1522
T. Konno et al. / Journal of Fluorine Chemistry 126 (2005) 1517–1523
14.5 Hz), 2.99 (1H, dd, J = 6.2, 14.5 Hz), 3.76 (3H, s), 3.84
(3H, s), 4.40 (1H, s), 5.10 (2H, m), 5.55 (1H, dt, J = 7.8,
substrate (condition: ethyl methallyl carbonate 1.2 equiv., reflux,
6 h; yield 84%). 1H NMR (CDCl3) d 2.82 (1H, d, J = 15.5 Hz),
2.94 (1H, d, J = 15.6 Hz), 3.75 (3H, s), 3.84 (3H, s), 4.44 (1H, s),
4.87 (2H, d, J = 21.7 Hz), 6.75 (2H, d, J = 9.0 Hz), 6.81 (2H, d,
J = 9.0 Hz); 13C NMR (CDCl3) d 23.7, 36.5, 53.5, 55.5, 67.8 (q,
J = 25.8 Hz), 114.2, 115.6, 121.1 (q, J = 1.5 Hz), 124.6 (q,
J = 289.9 Hz), 136.7, 138.8, 154.5, 169.1; 19F NMR (CDCl3)
16.9 Hz), 6.77 (2H, d, J = 9.0 Hz), 6.83 (2H, d, J = 9.0 Hz); 13
NMR (CDCl3) d 34.6, 53.5, 55.5, 68.0 (q, J = 11.1 Hz), 114.3,
C
121.5, 130.2, 136.4, 154.8, 168.9; 19F NMR (CDCl3) d 72:93F,
˜
˙
˙
s; IR (neat) n 3375, 2957, 1747, 1514, 1443 cmꢁ1; MS (FAB)
calcd. for C14H16F3NO3 303.1082, found 303.1082.
d 72:83F, s; IR (neat) n 3387, 2957, 1747, 1514 cmꢁ1; MS (FAB)
˜
˙
calcd. for C15H18F3NO3 317.1239, found 317.1238.
˙
4.2.2.2. Benzyl 2-[N-(anisyl)amino]-2-(trifluoromethyl)pent-
4-enoate (3c). Benzyl 2-[N-(anisyl)amino]-3,3,3-trifluoropro-
pionate (133 mg, 0.392 mmol) was used as a substrate
(condition: allyl ethyl carbonate 1.2 equiv., reflux, 6 h; yield
91%) (condition: allyl ethyl carbonate 1.2 equiv., room
temperature, 12 h; yield 96%). 1H NMR (CDCl3) d 2.81
(1H, dd, J = 8.0, 14.6 Hz), 2.99 (1H, dd, J = 6.2, 14.6 Hz), 3.75
(3H, s), 4.39 (1H, s), 5.01 (1H, dd, J = 1.4, 17.0 Hz), 5.05 (1H,
d, J = 10.2 Hz), 5.25 (2H, d, J = 2.8 Hz), 5.53 (1H, dt, J = 7.6,
16.8 Hz), 6.73 (2H, d, J = 9.0 Hz), 6.80 (2H, d, J = 9.0 Hz),
7.28–7.42 (5H, m); 13C NMR (CDCl3) d 34.7, 55.5, 68.1 (q,
J = 26.5 Hz), 68.6, 114.3, 120.7, 121.5, 124.6 (q, J = 288.1 Hz),
128.5, 128.6, 128.7, 129.9, 134.5, 136.5, 154.7, 168.2; 19F
4.2.2.6. Benzyl 2-[N-(anisyl)amino]-4-methyl-2-(trifluoro-
methyl)pent-4-enoate (3g). Benzyl 2-[N-(anisyl)amino]-3,3,3-
trifluoropropionate (1c) (136 mg, 0.401 mmol) was used as a
substrate (condition: ethyl methallyl carbonate 1.2 equiv.,
reflux, 6 h; yield 86%). 1H NMR (CDCl3) d 1.61 (3H, s),
2.82 (1H, d, J = 15.6 Hz), 2.93 (1H, d, J = 15.6 Hz), 3.75 (3H,
s), 4.84 (2H, s), 5.22 (1H, d, J = 12.2 Hz), 5.26 (1H, d,
J = 12.2 Hz), 6.73 (2H, d, J = 9.0 Hz), 6.79 (2H, d, J = 9.0 Hz),
7.29–7.40 (5H, m); 13C NMR (CDCl3) d 23.7, 36.7, 55.5, 67.8
(q, J = 26.0 Hz), 68.6, 114.2, 115.7, 121.1, 124.6 (q,
J = 290.4 Hz), 128.5, 128.6, 128.6, 134.4, 136.7, 138.7,
19
˜
˜
154.5, 168.4; F NMR (CDCl3) d 72:63F, s; IR (neat) n
NMR (CDCl3) d 72:73F, s; IR (neat) n 3375, 2937, 1746, 1514,
˙
˙
˙
˙
1456 cmꢁ1; MS (FAB) calcd. for C20H20F3NO3 379.1395,
found 379.1400.
3383, 2910, 1744, 1514 cmꢁ1
; MS (FAB) calcd. for
C21H22F3NO3 393.1552, found 393.1544.
