Dynamic Kinetic Activation of Aziridines Enables Radical-Polar Crossover (4 + 3) Cycloaddition with 1,3-Dienes

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Aziridine cycloaddition is key for nitrogen heterocycle synthesis but often lacks regioselectivity control.
• Substrate-controlled reactions present challenges in directing C-N bond cleavage.
• Developing catalyst-controlled methods is crucial for predictable synthetic outcomes.

Purpose of the Study:

• To develop a nickel-catalyzed dynamic kinetic activation strategy for aziridines.
• To achieve catalyst-controlled regioselectivity in aziridine C-N bond cleavage.
• To establish a novel radical-polar crossover (4 + 3) cycloaddition for azepine synthesis.

Main Methods:

• Nickel-catalyzed dynamic kinetic activation of diverse aziridines.
• Generation of 1,3-radical anion intermediates from aziridines.
• Regioselective cascade reaction with aromatic branched 1,3-dienes.
• Experimental studies and Density Functional Theory (DFT) calculations.

Main Results:

• Consistent cleavage of the sterically hindered C-N bond in various aziridines.
• Formation of 1,3-radical anion intermediates.
• Highly regioselective 1,4-Heck/allylic substitution cascade.
• Successful synthesis of seven-membered azepine products via a (4 + 3) cycloaddition.

Conclusions:

• The developed nickel-catalyzed strategy offers precise control over aziridine activation and regioselectivity.
• This method provides a complementary approach to traditional dipolar cycloadditions.
• An unusual cycloaddition mode for 1,3-dienes has been introduced, expanding synthetic possibilities.