1306.3, 1233.6, 914.6, 853.3, 840.9, 801.0; ee¼72%, [
a] 10.9 (c 0.8,
D
CH3Cl); HPLC (Chiralcel OJ-H, hexane/i-PrOH¼98:2, 0.5 ml/min):
(R)-enantiomer: 82.2 min, (S)-enantiomer: 92.9 min.
IR (KBr): 3494, 2982, 1758, 1087, 790; ee¼72%, [
a
]
ꢀ13.2 (c 0.2,
D
CH3Cl); HPLC (Chiralcel OJ-H, hexane/i-PrOH¼70:30, 1.0 ml/min):
(R)-enantiomer: 15.7 min, (S)-enantiomer: 18.4 min.
4.17. Ethyl (R)-2,2-difluoro-3-hydroxy-3-
(pentafluorophenyl)propanoate (3h)
4.22. Ethyl (S)-2,2-difluoro-3-propionyloxy-3-(1-naphthyl)-
propanoate (2j)
1H NMR (400 Hz, CDCl3) 5.56 (1H, m), 4.21 (1H, q, J¼7.2 Hz), 1.39
(3H, t, J¼7.2 Hz); 19F NMR (376 MHz, CDCl3): ꢀ111.24 (1F, m),
ꢀ122.75 (1H, m), ꢀ140.67 (2F, m), ꢀ151.30 (1F, m), ꢀ160.85 (2F, m);
MS (EI, 70 eV): m/z 321 (MþHþ, 71.76), 303 (61.29), 259 (37.88), 199
(46.26), 197 (100), 124 (76.92), 71 (34.96); EI-HRMS: m/z 320.0283
(Mþ, C11H7O3Fþ7 required 320.0283); IR (KBr): 3459.4, 2991.9,
2916.6, 1760.1, 1525.2, 1506.0, 1377.2, 1307.8, 1205.0, 1122.3, 1079.3,
993.9, 947.8, 777.3; ee¼23%.
1H NMR (400 Hz, CDCl3): 8.24 (1H, d, J¼8.6 Hz), 7.89 (2H, t,
J¼8.5 Hz), 7.43 (1H, d, J¼7.2 Hz), 7.59 (1H, m), 7.52 (2H, m), 7.14 (1H,
dd, J¼8.4, 16 Hz), 4.25 (2H, m), 2.46 (2H, m), 1.22 (3H, t, J¼7.1 Hz),
1.16 (3H, t, J¼7.2 Hz); 19F NMR (376 MHz, CDCl3): ꢀ112.26 (1F, dd,
J¼7.5, 263.2 Hz), ꢀ116.2 (1F, dd, J¼15.0, 263.2 Hz); MS (EI, 70 eV): m/
z 337 (Mþ1, 4.13), 336 (Mþ, 19.57), 213 (19.05), 158 (8.98), 157
(83.25),155 (3.98),129 (9.98), 57 (100); EI-HRMS: m/z 336.1176 (Mþ,
C
18H18O4Fþ2 required 336.1173); IR (KBr): 3052.0, 2982.5, 2945.7,
1760.7, 1329.9, 1294.5, 1214.7, 1159.0, 1086.8, 1067.3, 792.9; ee¼88%,
4.18. Ethyl (S)-2,2-difluoro-3-propionyloxy-3-
(pentafluorophenyl)propanoate (2h)
[
a
]D 25.4 (c 1.9, CH3Cl); HPLC (Chiralcel OJ-H, hexane/i-PrOH¼70:30,
1.0 ml/min): (S)-enantiomer: 18.2 min, (R)-enantiomer: 23.0 min.
1H NMR (400 Hz, CDCl3): 7.44 (1H, dd, J¼6.7, 17.5 Hz), 4.31 (2H,
m), 2.35 (2H, m),1.29 (3H, t, J¼7.2 Hz),1.08 (3H, t, J¼7.2 Hz); 19F NMR
(376 MHz, CDCl3): ꢀ110.26 (1F, m), ꢀ117.65 (1F, m), ꢀ138.81 (2F, m),
ꢀ150.55 (1F, m), ꢀ160.83 (2F, m); MS (EI, 70 eV): m/z 377 (MþHþ,
0.55), 230 (3.32), 180 (1.54), 161 (1.33), 71 (1.59), 58 (3.54), 57 (100),
55 (1.45), 43 (1.86); EI-HRMS: m/z 376.0543 (Mþ, C14H11O4F7þ
required 376.0546); IR (KBr): 2988.4, 2929.4, 1767.0, 1508.9, 1525.8,
4.23. Ethyl (R)-2,2-difluoro-3-hydroxy-3-(2-naphthyl)-
propanoate (3k)
1H NMR (400 Hz, CDCl3): 7.84 (4H, m), 7.50 (3H, m), 5.30 (1H, dd,
J¼8.0, 15.6 Hz), 4.26 (2H, q, J¼6.8 Hz), 1.22 (3H, t, J¼6.8 Hz); 19F
NMR (376 MHz, CDCl3): ꢀ113.29 (1F, dd, J¼7.5, 263.2 Hz), ꢀ119.80
(1F, dd, J¼15.0, 263.2 Hz); MS (EI, 70 eV): m/z 280 (Mþ, 14.78), 281
(MþHþ, 3), 157 (100), 129 (85); IR (KBr): 3484, 3059, 2986, 2935,
1305.5, 1150.9, 1079.2, 999.4, 912.5, 743.2; ee¼6%, [ D ꢀ1.0 (c 0.11,
a
]
CH3Cl); HPLC (Chiralcel OJ-H, hexane/i-PrOH¼70:30, 1.0 ml/min):
(R)-enantiomer: 12.3 min, (S)-enantiomer: 14.8 min.
