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Synlett 2009(13): 2162-2166  
DOI: 10.1055/s-0029-1217570
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

‘Click’ Chemistry on Sugar-Derived Alkynes: A Tandem ‘Click-Click’ Approach to Bistriazoles

Krishna P. Kaliappan*, Palanichamy Kalanidhi, Subham Mahapatra
Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India
Fax: +91(22)25723480; e-Mail: kpk@chem.iitb.ac.in;
Further Information

Publication History

Received 15 April 2009
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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10

For an updated list, see: http://www.scripps.edu/chem/sharpless/click.html

20

Typical 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.