Visible-light-promoted difluoroamidated oxindole synthesis via electron donor-acceptor complexes

Area of Science:

• Organic Chemistry
• Photochemistry
• Medicinal Chemistry

Background:

• Oxindoles are crucial heterocyclic compounds with diverse biological activities.
• Developing efficient and sustainable methods for synthesizing functionalized oxindoles is of significant interest.

Purpose of the Study:

• To develop a metal-free, visible-light-promoted synthetic route for difluoroalkylated oxindoles.
• To explore the scope and mechanism of this novel photochemical reaction.

Main Methods:

• Utilized N-phenylacrylamides and bromodifluoroacetamides as starting materials.
• Employed N,N,N',N'-tetramethylethylenediamine (TMEDA) as an electron donor under visible light irradiation.
• Investigated reaction mechanism through mechanistic studies.

Main Results:

• Successfully synthesized 24 examples of difluoroalkylated oxindoles with good to excellent yields (44-99%).
• Demonstrated excellent substrate adaptability and mild reaction conditions.
• Elucidated a mechanism involving radical addition, intramolecular cyclization, dehydrogenation, and rearomatization.

Conclusions:

• The developed protocol offers a promising, efficient, and sustainable photochemical method for difluoroalkylated oxindole synthesis.
• The method features mild conditions, simple operation, wide substrate scope, and high yields.
• The synthesized difluoroalkylated oxindoles hold potential for applications in medicinal chemistry.