Evaluating Participation Modes in Peracetylated Glycosyl Cations

Area of Science:

• Carbohydrate Chemistry
• Organic Chemistry
• Spectroscopy

Background:

• Neighboring group participation and remote participation are crucial for stereocontrol in glycosylation reactions.
• Glycosyl cations, key intermediates, are typically short-lived and difficult to characterize.
• Acetyl protecting groups are commonly used in carbohydrate synthesis.

Purpose of the Study:

• To directly assess and rank the participation modes of acetyl protecting groups in peracetylated glucosyl, galactosyl, and mannosyl cations.
• To understand the influence of hexose structure on remote protecting group participation.
• To provide fundamental insights into protecting group behavior in carbohydrate chemistry.

Main Methods:

• Gas-phase infrared spectroscopy was employed to study glycosyl cations.
• Density functional theory calculations were used to support experimental findings and rank theoretical structures.
• Analysis focused on the formation of dioxolenium ions, indicative of participation.

Main Results:

• Neighboring group participation, leading to C2-dioxolenium ion formation, was experimentally confirmed for all three hexoses (glucose, galactose, mannose).
• Energetic analysis revealed distinct remote participation preferences: C3-dioxolenium ions for glucose and mannose, and C4-dioxolenium ions for galactose.
• The stability of theoretical structures in vacuo differed based on the specific hexose.

Conclusions:

• Acetyl protecting groups actively participate in glycosyl cation intermediates, influencing reaction stereochemistry.
• The observed differences in remote participation highlight the importance of hexose structure in directing reaction pathways.
• These findings enhance the fundamental understanding of protecting group dynamics and can inform the design of novel glycosylation strategies.