The Journal of Organic Chemistry
Article
isolated in 75−92% overall yields. Compounds 2, 4−9, 19, 21 and 22
showed NMR spectral characteristics similar to those elsewhere
published for the same compounds obtained by other meth-
ods.9,27,28,39,51,61 The enantiomer D of 2 was prepared by the same
protocol starting from D-leucine.
2. Obtained as a pale yellow solid (343.5 mg, 91% yield): TLC Rf
0.40 (eluant: diethyl ether/petroleum ether 50:50); mp 92−94 °C
(lit.9 90−91 °C); 1H NMR (300 MHz, CDCl3) δ 0.91 (d, 6H, J = 6.2
Hz), 1.32−1.78 (m, 3H), 4.12−4.28 (m, 2H), 4.43 (m, 2H), 5.31 (s
broad, 1H), 5.46 (d, 1H, J = 8.1 Hz), 7.28 (t, 2H, J = 7.4 Hz), 7.37 (t,
2H, J = 7.4 Hz), 7.57 (t, 2H, J = 7.4 Hz), 7.73 (d, 2H, J = 7.4 Hz); 13C
NMR (75 MHz, CDCl3) δ 21.6, 23.0, 24.6, 41.1, 47.2, 53.7, 56.2, 66.5,
119.8, 124.9, 125.0, 127.0, 127.6, 141.2, 143.6, 155.9, 194.3. Anal.
Calcd for C22H23N3O3: C, 70.01; H, 6.14; N, 11.13. Found: C, 70.26;
H, 6.13; N, 11.09.
(t, 2H, J = 7.2 Hz), 7.40 (t, 2H, J = 7.2 Hz), 7.59 (d, 2H, J = 7.2 Hz),
7.77 (d, 2H, J = 7.2 Hz); 13C NMR (75 MHz, CDCl3) δ 24.9, 47.4,
52.2, 59.5, 65.9, 120.0, 124.9, 125.0, 127.0, 127.7, 141.3, 143.8, 154.9,
196.4. Anal. Calcd for C20H19N3O3: C, 68.75; H, 5.48; N, 12.03.
Found: C, 68.65; H, 5.46; N, 11.99.
28. Obtained as a pale yellow solid (318.0 mg, 88% yield): TLC Rf
0.45 (eluant: diethyl ether/petroleum ether 80:20); mp 135−137 °C.
1H NMR (300 MHz, CDCl3) indicated a 1:1 mixture of carbamate
conformers δ 1.72−2.18 (m, 8H), 3.47 (m, 4H), 3.96 (m, 1H), 4.16 (t,
1H, J = 5.7 Hz), 4.23 (t, 1H, J = 6.7 Hz), 4.30 (m, 1H), 4.39 (dd, 1H, J
= 10.5 and 6.7 Hz), 4.53 (m, 3H), 4.97 (s broad, 1H), 5.29 (s broad,
1H), 7.26−7.44 (m, 8H), 7.50−7.64 (m, 4H), 7.76 (m, 4H); 13C
NMR (75 MHz, CDCl3) δ 23.3, 24.2, 29.5, 30.9, 46.7, 47.2, 47.3, 52.6,
53.3, 63.5, 63.8, 66.9, 67.1, 119.8, 124.7, 124.8, 125.1, 127.0, 127.4,
127.6, 141.2, 143.8, 154.6, 155.0, 194.3, 164.7. Anal. Calcd for
C21H19N3O3: C, 69.79; H, 5.30; N, 11.63. Found: C, 69.83; H, 5.29;
N, 11.59.
31. Obtained as a pale yellow solid (325.7 mg, 83% yield): TLC Rf
0.30 (eluant: chloroform/methanol 95:5); mp 131−133 °C; 1H NMR
(300 MHz, DMSO-d6) δ 1.68 (m, 1H), 1.91 (m, 1H), 2.14 (t, 2H, J =
7.5 Hz), 3.97 (m, 1H), 4.18−4.40 (m, 3H), 5.96 (s broad, 1H), 6.77 (s
broad, 1H), 7.27 (s broad, 1H), 7.34 (t, 2H, J = 7.2 Hz), 7.42 (t, 2H, J
= 7.2 Hz), 7.74 (t. 2H, J = 7.2 Hz), 7.89 (d. 2H, J = 7.20 Hz); 13C
NMR (75 MHz, DMSO-d6) δ 26.9, 31.6, 47.2, 53.3, 58.5, 66.1, 120.6,
125.7, 127.5, 128.1, 141.2, 144.2, 156.4, 173.9, 195.5. Anal. Calcd for
C21H20N4O4: C, 64.28; H, 5.14; N, 14.28. Found: C, 64.47; H, 5.15;
N, 14.31.
