Job/Unit: O50137 /KAP1 Date: 07-05-15 11:28:13 Pages: 7 FULL PAPER DOI: 10.1002/ejoc.201500137 AuCl 3 – and AuCl 3 –Phenylacetylene-Catalyzed Glycosylations by Using Glycosyl Trichloroacetimidates Rashmi Roy, [a] Ashok Kumar Palanivel, [a] Asadulla Mallick, [a] and Yashwant D. Vankar* [a] Keywords: Synthetic methods / Homogeneous catalysis / Gold / Glycosylation / Glycosides / Carbohydrates / Amino acids Glycosylations of armed and disarmed trichloroacetimidate- based glycosyl donors were carried out by using the AuCl 3 – phenylacetylene relay catalyst system. The effectiveness of this catalytic system was also compared with that of using AuCl 3 alone as a catalyst. Glycosylations with these catalysts proceeded efficiently at room temperature within 5–45 min. Excellent diastereoselectivity was obtained for the glycosyl- Introduction Glycoproteins, glycolipids, and oligosaccharides are found in abundance at the outer surface of the cell mem- brane and play an important role in fundamental cell re- cognition processes. [1] Moreover, in biological processes, the functions of oligosaccharides involve the development and survival of an organism. [2] In living systems, protein glyc- osylation is a crucial post-translational process to impart structural stability to a native protein. [3] In the last few dec- ades, extensive studies have been done to introduce new glycosylation methodologies [4] with the goal to improve their synthetic repertoire, which should be useful for the syntheses of biologically important oligosaccharides, [5] glycopeptides, [6a–6c] and glycolipids. [6d] Glycosyl trichloro- acetimidates, which were introduced by Schmidt and Michel, [7] are one of the most efficient glycosyl donors for glycosylation reactions. The glycosyl trichloroacetimidates are not only easy to prepare and handle but also generally lead to the glycosylated products in high yields and excel- lent stereoselectivity. [7] For example, the synthesis of a tumor-associated mucin glycopeptide by Danishefsky et al. [8] involved O-glycosylation with a trichloroacetimidate donor as a crucial step. A recent report of the preparation of an anthrose analogue by Grandjean et al. [9] involves the use of trichloroacetimidate donors to carry out glycosyl- ation reactions. Popular promoters of the glycosylation of trichloroacetimidate donors include both protic as well as Lewis acids such as p-toluenesulfonic acid (TsOH), [7] [a] Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur, Uttar Pradesh 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.201500137. Eur. J. Org. Chem. 0000, 0–0 © 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 1 ation of 2-O-acetyl-protected disarmed glycosyl donors, whereas armed glycosyl trichloroacetimidates gave rise to a mixture of anomeric glycosides. Acid-sensitive nucleophiles such as Fmoc-serine tert-butyl ester or Fmoc-threonine tert- butyl ester successfully underwent the glycosylations, albeit in moderate yields, under mild conditions at room tempera- ture. BF 3 ·OEt 2 , [8] trimethylsilyl trifluoromethanesulfonate (TMSOTf), [9] HClO 4 -silica gel, [10] InCl 3 , [11] AgOTf, [12] LiOTf, [13] and sulfated zirconia in supercritical (sc) CO 2 . [14] In many cases, however, low temperatures are required for glycosylation to take place with glycosyl trichloroacetimid- ates. Moreover, some of these reactions specifically need to be conducted with some specific catalyst. [12] Thus, it is im- portant to discover mild reagent systems and user friendly protocols to carry out glycosylations of trichloroacetimid- ate-based glycosyl donors at room temperature. In recent years, gold-catalyzed glycosylations have gained importance, and a few interesting glycosyl donors have been introduced [15] for this purpose, keeping in mind the alkyno- philicity of gold salts. Interestingly, Kunz and co-workers have reported a clever use of AuCl-catalyzed glycosylations by using glycosyl trichloroacetimidates at room tempera- ture. [16] Recently, we reported about gold(III) chloride– phenylacetylene as an efficient catalytic system for the glycosylation of 1-O-acetyl sugars as well as for Ferrier re- arrangements of glycals and 2-acetoxymethyl glycals. [17] Furthermore, we discovered that AuCl 3 and AuCl 3 –phenyl- acetylene catalyst systems activate trichloroacetimidate glycosyl donors at room temperature to form O-glycosides. Results and Discussion We performed a comparative glycosylation study in the presence of the AuCl 3 –phenylacetylene and AuCl 3 catalyst systems by using disarmed trichloroacetimidate glycosyl do- nors 1 and 2 and armed glycosyl donor 3 [7] with a range of nonsugar (i.e., 4, 5, 6, 18, and 25), sugar-derived [18] (i.e., 7 and 8), and amino acid derived [19] (i.e., 9, 10, and 26) alcohols as depicted in Scheme 1. The reaction of trichloro- acetimidate 1 with allyl alcohol (4) smoothly underwent a