Ligand-enabled Ni-catalysed enantioconvergent intermolecular Alkyl-Alkyl cross-coupling between distinct Alkyl
Wen-Tao Zhao1, Jian-Xin Zhang1, Bi-Hong Chen1
1Shenzhen Grubbs Institute and Department of Chemistry, Southern University of Science and Technology, Shenzhen, 518055, Guangdong, P. R. China.
Abstract:
α-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 the most straightforward and efficient, yet highly challenging ways to build such stereogenic carbon centers. Herein, we report an enantioselective alkyl-alkyl cross-coupling between two different alkyl electrophiles to access α-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.
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