Bismuth(V)-Mediated Thioglycoside Activation

摘要

Chemical glycosylation is a crucial step in any oligosaccharide synthesis. Among the different classes of commonly used glycosyl donors, thioglycosides offer distinct advantages. Thioglycoside donors are relatively simple to prepare, are stable under various reactions for protectingI group manipulations, and offer orthogonality in their activa-tion in the presence of other glycosyl donors.[8] As a result, a wide variety of promoters have been developed for activation of these donors in the past 20 years : from heavy metal-cation-based promoters (Hg~(II) sulfate), to the current halonium-based reagents [e.g., N-iodosuccinimide/trifluoromethane sulfonic acid (NIS/TfOH), M-bromosuccinimide (NBS), IC1 or IBr/AgOTf, etc.], alkylating reagents [methyl triflate (MeOTf)] , and organosulfur-based promoters [e.g., dimethyl(thiomethyl)sulfonium triflate (DMTST), methylsulfenyl triflate (MeSOTf), dimethyl disulfide/triflic anhydride (Me2S/Tf2O), benzenesulfinylpiperidine/triflic anhydride (BSP/TTBP), N-(phenylthio)-ecaprolactam-Tf2O, etc]. A recent method applies single-electron transfer using ruthenium or iridium-containing catalysts that are active under visible light to activate thioglycosides. Although these methods have been effective in carrying out a range of glycosylations, most of these still have a limited scope. Generally, these activations need excess amounts of promoters, or require a co-promoter to form the reactive intermediates. Moreover, present methods often require extremely low temperatures (< —20 °C) as a result of generating reactive intermediates. Some of the popular halonium-based promoters are challenging to use in the presence of alkenes, because they tend to give various addition by-products, thereby ultimately resulting in the cleavage of the alkenyl moiety. These issues with solubility, undesired by-products, stability, or reagent handling are particularly problematic in the context of the development of robust automated protocols for oligosaccharide synthesis. To circumvent some of these issues with current promoter systems, we herein report a straightforward method for the activation of thiopropylglycosides for coupling to various acceptors in good to excellent yields by utilizing a bismuth(V) compound without additional additives/copromoters.