An aryne-based three-component access to α-aroylamino amides

Area of Science:

• Organic Chemistry
• Synthetic Chemistry

Background:

• Aryne chemistry is gaining attention.
• Isocyanides are effective nucleophilic partners in multicomponent reactions.

Purpose of the Study:

• To develop a direct, metal-free method for synthesizing functionalized α-benzoylamino amides.
• To explore the coupling of tertiary α-monosubstituted α-isocyanoacetamides with water and benzyne.

Main Methods:

• Utilizing tertiary α-monosubstituted α-isocyanoacetamides as substrates.
• Employing benzyne as a key reactant in a multicomponent reaction.
• Conducting the reaction under metal-free conditions.

Main Results:

• Achieved direct and metal-free access to densely functionalized α-benzoylamino amides.
• Demonstrated a stereoservative reaction course, yielding enantiomerically pure products.
• Avoided competing intramolecular cyclization to 5-aminooxazoles.

Conclusions:

• The developed multicomponent reaction offers a novel synthetic route to α-benzoylamino amides.
• The method is efficient for preparing enantiomerically pure compounds.
• The synthetic utility was confirmed by synthesizing proglumide, a cholecystokinin antagonist.