Elsevier

Carbohydrate Research

Volume 406, 10 April 2015, Pages 86-92
Carbohydrate Research

Ruthenium catalyzed synthesis of 2,3-unsaturated C-glycosides from glycals

https://doi.org/10.1016/j.carres.2015.01.009Get rights and content

Highlights

  • A mild and efficient Ferrier C-glycosylation protocol was developed.

  • Stereoselective synthesis of C-glycosides was achieved by employing Ru-catalysis.

  • The scope of reaction was well illustrated with diverse range of substrates.

Abstract

A highly efficient and convenient C-glycosylation method was developed using ruthenium(III) chloride for the synthesis of 2,3-unsaturated C-glycosides. Various nucleophiles such as allyl trimethylsilane, triethylsilane, trimethylsilyl cyanide, trimethylsilyl azide and heterocycles such as thiophene and furan reacted smoothly with glycals in the presence of catalytic amount of ruthenium trichloride under mild reaction conditions.

Introduction

The C-glycosides are subject of considerable interest due to the role played by them as versatile chiral synthons and key intermediates for the synthesis of several carbohydrate compounds of biological significance.1 Significantly, the C-glycosides are utilized as valuable intermediates in the synthesis of several natural products such as palytoxin, spongistatin, halichondrin,2 and various functionalized β-C-saccharides.3 Furthermore, they are employed as powerful synthetic tools for the synthesis of modified carbohydrates and analogs of naturally occurring C-nucleosides antibiotics4 and C-linked α(2,3)sialylgalactose lactone.5 Besides, the C-glycosides are more stable to hydrolytic cleavage hence utilized as glycosidase inhibitors and served as potential therapeutic agents for understanding the mechanism of carbohydrate-processing enzymes and other critical cellular processes.6 Particularly, 2,3-unsaturated C-glycosides are attractive due to the presence of 2,3-olefinic moiety in pyran rings, which could be further functionalized into other carbohydrates derivatives and useful chiral molecules by using various complexity generating reactions.7

As evident, several reagent systems have been evolved to effect the Ferrier glycosylation of glycals to obtain 2,3-unsaturated C-glycosides.8 Another reported procedure for the synthesis of 2,3-unsaturated C-glycosides involves a two step process, Tebbe methylenation and thermal Claisen rearrangement9, 9(a) On the other hand, the scope of Pd-mediated glycosylation9, 9(b), 9(c) has been demonstrated in the stereoselective and regioselective construction of glycosidic linkage via a Pd π-allyl intermediate. However, a combination of Pd-catalyst and phosphine ligand with a sub-stoichiometric amount of diethyl zinc as an additive at high temperature is required for the success of these reactions. In a recent report,9d Mukherjee and co-worker developed a highly efficient and reliable catalytic system for the C-glycosylation of glycals with unactivated alkynes using a combination of Cu(OTf)2 and ascorbic acid. Similarly, the Ferrier-type C-alkynylations with silylacetylene9e and alkynyltrifluoroborates9f compounds have been reported using stoichiometric amount of BF3·OEt2. However, the indium-mediated C-alkynylation with iodoalkynes using Barbier reaction required refluxing conditions and excess loading of indium metal and iodoalkyne.9g

Over the decade, the palladium-catalyzed Heck reaction has been employed for the syntheses of aryl-C-glycosides10 by cross coupling of glycals with aryl halides,10(b), 10(c) aryl boronic acids,10(d), 10(e) and benzoic acids.10f More recently, Liu and co-worker demonstrated the synthesis of aryl-C-glycosides by a Pd-catalyzed oxidative Heck cross-coupling of inactivated glycals and aryl hydrazines.10g However the Heck type C-glycosylation represent a significant approach of aryl-C-glycosylation, with restricted substrate scope, use for expensive and relatively toxic reagents, wherein less stable and moisture sensitive organometallic compounds, use of additives such as strong bases and phosphine ligands,10b harsh conditions and tedious work-up remains unsolved issues. Therefore, the development of an efficient and general protocol utilizing nontoxic and environmental friendly reagent system is desirable for the synthesis of C-glycosides and carbohydrate intermediates en route to several biologically important sugar molecules.

Section snippets

Results and discussion

Recently, we have demonstrated the expeditious synthesis of α-d-mannopyranosides and 2,3-unsaturated O-glycosides from glycal employing ruthenium catalysis.11(b), 11(d) In continuation of our research interest towards developing efficient glycosylation methods,11 we envisioned that the use of ruthenium(III) chloride as eco-friendly and economical catalyst would be advantage in the carbohydrate chemistry particularly in the C-glycosides syntheses. Herein, we report a novel, convenient and

Conclusions

In summary, we have demonstrated an efficient, convenient and highly catalytic system for the C-glycosylation of glycals to access C-glycosides under mild reaction conditions. In addition, the utility and flexibility of the current reagent system was successfully demonstrated for a wide range of substrates to achieve various functionalized 2,3-unsaturated C-glycosides of significant synthetic value. In the present C-glycosylation protocol, the use of environmental friendly reagent system and

General synthesis information, methods and materials

Unless otherwise noted, materials were obtained from commercial suppliers and used without purification. Reactions were run in screw capped glass vials (4 mL) stirred with Teflon®-coated magnetic stir bars. Moisture and air-sensitive reactions were performed in flame-dried round bottom flasks, fitted with rubber septa or glass gas adapters, under a positive pressure of nitrogen. Moisture and air-sensitive liquids or solutions were transferred via nitrogen-flushed syringe. Concentration of

Acknowledgments

This research is supported by Department of Science and Technology, New Delhi (GAP0397 & 0471). The authors are grateful to the Director CSIR-IICT for providing necessary infrastructure. B.S acknowledges a UGC Fellowship.

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