R. Goto et al. / Tetrahedron 67 (2011) 6659e6672
6669
128.7, 128.9, 133.4, 144.0, 146.7, 167.5, 167.6, 171.3, 174.2; HRMS (ESI)
162.8, 167.6, 167.7, 171.3, 173.8; HRMS (ESI) calcd for C27H35FN6O5Na
calcd for C28H36N6O5Na 559.2645 (MþNaþ), found 559.2643.
565.2551 (MþNaþ), found 565.2554.
4.24. Triazole 5d
4.27. Triazole 5g
To a solution of 4 (20.5 mg, 0.051 mmol), CuI (1.9 mg,
0.01 mmol), and tert-butylmethylazide in THF (0.5 mL) at room
temperature was added i-Pr2NEt (0.088 mL, 0.51 mmol). After being
stirred for 24.5 h at room temperature, the reaction mixture was
quenched with 1 M aqueous HCl, and extracted with EtOAc. The
organic layer was washed with brine, and dried over Na2SO4.
Concentration and flash column chromatography (hexane/
Triazole 5g was obtained in 85% yield by the same procedure for
25
5d using 4-methoxybenzylazide: [
(neat)
NMR (500 MHz, CDCl3)
a
]
ꢁ77.6 (c 0.42, CHCl3); IR
D
n
3269, 2965,1736,1682, 1636,1556,1515,1251, 756 cmꢁ1; 1H
d
0.84 (3H, d, J¼6.9 Hz, H140 or H150), 0.87
(3H, d, J¼6.9 Hz, H13), 0.95 (3H, d, J¼6.9 Hz, H140 or H150), 1.42 (3H,
d, J¼6.9 Hz, H110), 2.36 (1H, dqq, J¼6.9, 6.9, 10.9 Hz, H130), 2.45 (3H,
s, H120), 2.50 (1H, dq, J¼6.9,11.5 Hz, H4), 2.85 (1H, d, J¼13.2 Hz, H2),
3.01 (1H, d, J¼13.2 Hz, H2), 3.49 (1H, d, J¼18.9 Hz, H80), 3.79 (3H, s,
OMe), 4.17 (1H, d, J¼10.9 Hz, H50), 4.59 (1H, dd, J¼10.3,18.9 Hz, H80),
5.07 (1H, s, H12), 5.11 (1H, s, H12), 5.32 (1H, dq, J¼6.9, 9.8 Hz, H20),
5.35 (1H, d, J¼14.9 Hz, H9), 5.52 (1H, d, J¼14.9 Hz, H9), 6.15 (1H, d,
J¼11.5 Hz, H5), 6.59 (1H, d, J¼9.8 Hz, H10), 6.87 (2H, d, J¼8.6 Hz,
phenyl), 7.23 (2H, d, J¼8.6 Hz, phenyl), 7.74 (1H, s, H7), 7.96 (1H, d,
EtOAc¼3/4 to 0/100) gave 5d (20.0 mg) in 77% yield: [
a
]
23 ꢁ112 (c
D
0.660, CHCl3); IR (neat)
n 3439, 2965, 1740, 1634, 1553, 1259,
755 cmꢁ1; 1H NMR (500 MHz, CDCl3)
d
0.87 (3H, d, J¼7.5 Hz, H140 or
H150), 0.88 (3H, d, J¼6.9 Hz, H13), 0.90 (3H, d, J¼6.9 Hz, H140 or
H150), 0.96 (9H, s, t-Bu), 1.44 (3H, d, J¼6.9 Hz, H110), 2.40 (1H, dqq,
J¼6.9, 7.5, 10.9 Hz, H130), 2.60 (1H, dq, J¼6.9, 10.9 Hz, H4), 2.75 (3H,
s, H120), 2.91 (1H, d, 13.2 Hz, H2), 3.02 (1H, d, J¼13.2 Hz, H2), 3.52
(1H, dd, J¼1.7, 18.3 Hz, H80), 4.09 (1H, d, J¼13.7 Hz, H9), 4.13 (1H, d,
J¼13.7 Hz, H9), 4.23 (1H, d, J¼10.9 Hz, H50), 4.62 (1H, dd, J¼9.2,
18.3 Hz, H80), 5.09 (1H, s, H12), 5.13 (1H, s, H12), 5.34 (1H, dq, J¼6.9,
9.2 Hz, H20), 6.16 (1H, d, J¼10.9 Hz, H5), 6.74 (1H, d, J¼9.2 Hz, H10),
7.73 (1H, s, H7), 8.01 (1H, dd, J¼1.7, 9.2 Hz, H70); 13C NMR (500 MHz,
J¼10.3 Hz, H70); 13C NMR (500 MHz, CDCl3)
d 18.5, 18.6, 18.9, 19.2,
25.7, 28.5, 40.9, 42.0, 43.2, 46.1, 53.8, 55.3, 67.1, 71.3, 114.4, 114.5,
122.2, 126.4, 129.7, 144.1, 146.3, 159.9, 167.5, 167.6, 171.3, 173.8;
HRMS (ESI) calcd for C28H38N6O6Na 577.2751 (MþNaþ), found
577.2757.
