Exploiting the Strained Ion-Pair Interactions of Sterically Hindered Pyridinium Salts Toward S_N2 Glycosylation of Glycosyl Trichloroacetimidates

We demonstrate here that strained and sterically hindered protonated 2,4,6-tri-tert-butylpyridinium (TTBPy) tetrafluoroborate, a crystalline, bench stable salt serves as a mild and efficient organocatalyst for the S_N2 type displacement of glycosyl trichloroacetimidates toward the stereoselective synthesis of both α- and β-glycosides. The strained ion-pair interactions between the sterically hindered pyridinium cation and the tetrafluoroborate anion infuse unusual reactivity to the ions resulting in the unique anion assisted activation of alcohol. This mild activation of alcohol facilitates the S_N2 type displacement of glycosyl α-trichloroacetimidates into β-glycosides in a highly diastereoselective manner. These unique interactions were established based on extensive infrared and ¹H, ¹⁹F, ¹¹B NMR studies and theoretical studies.