Enantioselective polyene cyclization via organo-SOMO catalysis

Area of Science:

• Organic Chemistry
• Catalysis
• Asymmetric Synthesis

Background:

• Radical polycyclization reactions are powerful tools for constructing complex molecular architectures.
• Enantioselective control in radical reactions remains a significant challenge in synthetic organic chemistry.
• Organocatalysis offers a metal-free alternative for promoting asymmetric transformations.

Purpose of the Study:

• To achieve the first organocatalytic enantioselective radical polycyclization.
• To develop a novel strategy for the asymmetric synthesis of polycyclic aldehydes.
• To explore the mechanism of a single-electron oxidation-initiated cascade reaction.

Main Methods:

• Utilized chiral enamines derived from polyenals and an imidazolidinone catalyst.
• Employed a copper(II) oxidant for selective single-electron oxidation to generate radicals.
• Conducted reactions under mild acidic conditions at room temperature, followed by radical arylation.

Main Results:

• Successfully demonstrated the first organocatalytic enantioselective radical polycyclization.
• Synthesized 12 examples of polycyclic aldehydes with yields ranging from 54-77% and high enantioselectivity (85-93% ee).
• Achieved the formation of up to six new carbocycles in a single catalyst-controlled cascade.

Conclusions:

• The developed strategy provides an efficient route to enantiomerically enriched polycyclic aldehydes.
• The reaction proceeds via a radical-based cascade mechanism, initiated by SOMO catalysis.
• This method offers broad functional group compatibility, highlighting its synthetic utility.