Asymmetric Substitution by Alkynyl Copper Driven Dearomatization and Rearomatization

Area of Science:

• Organic Chemistry
• Catalysis
• Asymmetric Synthesis

Background:

• Catalytic asymmetric dearomatization is a key synthetic strategy.
• Existing methods often rely on heteroatom-containing arenes and p-orbital involvement.
• A new approach is needed to overcome these limitations.

Purpose of the Study:

• To develop a novel asymmetric alkynyl copper-catalyzed remote substitution reaction.
• To demonstrate transition-metal d-orbital activation as a driving force for dearomatization.
• To construct valuable diarylmethyl and triarylmethyl skeletons with high enantioselectivity.

Main Methods:

• Utilized a modified PyBox chiral ligand for copper catalysis.
• Employed a d-orbital electron activation mechanism for dearomatization.
• Investigated a tandem process involving remote substitution, cyclization, and 1,5-H shift.

Main Results:

• Achieved high enantioselectivities in the synthesis of diarylmethyl and triarylmethyl skeletons.
• Demonstrated a gram-scale reaction, highlighting the method's robustness.
• Identified an unexpected tandem process leading to enantioenriched C-N axis formation.
• Preliminary mechanistic studies indicated a mononuclear copper-catalyzed remote substitution process.

Conclusions:

• The developed method offers a novel route for catalytic asymmetric dearomatization.
• Transition-metal d-orbital activation provides a new driving force for dearomatization reactions.
• The reaction demonstrates broad applicability and potential for downstream transformations.