Sterically Strained Brønsted Pair Catalysis by Bulky Pyridinium Salts: Direct Stereoselective Synthesis of 2-Deoxy and 2,6-Dideoxy-β-thioglycosides from Glycals.

A sterically strained ionic Brønsted pair complex obtained from a sterically bulky base 2,4,6-tri--butylpyridine and hydrochloric acid imbues unusual reactivity to the anionic chloride. The complete shielding of the cationic [N-H] by the bulky ortho--butyl groups weakens the possible hydrogen-bonding interactions with the chloride anion, and the [N-H]···Cl distance is unusually longer (3.10 Å). This results in strained/frustrated electrostatic interactions between the ion-pair, thus infusing an increased reactivity in both of the ions, which results in the activation of a third molecule like thiol via hydrogen-bonding. This intriguing weak interaction-based reactivity has been utilized to develop an organocatalytic synthesis of 2-deoxy-β-thioglycosides from glycals. While the H NMR studies showcase the diamagnetic activation of thiols in the presence of the catalyst, the electron paramagnetic resonance (EPR) studies reveal the generation of a radical species that suggests a possible frustrated radical pair catalysis. Besides, IR spectroscopic studies explain the intriguing influence of size/charge density of the anion on the solvation-insusceptible, cationic [TTBPyH] and on the observed reactivity.