Alkyne Migratory Insertion Enabled Dynamic Kinetic Asymmetric Dearomatization of Unactivated Racemic Biaryls

Area of Science:

• Organic Chemistry
• Catalysis
• Asymmetric Synthesis

Background:

• Catalytic asymmetric dearomatization transforms planar aromatics into 3D chiral structures.
• Existing methods often require pre-activated substrates or do not address dynamic kinetic processes.

Purpose of the Study:

• To develop a novel palladium-catalyzed enantioconvergent dearomatization of non-activated naphthalene derivatives.
• To enable dynamic kinetic asymmetric dearomatization of racemic unactivated biaryl systems.

Main Methods:

• Palladium-catalyzed reaction utilizing alkyne migratory insertion.
• Employing a custom-designed asymmetric polyfluorinated phosphoramidite ligand.
• Mechanistic investigations including density functional theory calculations.

Main Results:

• Achieved enantioconvergent dearomatization of non-activated naphthalene derivatives.
• Demonstrated dynamic kinetic asymmetric dearomatization of racemic unactivated biaryl systems.
• High reactivity and stereocontrol were enabled by the specialized ligand.

Conclusions:

• The developed method provides a rare strategy for dynamic kinetic asymmetric dearomatization.
• The catalytic system efficiently converts labile biaryl substrates into enantioenriched spiro frameworks.
• Synthetic utility is confirmed by scale-up and downstream transformations, including chirality transfer.