Cascade Oxidative Coupling/Cyclization: A Gateway to 3-Amino Polysubstituted Five-Membered Heterocycles

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Heterocyclic Chemistry

Background:

• Cascade reactions offer efficient synthetic routes.
• Oxidative coupling and cyclization are key transformations in organic synthesis.
• Developing new methods for constructing five-membered heterocycles is important for medicinal chemistry.

Purpose of the Study:

• To develop a novel cascade oxidative coupling/cyclization reaction.
• To synthesize three types of five-membered heterocycles.
• To explore the use of α-amino acids and α-amino ketones as substrates.

Main Methods:

• Utilizing a coordinating activation strategy.
• Employing cascade oxidative coupling/cyclization of α-C(sp(3))-H bonds of amines with enamines or β-keto esters.
• Using air, dioxygen, or di-tert-butyl peroxide as oxidants.

Main Results:

• Successfully synthesized 3-amino 1,3-dihydro-2H-pyrrol-2-ones from α-amino acids using air.
• Synthesized furan-2(3H)-ones from α-amino acids using dioxygen.
• Produced 3-amino 1H-pyrroles from α-amino ketones using di-tert-butyl peroxide.
• Developed a three-component, one-pot reaction for 1H-pyrrole scaffolds.

Conclusions:

• The developed protocol is practical and modular for constructing 1H-pyrrole scaffolds.
• The reaction exhibits simple conditions, readily available starting materials, broad substrate scope, and high functional group tolerance.
• This method provides an efficient route to valuable five-membered heterocyclic compounds.