Copper-Mediated Synthesis of N-Aryl-Oxamic Acids

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Copper-catalyzed cross-coupling reactions are vital in organic synthesis.
• Oxamates and oxamic acids are important synthetic intermediates.
• Developing efficient methods for N-arylation and subsequent functionalization is crucial.

Purpose of the Study:

• To develop a robust method for synthesizing N-aryloxamates via Ullmann-Goldberg cross-coupling.
• To establish a facile route for generating oxamic acids from N-aryloxamates.
• To explore the synthesis of urethanes from oxamic acids using different catalytic systems.

Main Methods:

• Cu-catalyzed Ullmann-Goldberg cross-coupling of aryl iodides with oxamates bearing bulky tertiary alkyl groups.
• Acid hydrolysis of N-aryloxamates to yield oxamic acids.
• Conversion of oxamic acids to urethanes using PIDA (phenyliodine(III) diacetate) under thermal conditions or a visible-light Fe-LMCT (iron-based light-to-metal charge transfer) process.

Main Results:

• N-aryloxamates were synthesized in moderate to excellent yields, with bulky alkyl groups preventing degradation.
• Oxamic acids were obtained in high yields via acid hydrolysis.
• Urethanes were efficiently synthesized from electron-deficient N-aryl oxamic acids, but yields diminished for electron-rich counterparts due to over-oxidation.

Conclusions:

• The developed Cu-catalyzed cross-coupling provides a reliable route to N-aryloxamates and oxamic acids.
• Both thermal and visible-light catalytic methods can be employed for urethane synthesis from oxamic acids.
• The electronic nature of the N-aryl group significantly impacts the efficiency of urethane formation, particularly with PIDA.