Ligand-controlled sequential activation enables nickel-catalysed alkyl-alkynyl coupling.

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Cross-electrophile coupling between alkyl and alkynyl halides is difficult due to reactivity differences.
• Existing methods struggle with selectivity and activating unreactive substrates.

Purpose of the Study:

• To develop a nickel-catalyzed method for direct alkynyl-alkyl bond formation.
• To overcome challenges associated with reactivity mismatch and chemoselectivity in cross-electrophile couplings.

Main Methods:

• Utilized a nickel catalyst with a specifically designed tridentate ligand.
• Investigated sequential electrophile activation pathways.
• Employed mechanistic studies to understand the reaction mechanism.

Main Results:

• Achieved direct construction of internal alkynes from unactivated primary, secondary, and tertiary alkyl halides.
• Demonstrated broad functional-group tolerance.
• Enabled reductive coupling of tertiary alkyl electrophiles with alkynyl partners.
• Identified an alkyl-first activation mode mediated by the tridentate ligand.

Conclusions:

• The tridentate ligand controls electrophile activation sequence, enabling challenging C-C bond formation.
• This ligand-controlled strategy expands the scope of alkynyl-alkyl coupling.
• The alkyl-first activation pathway enhances chemoselectivity and suppresses homocoupling.