Enantioselective Radical Dearomative Conjugate Amination Enabled by Co(II)-Based Metalloradical Catalysis

Area of Science:

• Organic Synthesis
• Catalysis
• Radical Chemistry

Background:

• Controlling regioselectivity in delocalized radical systems is crucial but challenging.
• Previous research primarily focused on allylic radicals, limiting exploration of larger systems.
• Developing new methods for generating and utilizing extensively delocalized radicals is needed.

Purpose of the Study:

• To explore larger delocalized radical systems beyond allylic radicals.
• To develop a catalytic system for regioselective radical C-N bond formation.
• To synthesize chiral α-tertiary amino acid derivatives with high enantioselectivity.

Main Methods:

• Catalytic generation of extensively delocalized 4-vinylphenoxyl radicals.
• Cobalt(II)-based enantioselective metalloradical catalysis.
• Dearomative 1,7-conjugate amination of 4-vinylphenols with aryl azides.
• Hydrogen-atom abstraction from O-H bonds.

Main Results:

• Successful regioselective radical C-N bond formation.
• Synthesis of valuable chiral α-tertiary amino acid derivatives in high yields.
• Excellent enantioselectivities achieved for new tetrasubstituted stereocenters.
• Demonstration of 1,6-conjugate addition with various nucleophiles.

Conclusions:

• The developed Co(II) system enables efficient enantioselective dearomative amination of 4-vinylphenols.
• This method provides access to complex chiral α-tertiary amino acid derivatives.
• The resulting products possess a para-quinone methide (p-QM) functionality with potential synthetic utility.