Ligand-enabled Ni-catalysed enantioconvergent intermolecular Alkyl-Alkyl cross-coupling between distinct Alkyl halides

alpha-Tertiary aliphatic amides are key elements in organic molecules, which are abundantly present in natural products, pharmaceuticals, agrochemicals, and functional organic materials. Enantioconvergent alkyl-alkyl bond-forming process is one of themost straightforward and efficient, yet highly challenging ways to build such stereogenic carbon centers. Herein, we report an enantio-selective alkyl-alkyl cross-coupling between two different alkyl electrophiles to access alpha-tertiary aliphatic amides. With a newly-developed chiral tridentate ligand, two distinct alkyl halides were successfully cross-coupled together to forge an alkyl-alkyl bond enantioselectively under reductive conditions. Mechanistic investigations reveal that one alkyl halides exclusively undergo oxidative addition with nickel versus in-situ formation of alkyl zinc reagents from the other alkyl halides, rendering formal reductive alkyl-alkyl cross-coupling from easily available alkyl electrophiles without preformation of organometallic reagents.

Automated summary

This study reports an enantio-selective alkyl-alkyl cross-coupling reaction using a newly-developed chiral tridentate ligand. Two different alkyl halides were successfully cross-coupled to form α-tertiary aliphatic amides. The mechanism investigation revealed that one alkyl halide undergoes oxidative addition with nickel, while the other alkyl halide forms alkyl zinc reagents in situ, enabling reductive alkyl-alkyl cross-coupling without preformation of organometallic reagents.