The Journal of Organic Chemistry
Article
5
H), 7.45−7.50 (m, 2H), 7.73−7.78 (m, 2H). 13C NMR (50 MHz,
CDCl ): δ 26.4, 26.7, 72.2 (CH ), 76.1, 77.1, 81.4, 104.0, 113.4, 128.0,
1.33 (s, 3H), 1.44 (s, 3H), 3.34 (s, 3H), 3.38 (s, 3H), 3.44−3.52 (m,
1H), 3.96 (d, 1H, J = 3.0 Hz), 4.21−4.33 (m, 2H), 4.56−4.86 (m,
3
2
128.2, 128.5, 129.1, 129.5, 130.7, 136.8, 138.5, 140.0, 142.2. HRMS
9H), 5.19−5.23 (m, 1H), 5.42 (d, 1H, J = 3.0 Hz), 5.96 (d, 1H, J = 3.8
+
+
13
[
ES , (M + Na) ]: for C H O NaSCl found 473.0779, calcd
Hz), 7.22−7.32 (m, 10H), 7.79 (s, 1H). C NMR (50 MHz, CDCl ):
22
23
6
3
4
73.0802 (E).
General Procedure for the Synthesis of 1,5-Disubstituted
Triazole-Linked Disaccharides 28−32. A mixture of vinyl sulfone
1 equiv) and azidosugar (1.5 equiv) in water (5 mL/mmol) was
δ 26.3, 26.9, 55.6, 57.6, 57.7, 60.8 (CH ), 68.1, 72.4, 73.0 (CH ), 74.1
2
2
(CH ), 75.2, 76.7, 81.4, 84.5, 99.3, 104.8, 112.1, 127.5, 127.7, 127.8,
2
+
1
28.2, 128.4, 128.5, 133.4, 134.6, 138.1, 138.6. HRMS [ES , (M +
H) ]: for C H N O found 598.2744, calcd 598.2765.
+
(
31
40
3
9
heated under reflux for 36−48 h to afford 1,5-disubstituted triazole-
linked disaccharides. For vinyl sulfones 27a−c and azidosugars 8 and
Compound 31b. Following the general procedure, over 40 h
compound 27b (0.25 g, 0.67 mmol) was converted to 31b (0.34 g,
9
, NaHCO3 (1.5 equiv) was added to the reaction mixture. For
29
70%). Eluent: EtOAc/petroleum ether (1:4). Colorless gum. [α]
D
azidosugars 11 and 12 the reaction was performed in reluxing toluene.
Compound 31a. Following the general procedure, over 48 h
compound 27a (0.25 g, 0.55 mmol) was converted to 31a (0.31 g,
1
(
+): 90.0 (c 0.9, CHCl ). H NMR (200 MHz, CDCl ): δ 1.26 (s,
3
3
3
4
H), 1.55 (s, 3H), 3.10 (s, 3H), 3.18 (s, 3H), 3.75 (d, 1H, J = 3.2 Hz),
.29 (d, 1H, J = 3.8 Hz), 4.57−4.63 (m, 2H), 4.81−4.91 (m, 1H), 5.18
7
0%). Eluent: EtOAc/petroleum ether (1:4). White solid. Mp: 140 °C.
(
d, 1H, J = 3.6 Hz), 5.28 (dd, 1H, J = 3.6 Hz, 10.2 Hz), 5.41−5.50 (m,
2
9
1
[
(
α] (−): 28.3 (c 0.8, CHCl ). H NMR (400 MHz, CDCl ): δ 1.30
D
3
3
2H), 5.75 (d, 1H, J = 3.6 Hz), 6.18 (t, 1H, J = 9.8 Hz), 7.25−7.60 (m,
1
δ 26.1, 26.9, 50.5 (CH ), 55.6, 58.1, 69.0, 70.3, 71.3, 72.0, 73.5, 81.7,
s, 3H), 1.57 (s, 3H), 3.08 (s, 3H), 3.96 (d, 1H, J = 3.2 Hz), 4.22 (d,
H, J = 12.0 Hz), 4.32−4.38 (m, 1H), 4.43 (d, 1H, J = 3.6 Hz), 4.49
d, 1H, J = 12.4 Hz), 4.56−4.67 (m, 2H), 5.14 (d, 1H, J = 3.6 Hz),
.24 (dd, 1H, J = 3.6 Hz, 10.0 Hz), 5.39−5.46 (m, 2H), 5.83 (d, 1H, J
4.0 Hz), 6.17 (t, 1H, J = 9.8 Hz), 6.98 (d, 2H, J = 7.2 Hz), 7.17−7.59
m, 12H), 7.69 (s, 1H), 7.88 (d, 2H, J = 7.2 Hz), 7.96 (d, 2H, J = 7.2
13
0H), 7.69 (s, 1H), 7.85−8.03 (m, 6H). C NMR (50 MHz, CDCl ):
3
1
(
5
=
2
8
1
5.7, 96.8, 104.5, 112.1, 128.5, 128.6, 128.7, 129.0, 129.1, 129.3, 129.8,
30.1 (2 × C), 130.3, 132.3, 133.4, 133.6, 133.9, 165.9 (2C), 166.0.