1759, 1374, 1306, 1197, 1073, 796, 746, 479; ee¼85%, [
a
]
ꢀ13.1 (c
D
1.9, CH3Cl) {lit5b 83% ee, [
a
]
ꢀ10.3 (c 1, CH3Cl) for the (R)-enan-
D
4.19. Ethyl (E)-(R)-2,2-difluoro-3-hydroxy-5-phenylpent-4-
enoate (3i)
tiomer}; HPLC (Chiralcel OJ-H, hexane/i-PrOH¼70:30, 1.0 ml/min):
(R)-enantiomer: 13.2 min, (S)-enantiomer: 20.4 min.
1H NMR (400 MHz, CDCl3): 7.38 (5H, m), 6.85 (1H, d, J¼15.9 Hz),
6.28 (1H, dd, J¼6.7, 15.9 Hz), 4.78 (1H, m), 4.40 (2H, J¼7.15 Hz), 1.39
(3H, t, J¼7.02 Hz); 19F NMR (376 MHz, CDCl3): ꢀ114.21 (1F, dd,
J¼7.5, 263.6 Hz), ꢀ112.56 (1F, dd, J¼15.4, 263.6 Hz); MS (EI, 70 eV):
m/z 256 (Mþ, 7), 133 (100), 115 (33.41); IR (KBr): 3451, 1749, 1371,
4.24. Ethyl (S)-2,2-difluoro-3-propionyloxy-3-(2-naphthyl)-
propanoate (2k)
1H NMR (400 Hz, CDCl3): 7.94 (1H, s), 7.87 (3H, m), 7.53 (3H, m),
6.43 (1H, dd, J¼9.6, 16.0 Hz), 4.30 (2H, q, J¼7.2 Hz), 2.48 (2H, m),
1.28 (3H, t, J¼7.2 Hz), 1.17 (3H, t, J¼7.2 Hz); 19F NMR (376 MHz,
CDCl3): ꢀ113.24 (1F, dd, J¼7.5, 263.2 Hz), ꢀ116.66 (1F, dd, J¼15.0,
263.2 Hz); MS (EI, 70 eV): m/z 336 (Mþ, 18.58), 279 (14.64), 260
(11.52), 213 (11.15), 157 (60.42), 155 (7.55), 129 (8.12), 57 (100); EI-
HRMS: m/z 336.1162 (Mþ, C18H18O4Fþ2 required 336.1173); IR (KBr):
3061.3, 2984.3, 2943.8, 1761.1, 1463.4, 1372.8, 1295.6, 1156.1, 1125.0,
1200, 1094. ee¼39%, [
a
]
ꢀ0.6, (c 0.52, CH3Cl) {lit.5b 41% ee, [
a]
D
D
ꢀ1.0 (c 1, CH3Cl); lit.6b 96% ee, [
a]
ꢀ1.0 (c 1.1, CH3Cl) for the (R)-
D
enantiomer}; HPLC (Chiralcel OJ-H, hexane/i-PrOH¼70:30, 1.0 ml/
min): (R)-enantiomer: 6.25 min, (S)-enantiomer: 7.43 min.
4.20. Ethyl (E)-(S)-2,2-difluoro-3-propionyloxy-5-phenylpent-
4-enoate (2i)
1073.2, 802.3, 746.2; ee¼89%, [
a
]
10.3 (c¼1.9, CH3Cl); HPLC
D
(Chiralcel OJ-H, hexane/i-PrOH¼70: 30, 1.0 ml/min): (S)-enantio-
mer: 17.0 min, (R)-enantiomer: 31.6 min.
1H NMR (400 Hz, CDCl3): 7.41 (2H, m), 7.32 (3H, m), 6.83 (1H, d,
J¼16.0 Hz), 6.14 (1H, dd, J¼8.0, 15.6 Hz), 5.93 (1H, m), 4.33 (2H, q, J¼
7.2 Hz), 2.41 (2H, q, J¼7.2 Hz), 1.33 (3H, t, J¼7.2 Hz), 1.16 (3H, t,
J¼7.2 Hz); 19F NMR (376 MHz, CDCl3): ꢀ113.73 (1F, dd, J¼11.3,
263.2 Hz), ꢀ117.15 (1F, dd, J¼15.0, 263.2 Hz); MS (EI, 70 eV): m/z 312
(Mþ, 0.76), 292 (34.82), 255 (98.91), 236 (53.04), 170 (47.34), 165
(49.43), 133 (97.7), 115 (16.77), 57 (100); EI-HRMS: m/z 312.1176
(Mþ, C16H18O4Fþ2 required 312.1173); IR (KBr): 3116.3, 2986.8,
2099.9, 1760.7, 1399.7, 1205.0, 1161.1, 1106.3, 913.3, 745.8; ee¼36%,
4.25. Ethyl (S)-2,2-difluoro-3-hydroxy-3-(2-furyl)-
propanoate (3l)
1H NMR (400 Hz, CDCl3): 7.49 (1H, m), 6.54 (1H, d, J¼3.02 Hz),
6.44 (1H, dd, J¼2, 3.6 Hz), 5.23 (1H, m), 4.38 (2H, q, J¼7.2 Hz), 1.36
(3H, t, J¼7.6 Hz); 19F NMR (376 MHz, CDCl3): ꢀ114.41 (1F, dd, J¼7.5,
263.2 Hz), ꢀ119.60 (1F, dd, J¼11.3, 263.2 Hz); MS (EI, 70 eV): m/z