Reagent-dictated site selectivity in intermolecular aliphatic C-H functionalizations using nitrogen-centered radicals

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Site selectivity is crucial for C-H functionalization reactions.
• Current methods rely heavily on substrate C-H bond reactivity.
• Expanding selective functionalization methods is an ongoing challenge.

Purpose of the Study:

• To introduce reagent-dictated site selectivity in intermolecular aliphatic C-H functionalizations.
• To utilize nitrogen-centered amidyl radicals for controlled functionalization.
• To demonstrate high selectivity through simple amide modifications.

Main Methods:

• Employing nitrogen-centered amidyl radicals for C-H functionalization.
• Synthesizing and modifying amide precursors.
• Utilizing Density Functional Theory (DFT) calculations to study reaction mechanisms.
• Analyzing transition state structures for steric effects.

Main Results:

• Achieved high site selectivity in intermolecular C-H functionalizations.
• Demonstrated selectivity across diverse aliphatic substrates.
• DFT calculations confirmed that amide substitution patterns dictate radical steric demand.
• More hindered amides led to enhanced reagent-dictated steric selectivity.

Conclusions:

• Developed a novel strategy for reagent-controlled site selectivity in C-H functionalization.
• Amide modification offers a versatile approach to tune selectivity.
• This method provides a valuable synthetic tool for complex molecule synthesis.