Direct Dehydrative Glycosylation of C1‐Alcohols

Abstract

Due to the central role played by carbohydrates in a multitude of biological processes, there has been a sustained interest in developing effective glycosylation methods to enable more thorough investigation of their essential functions. Among the myriad technologies available for stereoselective glycoside bond formation, dehydrative glycosylation possesses a distinct advantage given the unique properties of C1-alcohols such as straightforward preparation, stability, and a general reactivity compatible with a diverse set of reaction conditions. In this Focus Review, a survey of direct dehydrative glycosylations of C1-alcohols is provided with an emphasis on recent achievements, pervading limitations, mechanistic insights, and applications in total synthesis.

Direct Dehydrative Glycosylation Catalyzed by Diphenylammonium Triflate

“…Under the same conditions, glycosylation of 1 with a range of primary (entries 1-2) and secondary (entries 3-4) alcohols proceeded smoothly to afford the corresponding glucosides in moderate to good yields. Less reactive acceptors including Cbz-protected amino acids 2f and 2g and primary monosaccharide 2h also worked, although two equivalents of the acceptor were required for reasonable conversion (entries [5][6][7]. No loss of the protecting groups on these acceptors was observed.…”

“…Glycosylation is one of the most important reactions in oligosaccharide synthesis [1]. Though monosaccharides in hemiacetal form are commercially available or easily prepared, use of them as glycosyl donors often requires prior elaboration of the anomeric hydroxyl to a good leaving group [2][3][4][5][6][7]. In contrast, direct dehydrative glycosylation is an atom economic and environmentally friendly method because only water is generated as a byproduct.…”

Trichloroisocyanuric acid (TCCA): A Suitable Reagent for Direct Glycosylations of C1‐Hemiacetals with Different Nucleophiles

“…Till date, several conditions have been used for dehydrative glycosylation including Brønsted or Lewis acid catalyzed the straightforward transformation of a glycosyl hydroxyl group (Fischer glycosylation) [5] as well as the electrophilic reagents [3a] or transition metals [6] promoted in situ activation in variable yields and selectivities. One of the elegant works related to in situ activation with electrophilic reagents was disclosed by Gin et al., [3c] which exploited anomeric oxosulfonium donors.…”

A De Novo Route to 3,6-Dideoxy Sugars

“…This was achieved by treatment of with aqueous trifluoroacetic acid, giving 23−25 in 77−88% yield. These compounds could be used directly in glycosylation sequences 34 Scheme 2. Synthesis of 15 and 16…”

“…This was achieved by treatment of with aqueous trifluoroacetic acid, giving 23 – 25 in 77–88% yield. These compounds could be used directly in glycosylation sequences or converted to other glycosyl donors ( e.g., imidates, halides) . Importantly, 23 – 25 possess a nonparticipatory protecting group at O2, which is crucial as these sugars are most commonly found in nature in the α-stereochemistry.…”