Decarboxylative Giese additions through electron donor-acceptor complexes under transition metal-free conditions

Area of Science:

• Organic Chemistry
• Synthetic Chemistry

Background:

• Giese addition reactions are important for C-C bond formation.
• Existing methods often require transition metals, limiting their scope and sustainability.

Purpose of the Study:

• To develop a transition metal-free Giese addition reaction.
• To utilize RAEs/HEH complexes for efficient radical generation and addition.

Main Methods:

• A novel Giese addition protocol employing RAEs/HEH complexes under thermal conditions.
• Mechanistic investigations including free radical decarboxylation studies.
• Density Functional Theory (DFT) calculations to understand radical formation.

Main Results:

• Successful transition metal-free Giese addition reaction achieved.
• RAEs/HEH complexes promote carboxyl radical formation more effectively than individual RAEs.
• The reaction proceeds via a necessary free radical decarboxylation process upon mild heating.
• Gram-scale synthesis was demonstrated, with applications to deuterated alkyl carboxylic acid and dehydrocholic acid.
• High tolerance to water and oxygen was observed.

Conclusions:

• The developed protocol offers a sustainable and efficient route for synthesizing carboxylic acid derivatives.
• The method is suitable for late-stage modification of complex molecules, including natural products.
• The use of RAEs/HEH complexes provides a robust platform for metal-free radical reactions.