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

Abstract

Activation of C-F bonds under acidic conditions results in the formation of hydrogen fluoride as the reaction progresses. In the following communication, the effect of the vessel material on such reactions has been investigated and a significant difference between an HF-resistant material and common borosilicate glassware has been found. HF was found to react rapidly with borosilicate glassware, seemingly leaching fluoro- [a] 140 silicate into solution, but persisted in HF-resistant materials. Several examples of C-F bond activation on glycosyl fluorides and benzyl fluorides as well as NMR-studies suggest a significant effect of the choice of the reaction vessel, leading to the discovery of an autocatalytic glycosylation and a revised mechanism for the activation of benzyl fluorides, suggesting activation by SiF 4 rather than HF. Scheme 1. Examples of C-F bond activation promoted by acid-or H-bond catalysis and the work presented in this paper.

Metal-free glycosylation with glycosyl fluorides in liquid SO2

“…Finally, full conversion of fluoride α-1a and sufficient yield of desired product 3a were reached with 3.0 equiv of nucleophile at 150 °C (Table 1, entry 5). Thus, in contrast to the previous report [63], in our case the reaction was not fully stopped by changing the reaction vessel from glass to PTFE tube. At this point, we can confirm the ability of SO 2 to activate the glycosyl fluoride with a probable co-promoting assistance of a glass vessel.…”

“…To note, at lower temperatures ( Table 1 , entry 1) no reaction was observed and mannosyl fluoride α- 1a was fully recovered. Recently, Pedersen et al have studied the vessel effect on the C–F bond activation of glucosyl fluorides [ 63 ]. They have proposed an autocatalytic glycosylation by SiF 4 generated in situ form initially released HF that reacts with silicates of the glassware surface.…”

Thiourea‐Catalyzed C−F Bond Activation: Amination of Benzylic Fluorides

“…entry 22 in Table 1);a sa mmonium cations generated from nucleophilic substitution are good HBDs,s ome fluoridem ight get trapped in complexes with the product, freeing the thiourea for another CÀFsubstitution. [26] Overall, HBD activation of CÀFb onds actually benefits from the weak natureo ft he interaction. As the hydrogen bond with the organofluoriner eactant is not favorable, there is no stabilization of the startingm aterials, which is key in catalytic processes.…”

3D Printed Reactionware for Synthetic Electrochemistry with Hydrogen Fluoride Reagents

“…This remarkable difference in yield on simply switching the cell material further emphasises the requirement to ensure an HF stable material is used for these reaction systems. The reaction of hydrogen fluoride with the silica in the glass vial presumably depletes the available HF that is necessary for successful reaction, or the generation of SiF 4 [41] may be detrimental to reaction progress. A 3D printed PP cell was designed with an internal cylindrical volume of 25 mL, which is capable of converting up to 6 mmol of substrate 1 at a concentration of 300 mM, Figure 3 A threaded lid was designed and printed that combines with an O-ring to compress onto the reactor body and seal it from the outside environment, reducing solvent evaporation and facilitating the creation of inert atmosphere when combined with an N 2 line.…”

“…Not only does the glassware etch and weaken, but silicon and boron contaminants leach into the solution, which can interfere with the chemistry. [41] Most commercially available electrochemical cells are produced using regular pyrex-based glass, and the HFcompatible polymer-based electrochemical cells are much rarer and more expensive (see SI for details). Therefore, it is most common to construct HF-compatible electrochemical cells inhouse, and most commonly from PTFE.…”