Manganese-catalyzed late-stage aliphatic C-H azidation

Area of Science:

• Organic Chemistry
• Catalysis
• Medicinal Chemistry

Background:

• Aliphatic C-H bonds are ubiquitous in organic molecules.
• Organic azides are versatile intermediates in synthesis.
• Efficient methods for C-H functionalization are highly sought after.

Purpose of the Study:

• To develop a manganese-catalyzed method for aliphatic C-H azidation.
• To demonstrate the utility of this reaction for late-stage functionalization of bioactive compounds.
• To achieve enantioselective C-H azidation.

Main Methods:

• Manganese-catalyzed reaction utilizing aqueous sodium azide.
• Reaction performed under aerobic conditions.
• Application to secondary, tertiary, and benzylic C-H bonds.

Main Results:

• Efficient conversion of C-H bonds to azides with yields up to 74%.
• Successful late-stage azidation of drugs like pregabalin, memantine, and artemisinin.
• Achieved 70% enantiomeric excess (ee) in Mn-catalyzed enantioselective azidation.

Conclusions:

• The developed Mn-azidation method is operationally simple and efficient.
• This method holds significant potential for drug discovery and chemical biology.
• Enantioselective C-H azidation expands the synthetic utility of this transformation.