+
+
HRMS [ES , (M + H) ]: for C H N O found 730.2636, calcd
38
40
3
12
(
7
30.2612.
Compound 32b. Following the general procedure, over 45 h
compound 27b (0.25 g, 0.67 mmol) was converted to 32b (0.16 g,
0%). Eluent: EtOAc/petroleum ether (1:3). Brownish yellow gum.
13
Hz). C NMR (100 MHz, CDCl ): δ 25.9, 26.7, 50.1 (CH ), 55.3,
6
1
1
3
2
8.7, 70.1, 70.9, 71.7, 72.0 (CH ), 73.6, 82.1, 82.4, 96.5, 104.4, 112.0,
2
27.8, 128.2 (2 × C), 128.3, 128.5, 128.6, 128.7, 128.8, 129.0, 129.6,
4
29.8, 129.9, 132.4, 133.1, 133.3, 133.6, 134.1, 136.2, 165.6 (2 × C),
29
1
[
α] (+): 62.9 (c 0.7, CHCl ). H NMR (200 MHz, CDCl ): δ 1.37
+
+
D
3
3
1
65.7. HRMS [ES , (M + H) ]: for C H N O found 806.2890,
44 44 3 12
(s, 3H), 1.57 (s, 3H), 1.99 (s, 3H), 2.00 (s, 3H), 2.02 (s, 3H), 2.09 (s,
calcd 806.2925.
3
4
=
H), 3.27 (s, 3H), 3.63−3.71 (m, 1H), 3.88 (d, 1H, J = 3.2 Hz), 4.05−
Compound 32a. Following the general procedure, over 48 h
.31 (m, 4H), 4.48−4.71 (m, 4H), 4.90−5.21 (m, 4H), 5.35 (d, 1H, J
compound 27a (0.25 g, 0.55 mmol) was converted to 32a (0.25 g,
6
13
3.0 Hz), 6.01 (d, 1H, J = 3.6 Hz), 7.65 (s, 1H). C NMR (50 MHz,
7%). Eluent: EtOAc/petroleum ether (1:1). Brownish yellow gum.
29
1
CDCl
3
): δ 20.8, 20.9, 26.3, 27.0, 48.9 (CH
2
), 58.2, 62.0 (CH
), 68.4,
2
[
(
α] (−) 40.0 (c 0.9, CHCl ). H NMR (200 MHz, CDCl ): δ 1.37
D
3
3
6
1
8.5 (CH ), 71.1, 72.1, 72.9, 73.6, 81.8, 85.6, 101.1, 104.8, 112.5,
32.1, 133.8, 169.6, 170.3, 170.8. HRMS [ES , (M + H) ]: for
2
s, 3H), 1.56 (s, 3H), 1.98 (s, 6H), 2.01 (s, 3H), 2.07 (s, 3H), 3.60−
+
+
3
3
2
2
.67 (m, 1H), 3.92−4.11 (m, 3H), 4.14−4.33 (m, 3H), 4.35−4.54 (m,
H), 4.74 (d, 1H, J = 3.6 Hz), 4.86−4.99 (m, 1H), 5.03−5.18 (m,
H), 5.36 (d, 1H, J = 3.2 Hz), 6.06 (d, 1H, J = 3.6 Hz), 6.97−7.02 (m,
C H N O found 616.2357, calcd 616.2354.
