Photoinduced Decarboxylative Radical Phosphinylation

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• C(sp3)-phosphinylation is a crucial transformation for synthesizing organophosphorus compounds.
• Existing methods often require harsh conditions or lack substrate scope.

Purpose of the Study:

• To develop an unprecedented, mild, and efficient protocol for C(sp3)-phosphinylation.
• To enable the late-stage functionalization of complex molecules and synthesis of bioactive phosphinic acids.

Main Methods:

• Visible light-induced reaction catalyzed by 4CzIPN (1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene).
• Utilized redox-active esters of aliphatic carboxylic acids and phosphonites.
• Operated at room temperature with low catalyst loading (1 mol%).

Main Results:

• Achieved satisfactory yields of decarboxylative phosphinylation products.
• Demonstrated broad substrate scope and wide functional-group compatibility.
• Successfully synthesized bioactive phosphinic acids, including phosphinothricin and a kynureninase inhibitor.

Conclusions:

• The developed protocol offers a novel and versatile route to C(sp3)-phosphinylated compounds.
• A radical-polar crossover mechanism is proposed, involving phosphoranyl radicals and nucleophilic demethylation/deethylation.
• This method facilitates the synthesis of complex organophosphorus molecules and drug candidates.