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123.10, 123.5 (ddd, J = 20.6, 269.7, 278.9 Hz), 123.6, 125.0, 126.0,
126.7, 127.8, 127.9, 128.1, 128.3, 128.4, 128.8 (d, J = 1.5 Hz), 129.4,
130.0 (d, J = 1.2 Hz), 131.4, 133.7, 133.8, 133.9, 163.5 (d, J = 26.5 Hz),
168.7 ppm. 19F NMR (84.10 MHz, CDCl3, CFCl3): δ = –105.87 (dd, J =
4.4, 239.9 Hz, 1 F), –110.29 (dd, J = 4.4, 239.9 Hz, 1 F), –163.56 (dt,
128.8, 132.5, 133.8, 134.2, 163.6 (d, J = 27.7 Hz), 169.2 (d, J = 2.8 Hz)
ppm. 19F NMR (84.10 MHz, CDCl3, CFCl3): δ = –104.10 (dd, J = 4.4,
243.1 Hz, 1 F), –109.65 (dd, J = 4.4, 243.1 Hz, 1 F), –165.07 (dd, J =
4.4, 13.2 Hz, 1 F) ppm. IR (KBr): ν = 3308, 3028, 2964, 2926, 1767,
˜
1746, 1497, 1458, 1437, 1288, 1207, 1184, 1074, 955, 899, 826, 754,
J = 4.4, 15.4 Hz, 1 F) ppm. IR (KBr): ν = 3200, 1744, 1726, 1458, 1067,
696, 621 cm–1. HRMS (FAB): calcd. for C21H2035ClF3NO4 [M + H]
˜
945, 905, 799, 737, 698 cm–1. HRMS (FAB): calcd. for C30H25F3NO4 442.1033; found 442.1037.
[M + H] 520.1736; found 520.1730.
4-Benzyl-2-methyl (2R*,4R*,5S*)-2-Benzyl-5-(4-chlorophenyl)-
4-Benzyl-2-methyl
3,3,4-Trifluoro-5-(1-naphthyl)-2-phenyl- 3,3,4-trifluoropyrrolidine-2,4-dicarboxylate (3Aj): 1H NMR
pyrrolidine-2,4-dicarboxylate (3Ae): An isomer other than
(2R*,4R*,5S*); the relative stereochemistry was not determined. 1H
NMR (500.13 MHz, CDCl3, TMS): δ = 3.82 (s, 3 H), 4.15–4.55 (m, 1 H),
4.70–4.76 (m, 1 H), 4.83 (d, J = 12.0 Hz, 1 H), 4.90 (d, J = 12.0 Hz, 1
H), 6.78–6.82 (m, 2 H), 6.96–7.01 (m, 2 H), 7.09–7.14 (m, 1 H), 7.35–
7.45 (m, 4 H), 7.50–7.54 (m, 2 H), 7.72–7.76 (m, 1 H), 7.78–7.84 (m,
2 H), 7.89 (s, 1 H), 7.95–7.99 (m, 2 H) ppm. 13C NMR (125.75 MHz,
CDCl3, TMS): δ = 53.6, 63.4 (dd, J = 4.5, 22.4 Hz), 67.9, 73.0 (t, J =
(500.13 MHz, CDCl3, TMS): δ = 3.10–3.14 (m, 1 H), 3.41 (dd, J = 2.1,
14.0 Hz, 1 H), 3.55–3.70 (m, 1 H), 3.74 (s, 3 H), 4.68–4.76 (m, 1 H),
4.94 (s, 2 H), 7.00–7.03 (m, 2 H), 7.15–7.20 (m, 2 H), 7.21–7.41 (m,
10 H) ppm. 13C NMR (125.75 MHz, CDCl3, TMS): δ = 36.6 (dd, J =
2.7, 6.8 Hz), 52.9, 62.5 (dd, J = 3.8, 22.4 Hz), 67.9, 72.6 (t, J = 22.2 Hz),
98.4 (ddd, J = 21.0, 28.2, 220.0 Hz), 124.8 (ddd, J = 19.4, 272.1,
281.4 Hz), 127.1, 127.2, 128.1, 128.4, 128.6, 128.7, 128.8, 130.5, 132.6,
133.8, 134.2, 134.4, 163.4 (d, J = 27.4 Hz), 167.7 ppm. 19F NMR
