L. Kiss et al. / Tetrahedron 72 (2016) 781e787
785
4.5. Ethyl (1R*,2S*,4S*,5R*)-5-azido-2-(tert-butox-
ycarbonylamino)-4-fluorocyclohexanecarboxylate, ( )-3
(Method B)
32.6, 44.6, 56.4, 60.9, 75.7, 78.7, 123.4, 156.2, 171.9. IR(KBr): nmax
1130, 1420, 1540, 1690, 1760, 2380, 2970, 3320. Anal. Calcd for
C14H22N2O5: C 56.36, H 7.43, N 9.39; found: C 56.01, H 7.12, N 9.08.
A white solid, mp 95e97 ꢁC; yield: 41%, (Rf¼0.65, n-hex-
4.10. Ethyl (1R*,2R*,3S*,4R*)-4-azido-2-(tert-butox-
ycarbonylamino)-3-fluorocyclopentanecarboxylate, ( )-15
(Method B)
aneeEtOAc 2:1). 1H NMR (400 MHz, CDCl3):
d
¼1.34 (t, 3H, CH3,
J¼7.10 Hz), 1.46 (s, 9H, t-Bu), 1.60e1.65 (m, 1H, CH2), 2.02e2.11 (m,
1H, CH2), 2.22e2.40 (m, 2H, CH2), 2.93e2.97 (m, 1H, H-1),
3.68e3.73 (m, 1H, H-2), 3.93e3.97 (m, 1H, H-5), 4.20e4.28 (m, 2H,
OCH2), 4.43e4.58 (m, 1H, H-4), 5.41 (br s, 1H, NeH). 13C NMR
A white solid, mp 94e96 ꢁC; yield: 45%, (Rf¼0.6, n-hex-
aneeEtOAc 2:1). 1H NMR (400 MHz, DMSO):
J¼7.10 Hz), 1.38 (s, 9H, t-Bu), 1.70e1.76 (m, 1H, CH2), 2.25e2.32 (m,
1H, CH2), 3.22e3.30 (m, 1H, H-1), 3.98e4.14 (m, 2H, OCH2),
4.28e4.32 (m, 2H, H-2 and H-4), 4.85e5.10 (m, 1H, H-3), 7.24 (br s,
d
¼1.15 (t, 3H, CH3,
(100 MHz, CDCl3):
d
¼14.5, 30.1, 31.8, 33.8, 42.5, 47.1, 60.4, 60.5
(2J¼20.3 Hz), 61.6, 77.7, 91.4, 93.1 (1J¼181.6 Hz), 168.5, 170.2. 19F
NMR (376 MHz, CDCl3):
1680, 1710, 2220, 2980, 3390. Anal. Calcd for C14H23FN4O4: C 50.90,
H 7.02, N 16.96; found: C 50.59, H 6.76, N 16.62.
d
¼ꢃ178.7. IR(KBr): nmax 1180, 1210, 1520,
1H, NeH). 13C NMR (100 MHz, CDCl3):
d
¼14.8, 28.9, 40.4, 43.6, 55.8,
60.1, 60.2 (2J¼24.5 Hz), 59.9, 60.1 (2J¼14.5 Hz), 63.1, 79.2, 96.0, 97.9
(1J¼190.2 Hz), 155.8, 172.4. 19F NMR (376 MHz, CDCl3):
¼ꢃ198.5.
d
4.6. Ethyl (1R*,2R*,3S*,4R*)-3-azido-2-(tert-butox-
ycarbonylamino)-4-fluorocyclohexanecarboxylate, ( )-8
(Method D)
IR(KBr): nmax 1150, 1330, 1560, 1680, 1720, 2120, 2350, 2930, 3320.
Anal. Calcd for C13H21FN4O4: C 49.36, H 6.69, N 17.71; found: C
49.02, H 6.33, N 17.48.
