Photosensitized O₂ enables intermolecular alkene cyclopropanation by active methylene compounds

Area of Science:

• Organic Chemistry
• Catalysis
• Medicinal Chemistry

Background:

• Cyclopropanes are crucial structural motifs in pharmaceuticals and natural products.
• Traditional cyclopropanation methods often rely on hazardous diazoalkanes, necessitating strict safety protocols.
• Developing safer and more accessible synthetic routes for cyclopropanes is an ongoing research objective.

Purpose of the Study:

• To report a novel photoredox-catalyzed intermolecular cyclopropanation reaction.
• To utilize readily available active methylene compounds as cyclopropane precursors.
• To establish a safer alternative to existing cyclopropanation methodologies.

Main Methods:

• Employing a photoredox catalyst activated by blue light-emitting diode (LED) light.
• Utilizing an iodine co-catalyst (molecular iodine or in situ generated).
• Conducting the reaction in neutral solvents under ambient air or dioxygen (O₂).

Main Results:

• Successful intermolecular cyclopropanation of unactivated alkenes with active methylene compounds.
• Demonstration of the reaction's efficacy under mild, aerobic conditions.
• Mechanistic studies revealing the crucial role of photosensitized O₂ in radical generation and cyclization.

Conclusions:

• The developed method offers a simple, safe, and efficient route to cyclopropanes.
• This photoredox catalysis approach provides a valuable alternative for synthesizing cyclopropane-containing molecules.
• The findings contribute to the advancement of sustainable and practical synthetic organic chemistry.