Oxidative Hetero-Coupling: Iron- and Copper-Mediated 1,2-Dicarbofunctionalization.

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Radical Chemistry

Background:

• 1,2-dicarbofunctionalization of alkenes typically uses two electrophiles or redox-neutral conditions.
• Oxidative hetero-1,2-dicarbofunctionalization with two nucleophiles is challenging due to byproduct formation.
• Direct utilization of carboxylic acids in such reactions is highly desirable but underexplored.

Purpose of the Study:

• To develop a novel method for the oxidative heterocoupling of two distinct nucleophiles.
• To enable the direct use of unprotected alkyl carboxylic acids in generating new C(sp3) centers.
• To overcome limitations associated with byproduct formation in previous dicarbofunctionalization strategies.

Main Methods:

• Application of the persistent radical effect to control radical coupling.
• Utilizing unprotected alkyl carboxylic acids as nucleophile precursors.
• Employing radical trapping experiments, binding energy analysis, and DFT calculations to elucidate the mechanism.

Main Results:

• Demonstrated successful heterocoupling of two distinct nucleophiles, including carboxylic acids.
• Generated two successive C(sp3) centers, including quaternary centers, in a single synthetic step.
• Provided mechanistic insights through computational studies and radical trapping.

Conclusions:

• The developed method offers an unprecedented route for oxidative hetero-1,2-dicarbofunctionalization.
• Directly using carboxylic acids simplifies synthetic pathways and enhances atom economy.
• This approach opens new avenues for constructing complex aliphatic architectures from readily available starting materials.