CDCl3)
d 18.5, 18.6, 18.9, 19.2, 25.8, 27.5, 28.9, 32.5, 41.0, 41.9, 43.3,
46.1, 61.8, 67.1, 71.3, 114.4, 123.9, 144.2, 145.1, 167.67, 167.72, 171.3,
173.8; HRMS (ESI) calcd for C25H40N6O5Na 527.2958 (MþNaþ),
found 527.2949.
4.28. Triazole 5h
Triazole 5h was obtained in 74% yield by the same procedure
23
for 5d using 2,4,6-trimethylbenzylazide: [
a]
ꢁ97.2 (c 1.63,
D
CHCl3); IR (neat)
n ;
3436, 2967, 1742, 1637, 1559, 1236, 756 cmꢁ1
4.25. Triazole 5e
1H NMR (500 MHz, CDCl3)
d
0.84 (3H, d, J¼6.9 Hz, H13 or H140 or
H150), 0.86 (3H, d, J¼7.5 Hz, H13 or H140 or H150), 0.94 (3H, d,
J¼6.9 Hz, H13 or H140 or H150), 1.42 (3H, d, J¼6.3 Hz, H110), 2.27
(3H, s, CH3Ph), 2.30 (6H, s, CH3Ph), 2.32e2.36 (1H, m, H130), 2.39
(3H, s, H120), 2.49 (1H, m, H4), 2.86 (1H, d, J¼12.6 Hz, H2), 2.99
(1H, d, J¼12.6 Hz, H2), 3.47 (1H, dd, J¼1.5, 18.9 Hz, H80), 4.15 (1H,
d, J¼11.5 Hz, H50), 4.57 (1H, dd, J¼9.2, 18.9 Hz, H80), 5.06 (1H, s,
H12), 5.10 (1H, s, H12), 5.29 (1H, dq, J¼6.3, 9.2 Hz, H20), 5.49 (1H,
d, J¼14.9 Hz, H9), 5.58 (1H, d, J¼14.9 Hz, H9), 6.10 (1H, d,
J¼11.5 Hz, H5), 6.69 (1H, d, J¼9.2 Hz, H10), 6.90 (2H, s, phenyl), 7.46
(1H, s, H7), 7.95 (1H, dd, J¼1.5, 9.2 Hz, H70); 13C NMR (500 MHz,
Triazole 5e was obtained in 65% yield by the same procedure for
5d using benzylazide: [
a
]
23 ꢁ86.6 (c 0.82, CHCl3); IR (neat)
n 3450,
D
3070, 1742, 1637, 1560, 1457, 1259, 756 cmꢁ1 1H NMR (500 MHz,
;
CDCl3)
d
0.84 (3H, d, J¼6.9 Hz, H150), 0.89 (3H, d, J¼7.5 Hz, H13),
0.94 (3H, d, J¼6.3 Hz, H140), 1.41 (3H, d, J¼6.9 Hz, H110), 2.23e2.37
(1H, m, H130), 2.39 (3H, s, H120), 2.53 (1H, dq, J¼7.5, 11.5 Hz, H4),
2.87 (1H, d, J¼12.6 Hz, H2), 3.00 (1H, d, J¼12.6 Hz, H2), 3.48 (1H, dd,
J¼1.8, 18.3 Hz, H80), 4.16 (1H, d, J¼10.9 Hz, H50), 4.58 (1H, dd, J¼9.2,
18.3 Hz, H80), 5.07 (1H, s, H12), 5.11 (1H, s, H12), 5.30 (1H, dq, J¼6.9,
9.2 Hz, H20), 5.41 (1H, d, J¼14.9 Hz, H9), 5.61 (1H, d, J¼14.9 Hz, H9),
6.16 (1H, d, J¼11.5 Hz, H5), 6.67 (1H, d, J¼9.2 Hz, H10), 7.26e7.37
(5H, m, phenyl), 7.76 (1H, s, H7), 7.96 (1H, dd, J¼1.8, 9.2 Hz, H70); 13C
CDCl3)
d 18.4, 18.6, 19.0, 19.2, 19.7, 20.9, 25.8, 28.3, 40.9, 41.6, 43.2,
46.1, 48.4, 67.0, 71.3, 114.1, 121.6, 127.2, 129.6, 137.9, 138.8, 144.4,
145.6, 167.6, 167.7, 171.3, 173.6; HRMS (ESI) calcd for C30H42N6O5Na
589.3114 (MþNaþ), found 589.3106.
