Catalytic Enantioselective Cross-Nucleophile Coupling via Valence Tautomerism

Area of Science:

• Organic Chemistry
• Catalysis
• Asymmetric Synthesis

Background:

• Valence tautomerism is underexplored in asymmetric catalysis compared to prototropic tautomerism.
• Novel catalytic methods are needed for creating complex molecular architectures.

Purpose of the Study:

• To harness one-electron valence tautomerism for enantioselective cross-nucleophile coupling (CNC).
• To develop an oxidant-free method for coupling diverse substrates.
• To establish a mechanistic understanding of the radical pathway.

Main Methods:

• Dual photoredox/nickel catalysis.
• Coupling of β-keto esters/amides with silyl enol ethers/allyl silanes.
• Mechanistic studies including EPR, DFT, and radical trapping.

Main Results:

• Efficient enantioselective synthesis of coupling products with quaternary stereocenters.
• Broad functional group and substrate tolerance.
• Confirmation of a radical mechanism involving valence tautomerism.

Conclusions:

• The developed method provides a powerful tool for asymmetric synthesis.
• Mechanistic insights into valence tautomerism in catalysis.
• Potential for inspiring new catalytic transformations and reaction frameworks.