Scientific Article:

Abstract:

A novel triply convergent Ni-electrocatalytic assembly has been developed for the efficient synthesis of 1,1-diaryl cyclobutanes, azetidines, and oxetanes. This method represents a significant advancement in electrocatalytic cross-coupling chemistry, providing a unified and modular platform for constructing structurally complex, bioactive molecular frameworks with high selectivity and atom economy.

Introduction:

The development of electrocatalytic methodologies has transformed synthetic organic chemistry, offering sustainable routes to carbon–carbon and carbon–heteroatom bond formation under mild conditions. Nickel-based electrocatalysis, in particular, has emerged as a powerful tool due to its tunable redox behavior, earth-abundant availability, and compatibility with diverse substrates.

Cyclobutanes, azetidines, and oxetanes are pharmaceutically valuable ring systems known for their rigidity, metabolic stability, and three-dimensional structural features. However, conventional synthetic routes often require multi-step procedures, photochemical conditions, or harsh reagents.

This work introduces a triply convergent electrochemical assembly that allows direct formation of these strained ring systems via a Ni(II)/Ni(I) redox cycle, eliminating the need for pre-functionalized substrates or external oxidants.

Results and Discussion:

The electrocatalytic system employs a nickel catalyst in conjunction with a tailored ligand framework and constant-current electrolysis in an undivided cell setup. Through precise modulation of the electrochemical potential, the method facilitates three distinct bond-forming events:

1. C–C coupling between aryl halides and olefinic precursors,
2. Cyclization via intramolecular radical addition, and
3. Ring closure to generate cyclobutane, azetidine, or oxetane frameworks depending on substrate structure.

Mechanistic studies, supported by cyclic voltammetry and radical trapping experiments, confirm the formation of organonickel intermediates and radical-polar crossover processes as key mechanistic steps.

The process exhibits broad substrate scope and functional group tolerance, delivering products in moderate to excellent yields (65–92%).

Conclusion:

This triply convergent Ni-electrocatalytic assembly provides a unified platform for the selective synthesis of 1,1-diaryl cyclobutanes, azetidines, and oxetanes. By leveraging electrochemical control and nickel catalysis, the method eliminates the need for external oxidants and enables atom-efficient, sustainable, and modular synthesis of complex molecular architectures.

This strategy opens new opportunities for drug discovery, materials chemistry, and green electrosynthetic applications.

Keywords:

Ni-electrocatalysis, 1,1-Diaryl Cyclobutanes, Azetidines, Oxetanes, Electrochemical Synthesis, Cross-Coupling, Nickel Catalysis, Sustainable Chemistry