Applying asymmetric-waveform alternating current in nickel-catalyzed asymmetric reductive cross-coupling.

Area of Science:

• Electrochemistry
• Organic Synthesis
• Catalysis

Background:

• Traditional direct current (DC) electrocatalysis faces limitations like over-reduction and metal salt deposition.
• Electrochemical reductive cross-coupling is crucial but challenging for certain substrates.
• Developing versatile electrocatalytic platforms is essential for efficient organic synthesis.

Purpose of the Study:

• Introduce asymmetric waveform alternating current electrocatalysis (asym. AC-eChem) as a novel platform.
• Overcome limitations of DC methods in electrochemical reductive cross-coupling.
• Enable challenging dialkylation of alkynes with non-activated alkyl halides.

Main Methods:

• Utilized nickel-catalyzed asymmetric reductive cross-coupling.
• Precisely tuned electrode materials, current parameters, duty ratio, and frequencies.
• Employed a custom-designed flow electrochemical system for scalability.

Main Results:

• Achieved dialkylation of alkynes with two non-activated alkyl halides.
• Demonstrated precise control over chemo-, regio-, E/Z-, and enantio-selectivities.
• Synthesized axially chiral compounds, including pharmaceutically relevant deuterated derivatives.
• Transformed products into effective phosphine ligands for palladium-catalyzed reactions.

Conclusions:

• Asymmetric waveform AC electrocatalysis is a powerful and versatile method.
• This protocol advances electrochemical reductive cross-coupling, overcoming key limitations.
• The strategy shows scalability and industrial viability for synthesizing complex chiral molecules.