The Need

Cross-electrophile coupling (XEC) reactions of aryl and alkyl electrophiles are desirable methodologies for C–C bond formation but are limited to specific substrate classes. Couplings of widely-available electrophiles such as aryl chlorides or triflates are currently unknown with any alkyl bromide. There is a need to establish a general solution to the limitations of alkyl-aryl XEC.

The Technology

Dr. Sevov’s technology details a general platform for electroreductive XEC of previously-incompatible electrophiles including tertiary alkyl bromides, aryl chlorides, and aryl/vinyl triflates. Reactions rely on the merger of an electro-chemically-active complex that selectively reacts with alkyl bromides via 1e- processes and an electrochemically-inactive Ni0(phosphine) complex that selectively reacts with aryl electrophiles via 2e- processes. Accessing Ni0(phosphine) intermediates is critical to the strategy but is often challenging. This technology uncovers a previously-unknown pathway for electrochemically-generating these key complexes at mild potentials through a choreographed series of ligand exchange reactions. Beyond the advances to XEC, these findings represent a fundamental solution to reductively accessing highly-reactive Ni0 complexes in preference to the NiI intermediates that currently dominate Ni-redox catalysis.

Benefits

• Expands C-C bond-forming methodologies as a whole

• XEC reactions are no longer limited to the canonical couplings of 1°/2° alkyl bromides and aryl iodides/bromides

• Reductively accesses highly-reactive Ni0 complexes

Commercial Applications

• Pharmaceuticals

• Natural product synthesis

• Agrochemical synthesis

• Medicinal chemistry

• Plastics