A metal free aqueous route to 1,5-disubstituted 1,2,3-triazolylated monofuranosides and difuranosides Anirban Kayet, Santu Dey, Tanmaya Pathak ⇑ Department of Chemistry, Indian Institute of Technology Kharagpur, Kharagpur 721 302, India article info Article history: Received 19 June 2015 Revised 9 August 2015 Accepted 11 August 2015 Available online xxxx Keywords: 1,5-Disubstituted 1,2,3-triazole Furanoside Vinylsulfone Aqueous Metal free abstract Vinyl sulfones and vinyl sulfone-modified carbohydrates were subjected to 1,3-dipolar-cycloaddition reactions with four different azidofuranosides having azido groups at the C5 and C6-positions under refluxing conditions in aqueous media without any metal catalyst to afford the 1,5-disubstituted 1,2,3- triazolylated monofuranosides and difuranosides in high yields. These syntheses of 1,5-disubstituted tri- azolylated monosaccharides as well as 1,5-disubstituted 1,2,3-triazole linked disaccharides open up a new possibility of connecting furanosides with a stable-triazole backbone. N 3 ArO 2 S X N N N X O OR OR RO O OR OR RO 1 5 water, reflux Ó 2015 Published by Elsevier Ltd. Cu(I) catalyzed azide–alkyne cycloaddition (CuAAC) reaction has been widely used for the synthesis of 1,4-disubstituted 1,2,3- triazoles (1,4-DTs). 1 Since carbohydrate molecules are widely used as a major source of chiral resources 2 and are increasingly consid- ered as a major source of drug molecules, 3 CuAAC has been widely applied in the synthesis of 1,4-DT functionalized carbohydrate derivatives. 4 Several 1,4-disubstituted 1,2,3-triazolylated furanosyl monosaccharides have also been prepared using this strategy (Fig. 1). 5a–c For example, the sugar triazoles 1a–e, 2a–e, 3a–e and 4a–e were evaluated against an avirulent strain, Mycobacterium tuberculosis H37Ra, and a virulent strain, M. tuberculosis H37Rv. Compound 4e of this series displayed a moderate antitubercular activity with an MIC of 12.5 lg/mL. 5a,b Compound 5 has also shown antitubercular activity. 5c The 1,4-DT linked disaccharides 6a–c were screened for their enzyme inhibitory activities against a-glucosidase, glycogen-phosphorylase and glucose-6- phosphatase. 5d Although the CuAAC reaction 6 triggered new developments in synthetic chemistry as well as biology 7 and material sciences, 8 effi- cient and general synthetic approaches towards 1,5-disubstituted 1,2,3-triazoles (1,5-DTs) have achieved limited success so far. 9 The methods available for the synthesis of 1,5-DTs 7 by different groups are summarized in Scheme 1. Amongst all the metal-medi- ated routes to 1,5-DTs, RuAAC remains the most popular method, 10 although the reaction conditions are much less efficient than the ‘Click’ reaction. 6b,11 Moreover, the possibility of toxicity of residual metal in metal-mediated triazolylation led to the quest for metal-free routes to 1,5-DTs which is also limited in number. 12,13 It is therefore not surprising that in general, the world-wide research is overwhelmingly biased towards the syn- thesis and applications of 1,4-DTs. The situation is far worse in the area of triazolylation of carbo- hydrates. As a result there are only few scattered reports on the synthesis of 1,5-DT functionalized carbohydrates. 14–16 However, to the best of our knowledge there are no reports on furanosides functionalized with 1,5-DTs at C5 or C6 although many of the cor- responding 1,4-triazolylated carbohydrates are known having http://dx.doi.org/10.1016/j.tetlet.2015.08.030 0040-4039/Ó 2015 Published by Elsevier Ltd. ⇑ Corresponding author. Tel.: +91 (3222)283342. E-mail address: tpathak@chem.iitkgp.ernet.in (T. Pathak). Tetrahedron Letters xxx (2015) xxx–xxx Contents lists available at ScienceDirect Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet Please cite this article in press as: Kayet, A.; et al. Tetrahedron Lett. (2015), http://dx.doi.org/10.1016/j.tetlet.2015.08.030