Intramolecular Amido Transfer Leading to Structurally Diverse Nitrogen-Containing Macrocycles

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Nitrogen-containing macrocycles are important structural motifs in pharmaceuticals and materials science.
• Efficient and selective synthetic routes to macrocycles remain a challenge in organic chemistry.

Purpose of the Study:

• To develop a novel rhodium-catalyzed intramolecular amido transfer reaction.
• To synthesize nitrogen-containing macrocycles from readily available precursors.

Main Methods:

• The study employed rhodium catalysis to mediate intramolecular amido transfer reactions.
• Acetophenone ketoximes tethered with aryl or alkyl azides were used as substrates.
• Mechanistic studies involving rhodacycle and metal imido intermediates were performed.

Main Results:

• A novel rhodium-catalyzed intramolecular amido transfer reaction was successfully developed.
• The reaction provides an efficient route to nitrogen-containing macrocycles.
• Substrates with aryl azides yielded monomeric macrocycles, while alkyl azides produced dimeric macrocycles up to 36-membered.
• This represents the first example of intramolecular inner-sphere C-H amination.

Conclusions:

• Rhodium-catalyzed intramolecular amido transfer is an effective strategy for macrocycle synthesis.
• The reaction pathway is dependent on the nature of the azide (aryl vs. alkyl).
• This methodology offers a new tool for constructing complex nitrogen-containing macrocyclic structures.