A Radical Activation Strategy for Versatile and Stereoselective N-Glycosylation

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Glycochemistry

Background:

• Traditional N-glycosylation methods often require acidic conditions, leading to poor stereoselectivity and limited substrate scope.
• Challenges include low yields and incompatibility with diverse functional groups in N-aglycones.

Purpose of the Study:

• To develop a novel, versatile, and stereoselective N-glycosylation strategy.
• To overcome the limitations of existing methods by employing a radical activation approach under basic conditions.

Main Methods:

• Utilized a radical activation strategy with glycosyl sulfinate donors.
• Employed readily accessible starting materials and basic reaction conditions.
• Investigated mechanistic pathways involving radical intermediates and iodide catalysis.

Main Results:

• Achieved versatile and stereoselective N-glycosylation with broad N-aglycone tolerance (alkyl, aryl, heteroaryl, nucleobase).
• Demonstrated a novel route via glycosyl iodide intermediate through S_N2 attack.
• Proposed an alternative pathway involving radical coupling yielding exclusive 1,2-trans products.

Conclusions:

• The novel radical activation approach offers a powerful new tool for N-glycoside synthesis.
• This method broadens the synthetic landscape for constructing complex glycosidic structures under mild conditions.
• The strategy enhances stereoselectivity and substrate scope compared to previous methods.