4.2.2.3. (E)-Methyl 2-[N-(anisyl)amino]-2-(trifluoromethyl)-
hex-4-enoate (3d). Methyl 2-[N-(anisyl)amino]-3,3,3-trifluor-
opropionate (95 mg, 0.361 mmol) was used as a substrate
(condition: crotyl ethyl carbonate 1.2 equiv., reflux, 6 h; yield
59%). 1H NMR (CDCl3) d 1.61 (3H, d, J = 6.4 Hz), 2.74 (1H,
dd, J = 8.0, 14.4 Hz), 2.90 (1H, dd, J = 6.3, 14.4 Hz), 3.76 (3H,
s), 3.83 (3H, s), 4.35 (1H, s), 5.17 (1H, dt, J = 14.6, 7.2 Hz),
5.49 (1H, dq, J = 15.1, 6.5 Hz), 6.72–6.85 (4H, m); 13C NMR
(CDCl3) d 18.1, 34.0, 53.4, 55.5, 68.1 (q, J = 26.4 Hz), 114.3,
121.1, 122.3, 124.7 (q, J = 288.2 Hz), 131.8, 136.7, 154.6,
4.2.2.7. 5-Benzyl 1-methyl 2-[N-(anisyl)amino]-4-methylene-
2-(trifluoromethyl)-dicarboxylate (3h). Methyl 2-[N-(anisyl)a-
mino]-3,3,3-trifluoropropionate (1b) (101 mg, 0.384 mmol) was
used as a substrate (condition: ethyl (3-benzyloxycarbonyl-2-
methylenepropyl) carbonate 1.2 equiv., reflux, 24 h; yield 40%).
1H NMR (CDCl3) d 3.17 (2H, s), 3.71 (3H, s), 3.74 (3H, s), 4.75
(1H, s), 5.20 (2H, s), 5.73 (1H, s), 6.37 (1H, s), 6.68 (2H, d,
J = 9.1 Hz), 6.73 (2H, d, J = 9.0 Hz), 7.27–7.39 (5H, m); 13C
NMR (CDCl3) d 33.2, 53.0, 55.5, 67.1, 68.2 (q, J = 26.1 Hz),
114.3, 119.7, 124.6 (q, J = 290.4 Hz), 128.2, 128.4, 128.6,
129.9, 134.0, 135.5, 136.9, 154.2, 166.9, 168.2; 19F NMR
19
˜
169.1; F NMR (CDCl3) d 72:53F, s; IR (neat) n 3375, 2957,
˙
˙
1747, 1514, 1443 cmꢁ1; MS (FAB) calcd. for C15H18F3NO3
317.1239, found 317.1241.
(CDCl3) d 71:923F, s; IR (neat) n 3379, 2955, 1747, 1717,
˜
˙
˙
1514 cmꢁ1; MS (FAB) calcd. for C22H22F3NO5 437.1450,
found 437.1455.
4.2.2.4. Methyl 2-[N-(anisyl)amino]-5-phenyl-2-(trifluoro-
methyl)pent-4-enoate (3e). Methyl 2-[N-(anisyl)amino]-
3,3,3-trifluoropropionate (101 mg, 0.384 mmol) was used as
a substrate (condition: cinnamyl ethyl carbonate 1.2 equiv.,
4.2.3. Synthesis of a-trifluoromethyl leucine
4.2.3.1. Benzyl 2-amino-4-methyl-2-(trifluoromethyl)pent-4-
enoate (6). Benzyl 2-[N-(anisyl)amino]-4-methyl-2-(trifluor-
omethyl)pent-4-enoate (3g) (128 mg, 0.325 mmol) (diluted
with 6.5 mL of CH3CN) was added to a solution of CAN
(ammonium cerium(IV) nitrate) (948 mg, 1.64 mmol) in H2O
(6.5 mL) at room temperature and stirred for 2 h. The resulting
solution was extracted with AcOEt and washed with brine. The
collected organic layers were dried over anhydrous sodium
sulfate, filtered and the solvent was removed under reduced
pressure. The residue was purified by column chromatography
on aluminum (hexane:AcOEt = 5:1 ! 3:1) to give benzyl 2-
amino-4-methyl-2-(trifluoromethyl)pent-4-enoate (6) (82 mg)
in 88% yield as a yellow liquid. 1H NMR (CDCl3) d 1.61 (3H,
s), 1.82 (2H, s), 2.47 (1H, d, J = 14.0 Hz), 2.91 (1H, d,
J = 14.0 Hz), 4.82 (1H, s), 4.94 (1H, t, J = 1.4 Hz), 5.21 (1H, d,
1
reflux, 6 h; yield 91%). H NMR (CDCl3) d 2.97 (1H, dd,
J = 8.2, 14.6 Hz), 3.13 (1H, ddd, J = 1.2, 6.5, 14.6 Hz), 3.77
(3H, s), 3.85 (3H, s), 4.45 (1H, s), 5.88 (1H, dt, J = 15.4,
7.6 Hz), 6.37 (1H, d, J = 15.8 Hz), 6.79 (2H, d, J = 8.9 Hz),
6.87 (2H, d, J = 8.9 Hz), 7.20–7.32 (5H, m); 13C NMR (CDCl3)
d 33.9, 53.6, 55.5, 68.4 (q, J = 26.6 Hz), 114.4, 121.3, 121.9,
124.6 (q, J = 288.1 Hz), 126.3, 127.7, 128.5, 135.3, 136.5,
154.9, 168.9; 19F NMR (CDCl3) d 72:93F, s; IR (neat) n 3373,
˜
˙
˙
2955, 1747, 1514 cmꢁ1; MS (FAB) calcd. for C20H20F3NO3
379.1395, found 379.1400.
4.2.2.5. Methyl 2-[N-(anisyl)amino]-4-methyl-2-(trifluoro-
methyl)pent-4-enoate (3f). Methyl 2-[N-(anisyl)amino]-3,3,3-
trifluoropropionate (127 mg, 0.483 mmol) was used as a
J = 12.2 Hz), 5.27 (1H, d, J = 12.2 Hz), 7.28–7.40 (5H, m); 13
C