Amide directed iridium C(sp³)-H borylation catalysis with high N-methyl selectivity

Area of Science:

• Organometallic Chemistry
• Catalysis
• Synthetic Organic Chemistry

Background:

• C(sp3)-H activation is a crucial transformation in organic synthesis.
• Developing selective and efficient methods for C-H functionalization remains a significant challenge.
• Amide functionalization offers a pathway to diverse chemical structures.

Purpose of the Study:

• To develop a novel ligand system for iridium-catalyzed C(sp3)-H activation borylation.
• To achieve selective mono-borylation of N-methyl amides.
• To elucidate the mechanism of the borylation reaction.

Main Methods:

• Synthesis of a bidentate monoanionic ligand system.
• Iridium-catalyzed C(sp3)-H activation borylation reactions.
• Kinetic studies, including competitive kinetic isotope effect measurements.

Main Results:

• Successful development of a ligand system enabling iridium-catalyzed C(sp3)-H activation borylation of N-methyl amides.
• Moderate to good isolated yields of borylated amides were achieved.
• Exclusive mono-borylation was observed, allowing the amide to be the limiting reagent.
• High selectivity for C(sp3)-H activation over other C-H bonds was demonstrated.
• A large primary kinetic isotope effect indicated C-H activation as the rate-limiting step.

Conclusions:

• The developed ligand system provides an efficient route for selective C(sp3)-H activation borylation of N-methyl amides.
• The reaction proceeds via a mechanism where C-H activation is the rate-determining step.
• This methodology expands the toolkit for functionalizing amides and related compounds.