Redox-Neutral Cu-Catalyzed Cyclative γ-C-H Functionalization Enroute to Aza- and Oxo-heterocycles

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Catalysis

Background:

• Saturated aza- and oxo-heterocycles are crucial scaffolds in drug design.
• Existing methods for synthesizing these heterocycles often require complex procedures or specific precursors.

Purpose of the Study:

• To develop a versatile and efficient method for constructing diverse saturated aza- and oxo-heterocycles.
• To utilize copper catalysis for cyclative C(sp3)-H functionalization of unactivated C-H bonds.

Main Methods:

• Employing N-methoxyamides with a pendant heteroatom as radical precursors.
• Utilizing a redox-neutral copper-catalyzed intramolecular H-abstraction and radical trapping mechanism.
• Synthesizing cyclic sulfonamides, cyclic ethers, and lactones of various ring sizes.

Main Results:

• Demonstrated successful synthesis of diverse saturated aza- and oxo-heterocycles.
• Established a versatile copper-catalyzed cyclative γ-C(sp3)-H functionalization.
• Showcased the method's applicability to different ring sizes and heteroatom-containing substrates.

Conclusions:

• The developed method provides a straightforward and versatile route to valuable saturated heterocycles.
• This approach expands the toolkit for synthesizing drug-like molecules.
• The copper-catalyzed cyclative functionalization offers a powerful strategy for heterocycle synthesis.