23.3 Hz), 98.8 (ddd, J = 20.7, 27.5, 221.6 Hz), 123.4, 124.3 (ddd, J = (282.38 MHz, CDCl3, CFCl3): δ = –106.80 (d, J = 242.8 Hz, 1 F),
19.1, 271.1, 289.5 Hz), 125.1, 126.4, 126.5, 127.7, 128.20, 128.23,
128.26, 128.32, 128.4, 128.6, 128.8, 131.6, 133.09, 133.12, 133.57,
133.58, 133.7, 163.9 (d, J = 28.0 Hz), 168.2 ppm. 19F NMR
(282.38 MHz, CDCl3, CFCl3): δ = –100.12 (d, J = 240.0 Hz, 1 F),
–107.17 (d, J = 240.0 Hz, 1 F), –166.20 to –166.30 (m, 1 F) ppm.
–107.86 (dd, J = 5.6, 242.8 Hz, 1 F), –165.28 (d, J = 19.8 Hz, 1 F)
ppm. IR (KBr): ν = 3317, 3036, 2953, 1736, 1495, 1458, 1439, 1379,
˜
1319, 1258, 1213, 1070, 1040, 1013, 932, 908, 826, 750, 719, 698,
604 cm–1. HRMS (FAB): calcd. for C27H2435ClF3NO4 [M + H] 518.1346;
found 518.1339.
4-Benzyl-2-methyl (2R*,4R*,5S*)-5-Cyclohexyl-3,3,4-trifluoro-2-
phenylpyrrolidine-2,4-dicarboxylate (3Af): H NMR (500.13 MHz,
CDCl3, TMS): δ = 0.82–1.83 (m, 11 H), 2.23–2.27 (m, 1 H), 2.92 (dd,
4-Benzyl-2-methyl
(2R*,4R*,5S*)-5-(4-Chlorophenyl)-3,3,4-tri-
fluoro-2-(2-propyl)pyrrolidine-2,4-dicarboxylate (3Ak): 1H NMR
(500.13 MHz, CDCl3, TMS): δ = 1.04 (d, J = 6.56 Hz, 3 H), 1.09 (d, J =
6.69 Hz, 3 H), 2.46–2.54 (m, 1 H), 3.70–3.81 (m, 4 H), 4.53–4.62 (m,
1 H), 4.91 (s, 2 H), 6.97–7.03 (m, 2 H), 7.13–7.21 (m, 4 H), 7.23–7.36
(m, 3 H) ppm. 19F NMR (282.38 MHz, CDCl3, CFCl3): δ = –105.92 (dd,
J = 8.5, 249.9 Hz, 1 F), –106.86 (d, J = 249.9 Hz, 1 F), –170.30 to
1
J = 10.5, 13.0 Hz, 1 H), 3.73 (s, 3 H), 5.30 (d, J = 12.0 Hz, 1 H), 5.34
(d, J = 12.0 Hz, 1 H), 7.24–7.45 (m, 8 H), 7.82–7.86 (m, 2 H) ppm. 13
C
NMR (125.75 MHz, CDCl3, TMS): δ = 25.2, 25.4, 26.1, 29.2, 30.7, 38.1,
53.5, 65.4 (dd, J = 4.1, 20.5 Hz), 68.0, 72.5 (t, J = 22.8 Hz), 98.0 (ddd,
J = 21.5, 27.7, 224.0 Hz), 124.6 (ddd, J = 18.4, 272.1, 281.2 Hz), 128.0,
128.3 (d, J = 3.4 Hz), 128.5, 128.7, 128.9, 129.2, 134.1, 134.4, 165.0
(d, J = 27.4 Hz), 168.3 ppm. 19F NMR (84.10 MHz, CDCl3, CFCl3): δ =
–98.61 (d, J = 237.7 Hz, 1 F), –107.89 (dd, J = 6.6, 237.7 Hz, 1 F),
–170.50 (m, 1 F) ppm. IR (neat): ν = 2957, 2885, 1747, 1705, 1597,
˜
1576, 1497, 1456, 1437, 1387, 1271, 1219, 1188, 1159, 1092, 1061,
1014, 947, 910, 824, 754, 731, 698 cm–1. HRMS (FAB): calcd. for
C23H2435ClF3NO4 [M + H] 470.1346; found 470.1344.
