Direct C(sp³)-H Acylation by Mechanistically Controlled Ni/Ir Photoredox Catalysis

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Ketones are crucial building blocks in organic chemistry and bioactive molecules.
• Photoredox catalysis offers novel activation modes for organic synthesis.
• Direct C(sp3)-H bond acylation is a key challenge in ketone synthesis.

Purpose of the Study:

• To develop efficient and versatile methods for direct ketone synthesis via C(sp3)-H bond acylation.
• To explore the use of different acyl electrophiles, including thioesters, amides, and N-acyllutidiniums.
• To investigate the mechanistic aspects of nickel/photoredox catalysis for ketone formation.

Main Methods:

• Exploration of nickel/iridium photocatalysis for direct hydrocarbon acylation.
• Optimization of reaction conditions and substrate scope evaluation.
• Mechanistic studies using experimental and computational methods to understand nickel catalyst behavior.

Main Results:

• Developed a method for direct acylation of simple hydrocarbons using amides as acyl electrophiles, revealing a substrate-assisted mechanism.
• Introduced N-acyllutidiniums as acyl electrophiles, enabling stereoselective synthesis of α-amino ketones from α-chiral substrates.
• Demonstrated that adjustments in nickel/photoredox catalysis conditions significantly influence reaction outcomes.

Conclusions:

• Successfully developed versatile methodologies for synthesizing diverse ketones, including valuable α-amino ketones.
• Gained mechanistic insights into nickel-catalyzed C-H activation and acylation processes.
• Highlighted the potential for tailored reaction design through nickel redox modulation in photoredox catalysis.