Persistent organonickel complexes as general platforms for Csp²-Csp³ coupling reactions.

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Constructing Csp2-Csp3 bonds is crucial in organic synthesis.
• Existing methods for reductive coupling of aryl and alkyl electrophiles are substrate-specific and require specialized conditions.

Purpose of the Study:

• To develop a consolidated, reliable method for alkyl-aryl couplings.
• To enable the formation of previously unknown Csp2-Csp3 bonds.
• To diversify drug-like molecules through efficient coupling reactions.

Main Methods:

• Discovery of persistent organonickel complexes as stoichiometric coupling platforms.
• Mild electroreduction of Csp2 electrophiles to prepare aryl, heteroaryl, or vinyl nickel complexes on a multigram scale.
• Miniaturization of the procedure to micromole scales using soluble battery chemistries as redox initiators.

Main Results:

• A single set of conditions enables reliable alkyl-aryl couplings, including previously inaccessible transformations.
• Organonickel complexes can be prepared affordably, stored, or used directly in subsequent reactions.
• High-throughput exploration of substrate diversity is achieved through miniaturization and integrated redox initiation.

Conclusions:

• The developed method offers a versatile and efficient approach to Csp2-Csp3 bond formation.
• The use of stable organonickel complexes simplifies and broadens the scope of reductive coupling reactions.
• The miniaturized procedure facilitates rapid screening and optimization for drug discovery and materials science.