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Synlett 2009(9): 1409-1412  
DOI: 10.1055/s-0029-1216744
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Procedure for Fast and Regioselective Copper-Free Click Chemistry at Room Temperature with p-Toluenesulfonyl Alkyne

Sébastien G. Gouin*, José Kovensky
Department of Chemistry, Laboratoire des Glucides UMR CNRS 6219, Institut de Chimie de Picardie, Université de Picardie Jules Verne, 33 Rue Saint-Leu, 80039 Amiens, France
Fax: +33(3)22827560; e-Mail: sebastien.gouin@u-picardie.fr;
Further Information

Publication History

Received 27 January 2009
Publication Date:
04 May 2009 (online)

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Abstract

Sulfonyl alkyne group can undergo copper-free cyclization at room temperature with diverse azido compounds. In solvent-free conditions the reaction was fast, yielding 1,4-disubstituted ­regioisomers with high regioselectivity.

Key words

cycloadditions - regioselectivity - copper-free click chemistry - solvent-free reaction - p-toluenesulfonyl alkyne

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23

General Procedure for the Copper-Free Cycloaddition
p-Toluenesulfonyl alkyne 3 (31 mg, 171 µmol) and 8-azido-3,6-dioxaoctadecanol 4 (30 mg, 171 µmol) were dissolved in CH2Cl2 (1 mL). The solvent was evaporated under reduced pressure at 16 ˚C (rotavapor, 20 mbar). Complete evap-oration was observed in less than 5 min, and the stirring was continued under the same conditions for 2 h. The residue was purified by flash chromatography on SiO2 (2:3 cyclohexane-EtOAc to EtOAc, then 39:1 EtOAc-MeOH) to give 5a (45 mg, 74%) and 5b (4 mg, 6%) as colorless oils.
1-[8-Hydroxy-3,6-dioxaoctyl]-4-[ p -toluenesulfonyl]-[1,2,3]-triazole (5a)
¹H NMR (300 MHz, CDCl3): δ = 8.48 (1 H, s, CHTri), 7.91 (2 H, d, J = 8.5 Hz, arom. H), 7.30 (2 H, d, arom. H), 4.54 (2 H, t, J = 4.6 Hz, CH2CH2N), 3.80 (2 H, t, J = 4.8 Hz, CH2) 3.73 (2 H, t, J = 4.8 Hz, CH2), 3.58-3.53 (6 H, m, 3 × CH2), 2.37 (3 H, s, CH3). ¹³C NMR (75 MHz, CDCl3): δ = 149.0 (CqTri), 145.0 (CqAr), 137.2 (CqAr), 129.9 (CHAr), 128.1 (CHAr), 127.5 (CHTri), 72.7, 72.5, 70.4, 70.2, 68.6 (CH2), 61.7 (CH2OH), 50.1 (CH2N), 21.7 (CH3Ar). HRMS (ES+): m/z calcd for C15H21N3O5NaS: 378.1100; found: 378.1105.
1-[1′,2′:3′,4′-Di- O -isopropylidene-6-deoxy-α- d -galactopyranosid-6-yl]-4-[ p -toluensulfonyl]-[1,2,3]-triazole (18) [α]D -58 (c 0.5, CH2Cl2). ¹H NMR (300 MHz, CDCl3): δ = 8.31 (1 H, s, CHTri), 7.92 (2 H, d, J = 8.1 Hz, arom. H), 7.30 (2 H, d, J = 8.1 Hz, arom. H), 5.50 (1 H, d, J 1,2 = 4.9 Hz, H-1), 4.64 (1 H, dd, J 5,6 = 3.7 Hz, J 6,6 ′ = 14.0 Hz, H-6), 4.63 (1 H, dd, J 2,3 = 2.6 Hz, J 3,4 = 7.8 Hz, H-3), 4.48 (1 H, dd,
J 5,6 ′ = 8.5 Hz, H-6¢), 4.34 (1 H, dd, H-2), 4.18 (1 H, dd,
J 4,5 = 1.9 Hz, H-4), 4.12 (1 H, ddd, H-5), 2.40 (3 H, s, CH3), 1.52, 1.37, 1.34, 1.32 (12 H, 4 Ž s, 4 Ž isop. CH3). ¹³C NMR (75 MHz, CDCl3): δ = 148.9 (CqTri), 145.0 (CqAr), 137.0 (CqAr), 129.9 (CHAr), 128.3 (CHAr), 127.2 (CHTri), 110.0 [C(CH3)2], 109.1 [C(CH3)2], 71.0, 70.3, 67.0, 66.7 (C-2,
C-3, C-4, C-5), 51.1 (C-6), 25.8, 24.9, 24.6 (CH3), 21.6 (CH3Ar). HRMS (ES+): m/z calcd for C21H27N3O7NaS: 488.1467; found: 488.1474.