The enantiomer D of 2 was obtained as a pale yellow oil (301.9 mg,
80%). Anal. Calcd for C22H23N3O3: C, 70.01; H, 6.14; N, 11.13.
Found: C, 70.18; H, 6.16; N, 11.16.
22. Obtained as a pale yellow solid (241.0 mg, 75% yield): TLC Rf
0.50 (eluant: chloroform/methanol 98:2); mp 109−111 °C (lit.28
1
110−112 °C); H NMR (300 MHz, CDCl3) δ 4.22 (t, 1H, J = 6.6
Hz), 4.30 (m, 1H), 4.45 (d, 2H, J = 6.6 Hz), 5.27 (s broad, 1H), 5.49
(m, 1H), 7.28−7.43 (m, 4H), 7.60 (m, 2H), 7.77 (d, 2H, J = 7.5 Hz);
13C NMR (75 MHz, CDCl3) δ 47.2, 50.3, 53.7, 67.0, 120.0, 125.1,
127.1, 127.7, 141.3, 143.7, 156.2, 190.0. Anal. Calcd for C18H15N3O3:
C, 67.28; H, 4.71; N, 13.08. Found: C, 67,31; H, 4.70; N, 13.12.
23. Obtained as a pale yellow solid (291.8 mg, 87% yield): TLC Rf
0.62 (eluant: diethyl ether/petroleum ether 80:20); mp 116−118 °C
(lit.9,49 110−112 °C and 118−119 °C); 1H NMR (300 MHz, CDCl3)
δ 1.37 (d, 3H, J = 7.1 Hz), 4.18−4.32 (m, 2H), 4.45 (m, 2H), 5.31 (s
broad, 1H), 5.45 (d, 1H, J = 7.5 Hz), 7.29−7.45 (m, 4H), 7.60 (m,
2H), 7.78 (d, 2H, J = 7.2 Hz); 13C NMR (75 MHz, CDCl3) δ 18.5,
47.2, 53.5, 53.6, 66.7, 120.0, 125.0, 125.1, 127.0, 127.7, 141.3, 143.7,
155.6, 193.8. Anal. Calcd for C19H17N3O3: C, 68.05; H, 5.11; N, 12.53.
Found: C, 68.28; H, 5.12; N, 12.50.
32. Obtained as a viscous pale yellow oil (366.7 mg, 90% yield):
1
TLC Rf 0.43 (eluant: diethyl ether/petroleum ether 60:40); H NMR
(300 MHz, CDCl3) δ 1.16 (s, 9H), 3.46 (dd, 1H, J = 9.0 and 5.4 Hz),
3.78 (dd, 1H, J = 9.0 and 3.3 Hz), 4.23 (t, 1H, J = 6.9 Hz), 4.28 (m,
1H), 4.43 (dd, 1H, J = 10.7 and 6.9 Hz), 4.57 (dd, 1H, J = 10.7 and 6.9
Hz), 5.40 (s broad, 1H), 5.68 (d, 1H, J = 7.8 Hz), 7.28−7.46 (m, 4H),
7.62 (m, 2H), 7.78 (d, 2H, J = 7.5 Hz); 13C NMR (75 MHz, CDCl3) δ
27.3, 47.2, 54.2, 58.3, 61.6, 66.5, 73.7, 119.4, 120.0, 124.9, 125.1, 126.9,
127.0, 127.6, 127.7, 141.2, 141.3, 143.6, 143.7, 155.9, 192.8. Anal.
Calcd for C23H25N3O4: C, 67.80; H, 6.18; N, 10.31. Found: C, 67.94;
H, 6.20; N, 10.29.
