Stereocontrolled Radical Thiophosphorylation.

Area of Science:

• Organic Chemistry
• Organophosphorus Chemistry
• Stereoselective Synthesis

Background:

• Phosphorus(V) chemistry offers unique properties but is underexplored.
• Stereoselective synthesis of chiral organophosphorus compounds remains a challenge.

Purpose of the Study:

• To develop a practical and fully stereoselective P(V)-radical hydrophosphorylation reaction.
• To create novel P-chiral building blocks for drug discovery and materials science.

Main Methods:

• Utilized simple, limonene-derived reagent systems for P(V)-radical hydrophosphorylation.
• Employed radical initiation to react reagents with olefins and other radical acceptors.
• Applied conventional 2e- chemistry for diversification of P-chiral products.

Main Results:

• Achieved the first practical, fully stereoselective P(V)-radical hydrophosphorylation.
• Generated a range of underexplored P-chiral bioisosteric building blocks.
• Demonstrated wide scope and excellent chemoselectivity with unexpected stereochemical outcomes, supported by computation and experimentation.

Conclusions:

• The developed methodology provides a novel and efficient route to P-chiral compounds.
• The generated building blocks represent a promising, rarely explored chemical space with potential applications.
• Initial ADME studies suggest favorable properties for further investigation.