NMR (500 MHz, CDCl3)
d 18.4, 18.6, 18.8, 19.2, 25.7, 28.5, 40.9, 41.8,
43.2, 46.0, 54.3, 67.1, 71.2, 114.4, 122.6, 128.2, 128.8, 129.1, 134.3,
144.1, 146.3, 167.5, 167.7, 171.3, 173.8; HRMS (ESI) calcd for
C27H36N6O5Na 547.2645 (MþNaþ), found 547.2636.
4.29. Triazole 5i
4.26. Triazole 5f
Triazole 5i was obtained in 76% yield by the same procedure for
24
5d using 4-biphenylazide: [
a
]
ꢁ70.9 (c 0.76, CHCl3); IR (neat)
n
D
Triazole 5f was obtained in 89% yield by the same procedure for
3436, 2966, 1734, 1636, 1552, 1258, 750 cmꢁ1 1H NMR (500 MHz,
;
28
5d using 4-fluorobenzylazide: [
(neat)
NMR (500 MHz, CDCl3)
a]
ꢁ70.5 (c 0.570, CHCl3); IR
CDCl3)
d
0.81 (3H, d, J¼6.9 Hz, H13 or H140 or H150), 0.91 (3H, d,
D
n
3271, 2968,1743, 1682,1636,1556,1512,1226, 755 cmꢁ1; 1H
J¼6.9 Hz, H13 or H140 or H150), 0.93 (3H, d, J¼6.3 Hz, H13 or H140 or
H150),1.41 (3H, d, J¼6.9 Hz, H110), 2.29e2.32 (1H, m, H130), 2.42 (3H,
s, H120), 2.56 (1H, m H4), 2.89 (1H, d, J¼12.6 Hz, H2), 3.00 (1H, d,
J¼12.6 Hz, H2), 3.49 (1H, d, J¼18.3 Hz, H80), 4.16 (1H, d, J¼10.9 Hz,
H50), 4.60 (1H, dd, J¼9.2, 18.3 Hz, H80), 5.07 (1H, s, H12), 5.11 (1H, s,
H12), 5.30 (1H, dq, J¼6.9, 9.8 Hz, H20), 5.46 (1H, d, J¼15.5 Hz, H9),
5.64 (1H, d, J¼15.5 Hz, H9), 6.17 (1H, d, J¼10.9 Hz, H5), 6.74 (1H, d,
J¼9.8 Hz, H10), 7.35e7.59 (9H, m, diphenyl), 7.81 (1H, s, H7), 7.97
d
0.86 (3H, d, J¼6.9 Hz, H13 or H140 or H150),
0.87 (3H, d J¼7.4 Hz, H13 or H140 or H150), 0.95 (3H, d, J¼6.9 Hz, H13
or H140 or H150), 1.42 (3H, d, J¼6.9 Hz, H110), 2.36 (1H, m, H130), 2.45
(3H, s, H120), 2.55 (1H, m, H4), 2.87 (1H, d, J¼12.6 Hz, H2), 3.00 (1H,
d, J¼12.6 Hz, H2), 3.49 (1H, d, J¼18.3 Hz, H80), 4.18 (1H, d, J¼11.5 Hz,
H50), 4.59 (1H, dd, J¼9.8, 18.3 Hz, H80), 5.06 (1H, s, H12), 5.11 (1H, s,
H12), 5.31 (1H, dq, J¼6.9, 9.2 Hz, H20), 5.40 (1H, d, J¼15.5 Hz, H9),
5.56 (1H, d, J¼15.5 Hz, H9), 6.15 (1H, d, J¼11.5 Hz, H5), 6.66 (1H, d,
J¼9.2 Hz, H10), 7.05 (2H, t, J¼8.6 Hz, phenyl), 7.27 (2H, dd, J¼5.2,
8.6 Hz, phenyl), 7.76 (1H, s, H7), 7.97 (1H, d, J¼9.8 Hz, H70); 13C NMR
(1H, d, J¼9.2 Hz, H70); 13C NMR (500 MHz, CDCl3)
d 18.5, 18.6, 18.9,
19.2, 25.7, 28.5, 40.9, 42.0, 43.2, 46.1, 54.0, 67.1, 71.3, 114.6, 122.6,
127.1, 127.6, 127.8, 128.7, 128.8, 133.3, 140.2, 141.7, 144.0, 146.4, 167.5,
167.6, 171.3, 173.8; HRMS (ESI) calcd for C33H40N6O5Na 623.2958
(MþNaþ), found 623.2947.
(500 MHz, CDCl3)
46.0, 53.5, 67.1, 71.2, 114.5, 116.1, 122.5, 130.1,130.2, 144.1, 146.4,
d 18.4, 18.6, 18.8, 19.1, 25.7, 28.5, 40.8, 41.8, 43.2,