Redox-neutral ketone-olefin coupling enabled by mild ketone-to-ketyl-type radical conversion

Area of Science:

• Organic Chemistry
• Radical Chemistry
• Catalysis

Background:

• Ketones are essential functional groups in organic synthesis.
• Generating ketyl-type radicals from aliphatic ketones under mild conditions remains a significant challenge.
• This limitation restricts the development of new ketone transformations, especially those involving transition-metal catalysis for C-C bond formation.

Purpose of the Study:

• To develop a mild and broadly compatible method for converting aliphatic ketones into ketyl-type radicals.
• To integrate ketyl-type radical generation with transition-metal catalysis for C-C bond formation.
• To establish a novel platform for unconventional ketone transformations.

Main Methods:

• Utilized a bifunctional silyl reagent for the mild conversion of aliphatic ketones to ketyl-type radicals.
• Employed a radical translocation strategy to bypass strongly reductive conditions.
• Integrated the generated ketyl-type radicals with palladium (Pd) catalysis for redox-neutral ketone-olefin couplings.

Main Results:

• Achieved efficient and mild generation of ketyl-type radicals from aliphatic ketones.
• Successfully merged radical generation with Pd catalysis, enabling redox-neutral ketone-olefin couplings.
• Synthesized diverse alkenylation and allylation products with broad functional group tolerance using readily available olefins.

Conclusions:

• The developed protocol offers an efficient and mild approach for generating ketyl-type radicals from aliphatic ketones.
• This method facilitates C-C bond formation via ketone-olefin couplings, bypassing harsh reductive conditions.
• The adaptable platform holds potential for various ketone transformations and C-C bond formations.