Evaluating C2-Neighbouring and C3-, C4-, C6-Remote Participation in Peracetylated Glycosyl Cations

Neighbouring group participation and remote participation are fundamental concepts in carbohydrate chemistry and are commonly applied to achieve stereocontrol in glycosylation reactions. The corresponding intermediates can be glycosyl cations, which are challenging to characterise due to their short-lived nature. Using gas-phase infrared spectroscopy supported by density functional theory calculations, we directly assess and rank the participation modes of acetyl protecting groups in peracetylated glucose, galactose, and mannose, showing that neighbouring group participation and hence the formation of C2-dioxolenium ions is found experimentally in all three cases. The energetical ranking revealed differences in the remote participation preferences depending on the hexose, showing that C3-dioxolenium ions are preferred for glucose and particularly mannose, whereas C4-dioxolenium ions are most stable in the case of galactose. These findings contribute to our fundamental understanding of protecting group participation and could facilitate glycosylation strategies in the future.