Synthesis of Cyclopropane and Spirocyclic γ-Lactams via Relay Reduction and Radical-Polar Crossover Cyclization

Area of Science:

• Organic Chemistry
• Photocatalysis
• Synthetic Methodology

Background:

• Cascade cyclization reactions are crucial for constructing complex molecular architectures.
• Photocatalysis offers a sustainable and mild approach for organic transformations.
• Developing new methods for cyclopropane synthesis is essential for accessing valuable chemical entities.

Purpose of the Study:

• To establish a novel RPCC/RPCCC cascade cyclization strategy for the synthesis of cyclopropane derivatives.
• To explore the use of a CO2•--mediated off-cycle photocatalytic approach for continuous reduction.
• To demonstrate the first application of the SET-HAT-SET relay process in cyclopropane synthesis.

Main Methods:

• Utilizing a radical cascade cyclization strategy involving photocatalysis.
• Employing a CO2•--mediated off-cycle photocatalytic cycle.
• Implementing a SET-HAT-SET relay process for cyclopropane ring formation.

Main Results:

• Successfully established a RPCC/RPCCC cascade cyclization strategy.
• Achieved continuous reduction of electrophilic aldehydes and imines.
• Demonstrated efficient synthesis of β-hydroxycyclopropanes and spirocyclopropane-γ-lactams.
• Showcased a broad substrate scope under mild reaction conditions.

Conclusions:

• The developed strategy provides a viable route for synthesizing cyclopropane derivatives.
• This method enables the introduction of 3D framework moieties into complex molecules.
• The photocatalytic approach offers a sustainable and efficient alternative for cyclopropane synthesis.