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Nickel-Catalyzed Suzuki-Miyaura Coupling of Aliphatic Amides
Timothy B Boit1, Nicholas A Weires1, Junyong Kim1
1Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, United States.
Abstract:
We report the Ni-catalyzed Suzuki-Miyaura coupling of aliphatic amide derivatives. Prior studies have shown that aliphatic amide derivatives can undergo Ni-catalyzed carbon-heteroatom bond formation but that Ni-mediated C-C bond formation using aliphatic amide derivatives has remained difficult. The coupling disclosed herein is tolerant of considerable variation with respect to both the amide-based substrate and the boronate coupling partner and proceeds in the presence of heterocycles and epimerizable stereocenters. Moreover, a gram-scale Suzuki-Miyaura coupling/Fischer indolization sequence demonstrates the ease with which unique polyheterocyclic scaffolds can be constructed, particularly by taking advantage of the enolizable ketone functionality present in the cross-coupled product. The methodology provides an efficient means to form C-C bonds from aliphatic amide derivatives using nonprecious-metal catalysis and offers a general platform for the heteroarylation of aliphatic acyl electrophiles.
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