Silicon Fluorides for Acid‐Base Catalysis in Glycosidations

Abstract

Adduct formation between alcohols as glycosyl acceptors and phenylsilicon trifluoride (PhSiF3) as catalyst permits acid‐base‐atalyzed glycosidations with O‐glycosyl trichloroacetimidates as glycosyl donors. In this way, from various glycosyl donors and acceptors 1,2‐trans‐ and some 1,2‐cis‐glycosides could be obtained with high anomeric selectivity. A preference for an intramolecular bimolecular nucleophilic substitution (SN2‐type) reaction course with concomitant donor and acceptor activation is supported by the results.

Predicting glycosylation stereoselectivity using machine learning

“…52,53 No influence of the /-orientation of the leaving group in dichloromethane was reported (Figure 7a), 24 and divergences in stereoselectivity based on this factor have sparingly been observed in the literature, e.g., when phenylsilicon trifluoride (PhSiF 3 ) is used as a catalyst. 54 The ability to use solvent to turn on and off the influence of leaving group orientation on glycosylation stereoselectivity has, to the best of our knowledge, not previously been reported. While essentially identical behavior is observed in DCM and chloroform, a slight divergence in MTBE at low temperatures is observed, with an 11% difference at -50 ˚C where the electrophile reaches 96% -selectivity.…”

Self-promoted and stereospecific formation of N-glycosides

“…Stereospecific glycosylations have previously been performed via pre-complexation in O -glycoside synthesis by using additives such as chloral,3 boron fluorides10 or silanes11 to complex the acceptor alcohol making it more acidic and hence able to activate the trichloroacetimidate. This method was however initially limited to a few glycosyl donor types and simple glycosyl acceptors.…”

Vessel Effect in C–F Bond Activation Prompts Revised Mechanism and Reveals an Autocatalytic Glycosylation

“…This explains why the reaction was so strongly influenced by the choice of reaction vessel as SiF 4 has been reported by Noyori as an efficient catalyst for the activation of glycosyl fluorides [40] and related fluorosilicates have previously been employed as Lewis acids in glycosylation chemistry. [41] Furthermore, the formation of large amounts of α/αand α/ -trehalose is a consequence of the reaction between HF with the glass surface which results in the release of water into solution, thus explaining the absence of trehalose in PTFE vessels. This can also explain why the consumption of glycosyl fluoride was much faster in glass vessels when weaker glycosyl nucleophiles ( Table 2, entries 5 and 7) were used as water simply outcompeted the 4-OH glycosyl nucleophile and resulted in trehalose formation.…”