Functionalization of α-C(sp³ )-H Bonds in Amides Using Radical Translocating Arylating Groups

Area of Science:

• Organic Chemistry
• Synthetic Methodology Development

Background:

• Constructing α-quaternary carbon centers in amides is synthetically challenging.
• Existing methods often lack efficiency or substrate scope for complex amide structures.

Purpose of the Study:

• To develop a novel method for α-C-H arylation of N-alkylamides.
• To enable the efficient synthesis of amides bearing α-quaternary carbon centers.

Main Methods:

• Utilized 2-iodoarylsulfonyl radical translocating arylating (RTA) groups for arylation.
• Applied the method to primary, secondary, and tertiary α-C(sp³)-H bonds in N-alkylamides.
• Investigated the use of various mono- and disubstituted RTA-groups.

Main Results:

• Achieved successful α-C-H arylation of N-alkylamides.
• Demonstrated the formation of α-quaternary carbon centers with good to excellent yields.
• Confirmed the reaction proceeds via a cascade mechanism involving hydrogen atom transfer, aryl migration, and SO₂ extrusion.

Conclusions:

• The reported method provides an effective strategy for synthesizing α-arylated N-alkylamides.
• This approach expands the toolkit for constructing complex amide derivatives with quaternary centers.
• The radical cascade mechanism offers insights into novel synthetic pathways.