Photoredox-Catalyzed Cyclopropanation via Ligated Boryl Radical-Mediated Nonstabilized Carbene Formation

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Cyclopropanes are vital structural motifs in pharmaceuticals.
• Traditional cyclopropanation methods using diazo compounds pose safety risks due to high reactivity.
• Alkyl-substituted diazo compounds are particularly hazardous carbene precursors.

Purpose of the Study:

• To develop a safer and more direct method for generating nonstabilized metal carbenes.
• To enable the use of readily available aliphatic aldehydes as carbene precursors.
• To circumvent the need for hazardous diazo compounds in cyclopropanation reactions.

Main Methods:

• Metallaphotoredox catalysis was employed for carbene generation.
• Ligated boryl radicals mediated the process.
• Bis(pinacolato)diboron (B₂cat₂) was used to activate the carbonyl group of aldehydes.

Main Results:

• A novel protocol for generating nonstabilized metal carbenes directly from aliphatic aldehydes was established.
• The method successfully avoided the use of diazo compounds, enhancing safety.
• The protocol demonstrated broad substrate scope (>88 examples) and good functional group tolerance.

Conclusions:

• This work presents a significant advancement in cyclopropanation chemistry by offering a safer alternative to diazo precursors.
• The developed method allows for direct utilization of aliphatic aldehydes, simplifying synthetic routes.
• The protocol's versatility extends to various cyclopropanation and sigma-bond insertion reactions, with mechanistic insights provided.