26
38
3
14
Compound 32b′: Following the general procedure, over 45 h
compound 27b (0.25 g, 0.67 mmol) was converted to 32b′ (0.12 g,
0%). Eluent: EtOAc/petroleum ether (1:3). Brownish yellow gum.
13
H), 7.27−7.30 (m, 4H), 7.63 (s, 1H). C NMR (50 MHz, CDCl ):
3
3
δ 20.6, 20.8, 26.2, 26.9, 48.7 (CH ), 61.8 (CH ), 68.2, 68.4 (CH ),
2
2
2
29
1
[
α] (+): 25.9 (c 0.5, CHCl ). H NMR (200 MHz, CDCl ): δ 1.36
D
3
3
7
1
+
0.9, 71.9, 72.2 (CH ), 72.7, 73.9, 82.4, 100.9, 104.8, 112.4, 127.9,
2
+
(s, 3H), 1.56 (s, 3H), 2.00 (s, 3H), 2.01 (s, 3H), 2.02 (s, 3H), 2.10 (s,
3H), 3.28 (s, 3H), 3.66−3.73 (m, 2H), 3.90−4.05 (m, 3H), 4.10−4.29
28.3, 128.7, 132.3, 133.6, 136.4, 169.4, 170.2, 170.7. HRMS [ES , (M
+
H) ]: for C H N O found 692.2656, calcd 692.2667.
32
42
3
14
(
m, 4H), 4.48−4.59 (m, 4H), 4.69 (d, 1H, J = 3.8 Hz), 4.94−5.23 (m,
Compound 28b. Following the general procedure, over 45 h
4
H), 5.47 (d, 1H, J = 3.0 Hz), 5.96 (d, 1H, J = 3.8 Hz), 7.70 (s, 1H).
compound 27b (0.25 g, 0.67 mmol) was converted to 28b (0.29 g,
7
13
29
C NMR (50 MHz, CDCl ): δ 20.7 (3 × C), 20.9, 26.4, 26.9, 50.2
3%). Eluent: EtOAc/petroleum ether (1:3). Brownish gum. [α]
3
D
1
(CH ), 58.3, 61.9 (CH ), 67.9 (CH ), 68.4, 71.1, 72.2, 72.8, 76.1, 82.3,
2 2 2
(
−): 42.3 (c 0.8, CHCl ). H NMR (200 MHz, CDCl ): δ 1.36 (s,
3
3
8
5.0, 100.8, 104.7, 112.1, 124.8, 143.4, 169.5, 170.3, 170.8. HRMS
3
3
4
H), 1.57 (s, 3H), 3.27 (s, 3H), 3.42 (s, 3H), 3.77 (d, 1H, J = 3.4 Hz),
.91−4.01 (m, 2H), 4.36−4.48 (m, 1H), 4.50−4.60 (m, 1H), 4.68−
.84 (m, 5H), 5.27 (d, 1H, J = 1.6 Hz), 5.40 (d, 1H, J = 3.2 Hz), 5.64
+
+
[
ES , (M + H) ]: for C H N O found 616.2371, calcd 616.2354.
26 38 3 14
Compound 28c. Following the general procedure, over 40 h
compound 27c (0.25 g, 0.55 mmol) was converted to 28c (0.30 g,
(
s, 1H), 5.99 (d, 1H, J = 3.8 Hz), 7.20−7.50 (m, 11H), 7.66 (s, 1H).
2
7
1
3
8
(
3
1%). Eluent: EtOAc/petroleum ether (1:3). Yellowish gum. [α]
C NMR (50 MHz, CDCl ): δ 26.2, 26.9, 55.6, 57.9, 58.3, 61.6, 69.6
D
3
1
−): 38.2 (c 0.5, CHCl ). H NMR (200 MHz, CDCl ): δ 1.39 (s,
(
CH ), 73.4 (CH ), 73.7, 75.0, 76.2, 81.2, 85.8, 99.9, 102.2, 104.8,
3
3
2
2
H), 1.65 (s, 3H), 3.35 (s, 3H), 3.78−3.92 (m, 2H), 4.18 (bs, 1H),
1
12.4, 126.4, 127.6, 127.9, 128.3, 129.1, 131.4, 133.7, 138.0, 138.6.