24. Obtained as a pale yellow solid (334.3 mg, 92% yield): TLC Rf
0.53 (eluant: diethyl ether/petroleum ether 70:30); mp 123−125 °C
(lit.9,49 123−124 °C, 125−127 °C and 123−125 °C); H NMR (300
1
MHz, CDCl3) δ 0.89 (d, 3H, J = 6.7 Hz), 0.98 (d, 3H, J = 6.7 Hz),
2.11 (m, 1H), 4.12 (m, 1H), 4.23 (t, 1H, J = 6.8 Hz), 4.44 (m, 2H),
5.34 (s broad, 1H), 5.46 (d, 1H, J = 7.1), 7.33 (t, 2H, J = 7.2 Hz), 7.41
(t, 2H, J = 7.2 Hz), 7.61 (m, 2H), 7.78 (d, 2H, J = 7.2 Hz); 13C NMR
(75 MHz, CDCl3) δ 15.3, 17.4, 29.7, 31.0, 47.2, 54.8, 62.8, 66.9, 119.9,
125.0, 125.1, 127.1, 127.7, 141.3, 143.7, 156.3, 193.3. Anal. Calcd for
C21H21N3O3: C, 69.41; H, 5.82; N, 11.56. Found: C, 69.58; H, 5.83;
N, 11.58.
33. Obtained as a viscous pale yellow oil (383.6 mg, 91% yield):
1
TLC Rf 0.73 (eluant: diethyl ether/petroleum ether 60:40); H NMR
(300 MHz, CDCl3) δ 1.08 (d, 3H, J = 6.3 Hz), 1.21 (s, 9H), 4.14 (m,
2H), 4.23 (t, 1H, J = 6.7 Hz), 4.44 (dd, 1H, J = 10.7, and 6.7), 4.51
(dd, 1H, J = 10.7 and 6.7), 5.60 (s broad, 1H), 5.86 (d, 1H, J = 6.9
Hz), 7.32 (t, 2H, J = 7.5 Hz), 7.40 (t, 2H, J = 7.5 Hz), 7.61 (d, 2H, J =
7.5 Hz), 7.77 (d, 2H, J = 7.5 Hz); 13C NMR (75 MHz, CDCl3) δ 18.8,
28.3, 47.3, 54.8, 63.5, 66.7, 67.1, 74.7, 120.0, 125.0, 125.1, 127.0, 127.7,
141.3, 143.7, 156.0, 192.5. Anal. Calcd for C24H27N3O4: C, 68.39; H,
6.46; N, 9.97. Found: C, 68.57; H, 6.44; N, 9.98.
25. Obtained as a pale yellow solid (335.9 mg, 89% yield): TLC
TLC Rf 0.42 (eluant: diethyl ether/petroleum ether 60:40); mp 141−
143 °C (lit.39,49 143−144 °C); H NMR (300 MHz, CDCl3) δ 0.97
34. Obtained as a pale yellow solid (413.8 mg, 84% yield): TLC Rf
1
(m, 6H), 1.18 (m, 1H), 1.49 (m, 1H), 1.80 (m, 1H), 4.21 (m, 1H),
4.26 (t, 1H, J = 6.6 Hz), 4.46 (m, 2H), 5.38 (s broad, 1H), 5.53 (d,
1H, J = 9.0 Hz), 7.34 (t, 2H, J = 7.2 Hz), 7.45 (t, 2H, J = 7.2 Hz), 7.64
(m, 2H), 7.82 (d, 2H, J = 7.2 Hz); 13C NMR (75 MHz, CDCl3) δ
11.4, 15.6, 24.5, 37.5, 47.2, 54.9, 62.2, 66.7, 119.9, 124.9, 125.0, 127.0,
127.6, 141.3, 143.7, 156.2, 193.3. Anal. Calcd for C22H23N3O3: C,
70.01; H, 6.14; N, 11.13. Found: C, 70.18; H, 6.14; N, 11.09.
