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DOI: 10.1055/s-0029-1217570
‘Click’ Chemistry on Sugar-Derived Alkynes: A Tandem ‘Click-Click’ Approach to Bistriazoles
Publication History
Publication Date:
15 July 2009 (online)
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Abstract
Development of a tandem ‘click-click’ approach to the formation of successive 1,4-disubstituted 1,2,3-triazole linkages and ‘click chemistry’ on sugar-derived alkynes are described.
Key words
C-glycoside - triazole - ‘click’ reaction - alkyne - azide - azido-alkyne - bistriazole
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References and Notes
For an updated list, see: http://www.scripps.edu/chem/sharpless/click.html
20Typical procedure for the simple ‘click’ reaction: To a solution of alkyne 3 (0.050 g, 0.19 mmol) and azide 5 (0.026 g, 0.19 mmol) in MeCN (1.9 mL) were added CuI (0.0746 g, 0.38 mmol) and DIPEA (0.1 mL, 0.57 mmol) successively at r.t. After stirring for 30 min, the reaction was quenched by adding sat. aq NH4Cl (10 mL). The organic layer was separated and the aqueous layer was extracted with EtOAc (3 × 20 mL). After washing with brine (20 mL), the organic layer was dried over Na2SO4, filtered and concentrated in vacuo to give the crude product, which was purified by recrystallisation from CH2Cl2-hexanes. The mother liquor was further purified by column chromatography (hexanes-EtOAc, 1.5:1) to afford triazole 12 (0.065 g, 85%). R f = 0.62 (EtOAc-hexanes, 1:1); mp 155-157 ˚C; [a]²0 D -83.880 (c 0.21, CHCl3); ¹H NMR (400 MHz, CDCl3): δ = 7.53 (s, 1 H), 7.38-7.25 (m, 5 H), 5.59 (d, J = 11.6 Hz, 1 H), 5.57 (d, J = 1.2 Hz, 1 H), 5.43 (d, J = 14.8 Hz, 1 H), 5.18 (d, J = 2 Hz, 1 H), 4.70 (dd, J = 8.0, 2.4 Hz, 1 H), 4.36 (dd, J = 4.8, 2.4 Hz, 1 H), 1.59 (s, 3 H), 1.41 (s, 3 H), 1.35 (s, 3 H), 1.31 (s, 3 H); ¹³C NMR (100 MHz, CDCl3): δ = 145.5, 134.5, 128.9, 128.5, 128.0, 123.0, 109.1, 108.9, 96.4, 72.5, 70.6, 70.5, 64.6, 54.0, 26.1, 25.8, 24.8, 24.1; IR (KBr): 3019, 2923, 2395, 1966, 1651, 1374, 1259, 1215, 1069 cm-¹; HRMS (EI): m/z calcd for C20H26N3O3: 388.1872; found: 388.1892.
22
Typical procedure
for the double ‘click’ reaction: To methyl
propiolate 32 (0.024 mL, 0.27 mmol) in
MeCN
(1.5 mL) was added CuI (0.105 g, 0.552 mmol) and
DIPEA (0.147 mL, 0.82 mmol). The reaction mixture became a clear solution.
The azido-alkyne 31 (0.050 g, 0.27 mmol)
was added and the reaction was stirred for 1 h (reaction moni-tored
by TLC). Then, azide 6 (0.27 mmol) was
added and the reaction was stirred for 15 minutes. The reaction
was quenched by the addition of sat. aq NH4Cl (10 mL),
the organic layer was separated and the aqueous layer was extracted
with EtOAc (3 × 20 mL). After washing
with brine (20 mL), the organic layer was dried over Na2SO4 and concentrated
in vacuo to give the crude product, which was purified by recrystallization
from CH2Cl2-hexanes. The mother liquor
was purified by column chromatography (hexanes-EtOAc, 1:1.5)
to afford triazole 35 (0.050 g, 46%). Compound 35: R
f
= 0.54
(EtOAc); mp 218-220 ˚C; [a]²0
D
-55.148
(c 0.38, CHCl3); ¹H
NMR (300 MHz, CDCl3): δ = 8.32 (s,
1 H), 7.97 (s, 1 H), 7.59 (d, J = 8.5
Hz, 2 H), 7.33 (d, J = 8.1
Hz, 2 H), 4.95-4.64 (m, 4 H), 3.96 (s,
3 H), 2.43 (s, 3 H), 1.51 (s, 3 H), 1.39
(s, 3 H); ¹³C NMR (75 MHz, CDCl3): δ = 145.8,
135.0, 130.2, 129.2, 129.1, 128.9, 128.2, 122.3, 109.3, 78.2, 72.1,
54.3, 52.2, 50.4, 26.7, 26.7, 21.1. IR (KBr): 3135, 3019, 2953,
2400, 1714, 1545, 1450, 1436, 1372, 1357, 1334, 1239, 1216, 1174,
1123, 1110, 1073, 1047 cm-¹; HRMS (EI): m/z calcd
for C19H23N6O4: 399.5706; found:
399.5701. Compound 36: R
f
= 0.68
(EtOAc); mp 134-136 ˚C; ¹H
NMR (CDCl3, 400 MHz): δ = 8.47 (s,
1 H), 7.63 (d, J = 8.5
Hz, 2 H), 7.35 (d, J = 8.1
Hz, 2 H), 3.99 (s, 3 H), 2.44 (s, 3 H); ¹³C
NMR (75 MHz, CDCl3): δ = 145.8, 135.0,
130.2, 121.5, 120.6, 109.3, 52.0, 21.1; IR (KBr): 3019, 2928, 2857,
1726, 1552, 1521, 1434, 1259, 1215, 1148, 1038 cm-¹;
HRMS (EI): m/z calcd
for C11H12 N3O2: 218.0861;
found: 218.0865.