Mechanistic insights into boron-catalysed direct amidation reactions

Area of Science:

• Organic Chemistry
• Catalysis
• Reaction Mechanisms

Background:

• The monoacyloxyboron mechanism is the accepted pathway for boron-catalyzed direct amidation.
• Understanding the precise mechanism is crucial for optimizing amidation reactions.
• Boron compounds, including borinic acids, boronic acids, and boric acid, are utilized in these reactions.

Purpose of the Study:

• To investigate and challenge the established monoacyloxyboron mechanism in boron-catalyzed amidation.
• To explore alternative reaction pathways and identify key intermediates.
• To elucidate the role of different boron species (borinic, boronic, boric acids) in amidation catalysis.

Main Methods:

• Detailed investigation of reactions between amines, carboxylic acids, and various boron compounds.
• Isolation and characterization of potential reaction intermediates using NMR spectroscopy and X-ray crystallography.
• Theoretical modeling, including quantum mechanical calculations (B3LYP+D3/Def2-TZVPP), to evaluate proposed mechanisms.

Main Results:

• Rapid amine-boron compound reactions indicate significant boron-nitrogen interactions.
• Borinic acids were found to be incompetent catalysts, forming unreactive complexes or undergoing protodeboronation.
• Evidence suggests at least three free coordination sites on boron are necessary for catalysis.
• Observations are inconsistent with the monomeric acyloxyboron intermediate mechanism.

Conclusions:

• The monoacyloxyboron mechanism is unlikely to be the primary pathway for boron-catalyzed amidation.
• Alternative mechanisms involving dimeric B-X-B motifs (X = O, NR) are proposed, facilitating carboxylic acid activation and amine delivery.
• Computational studies support these novel pathways as energetically favorable compared to the current mechanism.