DOI: 10.1002/ejoc.201501245 Full Paper Glycosylation Au III -Halide/Phenylacetylene-Catalysed Glycosylations Using 1-O-Acetylfuranoses and Pyranose 1,2-Orthoesters as Glycosyl Donors Asadulla Mallick, [a] Yakkala Mallikharjunarao, [a] Parasuraman Rajasekaran, [a] Rashmi Roy, [a] and Yashwant D. Vankar* [a] Abstract: 1-O-Acetylfuranoses and pyranose 1,2-orthoesters were activated with an Au III halide/phenylacetylene relay cata- lyst system, and they acted as excellent glycosyl donors. Thus, 1-O-acetyl-D-ribofuranose, 1-O-acetyl-D-lyxofuranose, and 1,2- Introduction The majority of carbohydrates are not found in their free forms in nature. Monosaccharides are linked through glycosidic bonds to other monosaccharides, or to aglycons such as lipids, pept- ides, or proteins to form oligosaccharides or glycoconjugates. Depending on the nature of the linkage, they can be classified as N-, O-, C-, or S-linked glycosides. O-Linked glycosides are most common and important. [1] For example, O-linked glycos- ides have been found to behave as antibacterial, [2] antiviral, [3] antifungal, [4] antitumor [5] and anti-HIV [6] agents. As a conse- quence, the synthesis of biologically important oligosaccharides and glycoconjugates has been a prime concern for chemists, and a large number of glycosylation methods have been devel- oped for this purpose. [7] Different kinds of glycosyl donors have been introduced, and many activators have been developed to effect glycosylation reactions. These glycosyl donors include thioglycosides, [8] glycosyl sulfoxides, [9] glycosyl sulfones, [10] tri- chloroacetimidates, [11] n-pentenyl glycosides, [12] 1,2-ortho- esters, [13] and many more. [7c] However, reports of the use of 1-O-acetyl sugars as glycosyl donors are few. [14] Glycosylation reactions of 1-O-acetyl sugars suffer from drawbacks such as requiring excess of the promoter, [14a–14c] long reaction times, [14d,14e] and harsh reaction conditions. [14a] In this context, we recently reported [15] a new relay catalyst system comprising Au III chloride and phenylacetylene, which was able to activate 1-O-acetyl pyranoses as glycosyl donors and overcome these drawbacks. In this approach, AuCl 3 and phenylacetylene were both used in only catalytic amounts. In recent years, gold-cata- lysed reactions have gained significant attention due to the high alkynophilicity and Lewis acidity of both gold(I) and [a] Department of Chemistry, Indian Institute of Technology, Kanpur 208016, India E-mail: vankar@iitk.ac.in http://home.iitk.ac.in/~vankar/ Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/ejoc.201501245. Eur. J. Org. Chem. 2016, 579–588 © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 579 orthoesters selectively gave the corresponding 1,2-trans glycos- ides, whereas 1-O-acetyl-D-arabinofuranose and 1-O-acetyl-D- xylofuranose both gave mixtures of 1,2-trans and 1,2-cis glycos- ides, with the 1,2-trans glycosides predominating. gold(III) salts. [16] These properties have been exploited in the synthesis of O-linked glycosides, using propargyl pyranosides, propargyl furanosides, and propargyl 1,2-orthoesters as glycosyl donors. [17] These methods, although efficient, require the do- nors to have an inbuilt acetylenic moiety for activation with gold salts. In contrast, our method [15] to activate OAc as an anomeric leaving group needs only catalytic amounts of both AuCl 3 and phenylacetylene. As an extension of our work, we report in this paper O-glycosylation using 1-O-acetylfuranoses and 1,2-orthoesters using Au III halide catalysts with or without a phenylacetylene cocatalyst. The glycosylation of furanoses is important as several glycoconjugates contain oligofuranoside units. [17,18] Glycosyl 1,2-orthoesters are also excellent glycosyl donors in carbohydrate chemistry. [13] As expected, we found that Au III halide/phenylacetylene relay catalyst systems are bet- ter than only gold-catalysed reactions in terms of time and yield. Results and Discussion We used four different benzyl-ether-protected furanose sugars 1a, [18] 1b, 1c, [19] and 1d (Figure 1) as glycosyl donors, and 2a– 2h (Figure 2) were used as glycosyl acceptors. We began our investigation with acetate-protected D-arabinofuranose-derived glycosyl donor D-Araf 3 [20] (Table 1) and acceptor 2a, which were treated with gold(III) chloride (5 mol-%) and phenyl- acetylene (5 mol-%) in CH 2 Cl 2 . This reaction did not lead to the desired compound (i.e., 4; Table 1, entry 1). We then carried out the same reaction using benzylated acetyl furanoside 1a with acceptor 2a (Table 1, entry 2), and to our delight we obtained the desired glycosylated product (i.e., 4a) [17a] within 2 h in mod- erate yield. We optimized the reaction conditions by varying the catalyst loading and changing the solvent of the reaction medium (Table 1). We found that a catalyst loading of 10 mol- % [gold(III) chloride/phenylacetylene (1:1)] and CH 2 Cl 2 as sol- vent gave the best results (Table 1, entry 4). So we took these