+
+
4.32−4.39 (m, 1H), 4.46−4.52 (m, 2H), 4.60−4.91 (m, 7H), 5.08 (d,
HRMS [ES , (M + H) ]: for C H N O found 596.2631, calcd
31
38
3
9
1
1
5
8
1
H, J = 9.2 Hz), 5.63 (s, 1H), 5.80 (d, 1H, J = 3.6 Hz), 7.20−7.49 (m,
5
96.2608.
Compound 29b. Following the general procedure, over 45 h
compound 27b (0.25 g, 0.67 mmol) was converted to 29b (0.29 g,
2%). Eluent: EtOAc/petroleum ether (1:3). White solid. Mp: 162 °C.
13
7H), 7.55 (s, 1H). C NMR (50 MHz, CDCl ): δ 26.4, 26.8, 55.6,
3
8.2, 61.0, 69.3 (CH ), 70.0, 72.1 (CH ), 73.5 (CH ), 74.4, 76.3, 76.6,
0.9, 99.6, 102.1, 104.2, 113.6, 126.3, 127.5, 128.1, 128.2, 128.5, 128.7,
29.0, 132.8, 134.2, 136.4, 137.8, 138.2. HRMS [ES , (M + H) ]: for
found 672.2941, calcd 672.2921.
Compound 29c. Following the general procedure, over 40 h
2
2
2
7
+
+
29
1
[
(
3
3
1
α] (−): 55.8 (c 0.8, CHCl ). H NMR (200 MHz, CDCl ): δ 1.32
D
3
3
s, 3H), 1.50 (s, 3H), 2.85 (s, 3H), 3.29 (s, 3H), 3.72−3.83 (m, 2H),
C H N O
37 42 3 9
.93 (s, 1H), 4.31−4.43 (m, 2H), 4.59 (d, 1H, J = 3.6 Hz), 4.71 (s,
H), 5.30−5.40 (m, 1H), 5.44−5.49 (m, 2H), 5.59 (s, 1H), 5.93 (d,
compound 27c (0.25 g, 0.55 mmol) was converted to 29c (0.30 g,
13
H, J = 3.8 Hz), 7.21−7.39 (m, 11H), 7.61 (s, 1H). C NMR (50
82%). Eluent: EtOAc/petroleum ether (1:3). Brownish yellow gum.
[α]27
(−): 39.8 (c 0.8, CHCl
). H NMR (200 MHz, CDCl
1
): δ 1.35
MHz, CDCl ): δ 26.2, 26.9, 55.1, 57.8, 58.9, 60.5, 70.2 (CH ), 73.3
D
3
3
3
2
(
CH ), 74.4, 74.7, 78.9, 82.5, 86.4, 98.9, 102.7, 104.8, 112.3, 126.5,
(s, 3H), 1.52 (s, 3H), 3.33 (s, 3H), 3.70−3.87 (m, 2H), 4.06−4.07 (m,
1H), 4.30−4.40 (m, 3H), 4.45−4.55 (m, 2H), 4.58−4.71 (m, 3H),
5.12−5.23 (m, 2H), 5.28−5.31 (m, 1H), 5.57 (s, 1H), 5.81 (d, 1H, J =
2
+
1
+
28.0, 128.1, 128.6, 129.0, 132.0, 132.6, 137.6 (2C). HRMS [ES , (M
+
H) ]: for C H N O found 596.2620, calcd 596.2608.
31 38 3 9
13
Compound 30b. Following the general procedure, over 42 h
compound 27b (0.25 g, 0.67 mmol) was converted to 30b (0.29g,
2%). Eluent: EtOAc/petroleum ether (1:1). Brownish yellow gum.
3.6 Hz), 7.13−7.37 (m, 17H), 7.56 (s, 1H). C NMR (50 MHz,
CDCl ): δ 26.4, 26.8, 55.2, 56.8, 60.0, 69.9 (CH ), 71.0, 72.5 (CH ),
3
2
2
7
73.2 (CH ), 74.5, 76.7, 78.4, 82.5, 99.6, 102.7, 104.2, 113.3, 126.6,
2
29
1
[α]
(+): 112.0 (c 0.6, CHCl ). H NMR (200 MHz, CDCl ): δ
127.9, 128.1, 128.3, 128.4, 128.6 (2 × C), 129.2, 132.0, 135.2, 136.7,
D
3
3
I
dx.doi.org/10.1021/jo401576n | J. Org. Chem. XXXX, XXX, XXX−XXX