Site-Selective Carbonylative Cyclization with Two Allylic C-H Bonds Enabled by Radical Differentiation

Area of Science:

• Synthetic organic chemistry
• Catalysis
• Sustainable chemistry

Background:

• Controlling site-selectivity in C-H functionalization is crucial but challenging.
• Methods for site-selective double C-H functionalization are scarce.
• Developing sustainable C-H activation technologies is an ongoing pursuit.

Purpose of the Study:

• To develop a new method for highly site-selective double C-H functionalization.
• To establish a stereoselective carbonylative formal [2 + 2] cycloaddition reaction.
• To synthesize synthetically and medicinally relevant allylic beta-lactams.

Main Methods:

• Implementation of a radical single-out strategy.
• Utilizing steric hindrance-sensitive CO-insertion for radical differentiation.
• Sequential double allylic C-H bond activation of imines and alkenes.

Main Results:

• Achieved high site-selectivity and stereoselectivity in the cycloaddition reaction.
• Demonstrated compatibility with a wide range of imines and alkenes.
• Successfully synthesized diverse allylic beta-lactams without specialized reagents.

Conclusions:

• The developed radical strategy offers a new approach to site-selective double C-H functionalization.
• The carbonylative formal [2 + 2] cycloaddition provides an efficient route to allylic beta-lactams.
• This method advances sustainable synthetic organic chemistry by enabling selective C-H bond activation.