Lewis acid-mediated formamidation employing carbohydrates as synthons

Area of Science:

• Organic Chemistry
• Catalysis
• Green Chemistry

Background:

• Formamidation reactions are crucial for synthesizing N-formamides.
• Traditional methods often require harsh conditions, stoichiometric oxidants, or additives.
• Developing sustainable and efficient formamidation processes is an ongoing challenge.

Purpose of the Study:

• To develop a practical and sustainable catalytic system for N-formamidation.
• To utilize air as the sole oxidant for the formamidation of glucose.
• To achieve high yields and turnover numbers under mild conditions.

Main Methods:

• A Lewis acid-catalyzed reaction system was employed.
• Glucose was reacted with various amines using air as the oxidant.
• Isotope labeling experiments (D-, 13C6-glucose, 18O2) were conducted for mechanistic studies.

Main Results:

• The catalytic system efficiently achieved N-formamidation of glucose with diverse amines.
• High yields of N-formamides were obtained under mild conditions.
• A record turnover number of 83,213 was achieved, demonstrating exceptional catalytic activity.

Conclusions:

• The developed method offers a practical and green approach to N-formamidation.
• The Lewis acid plays a dual role in promoting glucose isomerization and oxidation.
• This work provides a highly efficient catalytic system for synthesizing N-formamides from glucose.