C═C/N═O Metathesis Enables Oxidative Decarboxylation

Area of Science:

• Synthetic organic chemistry
• Catalysis
• Green chemistry

Background:

• Metathesis reactions involving (2 + 2) cycloaddition-(2 + 2) cycloreversion are crucial in synthesis.
• Limited substrate scope has historically restricted the application of this reaction class.

Purpose of the Study:

• To develop a novel iron(II)-catalyzed C═C/N═O metathesis reaction.
• To apply this new reaction to the mild oxidative decarboxylation of carboxylic acids.

Main Methods:

• Iron(II)-catalyzed C═C/N═O metathesis reaction development.
• Application to oxidative decarboxylation of carboxylic acids.
• Mechanistic studies including ReactIR and computational analysis.

Main Results:

• A novel iron-catalyzed C═C/N═O metathesis was successfully designed and implemented.
• The reaction enables mild, air-stable, one-pot oxidative decarboxylation of carboxylic acids using an earth-abundant iron catalyst.
• Broad functional group tolerance, scalability, and late-stage applicability to drug molecules were demonstrated.
• The method was extended to ester synthesis from α-aryloxy and α-alkoxy carboxylic acids.

Conclusions:

• The developed iron-catalyzed metathesis offers a versatile and sustainable method for carboxylic acid functionalization.
• This approach provides access to ketones and imines, expanding synthetic possibilities.
• The reaction's efficiency, scalability, and broad applicability highlight its potential impact on synthetic chemistry and drug discovery.