A Strategy for Amide C-N Bond Activation with Ruthenium Catalyst: Selective Aromatic Acylation

Area of Science:

• Organometallic Chemistry
• Catalysis
• Organic Synthesis

Background:

• Amide C-N bonds are typically inert and challenging to activate.
• Ruthenium catalysts are known for C-H activation but less explored for direct amide C-N bond cleavage.
• Developing new catalytic strategies for amide functionalization is crucial for synthetic chemistry.

Purpose of the Study:

• To describe a novel strategy for amide C-N bond activation using a ruthenium catalyst.
• To identify the active catalytic species involved in the reaction.
• To explore the tandem C-H and C-N bond activation of 2-arylpyridines with amides.

Main Methods:

• Utilized a ruthenium precatalyst for in situ generation of active species.
• Employed direct C-H bond activation of 2-arylpyridines.
• Investigated the subsequent amide C-N bond activation under the same reaction conditions.
• Analyzed reaction products to determine yield and selectivity.

Main Results:

• Bis-cycloruthenated ruthenium complexes were identified as the key active species.
• The method achieved direct amide C-N bond activation with superior oxidative addition ability.
• Tandem C-H/C-N bond activation of 2-arylpyridines and amides produced monoacylation products in moderate to good yields.
• Various functional groups (halogens, esters, acetyl, vinyl) were tolerated.

Conclusions:

• A first-time strategy for ruthenium-catalyzed amide C-N bond activation has been established.
• The in situ formed bis-cycloruthenated complexes are highly effective for activating inert amide bonds.
• The developed tandem reaction offers a versatile route for synthesizing functionalized molecules with high functional group tolerance.