A white solid, mp 90e93 ꢁC; yield: 32%, (Rf¼0.60, n-hex-
4.11. Ethyl (1R*,2S*)-2-(tert-butoxycarbonylamino)-4-
cyanocyclopent-3-enecarboxylate, ( )-16 (Method D)
aneeEtOAc 2:1); 1H NMR (400 MHz, CDCl3):
d¼1.36 (t, 3H, CH3),
1.41 (s, 9H, x), 1.52e1.60 (m, 2H, CH2), 2.08e2.14 (m, 1H, CH2),
2.15e2.26 (m, 1H, CH2), 2.96e3.01 (m, 1H, H-1), 3.75e3.84 (m, 1H,
H-2), 3.91e99 (m, 1H, H-3), 4.19e4.28 (m, 2H, OCH2), 4.29e4.45 (m,
A white solid, mp 145e148 ꢁC, n-hexane); yield: 56%, (Rf¼0.55,
n-hexaneeEtOAc 4:1). 1H NMR (400 MHz, CDCl3):
d
¼1.31 (t, 3H,
1H, H-4), 5.43 (br s, 1H, NeH). 13C NMR (100 MHz, CDCl3):
d¼14.5,
CH3, J¼7.10 Hz), 1.46 (s, 9H, t-Bu), 2.74e2.83 (m, 1H, CH2), 3.06e3.14
(m, 1H, CH2), 3.47e3.54 (m, 1H, H-1), 4.16e4.24 (m, 2H, OCH2), 4.88
23.1, 27.5, 28.7, 44.4, 51.9, 61.4, 65.5, 65.7 (2J¼17.9 Hz), 80.5, 92.3,
94.1 (1J¼179.1 Hz), 155.8, 173.4. 19F NMR (376 MHz, CDCl3):
(br s, 1H, NeH), 5.25e5.30 (m, 1H, H-2), 6.47e6.49 (m, 1H, H-3). 13
C
d
¼ꢃ177.2. IR(KBr): nmax 1110, 1200, 1290, 1520, 1680, 1720, 2110,
NMR (100 MHz, CDCl3):
d
¼14.5, 28.6, 36.4, 45.9, 57.7, 61.7, 80.2,
2980, 3390. Anal. Calcd for C14H23FN4O4: C 50.90, H 7.02, N 16.96;
found: C 51.29, H 6.77, N 16.65.
115.5, 116.7, 146.0, 158.5, 170.4. IR(KBr): nmax 1190, 1530, 1710,
29040, 3360. Anal. Calcd for C14H20N2O4: C 59.99, H 7.19, N 9.99;
found: C 59.70, H 6.86, N 9.69.
4.7. Ethyl 2-(tert-butoxycarbonylamino)cyclohexa-1,3-
dienecarboxylate, 9 (Method D)
4.12. Ethyl (1R*,2R*,3S*,5S*)-2-(tert-butoxycarbonylamino)-6-
oxabicyclo-[3.1.0]hexane-3-carboxylate, ( )-18 (Method A)
A white solid, mp 45e46 ꢁC; yield: 30%. 1H NMR (400 MHz,
DMSO):
d
¼1.31 (t, 3H, CH3, J¼7.10 Hz), 1.47 (s, 9H, t-Bu), 2.12e2.18
A white solid, mp 70e72 ꢁC, (n-hexane); yield: 59%, (Rf¼0.65, n-
(m, 2H, CH2), 2.36e2.43 (m, 2H, CH2), 4.08e4.15 (m, 2H, OCH2),
6.44e6.53 (m, 1H, H-4), 7.06e7.11 (m, 1H, H-3), 10.6 (br s, 1H, NeH).
hexaneeEtOAc 2:1). 1H NMR (CDCl3, 400 MHz)
d¼1.22 (t, 3H, CH3,
J¼7.10 Hz), 1.43 (s, 9H, t-Bu), 2.02e2.10 (m, 1H, CH2), 2.30e2.40 (m,
2H, CH2 and H-1), 3.51e3.54 (m, 1H, H-4), 3.59e3.61 (m, 1H, H-3),
4.15e4.21 (m, 2H, OCH2), 4.35e4.41 (m, 1H, H-2), 4.90 (br s, 1H,
13C NMR (100 MHz, DMSO):
d
¼15.0, 21.2, 22.8, 28.6, 60.9, 81.4,
100.4, 122.4, 137.8, 146.2, 152.3, 169.7. IR(KBr): nmax 1190, 1210, 1310,
1500, 1700, 1730, 2960, 3320. Anal. Calcd for C14H21NO4: C 62.90, H
7.92, N 5.24; found: C 62.60, H 7.61, N 4.92.