–168.20 to –168.60 (m, 1 F) ppm. IR (KBr): ν = 3348, 2926, 2855,
˜
4-Benzyl-2-methyl (2R*,4R*,5S*)-5-(4-Chlorophenyl)-3,3,4-tri-
fluoro-2-(2-thiomethoxyethyl)pyrrolidine-2,4-dicarboxylate
(3Al): 1H NMR (500.13 MHz, CDCl3, TMS): δ = 2.02–2.18 (m, 4 H),
2.30–2.38 (m, 1 H), 2.44–2.52 (m, 1 H), 2.66–2.73 (m, 1 H), 3.68–3.89
(m, 4 H), 4.46–4.53 (m, 1 H), 4.94 (s, 2 H), 6.96–7.38 (m, 9 H) ppm.
13C NMR (125.75 MHz, CDCl3, TMS): δ = 15.5, 28.3, 30.6 (d, J =
5.4 Hz), 53.3, 62.6 (dd, J = 4.8, 22.1 Hz), 68.0, 71.4 (t, J = 22.4 Hz),
98.3 (ddd, J = 20.2, 29.2, 221.7 Hz), 125.1 (ddd, J = 18.5, 268.7,
282.7 Hz), 126.9, 128.5, 128.69, 128.74, 128.8, 132.4, 133.8, 134.2,
163.5 (d, J = 28.3 Hz), 168.1 (d, J = 2.6 Hz) ppm. 19F NMR (84.10 MHz,
CDCl3, CFCl3): δ = –105.45 (d, J = 244.3 Hz, 1 F), –108.75 (dd, J =
1763, 1738, 1487, 1454, 1267, 1217, 1180, 1146, 1113, 1092, 1078,
1061, 1009, 737, 698 cm–1. HRMS (FAB): calcd. for C26H29F3NO4 [M
+ H] 476.2049; found 476.2039.
4-Benzyl-2-methyl (2R*,4R*,5S*)-3,3,4-Trifluoro-2-phenyl-5-(2-
phenylethenyl)pyrrolidine-2,4-dicarboxylate (3Ah): M.p. 74–
76 °C. 1H NMR (500.13 MHz, CDCl3, TMS): δ = 3.50–4.00 (m, 4 H),
4.08 (dd, J = 7.0, 16.5 Hz, 1 H), 5.25 (s, 2 H), 6.03 (dd, J = 7.0, 16.0 Hz,
1 H), 6.71 (d, J = 16.0 Hz, 1 H), 7.20–7.43 (m, 13 H), 7.89–7.93 (m, 2
H) ppm. 13C NMR (125.75 MHz, CDCl3, TMS): δ = 53.6, 63.2 (dd, J =
4.1, 24.6 Hz), 67.0, 72.7 (t, J = 22.8 Hz), 97.6 (ddd, J = 20.9, 27.4,
219.7 Hz), 121.4, 123.7 (ddd, J = 19.5, 269.6, 280.5 Hz), 126.8, 128.00, 4.4, 244.3 Hz, 1 F), –165.26 (dd, J = 4.4, 15.4 Hz, 1 F) ppm. IR (neat):
128.02, 128.1, 128.4, 128.59, 128.65, 128.71, 128.72, 133.9, 134.3,
135.56, 135.59, 164.0 (d, J = 27.5 Hz), 168.4 ppm. 19F NMR
(84.10 MHz, CDCl3, CFCl3): δ = –104.28 (dd, J = 4.4, 239.8 Hz, 1 F),
–109.81 (dd, J = 6.6, 239.8 Hz, 1 F), –169.06 (ddd, J = 4.5, 6.6, 15.4 Hz,
ν = 3314, 2955, 2918, 2851, 1751, 1601, 1497, 1437, 1406, 1381,
˜
1346, 1271, 1213, 1092, 1036, 1016, 911, 908, 827, 752 cm–1. HRMS
(FAB): calcd. for C23H2435ClF3NO4S [M + H] 502.1067; found
502.1064.