26. Obtained as a pale yellow solid (370.3 mg, 90% yield): TLC Rf
0.44 (eluant: diethyl ether/petroleum ether 70:30); mp 134−136 °C
0.48 (eluant: ethyl acetate/petroleum ether 50:50); mp 114−116 °C
9
1
(lit. 117−118 °C); H NMR (300 MHz, CDCl3) δ 1.70−1.89 (m,
1H), 1.30−1.67 (m, 5H), 1.43 (s, 9H), 3.09 (m, 2H), 4.13−4.32 (m,
1H), 4.20 (t, 1H, J = 6.6 Hz), 4.38 (dd, 1H, J = 10.8 and 6.6 Hz), 4.50
(dd, 1H, J = 10.8 and 6.6 Hz), 4.58 (s broad, 1H), 5.33 (s broad, 1H),
5.53 (d, 1H, J = 6.9 Hz), 7.30 (t, 1H, J = 7.5 Hz), 7.31 (t, 1H, J = 7.5
Hz), 7.39 (t, 2H, J = 7.5 Hz), 7.59 (m, 2H), 7.76 (d, 2H, J = 7.5 Hz);
13C NMR (75 MHz, CDCl3) δ 22.3, 28.4, 29.7, 31.8, 39.9, 47.3, 53.8,
60.4, 66.7, 79.20, 120.0, 125.0, 127.1, 127.7, 141.4, 143.7, 156.1, 192.9.
Anal. Calcd for C27H32N4O5: C, 65.84; H, 6.55; N, 11.37. Found: C,
65.92; H, 6.56; N, 11.40.
(lit.9,49 133−135 °C, 136−137 °C); H NMR (300 MHz, CDCl3) δ
1
3.05 (2 dd, 2H, J = 13.7 and 6.9 Hz), 4.19 (t, 1H, J = 6.8 Hz), 4.43 (d,
2H, J = 6.8 Hz), 4.49 (q, 1H, J = 6.9 Hz), 5.18 (s broad, 1H), 5.51 (d,
1H, J = 7.8 Hz), 7.15−7.36 (m, 7H), 7.42 (t, 2H, J = 7.5 Hz), 7.56 (t,
2H, J = 7.5 Hz), 7.78 (d, 2H, J = 7.5 Hz); 13C NMR (75 MHz,
CDCl3) δ 38.3, 47.1, 54.8, 58.7, 66.8, 120.0, 125.0, 127.0, 127.7, 128.6,
129.5, 135.9, 141.3, 143.7, 155.7, 192.9. Anal. Calcd for C25H21N3O3:
C, 72.98; H, 5.14; N, 10.21. Found: C, 73.08; H, 5.15; N, 10.24.
27. Obtained as a pale yellow solid (310.9 mg, 89% yield): TLC Rf
0.38 (eluant: diethyl ether/petroleum ether 70:30); mp 127−129 °C;
1H NMR (300 MHz, CDCl3) δ 1.45 (s, 6H), 4.19 (t, 1H, J = 6.3 Hz),
4.49 (d, 2H, J = 6.3 Hz), 5.29 (s broad, 1H), 5.38 (s broad, 1H), 7.32
35. Obtained as a pale yellow solid (370.1 mg, 85% yield): TLC Rf
0.46 (eluant: diethyl ether/petroleum ether 60:40); mp 72−74 °C
(lit.28,39 71−72 °C); 1H NMR (300 MHz, CDCl3) δ 1.43 (s, 9H), 2.58
(dd, 1H, J = 17.3 and 5.0 Hz), 2.92 (dd, 1H, J = 17.3 and 4.1), 4.22 (t,
1H, J = 6.2 Hz), 4.36−4.52 (m, 2H), 4.63 (m, 1H), 5.35 (s broad,
1H), 5 84 (d, 1H, J = 9.4 Hz), 7.31 (m, 2H), 7.39 (m. 2H), 7.58 (m,
2H), 7.78 (d, 2H, J = 7.2 Hz); 13C NMR (75 MHz, CDCl3) δ 28.0,
36.8, 47.4, 50.4, 53.8, 66.7, 81.9, 120.0, 124.9, 125.1, 127.1, 127.7,
141.5, 143.5, 155.9, 170.6, 192.6. Anal. Calcd for C24H25N3O5: C,
66.19; H, 5.79; N, 9.65. Found: C, 66.23; H, 5.80; N, 9.67.
F
dx.doi.org/10.1021/jo301657e | J. Org. Chem. XXXX, XXX, XXX−XXX