Controlling Ni redox states by dynamic ligand exchange for electroreductive Csp3-Csp2 coupling

Area of Science:

• Organic Chemistry
• Synthetic Methodology
• Electrochemistry

Background:

• Cross-electrophile coupling (XEC) reactions are valuable synthetic tools but face limitations with specific substrate classes.
• Existing methods often struggle with combining diverse electrophiles, such as tertiary alkyl bromides and aryl chlorides.

Purpose of the Study:

• To develop a novel electroreductive cross-electrophile coupling (XEC) strategy.
• To enable the coupling of previously incompatible electrophiles, including tertiary alkyl bromides, aryl chlorides, and aryl/vinyl triflates.
• To establish a mild and efficient method for generating key nickel intermediates.

Main Methods:

• Employing an electrochemically active complex for selective reaction with alkyl bromides via single-electron (1e-) processes.
• Utilizing an electrochemically inactive Ni0(phosphine) complex for selective reaction with aryl electrophiles via two-electron (2e-) processes.
• Discovering a new pathway for electrochemically generating Ni0(phosphine) intermediates at mild potentials through ligand-exchange reactions.

Main Results:

• Successfully achieved electroreductive XEC of previously incompatible electrophiles.
• Demonstrated the selective reactivity of the dual-complex system with different electrophile classes.
• Uncovered a mild electrochemical generation pathway for crucial Ni0(phosphine) intermediates.
• Applied the methodology to alkylate a variety of substrates, including natural products and pharmaceuticals.

Conclusions:

• The developed electroreductive XEC methodology significantly broadens the scope of compatible electrophiles.
• The novel electrochemical generation of Ni0(phosphine) intermediates overcomes a critical challenge in Ni-catalyzed cross-coupling.
• This mild and versatile method has potential applications in the synthesis of complex molecules, including pharmaceuticals.