Ruthenium-Catalyzed Aminocarbonylation with Isocyanates Through Weak Coordinating Groups

Area of Science:

• Organic Chemistry
• Catalysis
• Medicinal Chemistry

Background:

• Amide functional groups are crucial in biologically active molecules.
• Mild synthetic methods for introducing amides are highly sought after.
• Directed C-H functionalization offers efficient synthetic strategies.

Purpose of the Study:

• To develop a mild and efficient protocol for directed C-H aminocarbonylation.
• To utilize isocyanates as amidating agents in a ruthenium-catalyzed reaction.
• To enable the synthesis of anthranilamide derivatives.

Main Methods:

• Ruthenium-catalyzed C-H aminocarbonylation.
• High-throughput experimentation (HTE) for reaction optimization.
• Directed functionalization guided by Lewis basic groups (anilides, lactams, carbamates).

Main Results:

• A mild, redox-neutral, and base-free protocol for C-H aminocarbonylation was established.
• The reaction successfully synthesized anthranilamide derivatives.
• The method demonstrated utility in large-scale synthesis and late-stage functionalization.

Conclusions:

• The developed protocol provides a valuable method for synthesizing amide-containing compounds.
• This approach offers a mild and efficient route to important molecular scaffolds.
• The reaction's applicability in late-stage functionalization enhances its synthetic utility.