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Nickel-catalyzed transamidation of aliphatic amide derivatives

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Abstract

Transamidation, or the conversion of one amide to another, is a long-standing challenge in organic synthesis. Although notable progress has been made in the transamidation of primary amides, the transamidation of secondary amides has remained underdeveloped, especially when considering aliphatic substrates. Herein, we report a two-step approach to achieve the transamidation of secondary aliphatic amides, which relies on non-precious metal catalysis. The method involves initial Boc-functionalization of secondary amide substrates to weaken the amide C–N bond. Subsequent treatment with a nickel catalyst, in the presence of an appropriate amine coupling partner, then delivers the net transamidated products. The transformation proceeds in synthetically useful yields across a range of substrates. A series of competition experiments delineate selectivity patterns that should influence future synthetic design. Moreover, the transamidation of Boc-activated secondary amide derivatives bearing epimerizable stereocenters underscores the mildness and synthetic utility of this methodology. This study provides the most general solution to the classic problem of secondary amide transamidation reported to date.

Graphical abstract: Nickel-catalyzed transamidation of aliphatic amide derivatives

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Publication details

The article was received on 03 May 2017, accepted on 08 Jul 2017 and first published on 10 Jul 2017


Article type: Edge Article
DOI: 10.1039/C7SC01980G
Citation: Chem. Sci., 2017, Advance Article
  • Open access: Creative Commons BY license
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    Nickel-catalyzed transamidation of aliphatic amide derivatives

    J. E. Dander, Emma L. Baker and N. K. Garg, Chem. Sci., 2017, Advance Article , DOI: 10.1039/C7SC01980G

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