Transition Metal-Catalyzed Nitrogen Atom Insertion into Carbocycles

Area of Science:

• Synthetic Chemistry
• Organic Chemistry
• Catalysis

Background:

• N-heterocycles are crucial building blocks in pharmaceuticals, materials science, and synthetic chemistry.
• Skeletal editing, particularly nitrogen atom insertion into carbocycles, is a significant but challenging area in modern synthetic chemistry.
• Existing methods struggle with the inertness of carbon skeletons and C-C bond cleavage, limiting late-stage functionalization.

Purpose of the Study:

• To highlight advancements in nitrogen atom insertion into carbocycles for skeletal editing.
• To present novel catalytic strategies for synthesizing N-heterocycles through C-C bond functionalization.
• To showcase the laboratory's contributions and acknowledge key research in the field.

Main Methods:

• Co-catalyzed oxidative azidation for nitrogen insertion into cycloalkenes (cyclobutenes, cyclopentenes, cyclohexenes).
• Dirhodium-catalyzed intramolecular nitrogen insertion into the benzene rings of 2-amino biaryls.
• Cu-catalyzed and Fe-catalyzed dearomative azidation/aryl migration and subsequent ring contraction of arenols.

Main Results:

• Successful synthesis of polysubstituted pyridines from cycloalkenes, overcoming limitations of traditional cross-coupling.
• Site-selective skeletal editing of arenes via intramolecular nitrogen insertion into 2-amino biaryls.
• Development of Cu- and Fe-catalyzed methods for site-selective nitrogen incorporation and carbon-to-nitrogen transmutation in arenols.

Conclusions:

• Nitrogen atom insertion into carbocycles is a viable strategy for skeletal editing and N-heterocycle synthesis.
• Catalytic methods using Co, Rh, Cu, and Fe enable efficient and site-selective nitrogen incorporation.
• These advancements offer significant potential for late-stage functionalization and the synthesis of complex molecules for materials chemistry.