NeH). 13C NMR (100 MHz, CDCl3):
57.8, 61.1, 78.8, 156.2, 174.1. IR(KBr): nmax 1180, 1230, 1580, 1700,
1790, 2950, 3100, 3380. Anal. Calcd for C13H21NO5: C 57.55, H 7.80, N
5.16; found: C 57.90, H 7.47, N 4.79.
d
¼14.8, 29.1, 32.2, 42.3, 54.4, 56.1,
4.8. Ethyl (1R*,2S*)-2-(tert-butoxycarbonylamino)-4-
cyanocyclohex-3-en-ecarboxylate, ( )-10 (Method D)
4.13. Ethyl (1S*,2R*,3S*,4S*)-3-azido-2-(tert-butox-
ycarbonylamino)-4-hydroxycyclopentanecarboxylate, ( )-20
(Method B)
A white solid, mp 72e75 ꢁC, (n-hexane); yield: 53%, (Rf¼0.55, n-
hexaneeEtOAc 4:1). 1H NMR (400 MHz, CDCl3):
d¼1.23 (t, 3H, CH3,
J¼7.15 Hz), 1.30 (s, 9H, t-Bu), 1.76e2.02 (m, 2H, CH2), 2.17e2.23 (m,
2H, CH2), 2.76e2.80 (m, 1H, H-1), 4.02e2.21 (m, 2H, OCH2),
5.52e4.60 (m, 1H, H-2), 5.46 (br s, 1H, NeH), 6.42e6.48 (m, 1H, H-
A white solid, mp 102e104 ꢁC, (n-hexane); yield: 22%, (Rf¼0.60,
n-hexaneeEtOAc 2:1). 1H NMR (CDCl3, 400 MHz)
d
¼1.23 (t, 3H, CH3,
3). 13C NMR (100 MHz, CDCl3):
61.5, 80.9, 101.2, 113.9, 118.5, 144.7, 156.0. IR(KBr): nmax 1120, 1210,
1530, 1690, 1730, 2380, 2960, 3320. Anal. Calcd for C15H22N2O4: C
61.21, H 7.53, N 9.52; found: C 60.88, H 7.11, N 9.19.
d
¼14.5, 22.8, 25.0, 28.7, 31.3, 42.8,
J¼7.14 Hz), 1.44 (s, 9H, t-Bu), 2.06e2.12 (m, 1H, CH2), 2.14e2.20 (m,
1H, CH2), 3.17e3.22 (m, 1H, H-1), 3.81e3.92 (m, 2H, H-2, H-3),
4.16e4.19 (m, 1H, H-4), 4.20e4.27 (m, 2H, OCH2), 5.08 (br s, 1H,
NeH). 13C NMR (CDCl3, 100 MHz)
72.3, 75.0, 79.8, 152.6, 170.5. IR(KBr): nmax 1200, 1310, 1560, 1680,
1720, 2130, 2950, 3310, 3500. Anal. Calcd for C13H22N4O5: C 48.67, H
7.05, N 17.82; found: C 48.32, H 6.70, N 18.19.
d
¼14.6, 28.7, 35.1, 47.2, 59.3, 61.6,
4.9. Ethyl (1R*,2R*,3S*,4S*)-2-((tert-butoxycarbonyl)amino)-
4-cyano-3-hydoxycyclopentanecarboxylate, ( )-14 (Method C)
A white solid, mp 147e150 ꢁC; yield 61%, (Rf¼0.5, n-hex-
4.14. Ethyl (1S*,2R*,3S*,4R*)-4-azido-2-(tert-butox-
ycarbonylamino)-3-fluorocyclopentanecarboxylate, ( )-21
(Method D)
aneeEtOAc 2:1). 1H NMR (400 MHz, CDCl3):
d
¼1.28 (t, 3H, CH3,
J¼7.20 Hz), 1.45 (s, 9H, t-Bu), 2.12e2.22 (m, 1H, CH2), 2.51e2.59 (m,
1H, CH2), 3.05e3.09 (m, 1H, H-1), 3.37e3.41 (m, 1H, H-4), 3.90 (br s,
1H, OeH), 4.15e4.23 (2H, OCH2), 4.26e4.38 (m, 2H, H-2 and H-3),
A white solid, mp 92e95 ꢁC; yield: 35%, (Rf¼0.40, n-hex-
5.28 (br s, 1H, NeH). 13C NMR (100 MHz, DMSO):
d
¼14.7, 26.8, 29.0,
aneeEtOAc 2:1). 1H NMR (400 MHz, DMSO):
d¼1.17 (t, 3H, CH3,