1 F) ppm. IR (KBr): ν = 3333, 3061, 2962, 1770, 1732, 1495, 1450,
˜
4-Benzyl-2-methyl (2R*,4R*,5S*)-5-(4-Chlorophenyl)-3,3,4-tri-
1379, 1335, 1269, 1240, 1192, 1119, 1090, 1011, 970, 908, 802, 735,
698 cm–1. HRMS (FAB): calcd. for C28H25F3NO4 [M + H] 496.1736;
found 496.1747.
fluoro-2-(2-methoxycarbonylmethyl)pyrrolidine-2,4-dicarbox-
1
ylate (3Am): H NMR (500.13 MHz, CDCl3, TMS): δ = 2.88–2.94 (m,
1 H), 3.30 (dd, J = 2.2, 16.5 Hz, 1 H), 3.68 (s, 3 H), 3.84–4.03 (m, 4
H), 4.53–4.58 (m, 1 H), 4.92 (d, J = 11.5 Hz, 1 H), 4.97 (d, J = 11.5 Hz,
1 H), 7.01–7.35 (m, 9 H) ppm. 13C NMR (125.75 MHz, CDCl3, TMS):
δ = 36.8 (dd, J = 2.1, 6.7 Hz), 52.0, 53.5, 63.0 (dd, J = 4.8, 22.5 Hz),
68.0, 69.7 (t, J = 20.3 Hz), 98.1 (ddd, J = 19.4, 29.4, 219.3 Hz), 124.7
4-Benzyl-2-methyl
(2R*,4R*,5S*)-5-(4-Chlorophenyl)-3,3,4-tri-
fluoro-2-methylpyrrolidine-2,4-dicarboxylate (3Ai): 1H NMR
(500.13 MHz, CDCl3, TMS): δ = 1.60–1.63 (m, 3 H), 3.60–4.20 (m, 4
H), 4.58 (m, 1 H), 4.95 (d, J = 2.0 Hz, 2 H), 7.00–7.04 (m, 2 H), 7.12–
7.21 (m, 4 H), 7.25–7.35 (m, 3 H) ppm. 13C NMR (125.75 MHz, CDCl3, (ddd, J = 19.4, 269.1, 283.1 Hz), 127.1, 128.5, 128.7, 128.8, 128.9,
TMS): δ = 19.8 (dd, J = 1.9, 7.7 Hz), 53.3, 62.7 (dd, J = 5.2, 22.0 Hz),
67.9, 68.6 (dt, J = 1.3, 23.6 Hz), 98.3 (ddd, J = 20.0, 29.3, 221.7 Hz),
125.0 (ddd, J = 18.5, 268.2, 283.1 Hz), 127.0, 128.5, 128.68, 128.73,
132.1, 133.7, 134.2, 163.0 (d, J = 27.9 Hz), 167.4 (d, J = 3.0 Hz), 169.4
(d, J = 4.1 Hz) ppm. 19F NMR (84.10 MHz, CDCl3, CFCl3): δ = –104.73
(d, J = 246.4 Hz, 1 F), –109.35 (dd, J = 4.4, 246.4 Hz, 1 F), –164.35
Eur. J. Org. Chem. 0000, 0–0
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