Photocatalytic Trifluoromethyl Carbyne Equivalent Generation: A Modular Platform for Cascade Cycloannulation

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Heterocyclic Chemistry

Background:

• Trifluoromethylated heterocycles are crucial motifs in pharmaceuticals and materials science.
• Developing efficient methods for their synthesis, particularly oxindoles, remains an active research area.
• Radical cascade reactions offer powerful strategies for constructing complex molecular architectures.

Purpose of the Study:

• To develop a novel visible-light-induced radical cascade cyclization for trifluoromethylated oxindoles.
• To explore the use of trifluoromethyl carbyne equivalents in radical cascade reactions.
• To establish a new synthetic platform for fluorinated heterocycles and carbyne chemistry.

Main Methods:

• Visible-light photoredox catalysis.
• Radical cascade cyclization of N-aryl acrylamides with trifluoromethyl carbyne equivalents.
• Mechanistic studies including reductive quenching cycle investigation.

Main Results:

• Successful synthesis of structurally diverse trifluoromethylated oxindoles bearing a diazo moiety.
• Demonstrated broad substrate scope, excellent functional group tolerance, and high regioselectivity.
• Established a novel carbyne-equivalent-mediated radical cascade reaction proceeding via a diazotrifluoroethyl radical intermediate.

Conclusions:

• The developed method provides an efficient and versatile route to trifluoromethylated oxindoles.
• Gram-scale synthesis and product derivatizations highlight the practical utility of the methodology.
• This work establishes a new platform for fluorinated heterocycle synthesis and carbyne chemistry.