Ligand-Controlled Switchable Synthesis of Fused Polycycles by Selective 1,4-Palladium Migration.

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Medicinal Chemistry

Background:

• Palladium migration is a key strategy for C-H bond functionalization.
• Constructing fused heterocycles is crucial in drug discovery.
• Selective synthesis of complex organic molecules remains a challenge.

Purpose of the Study:

• To develop a novel ligand-controlled synthesis of fused quinolinone skeletons.
• To explore the selective 1,4-palladium migration of 1,7-enynes with perfluoroalkyl iodides.
• To demonstrate the utility of the protocol in modifying drug molecules.

Main Methods:

• Utilized a palladium migration strategy involving 1,7-enynes and perfluoroalkyl iodides.
• Employed different ligands (DPEphos and DPPPy) to control palladium migration pathways.
• Performed Density Functional Theory (DFT) calculations to understand reaction mechanisms.

Main Results:

• Achieved ligand-controlled switchable synthesis of fused quinolinones.
• DPEphos ligand promoted vinyl-to-aryl migration, yielding 4,5,10-fused quinolinones.
• DPPPy ligand facilitated vinyl-to-alkyl migration, producing 3,4-fused quinolinones.
• Demonstrated successful modification of drug molecules.

Conclusions:

• Developed a versatile and selective method for synthesizing perfluoroalkyl-containing fused quinolinones.
• Ligand choice is critical for controlling the regioselectivity of palladium migration.
• The protocol offers a valuable tool for medicinal chemistry and drug discovery.