Iron(iii) chloride-catalyzed activation of glycosyl chlorides

Abstract

Glycosyl chlorides have historically been activated using harsh conditions and/or toxic stoichiometric promoters. More recently, the Ye and the Jacobsen groups showed that glycosyl chlorides can be activated under organocatalytic conditions. However, those reactions are slow, require specialized catalysts and high temperatures, but still provide only moderate yields. Presented herein is a simple method for the activation of glycosyl chlorides using abundant and inexpensive ferric chloride in catalytic amounts. Our preliminary results indicate that both benzylated and benzoylated glycosyl chlorides can be activated with 20 mol% of FeCl3

Defining the Scope of the Acid‐Catalyzed Glycosidation of Glycosyl Bromides

“…Unpredictably, and to our delight, we observed that all glycosyl bromides generated in situ could be efficiently activated with Ag 2 SO 4 (0.70 equiv) and TfOH (0.40 equiv). Thus, when perbenzylated glycosyl bromides 36 – 38 generated from the corresponding ethylthio glycosides 33 – 35 were glycosidated with 2‐OH glycosyl acceptor 4 the respective disaccharides 39 – 41 were obtained in 87–92 % yield (Table , entries 1–3). We noted a somewhat low reaction rates because all glycosylations with perbenzylated bromides required 8 h to complete under these reaction conditions.…”

“…Traditional Koenigs–Knorr glycosylations are slow, and in subsequent decades, enhanced understanding of the reaction helped to evolve it into one of the most popular methods for glycosylation . We now know that glycosidation of halides can be significantly accelerated by using other metal salt‐based promoters including more reactive silver salts, mercury,– cadmium, zinc, indium, tin, iron, etc…”

A Highly Efficient Glycosidation of Glycosyl Chlorides by Using Cooperative Silver(I) Oxide–Triflic Acid Catalysis

“…[14] This approach is commonly used in expeditious oligosaccharide synthesis [15] because disaccharide 16 can be used as the glycosyl donor for subsequent chain elongation directly. However, glycosylation of thioglycoside acceptors was somewhat inefficient in our previous studies with ferric chloride promoter [8] or with glycosyl bromides as donors. [9][10] In addition, these glycosylations could be prone to competing aglycone transfer reactions, [16] which was not observed in this case.…”

“…was obtained from 2,3,4,6-tetra-O-benzyl-Dglucopyranose [30] as described previously, [8] and its analytical data for were the same as those reported previously.…”

“…We have recently reported that glycosyl chlorides can be activated with catalytic ferric chloride. [8] Glycosylation with benzylated donors under these benign reaction conditions was typically completed in a couple of hours. The activation of electronically deactivated, benzoylated glycosyl chlorides could also be achieved with catalytic ferric chloride.…”