Enhancing Memory of Chirality in Phosphorus-Centered Radicals by Inductive Deceleration of Pyramidal Inversion.

Area of Science:

• Organic Chemistry
• Stereochemistry
• Radical Chemistry

Background:

• Stereospecific radical reactions are challenging due to rapid inversion of chiral radical intermediates.
• Controlling chirality in radical reactions is crucial for synthesizing complex molecules.

Purpose of the Study:

• To develop a general strategy for enhancing memory of chirality (MOC) in radicals.
• To enable stereoretentive transformations of phosphorus-centered radicals.

Main Methods:

• Density Functional Theory (DFT) calculations to study pyramidal inversion barriers.
• Exploiting inductive effects of electronegative substituents to stabilize radical intermediates.
• Developing novel stereospecific phosphoryl radical reactions.

Main Results:

• Demonstrated significant increase in pyramidal inversion barrier for phosphorus-centered radicals.
• Achieved stereoretentive transformations of enantiopure H-phosphinates under mild radical conditions.
• Developed diverse P(V)-stereogenic compounds with high yield (up to 99%) and stereospecificity (up to >99% es).

Conclusions:

• Established a foundational principle for stereochemical control in radical reactions by tuning intermediate stability.
• The developed method allows for late-stage functionalization of complex molecules, including pharmaceuticals and liquid crystals.
• This approach provides efficient access to enantiopure organophosphorus compounds.