Fluoride Migration Catalysis Enables Simple, Stereoselective, and Iterative Glycosylation

Abstract

Challenges in the assembly of glycosidic bonds in oligosaccharides and glycoconjugates pose a bottleneck in enabling the remarkable promise of advances in the glycosciences. Here, we report a strategy that applies unique features of highly electrophilic boron catalysts, such as tris­(pentafluorophenyl)­borane, in addressing a number of the current limitations of methods in glycoside synthesis. This approach utilizes glycosyl fluoride donors and silyl ether acceptors while tolerating the Lewis basic environment found in carbohydrates. The method can be carried out at room temperature using air- and moisture-stable forms of the catalyst, with loadings as low as 0.5 mol %. These characteristics enable a wide array of glycosylation patterns to be accessed, including all C1–C2 stereochemical relationships in the glucose, mannose, and rhamnose series. This method allows one-pot, iterative glycosylations to generate oligosaccharides directly from monosaccharide building blocks. These advances enable the rapid and experimentally straightforward preparation of complex oligosaccharide units from simple building blocks.

Metal-free glycosylation with glycosyl fluorides in liquid SO2

“…Among these promoters Sn(II) species (SnCl 2 -AgX, X = ClO 4 or B(C 6 F 5 ) 4 ) [6,18], group IVB metallocenes (Cp 2 MCl 2 -AgClO 4 , M = Zr, Hf, Ti) [19][20][21], BF 3 •OEt 2 [22] and protic acids (TfOH, HClO 4 , HB(C 6 F 5 ) 4 ) [23] are the most frequently used. During the last decade, apart from reports on novel promoters (Hf(OTf) 4 [24], InI 3 [25], In(OTf) 3 [26], B(C 6 F 5 ) 3 [27]) and coupling partners [28], great attention has been paid to a stereoselective glycosylation by sterically fixed glycosyl fluorides as glycosyl donors [29][30][31]. The enhanced stability of glycosyl fluorides has also allowed to develop a straightforward protecting-group-free strategy towards oligosaccharides and glycopeptides under basic aqueous conditions [32,33].…”

Leveraging Trifluoromethylated Benzyl Groups toward the Highly 1,2-Cis-Selective Glucosylation of Reactive Alcohols

“…A final question regarding this set of transformations centered around the role of TMS ethers and HI derived from the reaction of 12 and TMSI. Thus (entry 11), the reaction of the TMS ether 18 derived from 12 under conditions identical to entry 8 did not result in a significant change in stereoselectivity while significantly increasing reaction time. Any HI formed in these reactions appears to have little effect on yield and selectivity, while TMS ethers are less nucleophilic than alcohols.…”

Stereoselective β-mannosylations and β-rhamnosylations from glycosyl hemiacetals mediated by lithium iodide

“…[4][5][6][7][8] Mannosylations and rhamnosylations tend to show a high preference for formation of aglycosides unless special measures are taken, as both the anomeric effect and neighbouring group participation favour alinkages, and approach to the b-face induces steric clashes with the 2-O-substituent. 9,10 Established methodologies for achieving stereoselective b-mannosylations 11,12 rely on: (a) conformational control [13][14][15] (b) intramolecular aglycone delivery [16][17][18][19][20][21][22][23] (c) use of directing groups 22 and (d) anomeric O-alkylations (Scheme 1A). 24,25 A general drawback of most of these approaches is the need for donors bearing specic protecting group patterns (oen requiring long synthetic sequences), which can be restrictive in designing multi-step syntheses of complex molecules.…”